Miracle-dz/UniFAR-FTUs huggingface dataset:
E3-Ubiquitin Ligase/E6-AP Links Multicopy Maintenance Protein 7 to the Ubiquitination Pathway by a Novel Motif, the L2G Box*

Ubiquitin ligases are generally assumed to play a major role in substrate recognition and thus provide specificity to a particular ubiquitin modification system. The multicopy maintenance protein (Mcm) 7 subunit of the replication licensing factor-M was identified as a substrate of the E3-ubiquitin ligase/E6-AP by its interaction with human papillomavirus-18E6. Mcm7 is ubiquitinated in vivo in both an E6-AP-dependent and -independent manner. E6-AP functions in these reactions independently of the viral oncogene E6. We show that recognition of Mcm7 by E6-AP is mediated by a homotypic interaction motif present in both proteins, called the L2G box. These findings served as the basis for the definition of substrate specificity for E6-AP. A small cluster of proteins whose function is intimately associated with the control of cell growth and/or proliferation contains the L2G box and is thereby implicated in an E6-AP and, by default, HPV-E6-dependent ubiquitination pathway.
Orange Juice Attenuates Circulating miR-150-5p, miR-25-3p, and miR-451a in Healthy Smokers: A Randomized Crossover Study

Introduction: Tobacco smoke is associated with oxidative and inflammatory pathways, increasing the risk of chronic-degenerative diseases. Our goal was to evaluate the effects of acute “Pera” and “Moro” orange juice consumption on inflammatory processes and oxidative stress in microRNA (miRNA) expression in plasma from healthy smokers. Methods: This was a randomized crossover study that included healthy smokers over 18 years old. Blood samples were collected before and 11 h after beverage ingestion. Participants were instructed to drink 400 mL of Pera orange juice (Citrus sinensis), Moro orange juice (Citrus sinensis L. Osbeck), or water. Each subject drank the beverages in a 3-way crossover study design. Inflammatory and oxidative stress biomarkers and circulating miRNA expression profiles were determined. The subjects maintained their usual tobacco exposure during the experiment. Results: We included 18 individuals (12 men and 6 women), with 37.0 ± 12.0 years old. All subjects received the 3 interventions. Increased expression of circulating miRNAs (miR-150-5p, miR-25-3p, and miR-451a) was verified after cigarette smoking, which were attenuated after intake of both types of orange juice. There was no difference regarding serum levels of TNF-α, IL-6, MMP-9, and C-reactive protein. Despite the increased activity of serum superoxide dismutase and glutathione peroxidase after “Pera” or “Moro” orange juice intake, respectively, no changes in lipid hydroperoxide levels were detected. Conclusion: Tobaccos smokers showed increased expression of miR-150-5p, miR-25-3p, and miR-451a was noted, and attenuated by orange juice intake. miRNAs were predicted to regulate 244 target genes with roles in oxidative stress, PI3K-Akt, and MAPK signaling, which are pathways frequently involved in smoking-related cardiovascular diseases and cancer.
Reinforcement of Gelatin-Based Nanofilled Polymer Biocomposite by Crystalline Cellulose from Cotton for Advanced Wound Dressing Applications

This study is designed to extract crystalline cellulose from cotton and reinforcing gelatin film for biomedical applications, especially as a wound dressing material for its exceptional biocompatibility and bio-activity. Moreover, gelatin helps in wound healing and crystalline cellulose as additive can improve its properties. Crystalline cellulose was prepared through hydrolysis and the effects of crystalline cellulose loading on the morphology, mechanical properties, and water sensitivity of the nanocomposite were investigated by means of scanning electron microscopy, tensile strength testing, and water absorption testing. Developed biocomposite film showed homogeneous dispersion of crystalline cellulose within the gelatin matrix and strong interfacial adherence between the matrix and reinforcement. Samples were tested for biocompatibility and in vitro cytotoxicity and found to have excellent biocompatibility without having any cytotoxicity. In vivo wound healing study in an animal model showed 40% increased healing than the model dressed by conventional dressing.
Neuropeptide S Attenuates the Alarm Pheromone-Evoked Defensive and Risk Assessment Behaviors Through Activation of Cognate Receptor-Expressing Neurons in the Posterior Medial Amygdala

