bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of high responsivity waveguide photodiode with a thin absorption layer
Authors: Park Jeong-Woo , Ko Hyun-Sung , Sim Eun-Deok , Baek Yong-Soon
Published: February 2007

The optimization of a waveguide photodiode (WGPD) having a thin absorption layer is discussed. With an absorption layer thickness of less than 0.1μm, responsivity of 1.09A∕W was achieved for lensed-fiber coupling. For flat-ended fiber coupling, responsivity of 0.93A∕W was achieved. An absorption layer thickness of more than 100Å is required for high responsivity and low polarization dependency. A formula for frequency response in a WGPD with a thin absorption layer is also obtained. This formula gives the optimized WGPD structure for high speed operation with high responsivity.
Shape memory piezoelectric actuator
Authors: Morita Takeshi , Kadota Yoichi , Hosaka Hiroshi
Published: February 2007

The shape memory piezoelectric actuator can be operated using a pulsed voltage, so that small energy consumption and small voltage operation can be realized. To realize shape memory operation, the imprint electrical field was induced by treatment with a high electrical field of 3.5kV∕mm in a 150°C environment. The actuator had two stable positions that were dependent on the piezoelectric polarization and could be maintained without the use of an external electrical field. This shape memory effect indicated that the imprint electrical field contributes to other functional properties, such as a permittivity, optical refractive index, and mechanical compliance.
Wavelength switching transition in quantum dot lasers
Authors: Wang Hsing-Yeh , Cheng Hsu-Chieh , Lin Sheng-Di , Lee Chien-Ping
Published: February 2007

Control and the selection of the ground state emission and/or the excited state emission of an InAs quantum dot laser have been demonstrated. By controlling the currents injected into each section of a two-section cavity, switching between the ground state emission and the excited state emission with a separation of 100nm was achieved. With a constant total current, either ground state lasing (∼1.3μm), excited state lasing (∼1.2μm), or dual state lasing can be obtained simply by adjusting the current ratio between the two sections.
Pretilt angle effects on critical voltage and dynamic response of pi cell
Authors: Sun Yubao , Ma Hongmei , Li Zaidong , Zhang Zhidong , Guan Ronghua
Published: February 2007

The critical voltage with an arbitrary pretilt angle is given analytically which is consistent with the numerical results [Acosta et al., Liq. Cryst. 27, 977 (2000)]. The author’s results show that the critical voltage is dependent on the parameters of liquid crystal and pretilt angle but is independent of the cell gap. By numerical simulation the authors find that the on time of pi cell decreases with the increasing pretilt at the same voltage, and the off time of the cell driven by the undershoot method is much faster than that of the normal driven method for the cell with nonzero critical voltage.
Three-dimensional imaging of stacked Pd nanoparticles by electron tomography
Authors: Park Jong-Bong , Lee Jun Ho , Choi Hye-Ran
Published: February 2007

Spatial distributed quantum-sized nanocrystals (<10nm) have considerable potential for various engineering applications, such as flash memory devices due to their charge-trap properties, efficient displays, solar cells, and biosensors. In the present study, stacked Pd nanoparticle (5–6nm in diameter) arrays were examined by different imaging techniques, including bright-field transmission electron microscopy, high-angle annular-dark-field scanning transmission electron microscopy, and three-dimensional (3D) electron tomography. Notably, the authors reliably found both the distribution and the location of the stacked Pd nanoparticles using 3D electron tomography. The authors’ approach offers potential solutions to the problem of enhancing the physicochemical properties of the applications.
Rapidly sheared homogeneous stratified turbulence in a rotating frame
Authors: Kassinos S. C. , Akylas E. , Langer C. A.
Published: February 2007

Rapid distortion theory is applied to stratified homogeneous turbulence that is sheared in a rotating frame. Insight into the stabilizing and destabilizing effects of the combined stratification and frame rotation is gained by considering initial fields that are two-dimensional, with the axis of independence aligned with the flow direction. For these conditions, we derive solutions for the Fourier components of the flow variables, and for one-point statistics in physical space. The analytical results are in qualitative agreement with the exact numerical solution for initially isotropic homogeneous turbulence, and they could be a reference point for the development of turbulence models.
Learning to Perceive with a Visuo — Auditory Substitution System: Localisation and Object Recognition with ‘The Voice’
Authors: Auvray Malika , Hanneton Sylvain , O'Regan J Kevin
Published: February 2007

We investigated to what extent participants can acquire the mastery of an auditory-substitution-of-vision device (‘The vOICe’) using dynamic tasks in a three-dimensional environment. After extensive training, participants took part in four experiments. In the first experiment we explored locomotion and localisation abilities. Participants, blindfolded and equipped with the device, had to localise a target by moving a hand-held camera, walk towards the target, and point at it. In the second experiment, we studied the localisation ability in a constrained pointing task. In the third experiment we explored participants' ability to recognise natural objects via their auditory rendering. In the fourth experiment we tested the ability of participants to discriminate objects belonging to the same category. We analysed participants' performance from both an objective and a subjective point of view. The results showed that participants, through sensorimotor interactions with the perceptual scene while using the hand-held camera, were able to make use of the auditory stimulation to obtain the information necessary for locomotor guidance, localisation, and pointing, as well as for object recognition. Furthermore, analysis from a subjective perspective yielded insights into participants' qualitative experience and into the strategies they used to master the device, and thus to pass from a kind of deductive reasoning to a form of immediate apprehension of what is being perceived.
Transgenic cyclin E triggers dysplasia and multiple pulmonary adenocarcinomas
Authors: Ma Yan , Fiering Steven , Black Candice , Liu Xi , Yuan Ziqiang , Memoli Vincent A. , Robbins David J. , Bentley Heather A. , Tsongalis Gregory J. , Demidenko Eugene , Freemantle Sarah J. , Dmitrovsky Ethan
Published: February 2007

