Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of human Ect2 depletion and overexpression on cleavage furrow formation and abscission

The guanine nucleotide-exchange factor (GEF) Ect2 is essential for cytokinesis. Here we studied the subcellular localization of Ect2 and examined the consequences of either depleting or overexpressing Ect2 in human cells. We show that in mitotic cells Ect2 localizes to the central spindle and to the cell cortex. The latter association is mediated through a PH domain in Ect2 and central spindle localization requires the MKlp1-MgcRacGAP and MKlp2–Aurora-B complexes. Ect2 directly interacts with MKlp1-MgcRacGAP through its BRCT domain, whereas MKlp2–Aurora-B probably exerts a regulatory role in Ect2 central spindle targeting. Depletion of Ect2 impaired cleavage furrow formation and RhoA and Citron kinase failed to accumulate at the cleavage furrow. Ect2 displacement from the central spindle revealed that physiological levels of this protein in this location are not crucial for RhoA activation and cytokinesis. In cells overexpressing appropriate N-terminal Ect2 fragments, RhoA and Citron kinase localized to the cleavage furrow and ingression occurred, but abscission failed. This failure could be correlated with the persistence of these fragments at structures surrounding the midbody, suggesting that abscission requires the displacement of Ect2 from the contractile ring and its re-import into the nucleus.
Faulds: A Non-Parametric Iterative Classifier for Internet-Wide OS Fingerprinting

Recent work in OS fingerprinting has focused on overcoming random distortion in network and user features during Internet-scale SYN scans. These classification techniques work under an assumption that all parameters of the profiled network are known a-priori – the likelihood of packet loss, the popularity of each OS, the distribution of network delay, and the probability of user modification to each default TCP/IP header value. However, it is currently unclear how to obtain realistic versions of these parameters for the public Internet and/or customize them to a particular network being analyzed. To address this issue, we derive a non-parametric Expectation-Maximization (EM) estimator, which we call Faulds, for the unknown distributions involved in single-probe OS fingerprinting and demonstrate its significantly higher robustness to noise compared to methods in prior work. We apply Faulds to a new scan of 67M webservers and discuss its findings.
Neuroglobin, a Novel Target for Endogenous Neuroprotection against Stroke and Neurodegenerative Disorders

Brain neurons and tissues respond to sublethal injury by activating endogenous protective pathways. Recently, following the failure of a large number of clinical trials for protective strategies against stroke that aim to inhibit a specific ischemia response pathway, endogenous neuroprotection has emerged as a more promising and hopeful strategy for development of therapeutics against stroke and neurodegenerative disorders. Neuroglobin (Ngb) is an oxygen-binding globin protein that is highly and specifically expressed in brain neurons. Accumulating evidence have clearly demonstrated that Ngb is an endogenous neuroprotective molecule against hypoxic/ischemic and oxidative stress-related insults in cultured neurons and animals, as well as neurodegenerative disorders such as Alzheimer’s disease, thus any pharmacological strategy that can up-regulate endogenous Ngb expression may lead to novel therapeutics against these brain disorders. In this review, we summarize recent studies about the biological function, regulation of gene expression, and neuroprotective mechanisms of Ngb. Furthermore, strategies for identification of chemical compounds that can up-regulate endogenous Ngb expression for neuroprotection against stroke and neurodegenerative disorders are discussed.
Toxin-Antitoxin Systems Influence Biofilm and Persister Cell Formation and the General Stress Response

ABSTRACT In many genomes, toxin-antitoxin (TA) systems have been identified; however, their role in cell physiology has been unclear. Here we examine the evidence that TA systems are involved in biofilm formation and persister cell formation and that these systems may be important regulators of the switch from the planktonic to the biofilm lifestyle as a stress response by their control of secondary messenger 3′,5′-cyclic diguanylic acid. Specifically, upon stress, the sequence-specific mRNA interferases MqsR and MazF mediate cell survival. In addition, we propose that TA systems are not redundant, as they may have developed to respond to specific stresses.
Serum Elastin-Derived Peptides and Anti-Elastin Antibody in Patients with Systemic Sclerosis

