bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon dioxide column abundances at the Wisconsin Tall Tower site
Authors: Washenfelder R. A. , Toon G. C. , Blavier J.‐F. , Yang Z. , Allen N. T. , Wennberg P. O. , Vay S. A. , Matross D. M. , Daube B. C.
Published: November 2006

We have developed an automated observatory for measuring atmospheric column abundances of CO2 and O2 using near‐infrared spectra of the Sun obtained with a high spectral resolution Fourier Transform Spectrometer (FTS). This is the first dedicated laboratory in a new network of ground‐based observatories named the Total Carbon Column Observing Network. This network will be used for carbon cycle studies and validation of spaceborne column measurements of greenhouse gases. The observatory was assembled in Pasadena, California, and then permanently deployed to northern Wisconsin during May 2004. It is located in the heavily forested Chequamegon National Forest at the WLEF Tall Tower site, 12 km east of Park Falls, Wisconsin. Under clear sky conditions, ∼0.1% measurement precision is demonstrated for the retrieved column CO2 abundances. During the Intercontinental Chemical Transport Experiment–North America and CO2 Boundary Layer Regional Airborne Experiment campaigns in summer 2004, the DC‐8 and King Air aircraft recorded eight in situ CO2 profiles over the WLEF site. Comparison of the integrated aircraft profiles and CO2 column abundances shows a small bias (∼2%) but an excellent correlation.
Influence of a complex land surface scheme on Arctic climate simulations
Authors: Saha S. K. , Rinke A. , Dethloff K. , Kuhry P.
Published: November 2006

The regional climate model HIRHAM4 coupled with two different land surface models (ECHAM4‐LSM and NCAR‐LSM) has been applied over the entire Arctic region. Model results have been compared with the observed monthly soil temperature and snow water equivalent from several weather stations in east Siberia and west Russia. Our study shows that the seasonal cycle of soil temperature is reasonably well reproduced by both versions of the model. HIRHAM4‐ECHAM4‐LSM produces cold soil temperature bias during winter, and the use of HIRHAM4‐NCAR‐LSM reduces such bias because of its more advanced land surface schemes. Insulation by snow on the ground surface is one of the main controlling factors of soil temperature, and the increased association between snow and soil temperature in HIRHAM4‐NCAR‐LSM has led to the improvement in winter soil temperature. We further established that the influences of land surface schemes and their coupling on the atmospheric conditions not only affect climate simulations on land but also in remote Arctic Ocean regions. Similarly as for the present day climate, two different land surface schemes can have significant influences on the simulated future climate. These influences imply an additional uncertainty in future climate projections.
Variability in clear‐sky longwave radiative cooling of the atmosphere
Authors: Allan Richard P.
Published: November 2006

The longwave radiative cooling of the clear‐sky atmosphere (QLWc) is a crucial component of the global hydrological cycle and is composed of the clear‐sky outgoing longwave radiation to space (OLRc) and the net downward minus upward clear‐sky longwave radiation to the surface (SNLc). Estimates of QLWc from reanalyses and observations are presented for the period 1979–2004. Compared to other reanalyses data sets, the European Centre for Medium‐range Weather Forecasts 40‐year reanalysis (ERA40) produces the largest QLWc over the tropical oceans (217 W m−2), explained by the least negative SNLc. On the basis of comparisons with data derived from satellite measurements, ERA40 provides the most realistic QLWc climatology over the tropical oceans but exhibits a spurious interannual variability for column integrated water vapor (CWV) and SNLc. Interannual monthly anomalies of QLWc are broadly consistent between data sets with large increases during the warm El Niño events. Since relative humidity (RH) errors applying throughout the troposphere result in compensating effects on the cooling to space and to the surface, they exert only a marginal effect on QLWc. An observed increase in CWV with surface temperature of 3 kg m−2 K−1 over the tropical oceans is important in explaining a positive relationship between QLWc and surface temperature, in particular over ascending regimes; over tropical ocean descending regions this relationship ranges from 3.6 to 4.6 ± 0.4 W m−2 K−1 for the data sets considered, consistent with idealized sensitivity tests in which tropospheric warming is applied and RH is held constant and implying an increase in precipitation with warming.
Observations of event‐based streambed deformation in a gravel bed channel
Authors: Haschenburger Judith K.
Published: November 2006

The streambed is the major source of bed load sediment in gravel bed channels and is necessarily deformed during floods that mobilize sediment. This study uses observations of scour and fill from Carnation Creek, Canada, to articulate at‐a‐point relations of the occurrence and magnitude of bed deformation and the resulting adjustments in bed configuration over a series of flood events. The likelihood of local bed deformation by scour, fill, or both depends on flow magnitude. At most locations, there is an imbalance of scour and fill that leads to adjustments in bed elevation, and these imbalances increase with flow. Persistent deformation of locations in lower portions of the bed topography tend to produce larger total exchanges between bed and mobile sediment over the flood series but locations that experience similar frequencies of bed deformation do not produce unique depth distributions. These results underscore the importance of understanding the coupling of scour and fill that produces streambed adjustment when modeling streambed evolution and managing river habitat.
The protein kinase TOUSLED is required for maintenance of transcriptional gene silencing in Arabidopsis
Authors: Wang Yu , Liu Jun , Xia Ran , Wang Junguo , Shen Jie , Cao Rui , Hong Xuhui , Zhu Jian‐Kang , Gong Zhizhong
Published: November 2006

