bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of DNA relaxation and cleavage activities of recombinant Mycobacterium tuberculosis DNA topoisomerase I from a new expression and purification protocol
Authors: Annamalai Thirunavukkarasu , Dani Neil , Cheng Bokun , Tse-Dinh Yuk-Ching
Published: June 2009

Background

Mycobacterium tuberculosis DNA topoisomerase I is an attractive target for discovery of novel TB drugs that act by enhancing the accumulation of the topoisomerase-DNA cleavage product. It shares a common transesterification domain with other type IA DNA topoisomerases. There is, however, no homology between the C-terminal DNA binding domains of Escherichia coli and M. tuberculosis DNA topoisomerase I proteins.

Results

A new protocol for expression and purification of recombinant M. tuberculosis DNA topoisomerase I (MtTOP) has been developed to produce enzyme of much higher specific activity than previously characterized recombinant enzyme. MtTOP was found to be less efficient than E. coli DNA topoisomerase I (EcTOP) in removal of remaining negative supercoils from partially relaxed DNA. DNA cleavage by MtTOP was characterized for the first time. Comparison of DNA cleavage site selectivity with EcTOP showed differences in cleavage site preferences, but the preferred sites of both enzymes have a C nucleotide in the -4 position.

Conclusion

Recombinant M. tuberculosis DNA topoisomerase I can be expressed as a soluble protein and purified in high yield from E. coli host with a new protocol. Analysis of DNA cleavage with M. tuberculosis DNA substrate showed that the preferred DNA cleavage sites have a C nucleotide in the -4 position.
Complete chloroplast genome sequence of a tree fern Alsophila spinulosa: insights into evolutionary changes in fern chloroplast genomes
Authors: Gao Lei , Yi Xuan , Yang Yong-Xia , Su Ying-Juan , Wang Ting
Published: June 2009

Background

Ferns have generally been neglected in studies of chloroplast genomics. Before this study, only one polypod and two basal ferns had their complete chloroplast (cp) genome reported. Tree ferns represent an ancient fern lineage that first occurred in the Late Triassic. In recent phylogenetic analyses, tree ferns were shown to be the sister group of polypods, the most diverse group of living ferns. Availability of cp genome sequence from a tree fern will facilitate interpretation of the evolutionary changes of fern cp genomes. Here we have sequenced the complete cp genome of a scaly tree fern Alsophila spinulosa (Cyatheaceae).

Results

The Alsophila cp genome is 156,661 base pairs (bp) in size, and has a typical quadripartite structure with the large (LSC, 86,308 bp) and small single copy (SSC, 21,623 bp) regions separated by two copies of an inverted repeat (IRs, 24,365 bp each). This genome contains 117 different genes encoding 85 proteins, 4 rRNAs and 28 tRNAs. Pseudogenes of ycf66 and trnT-UGU are also detected in this genome. A unique trnR-UCG gene (derived from trnR-CCG) is found between rbcL and accD. The Alsophila cp genome shares some unusual characteristics with the previously sequenced cp genome of the polypod fern Adiantum capillus-veneris, including the absence of 5 tRNA genes that exist in most other cp genomes. The genome shows a high degree of synteny with that of Adiantum, but differs considerably from two basal ferns (Angiopteris evecta and Psilotum nudum). At one endpoint of an ancient inversion we detected a highly repeated 565-bp-region that is absent from the Adiantum cp genome. An additional minor inversion of the trnD-GUC, which is possibly shared by all ferns, was identified by comparison between the fern and other land plant cp genomes.

Conclusion

By comparing four fern cp genome sequences it was confirmed that two major rearrangements distinguish higher leptosporangiate ferns from basal fern lineages. The Alsophila cp genome is very similar to that of the polypod fern Adiantum in terms of gene content, gene order and GC content. However, there exist some striking differences between them: the trnR-UCG gene represents a putative molecular apomorphy of tree ferns; and the repeats observed at one inversion endpoint may be a vestige of some unknown rearrangement(s). This work provided fresh insights into the fern cp genome evolution as well as useful data for future phylogenetic studies.
Toad radiation reveals into-India dispersal as a source of endemism in the Western Ghats-Sri Lanka biodiversity hotspot
Authors: Van Bocxlaer Ines , Biju SD , Loader Simon P , Bossuyt Franky
Published: June 2009

Background

High taxonomic level endemism in the Western Ghats-Sri Lanka biodiversity hotspot has been typically attributed to the subcontinent's geological history of long-term isolation. Subsequent out of – and into India dispersal of species after accretion to the Eurasian mainland is therefore often seen as a biogeographic factor that 'diluted' the composition of previously isolated Indian biota. However, few molecular studies have focussed on into-India dispersal as a possible source of endemism on the subcontinent. Using c. 6000 base pairs of mitochondrial and nuclear DNA, we investigated the evolutionary history and biogeography of true toads (Bufonidae), a group that colonized the Indian Subcontinent after the Indo-Asia collision.

Results

Contrary to previous studies, Old World toads were recovered as a nested clade within New World Bufonidae, indicating a single colonization event. Species currently classified asAnsoniaandPedostibeswere both recovered as being non-monophyletic, providing evidence for the independent origin of torrential and arboreal ecomorphs on the Indian subcontinent and in South-East Asia. Our analyses also revealed a previously unrecognized adaptive radiation of toads containing a variety of larval and adult ecomorphs. Molecular dating estimates and biogeographic analyses indicate that the early diversification of this clade happened in the Western Ghats and Sri Lanka during the Late Oligocene to Early Miocene.

