dataesr/scientific-paragraphs-categorization huggingface dataset:
The increase of imaging resolution highlights small lesions which are undetectable with traditional methods. At the moment, biodegradable polymers or lipid-based colloids are the only drug vehicles approved for clinical use. These materials offer promising possibilities to assure specific drug accumulation at the tumour site, improving the pharmacokinetic profile and safety of both drug and contrast imaging agents  [22]. The present review is focused on lipid-based nanocarriers which have classically received great attention due to their biodegradability, biocompatibility and targetability  [23]. Lipid nanocarriers used for drug delivery purposes include liposomes, micelles, nanoemulsions, nanosuspensions, solid-lipid nanoparticles and lipoproteins-containing systems. Liposomal systems attract a great deal of interest and a simple research on the PubMed database reveals that more than 150 review articles have been published within this field in the last year alone.
Acknowledgements Authors thank  Dr Victoria Franzinetti  for her suggestions in revising the manuscript. The authors would like to recognize that their work in this area has been sponsored by the  European Research Council  under the European Community's  Seventh Framework Programme   FP7/2007-2013 Grant Agreement N°249835. The authors acknowledge the  Università Italo Francese/Université Franco Italienne (UIF/UFI)  for the PhD co-tutoring agreement. This article has been published as part of Journal of Nanobiotechnology Volume 11 Supplement 1, 2013: Nanophysics for Health. The full contents of the supplement are available online at http://www. jnanobiotechnology. com/ supplements/11/S1. Publication charges for this tutorial were funded by the  CNRS School "Nanophysics for Health ", 5 -9 November 2012, Mittelwhir, France.
The instability of weakly-damped Alfvén eigenmodes (AEs) is of highest priority for the next step burning plasma on ITER due to a number of reasons. First, AEs are driven by radial gradient of energetic particle pressure and lead to enhanced alpha-particle radial transport, in contrast to CAEs excited by velocity space gradients. Second, AEs resonate with alpha-particles in the MeV energy range in contrast to, e. g. fishbones expected to resonate with alpha-particles of 300-400 keV in ITER. Third, due to their weak damping, AEs could be excited by alpha-particle population with lower energy content per volume as compared to linear Energetic Particle Modes (EPMs). Although amplitudes of Alfvén perturbations are usually not too high in present day experiments, the existing experimental data on energetic particle radial redistribution and losses is representative enough to gain important information on the processes involved.
Figures 3, 4 display an example of the ECE radial profiles for beam-driven ACs (RSAEs) and TAEs in DIII-D discharge  [13]. Both localisation and the radial widths of these FL modes are found to agree well with the linear MHD code NOVA, which also includes the relationships between the perturbed magnetic fields, density and electron temperature. The perturbed electron temperature associated with the modes is estimated to be  10 -4 for TAE. This information is necessary for computing the energetic particle redistribution due to the AEs described in the next Section. In addition to the Alfvén diagnostics, there has been an extensive development in diagnostics of confined and lost energetic particles on many machines world-wide  [18]. Description of these diagnostics goes beyond the scope of this paper, but some examples of their use will be presented.
The particle-following code HAGIS  [30]  was then employed to simulate the interaction between the energetic ions and TAEs. The unperturbed distribution function of fast D ions was assumed to be of the form             f P f E f P E f    , , , where the distribution function in E B / 0    for trapped energetic ions accelerated with onaxis ICRH was considered to be Gaussian centred on 1   with the width of   1. 5•10 -1.
Another example of energetic particle redistribution by AEs comes from DIII-D experiments showing significant modification of D beam profile in the presence of multiple TAEs and RSAEs (Alfvén cascades)  [32]. This observation and TRANSP predictions are shown in Figure  10 , and TAE and RSAE data is shown in Figs  3, 4. Based on the ECE measurements of AE amplitude and mode structure, accurate modelling was performed in  [33]  with the ORBIT code  [25]  to interpret the flat fast ion profile. In this case of multiple modes densely packed in frequency, a wide area of wave-particle resonance overlaps was found. A stochastic threshold for the beam transport was estimated, and the experimental amplitudes were found to be only slightly above this threshold  [33]. We thus observe that multiple low amplitude AEs can indeed be responsible for substantial central flattening of the beam distribution as Figure  11  shows.
