bluuebunny/crossref_metadata_2025 huggingface dataset:
Exciton fine structure splitting in dot-in-a-well structures
Authors: Tartakovskii A. I. , Kolodka R. S. , Liu H. Y. , Migliorato M. A. , Hopkinson M. , Makhonin M. N. , Mowbray D. J. , Skolnick M. S.
Published: March 2006

A range of dot-in-a-well structures designed for long-wavelength (>1.3μm) emission is studied in polarization- and time-resolved differential transmission measurements. Quantum beats observed in differential transmission are employed to measure the fine structure splitting (EFS) of the bright exciton states. A strong dependence of EFS on In content in the InGaAs well surrounding the dots is observed. Large magnitudes of EFS up to 87μeV are found.
Enhanced electrical polarization and ferromagnetic moment in a multiferroic BiFeO3∕Bi3.25Sm0.75Ti2.98V0.02O12 double-layered thin film
Authors: Cheng Zhenxiang , Wang Xiaolin , Kannan Chinna Venkatasamy , Ozawa Kyoshi , Kimura Hideo , Nishida Takashi , Zhang Shujun , Shrout Thomas R.
Published: March 2006

Multiferroic BiFeO3∕Bi3.25Sm0.75Ti2.98V0.02O12 double-layered thin films on Pt∕Ti∕SiO2∕Si were fabricated using the pulsed-laser deposition technique. The films showed greatly enhanced ferroelectric and ferromagnetic properties. The values of the remanent polarization (2Pr) and coercive field (Ec) were 71.8μC∕cm2 and 148kV∕cm at a maximum applied voltage of 13V, respectively. The value of the magnetic moment was found to be 17.5emu∕cm3. The enhancement of the polarization originated from the BiFeO3 with Bi3.25Sm0.75Ti2.98V0.02O12 working as a barrier layer. The enhancement of the magnetization is from the structural distortion of BiFeO3, due to partial epitaxial growth on the bismuth titanate surface.
Electron energy band alignment at interfaces of (100)Ge with rare-earth oxide insulators
Authors: Afanas’ev V. V. , Shamuilia S. , Stesmans A. , Dimoulas A. , Panayiotatos Y. , Sotiropoulos A. , Houssa M. , Brunco D. P.
Published: March 2006

Energy diagrams of interfaces between (100)Ge and several rare-earth oxide insulators deposited from a molecular beam are determined using a combination of internal photoemission and photoconductivity measurements. For the wide band gap (5.9eV) oxides Gd2O3 and LaHfOx, the band alignment at the interface is found to be close to that of HfO2 and is characterized by conduction/valence band offsets of ∼2∕∼3eV. In contrast, CeO2 which has a much narrower band gap (3.3eV) does not provide a band alignment diagram corresponding to sufficient insulation.
Phosphorus-doped SiC as an excellent p-type Si surface passivation layer
Authors: Janz S. , Riepe S. , Hofmann M. , Reber S. , Glunz S.
Published: March 2006

The passivation properties of phosphorus-doped amorphous silicon carbide (a-SixC1−x) layers on monocrystalline Si wafers (floating zone, 1Ωcm) have been investigated. The cleaning and the deposition process were performed in our two source (microwave, radio frequency) plasma-enhanced chemical vapor deposition reactor. In situ plasma etching and deposition at 350°C without any following annealing step led to extraordinary low surface recombination velocities of less than 5cm∕s for injection levels between 1×1014 and 1×1015cm−3. Characterization of the a-SixC1−x layer was done with quasi-steady-state photoconductance, microwave-detected photoconductance, and carrier density imaging techniques. For injection levels of more than 1×1015cm−3 the effective lifetime was limited only by intrinsic Auger recombination.
Impact of subsoil constraints on wheat yield and gross margin on fine-textured soils of the southern Victorian Mallee
Authors: Rodriguez D. , Nuttall J. , Sadras V. O. , van Rees H. , Armstrong R.
Published: March 2006

The APSIM-Wheat module was used to investigate our present capacity to simulate wheat yields in a semi-arid region of eastern Australia (the Victorian Mallee), where hostile subsoils associated with salinity, sodicity, and boron toxicity are known to limit grain yield. In this study we tested whether the effects of subsoil constraints on wheat growth and production could be modelled with APSIM-Wheat by assuming that either: (a) root exploration within a particular soil layer was reduced by the presence of toxic concentrations of salts, or (b) soil water uptake from a particular soil layer was reduced by high concentration of salts through osmotic effects. After evaluating the improved predictive capacity of the model we applied it to study the interactions between subsoil constraints and seasonal conditions, and to estimate the economic effect that subsoil constraints have on wheat farming in the Victorian Mallee under different climatic scenarios. Although the soils had high levels of salinity, sodicity, and boron, the observed variability in root abundance at different soil layers was mainly related to soil salinity. We concluded that: (i) whether the effect of subsoil limitations on growth and yield of wheat in the Victorian Mallee is driven by toxic, osmotic, or both effects acting simultaneously still requires further research, (ii) at present, the performance of APSIM-Wheat in the region can be improved either by assuming increased values of lower limit for soil water extraction, or by modifying the pattern of root exploration in the soil profile, both as a function of soil salinity. The effect of subsoil constraints on wheat yield and gross margin can be expected to be higher during drier than wetter seasons. In this region the interaction between climate and soil properties makes rainfall information alone, of little use for risk management and farm planning when not integrated with cropping systems models.
Sensitivity of response of multi-trait index selection to changes in genetic correlations between production traits in sheep
Authors: Safari E. , Fogarty N. M. , Gilmour A. R.
Published: March 2006

