Miracle-dz/UniFAR-FTUs huggingface dataset:
Melatonin protects against burn-induced hepatic oxidative injury by inducing HO-1 via the Nrf 2 pathway

Melatonin exerts beneficial effects on early liver injury by modulating hepatic oxidative stress. In order to understand the protective effect of melatonin against burn-induced hepatic injury we investigated the expression of 4-hydroxynonenal (4-HNE), a main product of lipid peroxidation and mediator of oxidative injury, the inducible heme-oxygenase-1 (HO-1), an antioxidant enzyme, and the anti-oxidative stress regulator erythroid 2-related factor 2 (Nrf2) in a burn rat model. Expression and localisation of HO-1, 4-HNE and Nrf2 in liver were investigated using light immunochemistry. Thermal skin injury caused a significant elevation in hepatic 4-HNE and degenerative liver changes. Concurrently, there was increased expression of HO-1, a rate-limiting enzyme for haem degradation and an oxidative stress marker in sinusoidal endothelial cells (SECs) and hepatocytes without changes in Nrf2 expression in the liver. Melatonin (20 mg/kg b.w.) augmented the increase in HO-1 expression, upregulated Nrf2 expression and also led to decreased 4-HNE levels and reduced levels of histopathological changes in rat liver. In conclusion, our results suggest that melatonin ameliorates burn-induced liver injury through the inhibition of oxidative stress, upregulation of the antioxidant enzyme HO-1 and activation of the antioxidant Nrf2 pathway. Stimulation of cellular protective mechanisms by activating the antioxidant stress response through Nrf2 is a new mechanism for protection against liver damage in burns.
Black hole thermodynamics and quantum hair.

A formula is derived for the Euclidean action of a black hole surrounded by Yang-Mills, scalar, and fermion fields. This is used to prove that the entropy of a black hole with classical hair is given by the usual formula, S=1/4 A, where A is the area of the event horizon, and the modifications for quantum hair are discussed
Évolution du VIH : méthodes, modèles et algorithmes

La donnee de sequences nucleotidiques permet d'inferer des arbres phylogenetiques, ou phylogenies, qui decrivent leurs liens de parente au cours de l'evolution. Associer a ces sequences leur date de prelevement ou leur pays de collecte, permet d'inferer la localisation temporelle ou spatiale de leurs ancetres communs. Ces donnees et procedures sont tres utilisees pour les sequences de virus et, notamment, celles du virus de l'immunodeficience humaine (VIH), afin d'en retracer l'histoire epidemique a la surface du globe et au cours du temps. L'utilisation de sequences echantillonnees a des moments differents (ou heterochrones) sert aussi a estimer leur taux de substitution, qui caracterise la vitesse a laquelle elles evoluent. Les methodes les plus couramment utilisees pour ces differentes tâches sont precises, mais lourdes en temps de calcul car basees sur des modeles complexes, et ne peuvent traiter que quelques centaines de sequences. Devant le nombre croissant de sequences disponibles dans les bases de donnees, souvent plusieurs milliers pour une etude donnee, le developpement de methodes rapides et efficaces devient indispensable. Nous presentons une methode de distances, Ultrametric Least Squares , basee sur le principe des moindres carres, souvent utilise en phylogenie, qui permet d'estimer le taux de substitution d'un ensemble de sequences heterochrones, dont on deduit ensuite facilement les dates des speciations ancestrales. Nous montrons que le critere a optimiser est parabolique par morceaux et proposons un algorithme efficace pour trouver l'optimum global. L'utilisation de sequences echantillonnees en des lieux differents permet aussi de retracer les chaines de transmission d'une epidemie. Dans ce cadre, nous utilisons la totalite des sequences disponibles (~3500) du sous-type C du VIH-1, responsable de pres de 50% des infections mondiales au VIH-1, pour estimer ses principaux flux migratoires a l'echelle mondiale, ainsi que son origine geographique. Des outils novateurs, bases sur le principe de parcimonie combine avec differents criteres statistiques, sont utilises afin de synthetiser et interpreter l'information contenue dans une grande phylogenie representant l'ensemble des sequences etudiees. Enfin, l'origine geographique et temporelle de ce variant (VIH-1 C) au Senegal est precisement exploree lors d'une seconde etude, portant notamment sur les hommes ayant des rapports sexuels avec des hommes.
Is it Time to Eliminate Confusion Regarding Cervical Lymph Node Levels According to the Scheme Originated at the Memorial Sloan-Kettering Cancer Center?

