julilili42/papers huggingface dataset:
Laser‐assisted microdissection for the study of the ecology of parasites in their hosts
2009-01-31

Abstract The population biology of internal parasites is difficult to study because the adult parasites are often inaccessible, deep within the host's body. Developing stages, such as eggs in the faeces or larvae in the skin are more easily obtained, but are difficult to handle because they are often very small and with a tough cuticle. This has limited their use in molecular ecology for estimating population biology parameters of the adults (their parents). We have used Onchocerca ochengi (a filarial nematode parasite of cattle) to describe a novel and generally applicable method of easily and conveniently isolating individual larvae (microfilariae) from the host using laser‐assisted microdissection. Furthermore, we have been able to improve the isolation of DNA by using the laser to bisect the larva to release DNA from the tissues enclosed within the parasite cuticle, and in this way we have achieved amplification of fragments over 1400 bp, and routinely PCR‐amplified single‐copy sequences from 5% of the DNA from a single larva (the equivalent of approximately 15 nuclei), and regularly from 0.5%.
Optical microresonator modifies the efficiency of the fluorescence resonance energy transfer in the autofluorescent protein DsRed
2009-01-31

We investigate experimentally the modifications of the fluorescence properties of the bichromophoric fluorescent resonance energy transfer (FRET) system DsRed imposed by optical confinement. The confinement-condition is realized by a novel λ/2-microresonator that modifies the local photonic mode density in the vicinity of the proteins while maintaining a physiological environment for the embedded biological molecules. The experimental ratio of the fluorescence intensities and lifetimes, respectively, of donor and acceptor chromophores varies by up to a one order of magnitude as we vary the mirror spacing of the microresonator with nanometer-precision. Since these ratios determine the FRET efficiency, we modify the yield of the excited state energy transfer in rigidly coupled FRET pairs without chemically or physically perturbating the chromophoric subunits. We show that the microresonator-controlled inhibition of the acceptor fluorescence results in a loss of transfer efficiency of excited state energy from donor to acceptor, an effect that enables the spectral isolation and efficient observation of donor chromophores both in DsRed ensembles and on the single protein level. This constitutes an important application of microcavity-enhanced single molecule spectroscopy of biological systems and shows the potential of optical confinement for applications in nano-biophotonics.
Multiparameter single molecule spectroscopy gives insight into the complex photophysics of fluorescence energy transfer (FRET) coupled biosystems
2009-01-31

Since the discovery of the technique in the early 1990s, single molecule spectroscopy has been used as a powerful tool to investigate and characterize fluorescent molecules, revealing insights into molecular behavior far beyond the information content that can be obtained by conventional ensemble studies. Several spectroscopic techniques have been established at the single molecule level, including spectrally resolved fluorescence, fluorescence lifetime investigations, or single molecule Raman measurements. However, the combination of two or more of these spectroscopies applied to the same individual molecule in multiparameter approaches yields a deeper understanding of molecular systems. In this contribution, we present our results of combined spectrally- and time-resolved fluorescence microscopy of the intrinsic fluorescence energy transfer (FRET) system of the red fluorescent protein DsRed. Correlating the results obtained from the two spectroscopic techniques, we are able to determine all relevant parameters to describe the energy transfer processes within the DsRed system without any further assumptions. We further discuss fluorescence and surface enhanced Raman scattering (SERS) spectroscopy of the same individual DsRed unit, which can help to propose mechanisms for photodegeneration of the distinct chromophores involved
mTOR inhibitors for hepatocellular cancer: a forward-moving target
2009-02-01