Complex sheep breeding objectives and the inclusion of more traits in genetic evaluation requires more accurate genetic parameters. There are few estimates of genetic correlations, especially between the major sheep production trait groups and they are generally variable with large standard errors. This study examines the sensitivity of response to multi-trait index selection for a range of genetic correlations between major traits (growth, wool, carcass, reproduction and worm resistance) under 3 breeding objectives (fine wool, dual-purpose wool/meat and meat) relevant to Australian sheep enterprises. Factor analysis identified the major factors explaining the underlying variability in the matrix of base genetic correlations for each breeding objective. Monte Carlo simulation studied the effect of changes in the genetic correlations under 3 index scenarios with the genetic and environmental variance–covariance matrices sampled independently from a Wishart distribution. The sensitivity of responses to selection over the range of correlations varied with the breeding objective. Selection responses were sensitive under all objectives for the range of correlations for reproduction with wool traits and in at least some objectives for reproduction with growth, worm resistance and carcass muscling. Selection responses in the fine wool objective were highly sensitive to the correlation between growth and fibre diameter. The results provide a logical basis for setting priorities for studies to obtain more accurate estimates of genetic correlations among sheep production traits.
In vivo
diffusion analysis with quantum dots and dextrans predicts the width of brain extracellular space
Authors: Thorne Robert G. , Nicholson Charles
Published: March 2006

Diffusion within the extracellular space (ECS) of the brain is necessary for chemical signaling and for neurons and glia to access nutrients and therapeutics; however, the width of the ECS in living tissue remains unknown. We used integrative optical imaging to show that dextrans and water-soluble quantum dots with Stokes–Einstein diameters as large as 35 nm diffuse within the ECS of adult rat neocortex
in vivo
. Modeling the ECS as fluid-filled “pores” predicts a normal width of 38–64 nm, at least 2-fold greater than estimates from EM of fixed tissue. ECS width falls below 10 nm after terminal ischemia, a likely explanation for the small ECS visualized in electron micrographs. Our results will improve modeling of neurotransmitter spread after spillover and ectopic release and establish size limits for diffusion of drug delivery vectors such as viruses, liposomes, and nanoparticles in brain ECS.
Controlled release of proteins from polymer-modified surfaces
Authors: Fang Fang , Szleifer I.
Published: March 2006

The ability to control the rate of adsorption and desorption of proteins from surfaces is studied by using a molecular theory. We show how changing the chemical structure and charge of short linear and branched grafted polymers to an electrode surface can be used to promote fast adsorption of charged proteins on a time scale of seconds and control the desorption in a time scale ranging from milliseconds to hours. The optimal controlled release is found from the interplay of electrostatic attractions at short distances from the surface and the proper electrostatic and steric repulsive barrier at distances from the surfaces larger than the proteins’ size. The implications of our results to the design of controlled-release devices is discussed.
The influence of chromosome flexibility on chromosome transport during anaphase A
Authors: Raj Arjun , Peskin Charles S.
Published: March 2006

The role of protein flexibility in molecular motor function has previously been studied by considering a Brownian ratchet motor that is connected to its cargo by an elastic spring, with the result that the average velocity of the motor/cargo system is increased by reducing the stiffness of the linkage. Here, we extend this investigation to the case of chromosome transport during anaphase A, in which the relevant flexibility is not primarily in the motor/cargo linkage but rather in the cargo itself, i.e., in the chromosome. We model the motor mechanism as an imperfect Brownian ratchet with a built-in opposing load and the chromosome as a collection of discrete segments linked by an elastic energy function that discretizes the potential energy of an elastic rod. Thermal fluctuations are produced in the model by random forces, as in Brownian dynamics. All of the parameters that characterize the chromosome are known or can be estimated from experimental data, as can all but one of the motor parameters, which is adjusted to give the correct transport velocity of normal-length chromosomes. With the parameters so determined, we then reproduce the experimental finding of Nicklas [Nicklas, R. B. (1965)
J. Cell Biol.
25, 119–135] that chromosome speed is essentially independent of chromosome length, even though our model contains no “velocity governor.” We find instead that this effect is a consequence of chromosome flexibility, as it disappears when stiffer than normal chromosomes are considered.
On the nature of low- and high-affinity EGF receptors on living cells
Authors: Özcan Ferruh , Klein Peter , Lemmon Mark A. , Lax Irit , Schlessinger Joseph
Published: March 2006

The small subpopulation of high-affinity EGF receptors (EGFRs) on living cells revealed by Scatchard analysis of
125
I-EGF binding results was discovered nearly three decades ago, yet not much is known about the underlying mechanism. After the determination of the structure of different forms of EGFR extracellular domain it was proposed that the monomeric tethered configuration corresponds to the majority of low-affinity receptors, whereas the extended dimeric configuration corresponds to the minority of the high-affinity class of EGFRs. Mathematical modeling of EGF-binding experiments to different conformational mutants of EGFR has shown that the high-affinity class of EGFR on living cells does not correspond to the extended configuration of EGFR and can only be accounted for by including in the mathematical model an additional binding event that is attributed to the dynamic nature of EGFR on living cells. To circumvent this problem we have performed similar experiments in the background of an EGFR mutant that does not form high-affinity sites. Quantitative analysis and mathematical modeling of these data show that release of the intramolecular tether causes a 2-fold increase in EGF-binding affinity, whereas elimination of the dimerization arm reduces EGF-binding affinity by ≈6-fold. These experiments confirm the salient features of the structural model for EGFR regulation and argue further that the intramolecular tether provides only limited autoinhibitory control of EGFR activity and that the low-affinity class of EGF-binding sites on living cells reflects interconverting, tethered, and extended receptor configurations.
Neonatal behavioural profile and crying in premature infants at term age
Authors: Ohgi Shohei , Gima Hirotaka , Akiyama Tomitaro
Published: March 2006