The elastin metabolism in systemic sclerosis (SSc) has been known to be abnormal. The authors investigated relationship between the clinical manifestations of systemic sclerosis (SSc) and serum levels of soluble elastin-derived peptide (S-EDP) and anti-elastin antibodies. Serum samples were obtained from 79 patients with SSc and 79 age- and sex-matched healthy controls. Concentrations of serum S-EDP and anti-elastin antibodies were measured by ELISA. The serum concentrations of S-EDP in SSc patients were significantly higher than in healthy controls (median, 144.44 ng/mL vs 79.59 ng/mL, P < 0.001). Serum EDP concentrations were found to be correlated with disease duration in SSc (P = 0.002) and particularly in diffuse cutaneous SSc (P = 0.005). Levels of anti-elastin antibodies were found to be more elevated in SSc patients than in healthy controls (median, 0.222 U vs 0.191 U, P = 0.049), more increased in diffuse cutaneous SSc than limited cutaneous SSc (median, 0.368 U vs 0.204 U, P = 0.031). In addition, levels of anti-elastin antibodies were also found to be negatively associated with presence of anti-centromere antibody (P = 0.023). The S-EDP levels were not found to be correlated with levels of anti-elastin antibodies. The increased S-EDP and anti-elastin antibody levels and association with clinical and laboratory characteristics may reflect the abnormal metabolism in SSc.
Immunity, immunoregulation and the ecology of trichuriasis and ascariasis

Immune responses to human roundworm (Ascaris lumbricoides) and whipworm (Trichuris trichiura) and their role in controlling worm populations are reviewed. Recent immunoepidemiological data implicate Th2‐mediated responses in limiting A. lumbricoides and T. trichiura populations. Reinfection studies further suggest that IL‐5 cytokine responses are negatively associated with adult recruitment in T. trichiura but not A. lumbricoides and may therefore be involved in negative intraspecific and interspecific interactions mediated through the host immune system. The importance of inducible immunoregulatory networks in the ecology of the host–parasite relationship is considered, with particular regard to possible manipulative strategies by the parasites. This aspect of the worms’ interaction with the host immune system is both poorly known and potentially central to an understanding of parasite population dynamics and the evolutionary pressures that have shaped present‐day host–parasite associations. Some possible implications of worm‐mediated immunomodulation for the occurrence of bystander infectious diseases in human populations and the management of de‐worming programmes are also discussed.
Optimal Spread in Network Consensus Models

In a model of network communication based on a random walk in an undirected graph, what subset of nodes (subject to constraints on the set size), enable the fastest spread of information? The dynamics of spread is described by a process dual to the movement from informed to uninformed nodes. In this setting, an optimal set $A$ minimizes the sum of the expected first hitting times $F(A)$, of random walks that start at nodes outside the set. In this paper,the problem is reformulated so that the search for solutions is restricted to a class of optimal and "near" optimal subsets of the graph. We introduce a submodular, non-decreasing rank function $\rho$, that permits some comparison between the solution obtained by the classical greedy algorithm and one obtained by our methods. The supermodularity and non-increasing properties of $F$ are used to show that the rank of our solution is at least $(1-\frac{1}{e})$ times the rank of the optimal set. When the solution has a higher rank than the greedy solution this constant can be improved to $(1-\frac{1}{e})(1+\chi)$ where $\chi >0$ is determined a posteriori. The method requires the evaluation of $F$ for sets of some fixed cardinality $m$, where $m$ is much smaller than the cardinality of the optimal set. When $F$ has forward elemental curvature $\kappa$, we can provide a rough description of the trade-off between solution quality and computational effort $m$ in terms of $\kappa$.
Modular isolated high frequency medium voltage (MV) step-up resonant DC/DC converters with high-gain rectifier for wind energy systems