TOUSLED‐like kinases (TLKs) are highly conserved in plants and animals, but direct evidence linking TLKs and transcriptional gene silencing is lacking. We isolated two new alleles of TOUSLED (TSL). Mutations of TSL in ros1 reactivate the transcriptionally silent 35S‐NPTII transgene and the transcriptionally silent endogenous loci TSI (TRANSCRIPTIONAL SILENCING INFORMATION). Chromatin immunoprecipitation (ChIP) analysis shows that histone H3Lys9 dimethylation is decreased in the reactivated transgene and endogenous TSI loci in the tsl ros1 mutant. However, there is no change in DNA methylation in the affected loci. Western blot and ChIP assay suggest that TSL might not be responsible for histone H3Ser10 phosphorylation. The tsl seedlings were more sensitive to DNA damage reagent methyl methanesulphonate and UV‐B light. Our results provide direct evidence for a crucial role of the TOUSLED protein kinase in the maintenance of transcriptional gene silencing in some genomic regions in a DNA‐methylation‐independent manner in Arabidopsis.
Drug Master file Review Issues at the Office of Generic Drugs
Authors: Schwartz Paul
Published: November 2006

The Office of Generic Drugs (OGD) in the US Food and Drug Adminstration's (FDA) Center for Drug Evaluation and Research (CDER) has recently been receiving unprecedented numbers of abbreviated new drug applications (ANDAs); currently, more than 700 per year. Each ANDA is supported by drug master files (DMFs), which are separate proprietary documents describing the chemistry, manufacture and associated controls for the active pharmaceutical ingredients (APIs). Usually, the firm submitting the ANDA purchases the API from a fine chemicals producer who has filed a DMF with the FDA. A Letter of Authorisation (LOA) from the DMF holder allows the FDA staff to review the DMF in conjunction with review of the ANDA. An adequate DMF is one requirement for approval of an ANDA. To date, over 18,000 DMFs have been submitted to the FDA. Very few of these are found to be adequate in an initial review and, consequently, approvals of ANDAs are delayed as additional information and data are needed from the DMF holder to ensure consistent production of high-quality APIs. Illustrative examples of typical DMF deficiencies are presented in this paper and suggestions for improved DMF submissions are given.
Equilibrium and stability studies of oblate field-reversed configurations in the Magnetic Reconnection Experiment
Authors: Gerhardt S. P. , Belova E. , Inomoto M. , Yamada M. , Ji H. , Ren Y. , Kuritsyn A.
Published: November 2006

The equilibrium and stability of oblate field-reversed configurations (FRCs) have been studied in the Magnetic Reconnection Experiment [M. Yamada et al., Phys. Plasmas 4, 1936 (1997)]. In the absence of a passive stabilization, tilt and shift instabilities often become unstable, with the tilt in particular limiting the plasma lifetime. The tilt instability can be mitigated by either including a passive stabilizing conductor, or by forming very oblate plasmas. Large perturbations (n=2 and 3) may still remain after passive stabilization is applied. These perturbations have the characteristics of co-interchange modes, which have never been observed, and can lead to the early termination of the plasma. The co-interchange modes can be minimized through the formation of plasmas with a very oblate shape, leading to the maximum FRC lifetime. A code has been developed to calculate equilibria for these plasmas. A rigid-body model explains the improved stability of oblate plasmas to n=1 tilt modes. Numerical calculations indicate improved stability to n⩾2 co-interchange modes for the very oblate plasma shapes.
Beam tracing description of non-Gaussian wave beams
Authors: Tsironis Christos , Poli Emanuele , Pereverzev Grigory V.
Published: November 2006

In experiments involving electron-cyclotron waves, beams with a non-Gaussian amplitude profile can be generated by the launching system or during the propagation in the plasma. The propagation and absorption of non-Gaussian beams is formulated in terms of the beam tracing asymptotic technique. The proper sequence for tracing arbitrary beams has been established, which involves the formulation of the decomposition of arbitrary electric field profiles into Gaussian-Hermite modes, the generalization of the beam width parameter, and the damping of higher-order modes. The effect of the phase-shift of the modes (with respect to the beam axis) is analyzed within beam tracing and included in the description of the beam. As an application, we consider the propagation and absorption of multimode beams in a simplified plasma geometry, where a comparison with an exact solution is possible. Also, the properties of the propagation of a non-Gaussian beam in the transmission line of an EC launching system are analyzed.
Optical limiting behavior of bismuth oxide-based glass in the visible range
Authors: Oliveira T. R. , de S. Menezes L. , Falcão-Filho E. L. , Gomes A. S. L. , de Araújo Cid B. , Sakaguchi K. , Mezzapesa F. P. , Carvalho I. C. S. , Kazansky P. G.
Published: November 2006

The authors report experimental results on the optical limiting behavior of a bismuth oxide-based glass by exciting the samples with nanosecond laser pulses at 532 and 598nm. The results show that two-photon and free-carrier absorption processes contribute for the nonlinear absorption. Values for β, the two-photon absorption coefficient, and σe, the absorption cross section due to free carriers, were determined. The values of β and σe are dependent on the amount of bismuth oxide in the glass composition.
Epitaxial growth and B-site cation ordering in layered double perovskite La2CuSnO6 thin films
Authors: Masuno A. , Haruta M. , Azuma M. , Kurata H. , Isoda S. , Takano M. , Shimakawa Y.
Published: November 2006