Cyclin E is a critical G
1
-S cell cycle regulator aberrantly expressed in bronchial premalignancy and lung cancer. Cyclin E expression negatively affects lung cancer prognosis. Its role in lung carcinogenesis was explored. Retroviral cyclin E transduction promoted pulmonary epithelial cell growth, and small interfering RNA targeting of cyclin E repressed this growth. Murine transgenic lines were engineered to mimic aberrant cyclin E expression in the lung. Wild-type and proteasome degradation-resistant human cyclin E transgenic lines were independently driven by the human surfactant C (SP-C) promoter. Chromosome instability (CIN), pulmonary dysplasia, sonic hedgehog (Shh) pathway activation, adenocarcinomas, and metastases occurred. Notably, high expression of degradation-resistant cyclin E frequently caused dysplasia and multiple lung adenocarcinomas. Thus, recapitulation of aberrant cyclin E expression as seen in human premalignant and malignant lung lesions reproduces in the mouse frequent features of lung carcinogenesis, including CIN, Shh pathway activation, dysplasia, single or multiple lung cancers, or presence of metastases. This article reports unique mouse lung cancer models that replicate many carcinogenic changes found in patients. These models provide insights into the carcinogenesis process and implicate cyclin E as a therapeutic target in the lung.
Mechanism for inactivation of the mitotic inhibitory kinase Wee1 at M phase
Authors: Okamoto Kengo , Sagata Noriyuki
Published: February 2007

Wee1, the inhibitory kinase of cyclin B/Cdc2, undergoes a phosphorylation-dependent catalytic inactivation at M phase of the mitotic cell cycle, but the precise mechanism for this inactivation is not known. Using
Xenopus
egg and extract systems, we show here that the kinase activity of
Xenopus
somatic Wee1 (XeWee1B) is regulated by its N-terminal, small, well conserved region, termed here the Wee-box. The Wee-box is essential for the normal kinase activity of XeWee1B during interphase, acting positively on the C-terminal catalytic domain, which alone cannot efficiently phosphorylate Cdc2. Significantly, a Thr-186-Pro (TP) motif within the Wee-box is phosphorylated by Cdc2 at M phase and specifically binds the cis/trans prolyl isomerase Pin1. This Pin1 binding is required for the inactivation of XeWee1B at M phase, presumably causing isomerization of the phospho-TP motif and thereby impairing the function of the Wee-box. These results provide important insights into the mechanism of Wee1 inactivation at M phase.
Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase
Authors: Manfredi Mark G. , Ecsedy Jeffrey A. , Meetze Kristan A. , Balani Suresh K. , Burenkova Olga , Chen Wei , Galvin Katherine M. , Hoar Kara M. , Huck Jessica J. , LeRoy Patrick J. , Ray Emily T. , Sells Todd B. , Stringer Bradley , Stroud Stephen G. , Vos Tricia J. , Weatherhead Gabriel S. , Wysong Deborah R. , Zhang Mengkun , Bolen Joseph B. , Claiborne Christopher F.
Published: February 2007

Increased Aurora A expression occurs in a variety of human cancers and induces chromosomal abnormalities during mitosis associated with tumor initiation and progression. MLN8054 is a selective small-molecule Aurora A kinase inhibitor that has entered Phase I clinical trials for advanced solid tumors. MLN8054 inhibits recombinant Aurora A kinase activity
in vitro
and is selective for Aurora A over the family member Aurora B in cultured cells. MLN8054 treatment results in G
2
/M accumulation and spindle defects and inhibits proliferation in multiple cultured human tumor cells lines. Growth of human tumor xenografts in nude mice was dramatically inhibited after oral administration of MLN8054 at well tolerated doses. Moreover, the tumor growth inhibition was sustained after discontinuing MLN8054 treatment. In human tumor xenografts, MLN8054 induced mitotic accumulation and apoptosis, phenotypes consistent with inhibition of Aurora A. MLN8054 is a selective inhibitor of Aurora A kinase that robustly inhibits growth of human tumor xenografts and represents an attractive modality for therapeutic intervention of human cancers.
Pollen tetrad-based visual assay for meiotic recombination in
Arabidopsis
Authors: Francis Kirk E. , Lam Sandy Y. , Harrison Benjamin D. , Bey Alexandra L. , Berchowitz Luke E. , Copenhaver Gregory P.
Published: February 2007

Recombination, in the form of cross-overs (COs) and gene conversion (GC), is a highly conserved feature of meiosis from fungi to mammals. Recombination helps ensure chromosome segregation and promotes allelic diversity. Lesions in the recombination machinery are often catastrophic for meiosis, resulting in sterility. We have developed a visual assay capable of detecting Cos and GCs and measuring CO interference in
Arabidopsis thaliana
. This flexible assay utilizes transgene constructs encoding pollen-expressed fluorescent proteins of three different colors in the
qrt1
mutant background. By observing the segregation of the fluorescent alleles in 92,489 pollen tetrads, we demonstrate (
i
) a correlation between developmental position and CO frequency, (
ii
) a temperature dependence for CO frequency, (
iii
) the ability to detect meiotic GC events, and (
iv
) the ability to rapidly assess CO interference.
Endogenous IL-12 triggers an antiangiogenic program in melanoma cells
Authors: Airoldi Irma , Di Carlo Emma , Cocco Claudia , Taverniti Giuseppe , D'Antuono Tommaso , Ognio Emanuela , Watanabe Morihiro , Ribatti Domenico , Pistoia Vito
Published: February 2007

