dataesr/scientific-paragraphs-categorization huggingface dataset:
Therefore, the competition between ICAT and these proteins likely occurs in this region. Slight variations in the consensus sequence may account for differences in ligand binding affinities  [27] , although the exact contribution of residues D, F and E in conferring binding energy to the groove remains debated. Indeed, in TCF7L2, residue F21 was found to be dispensable in one study  [28]  or essential in another one  [29]  for its binding to βcatenin. Additionally, the disruption of the salt bridge between residue E24 in TCF7L2 and K312 in β-catenin, only mildly affected the affinity  [28]. Therefore, the contribution of these residues to the interaction of ICAT with β-catenin needs clarification. Crystal structure of the β-catenin/ICAT complex. A Crystal structure of ICAT bound to the core domain of β-catenin (PDB code 1LUJ,  [22] ).
ICAT is shown as yellow ribbons and β-catenin as purple cylinders. The secondary structures were calculated using the program STRIDE  [37]. Residues mutated in this study are shown as hard spheres. ICAT residues are colored according to their characteristics: white for hydrophobic, green for polar, red for acidic and blue for basic residues. β-catenin F660 is in pink and the basic residues facing the Cterminal domain of ICAT are in cyan. B. Sequence alignment of the consensus peptide from several β-catenin binding proteins. The conserved acidic residues are in red and the aromatic residue in green. The first X residues, when they are hydrophilic, are boxed. C. β-catenin/ICAT complex showing the interaction between ICAT consensus peptide of the C-terminal domain (ribbon and sticks) and its facing β-catenin residues (surface).
All residues are colored according to their characteristics. Figures were drawn using VMD software  [38]. doi:10. 1371/journal. pone. 0172603. g001 Based on the crystal structure of the β-catenin/ICAT complex  [22, 23]  several contacts between the ICAT N-terminal domain and β-catenin were assumed to stabilize the two proteins interaction. This included the hydrophobic contacts between ICAT residues Y15, K19 and V22 and β-catenin F660. However, evaluation of their relative contribution is required. To investigate the importance of the highlighted residues for the ICAT/β-catenin interaction in melanoma cells, point mutations were introduced in ICAT and β-catenin by sitedirected mutagenesis. We selected six highly conserved ICAT residues, three being located in the N-terminal domain, and three in the C-terminal domain consensus peptide (Fig  1  and S2   Fig).
β-catenin is the main ICAT interactor in melanocytic cells So far, β-catenin is the only demonstrated protein known to interact directly with ICAT at the physiological level  [18, 12]. However, ICAT may also bind with high or mild affinity to other proteins. To identify interactors in the melanocyte lineage, a yeast two-hybrid screen using human ICAT as bait was performed with a human melanocyte cDNA library as prey. Although various putative partners were detected at low frequencies by sequencing of prey clones, most of the positive clones (80%) corresponded to CTNNB1/β-catenin cDNAs (S2 Table ). These results were compared to the interaction data originating from a large-scale mapping in HEK cells, using a mass spectrometry-based approach  [31] ; S3 Table ). Only two similar proteins, βcatenin and γ-catenin/plakoglobin, were identified in both studies.
In APC and E-cadherin, T1487 and S675 respectively form hydrogen bonds with the facing β-catenin R469. The color scheme of stick residues based on their characteristics is the same as in Fig 1. PDB codes: ICAT (1luj), LEF1 (3ouw), TCF3/TCF7L1 (1g3j), TCF4/TCF7L2 (1jdh), APC (1t08) and E-cadherin (1i7w).
In APC and E-cadherin, T1487 and S675 respectively form hydrogen bonds with the facing β-catenin R469. The color scheme of stick residues based on their characteristics is the same as in Fig 1. PDB codes: ICAT (1luj), LEF1 (3ouw), TCF3/TCF7L1 (1g3j), TCF4/TCF7L2 (1jdh), APC (1t08) and E-cadherin (1i7w). doi:10. 1371/journal. pone. 0172603. g008.