Epitaxial thin films of layered double perovskite La2CuSnO6 were fabricated on (001)-oriented SrTiO3, (LaAlO3)0.3–(SrAl0.5Ta0.5O3)0.7, and LaAlO3 substrates with a pulsed laser deposition method. B-site cation ordering of the layer structure can be controlled by tuning the substrate temperature during deposition. X-ray diffraction and scanning transmission electron microscopy revealed that the lattice parameters were strongly correlated with the degree of Cu∕Sn ordering. The relationship between the lattice parameters and the B-site cation ordering originates in the orientation of the Jahn-Teller distorted CuO6 octahedra.
Gradient refractive index planar microlens in Si using porous silicon
Authors: Ilyas S. , Gal M.
Published: November 2006

Significant effort is being expended on the integration of silicon electronics and optoelectronics. Here the authors describe a method to create planar gradient refractive index (GRIN) lenses in Si using porous silicon (PSi) technology. The authors’ approach allows the fabrication of a single planar lens or an array of such lenses with focal length that can be adjusted to match existing device(s) on the chip. The lenses are transparent in the near IR, including the optical communication window (1.3μm<λ<1.6μm). In addition to being potential components in future Si based integrated optical circuits, PSi GRIN lenses can also be used to improve the light coupling efficiency of existing Si based devices, such as sensors, detectors, and waveguides.
Enhanced coupling to whispering gallery modes by two-photon absorption induced by a highly focused field
Authors: Kuriakose Smitha , Morrish Dru , Gan Xiaosong , Chon James W. M. , Gu Min
Published: November 2006

The authors report on enhanced coupling to whispering gallery modes in fluorescent polystyrene microspheres using two-photon absorption induced by a highly focused field. Due to the highly confined excitation nature under focused evanescent illumination achieved by a circularly obstructed beam, the whispering gallery modes can be excited within a small volume near the perimeter of the microsphere. As a result, the visibility, the Q factor, and the degree of polarization of the fluorescence spectra induced in the microsphere are enhanced by 60%, 37%, and five times, respectively.
Controlled plasmon resonance in closed metal/insulator/metal nanocavities
Authors: Miyazaki Hideki T. , Kurokawa Yoichi
Published: November 2006

The controlled plasmon resonance in nanometer-sized optical cavities with a closed end has been demonstrated. A nanosheet plasmon cavity is a metal/insulator/metal waveguide with a finite length. Its lowest-order transverse-magnetic guided mode is reflected at the ends and exhibits the Fabry-Pérot resonance. In this study, one of the ends was closed by an obliquely evaporated Au film, and the so-called organ pipe resonances were observed as reflection dips. Since such closed configurations offer a higher field enhancement and higher detection efficiency of the scattered light, they are promising as fundamental structures for Raman enhancement.
Deriving Willingness-to-Pay Estimates of Travel-Time Savings from Individual-Based Parameters
Authors: Hensher David A , Greene William H , Rose John M
Published: November 2006

There is a small but growing literature that promotes the derivation of distributions of willingness-to-pay (WTP) estimates using information specific to each individual observation. These are referred to as individual conditional distributions, in contrast to approaches that rely on unconditional distributions that use random assignment in the construction of WTP distributions within a sampled population. The interest in alternative specifications is in large measure attributed to the search for empirical ways of deriving the WTP distribution that satisfies a behaviourally acceptable sign and range over the entire domain. In this paper we examine both conditional and unconditional approaches to establishing WTP distributions within the context of a mixed logit model. We find that calculating WTP measures from ratios of individual-level parameters in contrast to drawing them from unconditional population distributions empirically reduces the incidence of extreme values. Our results suggest that although problematic estimates cannot be ruled out, the use of the extra information on each individual's choices is a valuable input into the derivation of WTP distributions.
Regional Trade and Production Blocs in a Global Industry: Towards a Comparative Framework for Research
Authors: Bair Jennifer
Published: November 2006

While apparel manufacturing is often considered the quintessential global industry, the regional dimension of trade and production in the textile and clothing sector is less widely noted. In this paper I discuss two macroregional production blocs: North America (defined as the United States, Mexico, and the Caribbean Basin countries) and Greater Europe [which includes the European Union (EU), Central and Eastern Europe, Turkey, and North Africa]. Analyzing what opportunities regionalization might provide is particularly relevant given China's increasing dominance of both the EU and US import markets in the post-Multifibre Arrangement period. Drawing on the global commodity chains literature, I discuss three dimensions around which cross-regional comparative research on the European and North American apparel sectors can be organized: (1) production model; (2) institutional context; and (3) development outcomes. Several similarities between these production blocs are noted, particularly with regard to the intraregional division of labor expressed by networks connecting firms in higher-wage and lower-wage countries and the coexistence of assembly subcontracting and full-package manufacturing in both regions, but differences include the existence in Europe of a stronger textile base and a more expansive regionalization strategy (as suggested by the Euro–Mediterranean Partnership), which may strengthen the competitiveness of the Greater European bloc vis-à-vis its North American counterpart.
The Global Sourcing Patterns of French Clothing Retailers
Authors: Palpacuer Florence
Published: November 2006

