bluuebunny/crossref_metadata_2025 huggingface dataset:
Clarinet laser: Semiconductor laser design for high-brightness applications
Authors: Borruel Luis , Esquivias Ignacio , Moreno Pablo , Krakowski Michel , Auzanneau Sophie Charlotte , Calligaro Michel , Parillaud Olivier , Lecomte Michel , Sujecki Slawomir , Wykes Jim , Larkins Eric C.
Published: August 2005

High-power and high-brightness continuous-wave (cw) operation has been achieved with an optimized design of fully index-guided tapered laser emitting at 975 nm. The device achieves simultaneously negligible astigmatism and stable low divergence in the lateral axis at high-power operation. By using a quasi-three-dimensional simulation model, the different mechanisms modifying the slow axis beam divergence at high power have been carefully balanced in the clarinet design, easing the use of collective optics in laser bars. The devices consist of a relatively long ridge-waveguide filtering section coupled to a relatively short tapered section with an aperture angle of 2°. InGaAs∕InGaAsP lasers were fabricated with this design, demonstrating an output power of 1 W cw, a maximum wall-plug efficiency of 50%, negligible astigmatism, a slow-axis far-field divergence (measured at 1∕e2) of 5° at 1 W and beam quality parameter M2<3.
Annealing effects on the loss and birefringence of silicon oxynitride rectangular optical waveguides
Authors: Zhang Ailing , Chan Kam Tai , Demokan M. S. , Chan Victor W. C. , Chan Philip C. H. , Chan Andy H. P.
Published: August 2005

Silicon oxynitride rectangular optical waveguides have been fabricated by plasma-enhanced chemical vapor deposition and dry etching. The propagation loss and polarization dependent loss in as-grown samples show a substantial reduction after the samples have been annealed. Birefringence measurements before and after annealing on waveguides of different widths suggest that the waveguide modal birefringence is strongly affected by both waveguide geometry and stress in the material. Hence, the modal birefringence can be minimized by designing the appropriate waveguide geometry to compensate for any stress effects.
Free-volume evolution and its temperature dependence during rolling of Cu60Zr20Ti20 bulk metallic glass
Authors: Cao Q. P. , Li J. F. , Zhou Y. H. , Horsewell A. , Jiang J. Z.
Published: August 2005

The free-volume evolution during rolling Cu60Zr20Ti20 bulk metallic glass at room and cryogenic temperatures has been investigated by differential scanning calorimetry. When the specimen is rolled at cryogenic temperature, the free-volume content increases as the rolling proceeds first, and then saturates accompanied by the occurrence of phase separation as the thickness reduction exceeds 89%. If the rolling is performed at room temperature, although the free-volume content also rises in the earlier stage, it tends to decrease rather than saturate when the thickness reduction exceeds 87%, accompanied by partial crystallization. Phase separation does not change the annihilation rate of free volume, while the appearance of crystal/amorphous boundaries can enhance the annihilation.
Electrically tunable ferrite-ferroelectric microwave delay lines
Authors: Fetisov Y. K. , Srinivasan G.
Published: August 2005

The electric field control of delay time is observed in a ferrite-ferroelectric microwave delay line. A microstrip delay line with a bilayer of (111) yttrium iron garnet film and (001) lead magnesium niobate-lead titanate (PMN-PT) is studied. A 10–25% variation in delay time is measured when the electric field applied to the PMN-PT layer is increased from 0 to 8kV∕cm. The tunability is attributed to variations in the permittivity for PMN-PT in an electric field and its effect on the dispersion characteristics of hybrid spin electromagnetic waves that are excited in the bilayer.
Nonlinear current-voltage curves of gold quantum point contacts
Authors: Yoshida M. , Oshima Y. , Takayanagi K.
Published: August 2005

Nonlinear current-voltage (I-V) curves of gold quantum point contacts (QPC) were investigated using a transmission electron microscope–scanning tunneling microscope system. The I-V curves were measured by sweeping the bias voltage from 0 to 0.3 V at room temperature under ultrahigh vacuum. The results revealed that when the QPC formed a short nanowire, a nonlinear I-V curve was observed, while a long nanowire produced a linear I-V curve. The nonlinear I-V curves were found to be caused by a nanowire thickening that occurred during increases of the bias voltage. This thickening resulted from a shortened distance between electrodes.
A new inverted pendulum to determine anelastic behavior of metals: Design and characterization
Authors: Yagmur Levent , Gulmez Turgut , Hacizade Fikret , Kacmaz Sevda
Published: August 2005

An inverted pendulum with a copper-beryllium (Cu-Be) flexure element was designed and its performance was determined by detecting the respective angular changes of the pendulum using a CCD (charge-coupled device) camera within an oscillation period range of 2-30s. An arrangement was made by clamping the flexure element and pendulum rod to avoid subjecting them to compression stress due to the weight of the overall pendulum mass on the flexure. This form of inverted pendulum employs a flexure specially clamped to the pendulum rod to provide tension deformation under the weight of the mass and could be used for dynamic testing of highly sensitive flexure elements. The quality factors of the pendulum were determined with respect to flexure elements by measuring free oscillations decaying exponentially. The results showed that the inverted pendulum with a different connection between the flexure element, and pendulum rod can be used to measure the anelasticity of materials and to test elements under bending deformation in a dynamic way.
Time relaxation of ac susceptibility on very short time scales
Authors: Živković Ivica , Drobac Ðuro , Prester Mladen
Published: August 2005

