Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterisation of the SUMO-Like Domains of Schizosaccharomyces pombe Rad60

The S. pombe Rad60 protein is required for the repair of DNA double strand breaks, recovery from replication arrest, and is essential for cell viability. It has two SUMO-like domains (SLDs) at its C-terminus, an SXS motif and three sequences that have been proposed to be SUMO-binding motifs (SBMs). SMB1 is located in the middle of the protein, SBM2 is in SLD1 and SBM3 is at the C-terminus of SLD2. We have probed the functions of the two SUMO-like domains, SLD1 and SLD2, and the putative SBMs. SLD1 is essential for viability, while SLD2 is not. rad60-SLD2Δ cells are sensitive to DNA damaging agents and hydroxyurea. Neither ubiquitin nor SUMO can replace SLD1 or SLD2. Cells in which either SBM1 or SBM2 has been mutated are viable and are wild type for response to MMS and HU. In contrast mutation of SBM3 results in significant sensitivity to MMS and HU. These results indicate that the lethality resulting from deletion of SLD1 is not due to loss of SBM2, but that mutation of SBM3 produces a more severe phenotype than does deletion of SLD2. Using chemical denaturation studies, FPLC and dynamic light scattering we show this is likely due to the destabilisation of SLD2. Thus we propose that the region corresponding to the putative SBM3 forms part of the hydrophobic core of SLD2 and is not a SUMO-interacting motif. Over-expression of Hus5, which is the SUMO conjugating enzyme and known to interact with Rad60, does not rescue rad60-SLD2Δ, implying that as well as having a role in the sumoylation process as previously described [1], Rad60 has a Hus5-independent function.
Properties and Biological Role of Streptococcal Fratricins

ABSTRACT Competence for natural genetic transformation is widespread in the genus Streptococcus. The current view is that all streptococcal species possess this property. In addition to the proteins required for DNA uptake and recombination, competent streptococci secrete muralytic enzymes termed fratricins. Since the synthesis and secretion of these cell wall-degrading enzymes are always coupled to competence development in streptococci, fratricins are believed to carry out an important function associated with natural transformation. This minireview summarizes what is known about the properties of fratricins and discusses their possible biological roles in streptococcal transformation.
Constructing Robust and Resilient Framework for Cooperative Video Streaming

Peer-to-peer based streaming has been a promising solution for large-scale video broadcasting over the Internet. In a peer-to-peer video streaming framework, peers cooperate with each other for content distribution, so that the burden of the central server is greatly alleviated. Moreover, the peer-to-peer overlay is highly scalable to support a very large number of users. However, to support video streaming service, some strict performance issues need to be addressed, e.g., reliability, resilience and robustness to network dynamics. In this paper, we investigate several goals that a peer overlay should achieve in order to support good-quality video streaming. We then describe our work on organizing peers into such a robust and resilient framework. We have implemented a fully functional video broadcasting system based on the proposed peer-to-peer infrastructure. The prototype system has been successfully deployed and tested upon Planet-lab with encouraging experimental results
Pro-Secretory Activity and Pharmacology in Rabbits of an Aminophenyl-1,3,5-Triazine CFTR Activator for Dry Eye Disorders