Aim: To analyse behavioural characteristics of infants who cried more versus those who cried less, in a sample of low‐risk premature infants. Methods: Participants were 63 low‐risk healthy premature infants. At term age, the Neonatal Behavioral Assessment Scale (NBAS) was administered, and a 1‐d diary for crying was recorded starting on the following day. Infants were categorized into two groups: those with “high level of crying” (≥75th percentile) and those with “less crying” (<75th percentile), based on the total amount of crying time. Results: Some individual NBAS scores and “habituation” and “regulation of state” cluster scores were lower in the high‐level‐of‐crying group. Infants in the group with a high level of crying had lower thresholds for response in the “peak of excitement”, “rapidity of build‐up”, “irritability” and “general irritability” items. Logistic regression analysis revealed that lower “habituation” and “regulation of state” cluster scores were significantly associated with lower thresholds for crying.

Conclusion: These results suggest that neonatal behavioural characteristics, such as hyperresponsivity and poor state regulation, are associated with high levels of crying. Clinical assessments based on the NBAS may help parents elucidate their infant's level of tolerance for stimuli, and identify strategies to minimize their crying.
Immunogenicity of hepatitis A‐inactivated vaccine administered to seronegative infants, and serological follow‐up 12 months after second dose
Authors: DE SILVESTRI ANNALISA , ZARA FRANCESCA , TERULLA VIRGINIO , BRERRA ROBERTO , ZUCCA SILVANA , BELLONI CESARE
Published: March 2006

Aim: To evaluate a) the safety and immunogenicity of anti‐HAV‐inactivated vaccine administered during the first year of life to anti‐HAV seronegative babies, and b) the antibody persistence in a low/intermediate endemic area. Methods: After having obtained informed written consent from mothers, 92 babies were vaccinated at 4 and 10 mo of age. All babies were seronegative at birth and did not present HAV‐RNA shedding in three serial stool samples taken at 1, 2 and 3 mo of age. Results: No general side effects (fever>38°C) were observed. After the first dose of vaccine, 70/82 (85.4%) babies developed anti‐HAV>10 mIU/ml and 36/82 (43.9%)>20 mIU/ml. After the second dose of vaccine, all babies developed a titre>20 mIU/ml, and GMT was 877 mIU/ml. After 1 y of follow‐up, the decreasing rate was similar to that reported for adult populations. Furthermore, three babies doubled the titre observed 1 mo after the second dose, indicating the possible spread of HAV even in a low/intermediate endemic area.

Conclusion: Anti‐HAV vaccine is safe, immunogenic and able to induce immune memory, and can be integrated into the routine infant immunization schedule during the first year of life.
Brainstem auditory evoked response at term in preterm infants after perinatal hypoxia‐ischaemia
Authors: Jiang Ze D. , Wilkinson Andrew R.
Published: March 2006

Aim: To examine brainstem auditory function in preterm infants after perinatal hypoxia‐ischaemia (HI). Methods: Brainstem auditory evoked response (BAER) was studied at 37–42 wk postconceptional age in preterm infants who suffered perinatal HI, and were compared with those in preterm and term infants without any major perinatal problems. Results: None of the latencies of waves I, III and V in the BAER in preterm infants after perinatal HI differed significantly from those in preterm and term controls. There were also no significant differences in the I–V and I–III interpeak intervals between preterm infants after HI and the controls. However, III–V interval in infants after HI tended to increase, and was significantly longer than in term controls (p<0.01), although it did not differ significantly from that in preterm controls. Similarly, the III–V/I–III interval ratio was greater than in term controls (p<0.05), but was similar to that in preterm controls. All amplitude variables did not differ significantly from the controls.

Conclusion: BAER in preterm infants after perinatal HI did not differ significantly from that in preterm infants without perinatal problems, but differed slightly from that in normal term infants. The prolonged III–V interval as compared with the term controls suggests a minor impairment in central auditory function.
Atlantoaxial subluxation with recurrent consciousness disturbance in a boy with Lesch‐Nyhan syndrome
Authors: Hou Jia‐Woei
Published: March 2006

Deficiency of the purine salvage enzyme hypoxanthine‐guanine phosphoribosyltransferase (HPRT) may cause various clinical entities such as Lesch‐Nyhan syndrome (LNS). A 9.5‐y‐old boy with the phenotypic features of LNS, including hyperuricaemia, choreoathetosis, self‐mutilation and profound neurological dysfunction, was found to have HPRT deficiency. Normocytic anaemia, hyperuricaemia (uric acid 594.8 µmol/l) and microscopic haematuria with uric acid crystals were noted. Ultrasonography showed bilateral nephrocalcinosis and urinary bladder stones. In addition, he presented with three episodes of consciousness disturbance with limb paresis, possibly caused by atlantoaxial subluxation (AAS) with compression myelopathy. The diagnosis was made by the amount of residual enzyme activity and a single nucleotide substitution on the acceptor site region of intron 5 (IVS5–1 G→C) of the HPRT gene, inherited from his asymptomatic mother.