We present an experimental method enabling measurements of time dependence of ac susceptibility down to 1 ms after a steplike change of the applied dc magnetic field. An analog-digital converter has been used to collect the transient of the current, signaling the change of the dc magnetic field. The time window for investigation of magnetic time relaxation phenomena, as studied by the ac susceptibility technique, thus has been expanded in the range of short time scales for three orders of magnitudes.
Effects of long-term ionic and osmotic stress conditions on photosynthesis in the cyanobacterium Synechocystis sp. PCC 6803
Authors: Jantaro Saowarath , Mulo Paula , Jansén Tove , Incharoensakdi Aran , Mäenpää Pirkko
Published: August 2005

Salinity is considered to be one of the most severe problems in worldwide agricultural production, but the published investigations give contradictory results of the effect of ionic and osmotic stresses on photosynthesis. In the present study, long-term effects of both ionic and osmotic stresses, especially on photosynthesis, were investigated using the moderately halotolerant cyanobacterium Synechocystis sp. PCC 6803. Our results show that the PSII activity and the photosynthetic capacity tolerated NaCl but a high concentration of sorbitol completely inhibited both activities. In line with these results, we show that the amount of the D1 protein of PSII was decreased under severe osmotic stress, whereas the levels of PsaA / B and NdhF3 proteins remained unchanged. However, high concentrations of sorbitol stress led to a drastic decrease of both psbA (encoding D1) and psaA (encoding PsaA) transcripts, suggesting that severe osmotic stress may abolish the tight coordination of transcription and translation normally present in bacteria, at least in the case of the psaA gene. Taken together, our results indicate that the osmotic stress component is more detrimental to photosynthesis than the ionic one and, furthermore, under osmotic stress, the D1 protein appears to be the target of this stress treatment.
Binding of 3-phosphoglycerate leads to both activation and stabilisation of ADP-glucose pyrophosphorylase from apple leaves
Authors: Zhou Rui , Cheng Lailiang
Published: August 2005

Apple leaf ADP-glucose pyrophosphorylase was purified 1436-fold to apparent homogeneity with a specific activity of 58.9 units mg–1. The enzyme was activated by 3-phosphoglycerate (PGA) and inhibited by inorganic phosphate (Pi) in the ADPG synthesis direction. In the pyrophosphorolytic direction, however, high concentrations of PGA (> 2.5 mm) inhibited the enzyme activity. The enzyme was resistant to thermal inactivation with a T0.5 (temperature at which 50% of the enzyme activity is lost after 5 min incubation) of 52°C. Incubation with 2 mm PGA or 2 mm Pi increased T0.5 to 68°C. Incubation with 2 mm dithiothreitol (DTT) decreased T0.5 to 42°C, whereas inclusion of 2 mm PGA in the DTT incubation maintained T0.5 at 52°C. DTT-induced decrease in thermal stability was accompanied by monomerisation of the small subunits. Presence of PGA in the DTT incubation did not alter the monomerisation of the small subunits of the enzyme induced by DTT. These findings indicate that binding of PGA renders apple leaf AGPase with a conformation that is not only more efficient in catalysis but also more stable to heat treatment. The physiological significance of the protective effect of PGA on thermal inactivation of AGPase is discussed.
Characteristics of CO2 exchange between peach stems and the atmosphere
Authors: Alessio Giorgio A. , Pietrini Fabrizio , Brilli Federico , Loreto Francesco
Published: August 2005

Gas exchange by stems is dominated by respiratory CO2 emission, but photosynthetic CO2 uptake might also occur in stem bark. We show that light-dependent CO2 uptake was present and often exceeded CO2 release by respiration in illuminated current-year peach (Prunus persica L.) stems. Respiration of peach stems, as detected by 12CO2 release into air in which the natural concentration of 12CO2 was replaced with 13CO2, was lower in the light than in the dark, but this accounted for only a fraction of the observed total CO2 uptake by illuminated stems. Stem photosynthesis was saturated at low light and was negatively affected by elevated assay temperatures (30°C), especially when combined with light intensities above saturation. An inefficient mechanism of heat dissipation by transpiration in stomata-free stems might help explain this effect. Photosynthesis was rapidly stimulated and the electron transport rate was reduced when photorespiration was suppressed by exposure to low (2 kPa) oxygen. The time-course of these changes was closely associated with a transient burst of CO2 uptake concurrent with a reduced inhibition of fluorescence yield. Photosynthesis was also stimulated by exposure to elevated (twice ambient) CO2 concentration. These combined measurements of gas exchange and fluorescence suggested that (a) photorespiration may also be active in the bark of peach stems, (b) O2 and CO2 concentrations in the bark of peach stems may be similar to ambient concentrations, (c) a large amount of electron transport unrelated to photosynthesis and photorespiration may also be present in peach stems, and (d) stem photosynthesis may be enhanced under future atmospheric conditions.
Rapid and efficient production of transgenic bermudagrass and creeping bentgrass bypassing the callus formation phase
Authors: Wang Zeng-Yu , Ge Yaxin
Published: August 2005