The work was supported by a grant from  "La Fondation ARC contre le Cancer", Ligue Nationale contre le Cancer ,  INCa ,  Pair Melanoma  and  Canceropole IdF , and is under the program «Investissements d'Avenir» launched by the  French Government  and implemented by  ANR Labex CelTisPhyBio  ( ANR-11-LBX-0038  and  ANR-10-IDEX-0001-02 PSL ). M. J. Domingues was the recipient of a fellowship from the  Ministère de l'Education Nationale de la Recherche et de la Technologie (MENRT)  and  J. Martinez-Sanz  was financed by the  French program  " Investissements d'Avenir -Institut Carnot " managed by the  National Research Agency  ( ANR-11-CARN-008-01 ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
One of the main drawbacks of the approach proposed in this study is the lack of clinical data that can weaken the model reliability. To circumvent this difficulty, we assessed the model validity by comparing its results with clinical study results taken from the literature. Our model results correlated well with the literature and suggest that it can be consolidated and used in clinical studies. Another issue with the modelling approach is its only indirect prediction of the OS. Indeed, the model cannot take into account the OS rate as a formal output of the optimisation procedure. This is inherent to the modelling structure as the input variables consist of pharmacokinetic and pharmacodynamic parameters. Therefore, the model can only address the relationship of these input parameters to output variables, such as haematological profiles and tumour volume regression, according to the RECIST.
However, minimising toxicities while improving response rates might have the potential to produce better OS rates than standard protocols. This was proven in previous studies  (Henin et al, 2016; Meille et al, 2016)  where the good management of toxicity constraints was associated to a doubling of the median overall survival. Nonetheless, this remains to be prospectively tested in a properly designed randomised study The ultimate goal of this work is to establish a prospective phase I study in which patients are enrolled and treated according to the optimised regimens proposed in this study. During the first cycle, data samples measuring neutrophil and platelet counts, as well as drug concentrations, are collected for each patient and integrated into the model to recalibrate the parameters.
The World Bank and the Socio-Economic Database for Latin America and the Caribbean (sedlac) detected reversals in inequality in some parts of Central America's northern triangle and the Andean region since 2010  (Cord et al. , 2014). In fact, Latin America exhibits the most unequal distribution of income in the world: including 10 of the top 15 most unequal countries on the planet  (Deas and Daza, 1995; Fainzylber et al. , 2002; Sánchez and Núñez, 2001). There are at least two reasons why more inequality translates into more violence. First, large disparities in wealth create greater competition in and between populations experiencing high unemployment and limited upward mobility. Second, income inequality generates competition for public goods between the rich and poor. Given elites' capacity for appropriating or even eliminating services, the result is often substandard public services, including policing in poorer areas.
3�0 To better apprehend the scale and distribution of citizen security investments across Latin America and the Caribbean, the author worked with several partners to develop a citizen security dashboard. 25 The time period covered by the dashboard was from 1998 to 2015. Citizen security initiatives were categorised according to their spatial, temporal and thematic scale, distribution, and budgets. In addition to tracking regional, national and municipal activities in a number of countries, the dashboard also considers the activities of multilateral and non-governmental sources such as the iadb, oas, undp and World Bank, among others. While the assessment is not exhaustive, it is nevertheless complete and facilitates an analysis of trends  (Muggah and Aguirre, 2013). One of the core objectives of the creation of the citizen security mapping database for Latin America and the Caribbean was to assess the impact of discrete interventions.
The results of the benchmark show that a relatively high scatter in the predictions can arise between different models, in particular at early ages (e. g. elastic Young's modulus predicted at 1 d in the range 6-20 GPa), while it reduces at later age, providing relatively good agreement with experimental data. Even though the input data was based on a single experimental dataset, the large differences between the results of the different models were found to be caused by distinct assumed properties for the individual phases at the microstructural level, mainly because of the scatter in the nanoindentation-derived properties of the C-S-H phase.