Recently, a quasi-linear 1. 5D model has been developed and applied to this DIII-D data  [34]. The model gives the relaxed fast ion profile determined by the competition between the AE drive and damping. Figure  12  presents a comparison between the experimental data, the TRANSP modelling, and the 1. 5D quasi-linear model  [34]  for the slowing-down distribution function of the beam. It is important to point out that the ratio between the beam orbits and minor radius in the DIII-D experiments,   a h / 0. 1, was well above the value expected for ITER,   a h / 10 -2. This difference implies that a similar excitation of RSAEs localised at min q in ITER will not necessarily give a global transport similar to that observed on DIII-D. In another theory-to-experiment comparison aimed at explaining TFTR results  [35] , the role of nonlinear sidebands including zonal flows was shown to be significant in reducing the mode saturation level.
The beam ion losses caused by the AEs were proportional to   2 B  , although the simulation cannot yet match the experimental data precisely. In ASDEX-Upgrade experiments, detailed measurements of radial structures of AE driven by beams and ICRH were obtained using ECE imaging  [14] , SXR, and reflectometry. The fast-ion redistribution and loss is routinely monitored with scintillator based fast-ion loss detectors and fast-ion D-alpha spectroscopy. It was found that a radial chain of overlapping AEs enables the transport of fast-ions from the core all the way to the loss detector  [36, 37].
Conclusion This work presents a first look towards a combined spectrum sensing and localization task. These two tasks are fundamental in order to enable cognition in wireless networks. With the combination of the two tasks, we also considered a realistic data acquisition constraint, which is sparsity due to the ADC technology limits. Simulation results of the proposed technique show promising and interesting results for compressed sensing techniques applied to this formalism. The formalism that we derived here is the starting point of a whole location-aided cognitive radio framework that is being developed within the FP7 WHERE2 project. In this framework, once the radio map  [31]  is built thanks to the sensing and localization tasks, the CRS are thus able to communicate in the available bands in the available directions and thus the proposed framework is a key enabler for space division multiple access (SDMA) systems and spatial versions of CR paradigms (underlay, overlay, and interweave).
Moreover, an important role in survival of the ingested microbes seems to be played by host proteins and redox balance maintenance in the tick midgut. Here, we summarize recent knowledge about the major components of tick immune system and focus on their interaction with the relevant tick-transmitted pathogens, represented by spirochetes (Borrelia), rickettsiae (Anaplasma), and protozoans (Babesia). Availability of the tick genomic database and feasibility of functional genomics based on RNA interference greatly contribute to the understanding of molecular and cellular interplay at the tick-pathogen interface and may provide new targets for blocking the transmission of tick pathogens.
CONCLUSION-FUTURE PERSPECTIVES The overall knowledge of tick innate immunity still lags far beyond the model invertebrate organisms and arthropod disease vectors. However, the availability of I. scapularis genome database  (Megy et al. , 2012) , feasibility of functional genomics based on RNAi  (De La Fuente et al. , 2007b)  and extensive number of tissue transcriptomes obtained from a variety of tick species promise to counterbalance experimental difficulties associated with tick handling and manipulation. Furthermore, introduction of the artificial membrane feeding  (Krober and Guerin, 2007)  extends our possibilities how to simulate the natural infections of ticks without the need of using laboratory animal models. These favorable conditions offer almost unlimited perspectives for the advanced research of the tick immune system and its impact on pathogen transmission.
ACKNOWLEDGMENTS This work was supported by the  Grant Agency of the Czech Republic  (grant Nos. :  506/10/2136 ,  13-11043S ; postdoctoral grants No. 13-27630P  and No. 13-12816P ). Ondřej Hajdušek  is further supported by the  EU   FP7  project  MODBIOLIN  No. 316304  and  Radek Šíma  by the project  Postdok_BIOGLOBE  ( CZ. 1. 07/2. 3. 00/30. 0032 )co-financed by the  European Social Fund  and the state budget of the Czech Republic. The research at the  Institute of Parasitology, BC ASCR  is covered by  RVO   60077344. This work was also supported by grants  BFU2011-23896  and  EU   FP7   ANTIGONE  project number  278976. Nieves Ayllón  was funded by  MEC, Spain. We acknowledge  Marie Hajdušková  (www. biographix. cz)for the design of presented figures.
Plasmid construction and mutagenesis The ORF encoding human GLTP (NCBI GenBank Accession No. AF209704) was subcloned into the pET-30 Xa/LIC expression vector (Novagen) by ligation-independent cloning, enabling cleavage of the N-terminal His 6 -S tag to yield a protein identical in sequence to native GLTP. The sitedirected D48V-GLTP mutant was obtained using the Quik-Change Site-directed Mutagenesis Kit (Stratagene) and was verified by sequencing. A similar approach was applied to obtain the mutants T207L, ÁC-end and ÁT207 and the double mutant A47D/D48V.