Conclusion

Paleoclimate reconstructions have shown that the Early Neogene of India was marked by major environmental changes, with the transition from a zonal- to the current monsoon-dominated climate. After arrival in the Western Ghats-Sri Lanka hotspot, toads diversifiedin situ, with only one lineage able to successfully disperse out of these mountains. Consequently, higher taxonomic level endemism on the Indian Subcontinent is not only the result of Cretaceous isolation, but also of invasion, isolation and radiation of new elements after accretion to the Eurasian mainland.
Tissue micro array analysis of ganglioside N-glycolyl GM3 expression and signal transducer and activator of transcription (STAT)-3 activation in relation to dendritic cell infiltration and microvessel density in non-small cell lung cancer
Authors: van Cruijsen Hester , Ruiz Mariëlle Gallegos , van der Valk Paul , de Gruijl Tanja D , Giaccone Giuseppe
Published: June 2009

Background

Tumor immune escape and angiogenesis contribute to tumor progression, and gangliosides and activation of signal transducer and activator of transcription (STAT)-3 are implicated in these processes. As both are considered as novel therapeutic targets, we assessed the possible association of ganglioside GM3 expression and STAT3 activation with suppression of dendritic cell (DC) activation and angiogenesis in non-small cell lung cancer (NSCLC).

Methods

Immunohistochemistry was performed on a tissue array to determine N-glycolyl GM3 (GM3) and phosphorylated STAT3 (pSTAT3) expression in 176 primary NSCLC resections. Median values of GM3 and pSTAT3 expression were used as cut off. Microvessel density (MVD) was determined by CD34 staining and morphology. CD1a and CD83 were used to determine infiltrating immature and mature dendritic cells, respectively.

Results

94% and 71% of the NSCLC samples expressed GM3 and nuclear pSTAT3, respectively. Median overall survival was 40.0 months. Both low GM3 expression and high pSTAT3 expression were associated with a worse survival, which reached near significance for GM3 (P = 0.08). Microvessel density (MVD), determined by CD34 staining and morphology, was lower in NSCLC samples with high GM3 expression. CD1a+ cells (immature DCs) were more frequent in NSCLC tissues as compared to peritumoral lung tissue, while CD83+ cells (mature DCs) were more frequent in peritumoral lung tissue. CD83+ DCs were less frequent in NSCLC tissues with high GM3 expression.

Conclusion

GM3 and pSTAT3 are widely expressed in NSCLC. Based on CD83 expression, GM3, but not pSTAT3, appeared to be involved in tumor-induced DC suppression. pSTAT3 expression was not associated with MVD, while GM3 might play an anti-angiogenic role.
Conformational flexibility and molecular interactions of an archaeal homologue of the Shwachman-Bodian-Diamond syndrome protein
Authors: Ng C Leong , Waterman David G , Koonin Eugene V , Walters Alison D , Chong James PJ , Isupov Michail N , Lebedev Andrey A , Bunka David HJ , Stockley Peter G , Ortiz-Lombardía Miguel , Antson Alfred A
Published: June 2009

Background

Defects in the human Shwachman-Bodian-Diamond syndrome (SBDS) protein-coding gene lead to the autosomal recessive disorder characterised by bone marrow dysfunction, exocrine pancreatic insufficiency and skeletal abnormalities. This protein is highly conserved in eukaryotes and archaea but is not found in bacteria. Although genomic and biophysical studies have suggested involvement of this protein in RNA metabolism and in ribosome biogenesis, its interacting partners remain largely unknown.

Results

We determined the crystal structure of the SBDS orthologue from Methanothermobacter thermautotrophicus (mthSBDS). This structure shows that SBDS proteins are highly flexible, with the N-terminal FYSH domain and the C-terminal ferredoxin-like domain capable of undergoing substantial rotational adjustments with respect to the central domain. Affinity chromatography identified several proteins from the large ribosomal subunit as possible interacting partners of mthSBDS. Moreover, SELEX (Systematic Evolution of Ligands by EXponential enrichment) experiments, combined with electrophoretic mobility shift assays (EMSA) suggest that mthSBDS does not interact with RNA molecules in a sequence specific manner.

Conclusion

It is suggested that functional interactions of SBDS proteins with their partners could be facilitated by rotational adjustments of the N-terminal and the C-terminal domains with respect to the central domain. Examination of the SBDS protein structure and domain movements together with its possible interaction with large ribosomal subunit proteins suggest that these proteins could participate in ribosome function.
Italian healthcare workers' views on mandatory vaccination
Authors: Tafuri Silvio ST , Martinelli Domenico DM , Caputi Giovanni GC , Arbore Annamaria AA , Germinario Cinzia CG , Prato Rosa RP
Published: June 2009

Background

Mandatory vaccination has contributed to the success of immunisation programmes but voluntary vaccination allows people to be responsible for their own health. There are benefits from both policies and the arguments between them remain subject to debate within and without the scientific community, both nationally and internationally. The aim of this study is to assess the opinions of those who actually work in the Vaccination Service.