Callus culture has been an inevitable step in genetic transformation of monocotyledonous (monocot) species. The induction and maintenance of embryogenic calluses is time-consuming, laborious and also requires experience. A straightforward and callus-free transformation procedure was developed and demonstrated for two monocot species, bermudagrass (Cynodon spp.) and creeping bentgrass (Agrostis stolonifera). Stolon nodes were infected and co-cultivated with Agrobacterium tumefaciens harboring pCAMBIA or pTOK233 binary vectors. Green shoots were directly produced from infected stolon nodes 4–5 weeks after hygromycin selection. Without callus formation and with minimum tissue culture, this procedure allowed us to obtain well-rooted transgenic plantlets in only 7 weeks and greenhouse-grown plants in only 9 weeks. The established plants were screened by PCR; the transgenic nature of the plants was demonstrated by Southern hybridisation analysis. Expression of the transgenes was confirmed by northern hybridisation analysis and GUS staining. Based on the number of transgenic plants obtained and the number of stolon nodes inoculated, transformation frequencies of 4.8%–6.1% and 6.3%–11.3% were achieved for bermudagrass and creeping bentgrass, respectively. The rapid and efficient production of transgenic plants without callus induction is a significant improvement for genetic transformation of monocot species.
Protein “fingerprinting” in complex mixtures with peptoid microarrays
Authors: Reddy M. Muralidhar , Kodadek Thomas
Published: August 2005

We report here that microarrays comprised of several thousand peptoids (oligo-
N
-substituted glycines) are useful tools for the identification of proteins via a “fingerprinting” approach. By using maltose-binding protein, glutathione
S
-transferase, and ubiquitin, a specific and highly reproducible pattern of binding was observed when fluorescently labeled protein was hybridized to the array. A similar pattern was obtained when binding of an unlabeled protein to the array was visualized by secondary hybridization of a labeled antibody against that protein, showing that native proteins can be identified without the requirement for prior chemical labeling. This work suggests that small-molecule microarrays might be used for more complex fingerprinting assays of potential diagnostic value.
Flagellin induces innate immunity in nonhost interactions that is suppressed by
Pseudomonas syringae
effectors
Authors: Li Xinyan , Lin Huiqiong , Zhang Weiguo , Zou Yan , Zhang Jie , Tang Xiaoyan , Zhou Jian-Min
Published: August 2005

Arabidopsis NONHOST1
(
NHO1
) is required for limiting the
in planta
growth of nonhost
Pseudomonas
bacteria but completely ineffective against the virulent bacterium
Pseudomonas syringae
pv.
tomato
DC3000. However, the molecular basis underlying this observation remains unknown. Here we show that
NHO1
is transcriptionally activated by flagellin. The nonhost bacterium
P. syringae
pv.
tabaci
lacking flagellin is unable to induce
NHO1
, multiplies much better than does the wild-type bacterium, and causes disease symptoms on
Arabidopsis
. DC3000 also possesses flagellin that is potent in
NHO1
induction, but this induction is rapidly suppressed by DC3000 in a type III secretion system-dependent manner. Direct expression of DC3000 effectors in protoplasts indicated that at least nine effectors, HopS1, HopAI1, HopAF1, HopT1-1, HopT1-2, HopAA1-1, HopF2, HopC1, and AvrPto, are capable of suppressing the flagellin-induced
NHO1
expression. One of the effectors, HopAI1, is conserved in both animal and plant bacteria. When expressed in transgenic
Arabidopsis
plants, HopAI1 promotes growth of the nonpathogenic
hrpL
-
mutant bacteria. In addition, the purified phytotoxin coronatine, a known virulence factor of
P. syringae
, suppresses the flagellin-induced
NHO1
transcription. These results demonstrate that flagellin-induced defenses play an important role in nonhost resistance. A remarkable number of DC3000 virulence factors act in the plant cell by suppressing the species level defenses, and that contributes to the specialization of DC3000 on
Arabidopsis
.
The adjunction problem over torsion-free groups
Authors: Forester Max , Rourke Colin
Published: August 2005

We prove injectivity and relative asphericity for “layered” systems of equations over torsion-free groups, when the exponent matrix is invertible over

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.
Arabidopsis
TCP20 links regulation of growth and cell division control pathways
Authors: Li Chengxia , Potuschak Thomas , Colón-Carmona Adán , Gutiérrez Rodrigo A. , Doerner Peter
Published: August 2005

During postembryonic plant development, cell division is coupled to cell growth. There is a stringent requirement to couple these processes in shoot and root meristems. As cells pass through meristems, they transit through zones with high rates of cell growth and proliferation during organogenesis. This transition implies a need for coordinate regulation of genes underpinning these two fundamental cell functions. Here, we report a mechanism for coregulation of cell division control genes and cell growth effectors. We identified a GCCCR motif necessary and sufficient for high-level cyclin
CYCB1;1
expression at G
2
/M. This motif is overrepresented in many ribosomal protein gene promoters and is required for high-level expression of the S27 and L24 ribosomal subunit genes we examined. p33
TCP20
, encoded by the
Arabidopsis TCP20
gene, binds to the GCCCR element in the promoters of cyclin
CYCB1;1
and ribosomal protein genes
in vitro
and
in vivo
. We propose a model in which organ growth rates, and possibly shape in aerial organs, are regulated by the balance of positively and negatively acting teosinte-branched, cycloidea, PCNA factor (TCP) genes in the distal meristem boundary zone where cells become mitotically quiescent before expansion and differentiation.
Tumor-specific targeting of an anticancer drug delivery system by LHRH peptide
Authors: Dharap S. S. , Wang Y. , Chandna P. , Khandare J. J. , Qiu B. , Gunaseelan S. , Sinko P. J. , Stein S. , Farmanfarmaian A. , Minko T.
Published: August 2005