The IL12RB2 gene acts as a tumor suppressor in human B cell malignancies. Indeed, Il12rb2 knockout (KO) mice develop spontaneously B cell tumors, but also lung epithelial tumors. This latter phenotype may be related to (i) impairment of host IL-12-mediated immunosurveillance and/or (ii) IL-12 inability to inhibit directly the growth of IL-12 unresponsive malignant cells. To address this issue, we transplanted IL-12R+B16 melanoma cells into syngeneic Il12rb2 KO mice with the following rationale: (i) these mice have severe defects in IFN-γ production, as well as in cytotoxic T lymphocyte and natural killer cell cytotoxicity, and (ii) they produce but do not use IL-12 that can potentially bind to and target tumor cells only. Il12rb2 KO mice displayed higher endogenous serum levels of IL-12 and developed smaller B16 tumors than WT animals. These tumors showed reduced proliferation, increased apoptosis, and defective microvessel formation related to down-regulated expression of a set of proangiogenic genes previously unrelated to IL-12. Such effects depended on direct activity of endogenous IL-12 on tumor cells in KO mice, and hydrodynamic delivered IL-12 caused further reduced tumorigenicity of B16 cells in these mice. A previously undescribed mechanism of the IL-12 antitumor activity has been here identified and characterized.
Functional and morphometric brain dissociation between dyslexia and reading ability
Authors: Hoeft Fumiko , Meyler Ann , Hernandez Arvel , Juel Connie , Taylor-Hill Heather , Martindale Jennifer L. , McMillon Glenn , Kolchugina Galena , Black Jessica M. , Faizi Afrooz , Deutsch Gayle K. , Siok Wai Ting , Reiss Allan L. , Whitfield-Gabrieli Susan , Gabrieli John D. E.
Published: February 2007

In functional neuroimaging studies, individuals with dyslexia frequently exhibit both hypoactivation, often in the left parietotemporal cortex, and hyperactivation, often in the left inferior frontal cortex, but there has been no evidence to suggest how to interpret the differential relations of hypoactivation and hyperactivation to dyslexia. To address this question, we measured brain activation by functional MRI during visual word rhyme judgment compared with visual cross-hair fixation rest, and we measured gray matter morphology by voxel-based morphometry in dyslexic adolescents in comparison with (
i
) an age-matched group, and (
ii
) a reading-matched group younger than the dyslexic group but equal to the dyslexic group in reading performance. Relative to the age-matched group (
n
= 19; mean 14.4 years), the dyslexic group (
n
= 19; mean 14.4 years) exhibited hypoactivation in left parietal and bilateral fusiform cortices and hyperactivation in left inferior and middle frontal gyri, caudate, and thalamus. Relative to the reading-matched group (
n
= 12; mean 9.8 years), the dyslexic group (
n
= 12; mean 14.5 years) also exhibited hypoactivation in left parietal and fusiform regions but equal activation in all four areas that had exhibited hyperactivation relative to age-matched controls as well. In regions that exhibited atypical activation in the dyslexic group, only the left parietal region exhibited reduced gray matter volume relative to both control groups. Thus, areas of hyperactivation in dyslexia reflected processes related to the level of current reading ability independent of dyslexia. In contrast, areas of hypoactivation in dyslexia reflected functional atypicalities related to dyslexia itself, independent of current reading ability, and related to atypical brain morphology in dyslexia.
C-type natriuretic peptide regulates blood–testis barrier dynamics in adult rat testes
Authors: Xia Weiliang , Mruk Dolores D. , Cheng C. Yan
Published: February 2007

In adult rat testes, the blood–testis barrier (BTB) in the seminiferous epithelium must “open” (or “disassemble”) to accommodate the migration of preleptotene spermatocytes from the basal to the adluminal compartment that occurs at stage VIII of the epithelial cycle. However, the molecule(s) and/or mechanism(s) that regulate this event are unknown. In this report, C-type natriuretic peptide (CNP) was shown to be a regulator of BTB dynamics. Although Sertoli and germ cells contributed to the pool of CNP in the seminiferous epithelium, its receptor, natriuretic peptide receptor B, resided almost exclusively in Sertoli cells. CNP also expressed stage-specifically and localized predominantly at the BTB in the seminiferous epithelium at stage VIII of the epithelial cycle. A synthetic CNP-22 peptide, when added to Sertoli cell cultures, was shown to perturb Sertoli cell tight junctionin vitro, causing disappearance of BTB-associated proteins (JAM-A, occludin, N-cadherin, and β-catenin) from the cell–cell interface. This inhibitory effect of CNP on the tight junction was confirmed by transient overexpression of CNP in these cells, which was mediated, at least in part, by accelerating the internalization of BTB integral membrane proteins. To validate thesein vitrofindings, CNP-22 was administered to testes at a dose of 0.35 or 3.5 μg per testis, which was shown to perturb the BTB integrityIn vivowhen the barrier function was assessed by monitoring the diffusion of a small molecular probe across the BTB. In summary, CNP secreted by Sertoli and germ cells into the BTB microenvironment regulates BTB dynamics during spermatogenesis.
Inhibition of Cdk5 in the nucleus accumbens enhances the locomotor-activating and incentive-motivational effects of cocaine
Authors: Taylor Jane R. , Lynch Wendy J. , Sanchez Hayde , Olausson Peter , Nestler Eric J. , Bibb James A.
Published: February 2007