Experimental data used in the benchmark 2 The experimental dataset used in this benchmark was mostly obtained in previous works  [3, 4]. Some additional tests have been performed directly on the same batch of materials as in  [3, 4]  in order to provide necessary input for the specific models. The experiments were performed on cement paste at a water-to-cement ratio by mass (w/c) of 0. 30. The cement used was CEM I 42. 5 N with a Blaine fineness of 2. 91 m 2 /g, specific surface (determined with laser diffraction) of 1. 53 m 2 /g and density of 3. 09 g/cm 3. Oxide composition determined with XRF was (by mass): CaO 63% (free CaO 0. 52%, CaO in calcite 2. 32%), SiO 2 20%, Al 2 O 3 4. 5%, Fe 2 O 3 2. 9%, MgO 1. 9%, SO 3 2. 8%, K 2 O 0. 95%, Na 2 O 0. 19%. This yielded the following modified Bogue composition (SO 3 in clinker assumed as 0.
5%)  [5] : C 3 S 60. 8%, C 2 S 12. 5%, C 3 A 4. 3%, C 4 AF 9. 9%. The measured particle size distribution of the cement is presented in Fig. 1. The pastes were mixed in a vacuum mixer in order to minimize the effect of entrapped air voids. The mixes were prepared using deionized water and polycarboxylate-based superplasticizer (0. 5% by mass of cement). The samples were cured in moisture-sealed conditions at a temperature of 20±0. 5 °C. The basic property of the mixes used in this benchmark was evolution of hydration heat release, as shown in Fig. 2. It was measured with isothermal calorimetry on duplicate samples. Cement pastes were mixed externally and about 6 g of cement paste were used for a specimen. The measurements started 1h from mixing. The hydration heat data can be used for estimation of the hydration degree after estimating the heat released at complete hydration (the value of 454 J/g was estimated based on the phase composition of cement in  [3] ).
This produces two heat evolutions and two different microstructures. These two variants yield similar results, although the diffuse filling was developed for the purpose of modelling the evolution of mechanical properties, and the growing was focused on obtaining accurate kinetics. Next, the obtained microstructures were used for simulating the elastic Young's modulus. The same model of phase evolution was used in both set of generated microstructures. This was done using Automated Mechanics for Integrated Experiments (AMIE)  [8, 9]. AMIE is a FEM code for microstructural simulations. Based on the assumed values of stiffness of the individual hydration products and of unhydrated cement the stiffness of the microstructure is calculated from the stress and strain obtained when the generated microstructure is loaded.
C-S-H globules are assumed to be the weakest solid phase in a heterogeneous multiscale composite. They govern crack propagation and determine macroscopic strength of cement paste. Loading cement paste by compressive stress induces much larger stresses to C-S-H phase and consequently to C-S-H globules. Such stress magnification origins from stress concentration in heterogeneous microstructures and from the presence of capillary and gel pores. Inverse analysis of a large dataset resulted to identified tensile strength of the globule as 320 MPa  [29]. It should be noted that exceeding strength of a single globule leads only to further stress redistribution and damaging significant amount of globules is necessary to reach compressive strength of the paste.
In addition to the differences in the modelling schemes being one important origin of the scatter in the predictions between the different models, the used input data (elastic properties of the individual phases) should be considered as another important source of the scatter. The elastic properties of the individual phases used in modelling were obtained as follows. For the anhydrous cement, the data obtained with nanoindentation techniques  [38, 39]  was used in the models. Values for hydrated phases different than the C-S-H were assumed based on nanoindentation techniques with relatively low scatter. On the other hand, for the C-S-H, the majority hydration product by volume, the reported experimental data obtained with nanoindentation is characterized by a large scatter. Model 1 assumes that the Young's modulus of inner C-S-H is constant and uses the value from nanoindentation, but the outer C-S-H is assumed to densify with time.
Conclusions 5 The results of the numerical benchmark on modelling evolution of the microstructure of cement paste have been presented. The benchmark was based on an experimental dataset published previously, i. e. both the input data (material properties, mix compositions etc. ) and the experimental results were open to the participants. The part of the benchmark presented here focused on modeling a w/c 0. 30 cement paste hydrating in sealed conditions. 7 groups applying different analytical and numerical models of the evolution of microstructure and capable of simulating the evolution of concrete properties took part in the campaign. In this paper, a part of the results was presented comprising evolution of hydration heat release and mechanical properties (elastic Young's modulus, shear modulus and compressive strength).