mTOR is a central regulator of cell growth and angiogenesis. The mTOR pathway is activated in 40-50% of patients with hepatocellular cancer (HCC). In different models (i.e., hepatoma cell lines and implanted HCC tumors in rats), mTOR inhibitors (mTORIs) were effective in reducing cell growth and tumor vascularity. Synergistic effects were observed for mTORIs and chemotherapeutic agents in these studies, while other combinations involving mTORIs and inhibitors of growth hormones and angiogenesis are awaiting further clinical testing. A number of mTORIs are already clinically available (e.g., sirolimus, temsirolimus and everolimus), sharing similiar pharmacokinetic parameters (except for absorption) and side effects. Clinical data are, as yet, only preliminary and are mainly derived from retrospective studies in patients who underwent liver transplantation for HCC. Those patients had received sirolimus thereafter for immunosuppression, and a much lower rate of tumor recurrence than with calcineurin inhibitors alone was noted. Current prospective trials for treatment of advanced HCC include mTORIs alone or in combination with either transarterial chemoembolization or other systemic drugs, and will be discussed in detail in this review.
Contrasting community responses to fertilization and the role of the competitive ability of dominant species
2009-02-01

Abstract Question: Do contrasting biotic contexts in nutrient‐poor grasslands affect the predictability of invasion by exploitative species following fertilization? Location: French Alps. Methods: We examined community responses after 2 years of nutrient addition for two nutrient‐poor European calcareous grasslands, a mesoxeric community dominated by the short bunchgrass Bromus erectus and a mesic community dominated by the tall rhizomatous grass Brachypodium rupestre . We also performed reciprocal transplantations of these two dominant slow‐growing species and Arrhenatherum elatius , a tall fast‐growing grass that dominates nutrient‐rich communities and is likely to invade nutrient‐poor communities after fertilization. Transplants were grown with or without neighbors, in order to measure their individual responses (without neighbors) and competition intensity (by comparing performances with and without neighbors using the Relative Neighbor Effect index – RNE) during one growing season in all three communities. Results: In the Bromus community, fertilization induced a strong increase in fast‐growing grasses (including A. elatius ). Competition intensity was low for the three transplanted grasses, but strongly increased with resource addition, to reach values observed in the Arrhenatherum community. In the Brachypodium community, no change in competition intensity with fertilization was detected, because of the high mortality of the two “non‐resident” species, irrespective of the presence of neighbors. Conclusions: Community responses to nutrient improvement are context‐dependent and vary as a function of the biotic environment. Soil processes are proposed as the main drivers of community resistance to the invasion of fast‐growing species in the mesic, nutrient‐poor grassland dominated by the large conservative competitor B. rupestre .
Microstructure–critical current density model for MgB2 wires and tapes
2009-02-01

MgB 2 wires and tapes were prepared by the powder in tube method using different processing technologies and thoroughly characterized for their superconducting properties. Either prereacted MgB2 (ex situ) or a mixture of Mg+2B (in situ) was used as the precursor powder. In some wires the precursor powder was mixed with SiC. The critical current density (Jc) of these wires was found to differ by orders of magnitude, the highest Jc being 104 A cm−2 at 10.5 T and 4.2 K. The microstructure of these wires was investigated using quantitative electron microscopy and spectroscopy methods [B. Birajdar, N. Peranio, and O. Eibl, Supercond. Sci. Technol. 21, 073001 (2008)]: combined scanning electron microscopy, electron probe microanalysis, and transmission electron microscopy analysis with artifact-free sample preparation, elemental mapping, and advanced chemical quantification. Wires with prereacted MgB2 (ex situ) show oxygen-poor MgB2 colonies (a colony is a dense arrangement of several MgB2 grains) embedded in a porous oxygen-rich matrix introducing structural granularity. Wires with elemental precursors (in situ) are generally more dense but show inhibited MgB2 phase formation with significantly higher fraction of B-rich secondary phases in comparison to the ex situ wires. SiC in the in situ wires results in the formation of Mg2Si secondary phases. In situ and mechanically alloyed samples show smaller (20–100 nm) MgB2 grains, the grain size being slightly larger than the coherence length. All samples show Mg oxide. SiC added samples annealed beyond 950 °C yield formation of Si oxide compounds, whereas Mg2Si is found for annealing temperatures of less than 650 °C. The critical current is limited due to the anisotropy but also due to structural granularity. A microstructure–critical current density model is given to explain the large, orders of magnitude, differences in the Jc of MgB2 wires and tapes. The model contains the following microstructure parameters: (1) MgB2 grain size, (2) colony size, (3) volume fraction of B-rich secondary phases, and (4) oxygen mole fraction. The logarithmic critical current densities as a function of magnetic field were parametrized and the decay field and the critical current density at zero field (Jc0) was quantitatively correlated with the parameters of the microstructure. The MgB2 grain size is negatively correlated with the decay field and the three other microstructure parameters show correlation with Jc0. Sample preparation influencing the microstructure parameters is discussed. A detailed analysis is given to correlate the microstructural data with respect to fundamental parameters of a flux-line pinning model established for anisotropic superconductors.
Regulation of Cytochrome P450 Expression by Ras- and &#946;-Catenin-Dependent Signaling
2009-02-01