Methods

The survey was carried out using a self-administered standardised anonymous questionnaire given to all of the Vaccination Service employees in the Apulia Region.

Results

Of 302 completed questionnaire replies, 4.4% stated that mandatory vaccination should be abandoned now, 21.2% that it should be phased out, and 74.4% that it should be retained.

Conclusion

An educational program should be set up to explain to Vaccination staff the value and worth of voluntary compared to mandatory vaccination and why high vaccination rates do not have to depend on compulsion.
Comparison of a one-time educational intervention to a teach-to-goal educational intervention for self-management of heart failure: design of a randomized controlled trial
Authors: DeWalt Darren A , Broucksou Kimberly A , Hawk Victoria , Baker David W , Schillinger Dean , Ruo Bernice , Bibbins-Domingo Kirsten , Holmes Mark , Weinberger Morris , Macabasco-O'Connell Aurelia , Pignone Michael
Published: June 2009

Background

Heart failure (HF) is common, costly and associated with significant morbidity and poor quality of life, particularly for patients with low socioeconomic status. Self-management training has been shown to reduce HF related morbidity and hospitalization rates, but there is uncertainty about how best to deliver such training and what patients benefit. This study compares a single session self-management HF training program against a multiple session training intervention and examines whether their effects differ by literacy level.

Methods/Design

In this randomized controlled multi-site trial, English and Spanish-speaking patients are recruited from university-affiliated General Internal Medicine and Cardiology clinics at 4 sites across the United States. Eligible patients have HF with New York Heart Association class II-IV symptoms and are prescribed a loop diuretic. Baseline data, including literacy level, are collected at enrollment and follow-up surveys are conducted at 1, 6 and 12 months

Upon enrollment, both the control and intervention groups receive the same 40 minute, literacy-sensitive, in-person, HF education session covering the 4 key self-management components of daily self assessment and having a plan, salt avoidance, exercise, and medication adherence. All participants also receive a literacy-sensitive workbook and a digital bathroom scale. After the baseline education was completed, patients are randomly allocated to return to usual care or to receive ongoing education and training. The intervention group receives an additional 20 minutes of education on weight and symptom-based diuretic self-adjustment, as well as periodic follow-up phone calls from the educator over the course of 1 year. These phone calls are designed to reinforce the education, assess participant knowledge of the education and address barriers to success.

The primary outcome is the combined incidence of all cause hospitalization and death. Secondary outcomes include HF-related quality of life, HF-related hospitalizations, knowledge regarding HF, self-care behavior, and self-efficacy. The effects of each intervention will be stratified by patient literacy, in order to identify any differential effects.

Discussion

Enrollment of the proposed 660 subjects will continue through the end of 2009. Outcome assessments are projected to be completed by early 2011.

Trial Registration

ClinicalTrials.gov http://www.clinicaltrials.gov/ NCT00378950
Lactic acid bacteria affect serum cholesterol levels, harmful fecal enzyme activity, and fecal water content
Authors: Lee Do Kyung , Jang Seok , Baek Eun Hye , Kim Mi Jin , Lee Kyung Soon , Shin Hea Soon , Chung Myung Jun , Kim Jin Eung , Lee Kang Oh , Ha Nam Joo
Published: June 2009

Background

Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as lower cholesterol. Although present in many foods, most trials have been in spreads or dairy products. Here we tested whetherBifidobacteriaisolates could lower cholesterol, inhibit harmful enzyme activities, and control fecal water content.

Methods

In vitroculture experiments were performed to evaluate the ability ofBifidobacteriumspp. isolated from healthy Koreans (20~30 years old) to reduce cholesterol-levels in MRS broth containing polyoxyethanylcholesterol sebacate. Animal experiments were performed to investigate the effects on lowering cholesterol, inhibiting harmful enzyme activities, and controlling fecal water content. For animal studies, 0.2 ml of the selected strain cultures (108~109CFU/ml) were orally administered to SD rats (fed a high-cholesterol diet) every day for 2 weeks.

Results

B. longumSPM1207 reduced serum total cholesterol and LDL levels significantly (p< 0.05), and slightly increased serum HDL.B. longumSPM1207 also increased fecal LAB levels and fecal water content, and reduced body weight and harmful intestinal enzyme activities.

Conclusion

Daily consumption ofB. longumSPM1207 can help in managing mild to moderate hypercholesterolemia, with potential to improve human health by helping to prevent colon cancer and constipation.
Comparative analysis between a low pathogenic and a high pathogenic influenza H5 hemagglutinin in cell entry
Authors: Rumschlag-Booms Emily , Guo Ying , Wang Jizhen , Caffrey Michael , Rong Lijun
Published: June 2009

Avian influenza viruses continue to threaten globally with pandemic potential. The first step in a potential pandemic is the ability of the virus to enter human cells which is mediated by the viral surface glycoprotein hemagglutinin (HA). Viral entry of influenza is dependent upon the processing of the HA0 polypeptide precursor protein into HA1 and HA2 which is mediated by host cellular proteases. The sequence of the cleavage site which is recognized by host proteases has been linked with pathogenesis of various influenza viruses. Here we examined the effects of cleavage site sequences between a highly pathogenic H5N1 strain and a low pathogenic H5N2 strain to determine their effects on viral entry. From this analysis we determined that at the level of viral entry, the only observed difference between the low and high pathogenic strains is their ability to be cleaved by host cellular proteases.
Behavioral Phenotypes of Mice Lacking Purinergic P2X4 Receptors in Acute and Chronic Pain Assays
Authors: Tsuda Makoto , Kuboyama Kazuya , Inoue Tomoyuki , Nagata Kenichiro , Tozaki-Saitoh Hidetoshi , Inoue Kazuhide
Published: June 2009