Combining a business-system perspective and a global value-chain perspective, I draw on French clothing import data and interviews to characterize the sourcing patterns of French clothing retailers and analyze their determinants. The dominant pattern identified is one of dispersed, unstable, and informal supplier relations, which can be explained by the importance of small specialized chains, the predominance of family and management ownership, and a low concentration level in French clothing retailing. Since the late 1990s, however, the largest retailers operating in the standard-product segment, some of them engaged in ‘financialization’ strategies, have launched supply-chain rationalization policies aimed at reducing the number of suppliers, stabilizing relations with preferred suppliers, and externalizing manufacturing-related services. A new sourcing model of Anglo-Saxon origin can thus be seen to be diffusing under the combined influence of concentration and financialization in the French clothing retail scene.
In vitro characteristics of fresh and frozen - thawed ram spermatozoa after sex sorting and re-freezing
Authors: de Graaf S. P. , Evans G. , Maxwell W. M. C. , O'Brien J. K.
Published: November 2006

The in vitro function of sex-sorted, frozen–thawed ram spermatozoa derived from fresh or frozen semen was investigated. Sorted, frozen–thawed spermatozoa had higher (P < 0.05) motility, viability, acrosome integrity and mitochondrial activity than non-sorted, frozen–thawed controls immediately following thawing and after incubation at 37°C for 3 and 6 h. Similarly, frozen–thawed, sorted, re-frozen–thawed spermatozoa outperformed (P < 0.05) non-sorted controls upon thawing (mitochondrial activity) and following a 3-h incubation (motility, viability/acrosome integrity and mitochondrial activity), but there were no differences after incubation for 6 h (P > 0.05). Velocity characteristics (computer assisted sperm assessment 0–6 h post-thaw) of sorted spermatozoa derived from either fresh or frozen semen remained inferior (P < 0.05) to non-sorted spermatozoa, as did their ability to penetrate artificial cervical mucus after thawing. Direct comparison of cryopreserved spermatozoa derived from either fresh or frozen semen revealed that frozen–thawed, sorted, re-frozen–thawed spermatozoa had comparable (P > 0.05) motility, viability/acrosome integrity, mitochondrial activity, average path velocity and oviducal binding capacity immediately post-thaw, but reduced (P < 0.05) quality after 3 and 6 h of incubation. These findings indicate that, under the tested in vitro conditions, sex-sorted spermatozoa derived from fresh semen are superior in some respects to those derived from frozen semen. Further, that the use of either technique, while reducing velocity characteristics and cervical mucus penetration, results in comparable, if not enhanced motility, membrane and mitochondrial function in the post-thaw population of spermatozoa when compared with non-sorted, frozen–thawed controls.
The mitochondrial contribution to stem cell biology
Authors: Bavister Barry D.
Published: November 2006

The distribution and functions of mitochondria in stem cells have not been examined, yet the contributions of these organelles to stem cell viability and differentiation must be vitally important in view of their critical roles in all other cell types. A key role for mitochondria in stem cells is indicated by reports that they translocate in the oocyte during fertilisation to cluster around the pronuclei and can remain in a perinuclear pattern during embryo development. This clustering appears to be essential for normal embryonic development. Because embryonic stem cells are derived from fertilised oocytes, and eventually can differentiate into ‘adult’ stem cells, it was hypothesised that mitochondrial perinuclear clustering persists through preimplantation embryo development into the stem cells, and that this localisation is indicative of stem cell pluripotency. Further, it was predicted that mitochondrial activity, as measured by respiration and adenosine triphosphate (ATP) content, would correlate with the degree of perinuclear clustering. It was also predicted that these morphological and metabolic measurements could serve as indicators of ‘stemness.’ This article reviews the distribution and metabolism of mitochondria in a model stem cell line and how this information is related to passage number, differentiation and/or senescence. In addition, it describes mitochondrial DNA deletions in oocytes and embryos that could adversely affect stem cell performance.
The use of focus groups to design an internet-based program for chlamydia screening with self-administered vaginal swabs: what women want
Authors: Gaydos Charlotte A. , Rizzo-Price Patricia A. , Barnes Mathilda , Dwyer Karen , Wood Billie Jo , Hogan M. Terry
Published: November 2006

Objective: To ascertain the opinions, concerns and perceptions of sexually active women to guide the development of an internet-based chlamydia outreach and screening program using self-administered vaginal swabs as a first step to prevention. Methods: Seven focus groups were conducted by trained facilitators. Questions were designed to initially open the discussion and elicit the members’ own perceptions. Secondary, more probing questions were asked later to confirm participants’ responses and elicit truthful answers. The main discussion topics were women’s ideas about internet recruitment for chlamydia screening, preferred genital sample type, self-sampling at home using vaginal swabs and using the mail to return specimens. Participants were 42 women, aged 14–49 years. Structured discussions were facilitated using open-ended questions about access to chlamydia testing via the internet. Data were collected and reviewed for common themes and emphasis. Results: All women actively participated in the discussions, providing valuable information. The concepts of self-sampling and the overall project were viewed positively, along with draft advertisements, questionnaires and self-sampling instructions; some modifications were suggested. Common themes included offering free kits available within their community or by direct mail, as well as pre-addressed, stamped mailers for returning the kit to the laboratory for testing. Commonly perceived obstacles and potential risks included: maintenance of confidentiality; situations of embarrassment; and ensuring simplicity of packaging. Women indicated confidence in their ability to collect vaginal specimens and willingness to call for their test results. Conclusions: Focus-group surveys were a useful tool and provided valuable feedback to inform the design of a specialised website to educate and facilitate access to chlamydia screening through home sampling.
Erection loss in association with condom use among young men attending a public STI clinic: potential correlates and implications for risk behaviour
Authors: Graham Cynthia A. , Crosby Richard , Yarber William L. , Sanders Stephanie A. , McBride Kimberly , Milhausen Robin R. , Arno Janet N.
Published: November 2006