Conclusion: Lesch‐Nyhan syndrome is a devastating sex‐linked recessive disorder resulting from almost complete deficiency of the activity of HPRT. This report highlights the unusual AAS in a boy with LNS presenting recurrent consciousness change. The mutation described herein is a hitherto unreported splicing error leading to exon 6 skipping of the HPRT gene.
CD4+ T cells that enter the draining lymph nodes after antigen injection participate in the primary response and become central–memory cells
Authors: Catron Drew M. , Rusch Lori K. , Hataye Jason , Itano Andrea A. , Jenkins Marc K.
Published: March 2006

We explored the relationship between the time of naive CD4+ T cell exposure to antigen in the primary immune response and the quality of the memory cells produced. Naive CD4+ T cells that migrated into the skin-draining lymph nodes after subcutaneous antigen injection accounted for about half of the antigen-specific population present at the peak of clonal expansion. These late-arriving T cells divided less and more retained the central–memory marker CD62L than the T cells that resided in the draining lymph nodes at the time of antigen injection. The fewer cell divisions were related to competition with resident T cells that expanded earlier in the response and a reduction in the number of dendritic cells displaying peptide–major histocompatibility complex (MHC) II complexes at later times after antigen injection. The progeny of late-arriving T cells possessed the phenotype of central–memory cells, and proliferated more extensively during the secondary response than the progeny of the resident T cells. The results suggest that late arrival into lymph nodes and exposure to antigen-presenting cells displaying lower numbers of peptide–MHC II complexes in the presence of competing T cells ensures that some antigen-specific CD4+ T cells divide less in the primary response and become central–memory cells.
Preliminary Results for a New Final Package Test to Assess the Quality of Sterile Package Systems
Authors: Dunkelberg Hartmut , Wedekind Silke
Published: March 2006

Objectives:

To develop a microbial test method to ascertain the passage of airborne bacteria through the medical device packaging System after sterilization, and to apply this test method to flexible packages under mechanical pressure changes.

Methods:

Petri dishes filled with nutrient agar were integrated into the packaging unit prior to sterilization. We examined paper packaging consisting of 1 (single-paper packaging [P]), 2 (double-paper packaging [PP] and textile and paper double packaging [TP]), and 3 (double packaging with transport packaging [TPP]) layers. After sterilization, the test packages were pressed five times per minute for 1 or 3 hours by a mechanical device weighing 1 kg. This exposure took place in rooms with an average airborne bacterial count of 35 (room 1) or 440 (room 2) CFU/m3. The packaging was opened following culture at 37° C for 48 hours to determine the number of colonies formed.

Results:

The proportion of contaminated packages rose with the duration of mechanical stress and increased airborne bacteria concentration. Thus, mechanical pressure change for 3 hours resulted in the contamination of 60% (P), 15% (PP), 0% (TP), and 0% (TPP) of the packages in room 1, whereas 100% (P), 65% (PP), 73% (TP), and 0% (TPP) of the packages in room 2 were contaminated.

Conclusions:

This test method allows sterile packaging Systems to be tested for contamination under practical conditions without extensive laboratory preparation. Contamination as a resuit of laboratory errors can be ruled out almost certainly.
Serial Nosocomial Transmission of Plasmodium falciparum Malaria From Patient to Nurse to Patient
Authors: Alweis Richard L. , DiRosario Kerrie , Conidi Giuseppe , Kain Kevin C. , Olans Richard , Tully John L.
Published: March 2006

Background:

Nosocomial transmission of malaria is a rare phenomenon in the United States.

Objective:

To describe the probable transmission of Plasmodium falciparum malaria from a patient to a healthcare worker and then from the healthcare worker to another patient.

Design:

Case series.

Setting:

Two community hospitals in Massachusetts.

Intervention:

Routine medical and supportive care.

Measurements:

Clinical and laboratory evaluation.

Results:

A nurse developed falciparum malaria after a needlestick injury from a patient with documented falciparum malaria. Three days prior to her diagnosis, she cared for another patient, who subsequently developed falciparum malaria. That patient's parasite isolate genetically matched the nurse's isolate by two independent DNA fingerprinting techniques.

Conclusion:

After extensive evaluation, we believe that a nurse who had acquired falciparum malaria via needlestick subsequently transmitted malaria to another patient via a break in standard precautions. The implications of this mechanism of transmission are discussed.
Independent Prognostic Factors for Fatality in Patients With Urinary Tract Infection Caused by Serratia marcescens
Authors: Liu Jien-Wei , Hsu Yu-Mai , Huang Yen-Fen
Published: March 2006

In a retrospective study of 329 cases of nosocomial urinary tract infection caused by Serratia marcescens, 16 (4.9%) were fatal. Female gender (OR, 3.9; CI95, 1.3-11.7; P = .014) and secondary S. marcescens bacteremia (OR, 6.5; CI95, 1.5-28.6; P = .013) were independent prognostic factors for fatality.
The Regulation of Microtubule Dynamics in Saccharomyces cerevisiae by Three Interacting Plus-End Tracking Proteins
Authors: Wolyniak Michael J. , Blake-Hodek Kristina , Kosco Karena , Hwang Eric , You Liru , Huffaker Tim C.
Published: March 2006