The central problem in cancer chemotherapy is the severe toxic side effects of anticancer drugs on healthy tissues. Invariably the side effects impose dose reduction, treatment delay, or discontinuance of therapy. To limit the adverse side effects of cancer chemotherapy on healthy organs, we proposed a drug delivery system (DDS) with specific targeting ligands for cancer cells. The proposed DDS minimizes the uptake of the drug by normal cells and enhances the influx and retention of the drug in cancer cells. This delivery system includes three main components: (
i
) an apoptosis-inducing agent (anticancer drug), (
ii
) a targeting moiety-penetration enhancer, and (
iii
) a carrier. We describe one of the variants of such a system, which utilizes camptothecin as an apoptosis-inducing agent and poly(ethylene glycol) as a carrier. Luteinizing hormone-releasing hormone (LHRH) was used as a targeting moiety (ligand) to LHRH receptors that are overexpressed in the plasma membrane of several types of cancer cells and are not expressed detectably in normal visceral organs. The results showed that the use of LHRH peptide as a targeting moiety in the anticancer DDS substantially enhanced the efficacy of chemotherapy, led to amplified apoptosis induction in the tumor, and minimized the side effects of the anticancer drug on healthy organs. The LHRH receptor targeting DDS did not show
in vivo
pituitary toxicity and did not significantly influence the time course or the plasma concentration of luteinizing hormone and its physiological effects on the reproductive functions of mice.
Interferon function is not required for recovery from a secondary poxvirus infection
Authors: Panchanathan Vijay , Chaudhri Geeta , Karupiah Gunasegaran
Published: August 2005

IFN function is critical for recovery from most primary viral infections, including poxvirus infection. In contrast, very little is known about the requirement for IFN function in mediating recovery from a secondary virus infection. We have used ectromelia virus (ECTV), an orthopoxvirus very closely related to variola virus, to investigate the importance of IFN function in recovery from a secondary infection. Variola virus, the causative agent of smallpox in humans, and ECTV, which causes mousepox in mice, both encode receptor homologs that are thought to interfere with host IFN function. Using a prime-challenge regime, in which avirulent ECTV is used to prime mice deficient in type I/II IFN function or IFN regulatory factor 1 (IRF-1) and then challenging the mice with a virulent strain, we show that IFN function is redundant for virus clearance during a secondary ECTV infection. A neutralizing Ab response is generated in a secondary infection, even in the absence of IFN function, although when present, IFN strongly influences the neutralizing titer and subtype of IgG that is produced. Importantly, the depletion of CD8
+
T lymphocytes during a secondary challenge in IFN-deficient mice does not affect their capacity to clear ECTV, indicating that Ab is critical for the control of a secondary infection.
A third Na
+
-binding site in the sodium pump
Authors: Li Ciming , Capendeguy Oihana , Geering Käthi , Horisberger Jean-Daniel
Published: August 2005

The sodium pump, or Na,K-ATPase, exports three intracellular sodium ions in exchange for two extracellular potassium ions. In the high resolution structure of the related calcium pump, two cation-binding sites have been identified. The two corresponding sites in the sodium pump are expected to be alternatively occupied by sodium and potassium. The position of a third sodium-specific site is still hypothetical. Here, we report the large effects of single residue substitutions on the voltage-dependent kinetics of the release of sodium to the extracellular side of the membrane. These mutations also alter the apparent affinity for intracellular sodium while one of them does not affect the intrinsic affinity for potassium. These results enable us to locate the third sodium-specific site of the sodium pump in a space between the fifth, sixth, and ninth transmembrane helices of the α-subunit and provide an experimental validation of the model proposed by Ogawa and Toyoshima [Ogawa, H. & Toyoshima, C. (2002)
Proc. Natl. Acad. Sci. USA
99, 15977–15982].
Sequence conservation, relative isoform frequencies, and nonsense-mediated decay in evolutionarily conserved alternative splicing
Authors: Baek Daehyun , Green Phil
Published: August 2005

Studies of expressed sequence tag data sets have revealed large numbers of splicing variants for human genes, but it remains challenging to distinguish functionally important variants from aberrant splicing, clarify the nature of the alternative functions, and understand the signals that regulate splicing choices. To help address these issues, we have constructed and analyzed a large data set of 1,478 exon-skipping alternative splicing (AS) variants evolutionarily conserved in human and mouse. In about one-fifth of cases, one isoform appears subject to nonsense-mediated mRNA decay (NMD), supporting the idea that a major role of AS is to regulate gene expression; one-quarter of these NMD-inducing cases involve a conserved exon whose apparent sole purpose is to mediate destruction of the message when included. We explore sequence conservation likely related to splicing regulation, using in part a measure of the overall amount of conserved information in a sequence, and find that the increased conservation that has been observed within AS exons primarily affects synonymous sites, suggesting that regulatory signals significantly constrain synonymous substitution rates. We show that a lower frequency of the inclusion isoform relative to the exclusion isoform tends to be associated with weaker splice site signals, smaller exon size, and higher intronic sequence conservation, and provide evidence that all of these factors are under selection to control relative isoform frequencies. Some conserved instances of AS appear to represent aberrant splicing events that by chance have occurred in both species, and we develop a nonparametric likelihood approach to identify these.
A loop 2 cytidine-stem 1 minor groove interaction as a positive determinant for pseudoknot-stimulated –1 ribosomal frameshifting
Authors: Cornish Peter V. , Hennig Mirko , Giedroc David P.
Published: August 2005