Background: To assess prevalence of condom-associated erection loss and to identify correlates of erection loss among men attending a sexually transmissible infections (STI) clinic. Methods: Men (n = 278) attending an STI clinic responded to an anonymous questionnaire aided by a CD recording of the questions. The sample was screened to include only men who had used a condom during penile–vaginal sex at least three times in the past 3 months. Erection loss was assessed for ‘the last three times a condom was used’. Results: The mean age of the participants was 23.7 years (s.d. = 4.1); 37.1% of the men reported condom-associated erection loss on at least one occasion. Men who had reported condom-associated erection loss were also reported having more frequent unprotected vaginal sex (P = 0.04) and were less likely to use condoms consistently (P = 0.014) than men without erection loss. Men with erection loss were also more likely to remove condoms before sex was over (P = 0.001). Age and race/ethnicity were not associated with erection loss. In multivariate analysis, three significant statistical predictors were identified: low self-efficacy to use condoms (P = 0.001); problems with ‘fit or feel’ of condoms (P = 0.005); and having more than three sex partners during the previous 3 months (P = 0.02). Conclusions: Condom-associated erection loss may be common among men at risk for STIs. This problem may lead to incomplete or inconsistent condom use. Men may be more likely to experience condom-associated erection loss if they lack confidence to use condoms correctly, if they experience problems with the way condoms fit or feel, and if they have sex with multiple partners.
Alanine–glyoxylate aminotransferase-deficient mice, a model for primary hyperoxaluria that responds to adenoviral gene transfer
Authors: Salido Eduardo C. , Li Xiao M. , Lu Yang , Wang Xia , Santana Alfredo , Roy-Chowdhury Namita , Torres Armando , Shapiro Larry J. , Roy-Chowdhury Jayanta
Published: November 2006

Mutations in the alanine–glyoxylate amino transferase gene (
AGXT
) are responsible for primary hyperoxaluria type I, a rare disease characterized by excessive hepatic oxalate production that leads to renal failure. We generated a null mutant mouse by targeted mutagenesis of the homologous gene,
Agxt
, in embryonic stem cells. Mutant mice developed normally, and they exhibited hyperoxaluria and crystalluria. Approximately half of the male mice in mixed genetic background developed calcium oxalate urinary stones. Severe nephrocalcinosis and renal failure developed after enhancement of oxalate production by ethylene glycol administration. Hepatic expression of human AGT1, the protein encoded by
AGXT
, by adenoviral vector-mediated gene transfer in
Agxt
−/−
mice normalized urinary oxalate excretion and prevented oxalate crystalluria. Subcellular fractionation and immunofluorescence studies revealed that, as in the human liver, the expressed wild-type human AGT1 was predominantly localized in mouse hepatocellular peroxisomes, whereas the most common mutant form of AGT1 (G170R) was localized predominantly in the mitochondria.
A two-step mechanism underlies the planar polarization of regenerating sensory hair cells
Authors: López-Schier Hernán , Hudspeth A. J.
Published: November 2006

The restoration of planar cell polarity is an essential but poorly understood step toward physiological recovery during sensory-organ regeneration. Investigating this issue in the lateral line of the zebrafish, we found that hair cells regenerate in pairs along a single axis established by the restricted localization and oriented division of their progenitors. By analyzing mutants lacking the planar-polarity determinant Vangl2, we ascertained that the uniaxial production of hair cells and the subsequent orientation of their hair bundles are controlled by distinct pathways, whose combination underlies the establishment of hair-cell orientation during development and regeneration. This mechanism may represent a general principle governing the long-term maintenance of planar cell polarity in remodeling epithelia.
Emergence of the universal genetic code imprinted in an RNA record
Authors: Hohn Michael J. , Park Hee-Sung , O'Donoghue Patrick , Schnitzbauer Michael , Söll Dieter
Published: November 2006

The molecular basis of the genetic code manifests itself in the interaction of the aminoacyl-tRNA synthetases and their cognate tRNAs. The fundamental biological question regarding these enzymes' role in the evolution of the genetic code remains open. Here we probe this question in a system in which the same tRNA species is aminoacylated by two unrelated synthetases. Should this tRNA possess major identity elements common to both enzymes, this would favor a scenario where the aminoacyl-tRNA synthetases evolved in the context of preestablished tRNA identity, i.e., after the universal genetic code emerged. An experimental system is provided by the recently discovered
O
-phosphoseryl-tRNA synthetase (SepRS), which acylates tRNA
Cys
with phosphoserine (Sep), and the well known cysteinyl-tRNA synthetase, which charges the same tRNA with cysteine. We determined the identity elements of
Methanocaldococcus jannaschii
tRNA
Cys
in the aminoacylation reaction for the two
Methanococcus maripaludis
synthetases SepRS (forming Sep-tRNA
Cys
) and cysteinyl-tRNA synthetase (forming Cys-tRNA
Cys
). The major elements, the discriminator base and the three anticodon bases, are shared by both tRNA synthetases. An evolutionary analysis of archaeal, bacterial, and eukaryotic tRNA
Cys
sequences predicted additional SepRS-specific minor identity elements (G37, A47, and A59) and suggested the dominance of vertical inheritance for tRNA
Cys
from a single common ancestor. Transplantation of the identified identity elements into the
Escherichia coli
tRNA
Gly
scaffold endowed facile phosphoserylation activity on the resulting chimera. Thus, tRNA
Cys
identity is an ancient RNA record that depicts the emergence of the universal genetic code before the evolution of the modern aminoacylation systems.
Mitochondrial deoxynucleotide pool sizes in mouse liver and evidence for a transport mechanism for thymidine monophosphate
Authors: Ferraro Paola , Nicolosi Luca , Bernardi Paolo , Reichard Peter , Bianchi Vera
Published: November 2006