Purpose Pharmacological activation of ocular surface cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels is a potential pro-secretory approach to treat dry eye disorders. We previously reported the discovery of aminophenyl-1,3,5-triazines, one of which, N-methyl-N-phenyl-6-(2,2,3,3-tetrafluoropropoxy)-1,3,5-triazine-2,4-diamine (herein called CFTRact-K267), fully activated human wildtype CFTR with EC50 ∼ 30 nM and increased tear volume for 8 hours in mice. Here, functional and pharmacological studies of CFTRact-K267 were done in adult New Zealand white rabbits. Methods CFTR chloride conductance was measured in vivo by ocular surface potential differences and in ex vivo conjunctiva by short-circuit current. Tear volume was measured by the Schirmer tear test II and CFTRact-K267 pharmacokinetics and tissue distribution by liquid chromatography/mass spectrometry. Toxicity profile was studied for 28 days with twice-daily topical administration. Results Electrophysiological measurements in vivo and in ex vivo conjunctiva demonstrated CFTR activation by CFTRact-K267. A single topical dose of 3 nmol CFTRact-K267 increased tear production by >5 mm for 9 hours by the Schirmer tear test, with predicted therapeutic concentrations maintained in tear fluid. No tachyphylaxis was seen following 28-day twice-daily administration, and changes were not observed in corneal surface integrity or thickness, intraocular pressure, or ocular histology. At day 28, CFTRact-K267 was concentrated in the cornea and conjunctiva and was not detectable in blood or peripheral organs. Conclusions These studies support the development of CFTRact-K267 as a pro-secretory therapy for dry eye disorders.
Persistence of hepatitis B immune memory until 9–10 years of age following hepatitis B vaccination at birth and DTaP-IPV-HB-PRP∼T vaccination at 2, 4 and 6 months

ABSTRACT Objective: To evaluate the long-term persistence of anti-hepatitis B surface (HBs) antibodies and the response to a HB challenge re-vaccination in children who had received a primary series of DTaP-IPV-HB-PRP∼T (Hexaxim™) or DTaP-IPV-HB/PRP∼T (Infanrix hexa™). Methods: Two cohorts of participants who had previously received HB vaccine at birth followed by either DTaP-IPV-HB-PRP∼T or DTaP-IPV-HB/PRP∼T co-administered with PCV7 at 2, 4, 6 months of age in a randomized, Phase III, observer-blind study in Thailand, were followed up for anti-HBs antibodies (geometric mean concentrations [GMCs] and seroprotection [SP] rate [% of participants with a titer ≥10 mIU/mL]) at 12–18 months of age and 9–10 years of age. A monovalent HB challenge re-vaccination was administered at 9–10 years of age and the anamnestic response was evaluated. Results: Anti-HBs GMCs and SP rates in the DTaP-IPV-HB-PRP∼T and DTaP-IPV-HB/PRP∼T groups were high and similar post-primary vaccination series (2477 mIU/mL and 99.5% and 2442 mIU/mL and 99.5%, respectively) and declined to a similar extent in each group at 12–18 months (154.5 mIU/mL and 90.8% and 162.3 mIU/mL and 96.5%, respectively). Antibody levels further declined at 9–10 years of age (13.3 mIU/mL and 49.3% and 8.0 mIU/mL and 42.9%) and a strong anamnestic response occurred in each group post-HB challenge re-vaccination (92.8% and 98.7%, respectively). Conclusion: The kinetics of long-term anti-HBs antibody persistence were similar following a primary series of DTaP-IPV-HB-PRP∼T or DTaP-IPV-HB/PRP∼T. The response to a subsequent HB challenge re-vaccination was strong and similar in each group, demonstrating persisting immune memory.
Electrothermal propulsion system selection for communication satellite NSSK maneuver using multi criteria decision making method

Choosing proper space propulsion systems for communication satellites is an important issue for space system engineers. Although there are a lot of alternatives, selection of the system which fits well with the mission requirements depends on many parameters. In this study, thruster selection for the north-south station keeping maneuver of communication satellites is performed. Three kinds of electrothermal thrusters which are resistojet, arcjet and microwave electrothermal thruster considered as alternatives, and properties of the systems are defined. Fuzzy TOPSIS Multi Criteria Decision Making Method is used to evaluate the linguistic variables and their corresponding fuzzy numbers. Specifically, the feasibility of microwave electrothermal thruster for such a mission among the electrothermal thrusters is investigated.
stream p u Storage-centric Load Management for Data Streams with Update Semantics