The molecular determinants of stimulation of –1 programmed ribosomal frameshifting (–1 PRF) by RNA pseudoknots are poorly understood. Sugarcane yellow leaf virus (ScYLV) encodes a 28-nt mRNA pseudoknot that promotes –1 PRF between the P1 (protease) and P2 (polymerase) genes in plant luteoviruses. The solution structure of the ScYLV pseudoknot reveals a well ordered loop 2 (L2) that exhibits continuous stacking of A20 through C27 in the minor groove of the upper stem 1 (S1), with C25 flipped out of the triple-stranded stack. Five consecutive triple base pairs flank the helical junction where the 3′ nucleotide of L2, C27, adopts a cytidine 27 N3-cytidine 14 2′-OH hydrogen bonding interaction with the C14-G7 base pair. This interaction is isosteric with the adenosine N1–2′-OH interaction in the related mRNA from beet western yellows virus (BWYV); however, the ScYLV and BWYV mRNA structures differ in their detailed L2–S1 hydrogen bonding and L2 stacking interactions. Functional analyses of ScYLV/BWYV chimeric pseudoknots reveal that the ScYLV RNA stimulates a higher level of –1 PRF (15 ± 2%) relative to the BWYV pseudoknot (6 ± 1%), a difference traced largely to the identity of the 3′ nucleotide of L2 (C27 vs. A25 in BWYV). Strikingly, C27A ScYLV RNA is a poor frameshift stimulator (2.0%) and is destabilized by ≈1.5 kcal·mol
–1
(pH 7.0, 37°C) with respect to the wild-type pseudoknot. These studies establish that the precise network of weak interactions nearest the helical junction in structurally similar pseudoknots make an important contribution to setting the frameshift efficiency in mRNAs.
Inositol polyphosphate multikinase is a nuclear PI3-kinase with transcriptional regulatory activity
Authors: Resnick Adam C. , Snowman Adele M. , Kang Bingnan N. , Hurt K. Joseph , Snyder Solomon H. , Saiardi Adolfo
Published: August 2005

Phosphatidylinositol 3,4,5-trisphosphate is a major intracellular messenger molecule thought to be formed almost exclusively by cytosolic, wortmannin-inhibited phosphoinositide 3-kinase family members. Inositol polyphosphate multikinase was identified as an enzyme that generates a series of water-soluble inositol phosphates. We now report the robust, physiologic, and evolutionarily conserved phosphoinositide 3-kinase activity of inositol polyphosphate multikinase, which is localized to nuclei and unaffected by wortmannin. In yeast, this inositol lipid kinase activity physiologically regulates transcription.
The erythrocyte viral trap: Transgenic expression of viral receptor on erythrocytes attenuates coxsackievirus B infection
Authors: Asher Damon R. , Cerny Anna M. , Finberg Robert W.
Published: August 2005

Viruses rely on attachment to specific cell surface receptors to infect host cells. Selective expression of viral receptors has the potential to attenuate infection of susceptible tissues by redirecting virus to cells that cannot support viral replication. We propose that erythrocytes are an ideal instrument for this strategy, because they are present in vast numbers, permeate every organ, and cannot serve as hosts for viral propagation. To test this hypothesis, we generated a transgenic mouse, termed globin transcription factor 1 (GATA1)- coxsackie and adenovirus receptor (CAR), that expressed the CAR on erythrocytes. Coxsackievirus group B (CVB) adhered to the surface of CAR-expressing erythrocytes and was rendered noninfectious. Upon infection with CVB, GATA1-CAR mice had diminished viremia and reduced viral replication in heart, brain, and liver. Furthermore, when faced with a CVB challenge that was lethal to WT littermates, the survival of GATA1-CAR mice was prolonged, and their ultimate mortality was reduced. The GATA1-CAR mouse model presented here demonstrates that erythrocyte expression of CAR limits CVB pathogenesis. Erythrocytes also may be coated with a variety of receptors by nontransgenic methods, making this a very flexible model for the treatment of infectious diseases in humans.
A ROBUST ESTIMATION OF THE EFFECTS OF TAXATION ON CHARITABLE CONTRIBUTIONS
Authors: BRADLEY RALPH , HOLDEN STEVEN , MCCLELLAND ROBERT
Published: August 2005

In contrast to earlier studies, recent research finds that charitable contributions are tax‐price inelastic, suggesting that the itemized deduction for contributions loses more tax revenue than it increases in contributions. The estimates from parametric methods are similar to those in earlier studies that find that charity appears to be elastic with respect to the tax price. Because specification tests raise doubts about the consistency of these methods, the authors use a two‐stage semi‐parametric method and find that contributions are price inelastic. Contributions to social welfare organizations, however, are price elastic; their deductibility loses less in revenues than is contributed. (JEL C14, C34)
The folding energy landscape and phosphorylation: modeling the conformational switch of the NFAT regulatory domain
Authors: Shen Tongye , Zong Chenghang , Hamelberg Donald , Andrew Mccammon J. , Wolynes Peter G.
Published: August 2005

