bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-cost rapid detection of rifampicin resistant tuberculosis using bacteriophage in Kampala, Uganda
Authors: Traore Hamidou , Ogwang Sam , Mallard Kim , Joloba Moses L , Mumbowa Francis , Narayan Kalpana , Kayes Susan , Jones-Lopez Edward C , Smith Peter G , Ellner Jerrold J , Mugerwa Roy D , Eisenach Kathleen D , McNerney Ruth
Published: January 2007

Background

Resistance to anti-tuberculosis drugs is a serious public health problem. Multi-drug resistant tuberculosis (MDR-TB), defined as resistance to at least rifampicin and isoniazid, has been reported in all regions of the world. Current phenotypic methods of assessing drug susceptibility of M. tuberculosis are slow. Rapid molecular methods to detect resistance to rifampicin have been developed but they are not affordable in some high prevalence countries such as those in sub Saharan Africa. A simple multi-well plate assay using mycobacteriophage D29 has been developed to test M. tuberculosis isolates for resistance to rifampicin. The purpose of this study was to investigate the performance of this technology in Kampala, Uganda.

Methods

In a blinded study 149 M. tuberculosis isolates were tested for resistance to rifampicin by the phage assay and results compared to those from routine phenotypic testing in BACTEC 460. Three concentrations of drug were used 2, 4 and 10 μg/ml. Isolates found resistant by either assay were subjected to sequence analysis of a 81 bp fragment of the rpoB gene to identify mutations predictive of resistance. Four isolates with discrepant phage and BACTEC results were tested in a second phenotypic assay to determine minimal inhibitory concentrations.

Results

Initial analysis suggested a sensitivity and specificity of 100% and 96.5% respectively for the phage assay used at 4 and 10 μg/ml when compared to the BACTEC 460. However, further analysis revealed 4 false negative results from the BACTEC 460 and the phage assay proved the more sensitive and specific of the two tests. Of the 39 isolates found resistant by the phage assay 38 (97.4%) were found to have mutations predictive of resistance in the 81 bp region of the rpoB gene. When used at 2 μg/ml false resistant results were observed from the phage assay. The cost of reagents for testing each isolate was estimated to be 1.3US$ when testing a batch of 20 isolates on a single 96 well plate. Results were obtained in 48 hours.

Conclusion

The phage assay can be used for screening of isolates for resistance to rifampicin, with high sensitivity and specificity in Uganda. The test may be useful in poorly resourced laboratories as a rapid screen to differentiate between rifampicin susceptible and potential MDR-TB cases.
Evidence for recent gene flow between north-eastern and south-eastern Madagascan poison frogs from a phylogeography of the Mantella cowani group
Authors: Rabemananjara Falitiana CE , Chiari Ylenia , Ramilijaona Olga Ravoahangimalala , Vences Miguel
Published: January 2007

Background

The genusMantella, endemic poison frogs of Madagascar with 16 described species, are known in the field of international pet trade and entered under the CITES control for the last four years. The phylogeny and phylogeography of this genus have been recently subject of study for conservation purposes. Here we report on the studies of the phylogeography of theMantella cowanigroup using a fragment of 453 bp of the mitochondrial cytochromebgene from 195 individuals from 21 localities. This group is represented by five forms:M. cowani, a critically endangered species, a vulnerable species,M. haraldmeieri, and the non-threatenedM. baroni, M. aff.baroni, andM. nigricans.

Results

The Bayesian phylogenetic and haplotype network analyses revealed the presence of three separated haplotype clades: (1)M. baroni, M. aff.baroni, M. nigricans, and putative hybrids ofM. cowaniandM. baroni, (2)M. cowaniand putative hybrids ofM. cowaniandM. baroni, and (3)M. haraldmeieri. The putative hybrids were collected from sites whereM. cowaniandM. baronilive in sympatry.

Conclusion

These results suggest (a) a probable hybridization betweenM. cowaniandM. baroni, (b) a lack of genetic differentiation betweenM. baroni/M. aff.baroniandM. nigricans, (c) evidence of recent gene-flow between the northern (M. nigricans), eastern (M. baroni), and south-eastern (M. aff.baroni) forms of distinct coloration, and (d) the existence of at least three units for conservation in theMantella cowanigroup.
Methods for transient assay of gene function in floral tissues
Authors: Shang Yongjin , Schwinn Kathy E , Bennett Michael J , Hunter Donald A , Waugh Toni L , Pathirana Nilangani N , Brummell David A , Jameson Paula E , Davies Kevin M
Published: January 2007

Background

There is considerable interest in rapid assays or screening systems for assigning gene function. However, analysis of gene function in the flowers of some species is restricted due to the difficulty of producing stably transformed transgenic plants. As a result, experimental approaches based on transient gene expression assays are frequently used. Biolistics has long been used for transient over-expression of genes of interest, but has not been exploited for gene silencing studies. Agrobacterium-infiltration has also been used, but the focus primarily has been on the transient transformation of leaf tissue.