Most data stream processing systems model their inputs as append-only sequences dfg of data elements. In this model, the application expects to receive a query answer on the complete input stream. However, there are many situations in which each data element (or a window of data elements) in the stream is in fact an update to a previous one, and therefore, the most recent arrival is all that really matters to the application. UpStream defines a storage-centric approach to efficiently processing continuous queries under such an update-based stream data model. The goal is to provide the most up-to-date answers to the application with the lowest staleness possible. To achieve this, we developed a lossy tuple storage model (called an “update queue”), which under high load, will choose to sacrifice old tuples in favor of newer ones using a number of different update key scheduling heuristics. Our techniques can correctly process queries with different types of streaming operators (including sliding windows), while efficiently handling large numbers of update keys with different update frequencies. We present a detailed analysis and experimental evidence showing the effectiveness of our algorithms using both synthetic as well as real data sets.
Robust Beamforming for Wireless Information and Power Transmission

In this letter, we study the robust beamforming problem for the multi-antenna wireless broadcasting system with simultaneous information and power transmission, under the assumption of imperfect channel state information (CSI) at the transmitter. Following the worst-case deterministic model, our objective is to maximize the worst-case harvested energy for the energy receiver while guaranteeing that the rate for the information receiver is above a threshold for all possible channel realizations. Such problem is nonconvex with infinite number of constraints. Using certain transformation techniques, we convert this problem into a relaxed semidefinite programming problem (SDP) which can be solved efficiently. We further show that the solution of the relaxed SDP problem is always rank-one. This indicates that the relaxation is tight and we can get the optimal solution for the original problem. Simulation results are presented to validate the effectiveness of the proposed algorithm.
Determination of In Vitro and In Vivo Effects of Taxifolin and Epirubicin on Epithelial–Mesenchymal Transition in Mouse Breast Cancer Cells

Background: One of the most significant characteristics of cancer is epithelial–mesenchymal transition and research on the relationship between phenolic compounds and anticancer medications and epithelial–mesenchymal transition is widespread. Methods: In order to investigate the potential effects of Taxifolin on enhancing the effectiveness of Epirubicin in treating breast cancer, specifically in 4T1 cells and an allograft BALB/c model, the effects of Taxifolin and Epirubicin, both individually and in combination, were examined. Cell viability assays and cytotoxicity assays in 4T1 cells were performed. In addition, 4T1 cells were implanted into female BALB/c mice to conduct in vivo studies and evaluate the therapeutic efficacy of Taxifolin and Epirubicin alone or in combination. Tumor volumes and histological analysis were also assessed in mice. To further understand the mechanisms involved, we examined the messenger RNA and protein levels of epithelial–mesenchymal transition-related genes, as well as active Caspase-3/7 levels, using quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assays, respectively. Results: In vitro results demonstrated that the coadministration of Taxifolin and Epirubicin reduced cell viability and cytotoxicity in 4T1 cell lines. In vivo, coadministration of Taxifolin and Epirubicin suppressed tumor growth in BALB/c mice with 4T1 breast cancer cells. Additionally, this combination treatment significantly increased the levels of active caspase-3/7 and downregulated the messenger RNA and protein levels of N-cadherin, β-catenin, vimentin, snail, and slug, but upregulated the E-cadherin gene. It significantly decreased the messenger RNA levels of the Zeb1 and Zeb2 genes. Conclusion: The in vitro and in vivo results of our study indicate that the concurrent use of Epirubicin with Taxifolin has supportive effects on breast cancer treatment.
PEPINO: PEer-to-Peer network INspectOr

PEPINO is a simple and effective peer-to-peer network inspector. It visualises not only meaningful pointers and connections between peers, but also the exchange of messages between them, providing a useful tool for debugging purposes. It can monitor running networks, simulate them and log them in order to reproduce interesting case scenarios. Failures can be explicitly introduced to study fault tolerant algorithms. The graphical representation of the network uses a physical model to attract or repel peers, allowing the user to study the system from different points of view. This demo aims to present the use of PEPINO in the development of a novel relaxed-ring topology for fault tolerant networks, where the representation of the ring based on predecessors may differ from the ring based on successors. We show how PEPINO is also useful for visualising other network topologies such as perfect ring or unstructured networks.
Identification of early hippocampal dynamics during recognition memory with independent component analysis.