Neuropeptide S (NPS) acts by activating its cognate receptor (NPSR). High level expression of NPSR in the posterior medial amygdala suggests that NPS-NPSR system should be involved in regulation of social behaviors induced by social pheromones. The present study was undertaken to investigate the effects of central administration of NPS or with NPSR antagonist on the alarm pheromone (AP)-evoked defensive and risk assessment behaviors in mice. Furthermore, H129-H8, a novel high-brightness anterograde multiple trans-synaptic virus, c-Fos and NPSR immunostaining were employed to reveal the involved neurocircuits and targets of NPS action. The mice exposed to AP displayed an enhancement in defensive and risk assessment behaviors. NPS (0.1–1 nmol) intracerebroventricular (i.c.v.) injection significantly attenuated the AP-evoked defensive and risk assessment behaviors. NPSR antagonist [D-Val5]NPS at the dose of 40 nmol completely blocked the effect of 0.5 nmol of NPS which showed the best effective among dose range. The H129-H8-labeled neurons were observed in the bilateral posterodorsal medial amygdala (MePD) and posteroventral medial amygdala (MePV) 72 h after the virus injection into the unilateral olfactory bulb (OB), suggesting that the MePD and MePV receive olfactory information inputs from the OB. The percentage of H129-H8-labeled neurons that also express NPSR were 90.27 ± 3.56% and 91.67 ± 2.46% in the MePD and MePV, respectively. NPS (0.5 nmol, i.c.v.) remarkably increased the number of Fos immunoreactive (-ir) neurons in the MePD and MePV, and the majority of NPS-induced Fos-ir neurons also expressed NPSR. The behavior characteristic of NPS or with [D-Val5]NPS can be better replicated in MePD/MePV local injection within lower dose. The present findings demonstrated that NPS, via selective activation of the neurons bearing NPSR in the posterior medial amygdala, attenuates the AP-evoked defensive and risk assessment behaviors in mice.
M-GCF: Multicolor-Green Conflict Free scheduling algorithm for WSN

Applications for wireless sensor networks (WSNs) are increasing in numbers and are penetrating in areas of increasing importance. The requirements of these applications can only be fulfilled with efficient medium access control (MAC) layer protocols and this paper presents a cluster-based time division multiple access (TDMA) scheduling algorithm, Multicolor-Green Conflict Free (M-GCF), for WSNs. The proposed algorithm finds multiple conflict free slots across a three-hop neighbor view. The algorithm shows better slot sharing with fewer conflicts along with good energy efficiency, throughput and delay as compared with state-of-the-art solutions. The results also include the performance of M-GCF with varying traffic rates, which also shows good energy efficiency, throughput and delay. The contribution of this paper and the main reason for the improved performance with varying number of nodes and traffic rate is the multicoloring approach used.
Correlation of D‐dimer level with the radiological severity indexes of pulmonary embolism on computed tomography pulmonary angiography

Background It is known that the main role of D‐dimer has been as an exclusionary test in patients with suspected venous thromboembolism. However, the D‐dimer is increasingly beginning to find clinical utility as a marker in the evaluation of the extent of the embolic disease. The aim of the study was to determine whether D‐dimer levels predict the radiological markers of pulmonary embolism (PE) severity using Mastora score. Methods This prospective study involved 69 patients with acute PE proved by computed tomography pulmonary angiography (CTPA). The D‐dimer level was noted. A pulmonary artery obstruction index (PAOI; Mastora score) ≥21.3% indicated severe obstruction of PE. A right ventricle/left ventricle (RV/LV) ratio >0.9 indicated RV dysfunction. Results The median D‐dimer level and PAOI were 765 &mgr;g/L (95% CI: 750–1 205 &mgr;g/L) and 16.77% (95% CI: 16.32%‐23.06%), respectively. The D‐dimer level was positively correlated with PAOI (r=0.417, P <0.000 1). PAOI ≥21.3% was associated with high D‐dimer levels (median, 993 &mgr;g/L (95% CI: 856–1 841 &mgr;g/L), Z=‐2.991, P=0.003). The D‐dimer level was correlated with the RV/LV ratio (r=0.272, P=0.024). RV/LV ratios >0.9 were associated with high D‐dimer levels (median, 880 &mgr;g/L (95% CI: 764–1 360 &mgr;g/L), Z=‐2.070, P=0.038). PAOI was positively correlated with the RV/LV ratio (r =0.390, P=0.001). After three months, both the PAOI and D‐dimer levels decreased (Z=‐7.009, P <0.000 1; Z=‐6.976, P <0.000 1, respectively). Conclusion D‐dimer levels are positively correlated with PE burden and right ventricle dysfunction on CTPA, and can help monitor the therapeutic response.
A comparative study of machine learning methods for authorship attribution