Crystallization and X-ray data collection Crystals of wild-type GLTP, D48V-GLTP and A47D/D48V-GLTP complexed with 12:0 monoSF or 12:0 diSF were grown by the hanging-drop vapour-diffusion method using PEG 3350 or 8000 (15-20%) as precipitant and 100 mM MES pH 5-7 containing 30-150 mM NaCl as buffer  (Malinina et al. , 2004 (Malinina et al. , , 2006;; Samygina et al. , 2011). All lipids were obtained from Avanti Polar Lipids (Alabaster, AL, USA). Protein-lipid complexes were prepared by mixing protein and lipid in a 1:1 molar ratio using lipids dissolved in ethanol ($40% EtOH). Crystals were transferred into well solution containing 20% glycerol as cryoprotectant, mounted in a fibre loop and flashcooled in a cold nitrogen stream. X-ray data were collected at 100 K using synchrotron radiation on beamline ID 23-1 at the ESRF, Grenoble, France, except for crystal form 1 of wtGLTP complexed with 12:0 monoSF and crystal form 2 of wtGLTP complexed with 12:0 diSF, data for which were collected at CIC bioGUNE at the Cu K wavelength (1.
Structure determination and refinement All structures were determined by the molecular-replacement (MR) method using the programs AMoRe  (Navaza, 1994)  or MOLREP  (Vagin & Teplyakov, 2010)  with the previously refined complexes as models  (Malinina et al. , 2004 (Malinina et al. , , 2006;; Samygina et al. , 2011). Refinement was performed with REFMAC  (Murshudov et al. , 2011) , alternating with manual model rebuilding using TURBO-FRODO and Coot. The ARP/ wARP automatic procedure was used to add solvent molecules  (Lamzin & Wilson, 1993). Final structures were validated by PROCHECK. The coordinates have been deposited in the Protein Data Bank. Data-collection and refinement statistics, together with space groups and unit-cell parameters, are summarized in Tables  1  and 2.
Dynamic light scattering Dynamic light-scattering (DLS) measurements were performed using a DynaPro Titan instrument from Wyatt Technology Corporation (with a laser of $830 nm wavelength). Measurements were performed in the protein concentration range 1-4 mg ml À1 in 150 mM NaCl, 20 mM Tris-HCl buffer pH 8. 0 at 291 K. Complexes with lipid were prepared immediately prior to measurement using protein: lipid ratios in complexes of 1:1. All buffers were centrifuged at 27 000g for 30 min and filtered through 0. 2 mm membrane filters (Whatman). Data were collected and analyzed using the DYNAMICS software for the DynaPro Titan instrument (Wyatt Technology Corporation).
Towards a structural dynamics study: different crystal forms of the same complexes To explore the structural dynamics of GLTP-GSL dimers, we cocrystallized 12:0 monoSF and 12:0 diSF in complex with wtGLTP and the SF-selective mutants D48V and A47D/D48V in different crystal forms. We determined nine novel crystal structures that could be classified into two groups. Table  1  contains the X-ray data and refinement statistics for class 1 crystals, which are isomorphous to previously studied GLTP crystals  (Malinina et al. , 2004 (Malinina et al. , , 2006;; Samygina et al. , 2011). Table  2  shows the X-ray data parameters for the same complexes crystallized in distinct crystal forms. To highlight the general difference in crystal arrangements, Table  2  includes two additional parameters: N, the number of protein monomers in the asymmetric unit, and V, the mean volume per protein monomer calculated by dividing the asymmetric unit volume by N.
1a ). However, an essential distinction between the two dimers becomes apparent upon careful comparison: the wtGLTP dimeric arrangement is more 'open' than that of the mutant. A reasonable measure of 'dimer openness' is the angle between the two 2 helices of partner monomers, which is $80 in the wild-type complex (Fig. 1a ) and $65 in the mutant complex (Fig. 1b ). To elucidate the flexibility of the dimeric structure in different crystals/ complexes, we calculated the inter-helical 2-2 0 angle and the midpoint distance between these helices (hereafter referred to as the angle and the t distance, respectively) for all nine crystal structures and some related GLTP complexes previously deposited in the PDB (Table  3 ) using the program INTERHLX (K. Yap, University of Toronto). In addition, using the CCP4 suite, we estimated the size of each monomermonomer surface contact area, which is an usual measure of 'contact strength' in structural analyses  (Janin & Chothia, 1990; Bahadur & Zacharias, 2008).