A growing body of evidence indicates that P2X receptors (P2XRs), a family of ligand-gated cation channels activated by extracellular ATP, play an important role in pain signaling. In contrast to the role of the P2X3R subtype that has been extensively studied, the precise roles of others among the seven P2XR subtypes (P2X1R-P2X7R) remain to be determined because of a lack of sufficiently powerful tools to specifically block P2XR signaling in vivo. In the present study, we investigated the behavioral phenotypes of a line of mice in which the p2rx4 gene was disrupted in a series of acute and chronic pain assays. While p2rx4−/− mice showed no major defects in pain responses evoked by acute noxious stimuli and local tissue damage or in motor function as compared with wild-type mice, these mice displayed reduced pain responses in two models of chronic pain (inflammatory and neuropathic pain). In a model of chronic inflammatory pain developed by intraplantar injection of complete Freund's adjuvant (CFA), p2rx4−/− mice exhibited attenuations of pain hypersensitivity to innocuous mechanical stimuli (tactile allodynia) and also of the CFA-induced swelling of the hindpaw. A most striking phenotype was observed in a test of neuropathic pain: tactile allodynia caused by an injury to spinal nerve was markedly blunted in p2rx4−/− mice. By contrast, pain hypersensitivity to a cold stimulus (cold allodynia) after the injury was comparable in wild-type and p2rx4−/− mice. Together, these findings reveal a predominant contribution of P2X4R to nerve injury-induced tactile allodynia and, to the lesser extent, peripheral inflammation. Loss of P2X4R produced no defects in acute physiological pain or tissue damaged-induced pain, highlighting the possibility of a therapeutic benefit of blocking P2X4R in the treatment of chronic pain, especially tactile allodynia after nerve injury.
LOST to follow-up Information in Trials (LOST-IT): a protocol on the potential impact
Authors: Akl Elie A , Briel Matthias , You John J , Lamontagne Francois , Gangji Azim , Cukierman-Yaffe Tali , Alshurafa Mohamad , Sun Xin , Nerenberg Kara A , Johnston Bradley C , Vera Claudio , Mills Edward J , Bassler Dirk , Salazar Arturo , Bhatnagar Neera , Busse Jason W , Khalid Zara , Walter SD , Cook Deborah J , Schünemann Holger J , Altman Douglas G , Guyatt Gordon H
Published: June 2009

Background

Incomplete ascertainment of outcomes in randomized controlled trials (RCTs) is likely to bias final study results if reasons for unavailability of patient data are associated with the outcome of interest. The primary objective of this study is to assess the potential impact of loss to follow-up on the estimates of treatment effect. The secondary objectives are to describe, for published RCTs, (1) the reporting of loss to follow-up information, (2) the analytic methods used for handling loss to follow-up information, and (3) the extent of reported loss to follow-up.

Methods

We will conduct a systematic review of reports of RCTs recently published in five top general medical journals. Eligible RCTs will demonstrate statistically significant effect estimates with respect to primary outcomes that are patient-important and expressed as binary data. Teams of 2 reviewers will independently determine eligibility and extract relevant information from each eligible trial using standardized, pre-piloted forms. To assess the potential impact of loss to follow-up on the estimates of treatment effect we will, for varying assumptions about the outcomes of participants lost to follow-up (LTFU), calculate (1) the percentage of RCTs that lose statistical significance and (2) the mean change in effect estimate across RCTs. The different assumptions we will test are the following: (1) none of the LTFU participants had the event; (2) all LTFU participants had the event; (3) all LTFU participants in the treatment group had the event; none of those in the control group had it (worst case scenario); (4) the event incidence among LTFU participants (relative to observed participants) increased, with a higher relative increase in the intervention group; and (5) the event incidence among LTFU participants (relative to observed participants) increased in the intervention group and decreased in the control group.

Discussion

We aim to make our objectives and methods transparent. The results of this study may have important implications for both clinical trialists and users of the medical literature.
Smoking and nicotine exposure delay development of collagen-induced arthritis in mice
Authors: Lindblad Sofia S , Mydel Piotr , Jonsson Ing-Marie , Senior Robert M , Tarkowski Andrej , Bokarewa Maria
Published: June 2009

Introduction

Recent epidemiologic studies have implicated smoking as an environmental risk factor for the development of rheumatoid arthritis (RA). The aim of the present study is the evaluation of the role of cigarette smoke (CS) in the pathogenesis of collagen-induced arthritis in mice.

Methods

DBA/1 mice exposed to CS for 16 weeks (n = 25) and mice exposed to nicotine in drinking water (n = 10) were immunized with collagen type II (CII). Severity of arthritis was evaluated clinically and morphologically and compared with control mice (n = 35). Intensity of inflammation was evaluated by serum IL-6 and TNF-α levels. Additionally, antibody response to CII (anti-CII) and citrullinated peptides (aCCP) was measured.