As long as the evolution of hydration degree (estimated based on the hydration heat release) is in many models used directly as input data or fitted, the mechanical properties were simulated with no fitting, based only on previously established experimental input data. In all the models presented here, modelling of mechanical properties was carried out based on an established database of the mechanical properties of the individual phases of a hydrating cement paste. A considerable scatter between the predictions delivered by the different models could be observed, in particular at early ages before about 3 d (e. g. predicted Young's modulus at 1 d in the range 6-20 GPa), while lower spread of the predictions and better agreement with experimental data on dynamic Young's modulus was found at later ages, e.
Acknowledgements The benchmark presented in this paper was carried out within a framework of activities of work group 2 of the  COST Action TU1404  " Towards the next generation of standards for service life of cement-based materials and structures ". Financial support of  FEDER/COMPETE2020/FCT  through  POCI-01-0145-FEDER-007633  and  PTDC/ECM-EST/1056/2014  ( POCI-01-0145-FEDER-016841 ) is also acknowledged.
ROS1 rearrangement Data on the predictive value of ROS1 IHC are still evolving. Most studies on ROS1 IHC use the D4D6 rabbit monoclonal antibody (figure  3 ) (Cell Signaling Technology)  [80]. Although ROS1-rearranged tumours are invariably and diffusely positive with D4D6 antibody (cytoplasmic staining), ROS1 IHC positivity has been reported in some EGFR-or Her2-mutated or RET-rearranged tumours or in mucinous adenocarcinoma without ROS1 rearrangement; in addition, ROS1 is expressed in normal reactive pneumocytes and macrophages  [81]. In most cases, the expression in these cells is weak to moderate (+/++) in intensity  [50, 82]. In contrast to ALK, where the ganglion cells of the appendix serve as an adequate external control, there is currently no external benign tissue control for ROS1  [50, 82].
Subtyping of NSCLC using IHC in cytology has become a diagnostic standard in many laboratories  [111]. In contrast, predictive marker testing in cytology by IHC is more challenging, as it is connected to assays and scoring guidelines that have been established on histological material and validated in clinical trials  [104]. Predictive IHC markers that are most commonly used in NSCLC at the time of writing include ALK, ROS1 and PD-L1 (figure  1 ). FDA-approved assays exist for ALK and PD-L1 IHC in histology, but there are none yet for ROS1 or for cytological material. Notably, the EMA prescribes a robust and well-validated methodology for predictive ALK and ROS1 testing, but does not restrict it to a particular technique or histology. Although more data are needed, there is accumulating evidence that ALK testing using IHC can be reliably applied to both smears/cytospins/LBCs or cell blocks  [110, 112].
ACKNOWLEDGMENTS Biodiversity Heritage Library, Internet Archive, and la Fédération Française des Sociétés de Sciences Naturelles made available many difficult to find documents. Julia Dunaeva, from the Library of the Zoological Institute and Museum, Russian Academy of Sciences, Saint-Petersburg, provided a fine scan of Rathke's plates, and Tulio Villalobos one of Ehlers' plates. The careful reading and recommendations of an anonymous referee and of Daisy Cristina Arroyo Mora helped to improve this contribution. RESUMEN ¿Qué tan falsa es Nereis falsa (Annelida, Phyllodocida, Nereididae)? Entre los nombres de especies de poliquetos hay muchos problemas taxonómicos y resolver los procedimientos taxonómicos confusos o inadecuados consume mucho tiempo y es muy importante. Nuestro objetivo en esta contribución es analizar cuál es la situación para Nereis falsa de Quatrefages, 1866; fue basada en Nereis pulsatoria? Rathke, 1837 del Mar Negro, y se considera como una especie de amplia distribución.
Glucose measurements Patients from both arms were required to bring their blood glucose meters to clinic at T-0, T-3, and T-6 and their nurses used DiasendÔ software to download glucose values into the study database (Datava ¨gen, Sweden; www. glooko. com/ diasend). Patients were urged to perform glucose monitoring at least four times per day for the duration of the study. ''Frequent unexplained hypoglycemia'' was defined as hypoglycemia occurring one or more times weekly in the absence of a definable precipitating event such as a change in medication, diet, or activity. ''Glycemic variability'' was the presence of blood glucose oscillations from less than 3. 3 mM/L (60 mg/dL) to more than 10. 0 mM/L (180 mg/dL) at least thrice a week in an unpredictable and unexplained manner and evidence of such a pattern for at least the previous 6 months.
