dataesr/scientific-paragraphs-categorization huggingface dataset:
25 nM) was incubated with varying concentrations of wild-type or mutant Taq DNA polymerases (0. 5-1000 nM; bracketing the predicted K d ) in 1× Taq buffer at 37 • C for 30 min. DNA-protein complexes were run on 10% non-denaturing TBE gels (Life Technologies) in 0. 5× TBE buffer. Gels were dried down and exposed to film. The fraction of DNA bound was quantified by densitometry using AlphaView SA software (Alpha Innotech), and then plotted against enzyme concentration to determine K d values by interpolation.
We increased KCl concentration from 50 to 95 mM to eliminate non-specific amplification products that were generated by the majority of fast-cycling mutants (<30% of total amplified product as judged by agarose gels or qPCR melt curves; data not shown). Higher KCl concentrations (>50 mM) inhibit wild-type Taq DNA polymerase to the extent where no PCR products are generated at 95 mM KCl. The most active Taq mutants (1C2, 2C2, 3B, 42; see Table  1 ) were sub-cloned to remove the His-tag, purified using a standard wild-type Taq protocol, and characterized further by PCR. In endpoint PCRs employing longer (>1 kb) genomic targets, Taq 1C2, 2C2, 3B, and 42 efficiently amplified targets using 15-30 s/kb extension times whereas Taq required 1 min/kb to generate similar yields (data not shown). Taq 1C2, 2C2, 3B, and 42 were also tested with shorter targets to assess the benefits of fast cycling in quantitative PCR (qPCR) assays that traditionally employ targets of <300 bp (SYBR Green detection) or <200 bp (probe detection) to achieve amplification efficiencies as close to 100% as possible.
KINETIC PARAMETERS OF Taq MUTANTS Kinetic parameters were investigated at each enzyme's KCl optimum (50 or 95 mM for Taq or Taq mutants, respectively) to determine how E507K confers the fast-cycling phenotype. In radio-labeled primer extension assays, Taq E507K and Taq 42 exhibit somewhat higher (1. 7-fold) polymerization rates compared to wild-type Taq (85 vs. 50 nt s -1 ; Table  2 ), but no change in processivity (20 bases; Table  2 ). Measurements of steady-state kinetic parameters also show a moderate (2. 2-fold) increase in K cat values (2. 5 ± 0. 03 s -1 for Taq 42; 1. 1 ± 0. 04 s -1 for Taq; data not shown). The most compelling difference between wild-type and E507K mutants was observed in gel-based K d assays employing a hairpin oligonucleotide template. As shown in Table  2 , dissociation constants for Taq 42, 1C2, and E507K mutants (2.
, 2009). In these studies, inhibitor resistance was determined relative to wild-type Taq using standard PCR cycling times. Compared to wild-type Taq, Taq 2C2 shows significantly (≥4-fold) higher tolerance to dextran sulfate (50-fold; data not shown), NaCl (4-fold; Table  3 ), and whole blood (see below). Additional testing with single-and multi-site mutants revealed that E507K confers increased tolerance to NaCl (up to 100 mM) in addition to higher affinity for primed-template. In contrast, mutations at other positions result in equivalent (V155I, F749) or reduced (Taq G59W; by 2. 5-fold) tolerance to NaCl compared to wild-type Taq. Next, resistance to blood-associated inhibitors was investigated in more depth by amplifying endogenous targets directly from blood (EDTA tubes). As shown in Figure  5 , the E507K mutation also provides increased tolerance to blood, allowing amplification of a 322 bp IGF target from up to 45% EDTA-blood.
The management of unstable distal radial fractures in the superelderly (≥80 years old) remains controversial. The aim of this study was to compare the functional outcome of super-elderly patients with and without malunion after a distal radial fracture. Methods. We identified 51 superelderly patients living independently with displaced fractures from a prospective database of 4024 patients with distal radial fractures. Activities of daily living, presence of wrist pain, whether the wrist had returned to its normal level function, grip strength and ROM were recorded. The dorsal angulation was measured radiographically. Results. There were 17 (33. 3%) patients defined to have a malunion. The outcomes of the independent patients with and without malunion were compared at a mean follow-up of 15 months.