Results

Clinical evaluation of arthritis showed a delayed onset of arthritis in CS-exposed mice compared with non-smoking controls (P < 0.05). Histologic index and weight changes were comparable between the groups; however, smoking mice presented less weight loss during the acute phase of the disease and gained weight significantly faster in the recovery phase (P < 0.05). Similar results were obtained in the mice exposed to nicotine. Nicotine also showed a direct anti-inflammatory effect diminishing IL-6 production by stimulated splenocytes in vitro (P < 0.001). Additionally, smoking mice had lower levels of aCCP and anti-CII antibodies compared with non-smoking (P < 0.05).

Conclusions

Neither smoking nor nicotine exposure aggravates development of CII-induced arthritis in mouse model. Moreover, CS exposure was associated with a lower level of anti-CII antibodies, providing a possible explanation for a delay of arthritis onset in this group.
Anemia and red blood cell transfusion in neurocritical care
Authors: Kramer Andreas H , Zygun David A
Published: June 2009

Introduction

Anemia is one of the most common medical complications to be encountered in critically ill patients. Based on the results of clinical trials, transfusion practices across the world have generally become more restrictive. However, because reduced oxygen delivery contributes to 'secondary' cerebral injury, anemia may not be as well tolerated among neurocritical care patients.

Methods

The first portion of this paper is a narrative review of the physiologic implications of anemia, hemodilution, and transfusion in the setting of brain-injury and stroke. The second portion is a systematic review to identify studies assessing the association between anemia or the use of red blood cell transfusions and relevant clinical outcomes in various neurocritical care populations.

Results

There have been no randomized controlled trials that have adequately assessed optimal transfusion thresholds specifically among brain-injured patients. The importance of ischemia and the implications of anemia are not necessarily the same for all neurocritical care conditions. Nevertheless, there exists an extensive body of experimental work, as well as human observational and physiologic studies, which have advanced knowledge in this area and provide some guidance to clinicians. Lower hemoglobin concentrations are consistently associated with worse physiologic parameters and clinical outcomes; however, this relationship may not be altered by more aggressive use of red blood cell transfusions.

Conclusions

Although hemoglobin concentrations as low as 7 g/dl are well tolerated in most critical care patients, such a severe degree of anemia could be harmful in brain-injured patients. Randomized controlled trials of different transfusion thresholds, specifically in neurocritical care settings, are required. The impact of the duration of blood storage on the neurologic implications of transfusion also requires further investigation.
Seismic inversion tracks in situ combustion: A case study from Balol oil field, India
Authors: Vedanti Nimisha , Sen Mrinal K.
Published: June 2009

In situ combustion is one of the approaches used for secondary recovery of heavy oil in which time-lapse seismic data might be used to track the production process. We have analyzed three time-lapse seismic surveys carried out at a time interval of one year during pre- and postcombustion phases of in situ combustion at the Balol field in India. Interpretation of these land time-lapse data using standard seismic amplitude differences in terms of reservoir changes during production and injection can be erroneous. The Balol data, in particular, lacked calibration and had poor repeatability. We have addressed these issues by demonstrating the applicability of independent prestack inversion of baseline and monitor surveys to derive elastic attributes that help to produce clearer images of fluid movement. Independent estimates of wavelets from the baseline and two monitor surveys were used in prestack inversion to estimate acoustic impedance, shear impedance, and Poisson’s ratio. The results show unexpected movement of the thermal front away from the injection wells toward the north and northwest of the injection wells, farther from the production wells. These results have been confirmed by well production data from the field north and northwest of Balol.
1D subsurface electromagnetic fields excited by energized steel casing
Authors: Yang Wei , Torres-Verdín Carlos , Hou Junsheng , Zhang Zhiyi (Ian)
Published: June 2009

We use numerical simulations to investigate the possibility of enabling steel-cased wells as galvanic sources to detect and quantify spatial variations of electrical conductivity in the subsurface. The study assumes a vertical steel-cased well that penetrates electrically anisotropic horizontal layers. Simulations include a steel-cased vertical well with a finite-length thin wire of piecewise-constant electric conductivity and magnetic permeability. The steel-cased well is energized at the surface or within the borehole at an arbitrary depth with an electrode connected to a current source of variable frequency. Electromagnetic (EM) fields excited by the energized steel-cased well are simulated with an integral-equation approach. Results confirm the accuracy of the simulations when benchmarked against the whole-space solution of EM fields excited by a vertical electric dipole. Additional simulations consider a wide range of frequencies and subsurface conductivity values for several transmitter-receiver configurations, including borehole-to-surface and crosswell. The distribution of electric current along the steel-cased well is sensitive to vertical variations of electric conductivity in the host rock. In addition, numerical simulations indicate that crosswell and borehole-to-surface receiver configurations could reliably estimate vertical variations of electric conductivity within radial distances of up to [Formula: see text] for frequencies below [Formula: see text] and for average host rock electric conductivities below [Formula: see text].
Stressed swelling clay
Authors: Bathija Arpita Pal , Liang Haiyi , Lu Ning , Prasad Manika , Batzle Michael Lee
Published: June 2009