We compare and benchmark the performance of five classification methods, four of which are taken from the machine learning literature, in a classic authorship attribution problem involving the Federalist Papers. Cross-validation results are reported for each method, and each method is further employed in classifying the disputed papers and the few papers that are generally understood to be coauthored. These tests are performed using two separate feature sets: a ‘‘raw’’ feature set containing all words and word bigrams that are common to all of the authors, and a second ‘‘pre-processed’’ feature set derived by reducing the raw feature set to include only words meeting a minimum relative frequency threshold. Each of the methods tested performed well, but nearest shrunken centroids and regularized discriminant analysis had the best overall performances with 0/70 cross-validation errors.
Inhibition of mammalian target of rapamycin reduces epileptogenesis and blood–brain barrier leakage but not microglia activation

Purpose: Previous studies have shown that inhibition of the mammalian target of rapamycin (mTOR) pathway with rapamycin prevents epileptogenesis after pharmacologically induced status epilepticus (SE) in rat models of temporal lobe epilepsy. Because rapamycin is also known for its immunosuppressant properties we hypothesized that one of the mechanisms by which it exerts this effect could be via suppression of brain inflammation, a process that has been suggested to play a major role in the development and progression of epilepsy.
TIN2-Tethered TPP1 Recruits Human Telomerase to Telomeres In Vivo

ABSTRACT Recruitment to telomeres is a pivotal step in the function and regulation of human telomerase; however, the molecular basis for recruitment is not known. Here, we have directly investigated the process of telomerase recruitment via fluorescence in situ hybridization (FISH) and chromatin immunoprecipitation (ChIP). We find that depletion of two components of the shelterin complex that is found at telomeres—TPP1 and the protein that tethers TPP1 to the complex, TIN2—results in a loss of telomerase recruitment. On the other hand, we find that the majority of the observed telomerase association with telomeres does not require POT1, the shelterin protein that links TPP1 to the single-stranded region of the telomere. Deletion of the oligonucleotide/oligosaccharide binding fold (OB-fold) of TPP1 disrupts telomerase recruitment. In addition, while loss of TPP1 results in the appearance of DNA damage factors at telomeres, the DNA damage response per se does not account for the telomerase recruitment defect observed in the absence of TPP1. Our findings indicate that TIN2-anchored TPP1 plays a major role in the recruitment of telomerase to telomeres in human cells and that recruitment does not depend on POT1 or interaction of the shelterin complex with the single-stranded region of the telomere.
Rehabilitation of stroke and cerebellar patients