Signaling through the Ha-Ras/ mitogen-activated protein kinase cascade and through the Wnt/ beta-catenin signaling pathway has been implicated in various developmental processes as well as in carcinogenesis of different organs by regulating cell growth and differentiation. In particular, both pathways have been reported to play an important role in embryonic liver development as well as in liver regeneration after partial hepatectomy. More recently, there is accumulating evidence for a role of Ras- and beta catenin-dependent signal transduction in the regulation of zone-specific gene expression in healthy adult liver. An antagonistic interplay of both pathways was proposed: beta-catenin was established to function as a decisive regulator of 'perivenous' gene expression in hepatocytes neighboring branches of the central vein, whereas the Ras pathway was linked to transcription of 'periportal' genes. Xenobiotic-metabolizing enzymes constitute one of the largest functionally related groups of zonated genes with predominantly perivenous expression of the most abundant enzymes of xenobiotic metabolism. In this review, the current knowledge regarding the role of Ras and beta catenin signaling in the regulation of expression of xenobiotic-metabolizing enzymes from the cytochrome P450 superfamily will be summarized including both in vitro and in vivo observations.
Porphyroblast rotation versus nonrotation: Conflict resolution!
2009-02-01

[Fay et al. (2008)][1] present a few numerical simulations (with unspecified code or boundary conditions) as evidence for nonrotation of porphyroblasts during non-coaxial flow. However, the large body of work on the behavior of porphyroblasts in deforming ductile rocks is significantly undervalued.
Late JurassicSunosuchus(Crocodylomorpha, Neosuchia) from the Qigu Formation in the Junggar Basin (Xinjiang, China)
2009-02-01

Various bone fragments of the crocodylomorph Sunosuchus from the Late Jurassic (Oxfordian) Qigu Formation in the southern Junggar Basin (Xinjiang Province/China) can be assigned to a single specimen and comprise the occipital region of the skull, mandibular fragments, and few postcranial elements. The size of the reconstructed skull does not exceed 30 cm in length and 13 cm in width. After comparison with other Sunosuchus species, the generic diagnosis of the genus can be expanded with the character of a lobe-like and unsculptured posterolateral process of the squamosal. The specimen is the first evidence of a crocodylomorph from the Qigu Formation and extends the geographical and stratigraphical range of Sunosuchus.
WTO Membership and the Extensive Margin of World Trade: New Evidence
2009-02-01

Recent literature has argued that, contrary to the results of a seminal paper by Rose (2004), WTO membership does promote bilateral trade, at least for developed economies and if membership includes non-formal compliance. We review the literature in order to identify open issues. We then develop the simplest possible “corner-solutions" version of the gravity model which serves as a framework to readdress these issues. We focus on the extensive margin of trade that separates positive-trade from zero-trade country pairs. We argue that the model can be consistently estimated using Poisson pseudo-maximum-likelihood methods with exporter and importer fixed effects. We account for coding issues and the potential heterogeneity of the WTO membership which recent contributions have stressed. While we find that WTO membership increases the likelihood that a given country pair trades, we do not find that the extensive margin has a strong and systematic effect on the average trade-creating potential of the WTO.
ANALYSIS OF THE NEURONAL MARKER PROTEIN GENE PRODUCT 9.5 IN INTERNAL LIMITING MEMBRANES AFTER INDOCYANINE-GREEN ASSISTED PEELING
2009-02-01