Clay minerals are present in most sedimentary rocks. They find applicability in a wide range of disciplines, such as material, soil, earth, environmental, and biological sciences. Despite their abundance and use, swelling of clays under stress has not received enough scientific attention. We used a two-method approach, consisting of molecular simulation and nanoindentation measurements on montmorillonite. Our analyses of the molecular structure of montmorillonite at various stresses and hydration states showed that swelling behaves in a nonlinear way with stress. Nanoindentation results of Young’s modulus agree with our simulation results, showing the importance of the interlayer in composite clay properties.
Near-surface seismic traveltime tomography using a direct-push source and surface-planted geophones
Authors: Paasche Hendrik , Werban Ulrike , Dietrich Peter
Published: June 2009

Information about seismic velocity distribution in heterogeneous near-surface sedimentary deposits is essential for a variety of environmental and engineering geophysical applications. We have evaluated the suitability of the minimally invasive direct-push technology for near-surface seismic traveltime tomography. Geophones placed at the surface and a seismic source installed temporarily in the subsurface by direct-push technology quickly acquire reversed multioffset vertical seismic profiles (VSPs). The first-arrival traveltimes of these data were used to reconstruct the 2D seismic velocity distribution tomographically. After testing this approach on synthetic data, we applied it to field data collected over alluvial deposits in a former river floodplain. The resulting velocity model contains information about high- and low-velocity anomalies and offers a significantly deeper penetration depth than conventional refraction tomography using surface-planted sources and receivers at the investigated site. A combination of refraction seismic and direct-push data increases resolution capabilities in the unsaturated zone and enables reliable reconstruction of velocity variations in near-surface unconsolidated sediments. The final velocity model structurally matches the results of cone-penetration tests and natural gamma-radiation data acquired along the profile. The suitability of multiple rapidly acquired reverse VSP surveys for 2D tomographic velocity imaging of near-surface unconsolidated sediments was explored.
Borehole flexural modes in transversely isotropic formations: Low-frequency asymptotic velocity
Authors: He Xiao , Hu Hengshan
Published: June 2009

Dipole acoustic logging is widely used for in situ measurement of formation shear velocity. This technique is based on the theoretical result in isotropic formations that the velocity of the dispersive flexural mode approaches the shear velocity at the low-frequency limit. Transversely isotropic (TI) formations frequently are encountered in petroleum engineering, so it is necessary to determine if shear velocity along the borehole can be determined from the low-frequency flexural wave in TI cases. The flexural wave in a borehole parallel to the symmetry axis of a TI formation is investigated. The borehole acoustic field is formulated in the frequency-wavenumber domain as the sum of a direct field from the source and a reflected field from the borehole wall. Poles and branch points of the reflection coefficient are analyzed, and component waves contributed by those singularities are calculated. The dispersion feature of the flexural mode in some TI formations differs from isotropic cases. The low-frequency limit of flexural-mode velocity trends to a value lower than the shear velocity when parameters of the formation satisfy [Formula: see text], where [Formula: see text] and [Formula: see text] are Thomsen parameters and [Formula: see text] and [Formula: see text] are the elastic moduli. That asymptotic value corresponds to a newly found branch point of the reflection function. Numerical results show that the low-frequency flexural wave travels slower than the shear wave in the synthetic full waveforms in Mesaverde clayshale 5501. Extracting the shear velocity from the flexural arrival leads to inaccuracy on the order of 10% in this formation.
The concept of double blending: Combining incoherent shooting with incoherent sensing
Authors: Berkhout A. J. , Blacquière G. , Verschuur D. J.
Published: June 2009

Seismic surveys are designed so that the time interval between shots is sufficiently large to avoid temporal overlap between records. To economize on survey time, the current compromise is to keep the number of shots to an acceptable minimum. The result is a poorly sampled source domain. We propose to abandon the condition of nonoverlapping shot records to allow densely sampled, wide-azimuth source distributions (source blending). The rationale is that interpolation is much harder than separation. Source blending has significant implications for quality (source density) and economics (survey time). In addition to source blending, detector blending is introduced by which every channel records a superposition of detected signals, each with its own particular code. With detector blending, many more detectors can be used for the same number of recording channels. This is particularly beneficial when the number of detectors is very large (mass sensoring) or the number of channels is limited (wireless recording). The concept of double blending is defined as the case in which both source blending and detector blending are applied. Double blending allows a significant trace-compression factor during acquisition.
Sns and Kirre, theDrosophilaorthologs of Nephrin and Neph1,direct adhesion, fusion and formation of a slit diaphragm-like structure in insect nephrocytes
Authors: Zhuang Shufei , Shao Huanjie , Guo Fengli , Trimble Rhonda , Pearce Elspeth , Abmayr Susan M.
Published: June 2009