Le but de cette these est celui d’analyser, d’une part, comment la performance motrice des patients avec des attaques cerebrales peut etre ameliore a travers un entrainement avec un ergometre a bras et, d’autre part, et la performance des patients cerebelleux qui s’entrainent avec l’escalade. La these consiste dans trois parties experimentales. La premiere partie concerne la rehabilitation des patients avec des attaques cerebrales parmi un ergometre a bras et le developpement d’un index qui puisse quantifier le degre se spasticite d’un muscle donne. La deuxieme partie est un avant-projet sur les patients cerebelleux qui pratiquaient l’escalade. La troisieme partie concerne l’etude principale sur les patients cerebelleux, qui se base sur les resultats obtenus dans l’avant-projet. L’objectif de la premiere partie est double : premierement il s’agit d’analyser si l’entrainement avec un ergometre a bras, sur les patients avec des attaques cerebrales, reduit la spasticite, s’il augmente la puissance du muscle et s’il augmente l’etendue du mouvement du muscle; deuxiemes il s’agit de developper une technique qui nous permet de quantifier la spasticite individuelle d’un muscle. Neuf patients avec niveau stable de hemisyndrome cerebelleux ont ete soumis a un entraiment avec l’ergometre de trois semaines pendants cinq jours/semaines. Le test sur les patients a ete conduit quatre fois : une semaine avant l’entrainement, pendant l’entrainement, a la fin de celui-ci, et deux semaines apres l’entrainement. La spasticite a ete quantifiee a travers trois moyens: l’echelle d’Ashworth, l’extension maximale du biceps, et la torque minimale sur la partie lesinee pendant la rotation du bras. La puissance du muscle est evalue grâce au «Rivermead Motorik Assessment», au «Motrocity Index» et la puissance de la rotation; en outre, l’etendue du mouvement actif a ete mesure par la somme des inclinations maximales crees par une flexion de l’epaule, par une abduction de l’epaule, par une flexion de la coude, et par une extension de la coude. Pendant l’entrainement on a pu constater une reduction de la spasticite ainsi qu’une augmentation remarquable de la puissance du muscle et de l’etendue du mouvement. L’index de spasticite- a savoir, la relation entre la modulation de l’activite musculaire sur la partie normale et sur la partie lesinee - a montre de pouvoir etre un important outil dans la quantification de la spasticite musculaire. On a pu conclure que la rotation avec un ergometre a bras est un outil important pour la rehabilitation. L’objectif de l’avant-projet etait celui d’evaluer l’amelioration de la performance motrice des patients cerebelleux suite a un entrainement en escalade sur mur artificiel. Cinq patients ont participe a un entrainement de 45 minutes par jour, pour cinq jours la semaine et sur une periode de trois semaines. Chaque patient a ete teste sur les suivants criteres : la performance en escalade, le temps de reaction, le mouvement, et la flexion/extension de la partie superieure du membre. Les sessions du test ont ete…
Phosphorylation of Dopamine Transporter Serine 7 Modulates Cocaine Analog Binding*

Background: Dopamine transporter (DAT) activity is regulated by PKC. Results: We identify Ser-7 as a PKC phosphorylation site on DAT and show that phosphorylation conditions and Ser-7 mutation alter cocaine analog binding characteristics. Conclusion: Ser-7 phosphorylation affects cocaine analog binding by altering DAT conformational equilibrium. Significance: Ser-7 phosphorylation of DAT may impact recognition and action of cocaine. As an approach to elucidating dopamine transporter (DAT) phosphorylation characteristics, we examined in vitro phosphorylation of a recombinant rat DAT N-terminal peptide (NDAT) using purified protein kinases. We found that NDAT becomes phosphorylated at single distinct sites by protein kinase A (Ser-7) and calcium-calmodulin-dependent protein kinase II (Ser-13) and at multiple sites (Ser-4, Ser-7, and Ser-13) by protein kinase C (PKC), implicating these residues as potential sites of DAT phosphorylation by these kinases. Mapping of rat striatal DAT phosphopeptides by two-dimensional thin layer chromatography revealed basal and PKC-stimulated phosphorylation of the same peptide fragments and comigration of PKC-stimulated phosphopeptide fragments with NDAT Ser-7 phosphopeptide markers. We further confirmed by site-directed mutagenesis and mass spectrometry that Ser-7 is a site for PKC-stimulated phosphorylation in heterologously expressed rat and human DATs. Mutation of Ser-7 and nearby residues strongly reduced the affinity of rat DAT for the cocaine analog (−)-2β-carbomethoxy-3β-(4-fluorophenyl) tropane (CFT), whereas in rat striatal tissue, conditions that promote DAT phosphorylation caused increased CFT affinity. Ser-7 mutation also affected zinc modulation of CFT binding, with Ala and Asp substitutions inducing opposing effects. These results identify Ser-7 as a major site for basal and PKC-stimulated phosphorylation of native and expressed DAT and suggest that Ser-7 phosphorylation modulates transporter conformational equilibria, shifting the transporter between high and low affinity cocaine binding states.
Language models and smoothing methods for information retrieval