Dividing cultured cells contain much larger pools of the four dNTPs than resting cells. In both cases the sizes of the individual pools are only moderately different. The same applies to mitochondrial (mt) pools of cultured cells. Song
et al
. [Song S, Pursell ZF, Copeland WC, Longley MJ, Kunkel TA, Mathews CK (2005)
Proc Natl Acad Sci USA
102:4990–4995] reported that mt pools of rat tissues instead are highly asymmetric, with the dGTP pool in some cases being several-hundred-fold larger than the dTTP pool, and suggested that the asymmetry contributes to increased mutagenesis during mt DNA replication. We have now investigated this discrepancy and determined the size of each dNTP pool in mouse liver mitochondria. We found large variations in pool sizes that closely followed variations in the ATP pool and depended on the length of time spent in the preparation of mitochondria. The proportion between dNTPs was in all cases without major asymmetries and similar to those found earlier in cultured resting cells. We also investigated the import and export of thymidine phosphates in mouse liver mitochondria and provide evidence for a rapid, highly selective, and saturable import of dTMP, not depending on a functional respiratory chain. At nM external dTMP the nucleotide is concentrated 100-fold inside the mt matrix. Export of thymidine phosphates was much slower and possibly occurred at the level of dTDP.
Immunoglobulin G signaling activates lysosome/phagosome docking
Authors: Trivedi Vishal , Zhang Shao C. , Castoreno Adam B. , Stockinger Walter , Shieh Eugenie C. , Vyas Jatin M. , Frickel Eva-Maria , Nohturfft Axel
Published: November 2006

An important role of IgG antibodies in the defense against microbial infections is to promote the ingestion and killing of microbes by phagocytes. Here, we developed
in vivo
and
in vitro
approaches to ask whether opsonization of particles with IgG enhances intracellular targeting of lysosomes to phagosomes. To eliminate the effect of IgG on the ingestion process, cells were exposed to latex beads at 15–20°C, which allows engulfment of both IgG-coated and uncoated beads but prevents the fusion of lysosomes with phagosomes. Upon shifting the temperature to 37°C, phagosomes containing IgG beads matured significantly faster into phagolysosomes as judged by colocalization with lysosomal markers. The IgG effect was independent of other particle-associated antigens or serum factors. Lysosome/phagosome attachment was also quantified biochemically with a cytosol-dependent scintillation proximity assay. Interactions were enhanced significantly in reactions containing cytosol from mouse macrophages that had been exposed to IgG-coated beads, indicating that IgG signaling modulates the cytosolic-targeting machinery. Similar results were obtained with cytosol from primary human monocytes, human U-937 histiocytic lymphoma cells and from Chinese hamster ovary (CHO) cells transfected with a human IgG (Fcγ) receptor. IgG-induced activation is shown to affect the actin-dependent tethering/docking stage of the targeting process and to proceed through a pathway involving protein kinase C. These results provide a rare example of an extracellular signal controlling membrane targeting on the level of tethering and docking. We propose that this pathway contributes to the role of antibodies in the protection against microbial infections.
Becoming Visible: Women and Conflicts in the Quebec Metropolitan Areas, 1965-2000
Authors: Trudelle Catherine , Villeneuve Paul , Theriault Marius , Pelletier Mathieu
Published: November 2006

Since the 1960s, urban conflicts have tended to gain prominence in most cities of advanced economies. During the same period, women have also gained prominence in urban public life, including conflict activity. Have their roles in these conflicts had possible humanising effects on urban life? More than 2000 conflicts are analysed, hypothesising that characteristics of conflicts influence the probability of women participating in them. It is found that this probability is much higher when actors come from civil society rather than from the state or the private sector and when conflicts deal with social issues rather than economic or, surprisingly, environmental issues. It is also found that this probability diminishes with time, indicating increasing institutionalisation and diversification of women's roles in urban public life.
Gene Expression Analysis on the Dicyclanil-Induced Hepatocellular Tumors in Mice
Authors: Moto Mitsuyoshi , Okamura Miwa , Muguruma Masako , Ito Tadasi , Jin Meilan , Kashida Yoko , Mitsumori Kunitoshi
Published: November 2006