Conventional offshore wind farms with medium voltage (MV) AC grid require low frequency step-up transformer to boost the output voltage of the wind turbine. In order to eliminate the bulky MV step-up transformers in MVAC grid, the use of a MV step-up DC/DC converter in MVDC grid is an attractive alternative. In this paper, two modular MV step-up DC/DC converter topologies that combine multiple modules of step-up resonant circuits and high frequency high gain rectifiers are proposed for MVDC grid in wind energy system. Due to the combination of multiple step-up resonant circuits and the high gain rectifiers, the proposed converters are able to achieve high voltage gain without using large turns ratio high frequency step-up transformers. In addition, ZVS turn-on ZCS turn-off are achieved on the inverter side switches to minimize the switching losses. The switching frequency is varied to regulate the output medium voltage for different wind speed conditions. The description and the operating principles of the proposed converter are provided in this paper. Results on a 5MW, 3.3kVac/40kV wind turbine system are presented to highlight the merits of this work.
The evolution of phenylpropanoid metabolism in the green lineage

Abstract Phenolic secondary metabolites are only produced by plants wherein they play important roles in both biotic and abiotic defense in seed plants as well as being potentially important bioactive compounds with both nutritional and medicinal benefits reported for animals and humans as a consequence of their potent antioxidant activity. During the long evolutionary period in which plants have adapted to the environmental niches in which they exist (and especially during the evolution of land plants from their aquatic algal ancestors), several strategies such as gene duplication and convergent evolution have contributed to the evolution of this pathway. In this respect, diversity and redundancy of several key genes of phenolic secondary metabolism such as polyketide synthases, cytochrome P450s, Fe2+/2-oxoglutarate-dependent dioxygenases and UDP-glycosyltransferases have played an essential role. Recent technical developments allowing affordable whole genome sequencing as well as a better inventory of species-by-species chemical diversity have resulted in a dramatic increase in the number of tools we have to assess how these pathways evolved. In parallel, reverse genetics combined with detailed molecular phenotyping is allowing us to elucidate the functional importance of individual genes and metabolites and by this means to provide further mechanistic insight into their biological roles. In this review, phenolic metabolite-related gene sequences (for a total of 65 gene families including shikimate biosynthetic genes) are compared across 23 independent species, and the phenolic metabolic complement of various plant species are compared with one another, in attempt to better understand the evolution of diversity in this crucial pathway.
Serially-Concatenated LDGM Codes for MIMO Channels

We investigate the ability of serially-concatenated low density generator matrix (SCLDGM) codes to approach the capacity of ergodic multiple-input multiple-output (MIMO) channels. First, we explain how to design good SCLDGM codes using extrinsic information transfer (EXIT) analysis and optimum detection. However, optimum detection becomes unfeasible in many cases of practical interest where the number of transmitting antennas and/or the number of bits per constellation symbol is large. In this case, we resort to list sphere detection (LSD), considering two versions: maximum likelihood (ML) and maximum a posteriori (MAP). Again, we use EXIT analysis to obtain good SCLDGM codes for these specific LSD versions. We provide examples of optimized rate 1/2 SCLDGM codes and show that they perform within 1 dB from the theoretical capacity limit for a large number of antenna configurations and modulation formats. Finally, we discuss how to iteratively improve channel estimation using the soft information computed during the decoding process. We also show how the complexity of channel estimation is reduced by utilizing the candidate list calculated by the LSD.
Pain Measurement Scales: A Comparison of the Visual Analogue and Faces Rating Scales in Measuring Pressure Ulcer Pain