Demographic Data. A prospective database of 4024 distal radial fractures was compiled over a 67-month period at the study centre, which recorded the following: demographic, radiographic, management, and outcome of all patients. The mean age for all patients was 59 (14 to 100) years. Fifty-one patients who aged 80 years or older sustaining a displaced distal radial fracture with outcome data at one year and lived independently were retrospectively identified from this database and were defined as the study population. There were 50 females and one male with a mean age of 83. 1 (80 to 93) years. Forty-eight patients (94%) were right-hand dominant. All fractures were unilateral.
Database Construction. Fracture management followed a standard protocol. The emergency room staff undertook the initial assessment and treatment. Fractures deemed to be in an acceptable position were managed with a dorsal plaster slab. If the fracture position was thought to be unacceptable, the emergency room staff, prior to application of a dorsal plaster slab, performed closed reduction using intravenous regional anaesthesia. The patients were evaluated clinically and radiographically at approximately one and six weeks after the injury as per the protocol of the study unit, which included radiographs of the normal, uninjured wrist performed at one week. At approximately one week following the injury, the patients were reviewed by the senior author in a dedicated research clinic. The clinical, demographic, and radiographic data were recorded and entered into a database either by the senior author or a research nurse.
Statistical Analysis. SPSS version 16. 0 software was used for statistical analysis (SPSS Inc. , Chicago, IL, USA). Fisher's exact test was used to compare the dichotomous variables (activities of daily living, presence of wrist pain, and return to normal use) and an unpaired -test was used to compare differences of liner variables (grip strength and ROM) between patients with and without malunion. Pearson's correlation coefficient was used to assess the relationship between dorsal angulation and radial shortening and ROM at the wrist. A  value of ≤0. 05 determined statistical significance.
This technique could be offered to those superelderly patients who develop a symptomatic malunion, if conservative methods fail to provide a satisfactory functional outcome. There are several limitations to this study. The major limitation is the retrospective nature of this study and the small cohort analysed. However, the prospective data capture was of high quality, with only a single data point being absent (ROM of opposite wrist) for a single patient. In addition, this is the only case series reporting the outcome for superelderly (≥80 years) patients in the current literature. We also included both extra-and intra-articular fractures which may have skewed our results. However, on post hoc analysis, no statistical difference was observed between extraarticular (AO/OTA type A) and intra-articular (AO/OTA type B and C) fractures for rate of malunion, ROM, or functional outcome.
PARTICIPANTS Two groups were included in the experiment. The first group comprehended 13 high-functioning adults males with autistic spectrum disorder (ASD) recruited from the database of the Specialized Clinic for Pervasive Developmental Disorders of Rivière-des-Prairies Hospital. Diagnosis of autism was established with the Autism Diagnostic Interview-Revised (ADI-R;  Lord et al. , 1994)  and validated by a standardized assessment with the Autism Diagnosis Observation Schedule (ADOS-G, module 3 or 4;  Lord et al. , 2000). All participants from the clinical group met the diagnostic criteria for autism or Asperger syndrome according to both instruments. The second group comprehended 15 matched male participants with typical development recruited from the same database. Some of the participants were excluded from the overall analysis due to technical problems occurred during the acquisition phase and due to head-movement artifacts in the BOLD signal.
STIMULI Our experimental stimuli were hybrid images built by combining a face composed only by HSFs with a face composed only by LSFs of opposite gender, whose expression was also separately manipulated (see Figure  2 ). The detailed procedure was adapted from the one used by previous studies  (Schyns and Oliva, 1999; Winston et al. , 2003b)  and can be summarized as follows. We took pictures of emotional (happy and fearful) and neutral facial expression, displayed from a frontal point-of-view, from the Karolinska Directed Emotional Faces database (A series). Validation studies on stimuli from this database  (Goeleven et al. , 2008)  confirmed that happy and fearful expressions were matched for intensity and arousal, and both associated with higher recognition scores than neutral expressions.