Our previous studies showed the possibility that oxidative stress, including oxidative DNA damage, is involved in the mechanism of dicyclanil (DC)-induced hepatocarcinogenesis at the preneoplastic stage in mice. In this study, the expression analyses of genes, including oxidative stress-related genes, were performed on the tissues of hepatocellular tumors in a two-stage liver carcinogenesis model in mice. After partial hepatectomy, male ICR mice were injected with N-diethylnitrosamine (DEN) and given a diet containing 0 or 1500 ppm of DC for 20 weeks. Histopathological examinations revealed that the incidence of hepatocellular tumors (adenomas and carcinomas) significantly increased in the DEN + DC group. Gene expression analysis on the microdissected liver tissues of the mice in the DEN + DC group showed the highest expression levels of oxidative stress-related genes, such as Cyp1a1 and Txnrd1, in the tumor areas. However, no remarkable up-regulation of Ogg1—an oxidative DNA damage repair gene—was observed in the tumor areas, but the expression of Trail—an apoptosis-signaling ligand gene—was significantly down-regulated in the tumor tissues. These results suggest the possibility that the inhibition of apoptosis and a failure in the ability to repair oxidative DNA damage occur in the hepatocellular DC-induced tumors in mice.
BEYOND ACTIVATION REFORMING EUROPEAN UNEMPLOYMENT PROTECTION SYSTEMS IN POST-INDUSTRIAL LABOUR MARKETS
Authors: Clasen Jochen , Clegg Daniel
Published: November 2006

Though activation has been a key theme in recent comparative scholarship on social policy, existing research has arguably failed to capture some important cross-national differences in the extent of welfare state adaptation it entails. Conceptualising activation as but one unemployment policy reform indicator alongside ‘unemployment support homogenisation’ and ‘unemployment policy co-ordination’, and empirically sketching reform trends in four European states, this article argues it is possible to identify a cleavage between countries where activation policies are part of an unambiguous adaptation of labour market policies to the emergent post-industrial economy, and countries in which similar trends of policy adaptation have been more constrained, hesitant and uneven. To account for this fracture it is necessary to understand the differing ways that conventional unemployment policies were institutionally articulated within national political economies, as this bears on the feasibility of a new paradigm of labour market regulation emerging.
ATTITUDES TO GENE TECHNOLOGY: THE SIGNIFICANCE OF TRUST IN INSTITUTIONS
Authors: Olofsson Anna , Öhman Susanna , Rashid Saman
Published: November 2006

This is a study of the relationship between trust in institutions and attitudes to gene technology in general, and GM food and stem cell research in particular. The role of so-called active trust is emphasised, meaning that trust is neither conceived as a trait nor a one-dimensional concept. The study uses data from a Eurobarometer survey of gene technology in Europe, conducted in 2002. People's attitudes in five European counties, France, Germany, Italy, Sweden and United Kingdom are compared, and the significance of trust in institutions in these countries is investigated. The results show that trust in institutions has an impact on attitudes to gene technology. Trust in experts, stakeholders and official bodies are associated with positive attitudes to GM food and stem cell research, whereas trust in Non-Governmental Organisations is associated with negative perceptions of these technologies. This confirms the significant role of active trust.
Effects of carbohydrate ingestion on skill maintenance in squash players
Authors: Bottoms Lindsay M. , Hunter Angus M. , Galloway Stuart D.R.
Published: November 2006

The effects of carbohydrate (CHO) ingestion during sports which require high levels of motor and cognitive skill, such as squash, have produced conflicting results. This study aimed to explore the effect of CHO ingestion on squash skill following short duration exercise simulating the demands of squash play. Sixteen male squash players of a high standard were recruited. Following a VO2max test, and familiarisation trial, subjects completed two further trials assessing skill pre‐ and post‐exercise designed to simulate the demands of squash play. A squash skill test assessed accuracy of the forehand and backhand straight drives. Exercise consisted of 20 minutes of shuttle running at 82(±5)% HRmax, and 9 minutes of ghosting at 94(±4)% HRmax. Capillary blood samples (20 µl) were taken at five intervals for measurement of glucose and lactate. Cognitive function was measured with choice visual and auditory reaction time (RT) tests pre‐ and post‐exercise, as was forearm wrist flexor MVC and fatigue profile. CHO drink (6.4% CHO) or matched placebo (PL) were administered after the initial skill test (500 ml), after the shuttle running (250 ml), and after the ghosting (250 ml) in a double blind crossover design. There was no overall effect of CHO ingestion on skill maintenance (p=0.10) however, significantly fewer balls landed outside the scoring zone (p=0.03) on the CHO ingestion trial. There was no change of visual RT pre‐ to post‐exercise on PL (+0.01±0.03s), but a significant improvement (−0.07±0.05s) was observed in the CHO trial. Auditory RT improved pre‐ to post‐exercise during both trials. MVC and fatigue profile of the wrist flexors was not different between trials but showed a force decrement pre‐ to post‐exercise (p<0.05). A significant difference in blood glucose was observed between trials (p<0.01) but blood lactate response during both trials was similar. These results lend some support to a beneficial effect of CHO ingestion on skill during game sports.
GARD: a genetic algorithm for recombination detection
Authors: Kosakovsky Pond Sergei L. , Posada David , Gravenor Michael B. , Woelk Christopher H. , Frost Simon D.W.
Published: November 2006

Motivation: Phylogenetic and evolutionary inference can be severely misled if recombination is not accounted for, hence screening for it should be an essential component of nearly every comparative study. The evolution of recombinant sequences can not be properly explained by a single phylogenetic tree, but several phylogenies may be used to correctly model the evolution of non-recombinant fragments.