The Immunoglobulin superfamily (IgSF) proteins Neph1 and Nephrin are co-expressed within podocytes in the kidney glomerulus, where they localize to the slit diaphragm (SD) and contribute to filtration between blood and urine. Herein, we demonstrate that their Drosophila orthologs Kirre (Duf)and Sns are co-expressed within binucleate garland cell nephrocytes (GCNs)that contribute to detoxification of the insect hemolymph by uptake of molecules through an SD-like nephrocyte diaphragm (ND) into labyrinthine channels that are active sites of endocytosis. The functions of Kirre and Sns in the embryonic musculature, to mediate adhesion and fusion between myoblasts to form multinucleate muscle fibers, have been conserved in the GCNs, where they contribute to adhesion of GCNs in the `garland' and to their fusion into binucleate cells. Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation. Knockdown of Kirre or Sns drastically reduces the number of NDs at the cell surface. These defects are associated with a decrease in uptake of large proteins, suggesting that the ND distinguishes molecules of different sizes and controls access to the channels. Moreover,mutations in the Sns fibronectin-binding or immunoglobulin domains lead to morphologically abnormal NDs and to reduced passage of proteins into the labyrinthine channels for uptake by endocytosis, suggesting a crucial and direct role for Sns in ND formation and function. These data reveal significant similarities between the insect ND and the SD in mammalian podocytes at the level of structure and function.
The Ecdysone receptor controls the post-critical weight switch to nutrition-independent differentiation inDrosophilawing imaginal discs
Authors: Mirth Christen K. , Truman James W. , Riddiford Lynn M.
Published: June 2009

In holometabolous insects, a species-specific size, known as critical weight, needs to be reached for metamorphosis to be initiated in the absence of further nutritional input. Previously, we found that reaching critical weight depends on the insulin-dependent growth of the prothoracic glands (PGs)in Drosophila larvae. Because the PGs produce the molting hormone ecdysone, we hypothesized that ecdysone signaling switches the larva to a nutrition-independent mode of development post-critical weight. Wing discs from pre-critical weight larvae [5 hours after third instar ecdysis (AL3E)]fed on sucrose alone showed suppressed Wingless (WG), Cut (CT) and Senseless(SENS) expression. Post-critical weight, a sucrose-only diet no longer suppressed the expression of these proteins. Feeding larvae that exhibit enhanced insulin signaling in their PGs at 5 hours AL3E on sucrose alone produced wing discs with precocious WG, CT and SENS expression. In addition,knocking down the Ecdysone receptor (EcR) selectively in the discs also promoted premature WG, CUT and SENS expression in the wing discs of sucrose-fed pre-critical weight larvae. EcR is involved in gene activation when ecdysone is present, and gene repression in its absence. Thus, knocking down EcR derepresses genes that are normally repressed by unliganded EcR,thereby allowing wing patterning to progress. In addition, knocking down EcR in the wing discs caused precocious expression of the ecdysone-responsive gene broad. These results suggest that post-critical weight, EcR signaling switches wing discs to a nutrition-independent mode of development via derepression.
Suppression of the immune response potentiates tadpole tail regeneration during the refractory period
Authors: Fukazawa Taro , Naora Yuko , Kunieda Takekazu , Kubo Takeo
Published: June 2009

Regenerative ability varies depending on animal species and developmental stage, but the factors that determine this variability remain unclear. Although Xenopus laevis tadpole tails possess high regenerative ability, this is transiently lost during the `refractory period'. Here, we show that tail amputation evokes different immune responses in wound tail stumps between the `refractory' and `regeneration' periods: there was delayed or prolonged expression of some immune-related genes in the refractory period,whereas there was no obvious or transient expression of other immune-related genes in the regeneration periods. In addition, immune suppression induced by either immunosuppressant treatment or immune cell depletion by knockdown of PU.1 significantly restored regenerative ability during the refractory period. These findings indicate that immune responses have a crucial role in determining regenerative ability in Xenopus tadpole tails.
Rho-regulated Myosin phosphatase establishes the level of protrusive activity required for cell movements during zebrafish gastrulation
Authors: Weiser Douglas C. , Row Richard H. , Kimelman David
Published: June 2009

Rho-dependent amoeboid cell movement is a crucial mechanism in both tumor cell invasion and morphogenetic cell movements during fish gastrulation. Amoeboid movement is characterized by relatively non-polarized cells displaying a high level of bleb-like protrusions. During gastrulation,zebrafish mesodermal cells undergo a series of conversions from amoeboid cell behaviors to more mesenchymal and finally highly polarized and intercalative cell behaviors. We demonstrate that Myosin phosphatase, a complex of Protein phosphatase 1 and the scaffolding protein Mypt1, functions to maintain the precise balance between amoeboid and mesenchymal cell behaviors required for cells to undergo convergence and extension. Importantly, Mypt1 has different cell-autonomous and non-cell-autonomous roles. Loss of Mypt1 throughout the embryo causes severe convergence defects, demonstrating that Mypt1 is required for the cell-cell interactions involved in dorsal convergence. By contrast,mesodermal Mypt1 morphant cells transplanted into wild-type hosts undergo dorsally directed cell migration, but they fail to shut down their protrusive behavior and undergo the normal intercalation required for extension. We further show that Mypt1 activity is regulated in embryos by Rho-mediated inhibitory phosphorylation, which is promoted by non-canonical Wnt signaling. We propose that Myosin phosphatase is a crucial and tightly controlled regulator of cell behaviors during gastrulation and that understanding its role in early development also provides insight into the mechanism of cancer cell invasion.
Differential and overlapping functions of two closely relatedDrosophilaFGF8-like growth factors in mesoderm development
Authors: Klingseisen Anna , Clark Ivan B. N. , Gryzik Tanja , Müller H.-Arno J.
Published: June 2009