Results

Two constructs, one expressing an inverted repeat of the Antirrhinum majus (Antirrhinum) chalcone synthase gene (CHS) and the other an inverted repeat of the Antirrhinum transcription factor gene Rosea1, were shown to effectively induce CHS and Rosea1 gene silencing, respectively, when introduced biolistically into petal tissue of Antirrhinum flowers developing in vitro. A high-throughput vector expressing the Antirrhinum CHS gene attached to an inverted repeat of the nos terminator was also shown to be effective. Silencing spread systemically to create large zones of petal tissue lacking pigmentation, with transmission of the silenced state spreading both laterally within the affected epidermal cell layer and into lower cell layers, including the epidermis of the other petal surface. Transient Agrobacterium-mediated transformation of petal tissue of tobacco and petunia flowers in situ or detached was also achieved, using expression of the reporter genes GUS and GFP to visualise transgene expression.

Conclusion

We demonstrate the feasibility of using biolistics-based transient RNAi, and transient transformation of petal tissue via Agrobacterium infiltration to study gene function in petals. We have also produced a vector for high throughput gene silencing studies, incorporating the option of using T-A cloning to insert the gene sequence of interest. These techniques should allow analysis of gene function in a much broader range of flower species.
Counting colonies of clonogenic assays by using densitometric software
Authors: Niyazi Maximilian , Niyazi Ismat , Belka Claus
Published: January 2007

Clonogenic assays are a useful tool to test whether a given cancer therapy can reduce the clonogenic survival of tumour cells. A colony is defined as a cluster of at least 50 cells which can often only be determined microscopically. The process of counting colonies is very extensive work and so we developed software that is able to count the colonies automatically from scanned flasks. This software is made freely available by us with a detailed description how to use and install the necessary features.
Temporomandibular disorder is associated with a serotonin transporter gene polymorphism in the Japanese population
Authors: Ojima Kiyomi , Watanabe Nagaoki , Narita Naoko , Narita Masaaki
Published: January 2007

Aims

Recent genetic studies have linked serotonin-related genetic polymorphisms with diverse disorders characterized by functional somatic symptoms, including chronic fatigue syndrome, irritable bowel syndrome, and premenstrual dysphoric disorder.

Methods

We investigated three serotonin-related genetic polymorphisms by screening genomic DNA of 36 temporomandibular disorder (TMD) patients.

Results

A significant increase of longer alleles (l and xl) was found in the TMD patients compared to the controls both by the genotype-wise and the allele-wise analyses (both p < 0.01 by χ2 test and Fisher's exact test).

Conclusion

Genetic factors that involve the serotonergic system may play a role in the pathogenesis of TMD.
Qualitative networks: a symbolic approach to analyze biological signaling networks
Authors: Schaub Marc A , Henzinger Thomas A , Fisher Jasmin
Published: January 2007

Background

A central goal of Systems Biology is to model and analyze biological signaling pathways that interact with one another to form complex networks. Here we introduce Qualitative networks, an extension of Boolean networks. With this framework, we use formal verification methods to check whether a model is consistent with the laboratory experimental observations on which it is based. If the model does not conform to the data, we suggest a revised model and the new hypotheses are tested in-silico.

Results

We consider networks in which elements range over a small finite domain allowing more flexibility than Boolean values, and add target functions that allow to model a rich set of behaviors. We propose a symbolic algorithm for analyzing the steady state of these networks, allowing us to scale up to a system consisting of 144 elements and state spaces of approximately 1086 states. We illustrate the usefulness of this approach through a model of the interaction between the Notch and the Wnt signaling pathways in mammalian skin, and its extensive analysis.

Conclusion

We introduce an approach for constructing computational models of biological systems that extends the framework of Boolean networks and uses formal verification methods for the analysis of the model. This approach can scale to multicellular models of complex pathways, and is therefore a useful tool for the analysis of complex biological systems. The hypotheses formulated during in-silico testing suggest new avenues to explore experimentally. Hence, this approach has the potential to efficiently complement experimental studies in biology.
Adaptive wavelets for analyzing dispersive seismic waves
Authors: Kritski A. , Vincent A. P. , Yuen D. A. , Carlsen T.
Published: January 2007

Our primary objective is to develop an efficient and accurate method for analyzing time series with a multiscale character. Our motivation stems from the studies of the physical properties of marine sediment (stiffness and density) derived from seismic acoustic records of surface/interface waves along the water-seabed boundary. These studies depend on the dispersive characteristics of water-sediment surface waves. To obtain a reliable retrieval of the shear-wave velocities, we need a very accurate time-frequency record of the surface waves. Such a time-frequency analysis is best carried out by a wavelet-transform of the seismic records. We have employed the wavelet crosscorrelation technique for estimating the shear-wave propagational parameters as a function of depth and horizontal distance. For achieving a greatly improved resolution in time-frequency space, we have developed a new set of adaptive wavelets, which are driven by the data. This approach is based on a Karhunen-Loeve (KL) decomposition of the seismograms. This KL decomposition allows us to obtain a set of wavelet functions that are naturally adapted to the scales of the surface-wave modes. We demonstrate the superiority of these adaptive wavelets over standard wavelets in their ability to simultaneously discriminate the different surface-wave modes. The results can also be useful for imaging and statistical data analysis in exploration geophysics and in other disciplines in the environmental sciences.
On the relationship between iron concentration and induced polarization in marsh soils
Authors: Mansoor Nasser , Slater Lee
Published: January 2007

