Miracle-dz/UniFAR-FTUs huggingface dataset:
Zebrafish reporter lines reveal in vivo signaling pathway activities involved in pancreatic cancer

Pancreatic adenocarcinoma, one of the worst malignancies of the exocrine pancreas, is a solid tumor with increasing incidence and mortality in industrialized countries. This condition is usually driven by oncogenic KRAS point mutations and evolves into a highly aggressive metastatic carcinoma due to secondary gene mutations and unbalanced expression of genes involved in the specific signaling pathways. To examine in vivo the effects of KRASG12D during pancreatic cancer progression and time correlation with cancer signaling pathway activities, we have generated a zebrafish model of pancreatic adenocarcinoma in which eGFP-KRASG12D expression was specifically driven to the pancreatic tissue by using the GAL4/UAS conditional expression system. Outcrossing the inducible oncogenic KRASG12D line with transgenic zebrafish reporters, harboring specific signaling responsive elements of transcriptional effectors, we were able to follow TGFβ, Notch, Bmp and Shh activities during tumor development. Zebrafish transgenic lines expressing eGFP-KRASG12D showed normal exocrine pancreas development until 3 weeks post fertilization (wpf). From 4 to 24 wpf we observed several degrees of acinar lesions, characterized by an increase in mesenchymal cells and mixed acinar/ductal features, followed by progressive bowel and liver infiltrations and, finally, highly aggressive carcinoma. Moreover, live imaging analysis of the exocrine pancreatic tissue revealed an increasing number of KRAS-positive cells and progressive activation of TGFβ and Notch pathways. Increase in TGFβ, following KRASG12D activation, was confirmed in a concomitant model of medulloblastoma (MDB). Notch and Shh signaling activities during tumor onset were different between MDB and pancreatic adenocarcinoma, indicating a tissue-specific regulation of cell signaling pathways. Moreover, our results show that a living model of pancreatic adenocarcinoma joined with cell signaling reporters is a suitable tool for describing in vivo the signaling cascades and molecular mechanisms involved in tumor development and a potential platform to screen for novel oncostatic drugs.
No indications of persistent oxidative stress in response to an ironman triathlon.

INTRODUCTION Training for and competing in ultraendurance exercise events is associated with an improvement in endogenous antioxidant defenses as well as increased oxidative stress. However, consequences on health are currently unclear. PURPOSE We aimed to examine the impact of training- and acute exercise-induced changes in the antioxidant capacity on the oxidant/antioxidant balance after an ironman triathlon and whether there are indications for sustained oxidative damage. METHODS Blood samples were taken from 42 well-trained male triathletes 2 d before an ironman triathlon, then immediately postrace, 1, 5, and 19 d later. Blood was analyzed for conjugated dienes (CD), malondialdehyde (MDA), oxidized low-density lipoprotein (oxLDL), oxLDL:LDL ratio, advanced oxidation protein products (AOPP), AOPP:total protein (TP) ratio, Trolox equivalent antioxidant capacity (TEAC), uric acid (UA) in plasma, and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in erythrocytes. RESULTS Immediately postrace, there were significant increases in CD, AOPP, TEAC, UA (for all P < 0.001), and AOPP:TP (P < 0.01). MDA rose significantly (P < 0.01) 1 d postrace, whereas CD (P < 0.01), AOPP (P = 0.01), AOPP:TP (P < 0.05), and TEAC (P < 0.001) remained elevated. OxLDL:LDL trended to increase, whereas oxLDL significantly (P < 0.01) decreased 1 d postrace. Except for GSH-Px (P = 0.08), activities of SOD (P < 0.001) and CAT (P < 0.05) significantly decreased postrace. All oxidative stress markers had returned to prerace values 5 d postrace. Furthermore, several relationships between training status and oxidative stress markers, TEAC, and antioxidant enzyme activities were noted. CONCLUSIONS This study indicates that despite a temporary increase in most (but not all) oxidative stress markers, there is no persistent oxidative stress in response to an ironman triathlon, probably due to training- and exercise-induced protective alterations in the antioxidant defense system.
A Stretch of 11 Amino Acids in the βB-βC Loop of the Coat Protein of Grapevine Fanleaf Virus Is Essential for Transmission by the Nematode Xiphinema index