5a-5c ) is intriguing compared with fungal and algal GLTPs. In the GLTP-like proteins from the alga Galdieria sulphuraria (PDB entry 2q52;  Levin et al. , 2007)  and the fungus Podospora anserina (PDB entry 3kv0;  Kenoth et al. , 2010) , the C-end seems to be involved in supporting other important parts of the GLTP fold. We suggest, therefore, that the C-end plays a unique role in each case and is an important contributor to the functional diversity of the GLTP folds. In human GLTP, the C-terminus serves as an indicator of the openness of the homodimeric structure while also being indirectly involved in supporting the ceramide amide group of the bound GSL. The new structural insights into the ligand-dependent reversible dimerization of human GLTP changes our understanding of GLTP functionality and suggests that control of dimerization contact regions might provide a new strategy for targeting GSL-mediated pathologies.
This research was supported by Spanish Ministerio de Ciencia e Innovacion MICINN BFU2010-17711 and USPHS (NIGMS GM45928 and NCI CA121493), RFBR 12-04-00168, the Abby Rockefeller MauzeTrust and the Maloris and Hormel Foundations. We thank the personnel at ESRF beamline ID 23-1 for assistance with X-ray data collection, Sandra Delgado from CIC bioGUNE for help with fluorescence measurements, and Dr Margarita Malakhova, Dr Xiuhong Zhai and Helen Pike from the UMN-Hormel Institute for valuable advice, transfer activity plots and for expressing and purifying the protein used for transfer activity measurements, respectively.
7/44. 1 34. 8/47. 0 44. 5 36. 64 47. 08/57. 0 R. m. s. deviations Bond lengths (A ˚) 0. 018 0. 015 0. 018 0. 014 0. 018 Bond angles ( ) 1. 74 1. 56 1. 46 1. 38 1. 69 PDB entry 4h2z 4gh0 4ghp 4gix 4gxd.
Acknowledgments We would like to acknowledge and thank  Dr. A. E. Fink  for drawing the illustrations in Figures 1 and3. We would like to thank  Drs. C. K. Cain  and  M. J. Sanders  for their helpful comments on the manuscript. B. G. was supported by fellowships from  INSERM , as well as financial support from  IRS, Servier Company. This work was partially funded by Grants from  INSERM ,  IRS , and  NEWMEDS. The  NEWMEDS  project has been funded by the  Innovative Medicines Initiative Joint Undertaking (IMI)  under Grant Agreement  N_115008  (NEWMEDS). IMI is a public-private partnership between the  European Union  and the  European Federation of Pharmaceutical Industries and Associations. The H-PFC pathway The H-PFC pathway.
In a complementary analysis, 11 patients with amnestic MCI, coming from our previously reported cohort  [13] , were assessed for conversion. These patients were categorized into two groups; those who have converted to AD (converters) or those who have not converted (non-converters) at the end of the follow-up period. Mean levels of the various CSF biomarkers between these 2 groups were compared using Kruskal-Wallis non parametric analysis. P-values were two-tailed and values #0. 05 considered as statistically significant. Analyses were performed using SAS 9. 2 (SAS Institute, Cary, North Carolina, USA).
Acknowledgments List of the  Groupe d'Investigation du LCR (GIL) Network Members :  Catherine Belin , M. D. ,  Department of Neurology Centre Hospitalo-Universitaire (CHU) Avicenne Assistance Publique -Hopitaux de Paris (APHP) Bobigny France ;  Lucie Cabrejo , M. D. ,  Department of Neurology CHU Bichat APHP, Paris France ;  Hugues Chabriat , M. D. ,  Department of Neurology CHU Lariboisiere APHP Paris ;  Sarah Benisty, M. D. ,  Memory Center CHU Lariboisiere APHP Paris ;  Olivier Drunat , M. D. ,  Department of Psycho Geriatrics CHU Bretonneau APHP Paris ;  Katell Peoch ,  Department of Biochemistry Lariboisiere Hospital Paris ;  Sarah Gourmaud MS Inserm U 839 Paris.
Measurements are said to be in straylight conditions if the instrument is illuminated by light coming from the scattering of solar light. Straylight measurements are considered as of good quality (more details can be found in the GOMOS product handbook at http://envisat. esa. int/handbooks/gomos/toc. htm). -the GOMOS data used here are obtained with the version 5 of the ESA level 1 operational processor. -all the selected spectra are linearly interpolated on a common vertical grid of tangent altitudes from 0 to 60 km with 1 km steps. Figure  2  shows the latitudinal distribution of the GOMOS data used in our study to retrieve OClO. A total number of about 162 000 GOMOS measurements have been processed. While both polar regions are well covered during the winters and much less outside these periods, the other latitudes are very well sampled during all years (except in 2005).