Induced polarization (IP) measurements [Formula: see text] were conducted on seventeen clay and peat marsh soils that were subsequently analyzed for heavy metal concentrations, moisture content, organic matter, porosity, specific surface area, and pore fluid conductivity. A Cole-Cole model was fit to each sample and model parameters analyzed in terms of physicochemical properties. We found a linear relation between the normalized chargeability [Formula: see text] and estimated surface area to pore volume [Formula: see text] when iron content (ranging from 0.25% to 1.63% by volume) is accounted for as a polarizable element of the soil. In fact, the dependence of [Formula: see text] on volumetric Fe concentration per unit volume of the bulk soil is described by a linear relationship with a correlation coefficient [Formula: see text] of 0.94. As Fe concentration is a critical biogeochemical parameter, our findings suggest that IP measurements may provide a hitherto unrecognized approach to probing soil geochemistry, iron cycling and anaerobic microbial activity. Furthermore, our results yield insights into physicochemical controls on IP in natural soils.
Lineament-preserving filtering
Authors: Al-Dossary Saleh , Marfurt Kurt J.
Published: January 2007

Recently developed seismic attributes such as volumetric curvature and amplitude gradients enhance our ability to detect lineaments. However, because these attributes are based on derivatives of either dip and azimuth or the seismic data themselves, they can also enhance high-frequency noise. Recently published structure-oriented filtering algorithms show that noise in seismic data can be removed along reflectors while preserving major structural and stratigraphic discontinuities. In one implementation, the smoothing process tries to select the most homogenous window from a suite of candidate windows containing the analysis point. A second implementation damps the smoothing operation if a discontinuity is detected. Unfortunately, neither of these algorithms preserves thin or small lineaments that are only one voxel in width. To overcome this defect, we evaluate a suite of nonlinear feature-preserving filters developed in the image-processing and synthetic aperture radar (SAR) world and apply them to both synthetic and real 3D dip-and-azimuth volumes of fractured geology from the Forth Worth Basin, USA. We find that the multistage, median-based, modified trimmed-mean algorithm preserves narrow geologically significant features of interest, while suppressing random noise and acquisition footprint.
Unsupervised seismic facies analysis using wavelet transform and self-organizing maps
Authors: de Matos Marcílio Castro , Osorio Paulo Léo , Johann Paulo Roberto
Published: January 2007

Unsupervised seismic facies analysis provides an effective way to estimate reservoir properties by combining different seismic attributes through pattern recognition algorithms. However, without consistent geological information, parameters such as the number of facies and even the input seismic attributes are usually chosen in an empirical way. In this context, we propose two new semiautomatic alternative methods. In the first one, we use the clustering of the Kohonen self-organizing maps (SOMs) as a new way to build seismic facies maps and to estimate the number of seismic facies. In the second method, we use wavelet transforms to identify seismic trace singularities in each geologically oriented segment, and then we build the seismic facies map using the clustering of the SOM. We tested both methods using synthetic and real seismic data from the Namorado deepwater giant oilfield in Campos Basin, offshore Brazil. The results confirm that we can estimate the appropriate number of seismic facies through the clustering of the SOM. We also showed that we can improve the seismic facies analysis by using trace singularities detected by the wavelet transform technique. This workflow presents the advantage of being less sensitive to horizon interpretation errors, thus resulting in an improved seismic facies analysis.
True-amplitude, angle-domain, common-image gathers from one-way wave-equation migrations
Authors: Zhang Yu , Xu Sheng , Bleistein Norman , Zhang Guanquan
Published: January 2007

True-amplitude wave-equation migration provides a quality migrated image of the earth’s interior. In addition, the amplitude of the output provides an estimate of the angular-dependent reflection coefficient, similar to the output of Kirchhoff inversion. Recently, true-amplitude wave-equation migration for common-shot data has been proposed to generate amplitude-reliable, shot-domain, common-image gathers in heterogeneous media. We present a method to directly produce angle-domain common-image gathers from both common-shot and shot-receiver wave-equation migration. Generating true-amplitude, shot-domain, common-image gathers requires a deconvolution-type imaging condition using the ratio of the upgoing and downgoing wavefield, each downward-projected to the image point. Producing true-amplitude, angle-domain, common-image gathers requires, instead, the product of the upgoing wavefield and the complexconjugate of the downgoing wavefield in the imaging condition. Since multiplication is a more stable computational process than division, the new methods proposed provide more stable ways of inverting seismic data. Furthermore, the resulting common-image gathers can be directly used for migrated amplitude-variation-with angle analysis and tomography-based velocity analysis. Shot-receiver wave-equation migration requires new true-amplitude, one-way wave equations with one depth variable and transverse variables for the coordinates corresponding to sources and receivers, hence, two transverse coordinates in 2D and four transverse coordinates in 3D. We propose a modified double-square-root one-way wave equation to produce true amplitude common-image angle gathers. We also demonstrate the new methods with some synthetic examples. Some numerical examples show that the new methods we propose give better amplitude performance on the migrated angle gathers.
Fourier reconstruction of nonuniformly sampled, aliased seismic data
Authors: Zwartjes P. M. , Sacchi M. D.
Published: January 2007