The hippocampus is generally considered to have relatively late involvement in recognition memory, its main electrophysiological signature being between 400 and 800 ms after stimulus onset. However, most electrophysiological studies have analyzed the hippocampus as a single responsive area, selecting only a single-site signal exhibiting the strongest effect in terms of amplitude. These classical approaches may not capture all the dynamics of this structure, hindering the contribution of other hippocampal sources that are not located in the vicinity of the selected site. We combined intracerebral electroencephalogram recordings from epileptic patients with independent component analysis (ICA) during a recognition memory task involving the recognition of old and new images. We identified two sources with different responses emerging from the hippocampus: a fast one (maximal amplitude at ∼250 ms) that could not be directly identified from raw recordings, and a later one, peaking at ∼400 ms. The earliest component presented different amplitudes between old and new items in 6 out of 10 patients. The latter component had different delays for each condition, with a faster activation (∼290 ms after stimulus onset) for recognized items. We hypothesize that both sources represent two steps of hippocampal recognition memory, the faster reflecting the input from other structures and the latter the hippocampal internal processing. Recognized images evoking early activations would facilitate neural computation in the hippocampus, accelerating memory retrieval of complementary information. Overall, our results suggest that hippocampal activity is composed by several sources with an early activation related to recognition memory.Significance Statement In the human memory circuit, the hippocampus is considered as a structure with relatively late activation, associated to the retrieval of elaborate memories. However, in most electrophysiological studies, it is characterized by the activity of a single contact, which may not represent the entire dynamics of this structure. Here, we combined intracerebral recordings with independent component analysis to separate the activity from two different neural sources generated in the hippocampus. We analyzed the responses of both sources during the recognition of old and new images. Our results reveal new dynamics associated to different neuronal sources within the hippocampus, with recognition memory occurring much faster than previously reported.
Plate tectonic modelling: review and perspectives

Abstract Since the 1970s, numerous global plate tectonic models have been proposed to reconstruct the Earth's evolution through deep time. The reconstructions have proven immensely useful for the scientific community. However, we are now at a time when plate tectonic models must take a new step forward. There are two types of reconstructions: those using a ‘single control’ approach and those with a ‘dual control’ approach. Models using the ‘single control’ approach compile quantitative and/or semi-quantitative data from the present-day world and transfer them to the chosen time slices back in time. The reconstructions focus therefore on the position of tectonic elements but may ignore (partially or entirely) tectonic plates and in particular closed tectonic plate boundaries. For the readers, continents seem to float on the Earth's surface. Hence, the resulting maps look closer to what Alfred Wegener did in the early twentieth century and confuse many people, particularly the general public. With the ‘dual control’ approach, not only are data from the present-day world transferred back to the chosen time slices, but closed plate tectonic boundaries are defined iteratively from one reconstruction to the next. Thus, reconstructions benefit from the wealth of the plate tectonic theory. They are physically coherent and are suited to the new frontier of global reconstruction: the coupling of plate tectonic models with other global models. A joint effort of the whole community of geosciences will surely be necessary to develop the next generation of plate tectonic models.
Microscopic Social Influence

Social influences, the phenomena that one individual’s actions can induce similar behaviors among his/her friends via their social ties, have been observed prevailingly in socially networked systems. While most existing work focuses on studying general, macro-level influence (e.g., diffusion); equally important is to understand social influence at microscopic scales (i.e., at the granularity of single individuals, actions, and time-stamps), which may benefit a range of applications. We propose μSI, a microscopic social-influence model wherein: individuals’ actions are modeled as temporary interactions between social network (formed by individuals) and object network (formed by targets of actions); one individual’s actions influence his/her friends in a dynamic, network-wise manner (i.e., dependent on both social and object networks). We develop for μSI a suite of novel inference tools that enable to answer questions of the form: How may an occurred interaction trigger another? More importantly, when and where may a new interaction be observed? We carefully address the computational challenges for inferencing over such semantically rich models by dynamically identifying sub-domains of interest and varying the precision of solutions over different subdomains. We demonstrate the breadth and generality of μSI using two seemingly disparate applications. In the context of social tagging service, we show how it can help improve the accuracy and freshness of resource recommendation; in the context of mobile phone call service, we show how it can help improve the efficiency of paging operation.
Sparse principal component of a rank-deficient matrix