5% of control patients did so by T-3 and 35. 4% by T-6. Quality of life was assessed using the WHO-5 questionnaire. At T-0, 79% of analyzed patients reported they had an acceptable quality of life, 17% had a low quality of life, and 5% were in probable depression. No significant differences were found at 3 and 6 months compared to T-0, and no significant difference between the intervention and control groups was noted (data not shown).
Methods and results We conducted a retrospective study of all suspected cases of PH (echocardiographically estimated systolic pulmonary artery pressure [sPAP] ! 40 mmHg) in patients with definite HHT recorded in the French National Reference Centre for HHT database. When right heart catheterization (RHC) was performed, PH cases were confirmed and classified among the PH groups according to the European guidelines. Among 2,598 patients in the database, 110 (4. 2%) had suspected PH. Forty-seven of these 110 patients had RHC: 38/47 (81%) had a confirmed diagnosis of PH. The majority of these had isolated post-capillary PH (n = 20). We identified for the first time other haemodynamic profiles: pre-capillary pulmonary arterial hypertension (PAH) cases (n = 3) with slightly raised pulmonary vascular resistances.
Methods This retrospective, multicentre, descriptive study was based on data from the French national HHT database CIROCO ('Clinical Investigation and Research for the Rendu-Osler Cohort') in June 2014, provided by the French HHT reference centre (Lyon) and  13  French HHT skill centres. Data are recorded in the database either by each HHT specialist physician or by the National Reference Centre for HHT clinical research associate. Medical information is not available for all persons entered in the CIROCO database as relatives of patients can also be included. Possible or potential HHT cases can also be entered in this database: among the 5,628 cases reported in the French database as possible HHT cases or HHT relatives, 2,598 cases had a definite HHT diagnosis (i. e. , fulfilled 3 or 4 Curacao criteria or had an HHT pathogenic mutation).
Patient selection Among patients who received at least one echocardiography, those with PH reported in the CIROCO database at least once during follow-up were analyzed if they had definite HHT and an estimated sPAP, evaluated by echocardiography (regardless of the reason echocardiography was performed), ! 40 mmHg (based on peak tricuspid regurgitant jet velocity and right atrial pressure estimation)  [15]. Patients with definite HHT diagnosis, reliable echocardiographic data (i. e. , if sPAP ! 40 mmHg only once during follow-up without confirmation by other echocardiography or RHC, patients were not included) and information available on all the variables of interest were included in the study.
Groups and PH types HHT diagnosis was based on the Curacao criteria, namely at least 3 of the following signs: epistaxis, telangiectasia, first degree relative who meets diagnostic criteria, visceral signs  [1]. Two nested case-control studies were done according to whether exploration was solely echocardiographic or also invasive haemodynamic based on the first data reported in the medical file (time between the first echocardiography and the RHC ranging from 0 to 998 days [median 32]): • "Echocardiographic PH cohort": echocardiographic suspicion of PH with or without confirmation by RHC (not systematically performed by some centres). The patients who underwent an RHC excluding the diagnosis of PH were included in this group. • "RHC PH cohort": PH confirmed by RHC. These patients were then classified into PH groups as defined in the latest European guidelines (Fig  1 )  [5].
They were considered post-and pre-capillary PH cases when the DPG was ! 7 mmHg and/or PVR > 3 WU whatever the cardiac index, according to the latest European guidelines  [5]. In parallel, we defined "presence of high CO" as a cardiac index at rest > 4. 0 L/min/m 2. Left ventricle end-diastolic pressure was not reported. Group 3 comprised patients with PH due to lung diseases. Group 4 comprised patients with chronic thromboembolic PH. All haemodynamic data were analysed retrospectively by three PH specialist physicians, regardless of the first interpretation. "Liver vascular impairment" was defined as the presence of hepatic shunts, elevation of hepatic artery diameter or flow rate, lesions such as telangiectases, or nodular and focal hyperplasia, seen on echo-Doppler. "Significant hepatic vascular involvement" was defined as a hepatic artery diameter > 6.