Microtubule plus-end tracking proteins (+TIPs) are a diverse group of molecules that regulate microtubule dynamics and interactions of microtubules with other cellular structures. Many +TIPs have affinity for each other but the functional significance of these associations is unclear. Here we investigate the physical and functional interactions among three +TIPs in S. cerevisiae, Stu2, Bik1, and Bim1. Two-hybrid, coimmunoprecipitation, and in vitro binding assays demonstrate that they associate in all pairwise combinations, although the interaction between Stu2 and Bim1 may be indirect. Three-hybrid assays indicate that these proteins compete for binding to each other. Thus, Stu2, Bik1, and Bim1 interact physically but do not appear to be arranged in a single unique complex. We examined the functional interactions among pairs of proteins by comparing cytoplasmic and spindle microtubule dynamics in cells lacking either one or both proteins. On cytoplasmic microtubules, Stu2 and Bim1 act cooperatively to regulate dynamics in G1 but not in preanaphase, whereas Bik1 acts independently from Stu2 and Bim1. On kinetochore microtubules, Bik1 and Bim1 are redundant for regulating dynamics, whereas Stu2 acts independently from Bik1 and Bim1. These results indicate that interactions among +TIPS can play important roles in the regulation of microtubule dynamics.
SMAP2, a Novel ARF GTPase-activating Protein, Interacts with Clathrin and Clathrin Assembly Protein and Functions on the AP-1–positive Early Endosome/Trans-Golgi Network
Authors: Natsume Waka , Tanabe Kenji , Kon Shunsuke , Yoshida Naomi , Watanabe Toshio , Torii Tetsuo , Satake Masanobu
Published: March 2006

We recently reported that SMAP1, a GTPase-activating protein (GAP) for Arf6, directly interacts with clathrin and regulates the clathrin-dependent endocytosis of transferrin receptors from the plasma membrane. Here, we identified a SMAP1 homologue that we named SMAP2. Like SMAP1, SMAP2 exhibits GAP activity and interacts with clathrin heavy chain (CHC). Furthermore, we show that SMAP2 interacts with the clathrin assembly protein CALM. Unlike SMAP1, however, SMAP2 appears to be a regulator of Arf1 in vivo, because cells transfected with a GAP-negative SMAP2 mutant were resistant to brefeldin A. SMAP2 colocalized with the adaptor proteins for clathrin AP-1 and EpsinR on the early endosomes/trans-Golgi-network (TGN). Moreover, overexpression of SMAP2 delayed the accumulation of TGN38/46 molecule on the TGN. This suggests that SMAP2 functions in the retrograde, early endosome-to-TGN pathway in a clathrin- and AP-1–dependent manner. Thus, the SMAP gene family constitutes an important ArfGAP subfamily, with each SMAP member exerting both common and distinct functions in vesicle trafficking.
RINT-1 Regulates the Localization and Entry of ZW10 to the Syntaxin 18 Complex
Authors: Arasaki Kohei , Taniguchi May , Tani Katsuko , Tagaya Mitsuo
Published: March 2006

RINT-1 was first identified as a Rad50-interacting protein that participates in radiation-induced G2/M checkpoint control. We have recently reported that RINT-1, together with the dynamitin-interacting protein ZW10 and others, is associated with syntaxin 18, an endoplasmic reticulum (ER)-localized SNARE involved in membrane trafficking between the ER and Golgi. To address the role of RINT-1 in membrane trafficking, we examined the effects of overexpression and knockdown of RINT-1 on Golgi morphology and protein transport from the ER. Overexpression of the N-terminal region of RINT-1, which is responsible for the interaction with ZW10, caused redistribution of ZW10. Concomitantly, ER-to-Golgi transport was blocked and the Golgi was dispersed. Knockdown of RINT-1 also disrupted membrane trafficking between the ER and Golgi. Notably, silencing of RINT-1 resulted in a reduction in the amount of ZW10 associated with syntaxin 18, concomitant with ZW10 redistribution. In contrast, no redistribution or release of RINT-1 from the syntaxin 18 complex was observed when ZW10 expression was reduced. These results taken together suggest that RINT-1 coordinates the localization and function of ZW10 by serving as a link between ZW10 and the SNARE complex comprising syntaxin 18.
The Function and Regulation of Budding Yeast Swe1 in Response to Interrupted DNA Synthesis
Authors: Liu Hong , Wang Yanchang
Published: March 2006

Periodically regulated cyclin-dependent kinase (Cdk) is required for DNA synthesis and mitosis. Hydroxyurea (HU) inhibits DNA synthesis by depleting dNTPs, the basic unit for DNA synthesis. HU treatment triggers the S-phase checkpoint, which arrests cells at S-phase, inhibits late origin firing and stabilizes replication forks. Using budding yeast as a model system, we found that Swe1, a negative regulator of Cdk, appears at S-phase and accumulates in HU treatment cells. Interestingly, this accumulation is not dependent on S-phase checkpoint. Δhsl1, Δhsl7, and cdc5-2 mutants, which have defects in Swe1 degradation, show HU sensitivity because of high Swe1 protein levels. We further demonstrated that their HU sensitivity is not a result of DNA damage accumulation or incomplete DNA synthesis; instead the sensitivity is due to their dramatically delayed recovery from HU-induced S-phase arrest. Strikingly, our in vivo data indicate that Swe1 inhibits the kinase activity of Clb2-Cdk1, but not that of Clb5-Cdk1. Therefore, S-phase accumulated Swe1 prevents Clb2-Cdk1–mediated mitotic activities, but has little effects on Clb5-Cdk1–associated S-phase progression.
Involvement of Akt in ER-to-Golgi Transport of SCAP/SREBP: A Link between a Key Cell Proliferative Pathway and Membrane Synthesis
Authors: Du Ximing , Kristiana Ika , Wong Jenny , Brown Andrew J.
Published: March 2006