Objective Although different pain scales often have been used interchangeably, it is not known whether interchanging them is appropriate. The purpose of this report was twofold: to better understand the statistical properties of the Faces Rating Scale (FRS) so it can be used appropriately in clinical settings and to describe the mathematical relationship between the Visual Analogue Scale (VAS) and the FRS when they are used to quantify pressure ulcer pain in hospitalized elderly patients. Design Secondary data analyses were performed as part of a cross-sectional study. Setting and Subjects A quality assurance program was undertaken to evaluate pressure ulcer pain perceived by elderly hospitalized patients. All patients without aphasia participated. Instruments The VAS used was a 0 to 100 mm horizontal line demonstrated to have ratio scale properties with high validity and reproducibility, and the FRS used was 6 faces ordered horizontally from smiling to crying, labeled 0 to 5 beneath each face, respectively. Methods Nonlinear least squares regression with a Gauss-Newton iterative procedure was used. Results Among models with cubic, quadratic, and linear terms, only the quadratic term was significant (P < .05). With use of the equation derived, VAS = 3.33*(FRS)2, the resulting reliability coefficient was r = 0.92. Conclusions The nonlinear relationship indicated high reliability between VAS and FRS for pain assessment in populations with diminished verbal and abstract thinking abilities. For readers who would like to translate results from one scale to another, a quadratic equation is provided.
Immediate removal of femoral-sheath following protamine administration in patients undergoing intracoronary paclitaxel-eluting-stent implantation

Background: Immediate sheath-removal using post-procedural reversal of heparin with protamine reduces groin complications, shortens bed rest and hospital stay after percutaneous coronary intervention (PCI) with bare-metal stents. No data are available with newer and possibly more thrombogenic paclitaxel-eluting stents (PES). Aim: We assessed the safety and efficacy of post-procedural protamine administration after successful coronary PES implantation in elective PCI and in patients with acute coronary syndromes (ACS). Methods: A consecutive series of 291 patients received 0.5 mg of protamine per 100 units of heparin whenever the post-procedural ACT was > 180 seconds, followed by immediate removal of the sheath (protamine group). Outcomes were compared to a historic control group comprising 291 consecutive patients, who also underwent PCI with PES, but without reversal of anticoagulation by protamine (non protamine group). The incidence of post-procedural vascular complications and bleeding complications, as well as hospital stay, were compared; as were the incidence of major cardiac events at 24 h, 30 days and 6 months. Results: The post-procedural bleeding complications were significantly higher in the non-protamine group. Vascular complications were also more frequent in patients who were not treated with protamine. Hospitalisation length was significantly lower in the protamine group than in the non-protamine group (13.6 ± 7 h versus 20.41 ± 3.9 h; p < 0.001). The protamine-group patients also had a significantly reduced bed rest (10.3 h ± 5.6 h versus 18 h ± 3.5 h; p < 0.001). During hospitalisation, after PES implantation, no deaths or acute stent thrombosis were observed in either group. The overall incidence of thrombosis and major adverse cardiac events at follow-up were similar in the two groups. Conclusions: Immediate heparin neutralisation by protamine after successful PES implantation appears to be safe and feasible, also in patients with ACS. Use of protamine and early sheath removal after PCI confers early deambulation and may significantly limit healthcare cost, reduce vascular complications, bedrest, delayed discharge and patient discomfort.
Does Prior Knowledge Facilitate the Development of Knowledge-based Systems?

One factor that affects the rate of knowledge base construction is the availability and reuse of prior knowledge in ontologies and domain-specific knowledge bases. This paper reports an empirical study of reuse performed in the first year of the High Performance Knowledge Bases (HPKB) initiative. The study shows that some kinds of prior knowledge help more than others, and that several factors affect how much use is made of the knowledge.
UTRdb and UTRsite (RELEASE 2010): a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs

The 5′ and 3′ untranslated regions of eukaryotic mRNAs (UTRs) play crucial roles in the post-transcriptional regulation of gene expression through the modulation of nucleo-cytoplasmic mRNA transport, translation efficiency, subcellular localization and message stability. UTRdb is a curated database of 5′ and 3′ untranslated sequences of eukaryotic mRNAs, derived from several sources of primary data. Experimentally validated functional motifs are annotated and also collated as the UTRsite database where more specific information on the functional motifs and cross-links to interacting regulatory protein are provided. In the current update, the UTR entries have been organized in a gene-centric structure to better visualize and retrieve 5′ and 3′UTR variants generated by alternative initiation and termination of transcription and alternative splicing. Experimentally validated miRNA targets and conserved sequence elements are also annotated. The integration of UTRdb with genomic data has allowed the implementation of an efficient annotation system and a powerful retrieval resource for the selection and extraction of specific UTR subsets. All internet resources implemented for retrieval and functional analysis of 5′ and 3′ untranslated regions of eukaryotic mRNAs are accessible at http://utrdb.ba. itb.cnr. it/.
Efficient use of a translation start codon in BDNF exon I

The brain‐derived neurotrophic factor (BDNF) gene contains a number of 5′ exons alternatively spliced with a common 3′ exon. BDNF protein is synthesized from alternative transcripts as a prepro‐precursor encoded by the common 3′ exon IX, which has a translation start site 21 bp downstream of the splicing site. BDNF mRNAs containing exon I are an exception to this arrangement as the last three nucleotides of this exon constitute an in‐frame AUG. Here, we show that this AUG is efficiently used for translation initiation in PC12 cells and cultured cortical neurons. Use of exon I‐specific AUG produces higher levels of BDNF protein than use of the common translation start site, resulting from a higher translation rate. No differences in protein degradation, constitutive or regulated secretion were detected between BDNF isoforms with alternative 5′ termini. As the BDNF promoter preceding exon I is known to be highly regulated by neuronal activity, our results suggest that the function of this translation start site may be efficient stimulus‐dependent synthesis of BDNF protein. The brain‐derived neurotrophic factor (BDNF) gene contains multiple untranslated 5′ exons alternatively spliced to one common protein‐coding 3′ exon. However, exon I contains an in‐frame ATG in a favorable translation context. Here, we show that use of this ATG is associated with more efficient protein synthesis than the commonly used ATG in exon IX.
Adjuvant-dependent immune response to malarial transmission-blocking vaccine candidate antigens [published erratum appears in J Exp Med 1993 Feb 1;177(2):following 576]

Immune responses in major histocompatibility complex (MHC)-disparate congenic mouse strains immunized with sexual stage malaria parasites or purified recombinant protein were adjuvant dependent. Whereas mice exhibited a limited antibody response to immunization with newly emerged Plasmodium falciparum gametes in Freund's adjuvant, all five congenic mouse strains responded to several transmission-blocking vaccine candidate antigens, when parasites were emulsified in a monophosphoryl lipid A (MPL) and trehalose dimycolate (TDM) adjuvant. The humoral response in those animals immunized with the antigen in a MPL/TDM adjuvant was helper T cell dependent, as evident by boosting of the antibody response after a second immunization. If the immunogen consisted of purified recombinant protein, then the immune response was not MHC class II limited in mice immunized with either complete Freund's adjuvant or TDM/MPL. The potential role of adjuvants in overcoming apparent immune nonresponsiveness and the implications for development of a malaria transmission-blocking vaccine are discussed.
ISN/RPS 2003 classification of lupus nephritis: time to take a look on the achievements and limitations of the schema

Implication for health policy/practice/research/medical education: Lupus nephritis (LN) is the most dreadful complication of systemic lupus erythematosus (SLE) and is responsible for the major share of morbidity and mortality of this disease. Its diagnosis, classification and management have posed significant challenges to the nephrologists and pathologists over the past several decades. A series of WHO classifications of LN were followed by the development of the international society of nephrology/renal pathology society (ISN/RPS) classification of LN in 2003. The classification has largely succeeded in achieving its goals, but a few limitations have also been exposed. It is time to revisit the classification in the light of experience of validation studies and new emerging data on this disease.