Data acquisition The study was conducted in the neurofunctional imagery unit at the research center of the geriatric institute of Montreal. A Siemens Trio 3-T whole-body scanner was used to acquire gradient-echo planar T2-weighted MRI images with blood oxygenation level dependent (BOLD) contrast. The scanning sequence was a trajectory-based reconstruction sequence with repetition time (TR) of 2160 ms, echo time (TE) of 30 ms, flip angle of 90 • , in-plane resolution 64 × 64, 36 slices, slice thickness of 3 mm, and no gap between slices. A structural image was of each participant was also recorded with a T1-weighted MPRAGE sequence (176 slices, TR = 9. 7 msec, TE = 4 ms, flip angle = 12 • , in-plane resolution = 256 × 256, 1 × 1 × 1 mm voxel size).
Preprocessing Statistical analysis was performed using the SPM software (http:// www. fil. ion. ucl. ac. uk/spm/). For each subject, all functional images were realigned, slice-time corrected to allow a whole volume to be treated as a single data point, normalized to a template based on 152 brains from the Montreal Neurological Institute (MNI), resliced at a voxel size of 3 × 3 × 3 mm, and then smoothed by convolution with a 8 mm full-width at halfmaximum (FWHM) Gaussian kernel.
First-level analysis Data from each participant were analyzed using the General Linear Model (GLM) framework implemented in SPM. For the face localizer session, we modeled each of the two active conditions (faces, houses) with a boxcar function. For the main experimental sessions, the trial onsets from each condition of our design were modeled with a delta (stick) function. Critically, whereas in the two passive viewing sessions we modeled only the main five conditions of our design (HF, HH, LF, LH, N), in the gender discrimination task we also took into account participants' response on every trial (see  Winston et al. , 2003b). Thus, for each of the five main conditions, we modeled separately those trials in which participants made their gender judgments on the basis on visual cues conveyed by LSFs (e.
NEURAL RESPONSES Face Localizer. Data from the Face localizer are displayed in Table  2  and Figure 4. We tested, in each group, whether there were significant differences in neural activity between the Face and House categories. The contrast Faces > Houses confirmed, in both neurotypical (Figure  4 , red clusters) and ASD individuals (green clusters), an involvement of the amygdala and of the posterior portion of the superior temporal sulcus in the two hemispheres. Controls also exhibited activation the medial orbitofrontal cortex. No fusiform activation was found in either group at the whole-brain threshold. We therefore performed additional region-of-interest analyses restricted to those voxels that were part of these fusiform gyrus as described by predefined anatomical masks  (AAL database-Tzourio-Mazoyer et al.
When testing for the interaction between the grouping factor and the stimuli employed (Faces vs. Houses), we found no suprathreshold effects. In sum, data from this localizer session successfully identified neural structures most sensitive to face stimuli, indicating the recruitment of similar portions of the fusiform cortex and amygdala in each group (although the evidence of FFA activity in ASD individuals was obtained with a more liberal threshold). As the functional localizer aimed at mapping in our population those portions in fusiform cortex and amygdala that were most sensitive to full-band face stimuli in each group, we then used the results of the localizer session to create a mask which could serve as region of interest in all subsequent analyses. This mask was built following anatomical and functional criteria, as it included voxels which (1) were part of either the fusiform gyrus or the amygdala according to predefined anatomical masks (AAL database) and (2) exhibited significant [t (18) > 1.
LIMITATIONS OF THE STUDY AND FUTURE RESEARCH Like many other neuroimaging investigations on autism, including those reviewed in this article, our dataset is penalized by the limited number of participants and by an ASD population including both individuals affected by Asperger Syndrome and High Functioning Autism (see Table  1 ). Low power is not necessarily detrimental for positive results, which in our case were all obtained under corrected statistical thresholds (see also  Friston, 2012) , but it is problematic for those tests producing null or marginal results and for which an effect could potentially still be found with a larger sample. Also the heterogeneity of the clinical sample might be an additional source of noise with detrimental effects on the power of statistical analysis. Furthermore, some of the effects might be driven by only one of the two clinical sub-groups without a possibility of further verification on corresponding subsamples.