Akt is a critical regulator of cell growth, proliferation, and survival that is activated by phosphatidylinositol 3-kinase (PI3K). We investigated the effect of PI3K inhibition on activation of sterol regulatory element binding protein-2 (SREBP-2), a master regulator of cholesterol homeostasis. SREBP-2 processing increased in response to various cholesterol depletion approaches (including statin treatment) and this increase was blunted by treatment with a potent and specific inhibitor of PI3K, LY294002, or when a plasmid encoding a dominant-negative form of Akt (DN-Akt) was expressed. LY294002 also suppressed SREBP-2 processing induced by insulin-like growth factor-1. Furthermore, LY294002 treatment down-regulated SREBP-2 or -1c gene targets and decreased cholesterol and fatty acid synthesis. Fluorescence microscopy studies indicated that LY294002 disrupts transport of the SREBP escort protein, SCAP, from the endoplasmic reticulum to the Golgi. This disruption was also shown by immunofluorescence staining when DN-Akt was expressed. Taken together, our studies indicate that the PI3K/Akt pathway is involved in SREBP-2 transport to the Golgi, contributing to the control of SREBP-2 activation. Our results provide a crucial mechanistic link between the SREBP and PI3K/Akt pathways that may be reconciled teleologically because synthesis of new membrane is an absolute requirement for cell growth and proliferation.
Engrailed-1 Negatively Regulates β-Catenin Transcriptional Activity by Destabilizing β-Catenin via a Glycogen Synthase Kinase-3β–independent Pathway
Authors: Bachar-Dahan Liora , Goltzmann Janna , Yaniv Abraham , Gazit Arnona
Published: March 2006

The Wnt signaling pathway plays a major role in development, and upon deregulation it is implicated in neoplasia. The hallmark of the canonical Wnt signal is the protection of β-catenin from ubiquitination and proteasomal degradation induced by glycogen synthase kinase (GSK)-3β inhibition. The stabilized β-catenin translocates to the nucleus where it binds to T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors, activating the expression of Wnt target genes. In the absence of Wnt signal, TCF/LEF bind to Groucho (Gro)/TLE corepressors and repress Wnt target genes. Gro/TLE bind also to Engrailed (En) transcription factors mediating En-repressive activity on En target genes. Here, we present data suggesting that En-1 serves also as a negative regulator of β-catenin transcriptional activity; however, its repressive effect is independent of Gro/TLE. Our data suggest that En-1 acts by destabilizing β-catenin via a proteasomal degradation pathway that is GSK-3β–independent. Moreover, because En-1-mediated β-catenin degradation is also Siah independent, our data imply that En-1 exerts its repressive effect by a novel mechanism negatively controlling the level of β-catenin.
Disruption of the A-Kinase Anchoring Domain in Flagellar Radial Spoke Protein 3 Results in Unregulated Axonemal cAMP-dependent Protein Kinase Activity and Abnormal Flagellar Motility
Authors: Gaillard Anne R. , Fox Laura A. , Rhea Jeanne M. , Craige Branch , Sale Winfield S.
Published: March 2006

Biochemical studies of Chlamydomonas flagellar axonemes revealed that radial spoke protein (RSP) 3 is an A-kinase anchoring protein (AKAP). To determine the physiological role of PKA anchoring in the axoneme, an RSP3 mutant, pf14, was transformed with an RSP3 gene containing a mutation in the PKA-binding domain. Analysis of several independent transformants revealed that the transformed cells exhibit an unusual phenotype: a fraction of the cells swim normally; the remainder of the cells twitch feebly or are paralyzed. The abnormal/paralyzed motility is not due to an obvious deficiency of radial spoke assembly, and the phenotype cosegregates with the mutant RSP3. We postulated that paralysis was due to failure in targeting and regulation of axonemal cAMP-dependent protein kinase (PKA). To test this, reactivation experiments of demembranated cells were performed in the absence or presence of PKA inhibitors. Importantly, motility in reactivated cell models mimicked the live cell phenotype with nearly equal fractions of motile and paralyzed cells. PKA inhibitors resulted in a twofold increase in the number of motile cells, rescuing paralysis. These results confirm that flagellar RSP3 is an AKAP and reveal that a mutation in the PKA binding domain results in unregulated axonemal PKA activity and inhibition of normal motility.
The Enforcement of Jurisdiction Agreements Within The Brussels Regime
Authors: Merrett Louise
Published: March 2006

Until relatively recently the question of whether it is possible to get damages for breach of an exclusive jurisdiction clause was very rarely considered by the courts and had attracted little academic interest. But when considered alongside recent developments in cases covered by the Brussels regime, the subject becomes of potentially much greater practical significance. The main purpose of this article is to consider how the newly developing common law principles might apply in that context.
Legal Implications Of Australia's Maritime Indentification System
Authors: Klein Natalie
Published: March 2006