Neuronal adaptations in striatal dopamine signaling have been implicated in enhanced responses to addictive drugs. Cyclin-dependent kinase 5 (Cdk5) regulates striatal dopamine signaling and is a downstream target gene of the transcription factor ΔFosB, which accumulates in striatal neurons after chronic cocaine exposure. Here we investigated the role of Cdk5 activity in the nucleus accumbens (NAc) on cocaine-induced locomotor sensitization, responding for reward-associated stimuli (conditioned reinforcement), and cocaine self-administration under a progressive ratio schedule. Repeated infusions of the Cdk5 inhibitor roscovitine into the NAc before cocaine injections augmented both the development and expression of cocaine sensitization without having any intrinsic stimulant actions of its own. Additionally, repeated intra-NAc infusions of roscovitine to saline-injected rats enhanced locomotor responses to a subsequent cocaine challenge. Similar effects were found after infusions of another Cdk5 inhibitor, olomoucine, but not its inactive congener, iso-olomoucine. Repeated inhibition of Cdk5 within the NAc also robustly enhanced the incentive-motivational effects of cocaine, similar to the effect of prior repeated cocaine exposure. The enhanced responding with conditioned reinforcement induced by cocaine persisted at least 2 weeks after the final roscovitine infusion. NAc infusions of olomoucine also produced acute and enduring increases in “breakpoints” achieved on a progressive ratio schedule for cocaine reinforcement. These results demonstrate profound and persistent effects of NAc Cdk5 inhibition on locomotor sensitization and incentive-motivational processes and provide direct evidence for a role for striatal Cdk5-induced alterations in the brain's long-term adaptations to cocaine.
Myosin Va maneuvers through actin intersections and diffuses along microtubules
Authors: Ali M. Yusuf , Krementsova Elena B. , Kennedy Guy G. , Mahaffy Rachel , Pollard Thomas D. , Trybus Kathleen M. , Warshaw David M.
Published: February 2007

Certain types of intracellular organelle transport to the cell periphery are thought to involve long-range movement on microtubules by kinesin with subsequent handoff to vertebrate myosin Va (myoVa) for local delivery on actin tracks. This process may involve direct interactions between these two processive motors. Here we demonstrate using single molecule
in vitro
techniques that myoVa is flexible enough to effectively maneuver its way through actin filament intersections and Arp2/3 branches. In addition, myoVa surprisingly undergoes a one-dimensional diffusive search along microtubules, which may allow it to scan efficiently for kinesin and/or its cargo. These features of myoVa may help ensure efficient cargo delivery from the cell center to the periphery.
Differential binding of calmodulin-related proteins to their targets revealed through high-density
Arabidopsis
protein microarrays
Authors: Popescu Sorina C. , Popescu George V. , Bachan Shawn , Zhang Zimei , Seay Montrell , Gerstein Mark , Snyder Michael , Dinesh-Kumar S. P.
Published: February 2007

Calmodulins (CaMs) are the most ubiquitous calcium sensors in eukaryotes. A number of CaM-binding proteins have been identified through classical methods, and many proteins have been predicted to bind CaMs based on their structural homology with known targets. However, multicellular organisms typically contain many CaM-like (CML) proteins, and a global identification of their targets and specificity of interaction is lacking. In an effort to develop a platform for large-scale analysis of proteins in plants we have developed a protein microarray and used it to study the global analysis of CaM/CML interactions. An
Arabidopsis thaliana
expression collection containing 1,133 ORFs was generated and used to produce proteins with an optimized medium-throughput plant-based expression system. Protein microarrays were prepared and screened with several CaMs/CMLs. A large number of previously known and novel CaM/CML targets were identified, including transcription factors, receptor and intracellular protein kinases, F-box proteins, RNA-binding proteins, and proteins of unknown function. Multiple CaM/CML proteins bound many binding partners, but the majority of targets were specific to one or a few CaMs/CMLs indicating that different CaM family members function through different targets. Based on our analyses, the emergent CaM/CML interactome is more extensive than previously predicted. Our results suggest that calcium functions through distinct CaM/CML proteins to regulate a wide range of targets and cellular activities.
CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma
Authors: Sharma Padmanee , Shen Yu , Wen Sijin , Yamada Sachiko , Jungbluth Achim A. , Gnjatic Sacha , Bajorin Dean F. , Reuter Victor E. , Herr Harry , Old Lloyd J. , Sato Eiichi
Published: February 2007

Tumor-infiltrating cytotoxic T lymphocytes (TILs), including CD8 TILs, have been associated with favorable clinical outcomes in multiple tumor types. Tumor-infiltrating CD8 T cells and major histocompatibility complex (MHC) class I expression in urothelial carcinoma (UC) have not been previously reported. Most immune responses are mediated by local cytotoxic lymphocytes (CD8 T cells), which can eradicate tumor cells by recognizing tumor-associated antigens presented by MHC class I molecules. Here we analyzed the presence of intratumoral CD8 T cells, the expression of MHC class I antigen, and the expression of the NY-ESO-1 tumor antigen in UC samples and correlated our findings with clinical outcome. Immunohistochemical staining for intratumoral CD8 T cells in tissue samples from 69 patients with UC showed that patients with advanced UC (pT2, pT3, or pT4) and higher numbers of CD8 TILs within the tumor (≥8) had better disease-free survival (
P
< 0.001) and overall survival (
P
= 0.018) than did patients with similar-staged UC and fewer intratumoral CD8 TILs. We conclude that the extent of intratumoral CD8 TILs is an important prognostic indicator in advanced UC.
Skeletal overgrowth is mediated by deficiency in a specific isoform of fibroblast growth factor receptor 3
Authors: Eswarakumar Veraragavan P. , Schlessinger Joseph
Published: February 2007