We consider the problem of identifying the sparse principal component of a rank-deficient matrix. We introduce auxiliary spherical variables and prove that there exists a set of candidate index-sets (that is, sets of indices to the nonzero elements of the vector argument) whose size is polynomially bounded, in terms of rank, and contains the optimal index-set, i.e. the index-set of the nonzero elements of the optimal solution. Finally, we develop an algorithm that computes the optimal sparse principal component in polynomial time for any sparsity degree.
The phase transition in inhomogeneous random graphs

The “classical” random graph models, in particular G(n,p), are “homogeneous,” in the sense that the degrees (for example) tend to be concentrated around a typical value. Many graphs arising in the real world do not have this property, having, for example, power‐law degree distributions. Thus there has been a lot of recent interest in defining and studying “inhomogeneous” random graph models.
Proteomic Identification of 14-3-3ζ as a Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 Substrate: Role in Dimer Formation and Ligand Binding

ABSTRACT Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MAPKAPK2) mediates multiple p38 MAPK-dependent inflammatory responses. To define the signal transduction pathways activated by MAPKAPK2, we identified potential MAPKAPK2 substrates by using a functional proteomic approach consisting of in vitro phosphorylation of neutrophil lysate by active recombinant MAPKAPK2, protein separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and phosphoprotein identification by peptide mass fingerprinting with matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and protein database analysis. One of the eight candidate MAPKAPK2 substrates identified was the adaptor protein, 14-3-3ζ. We confirmed that MAPKAPK2 interacted with and phosphorylated 14-3-3ζ in vitro and in HEK293 cells. The chemoattractant formyl-methionyl-leucyl-phenylalanine (fMLP) stimulated p38-MAPK-dependent phosphorylation of 14-3-3 proteins in human neutrophils. Mutation analysis showed that MAPKAPK2 phosphorylated 14-3-3ζ at Ser-58. Computational modeling and calculation of theoretical binding energies predicted that both phosphorylation at Ser-58 and mutation of Ser-58 to Asp (S58D) compromised the ability of 14-3-3ζ to dimerize. Experimentally, S58D mutation significantly impaired both 14-3-3ζ dimerization and binding to Raf-1. These data suggest that MAPKAPK2-mediated phosphorylation regulates 14-3-3ζ functions, and this MAPKAPK2 activity may represent a novel pathway mediating p38 MAPK-dependent inflammation.
GFOLD: a generalized fold change for ranking differentially expressed genes from RNA-seq data

MOTIVATION RNA-seq has been widely used in transcriptome analysis to effectively measure gene expression levels. Although sequencing costs are rapidly decreasing, almost 70% of all the human RNA-seq samples in the gene expression omnibus do not have biological replicates and more unreplicated RNA-seq data were published than replicated RNA-seq data in 2011. Despite the large amount of single replicate studies, there is currently no satisfactory method for detecting differentially expressed genes when only a single biological replicate is available. RESULTS We present the GFOLD (generalized fold change) algorithm to produce biologically meaningful rankings of differentially expressed genes from RNA-seq data. GFOLD assigns reliable statistics for expression changes based on the posterior distribution of log fold change. In this way, GFOLD overcomes the shortcomings of P-value and fold change calculated by existing RNA-seq analysis methods and gives more stable and biological meaningful gene rankings when only a single biological replicate is available. AVAILABILITY The open source C/C++ program is available at http://www.tongji. edu.cn/∼zhanglab/GFOLD/index.html