There are numerous methods for interpolating uniformly sampled, aliased seismic data, but few can handle the combination of nonuniform sampling and aliasing. We combine the principles of Fourier reconstruction of nonaliased, nonuniformly sampled data with the ideas of frequency-wavenumber [Formula: see text] interpolation of aliased, uniformly sampled data in a new two-step algorithm. In the first step, we estimate the Fourier coefficients at the lower nonaliased temporal frequencies from the nonuniformly sampled data. The coefficients are then used in the second step as an a priori model to distinguish between aliased and nonaliased energy at the higher, aliased temporal frequencies. By using a nonquadratic model penalty in the inversion, both the artifacts in the Fourier domain from nonuniform sampling and the aliased energy are suppressed. The underlying assumption is that events are planar; therefore, the algorithm is applied to seismic data in overlapping spatiotemporal windows.
DEXP: A fast method to determine the depth and the structural index of potential fields sources
Authors: Fedi Maurizio
Published: January 2007

We show that potential fields enjoy valuable properties when they are scaled by specific power laws of the altitude. We describe the theory for the gravity field, the magnetic field, and their derivatives of any order and propose a method, called here Depth from Extreme Points (DEXP), to interpret any potential field. The DEXP method allows estimates of source depths, density, and structural index from the extreme points of a 3D field scaled according to specific power laws of the altitude. Depths to sources are obtained from the position of the extreme points of the scaled field, and the excess mass (or dipole moment) is obtained from the scaled field values. Although the scaling laws are theoretically derived for sources such as poles, dipoles, lines of poles, and lines of dipoles, we give also criteria to estimate the correct scaling law directly from the data. The scaling exponent of such laws is shown to be related to the structural index involved in Euler Deconvolution theory. The method is fast and stable because it takes advantage of the regular behavior of potential field data versus the altitude [Formula: see text]. As a result of stability, the DEXP method may be applied to anomalies with rather low SNRs. Also stable are DEXP applications to vertical and horizontal derivatives of a Newtonian potential of various orders in which we use theoretically determined scaling functions for each order of a derivative. This helps to reduce mutual interference effects and to obtain meaningful representations of the distribution of sources versus depth, with no prefiltering. The DEXP method does not require that magnetic anomalies to be reduced to the pole, and meaningful results are obtained by processing its analytical signal. Application to different cases of either synthetic or real data shows its applicability to any type of potential field investigation, including geological, petroleum, mining, archeological, and environmental studies.
Seismic velocities of unconsolidated sands: Part 1 — Pressure trends from 0.1 to 20 MPa
Authors: Zimmer Michael A. , Prasad Manika , Mavko Gary , Nur Amos
Published: January 2007

Knowledge of the pressure dependences of seismic velocities in unconsolidated sands is necessary for the remote prediction of effective pressures and for the projection of velocities to unsampled locations within shallow sand layers. We have measured the compressional- and shear-wave velocities and bulk, shear, and P-wave moduli at pressures from [Formula: see text] in a series of unconsolidated granular samples including dry and water-saturated natural sands and dry synthetic sand and glass-bead samples. The shear-wave velocities in these samples demonstrate an average pressure dependence approximately proportional to the fourth root of the effective pressure [Formula: see text], as commonly observed at lower pressures. For the compressional-wave velocities, theexponent in the pressure dependence of individual dry samples is consistently less than the exponent for the shear-wave velocity of the same sample, averaging 0.23 for the dry sands and 0.20 for the glass-bead samples. These pressure dependences are generally consistent over the entire pressure range measured. A comparison of the empirical results to theoretical predictions based on Hertz-Mindlin effective-medium models demonstrates that the theoretical models vastly overpredict the shear moduli of the dry granular frame unless the contacts are assumed to have no tangential stiffness. The models also predict a lower pressure exponent for the moduli and velocities [Formula: see text] than is generally observed in the data. We attribute this discrepancy in part to the inability of the models to account for decreases in the amount of slip or grain rotation occurring at grain-to-grain contacts with increasing pressure.
Ductal Carcinoma In Situ in BRCA Mutation Carriers
Authors: Hwang E. Shelley , McLennan Jane L. , Moore Dan H. , Crawford Beth B. , Esserman Laura J. , Ziegler John L.
Published: January 2007

Purpose

The current literature suggests that ductal carcinoma in situ (DCIS) of the breast is infrequently diagnosed in patients with BRCA germline mutations. We studied women at high risk of hereditary breast cancer syndromes who underwent testing for BRCA1 and BRCA2 to estimate DCIS prevalence and incidence in known BRCA-positive women compared with high-risk women who were mutation negative.

Methods

We analyzed breast event outcomes in a retrospective cohort of 129 BRCA-positive and 269 BRCA-negative women undergoing genetic testing for a BRCA mutation between September 1996 and December 2003 at University of California, San Francisco. We estimated the frequency of DCIS and invasive cancer and time to breast events from birth using a Cox proportional hazard model for competing risks. Histologic grade of DCIS was also compared between groups.