Fibroblast growth factor receptor 3 (FGFR3) plays an important role in the control of chondrocyte proliferation and differentiation, a process critical for normal development of the skeleton. To reveal the contributions of the epithelial Fgfr3b isoform and the mesenchymal Fgfr3c isoform to skeletal overgrowth seen in mice, in which both isoforms have been inactivated (
Fgf3c
−/−
mice), we have generated mice in which each of the two Fgfr3 isoforms has been selectively inactivated. Whereas no apparent phenotype was detected in
Fgfr3b
−/−
mice, strong stimulation of chondrocyte proliferation in the growth plates of
Fgf3c
−/−
mice caused dramatic skeletal overgrowth and other skeletal abnormalities resembling the phenotype of mice deficient in both Fgfr3 isoforms. In addition,
Fgfr3c
−/−
mice exhibited decreased bone mineral density in the cortical and trabecular bone, whereas the bone mineral density of
Fgfr3b
−/−
mice resembled that of WT mice. These experiments demonstrated that the mesenchymal Fgfr3c isoform is responsible for controlling chondrocyte proliferation and differentiation that mediate normal skeletal development, whereas the epithelial Fgfr3b isoform does not contribute toward this process.
Invariant NKT cells sustain specific B cell responses and memory
Authors: Galli Grazia , Pittoni Paola , Tonti Elena , Malzone Carmine , Uematsu Yasushi , Tortoli Marco , Maione Domenico , Volpini Gianfranco , Finco Oretta , Nuti Sandra , Tavarini Simona , Dellabona Paolo , Rappuoli Rino , Casorati Giulia , Abrignani Sergio
Published: February 2007

Invariant natural killer T (iNKT) cells are innate-like lymphocytes recognizing CD1d-restricted glycolipid antigens, such as α-galactosylceramide (αGC). We assessed whether iNKT cells help B lymphocyte responses and found that mice immunized with proteins and αGC develop antibody titers 1–2 logs higher than those induced by proteins alone. Activation of iNKT cells enhances protection against infections such as influenza and elicits higher frequencies of memory B cells and higher antibody responses to booster immunizations. Protein vaccination with αGC, but not with conventional adjuvants, elicits IgG responses in mice lacking MHC class II molecules, demonstrating that iNKT cells can substitute for CD4+T cell help to B cells. Interestingly, the decay of circulating antibodies is faster in mice lacking iNKT cells. These findings point to a homeostatic role for iNKT cells on critical features of the antibody response such as immunity and B cell memory.
α-Lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway
Authors: Zhang Wei-Jian , Wei Hao , Hagen Tory , Frei Balz
Published: February 2007

The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was recently shown to negatively regulate LPS-induced acute inflammatory responses. We previously observed that the metabolic thiol antioxidant α-lipoic acid (LA) inhibits LPS-induced expression of cellular adhesion molecules and adherence of monocytes to human aortic endothelial cells. Here we investigated the mechanism by which LA attenuates LPS-induced monocyte activationin vitroand acute inflammatory responsesin vivo. Incubation of human monocytic THP-1 cells with LA induced phosphorylation of Akt in a time- and dose-dependent manner. In cells pretreated with LA followed by LPS, Akt phosphorylation was elevated initially and further increased during incubation with LPS. This LA-dependent increase in Akt phosphorylation was accompanied by inhibition of LPS-induced NF-κB DNA binding activity and up-regulation of TNFα and monocyte chemoattractant protein 1. Lipoic acid-dependent Akt phosphorylation and inhibition of NF-κB activity were abolished by the PI3K inhibitors LY294002 and wortmannin. Furthermore, LA treatment of LPS-exposed C57BL/6N mice strongly enhanced phosphorylation of Akt and glycogen synthase kinase 3β in blood cells; inhibited the LPS-induced increase in serum concentrations and/or tissue expression of adhesion molecules, monocyte chemoattractant protein 1, and TNFα; and attenuated NF-κB activation in lung, heart, and aorta. Lipoic acid also improved survival of endotoxemic mice. All of these antiinflammatory effects of LA were abolished by treatment of the animals with wortmannin. We conclude that LA inhibits LPS-induced monocyte activation and acute inflammatory responsesin vitroandin vivoby activating the PI3K/Akt pathway. Lipoic acid may be useful in the prevention of sepsis and inflammatory vascular diseases.
Delayed upwelling alters nearshore coastal ocean ecosystems in the northern California current
Authors: Barth John A. , Menge Bruce A. , Lubchenco Jane , Chan Francis , Bane John M. , Kirincich Anthony R. , McManus Margaret A. , Nielsen Karina J. , Pierce Stephen D. , Washburn Libe
Published: February 2007