An energy landscape approach predicts the conformational changes of the configurations of the regulatory domain of the protein nuclear factor of activated T cells (NFAT) caused by phosphorylation of specific multiple sites. Structurally local effects and secondary structural changes are modeled using allatom Brownian dynamics to investigate the changes of the backbone torsional distributions upon phosphorylation. For tertiary and global changes' we employ a coarse‐grained model to sample ensembles of conformations both with and without phosphorylation. At the secondary structure level' phosphorylation moderately increases the helical propensity and gives a more rigid local backbone conformation. The tertiary effects of phosphorylation caused by the extensive charge modification are more pronounced and collectively change the conformation of the regulatory domain of NFAT from a flexible globular ensemble to a rather rigid helical bundle, blocking access to the nuclear localization sequence. These studies give computational support to one scenario conjectured from experiments. Shen, T., Zong, C., Hamelberg, D., McCammon, J. A., Wolynes, P. G. The folding energy landscape and phosphorylation: modeling the conformational switch of the NFAT regulatory domain. FASEB J. 19, 1389–1395 (2005)
Serotonin, l‐tryptophan, and tryptamine are effective inhibitors of the amino acid transport system PAT1
Authors: Metzner Linda , Kottra Gabor , Neubert Klaus , Daniel Hannelore , Brandsch Matthias
Published: August 2005

The proton‐coupled amino acid transporter PAT1, cloned recently from brain and intestine, mediates the uphill transport of l‐ and d‐proline, l‐alanine, glycine, taurine, d‐serine, GABA, and many other related compounds and drugs. Here we describe the novel finding that l‐tryptophan and its derivatives tryptamine, 5‐hydroxy‐l‐tryptophan, serotonin, and indoles‐propionic acid strongly inhibit H+‐dependent l‐[3H]proline uptake into Caco‐2 cells with inhibition constants (Ki) of 0.9 to 6.1 mM. Uptake of l‐[3H]tryptophan into Caco‐2 cells on the other hand was not inhibited by l‐proline. Whereas PAT1 substrates produced significant changes in a membrane potential assay for electrogenic transport in Caco‐2 cells, l‐tryptophan, tryptamine, and 5‐hydroxy‐l‐tryptophan failed to alter membrane voltage. When PAT1 was expressed in Xenopus laevis oocytes and analyzed by the two‐electrode voltage clamp technique, glycine elicited high inward currents that were dependent on membrane potential but no currents were observed with l‐tryptophan, tryptamine, 5‐hydroxy‐l‐tryptophan, or serotonin. Although not transported electrogenically by PAT1, l‐tryptophan and its derivatives inhibited glycine‐evoked currents dose‐dependently. We conclude that serotonin, l‐tryptophan, and tryptamine bind to PAT1 with potencies similar to the prototype substrates, inhibit transport function but are not transported by this carrier protein. They may be considered as the carriers' naturally occurring inhibitors that may alter the transport function of PAT1. Metzner, L., Kottra, G., Neubert, K., Daniel, H., Brandsch, M. Serotonin, l‐tryptophan, and tryptamine are effective inhibitors of the amino acid transport system PAT1. FASEB J. 19, 1468–1473 (2005)
Regulation of phosphoglucose isomerase/autocrine motility factor expression by hypoxia
Authors: Funasaka Tatsuyoshi , Yanagawa Takashi , Hogan Victor , Raz Avraham
Published: August 2005

Phosphoglucose isomerase (PGI; EC 5.3.1.9) is a housekeeping cytosolic enzyme of the sugar metabolism pathways that plays a key role in glycolysis and gluconeogenesis. PGI is a multifunctional dimeric protein that extracellularly acts as a cytokine with properties that include autocrine motility factor (AMF) eliciting mitogenic, motogenic, differentiation functions and has been implicated in tumor progression and metastasis. Since metastasis is regulated in part by hypoxia, which induces the transcription of metastasis‐associated genes and anaerobic glycolic metabolism, we questioned whether hypoxia also regulates the expression level of tumor cells' PGI/AMF. We establish here that in the human breast carcinoma BT‐549 cells hypoxia enhanced expression of the transcription factor hypoxia‐inducible factor (HIF) ‐1, which in turn led to the up‐regulation of PGI/AMF expression and was specifically inhibited by inhibitors of the phosphatidylinositol 3′‐kinase signaling pathway. In addition, the hypoxia induction of PGI/AMF expression was suppressed by inhibitors of vascular endothelial growth factor (VEGF) or VEGF receptors, suggesting that hypoxia‐inducible VEGF regulates the PGI/AMF expression. Hypoxia also enhanced cancer cell motility, and these effects were strongly inhibited by the PGI/AMF, VEGF, or VEGF receptor inhibitors. The results presented here suggest that under hypoxic conditions the expression of PGI/AMF is regulated in part by the HIF pathway, which in turn increases the flow of the glycolytic cascade leading to an increased anaerobic energy generation; thus, inhibition of PGI/AMF expression and activities may provide a new therapeutic modality for treatment of hypoxic tumors. Funasaka, T., Yanagawa, T., Hogan, V., Raz, A. Regulation of phosphoglucose isomerase/autocrine motility factor expression by hypoxia. FASEB J. 19, 1422–1430 (2005)
Central angiotensin II controls alcohol consumption via its AT1 receptor
Authors: Maul Björn , Krause Winfried , Pankow Kristin , Becker Matthias , Gembardt Florian , Alenina Natalia , Walther Thomas , Bader Michael , Siems Wolf‐Eberhard
Published: August 2005