Results

Among BRCA carriers, 48 (37%) had DCIS (with or without invasive cancer) compared with 92 noncarriers (34%). Univariate analysis showed that both DCIS and invasive cancer had an earlier onset in mutation carriers than in noncarriers, although on a per-woman basis, this difference was not statistically significant. High-grade DCIS was more common in BRCA1 mutation carriers than in patients without a mutation (P = .02).

Conclusion

DCIS is equally as prevalent in patients who carry deleterious BRCA mutations as in high familial-risk women who are noncarriers, but occurs at an earlier age. Our results argue for the consideration of DCIS as a criterion for BRCA risk assessments with appropriate weighting in prediction models such as BRCAPRO.
Prevalence of Permanent Neonatal Diabetes in Slovakia and Successful Replacement of Insulin with Sulfonylurea Therapy in KCNJ11 and ABCC8 Mutation Carriers
Authors: Stanik Juraj , Gasperikova Daniela , Paskova Magdalena , Barak Lubomir , Javorkova Jana , Jancova Emilia , Ciljakova Miriam , Hlava Peter , Michalek Jozef , Flanagan Sarah E. , Pearson Ewan , Hattersley Andrew T. , Ellard Sian , Klimes Iwar
Published: January 2007

Context: Mutations in the KCNJ11 and ABCC8 genes encoding the pancreatic β-cell KATP channel have recently been shown to be the most common cause of permanent neonatal diabetes mellitus (PNDM). Information regarding the frequency of PNDM has been based mainly on nonpopulation or short-term collections only. Thus, the aim of this study was to identify the incidence of PNDM in Slovakia and to switch patients to sulfonylurea (SU) where applicable.

Design: We searched for PNDM patients in the Slovak Children Diabetes Registry. In insulin-treated patients who matched the clinical criteria for PNDM, the KCNJ11 or ABCC8 genes were sequenced, and mutation carriers were invited for replacement of insulin with SU.

Results: Eight patients with diabetes onset before the sixth month of life without remission were identified since 1981, which corresponds to the PNDM incidence in Slovakia of one case in 215,417 live births. In four patients, three different KCNJ11 mutations were found (R201H, H46Y, and L164P). Three patients with the KCNJ11 mutations (R201H and H46Y) were switched from insulin to SU, decreasing their glycosylated hemoglobin from 9.3–11.0% on insulin to 5.7–6.6% on SU treatment. One patient has a novel V86A mutation in the ABCC8 gene and was also substituted with SU.

Conclusions: PNDM frequency in Slovakia is much higher (one in 215,417 live births) than previously suggested from international estimates (about one in 800,000). We identified one ABCC8 and four KCNJ11 mutation carriers, of whom four were successfully transferred to SU, dramatically improving their diabetes control and quality of life.
Patient Inducement, Provider Priorities, and Resource Allocation in Public Mental Health Systems
Authors: Sinaiko Anna D. , McGuire Thomas G.
Published: January 2007

Public mental health systems are increasingly facing demands from the criminal justice system and social services agencies to provide services and support in cases in which mental illness contributes to crime, homelessness, or poverty. In this article we analyze how policies from outside public mental health systems affect resource allocation within these systems, using examples from criminal justice. These policies use two types of mechanisms: inducing patients to consume treatment (by offering rewards or imposing penalties) and inducing clinicians to provide treatment (by creating priorities). We propose a classification of these social policies based on whether they affect demand through rewards or penalties or supply through priorities. We then relate the classification to data on patients treated in public systems to evaluate the current prevalence and potential for growth in these outside demands. These inducements impose a set of nonobvious costs on other patients who are not targeted by the policies. Furthermore, they create incentives for both patients and providers to modify their behavior in order to take advantage of rewards, avoid penalties, or better compete for resources with prioritized patients. We consider some policy implications for avoiding unintended consequences of these policies.
Mapping the consequence of Notch1 proteolysis in vivo with NIP-CRE
Authors: Vooijs Marc , Ong Chin-Tong , Hadland Brandon , Huppert Stacey , Liu Zhenyi , Korving Jeroen , van den Born Maaike , Stappenbeck Thaddeus , Wu Yumei , Clevers Hans , Kopan Raphael
Published: January 2007

The four highly conserved Notch receptors receive short-range signals that control many biological processes during development and in adult vertebrate tissues. The involvement of Notch1 signaling in tissue self-renewal is less clear, however. We developed a novel genetic approach N1IP-CRE(Notch1 Intramembrane Proteolysis) to follow, at high resolution, the descendents of cells experiencing Notch1 activation in the mouse. By combining N1IP-CRE with loss-of-function analysis, Notch activation patterns were correlated with function during development, self-renewal and malignancy in selected tissues. Identification of many known functions of Notch1 throughout development validated the utility of this approach. Importantly,novel roles for Notch1 signaling were identified in heart, vasculature, retina and in the stem cell compartments of self-renewing epithelia. We find that the probability of Notch1 activation in different tissues does not always indicate a requirement for this receptor and that gradients of Notch1 activation are evident within one organ. These findings highlight an underappreciated layer of complexity of Notch signaling in vivo. Moreover, NIP-CRE represents a general strategy applicable for monitoring proteolysis-dependent signaling in vivo.
Mammalian Polycomb Scmh1 mediates exclusion of Polycomb complexes from the XY body in the pachytene spermatocytes
Authors: Takada Yuki , Isono Kyo-ichi , Shinga Jun , Turner James M. A. , Kitamura Hiroshi , Ohara Osamu , Watanabe Gen , Singh Prim B. , Kamijo Takehiko , Jenuwein Thomas , Burgoyne Paul S. , Koseki Haruhiko
Published: January 2007