Wind-driven coastal ocean upwelling supplies nutrients to the euphotic zone near the coast. Nutrients fuel the growth of phytoplankton, the base of a very productive coastal marine ecosystem [Pauly D, Christensen V (1995)
Nature
374:255–257]. Because nutrient supply and phytoplankton biomass in shelf waters are highly sensitive to variation in upwelling-driven circulation, shifts in the timing and strength of upwelling may alter basic nutrient and carbon fluxes through marine food webs. We show how a 1-month delay in the 2005 spring transition to upwelling-favorable wind stress in the northern California Current Large Marine Ecosystem resulted in numerous anomalies: warm water, low nutrient levels, low primary productivity, and an unprecedented low recruitment of rocky intertidal organisms. The delay was associated with 20- to 40-day wind oscillations accompanying a southward shift of the jet stream. Early in the upwelling season (May–July) off Oregon, the cumulative upwelling-favorable wind stress was the lowest in 20 years, nearshore surface waters averaged 2°C warmer than normal, surf-zone chlorophyll-
a
and nutrients were 50% and 30% less than normal, respectively, and densities of recruits of mussels and barnacles were reduced by 83% and 66%, respectively. Delayed early-season upwelling and stronger late-season upwelling are consistent with predictions of the influence of global warming on coastal upwelling regions.
Compliance With Isolation Precautions at a University Hospital
Authors: Weber David J. , Sickbert-Bennett Emily E. , Brown Vickie M. , Brooks Rebecca H. , Kittrell Irene P. , Featherstone Brenda J. , Adams Tina L. , Rutala William A.
Published: February 2007

Compliance with isolation precautions recommended by the Centers for Disease Control and Prevention (CDC) was evaluated in 3 hospital-wide observational surveys. The compliance rate, by type of isolation, was as follows: droplet transmission, 100% (4 observations); airborne transmission, 61.5% (13 observations); contact isolation, 73.3% (165 observations); and protective isolation, 73.6% (72 observations). As with hand hygiene, there is suboptimal compliance with recommended isolation precautions.
Risk Factors Associated With Resistance to Ciprofloxacin in Clinical Bacterial Isolates From Intensive Care Unit Patients
Authors: Levin Phillip D. , Fowler Robert A. , Guest Cameron , Sibbald William J. , Kiss Alex , Simor Andrew E.
Published: February 2007

Objective.

To determine risk factors and outcomes associated with ciprofloxacin resistance in clinical bacterial isolates from intensive care unit (ICU) patients.

Design.

Prospective cohort study.

Setting.

Twenty-bed medical-surgical ICU in a Canadian tertiary care teaching hospital.

Patients.

All patients admitted to the ICU with a stay of at least 72 hours between January 1 and December 31, 2003.

Methods.

Prospective surveillance to determine patient comorbidities, use of medical devices, nosocomial infections, use of antimicrobials, and outcomes. Characteristics of patients with a ciprofloxacin-resistant gram-negative bacterial organism were compared with characteristics of patients without these pathogens.

Results.

Ciprofloxacin-resistant organisms were recovered from 20 (6%) of 338 ICU patients, representing 38 (21%) of 178 nonduplicate isolates of gram-negative bacilli. Forty-nine percent ofPseudomonas aeruginosaisolates and 29% ofEscherichia coliisolates were resistant to ciprofloxacin. In a multivariate analysis, independent risk factors associated with the recovery of a ciprofloxacin-resistant organism included duration of prior treatment with ciprofloxacin (relative risk [RR], 1.15 per day [95% confidence interval {CI}, 1.08-1.23];P< .001), duration of prior treatment with levofloxacin (RR, 1.39 per day [95% CI, 1.01-1.91];P= .04), and length of hospital stay prior to ICU admission (RR, 1.02 per day [95% CI, 1.01-1.03];P= .005). Neither ICU mortality (15% of patients with a ciprofloxacin-resistant isolate vs 23% of patients with a ciprofloxacin-susceptible isolate;P= .58 ) nor in-hospital mortality (30% vs 34%;P= .81 ) were statistically significantly associated with ciprofloxacin resistance.

Conclusions.

ICU patients are at risk of developing infections due to ciprofloxacin-resistant organisms. Variables associated with ciprofloxacin resistance include prior use of fluoroquinolones and duration of hospitalization prior to ICU admission. Recognition of these risk factors may influence antibiotic treatment decisions.
Effect of Healthcare-Acquired Infection on Length of Hospital Stay and Cost
Authors: Graves Nicholas , Weinhold Diana , Tong Edward , Birrell Frances , Doidge Shane , Ramritu Prabha , Halton Kate , Lairson David , Whitby Michael
Published: February 2007

Objective.

To estimate the independent effect of a single lower respiratory tract infection, urinary tract infection, or other healthcare-acquired infection on length-of-stay and variable costs and to demonstrate the bias from omitted variables that is present in previous estimates.

Design.

Prospective cohort study.

Setting.

A tertiary care referral hospital and regional district hospital in southeast Queensland, Australia.

Patients.

Adults aged 18 years or older with a minimum inpatient stay of 1 night who were admitted to selected clinical specialities.

Results.

Urinary tract infection was not associated with an increase in length of hospital stay or variable costs. Lower respiratory tract infection was associated with an increase of 2.58 days in the hospital and variable costs of AU$24, whereas other types of infection were associated with an increased length of stay of 2.61 days but not with variable costs. Many other factors were found to be associated with increased length of stay and variable costs alongside healthcare-acquired infection. The exclusion of these variables caused a positive bias in the estimates of the costs of healthcare-acquired infection.

Conclusions.