Focal expression of protein gene product 9.5 in only 1 of 10 surgical ILM specimens argues against a general indocyanine green-related disruption of the innermost retinal layers. However, higher concentrations of the dye, longer incubation times or different solvents than used in this study may lead to different results.
Double-Pionic Fusion of Nuclear Systems and the “ABC” Effect: Approaching a Puzzle by Exclusive and Kinematically Complete Measurements
2009-02-02

The ABC effect-a puzzling low-mass enhancement in the pipi invariant mass spectrum, first observed by Abashian, Booth, and Crowe-is well known from inclusive measurements of two-pion production in nuclear fusion reactions. Here we report on the first exclusive and kinematically complete measurements of the most basic double-pionic fusion reaction pn-->dpi;{0}pi;{0} at beam energies of 1.03 and 1.35 GeV. The measurements, which have been carried out at CELSIUS-WASA, reveal the ABC effect to be a (pipi)_{I=L=0} channel phenomenon associated with both a resonancelike energy dependence in the integral cross section and the formation of a DeltaDelta system in the intermediate state. A corresponding simple s-channel resonance ansatz provides a surprisingly good description of the data.
Influence of aquifer and streambed heterogeneity on the distribution of groundwater discharge
2009-02-02

Abstract. The spatial distribution of groundwater fluxes through a streambed can be highly variable, most often resulting from a heterogeneous distribution of aquifer and streambed permeabilities along the flow pathways. Using a groundwater flow and heat transport model, we defined four scenarios of aquifer and streambed permeability distributions to simulate and assess the impact of subsurface heterogeneity on the distribution of groundwater fluxes through the streambed: (a) a homogeneous low-K streambed within a heterogeneous aquifer; (b) a heterogeneous streambed within a homogeneous aquifer; (c) a well connected heterogeneous low-K streambed within a heterogeneous aquifer; and (d) a poorly connected heterogeneous low-K streambed within a heterogeneous aquifer. The simulation results were compared with a base case scenario, in which the streambed had the same properties as the aquifer, and with observed data. The results indicated that the aquifer has a stronger influence on the distribution of groundwater fluxes through the streambed than the streambed itself. However, a homogeneous low-K streambed, a case often implemented in regional-scale groundwater flow models, resulted in a strong homogenization of fluxes, which may have important implications for the estimation of peak mass flows. The flux distributions simulated with heterogeneous low-K streambeds were similar to the flux distributions of the base case scenario, despite the lower permeability. The representation of heterogeneous distributions of aquifer and streambed properties in the model has been proven to be beneficial for the accuracy of flow simulations.
Spinocerebellar ataxia type 6 (SCA6): neurodegeneration goes beyond the known brain predilection sites
2009-02-02

Aims: Spinocerebellar ataxia type 6 (SCA6) is a late onset autosomal dominantly inherited ataxic disorder, which belongs to the group of CAG repeat, or polyglutamine, diseases. Although, it has long been regarded as a ‘pure’ cerebellar disease, recent clinical studies have demonstrated disease signs challenging the view that neurodegeneration in SCA6 is confined to the well‐known lesions in the cerebellum and inferior olive. Methods: We performed a systematic pathoanatomical study throughout the brains of three clinically diagnosed and genetically confirmed SCA6 patients. Results: This study confirmed that brain damage in SCA6 goes beyond the known brain predilection sites. In all of the SCA6 patients studied loss of cerebellar Purkinje cells and absence of morphologically intact layer V giant Betz pyramidal cells in the primary motor cortex, as well as widespread degeneration of brainstem nuclei was present. Additional damage to the deep cerebellar nuclei was observed in two of three SCA6 patients. Conclusions: In view of the known functional role of affected central nervous grey components it is likely that their degeneration at least in part is responsible for the occurrence of a variety of SCA6 disease symptoms.
Long-Term Survival of Patients With Glioblastoma Treated With Radiotherapy and Lomustine Plus Temozolomide
2009-02-03