ABSTRACT Grapevine fanleaf virus (GFLV) and Arabis mosaic virus (ArMV) from the genus Nepovirus, family Secoviridae, cause a severe degeneration of grapevines. GFLV and ArMV have a bipartite RNA genome and are transmitted specifically by the ectoparasitic nematodes Xiphinema index and Xiphinema diversicaudatum, respectively. The transmission specificity of both viruses maps to their respective RNA2-encoded coat protein (CP). To further delineate the GFLV CP determinants of transmission specificity, three-dimensional (3D) homology structure models of virions and CP subunits were constructed based on the crystal structure of Tobacco ringspot virus, the type member of the genus Nepovirus. The 3D models were examined to predict amino acids that are exposed at the external virion surface, highly conserved among GFLV isolates but divergent between GFLV and ArMV. Five short amino acid stretches that matched these topographical and sequence conservation criteria were selected and substituted in single and multiple combinations by their ArMV counterparts in a GFLV RNA2 cDNA clone. Among the 21 chimeric RNA2 molecules engineered, transcripts of only three of them induced systemic plant infection in the presence of GFLV RNA1. Nematode transmission assays of the three viable recombinant viruses showed that swapping a stretch of (i) 11 residues in the βB-βC loop near the icosahedral 3-fold axis abolished transmission by X. index but was insufficient to restore transmission by X. diversicaudatum and (ii) 7 residues in the βE-αB loop did not interfere with transmission by the two Xiphinema species. This study provides new insights into GFLV CP determinants of nematode transmission.
Stable carbon isotope analysis of dissolved inorganic carbon (DIC) and dissolved organic carbon (DOC) in natural waters--results from a worldwide proficiency test.

RATIONALE Stable carbon isotope ratios of dissolved inorganic (DIC) and organic carbon (DOC) are of particular interest in aquatic geochemistry. The precision for this type of analysis is typically reported in the range of 0.1‰ to 0.5‰. However, there is no published attempt that compares δ(13)C measurements of DIC and DOC among different laboratories for natural water samples. METHODS Five natural water samples (lake water, seawater, two geothermal waters, and petroleum well water) were analyzed for δ(13)CDIC and δ(13)CDOC values by five laboratories with isotope ratio mass spectrometry (IRMS) in an international proficiency test. RESULTS The reported δ(13)CDIC values for lake water and seawater showed fairly good agreement within a range of about 1‰, whereas geothermal and petroleum waters were characterized by much larger differences (up to 6.6‰ between laboratories). δ(13)CDOC values were only comparable for seawater and showed differences of 10 to 21‰ for other samples. CONCLUSIONS This study indicates that scatter in δ(13)CDIC isotope data can be in the range of several per mil for samples from extreme environments (geothermal waters) and may not yield reliable information with respect to dissolved carbon (petroleum wells). The analyses of lake water and seawater also revealed a larger than expected difference and researchers from various disciplines should be aware of this. Evaluation of analytical procedures of the participating laboratories indicated that the differences cannot be explained by analytical errors or different data normalization procedures and must be related to specific sample characteristics or secondary effects during sample storage and handling. Our results reveal the need for further research on sources of error and on method standardization.
Programming the K-means clustering algorithm in SQL

Using SQL has not been considered an efficient and feasible way to implement data mining algorithms. Although this is true for many data mining, machine learning and statistical algorithms, this work shows it is feasible to get an efficient SQL implementation of the well-known K-means clustering algorithm that can work on top of a relational DBMS. The article emphasizes both correctness and performance. From a correctness point of view the article explains how to compute Euclidean distance, nearest-cluster queries and updating clustering results in SQL. From a performance point of view it is explained how to cluster large data sets defining and indexing tables to store and retrieve intermediate and final results, optimizing and avoiding joins, optimizing and simplifying clustering aggregations, and taking advantage of sufficient statistics. Experiments evaluate scalability with synthetic data sets varying size and dimensionality. The proposed K-means implementation can cluster large data sets and exhibits linear scalability.
Insertion Depth in Cochlear Implantation and Outcome in Residual Hearing and Vestibular Function

Objectives: It has long been known that cochlear implantation may cause loss of residual hearing and vestibular function. Different insertion depths may cause varying degrees of intracochlear trauma in the apical region of the cochlea. The present study investigated the correlation between the insertion depth and postoperative loss of residual hearing and vestibular function. Design: Thirty-nine adults underwent unilateral cochlear implantation. One group received a Med-El +Flex24 electrode array (24 mm; n = 4), 1 group received a Med-El +Flex28 electrode array (28 mm; n = 18), and 1 group received a Med-El +FlexSOFT electrode array (31.5 mm; n = 17). Residual hearing, cervical vestibular-evoked myogenic potentials, videonystagmography, and subjective visual vertical/horizontal were explored before and after surgery. The electrode insertion depth and scalar position were examined with high-resolution rotational tomography after implantation in 29 subjects. Results: There was no observed relationship between the angular insertion depth (405° to 708°) and loss of low-frequency pure-tone average. Frequency-specific analysis revealed a weak relationship between the angular insertion depth and loss of hearing at 250 Hz (R2= 0.20; p = 0.02). There was no statistically significant difference in the residual hearing and vestibular function between the +Flex28 and the +FlexSOFT electrode array. Eight percent of the cases had vertigo after surgery. The electrode arrays were positioned inside the scala tympani and not scala vestibuli in all subjects. In 18% of the cases, the +FlexSOFT electrode array was not fully inserted. Conclusions: The final outcome in residual hearing correlates very weakly with the angular insertion depth for depths above 405°. Postoperative loss of vestibular function did not correlate with the angular insertion depth or age at implantation. The surgical protocol used in this study seems to minimize the risk of postoperative vertigo symptoms.
TCP-polite rate control based on cooperative measurement