Monthly climatology of OClO In Fig. 9  we show the time series of OClO SCDs in three latitude bands: the equatorial band (10 • S-10 • N, middle panel), the north polar band (60-90 • N, top panel) and the south polar band (60-90 • S , bottom panel). In the equatorial region, the missing data in 2005 are due to a GOMOS failure. The discontinuity observed in the two polar time series are due to the spatial coverage of GOMOS at these altitudes (cf. Fig. 2 ). Figure  10  exhibits the same time series but the color scale corresponds to OClO concentrations. Regarding the northern latitude band, we can clearly observe an annual increase of OClO followed by a decrease in the lower stratosphere (below about 25 km). The increase begins in December and reaches a maximum of about 5 × 10 15 cm -2 to 3 × 10 16 cm -2.
dist. , F N -1 [(i-0. 5)/N]) standardised residuals, e i|N /σ N r = 0 -3 -2 -1 0 1 2 3 quantiles of norm. dist. , F N -1 [(i-0. 5)/N]) N r = 4 Using the regression for N r = 4, the 27 d IDV(1d) HLS data are re-scaled and appended to the start of the NGK data, giving a composite of the HLS and NGK data sets. The re-scaled HLS data are used where available, but data gaps in that sequence are filled using the NGK data. The uncertainty is set by the full range of the effect of removing the top 8 outliers. Tests of this joining of the HLS and NGK data will be made later in this paper using fully independent data from different stations in the European sector.
Joining the NGK/HLS composite to ESK data The NGK/HLS data composite is then re-scaled in the same way and appended to the start of the ESK data. The scatter plot corresponding to Fig. 6  is shown in Fig. 9. Although the correlation was higher (correlation 0. 932 before the removal of outliers from the 123 pairs of 27 d means), in this case the removal of outliers did not cause the fit to converge as rapidly because, as shown in Fig. 9 , most of the largest N r = 8 outliers lay above the regression fits. However, increasing N r further did not change the slope further nor did it further improve the distribution of residuals. One point to note is that this correlation was taken over the interval between the start of the ESK data  (1911)  and 1920. This upper date could have been chosen to be later as both the data sets continue after it.
The complete composite and allowing for the secular field change Using the two regressions discussed in the previous two subsections, a single composite data sequence was generated. This would be the final composite, however there is a final correction to make first. The secular change in the geomagnetic field means that the magnetic latitude of the stations has drifted with time. Figure  10a  shows the predicted CGM  (Gustafsson et al. , 1992)   (Finlay et al. , 2010) ; before then they are from the gufm1 model  (Jackson et al. , 2000)  with a smooth transition in value and slope implemented over 1890-1900. The green point is the estimate of  [HLS,1840]  of 56. 50 • from  Nevanlinna (2006). The small discontinuities in the [NGK] curve at 1907 and 1931 arise from the moves of the NGK station from Potsdam to Seddin and from Seddin to Niemegk.
(1). We normalise to ESK in the year 2000 (so that it will be relatively straightforward to update the data sequence using future ESK data), so normalised data are given by IDV(1d) = IDV(1d) [X,d] × f [X,d] /f [ESK,2000]. (2) Figure  10  shows the factor needed to normalise the contributing station (X) at a given date d to the ESK in the year 2000, f [X,d] /f  [ESK,2000]  , computed from the  [X,d]  shown in the upper panel. These sequences have been splined together using the regression coefficients found in Sects. 5. 1 and 5. 2, such that the full sequence can be applied to the intercalibrated HLS-NGK-ESK composite. By definition the factor is unity in 2000 and between 1840 and 2015 it is within 0. 5 % of this value at all times. The motion of the geomagnetic pole has been such that the correction for the stations chosen is very small.
10. The coloured lines show 27 d Bartels rotation means (red for data originating from ESK, blue from NGK and green from HLS), the black line shows annual means. Figure  12  shows the scatter plot of annual means of the IDV(1d) composite as a function of the IDV index, as derived using many stations by SC10. This plot is for data after 1880 and it can be seen that the agreement is excellent. Figure  13  uses the best-fit regression to scale IDV   8 , as a function of the IDV index, as derived by SC10, against those for 1880-2013, using the same format as Fig. 3. The correlation coefficient is r = 0. 957 and removing outliers makes almost no difference to the regression fit because the correlation coefficient is so high. The best-fit regression slope is s = 0. 678 and the intercept is c = -0.