The existing literature may overstate the costs of healthcare-acquired infection because of bias, and the existing estimates of excess costs may not make intuitive sense to clinicians and policy makers. Accurate estimates of the costs of healthcare-acquired infection should be made and used in appropriately designed decision-analytic economic models (ie, cost-effectiveness models) that will make valid and believable predictions of the economic value of increased infection control.
The inert doublet model: an archetype for dark matter
Authors: Honorez Laura Lopez , Nezri Emmanuel , Oliver Josep F , Tytgat Michel H G
Published: February 2007

The inert doublet model (IDM), a two Higgs extension of the standard model with an unbroken
Z
2
symmetry, is a simple and yet rich model of dark matter. We present a systematic analysis
of the dark matter abundance and investigate the potentialities for direct and
gamma indirect detection. We show that the model should be within the range of
future experiments, like GLAST and ZEPLIN. The lightest stable scalar in the
IDM is a perfect example, or archetype of a weakly interacting massive particle.
From Statistical Nuisances to Serious Modeling: Changing How We Think About the Analysis of Time-Series—Cross-Section Data
Authors: Beck Nathaniel
Published: February 2007

This special issue of Political Analysis hopefully marks a watershed in how we as a discipline think about modeling time-series—cross-section (TSCS) data. By that I mean moving beyond thinking of TSCS data as only presenting a series of technical estimation problems that are seen as violations of the Gauss-Markov assumptions, problems that can be treated by better estimation methods. The articles in this special issue point to ways of moving forward in thinking of TSCS data as providing opportunities to model intrinsic and important features of the data (while also paying attention to the various statistical issues).
Using genomic data to unravel the root of the placental mammal phylogeny
Authors: Murphy William J. , Pringle Thomas H. , Crider Tess A. , Springer Mark S. , Miller Webb
Published: February 2007

The phylogeny of placental mammals is a critical framework for choosing future genome sequencing targets and for resolving the ancestral mammalian genome at the nucleotide level. Despite considerable recent progress defining superordinal relationships, several branches remain poorly resolved, including the root of the placental tree. Here we analyzed the genome sequence assemblies of human, armadillo, elephant, and opossum to identify informative coding indels that would serve as rare genomic changes to infer early events in placental mammal phylogeny. We also expanded our species sampling by including sequence data from >30 ongoing genome projects, followed by PCR and sequencing validation of each indel in additional taxa. Our data provide support for a sister-group relationship between Afrotheria and Xenarthra (the Atlantogenata hypothesis), which is in turn the sister-taxon to Boreoeutheria. We failed to recover any indels in support of a basal position for Xenarthra (Epitheria), which is suggested by morphology and a recent retroposon analysis, or a hypothesis with Afrotheria basal (Exafricoplacentalia), which is favored by phylogenetic analysis of large nuclear gene data sets. In addition, we identified two retroposon insertions that also support Atlantogenata and none for the alternative hypotheses. A revised molecular timescale based on these phylogenetic inferences suggests Afrotheria and Xenarthra diverged from other placental mammals ∼103 (95–114) million years ago. We discuss the impacts of this topology on earlier phylogenetic reconstructions and repeat-based inferences of phylogeny.
Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae
Authors: Hu Yanhui , Rolfs Andreas , Bhullar Bhupinder , Murthy Tellamraju V. S. , Zhu Cong , Berger Michael F. , Camargo Anamaria A. , Kelley Fontina , McCarron Seamus , Jepson Daniel , Richardson Aaron , Raphael Jacob , Moreira Donna , Taycher Elena , Zuo Dongmei , Mohr Stephanie , Kane Michael F. , Williamson Janice , Simpson Andrew , Bulyk Martha L. , Harlow Edward , Marsischky Gerald , Kolodner Richard D. , LaBaer Joshua
Published: February 2007

The availability of an annotated genome sequence for the yeast Saccharomyces cerevisiae has made possible the proteome-scale study of protein function and protein–protein interactions. These studies rely on availability of cloned open reading frame (ORF) collections that can be used for cell-free or cell-based protein expression. Several yeast ORF collections are available, but their use and data interpretation can be hindered by reliance on now out-of-date annotations, the inflexible presence of N- or C-terminal tags, and/or the unknown presence of mutations introduced during the cloning process. High-throughput biochemical and genetic analyses would benefit from a “gold standard” (fully sequence-verified, high-quality) ORF collection, which allows for high confidence in and reproducibility of experimental results. Here, we describe Yeast FLEXGene, a S. cerevisiae protein-coding clone collection that covers over 5000 predicted protein-coding sequences. The clone set covers 87% of the current S. cerevisiae genome annotation and includes full sequencing of each ORF insert. Availability of this collection makes possible a wide variety of studies from purified proteins to mutation suppression analysis, which should contribute to a global understanding of yeast protein function.
The GCR1, GPA1, PRN1, NF-Y Signal Chain Mediates Both Blue Light and Abscisic Acid Responses in Arabidopsis
Authors: Warpeha Katherine M. , Upadhyay Snehali , Yeh Jennifer , Adamiak Julia , Hawkins Samuel I. , Lapik Yevgeniya R. , Anderson Mary Beth , Kaufman Lon S.
Published: February 2007

Different classes of biotic (e.g. plant hormones) and abiotic (e.g. different wavelengths of light) signals act through specific signal transduction mechanisms to coordinate higher plant development. While a great deal of progress has been made, full signal transduction chains have not yet been described for most blue light- or abscisic acid-mediated events. Based on data derived from T-DNA insertion mutants and yeast (Saccharomyces cerevisiae) two-hybrid and coprecipitation assays, we report a signal transduction chain shared by blue light and abscisic acid leading to light-harvesting chlorophyll a/b-binding protein expression in etiolated Arabidopsis (Arabidopsis thaliana) seedlings. The chain consists of GCR1 (the sole Arabidopsis protein coding for a potential G-protein-coupled receptor), GPA1 (the sole Arabidopsis Gα-subunit), Pirin1 (PRN1; one of four members of an iron-containing subgroup of the cupin superfamily), and a nuclear factor Y heterotrimer comprised of A5, B9, and possibly C9. We also demonstrate that this mechanism is present in imbibed seeds wherein it affects germination rate.
Characterization of the Regulatory and Expression Context of an Alternative Oxidase Gene Provides Insights into Cyanide-Insensitive Respiration during Growth and Development
Authors: Ho Lois H.M. , Giraud Estelle , Lister Ryan , Thirkettle-Watts David , Low Jasmine , Clifton Rachel , Howell Katharine A. , Carrie Chris , Donald Tamzin , Whelan James
Published: February 2007