Based on the cooperative measurement of new congestion metric instead of drop ratio and round-trip time, a new cooperative transmission control mechanism, called TCP-polite rate control TPRC, is proposed. In this scheme, the congestion metric of network is obtained with cooperative measurement and feeds back to rate-based pacing mechanism, thus keeping the transmission rate at the lower bound of available bandwidth. Simulation results show that TPRC scheme outperforms TCP and TCP-friendly rate control protocol in terms of fast-start, efficiency, and fairness. Copyright © 2013 John Wiley & Sons, Ltd.
The Hrs/Stam Complex Acts as a Positive and Negative Regulator of RTK Signaling during Drosophila Development

Background Endocytosis is a key regulatory step of diverse signalling pathways, including receptor tyrosine kinase (RTK) signalling. Hrs and Stam constitute the ESCRT-0 complex that controls the initial selection of ubiquitinated proteins, which will subsequently be degraded in lysosomes. It has been well established ex vivo and during Drosophila embryogenesis that Hrs promotes EGFR down regulation. We have recently isolated the first mutations of stam in flies and shown that Stam is required for air sac morphogenesis, a larval respiratory structure whose formation critically depends on finely tuned levels of FGFR activity. This suggest that Stam, putatively within the ESCRT-0 complex, modulates FGF signalling, a possibility that has not been examined in Drosophila yet. Principal Findings Here, we assessed the role of the Hrs/Stam complex in the regulation of signalling activity during Drosophila development. We show that stam and hrs are required for efficient FGFR signalling in the tracheal system, both during cell migration in the air sac primordium and during the formation of fine cytoplasmic extensions in terminal cells. We find that stam and hrs mutant cells display altered FGFR/Btl localisation, likely contributing to impaired signalling levels. Electron microscopy analyses indicate that endosome maturation is impaired at distinct steps by hrs and stam mutations. These somewhat unexpected results prompted us to further explore the function of stam and hrs in EGFR signalling. We show that while stam and hrs together downregulate EGFR signalling in the embryo, they are required for full activation of EGFR signalling during wing development. Conclusions/Significance Our study shows that the ESCRT-0 complex differentially regulates RTK signalling, either positively or negatively depending on tissues and developmental stages, further highlighting the importance of endocytosis in modulating signalling pathways during development.
Upwind Schemes with Exact Conservation Property for One-Dimensional Open Channel Flow Equations

In this paper we present an application and extension of the upwind schemes with source terms decomposed, developed by Bermudez, Vazquez, Hubbard, and Garcia-Navarro, to the one-dimensional open channel flow equations with general, i.e., nonprismatic and nonrectangular, geometries. Our specific numerical approximations for terms that appear in these equations and are related to the channel's geometrical properties are quite straightforward and natural, and at the same time respect the balancing of the flux gradient and the source term. As a consequence, the resulting upwind schemes have the exact conservation property. In several test problems we illustrate the achieved improvement, particularly significant for applications to natural watercourses due to their irregular riverbed geometries.
Measles virus protein‐specific IgM, IgA, and IgG subclass responses during the acute and convalescent phase of infection

The availability of new generation serological assays allowed re‐evaluation of the antibody response to measles virus. IgM, IgA, total IgG, and IgG subclass responses were studied to the three major immunogenic measles virus proteins: the fusion protein (F), haemagglutinin (H), and nucleoprotein (N). Plasma samples were obtained from clinically diagnosed measles cases (n = 146) in Khartoum (Sudan) within a week after onset of the rash. Convalescent phase samples were collected from 32 of 117 laboratory‐confirmed measles cases at different time points after onset of rash. Glycoprotein‐specific IgM, IgG, and IgA antibody levels correlated well to the N‐specific response. For IgG and IgA, responses to F were higher than to H. IgA antibody levels were undetectable in about one third of the laboratory‐confirmed cases during the acute phase, but positive in all patients tested 1–4 weeks after infection. IgM levels declined rapidly and were lost 3–6 months after infection. IgA levels declined slowly during the first year but did not return to background levels during the subsequent 2 years. IgG avidity maturation was detected during a 3–6 month period after infection. The predominant IgG subclasses during the acute phase were IgG1 and IgG3. The latter was lost in the convalescent phase, while the IgG4 isotype showed a slight rise afterwards. Interestingly, acute phase IgG3 and IgA responses were associated, and were only detected in samples with high IgG. This study provides a comprehensive perspective on the antibody response to wild‐type measles virus infection. J. Med. Virol. 72:290–298, 2004. © 2004 Wiley‐Liss, Inc.
Hierarchical Minimization with Distance and Angle Constraints