Purpose To evaluate long-term survival in a prospective series of patients newly diagnosed with glioblastoma and treated with a combination of lomustine (CCNU), temozolomide (TMZ), and radiotherapy. Patients and Methods Thirty-nine patients received radiotherapy of the tumor site only (60 Gy) and CCNU/TMZ chemotherapy (n = 31 received standard-dose CCNU, 100 mg/m 2 on day 1 and TMZ 100 mg/m 2 /d on days 2 to 6; n = 8 received intensified-dose CCNU 110 mg/m 2 on day 1 and TMZ 150 mg/m 2 on days 2 to 6) for up to six courses. Results In the whole cohort, the median overall survival (mOS) was 23.1 months; 47.4% survived for 2 years, and 18.5% survived for 4 years. After a median follow-up of 41.5 months, mOS had not been reached in the intensified group and was significantly higher than in the standard group (22.6 months; P = .024). In the intensified group, four of eight patients survived for at least 56 months, two of them without recurrence. O 6 -methylguanine–DNA methyltransferase (MGMT) gene promotor methylation in the tumor tissue was associated with significantly longer mOS (methylated, 34.3 months v nonmethylated, 12.5 months). A multivariate Cox proportional hazard model revealed MGMT status (methylated v nonmethylated; relative risk [RR] of death, 0.43; P = .003) and chemotherapy dose (intensified v standard; RR, 0.37; P = .012) as independent prognostic factors. WHO grade 4 hematoxicity was observed more frequently in the intensified group (57% v 16%). Conclusion The combination of radiotherapy, CCNU, and TMZ yielded promising long-term survival data in patients with newly diagnosed glioblastoma. Intensification of CCNU/TMZ chemotherapy may add an additional survival benefit, albeit with greater acute toxicity.
Defocused Wide‐field Imaging Unravels Structural and Temporal Heterogeneity in Complex Systems
2009-02-03

Abstract Today's miniature devices and biological systems share the fact that their dynamics and properties cannot be understood in terms of macroscopic concepts, but require a thorough understanding of the nanoscale structuring. This structuring is often very heterogeneous, both in time and in space, and is difficult or impossible to resolve with traditional approaches. In this Progress Report, we will discuss how single‐molecule microscopy—and defocused wide‐field imaging in particular—can be used to shed light on these phenomena.
EpCAM, a human tumor-associated antigen promotes Th2 development and tumor immune evasion
2009-02-03

Abstract Experimental tumor vaccination and adoptive T-cell therapies show that interferon-γ (IFN-γ)–producing CD4+ T helper cells (Th1) can be highly effective in tumor prevention and therapy. Unexpectedly, first vaccine trials in humans revealed that tumor immune therapy may not only be protective, but, on the contrary, even promote tumor progression. Here, we analyzed T-cell immune responses to the epithelial cell adhesion molecule (EpCAM), one of the most common tumor-associated antigens (TAA) serving as immune target in colon cancer patients. Th-cell priming against EpCAM inevitably resulted in interleukin-4 (IL-4)–dominated Th2 responses, even under most stringent Th1-inducing conditions. These EpCAM-reactive Th2 cells rather promoted growth of EpCAM-expressing tumors. To analyze the role of IL-4 in tumor immune evasion, we generated EpCAM-reactive Th1 cells from IL-4.ko mice. These Th1 cells provided tumor-specific protection and established highly protective Th1 memory responses, even in naive BALB/c mice. Inhibition of tumor growth by Th1 cells resulted in intra-tumoral expression of cytokines of the IL-12 family and of IFN-γ. Preventing activation-associated death of Th1 cells further increased intratumoral IFN-γ expression and improved therapeutic efficacy. Thus, human TAA may promote tumor immune evasion by strongly favoring Th2 development.