Statistical analysis All statistical analyses were done using the statistical environment R 2. 15. 1  [39]. Similarities between pollen spectra were computed using two indices: binary Bray-Curtis' index (bBC) and Bray-Curtis' index (BC). These two indices compare pollen presence/absence and pollen frequencies between samples, respectively, and are calculated as follows  [39] : bBC jk ~bBC kj ~AzB{2J AzB and BC jk ~BC kj ~Pn i x ij {x ik P n i (x ij zx ik ) For the bBC index, A and B are the numbers of species in samples j and k, and J is the number of species found in the two samples. The BC index uses the absolute distance between x ij and x ik , which are pollen frequencies for the i th over n species in samples j and k. Multivariate analyses of variance (MANOVA) were performed to test the effects of the independent variables Month, Year and Location on the pollen spectra, the latter being the dependent variable since we aimed at testing if the pollen spectra vary between Months between Years, and between the Locations and if any interaction between these factors exists in our dataset.
Principal Component Analyses (PCA) explored how the structure of our experimental design (Month, Year, Location) interplay in the total variance of our dataset as summarized by the principal components. In other words, if the replicability is high among sites, we expect samples of each site to cluster together, no matter which Year or Month they were collected. Then, Linear Discriminant Analyses (LDA) with and without cross-validation (leave-one-out) determined the classification error, i. e. , the value of previous knowledge. In other words, if for every sample, we use the grouping structure of all the samples collected but one, and then introduced the left out sample, do we classify it correctly? PCA was performed and illustrated using the ade4 package  [40]  to explore how pollen taxa and different Months, Years, and Locations are distributed.
Confidence ellipses (61. 5SD on every PC), corresponding to the categories of every factor and drawn a posteriori on the factorial map, help graphically to understand the patterns observed. Scatter correlation circles were then used to explore and attribute the influences of each pollen taxon. Percentages of the variance explained by the successive PC axes were calculated using the Eigen values of the variance/covariance matrix. LDA was performed using the package MASS  [41]  to test whether the discriminant linear combinations of pollen taxa were able to discriminate between groups. The standardized discriminant coefficients were used to compare the relative importance of the pollen taxa in order to discriminate within/between groups of samples. Three LD axes were obtained for Month and Location (4 levels each) and two LD axes were obtained for the factor Year (3 levels each).
The LD axes that brought the maximum between-groups differences were considered for each of the factors. LDA was first performed on the complete dataset of 80 taxa. We then tested if LDA can also be used in our case as a tool to classify additional pollen spectra based on this discriminant function, using the leaveone-out cross-validation implemented in the MASS package  [41]. The idea behind this validation is simple: every pollen spectrum is successively removed from the dataset and an LDA is performed and then used to classify the pollen spectrum removed. For the final analyses, we retained only the 51 taxa that occurred at least 3 times in our dataset of 42 samples.
Acknowledgments We are thankful to the team members of Project Ecolake for facilitating and helping with the fieldwork and colleagues at the  Ecology Department, French Institute of Pondicherry  for useful discussions during this project. We thank  Dr. Nina Sengupta , Auroville and  Dr. Gary Burkhart ,  School of Medicine, Marseille  for reading earlier versions of this manuscript. We thank the two reviewers for their suggestions on our manuscript.
Purpose We describe our protocol of three-dimensional (3D) Roadmap intracranial navigation and image fusion for analysis of the angioarchitecture and endovascular treatment of brain arteriovenous malformations (AVMs). Methods We performed superselective catheterization of brain AVMs feeders under 3D-Roadmap navigation. Angiograms of each catheterized artery on two registered orthogonal views were transferred to the imaging workstations, and dedicated postprocessing imaging software allowed automated multiple overlays of the arterial supply of the AVM superselective acquisitions on the global angiogram in angiographic or 3D views and on coregistered MRI datasets. Results 11 untreated brain AVMs (4 with hemorrhagic presentation) were explored. The superselective acquisitions were performed under 3D-Roadmap navigation in 74 arteries, for a total of 79 targeted arteries.
Imaging analysis was available at table side or postoperatively for discussion of the therapeutic strategy. No complications occurred during superselective catheterization. The accuracy of the coregistration of angiogram and MRI was submillimetric after automated mutual information coregistration, with manual reregistration by the physicians. Conclusions Superselective angiograms acquired under 3D-Roadmap navigation can be postprocessed with multiple overlays. The fluoroscopic navigation under 3D-Roadmapping and the coregistration of 3D rotational angiography, selective angiography, and 3D MR datasets appears reliable with millimeter accuracy, and could be implemented in the critical brain AVM embolization setting to allow refined analysis of AVM angioarchitecture.