Thisbe (Ths) and Pyramus (Pyr), two closely related Drosophilahomologues of the vertebrate fibroblast growth factor (FGF) 8/17/18 subfamily,are ligands for the FGF receptor Heartless (Htl). Both ligands are required for mesoderm development, but their differential expression patterns suggest distinct functions during development. We generated single mutants and found that ths or pyr loss-of-function mutations are semi-lethal and mutants exhibit much weaker phenotypes as compared with loss of both ligands or htl. Thus, pyr and ths display partial redundancy in their requirement in embryogenesis and viability. Nevertheless,we find that pyr and ths single mutants display defects in gastrulation and mesoderm differentiation. We show that localised expression of pyr is required for normal cell protrusions and high levels of MAPK activation in migrating mesoderm cells. The results support the model that Pyr acts as an instructive cue for mesoderm migration during gastrulation. Consistent with this function, mutations in pyr affect the normal segmental number of cardioblasts. Furthermore, Pyr is essential for the specification of even-skipped-positive mesodermal precursors and Pyr and Ths are both required for the specification of a subset of somatic muscles. The results demonstrate both independent and overlapping functions of two FGF8 homologues in mesoderm morphogenesis and differentiation. We propose that the integration of Pyr and Ths function is required for robustness of Htl-dependent mesoderm spreading and differentiation, but that the functions of Pyr have become more specific, possibly representing an early stage of functional divergence after gene duplication of a common ancestor.
Identification ofDlk1, PtpruandKlhl1as novel Nurr1 target genes in meso-diencephalic dopamine neurons
Authors: Jacobs Frank M. J. , van der Linden Annemarie J. A. , Wang Yuhui , von Oerthel Lars , Sul Hei Sook , Burbach J. Peter H. , Smidt Marten P.
Published: June 2009

The orphan nuclear receptor Nurr1 is essential for the development of meso-diencephalic dopamine (mdDA) neurons and is required, together with the homeobox transcription factor Pitx3, for the expression of genes involved in dopamine metabolism. In order to elucidate the molecular mechanisms that underlie the neuronal deficits in Nurr1-/- mice, we performed combined gene expression microarrays and ChIP-on-chip analysis and thereby identified Dlk1, Ptpru and Klhl1 as novel Nurr1 target genes in vivo. In line with the previously described cooperativity between Nurr1 and Pitx3, we show that the expression of Ptpru and Klhl1 in mdDA neurons is also dependent on Pitx3. Furthermore, we demonstrate that Nurr1 interacts with the Ptpru promoter directly and requires Pitx3 for full expression of Ptpru in mdDA neurons. By contrast, the expression of Dlk1 is maintained in Pitx3-/- embryos and is even expanded into the rostral part of the mdDA area, suggesting a unique position of Dlk1 in the Nurr1 and Pitx3 transcriptional cascades. Expression analysis in Dlk1-/- embryos reveals that Dlk1 is required to prevent premature expression of Dat in mdDA neuronal precursors as part of the multifaceted process of mdDA neuronal differentiation driven by Nurr1 and Pitx3. Taken together, the involvement of Nurr1 and Pitx3 in the expression of novel target genes involved in important neuronal processes such as neuronal patterning, axon outgrowth and terminal differentiation, opens up new avenues to study the properties of mdDA neurons during development and in neuronal pathology as observed in Parkinson's disease.
Under the Weather: Health, Schooling, and Economic Consequences of Early-Life Rainfall
Authors: Maccini Sharon , Yang Dean
Published: June 2009

We examine the effect of early-life rainfall on the health, education, and socioeconomic outcomes of Indonesian adults. We link historical rainfall for each individual's birth year and birth location with adult outcomes from the 2000 Indonesia Family Life Survey (IFLS). Higher early-life rainfall has large positive effects on the adult outcomes of women, but not of men. Women with 20 percent higher rainfall (relative to the local norm) are 0.57 centimeters taller, complete 0.22 more schooling grades, and live in households scoring 0.12 standard deviations higher on an asset index. Schooling attainment appears to mediate the impact on adult women's socioeconomic status. (JEL I12, I21, J16, O15)
On the Welfare Cost of Inflation and the Recent Behavior of Money Demand
Authors: Ireland Peter N
Published: June 2009

Post-1980 US data trace out a stable long-run money demand relationship of Cagan's semi-log form between the M1-income ratio and the nominal interest rate, with an interest semielasticity below 2. Integrating under this money demand curve yields estimates of the welfare costs of modest departures from Friedman's zero nominal interest rate rule for the optimum quantity of money that are quite small. The results suggest that the Federal Reserve's current policy, which generates low but still positive rates of inflation, provides an adequate approximation in welfare terms to the alternative of moving all the way to the Friedman rule. (JEL E31, E41, E52)
Bureaucratic Minimal Squawk Behavior: Theory and Evidence from Regulatory Agencies
Authors: Leaver Clare
Published: June 2009

This paper develops a model in which a desire to avoid criticism prompts otherwise public-spirited bureaucrats to behave inefficiently. Decisions are taken to keep interest groups quiet and to keep mistakes out of the public eye. The policy implications of this “minimal squawk” behavior are at odds with the view that agencies should be structured to minimize the threat of “capture.” An empirical test using data from US State Public Utility Commissions rejects the capture hypothesis and is consistent with the squawk hypothesis: longer PUC terms of office are associated with a higher incidence of rate reviews and lower household electricity bills. (JEL D73, L51, L97, L98)