Pharmacological and genetic manipulations of the renin‐angiotensin system (RAS) have been found to alter the voluntary consumption of alcohol. Here we characterize the role of central angiotensin II (Ang II) in alcohol intake first by using transgenic rats that express an antisense RNA against angiotensinogen and consequently have reduced Ang II levels exclusively in the central nervous system [TGR(ASrAOGEN)680]. These rats consumed markedly less alcohol in comparison to their wild‐type controls. Second, Spirapril, an inhibitor of the angiotensin‐converting enzyme (ACE), which passes the blood‐brain barrier, did not influence the alcohol consumption in the TGR(ASrAOGEN)680, but it significantly reduced alcohol intake in wild‐type rats. Studies in knockout mice indicated that the central effect of Ang II on alcohol consumption is mediated by the angiotensin receptor ATI whereas the AT2 receptor and the bradykinin B2 receptor are not involved. Furthermore, the dopamine concentration in the ventral tegmental area (VTA) is markedly reduced in rats with low central Ang II, strengthening our hypothesis of a role of dopaminergic transmission in Ang II‐controlled alcohol preference. Our results indicate that a distinct drug‐mediated control of the central RAS could be a promising therapy for alcohol disease. Maul, B., Krause, W., Pankow, K., Becker, M., Gembardt, F., Alenina N., Walther, T., Bader, M., Siems, W.‐E. Central angiotensin II controls alcohol consumption via its ATI receptor. FASEB J. 19, 1474–1481 (2005)
Targeted deletion of melanocortin receptor subtypes 3 and 4, but not CART, alters nutrient partitioning and compromises behavioral and metabolic responses to leptin
Authors: Zhang Yubin , Kilroy Gail E , Henagan Tara M. , Prpic‐Uhing Vera , Richards William G. , Bannon Anthony W. , Mynatt Randall L. , Gettys Thomas W.
Published: August 2005

Mouse lines with targeted disruption of the cocaine amphetamine‐related transcript (CART), melanocortin receptor 3 (MCR3), or melanocortin receptor 4 (MCR4) were used to assess the role of each component in mediating the anorectic and metabolic effects of leptin, and in regulating the partitioning of nutrient energy between fat and protein deposition. Leptin was administered over a 3 day period using either intraperitoneal or intracerebroventricular routes of injection. The absence of MCR4 blocked leptin's ability to increase UCP1 mRNA in both brown and white adipose tissue, but not its ability to reduce food consumption. In contrast, deletion of MCR3 compromised leptin's ability to reduce food consumption, but not its ability to reduce fat deposition or increase UCP1 expression in adipose tissue. Leptin‐dependent effects on food consumption and adipocyte gene expression were unaffected by the absence of CART. Repeated measures of body composition over time indicate that the absence of either MCR3 or MCR4, but not CART, increased lipid deposition and produced comparable degrees of adiposity in both lines. Moreover, modest increases in fat content of the diet (4 to 11%) accentuated fat deposition and produced a rapid and comparable 10–12% increase in % body fat in both genotypes. The results indicate that nutrient partitioning, as well as the anorectic and metabolic responses to leptin, are dependent onintegrated but separable inputs from the melanocortin 3 and 4 receptor subtypes. Zhang, Y., Kilroy, G. E., Henagan, T. M., Prpic‐Uhing, V. Richards, W. G., Bannon, A. W., Mynatt, R. L., Gettys, T. W. Targeted deletion of melanocortin receptor subtypes 3 and 4, but not CART, alters nutrient partitioning and compromises behavioral and metabolic responses to leptin. FASEB J. 19, 1482–1491 (2005)
HMG‐CoA reductase inhibitor augments survival and differentiation of oligodendrocyte progenitors in animal model of multiple sclerosis
Authors: Paintlia Ajaib S. , Paintlia Manjeet K. , Khan Mushfiquddin , Vollmer Timothy , Singh Avtar K. , Singh Inderjit
Published: August 2005

Impaired remyelination due to degeneration of both postmitotic oligodendrocytes and oligodendrocyte progenitors (OPs) is the major hallmark of inflammatory demyelination in multiple sclerosis (MS) lesions and experimental autoimmune encephalomyelitis (EAE). Here, we have demonstrated the potential of lovastatin, a HMG‐CoA reductase inhibitor, for the restoration of impaired remyelination mediated through enhanced survival and differentiation of OPs in the spinal cord of treated EAE animals. Lovastatin treatment significantly increased the level of myelin lipids in the spinal cord of treated EAE animals, coinciding with the attenuation of disease severity and inflammatory demyelination as compared with untreated EAE animals. The increased expression of myelin proteins and transcription factors associated with differentiating oligodendrocytes along with the increase in number of NG2+/BrdU− and NG2+/BrdU+ cells, and the expression of proliferating OP‐specific proteins, demonstrated the restoration of remyelination in the spinal cord of lovastatin‐treated EAE animals. Corresponding to this, in vitro studies further corroborated the increased survival and differentiation of OPs in lovastatin‐treated activated mixed glial cells suggesting that lovastatin protects against the degeneration of OPs and enhances their differentiation through induction of a pro‐remyelinating environment in the spinal cord of treated EAE animals. Together, these data demonstrate that lovastatin has the potential to augment remyelination in MS lesions and other neuroinflammatory diseases. Paintlia, A. S., Paintlia, M. K., Khan, M., Vollmer, T., Singh, A. K., Singh, I. HMG‐CoA reductase inhibitor augments survival and differentiation of oligodendrocyte progenitors in animal model of multiple sclerosis. FASEB J. 19, 1407–1421 (2005)
Kinetics and Extravascular Retention of Acetated Ringer’s Solution during Isoflurane or Propofol Anesthesia for Thyroid Surgery
Authors: Ewaldsson Carl-Arne , Hahn Robert G.
Published: August 2005

Background

In sheep, isoflurane causes extravascular accumulation of infused crystalloid fluid. The current study evaluates whether isoflurane has a greater tendency than propofol to cause extravascular retention in surgical patients.