Results: We developed a likelihood-based model selection procedure that uses a genetic algorithm to search multiple sequence alignments for evidence of recombination breakpoints and identify putative recombinant sequences. GARD is an extensible and intuitive method that can be run efficiently in parallel. Extensive simulation studies show that the method nearly always outperforms other available tools, both in terms of power and accuracy and that the use of GARD to screen sequences for recombination ensures good statistical properties for methods aimed at detecting positive selection.

Availability: Freely available

Contact:  spond@ucsd.edu
Tree and rate estimation by local evaluation of heterochronous nucleotide data
Authors: Yang Zhu , O'Brien John D. , Zheng Xiaobin , Zhu Huai-Qiu , She Zhen-Su
Published: November 2006

Motivation: Heterochronous gene sequence data is important for characterizing the evolutionary processes of fast-evolving organisms such as RNA viruses. A limited set of algorithms exists for estimating the rate of nucleotide substitution and inferring phylogenetic trees from such data. The authors here present a new method, Tree and Rate Estimation by Local Evaluation (TREBLE) that robustly calculates the rate of nucleotide substitution and phylogeny with several orders of magnitude improvement in computational time.

Methods: For the basis of its rate estimation TREBLE novelly utilizes a geometric interpretation of the molecular clock assumption to deduce a local estimate of the rate of nucleotide substitution for triplets of dated sequences. Averaging the triplet estimates via a variance weighting yields a global estimate of the rate. From this value, an iterative refinement procedure relying on statistical properties of the triplets then generates a final estimate of the global rate of nucleotide substitution. The estimated global rate is then utilized to find the tree from the pairwise distance matrix via an UPGMA-like algorithm.

Results: Simulation studies show that TREBLE estimates the rate of nucleotide substitution with point estimates comparable with the best of available methods. Confidence intervals are comparable with that of BEAST. TREBLE's phylogenetic reconstruction is significantly improved over the other distance matrix method but not as accurate as the Bayesian algorithm. Compared with three other algorithms, TREBLE reduces computational time by a minimum factor of 3000. Relative to the algorithm with the most accurate estimates for the rate of nucleotide substitution (i.e. BEAST), TREBLE is over 10 000 times more computationally efficient.

Availability:  

Contact:  jdobrien@ucla.edu
Striped Smith–Waterman speeds database searches six times over other SIMD implementations
Authors: Farrar Michael
Published: November 2006

Motivation: The only algorithm guaranteed to find the optimal local alignment is the Smith–Waterman. It is also one of the slowest due to the number of computations required for the search. To speed up the algorithm, Single-Instruction Multiple-Data (SIMD) instructions have been used to parallelize the algorithm at the instruction level.

Results: A faster implementation of the Smith–Waterman algorithm is presented. This algorithm achieved 2–8 times performance improvement over other SIMD based Smith–Waterman implementations. On a 2.0 GHz Xeon Core 2 Duo processor, speeds of >3.0 billion cell updates/s were achieved.

Availability:  

Contact:  farrar.michael@gmail.com
The Logic of the Survey Experiment Reexamined
Authors: Gaines Brian J. , Kuklinski James H. , Quirk Paul J.
Published: November 2006

Scholars of political behavior increasingly embed experimental designs in opinion surveys by randomly assigning respondents alternative versions of questionnaire items. Such experiments have major advantages: they are simple to implement and they dodge some of the difficulties of making inferences from conventional survey data. But survey experiments are no panacea. We identify problems of inference associated with typical uses of survey experiments in political science and highlight a range of difficulties, some of which have straightforward solutions within the survey-experimental approach and some of which can be dealt with only by exercising greater caution in interpreting findings and bringing to bear alternative strategies of research.
Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-β signaling in cooperation with active Kras expression
Authors: Ijichi Hideaki , Chytil Anna , Gorska Agnieszka E. , Aakre Mary E. , Fujitani Yoshio , Fujitani Shuko , Wright Christopher V.E. , Moses Harold L.
Published: November 2006

Pancreatic ductal adenocarcinoma (PDAC) is an almost uniformly lethal disease in humans. Transforming growth factor-β (TGF-β) signaling plays an important role in PDAC progression, as indicated by the fact that Smad4, which encodes a central signal mediator downstream from TGF-β, is deleted or mutated in 55% and the type II TGF-β receptor (Tgfbr2) gene is altered in a smaller subset of human PDAC. Pancreas-specific Tgfbr2 knockout mice have been generated, alone or in the context of active Kras (KrasG12D) expression, using the Cre-loxP system driven by the endogenous Ptf1a (pancreatic transcription factor-1a) locus. Pancreas-selective Tgfbr2 knockout alone gave no discernable phenotype in 1.5 yr. Pancreas-specific KrasG12D activation alone essentially generated only intraepithelial neoplasia within 1 yr. In contrast, the Tgfbr2 knockout combined with KrasG12D expression developed well-differentiated PDAC with 100% penetrance and a median survival of 59 d. Heterozygous deletion of Tgfbr2 with KrasG12D expression also developed PDAC, which indicated a haploinsufficiency of TGF-β signaling in this genetic context. The clinical and histopathological manifestations of the combined KrasG12D expression and Tgfbr2 knockout mice recapitulated human PDAC. The data show that blockade of TGF-β signaling and activated Ras signaling cooperate to promote PDAC progression.