The incorporation of experimentally-determined constraints into structure-prediction methods based on energy minimization leads to both improved selectivity with empirical potential functions and structure determination with far fewer constraints than are required for distance-geometry calculations. Some methods will be described for using both distance and angle constraints with the hierarchical minimization algorithm. The simulation is based on a combination of Monte Carlo Simulated Annealing and Genetic Algorithm techniques which are integrated into a single framework. The selection cycle of the genetic algorithm is carried out at the same temperature as the mutations, or alternatively the crossover cycle can be considered as a type of Monte Carlo trial move, such that each temperature annealing step corresponds to a new generation. The sequence is divided up into segments, and the mutation step consists of replacing an entire segment with a choice from a pre-selected list. This list is in turn constructed from a list of smaller segments, and the number of overall conformations can thus be pruned at each level of selection. Results will be shown for test cases using a small number of flexible distance constraints used as an additional term in the potential, and for restrictions placed on backbone dihedral angles used as an additional screening criterion for constructing trial moves.
Quality metric to assess video streaming service over TCP considering temporal location of pauses

There is a wide range of video services over complex transmission networks, and in some cases end users fail to receive an acceptable quality level. In this paper, the different factors that degrade users' quality of experience (QoE) in video streaming service that use TCP as transmission protocol are studied. In this specific service, impairment factors are: number of pauses, their duration and temporal location. In order to measure the effect that each temporal segment has in the overall video quality, subjective tests. Because current subjective test methodologies are not adequate to assess video streaming over TCP, some recommendations are provided here. At the application layer, a customized player is used to evaluate the behavior of player buffer, and consequently, the end user QoE. Video subjective test results demonstrate that there is a close correlation between application parameters and subjective scores. Based on this fact, a new metrics named VsQM is defined, which considers the importance of temporal location of pauses to assess the user QoE of video streaming service. A useful application scenario is also presented, in which the metrics proposed herein is used to improve video services.
Leptospira interrogans lpxD Homologue Is Required for Thermal Acclimatization and Virulence

ABSTRACT Leptospirosis is an emerging disease with an annual occurrence of over 1 million human cases worldwide. Pathogenic Leptospira bacteria are maintained in zoonotic cycles involving a diverse array of mammals, with the capacity to survive outside the host in aquatic environments. Survival in the diverse environments encountered by Leptospira likely requires various adaptive mechanisms. Little is known about Leptospira outer membrane modification systems, which may contribute to the capacity of these bacteria to successfully inhabit and colonize diverse environments and animal hosts. Leptospira bacteria carry two genes annotated as UDP-3-O-[3-hydroxymyristoyl] glucosamine N-acyltransferase genes (la0512 and la4326 [lpxD1 and lpxD2]) that in other bacteria are involved in the early steps of biosynthesis of lipid A, the membrane lipid anchor of lipopolysaccharide. Inactivation of only one of these genes, la0512/lpxD1, imparted sensitivity to the host physiological temperature (37°C) and rendered the bacteria avirulent in an animal infection model. Polymyxin B sensitivity assays revealed compromised outer membrane integrity in the lpxD1 mutant at host physiological temperature, but structural analysis of lipid A in the mutant revealed only minor changes in the lipid A moiety compared to that found in the wild-type strain. In accordance with this, an in trans complementation restored the phenotypes to a level comparable to that of the wild-type strain. These results suggest that the gene annotated as lpxD1 in Leptospira interrogans plays an important role in temperature adaptation and virulence in the animal infection model.
Accelerating and Evaluation of Syntactic Parsing in Natural Language Question Answering Systems

With the development of Natural Language Processing (NLP), more and more systems want to adopt NLP in User Interface Module to process user input, in order to communicate with user in a natural way. However, this raises a speed problem. That is, if NLP module can not process sentences in durable time delay, users will never use the system. As a result, systems which are strict with processing time, such as dialogue systems, web search systems, automatic customer service systems, especially real-time systems, have to abandon NLP module in order to get a faster system response. This paper aims to solve the speed problem. In this paper, at first, the construction of a syntactic parser which is based on corpus machine learning and statistics model is introduced, and then a speed problem analysis is performed on the parser and its algorithms. Based on the analysis, two accelerating methods, Compressed POS Set and Syntactic Patterns Pruning, are proposed, which can effectively improve the time efficiency of parsing in NLP module. To evaluate different parameters in the accelerating algorithms, two new factors, PT and RT, are introduced and explained in detail. Experiments are also completed to prove and test these methods, which will surely contribute to the application of NLP.