On 14 December 2004, Australia announced the institution of a ‘Maritime Identification Zone’, extending 1000 nautical miles from its coast and involving the identification of vessels seeking to enter Australian ports, as well as vessels transiting Australia' Exclusive Economic Zone. This Article analyses the legality of these security measures under the UN Convention on the Law of the Sea, new developments through the International Maritime Organization and the Proliferation Security Initiative. The implications of prescribing and enforcing identification requirements on the high seas and in the EEZ, the impact on maritime boundaries and avenues for dispute settlement are all explored.
In Defence of State Immunity: Why the UN: Convention on State Immunity is Important
Authors: Fox Hazel
Published: March 2006

The Convention on State Immunity adopted by the UN General Assembly in 2004 represents in treaty form a finished product of some 22 years of work 1 It indicates a consensus of State support for the restrictive doctrine of State immunity in its application to civil proceedings relating to commercial matters in national courts. It is a considerable achievement from the view point of the specialist lawyers and diplomats who have steered the project to UN endorsement.
UN Convention on State Immunity: the Need for a Human Rights Protocol
Authors: Hall Christopher Keith
Published: March 2006

The United Kingdom (UK) signed the UN Convention on Jurisdictional Immunities of States and their property (Convention) less than a year after it was adopted by the UN General Assembly.1 The signature came only a few months after an open, but not well publicized, consultation with academics and society,2 and several months before a crucial appeal, in which the Secretary of State for Constitutional Affairs is a party, is heard by the House of Lords of a decision permitting a civil suit to proceed against foreign government officials for torture committed abroad.3 Despite the signature, the UK has not yet announced whether it will ratify the Convention and, if so, whether it intends to do so with an understanding, declaration or reservation.4 As discussed below, it appears that the Convention might preclude victims of genocide, crimes against humanity, war crimes, torture and other crimes under international law, as well as other human rights violations, committed abroad from recovering civil reparations in UK courts against states or their current of former officials or agents. In the light of the numerous ambiguities in the Convention and the risk that it will be interpreted by national courts as barring such reparations in those courts, the UK should not ratify it until a protocol is adopted expressly guaranteeing victims and their families the right to recover reparations in such cases.
State Immunity Jus Cogens
Authors: McGregor Lorna
Published: March 2006

The General Assembly first proposed that the International Law Commission look into the issue of state immunity in 1977. As State immunity, by its very nature, sits at the interface between traditional and contemporary notions of international law, the span of the negotiations over three decades inevitably exposed the resulting Convention to gaps and inconsistencies with evolving areas of international law. In 1999 the International Law Commission established a Working Group on Jurisdictional immunities of States and their property,
III. Social Policy
Authors: Szyszczak Erika
Published: March 2006

Social policy is undergoing review, the aim being to consolidate the fragmented nature of social policy law, and to provide for the integration of all Community policies. This is part of a larger where the EU is attempting to provide a holistic approach towards all policies, ensuring that they meet the demands placed upon governments, as well as private undertakings, in the enlarged single market. Of particular significance is the interaction between social policy law and competition law, especially in relation to state aid and merger policy. The Lisbon Process, now at mid-term, has not been successful in delivering the projected results. Thus throughout 2005 the European Union focused upon revitalizing the Lisbon agenda with the focus upon improving the quality of work as well as combating unemployment.1
Titration of Propofol for Anesthetic Induction and Maintenance Guided by the Bispectral Index: Closed-loop versus Manual Control
Authors: Liu Ngai , Chazot Thierry , Genty Antoine , Landais Alain , Restoux Aymeric , McGee Kathleen , Laloë Pierre-Antoine , Trillat Bernard , Barvais Luc , Fischler Marc
Published: March 2006

Background

This report describes a closed-loop titration of propofol target control infusion based on a proportional-differential algorithm guided by the Bispectral Index (BIS) allowing induction and maintenance of general anesthesia and compares this to manual propofol target control infusion.

Methods

One hundred sixty-four patients scheduled to undergo elective minor or major surgery were prospectively randomized in a multicenter study into the closed-loop (n = 83) or manual target control infusion group (n = 81). The goal was to reach a BIS target of 50 during induction and to maintain it between 40 and 60 during maintenance. For both groups, remifentanil target control infusion was adjusted manually, and ventilation was without nitrous oxide.

Results

Closed-loop control was able to provide anesthesia induction and maintenance for all patients. During induction, propofol consumption was lower in the closed-loop group (1.4 +/- 0.5 vs. 1.8 +/- 0.6 mg/kg; P < 0.0001), but the duration was longer (320 +/- 125 vs. 271 +/- 120 s; P < 0.0002). Adequate anesthesia maintenance, defined as the BIS in the range of 40-60, was significantly higher in the closed-loop group (89 +/- 9 vs. 70 +/- 21%; P < 0.0001), with a decrease of the occurrence of BIS less than 40 (8 +/- 8 vs. 26 +/- 22%; P < 0.0001). Time from discontinuation of propofol infusion to tracheal extubation was shorter in the closed-loop group (7 +/- 4 vs. 10 +/- 7 min; P < 0.017). Unwanted somatic events and hemodynamic instability were similar.