Designing an effective retrieval model that can rank documents accurately for a given query has been a central problem in information retrieval for several decades. An optimal retrieval model that is both effective and efficient and that can learn from feedback information over time is needed. Language models are new generation of retrieval models and have been applied since the last ten years to solve many different information retrieval problems. Compared with the traditional models such as the vector space model, they can be more easily adapted to model non traditional and complex retrieval problems and empirically they tend to achieve comparable or better performance than the traditional models. Developing new language models is currently an active research area in information retrieval. In the first stage of this thesis we present a new language model based on an odds formula, which explicitly incorporates document length as a parameter. To address the problem of data sparsity where there is rarely enough data to accurately estimate the parameters of a language model, smoothing gives a way to combine less specific, more accurate information with more specific, but noisier data. We introduce a new smoothing method called exponential smoothing, which can be combined with most language models. We present experimental results for various language models and smoothing methods on a collection with large document length variation, and show that our new methods compare favourably with the best approaches known so far. We discuss the collection effect on the retrieval function, where we investigate the performance of well known models and compare the results conducted using two variant collections. In the second stage we extend the current model from flat text retrieval to XML retrieval since there is a need for content-oriented XML retrieval systems that can efficiently and effectively store, search and retrieve information from XML document collections. Compared to traditional information retrieval, where whole documents are usually indexed and retrieved as single complete units, information retrieval from XML documents creates additional retrieval challenges. By exploiting the logical document structure, XML allows for more focussed retrieval that identifies elements rather than documents as answers to user queries. Finally we show how smoothing plays a role very similar to that of the idf function: beside the obvious role of smoothing, it also improves the accuracy of the estimated language model. The within document frequency and the collection frequency of a term actually influence the probability of relevance, which led us to a new class of smoothing function based on numeric prediction, which we call empirical smoothing. Its retrieval quality outperforms that of other smoothing methods.
Camptothecin and its analogues: a review on their chemotherapeutic potential

Topoisomerase I (Topo-I) is a major target for anticancer drug discovery and design. As a result, Topo-I inhibitors constitute an important class of the current anticancer drugs. To date, all of the Topo-I inhibitors that have been clinically evaluated are analogues of camptothecin (CPT), an extract of the Chinese tree Camptotheca acuminata. CPT has shown significant antitumor activity to lung, ovarian, breast, pancreas and stomach cancers. In this article the, phytochemical aspect, and various structural modifications are comprehensively reviewed as in rings A, B, C, D and E. Biological activity of camptothecin, other than anticancer, reported till the year 2003 has also been discussed.
Co-circulation of Orthobunyaviruses and Rift Valley Fever Virus in Mauritania, 2015

Ngari virus (NRIV) has been mostly detected during concurrent outbreaks of Rift Valley fever virus (RVFV). NRIV is grouped in the genus Orthobunyavirus within the Bunyaviridae family and RVFV in the genus Phlebovirus in the family Phenuiviridae. Both are zoonotic arboviruses and can induce hemorrhagic fever displaying the same clinical picture in humans and small ruminants. To investigate if NRIV and its parental viruses, Bunyamwera virus (BUNV) and Batai virus (BATV), played a role during the Mauritanian RVF outbreak in 2015/16, we analyzed serum samples of sheep and goats from central and southern regions in Mauritania by quantitative real-time RT-PCR, serum neutralization test (SNT) and ELISA. 41 of 458 samples exhibited neutralizing reactivity against NRIV, nine against BATV and three against BUNV. Moreover, complete virus genomes from BUNV could be recovered from two sheep as well as two NRIV isolates from a goat and a sheep. No RVFV-derived viral RNA was detected, but 81 seropositive animals including 22 IgM-positive individuals were found. Of these specimens, 61 samples revealed antibodies against RVFV and at least against one of the three orthobunyaviruses. An indirect ELISA based on NRIV/BATV and BUNV derived Gc protein was established as complement to SNT, which showed high performance regarding NRIV, but decreased sensitivity and specificity regarding BATV and BUNV. Moreover, we observed high cross-reactivity among NRIV and BATV serological assays. Taken together, the data indicate the co-circulation of at least BUNV and NRIV in the Mauritanian sheep and goat populations.
Using relational concept knowledge to improve search in referral networks

The notion of referral networks, as presented in the work of Singh and Yolum, and their application to knowledge management, lacks two fundamental aspects; the relation of concepts within a domain, and the ability of an agent to dynamically change their interests based on suggestions in the form of concept relations. This paper introduces the concept of an oracle agent, which is an agent with relational concept knowledge that can supply suggestions to a querying agent on how to adapt their interests. These new features allow agents to search in new ways so as to achieve superior results and as a consequence outperform agents in a traditional referral network.