Methods

Thirty patients undergoing thyroid surgery lasting for 143 +/- 32 min (mean +/- SD) received an intravenous infusion of 25 ml/kg acetated Ringer's solution over 30 min. Anesthesia was randomized to consist of isoflurane or propofol supplemented by fentanyl. The distribution and elimination of the infused fluid was estimated using volume kinetics based on the fractional dilution of blood hemoglobin over 150 min. Extravascular retention of infused fluid was taken as the difference between the model-predicted elimination and the urinary excretion. The sodium and fluid balances were measured.

Results

The fractional plasma dilution increased gradually to approximately 30% during the infusion and thereafter remained at 15-20%. Urinary excretion averaged 11% of the infused volume. Mean arterial pressure was 10 mmHg lower in the isoflurane group (P < 0.001). The excess fluid volumes in the central and peripheral functional body fluid spaces were virtually identical in the groups. The sum of water losses by evaporation and extravascular fluid retention amounted to 2.0 +/- 2.5 ml/min for isoflurane and 2.2 +/- 2.1 ml/min for propofol. The sodium balance refuted that major fluid shifts occurred between the extracellular and intracellular spaces.

Conclusions

The amount of evaporation and extravascular retention of fluid was small during thyroid surgery, irrespective of whether anesthesia was maintained by isoflurane or propofol.
Collapsibility of the Upper Airway at Different Concentrations of Propofol Anesthesia
Authors: Eastwood Peter R. , Platt Peter R. , Shepherd Kelly , Maddison Kathy , Hillman David R.
Published: August 2005

Background

This study investigated the effect of varying concentrations of propofol on upper airway collapsibility and the mechanisms responsible for it.

Methods

Upper airway collapsibility was determined from pressure-flow relations at three concentrations of propofol anesthesia (effect site concentration = 2.5, 4.0, and 6.0 mug/ml) in 12 subjects spontaneously breathing on continuous positive airway pressure. At each level of anesthesia, mask pressure was transiently reduced from a pressure sufficient to abolish inspiratory flow limitation (maintenance pressure = 12 +/- 1 cm H2O) to pressures resulting in variable degrees of flow limitation. The relation between mask pressure and maximal inspiratory flow was determined, and the critical pressure at which the airway occluded was recorded. Electromyographic activity of the genioglossus muscle (EMGgg) was obtained via intramuscular electrodes in 8 subjects.

Results

With increasing depth of anesthesia, (1) critical closing pressure progressively increased (-0.3 +/- 3.5, 0.5 +/- 3.7, and 1.4 +/- 3.5 cm H2O at propofol concentrations of 2.5, 4.0, and 6.0 microg/ml respectively; P < 0.05 between each level), indicating a more collapsible upper airway; (2) inspiratory flow at the maintenance pressure significantly decreased; and (3) respiration-related phasic changes in EMGgg at the maintenance pressure decreased from 7.3 +/- 9.9% of maximum at 2.5 microg/ml to 0.8 +/- 0.5% of maximum at 6.0 microg/ml, whereas tonic EMGgg was unchanged. Relative to the levels of phasic and tonic EMGgg at the maintenance pressure immediately before a decrease in mask pressure, tonic activity tended to increase over the course of five flow-limited breaths at a propofol concentration of 2.5 microg/ml but not at propofol concentrations of 4.0 and 6.0 microg/ml, whereas phasic EMGgg was unchanged.

Conclusions

Increasing depth of propofol anesthesia is associated with increased collapsibility of the upper airway. This was associated with profound inhibition of genioglossus muscle activity. This dose-related inhibition seems to be the combined result of depression of central respiratory output to upper airway dilator muscles and of upper airway reflexes.
Sniffing Position Improves Pharyngeal Airway Patency in Anesthetized Patients with Obstructive Sleep Apnea
Authors: Isono Shiroh , Tanaka Atsuko , Ishikawa Teruhiko , Tagaito Yugo , Nishino Takashi
Published: August 2005

Background

Appropriate bag-and-mask ventilation with patent airway is mandatory during induction of general anesthesia. Although the sniffing neck position is a traditionally recommended head and neck position during this critical period, knowledge of the influences of this position on the pharyngeal airway patency is still inadequate.

Methods

Total muscle paralysis was induced with general anesthesia in 12 patients with obstructive sleep apnea, eliminating neuromuscular factors contributing to pharyngeal patency. The cross-sectional area of the pharynx was measured endoscopically at different static airway pressures. Comparison of static pressure-area plot between the neutral and sniffing neck positions allowed assessment of the influence of the neck position change on the mechanical properties of the pharynx.

Results

The static pressure-area curves of the sniffing position were above those of neutral neck position, with increasing maximum cross-sectional area and decreasing the closing pressure at both retropalatal and retroglossal airways. The beneficial effects of the sniffing position were greater in obstructive sleep apnea patients with higher closing pressure and smaller body mass index.

Conclusions

Sniffing position structurally improves maintenance of the passive pharyngeal airway in patients with obstructive sleep apnea and may be beneficial for both mask ventilation and tracheal intubation during anesthesia induction.