Conclusion

Automatic control of consciousness using the BIS is clinically feasible and outperforms manual control.
Spectral Entropy as a Measure of Hypnosis in Children
Authors: Klockars Jaakko G. M. , Hiller Arja , Ranta Seppo , Talja Pia , van Gils Mark J. , Taivainen Tomi
Published: March 2006

Background

The Datex-Ohmeda S/5 Entropy Module (Datex-Ohmeda Division, Instrumentarium Corp., Helsinki, Finland), using time-frequency balanced Spectral Entropy, is a novel tool for monitoring the hypnotic state during anesthesia. The Entropy Module produces two values, State Entropy (SE) and Response Entropy (RE), and in adults, it has been shown to measure reliably the hypnotic effects of various drugs. In children, Spectral Entropy has been only preliminary studied. The authors' aim was to study Spectral Entropy as a marker of hypnotic state during general anesthesia in infants and children.

Methods

Twenty infants (aged 1 month-1 yr) and 40 children (aged 1-15 yr) were anesthetized for surgery using standardized sevoflurane-nitrous oxide-based anesthesia. The relationships between SE, RE, or Bispectral Index (BIS) and (1) a modified Observer's Assessment of Alertness/Sedation Scale, (2) non-steady state end-tidal concentration of sevoflurane, (3) steady state end-tidal concentration of sevoflurane, and (4) hemodynamic values were calculated using prediction probability, nonlinear regression, and correlation coefficients, as appropriate. The performances of SE, RE, and BIS were compared.

Results

The prediction probability values (+/- SEM) of SE, RE, and BIS versus the modified Observer's Assessment of Alertness/Sedation Scale in the induction phase were 0.83 +/- 0.06, 0.88 +/- 0.06, and 0.87 +/- 0.08 for children and 0.76 +/- 0.08,0.79 +/- 0.08, and 0.73 +/- 0.10 for infants; values in the emergence phase were 0.68 +/- 0.05, 0.74 +/- 0.04, and 0.64 +/- 0.05 for children and 0.64 +/- 0.07, 0.69 +/- 0.06, and 0.72 +/- 0.06 for infants, respectively. SE, RE, and BIS values were inversely proportionally related to the end-tidal concentration of sevoflurane for children, but for infants, the correlation was much less clear. No significant correlations were found between SE, RE, or BIS values and the hemodynamic values.

Conclusions

Spectral Entropy may be a useful tool for measuring the level of hypnosis in anesthetized children and seems to perform as well as BIS. In infants, the clinical usefulness of both these electroencephalogram-derived methods must be evaluated in further controlled studies.
Propofol Increases Presynaptic Inhibition of Ia Afferents in the Intact Human Spinal Cord
Authors: Baars Jan H. , von Dincklage Falk , Reiche Josephine , Rehberg Benno
Published: March 2006

Background

In vitro studies indicate that the primary molecular targets of propofol in the spinal cord are gamma-aminobutyric acid (GABA) type A receptors. Because of the complexity of the central nervous system, specific GABA-mediated effects have not yet been isolated in humans. Here, the authors used heteronymous Ia facilitation of the soleus H-reflex from the femoral nerve as a specific pathway involving GABA to demonstrate a presynaptic GABA-mediated effect of propofol in humans.

Methods

The study was performed in 10 volunteers aged 23-32 yr. The soleus H-reflex was evoked by stimulation of the tibial nerve in the popliteal fossa. The stimulation current was adjusted to yield an unconditioned H-reflex of 15% of the maximal muscle response to electric stimulation of the tibial nerve. The soleus H-reflex was conditioned by stimulating Ia afferents from the quadriceps femoris in the femoral triangle. The stimulus was applied 0.3-0.4 ms after the onset of facilitation, to assure a purely monosynaptic excitatory postsynaptic potential from quadriceps Ia afferents to the soleus motoneuron. At least 45 conditioned (femoral and tibial) and unconditioned (only tibial) stimuli were applied in random order. The authors compared the amount of heteronymous H-reflex facilitation under a concentration of 2 microg/ml propofol with control values obtained before and after the propofol infusion.

Results

H-reflex facilitation due to the conditioning stimulus during propofol administration was significantly (P < 0.05, t test) decreased by an average of 43% in all patients in comparison with the control values.

Conclusions

Although alternative explanations such as supraspinal effects cannot be ruled out completely, the findings of this study are most likely explained by a specific presynaptic effect of propofol. Strong evidence form neurophysiologic studies indicates that this effect is mediated by the GABA type A receptors.
Analgesic Treatment after Laparoscopic Cholecystectomy
Authors: Bisgaard Thue , Warltier David C.
Published: March 2006

Acute pain after laparoscopic cholecystectomy is complex in nature. The pain pattern does not resemble pain after other laparoscopic procedures, suggesting that analgesic treatment might be procedure specific and multimodal. Randomized trials of analgesia after laparoscopic cholecystectomy were identified by systematic electronic literature searches (1985 to June 2005) supplemented with manual searching. The trials were categorized by well-defined criteria into high, moderate, or poor methodologic quality. Conclusions were based on trials of high and moderate methodologic quality. In total, 64 randomized analgesic trials were identified, comprising a total of 5,018 evaluated patients. The literature suggests a multimodal analgesic regimen consisting of a preoperative single dose of dexamethasone, incisional local anesthetics (at the beginning or at the end of surgery, depending on preference), and continuous treatment with nonsteroidal antiinflammatory drugs (or cyclooxygenase-2 inhibitors) during the first 3-4 days. Opioids should be used only when other analgesic techniques fail.