The product of the Scmh1 gene, a mammalian homolog of DrosophilaSex comb on midleg, is a constituent of the mammalian Polycomb repressive complexes 1 (Prc1). We have identified Scmh1 as an indispensable component of the Prc1. During progression through pachytene, Scmh1 was shown to be excluded from the XY body at late pachytene, together with other Prc1 components such as Phc1, Phc2, Rnf110 (Pcgf2), Bmi1 and Cbx2. We have identified the role of Scmh1 in mediating the survival of late pachytene spermatocytes. Apoptotic elimination of Scmh1-/- spermatocytes is accompanied by the preceding failure of several specific chromatin modifications at the XY body, whereas synapsis of homologous autosomes is not affected. It is therefore suggested that Scmh1 is involved in regulating the sequential changes in chromatin modifications at the XY chromatin domain of the pachytene spermatocytes. Restoration of defects in Scmh1-/-spermatocytes by Phc2 mutation indicates that Scmh1 exerts its molecular functions via its interaction with Prc1. Therefore, for the first time, we are able to indicate a functional involvement of Prc1 during the meiotic prophase of male germ cells and a regulatory role of Scmh1 for Prc1,which involves sex chromosomes.
Neurogenic role of Gcm transcription factors is conserved in chicken spinal cord
Authors: Soustelle Laurent , Trousse Françoise , Jacques Cécile , Ceron Julian , Cochard Philippe , Soula Cathy , Giangrande Angela
Published: January 2007

Although glial cells missing (gcm) genes are known as glial determinants in the fly embryo, the role of vertebrate orthologs in the central nervous system is still under debate. Here we show for the first time that the chicken ortholog of fly gcm (herein referred to as c-Gcm1), is expressed in early neuronal lineages of the developing spinal cord and is required for neural progenitors to differentiate as neurons. Moreover, c-Gcm1 overexpression is sufficient to trigger cell cycle exit and neuronal differentiation in neural progenitors. Thus, c-Gcm1 expression constitutes a crucial step in the developmental cascade that prompts progenitors to generate neurons: c-Gcm1 acts downstream of proneural (neurogenin) and progenitor (Sox1-3) factors and upstream of NeuroM neuronal differentiation factor. Strikingly, this neurogenic role is not specific to the vertebrate gene, as fly gcmand gcm2 are also sufficient to induce the expression of neuronal markers. Interestingly, the neurogenic role is restricted to post-embryonic stages and we identify two novel brain neuronal lineages expressing and requiring gcm genes. Finally, we show that fly gcm and the chick and mouse orthologs induce expression of neural markers in HeLa cells. These data, which demonstrate a conserved neurogenic role for Gcm transcription factors, call for a re-evaluation of the mode of action of these genes during evolution.
The Respective Roles of Risk and Decision Analyses in Decision Support
Authors: Paté-Cornell M. Elisabeth , Dillon Robin L.
Published: January 2007

Decision support models help structure and inform complex choices under uncertainty. Two classic models are risk analysis and decision analysis. Risk analysis is understood here as risk characterization, and in some cases, the identification and benefit assessment of some risk management options. It is based on systems analysis and probability, and it excludes the actual decision phase, which requires the preferences, e.g., the utility function, of the decision maker(s). Risk analysis and decision analysis have some similarities and are often complementary. To model uncertainties, both rely on probability, generally a subjective Bayesian degree of belief. A decision analysis can include a risk analysis component, and the design of a risk management plan may require decision analysis support. The challenge for risk analysts is to characterize potential failure problems before decision options have been identified, and when there is no single decision maker, or group of decision makers, who can provide preference functions and degrees of belief. Yet, a correct and complete model of uncertainties in the probabilistic risk analysis phase is important if the results are to be used later for decision support, especially when the number of systems involved and the duration of their operations is unknown. In this paper, we explore some of the challenges inherent to probabilistic risk analysis that should be of interest to the decision analysts who intend to use risk analysis results.
Rotigotine: Transdermal Dopamine Agonist Treatment of Parkinson's Disease and Restless Legs Syndrome
Authors: Splinter Michele Y
Published: January 2007

Objective:

To evaluate the pharmacology, pharmacokinetics, clinical efficacy, and tolerability of rotigotine, a nonergoline D3/D2/D1 dopamine receptor agonist in the treatment of Parkinson's disease and restless legs syndrome (RLS).

Data Sources:

A literature search was conducted using MEDLINE (1996–December 2006) and International Pharmaceutical Abstracts, using the search terms rotigotine and dopamine agonist. References cited in the articles were reviewed for additional information. Information was also obtained from Schwarz Pharma. Abstracts for posters at scientific conferences were accessed from conference Web sites.