Alternative oxidase (AOX) is encoded in small multigene families in plants. Functional analysis of the Arabidopsis (Arabidopsis thaliana) alternative oxidase 1c (AtAOX1c) promoter, an AOX gene not induced by oxidative stress, indicated that regulation of expression was complex, with the upstream promoter region containing positive and negative response regions. Comparison to the promoter region of soybean (Glycine max) alternative oxidase 2b (GmAOX2b), another AOX gene not induced by oxidative stress, revealed that they contained seven sequence elements in common. All elements were active in the promoter region of AtAOX1c in suspension cells and in leaf tissue from Columbia and mutant plants, where a mitochondrial protein import receptor was inactivated. Analysis of coexpressed and putatively coregulated genes, the latter defined as containing five or more sequence elements functional in AtAOX1c, indicated that AtAOX1c was coregulated with components involved with cell division and growth. Consistent with this analysis, we demonstrated that site II elements, previously shown to regulate the proliferating cell nuclear antigen, are present in the upstream promoter region of AtAOX1c and were strong negative regulators of AtAOX1c expression. It was demonstrated that NDB4, a gene encoding an external NAD(P)H dehydrogenase, displayed strong coexpression with AtAOX1c. Overall, these results indicate that AtAOX1c is regulated by growth and developmental signals.
Characterization of Two Brassinosteroid C-6 Oxidase Genes in Pea
Authors: Jager Corinne E. , Symons Gregory M. , Nomura Takahito , Yamada Yumiko , Smith Jennifer J. , Yamaguchi Shinjiro , Kamiya Yuji , Weller James L. , Yokota Takao , Reid James B.
Published: February 2007

C-6 oxidation genes play a key role in the regulation of biologically active brassinosteroid (BR) levels in the plant. They control BR activation, which involves the C-6 oxidation of 6-deoxocastasterone (6-DeoxoCS) to castasterone (CS) and in some cases the further conversion of CS to brassinolide (BL). C-6 oxidation is controlled by the CYP85A family of cytochrome P450s, and to date, two CYP85As have been isolated in tomato (Solanum lycopersicum), two in Arabidopsis (Arabidopsis thaliana), one in rice (Oryza sativa), and one in grape (Vitis vinifera). We have now isolated two CYP85As (CYP85A1 and CYP85A6) from pea (Pisum sativum). However, unlike Arabidopsis and tomato, which both contain one BR C-6 oxidase that converts 6-DeoxoCS to CS and one BR C-6 Baeyer-Villiger oxidase that converts 6-DeoxoCS right through to BL, the two BR C-6 oxidases in pea both act principally to convert 6-DeoxoCS to CS. The isolation of these two BR C-6 oxidation genes in pea highlights the species-specific differences associated with C-6 oxidation. In addition, we have isolated a novel BR-deficient mutant, lke, which blocks the function of one of these two BR C-6 oxidases (CYP85A6). The lke mutant exhibits a phenotype intermediate between wild-type plants and previously characterized pea BR mutants (lk, lka, and lkb) and contains reduced levels of CS and increased levels of 6-DeoxoCS. To date, lke is the only mutant identified in pea that blocks the latter steps of BR biosynthesis and it will therefore provide an excellent tool to further examine the regulation of BR biosynthesis and the relative biological activities of CS and BL in pea.
Roles of Brassinosteroids and Related mRNAs in Pea Seed Growth and Germination
Authors: Nomura Takahito , Ueno Masaaki , Yamada Yumiko , Takatsuto Suguru , Takeuchi Yasutomo , Yokota Takao
Published: February 2007

The levels of endogenous brassinosteroids (BRs) and the expression of the biosynthesis/metabolism/perception genes involved have been investigated during the development and germination of pea (Pisum sativum) seeds. When seeds were rapidly growing, the level of biologically active BRs (brassinolide [BL] and castasterone [CS]) and the transcript levels of two BR C-6 oxidases (CYP85A1 and CYP85A6) reached a maximum, suggesting the significance of BL and CS in seed development. In the early stages of germination, CS, but not BL, appeared and its level increased in the growing tissues in which the transcript level of CYP85A1 and CYP85A6 was high, suggesting the significance of CS in seed germination and early seedling growth of pea. 6-Deoxocathasterone (6-deoxoCT) was the quantitatively major BR in mature seeds. At the early stage of germination, the level of 6-deoxoCT was specifically decreased, whereas the levels of downstream intermediates were increased. It seems that 6-deoxoCT is the major storage BR and is utilized during germination and early growth stages. The level of the mRNAs of BR biosynthesis and perception genes fluctuated during seed development. In mature seeds, most of mRNAs were present, but the level was generally lower compared with immature seeds. However, CYP90A9 mRNA rapidly increased during seed development and reached the maximum in mature seeds. The mRNAs stored in mature pea seeds seem to be utilized when seeds germinate. However, it was found that de novo transcription of mRNAs also starts as early as during seed imbibition.