3D rotational angiography A total volume of 28 mL of iodine contrast material (Iomeron 300, Bracco, Milan, Italy), at a rate of 4 mL/s, were injected. The rotation started 3 s after the injection for the vessels with feeding arteries to the AVM. To obtain a 3D reconstruction, 120 two-dimensional (2D) images were registered at a rate of 30 frames/s, from -120°to +120°, at a speed of 55°/s. The datasets acquired into a 256 3 pixel matrix were directly transferred to a 3D workstation (Xtravision, Philips Healthcare), and reconstruction of the 3D volume was made from 100% to 140%, in order to obtain more information with a better resolution.
Image postprocessing Each superselective angiogram was overlaid automatically and in real time with 3D RA using the Xtravision workstation (figure  3 ). For the purpose of specific analysis of the AVM angioarchitecture, superselective acquisitions realized on a machine based registration in orthonormal projections could be overlaid on one another, or on the selective angiogram of other feeding arteries with the help of a software Plug-in developed for this purpose under OsiriX (see online supplemental data). The angiographic acquisitions could be overlaid with 3D MR datasets.
Mutual information coregistration technique 3D MR/ angiographic fusion Three-dimensional MR datasets available on the PACS system of our institution (Isite, Philips Healthcare) were uploaded onto the dedicated workstation (Xtravision, Philips Healthcare) and coregistered to the perioperative 3D RA by semi-automatic registration according to the mutual information criterion (figure  4 ). 24 This automated registration process takes less than 30 s per case. We validated and manually fine tuned the coregistration by applying correction in the three different planes by panning the 3D RA volume ( primary volume) slice to overlay with the underlying pre-acquired MR displayed as an MIP slice (overlay volume). The time taken to realize this registration was noted. After registration the two volumes were fused and could be handled in a 3D space environment by rotating, zooming, and panning with selected rendering (maximum intensity projection (MIP), multiplanar reformation (MPR)) and slice thickness options.
As the C arm system is used to obtain the 3D RA data, as well as the 2D fluoroscopy data, the relation between their respective coordinate systems is inherently known, as long as there is no patient motion. As a consequence, the image based registration of the MR and 3D RA datasets also registered the 3D RA and C arm coordinate systems. The live fluoroscopy images and superselective angiography could thus be overlaid with the 3D RA/MR fused data. Evaluation of the accuracy of the image based registration of 3D RA/3D MR was retrospectively and independently performed after the treatment procedure on the dedicated workstation (Xtravision, Philips Healthcare) with the aim of analyzing the maximal discrepancy between arterial feeders imaged by angiograms and arterial feeders visible on 3D MR for the image based registration technique.
Analysis of superselective imaging We recorded the number of vessels that were superselectively catheterized. A classification of anatomic subgroups for these vessels, according to previously published neurosurgical  15 25  and neuroradiologic descriptions,  18  was determined as follows: (1) terminal type arterial feeder; (2) collateral type arterial feeder; (3) 'en passant' branches; (4) normal vessels catheterized (blood flow to normal brain with no early venous drainage); and (5) arterial pedicles from border territories that corresponded to pial to pial collateral circulation. We recorded the total number of arterial aneurysms, either proximal (visualized proximally on the circle of Willis) or more distal (observed on the superselectively catheterized branches). We analyzed the superselective angiograms fused with the 3D MR datasets for correlation of vessel type with surrounding brain parenchyma.
The 3D-Roadmap technique allows you to switch quickly in between these various scenarios  22  without patient or table movements. The processed 3D RA images are static, ignoring critical information of the angiogram, especially superimposition of the veins obscuring nidus details. The ability to overlay dynamic datasets from superselective angiography on 3D RA images is thus interesting. The accuracy and speed of realizing the superimposition of each superselective angiogram by dedicated software greatly benefits from acquisitions in orthonormal projections. We are able, per procedure, to analyze separately or in combination each type of feeding artery supplying the AVM, as well as the arterial supply to the normal brain, which could help define a treatment strategy with regard to embolization sessions.