Study Selection and Data Extraction:

English-language literature reporting controlled animal and human clinical studies was reviewed to evaluate the pharmacology, pharmacokinetics, therapeutic use, and adverse effects of rotigotine. Clinical trials selected for inclusion were limited to those with human subjects; data from animal studies were included if human data were not available.

Data Synthesis:

Rotigotine has been investigated in early Parkinson's disease, as adjuvant therapy to levodopa in advanced Parkinson's disease, and in RLS. It is administered transdermally, which provides the convenience of once-daily dosing, constant drug delivery, and sustained stable plasma concentrations. In clinical trials of patients with early Parkinson's disease, rotigotine has decreased combined scores on the motor and activities of daily living sections of the Unified Parkinson's Disease Rating Scale up to 85 weeks. In patients with advanced Parkinson's disease, rotigotine reduced mean off-time when used as an adjuvant to levodopa. Rotigotine has decreased the severity of RLS in Phase III trials. Acute adverse events are similar to those of other dopamine agonists and are most common during the titration phase. Mild-to-moderate application site reactions are common.

Conclusions:

Longer trials are required to determine whether transdermal rotigotine will reduce development of dyskinesias and motor fluctuations in Parkinson's disease and augmentation and rebound in RLS by preventing pulsatile dopamine stimulation associated with levodopa and other dopamine agonists.
Validity of a Stage of Change Instrument in Assessing Medication Adherence in Indigent Patients with HIV Infection
Authors: Rathbun R Chris , Farmer Kevin C , Lockhart Staci M , Stephens Johnny R
Published: January 2007

Background:

Adherence to antiretroviral therapy (ART) is vital to achieve durable suppression of viral replication. Effective mechanisms to predict adherence can be difficult to implement in clinical practice settings. Self-administered questionnaires are a practical option for assessing patient adherence but may lack validation with objective measures of adherence.

Objective:

To examine the ability of a 2 item stage of change (SOC) questionnaire to predict medication adherence in indigent patients receiving ART.

Methods:

Patients participating in an ongoing study to examine adherence interventions were administered a 2 item SOC instrument to assess readiness for adherence behavior. The SOC instrument was given to patients prior to beginning ART and readministered after they had received 16 weeks of treatment. Electronic monitoring was used to examine the validity of the SOC instrument to predict patient readiness for adherence behavior.

Results:

Thirty-one patients completed the SOC questionnaire prior to beginning a new ART regimen. Most (87%) patients were male, had previously received antiretroviral therapy (77%). and had an AIDS diagnosis (77%). The SOC category determined at baseline was a poor predictor of adherence at 4 and 16 weeks; however, the SOC category determined after treatment onset (week 16) was a strong predictor of adherence at both time points (p < 0.001 for 4 and 16 weeks; one way ANOVA).

Conclusions:

The SOC category determined at baseline correlated poorly with subsequent medication adherence in our indigent, HIV-infected patient population. Prediction of adherence based on SOC after treatment initiation may provide a better estimate of adherence behavior. Recognition of this limitation may help clinicians more accurately interpret predicted adherence behavior from self-report instruments.
Explaining inappropriate strategy selection in a simple reasoning task
Authors: Roberts Maxwell J. , Taylor Richard J. , Newton Elizabeth J.
Published: January 2007

People's strategy selections appear to reflect attempts to maximize performance by selecting the most effective option for a particular task or format. Theories that account for such behaviour will be named rational models of strategy selection. However, it is possible to find instances where people are apparently biased towards using less effective strategies, and such behaviour appears to go against these models. Two experiments are reported in which participants were instructed to use first one, and then the other of two possible strategies for solving a compass point directions task (the instructed phase), and were subsequently permitted to use any strategy (the free‐choice phase). A substantial minority of participants selected the less effective spatial strategy during the free‐choice phase. Overall, it was found that people who rely on the spatial strategy when given a free‐choice tend to be those who: (1) have not been given particular incentive to perform as well as possible; (2) have difficulty executing the better alternative, cancellation and (3) are particularly prone to making errors at the spatial strategy. Hence, although evidence was found in support of rational models of strategy selection, it is also suggested that these must additionally take account of the motivational and conceptual difficulties that people may have with a task.
Cognitive biases for trauma stimuli in people with schizophrenia
Authors: Klewchuk Elaine M. , McCusker Christopher G. , Mulholland Ciaran , Shannon Ciaran
Published: January 2007

Objectives. This study investigates whether cognitive biases related to trauma (physical and sexual trauma) are present in a sample of participants with a diagnosis of schizophrenia.

Method. Fifty‐three participants, with a DSM‐IV diagnosis of schizophrenia, completed tasks of attentional and memory bias, followed by several trauma report questionnaires. Those who reported a history of sexual and/or physical trauma were compared with a ‘non‐specific/no‐trauma’ subgroup. The reliability of trauma reports was determined by comparing current data on the Trauma History Questionnaire to that gathered one year previously, for a subsample of participants. Concordance rates and kappa coefficients suggested moderate to high reliability for reports of sexual and physical trauma. Attentional bias was assessed by comparing colour‐naming times on modified Stroops, of either a sexual or physical nature, with control Stroops with negative, positive and neutral emotionally valenced stimuli. A subsequent incidental recall memory task was then employed.

Results. High rates of sexual and/or physical trauma were found. Those who reported a history of sexual trauma evidenced a statistically significant increase in colour‐naming times for sexual trauma stimuli, compared to both the ‘physical trauma only’ and the ‘non‐specific/no trauma’ control groups. They also showed greater incidental recall of sexual trauma words in comparison to the other groups. Such a pattern was not, however, discerned for those reporting histories of physical trauma.

Conclusions. Findings suggest cognitive schemata related to sexual trauma remains ‘active’ in those people with schizophrenia who report a related history.
Hénon-like mappings in [inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="01i" /]
Authors: Dujardin Romain
Published: January 2007

We study the dynamics of a class of nonalgebraic holomorphic diffeomorphisms, topological analogues in the unit bidisk of complex Hénon mappings in [inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="02i" /]. In particular a dynamical degree is defined, which is related to topological entropy, and we construct stable/unstable invariant currents, and prove there is a unique, mixing, measure of maximal entropy, with product structure.
On the moduli scheme of stable sheaves supported on cubic space curves
Authors: Freiermuth Hans Georg , Trautmann Günther
Published: January 2007

We investigate the geometry of the Simpson moduli space M P ([inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="01i" /]) of stable sheaves with Hilbert polynomial P ( m ) = 3 m + 1. It consists of two smooth, rational components M 0 and M 1 of dimensions 12 and 13 intersecting each other transversally along an 11-dimensional, smooth, rational subvariety. The component M 0 is isomorphic to the closure of the space of twisted cubics in the Hilbert scheme Hilb P ([inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="02i" /]) and M 1 is isomorphic to the incidence variety of the relative Hilbert scheme of cubic curves contained in planes. In order to obtain the result and to classify the sheaves, we characterize MP ([inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="03i" /]) as geometric quotient of a certain matrix parameter space by a nonreductive group. We also compute the Betti numbers of the Chow groups of the moduli space.
Why Were the Vestals Virgins? Or the Chastity of Women and the Safety of the Roman State
Authors: Parker Holt N
Published: January 2007

Why were the Vestals virgins? An explanation drawing on anthropological studies of witchcraft and the work of Giovannini, Girard, and Douglas allows a partial solution to this and three other puzzles: 1) their unique legal status; 2) their murder at moments of political crisis; 3) the odd details of those murders. The untouched body of the Vestal Virgin is a metonymy for the untouched city of Rome. Her unique legal status frees her from all family ties so that she can incarnate the collective. Thus, in times of crisis, she serves as a pharmakos/pharmakon. Equally, Roman society reveals a deep fear of witchcraft directed at its own matrons. Danger to the urbs is warded off by the punishment of women, both Vestals and wives, and the foundation of public cults of chastity with admonitory and apotropaic functions. A series of incidents over a thousand-year span reveals a world view deeply rooted in sympathetic magic, where the women embody the state and their inviolability is objectified as the inviolability of the community.
The Poetics of the Kōmos -Chorus in Menander's Comedy
Authors: Lape Susan
Published: January 2007

This article investigates the functions of the kōmos-chorus in Menander"s comedies. It first reviews the evidence for the diminished role of the comic chorus in the fourth century and then considers Menander"s practice of deploying a kōmos instead of a chorus. It argues that the performance contexts of the kōmos allowed it to serve multiple functions. The association of the kōmos with symposia and aristocratic violence rendered it a realistic device for clearing the stage after the first act. In addition, the conclusion of the romantic plot with a wedding or pre-wedding celebration created the occasion for receiving a wedding kōmos, suggesting that the kōmos may have finally been greeted or received at the end of the fifth act.
"This is not a true story": Stesichorus's Palinode and the Revenge of the Epichoric
Authors: Beecroft Alexander J
Published: January 2007

While many have written on the fragment of Stesichorus's Palinode presented to us in the Phaedrus, most of this work has focused on attempting to understand the function the palinode may have played within Stesichorus's work or his performance tradition, and on the nature of Stesichorus's offense against Helen, the offense which prompted her blinding of him and his subsequent creation of the Palinode fragment itself. Careful examination shows that the language it uses is carefully chosen to situate Stesichorus's work in opposition to epic and Panhellenic versions of the story of Helen.
Commanding Constantia in Senecan Tragedy
Authors: Star Christopher
Published: January 2007

This paper investigates the language of self-address in Seneca's tragedies. I show that the rhetorical language Seneca's characters direct at themselves constitutes a key similarity to the techniques Seneca recommends in his philosophical works. Initially, I demonstrate how Seneca urges Lucilius and even instructs the Emperor Nero (if only indirectly) to battle for consistency through self-command. Secondly, through careful explication of passages from Agamemnon, Thyestes, and Medea, I show how this same rhetorical figure, self-apostrophe, is used by Seneca's characters to achieve their criminal self-fulfillment. In Senecan tragedy as well as philosophy, consistency is achieved by self-command regardless of whether consistency results in knowledge for Lucilius, clemency for Nero, or revenge for Seneca's tragic characters.