ALFIO FERLITO, K. THOMAS ROBBINS, JESUS E. MEDINA, ASHOK R. SHAHA, PETER M. SOM and ALESSANDRA RINALDO From the Department of Otolaryngology—Head and Neck Surgery, University of Udine, Udine, Italy, Department of Otolaryngology, University of Florida, Gainesville, Florida, USA, Department of Otolaryngology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA, Head and Neck Service, Memorial Sloan–Kettering Cancer Center, New York, New York, USA, Department of Radiology, Mount Sinai School of Medicine, City University of New York, New York, New York, USA
Molecular Epidemiology of Metallo-β-Lactamase-Producing Pseudomonas aeruginosa Isolates from Norway and Sweden Shows Import of International Clones and Local Clonal Expansion

ABSTRACT Scandinavia is considered a region with a low prevalence of antimicrobial resistance. However, the number of multidrug-resistant (MDR) Gram-negative bacteria is increasing, including metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa. In this study MBL-producing P. aeruginosa isolates identified in Norway (n = 4) and Sweden (n = 9) from 1999 to 2007 were characterized. Two international clonal complexes (CC), CC111 (n = 8) and CC235 (n = 2), previously associated with MBL-producing isolates, were dominant. CC111 isolates (ST111/229; serotype O12; blaVIM-2) included clonally related isolates identified in Skåne County, Sweden (n = 6), and two isolates associated with importation from Greece and Denmark. In all CC111 isolates, blaVIM-2 was located in integron In59.2 or In59 variants. The two CC235 isolates (ST235/ST230; serotype O11; blaVIM-4) were imported from Greece and Cyprus, were possibly clonally related, and carried blaVIM-4 in two different integron structures. Three isolates imported from Ghana (ST233; serotype O6; blaVIM-2), Tunisia (ST654; serotype O11; blaVIM-2), and Thailand (ST260; serotype O6; blaIMP-14) were clonally unrelated. ST233 was part of a new CC (CC233) that included other MBL-producing isolates, while ST654 could also be part of a new CC associated with MBL producers. In the isolates imported from Ghana and Tunisia, blaVIM-2 was part of unusual integron structures lacking the 3′ conserved segment and associated with transposons. The blaVIM gene was found to be located on the chromosome in all isolates. Known risk factors for acquisition of MBL were reported for all patients except one. The findings suggest that both import of successful international clones and local clonal expansion contribute to the emergence of MBL-producing P. aeruginosa in Scandinavia.
Stability of a biological tissue fixed with a naturally occurring crosslinking agent (genipin).

The study was undertaken to investigate the stability of a biological tissue fixed with a naturally occurring crosslinking agent (genipin) at distinct elapsed storage durations. The glutaraldehyde-fixed counterpart was used as a control. Porcine pericardia procured from a slaughterhouse were used as raw materials. After fixation, the fixed tissues were sterilized in a graded series of ethanol solutions and thoroughly rinsed in phosphate buffered saline for 1 day, and then stored in a jar containing sterilized water. The samples were taken out and tested for their stability during the durations of 1day through 6 months after storage. The stability of each study group was tested by measuring its tensile strength, free-amino-group content, and denaturation temperature. Additionally, the cytotoxicity of each test sample and its corresponding storage solution were investigated in vitro using 3T3 fibroblasts. The results were examined using a microscope and 3-(4,5-dimethylthiazol-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It was found that the stability of the genipin-fixed tissue during storage was superior to its glutaraldehyde-fixed counterpart. The differences in stability between the genipin- and glutaraldehyde-fixed tissues during storage may be caused by their differences in crosslinking structure. There was no apparent cytotoxicity for both the genipin-fixed tissue and its corresponding storage solution throughout the entire course of the study, whereas significant cytotoxicity was observed for both the glutaraldehyde-fixed tissue and its storage solution. However, the cytotoxicity of the glutaraldehyde-fixed tissue decreased with increasing elapsed storage duration, whereas that of its corresponding storage solution increased. This suggested that the toxic residues remaining in the glutaraldehyde-fixed tissue leached out slowly into its corresponding storage solution during the course of storage.
Training and retaining more rural doctors for South Africa.

The guidebooks call Mpumalanga one of the "often overlooked provinces" of South Africa. [1] Northeast of Johannesburg, its grassy hills are just a blur on the highway for foreign visitors heading to the spectacular game reserves of Kruger National Park. They will not often get to Themba Hospital in White River, just 50 miles from the border with Mozambique, serving over three million of Mpumalanga's overwhelmingly rural population.
The Abundant R2 mRNA Generated by Aleutian Mink Disease Parvovirus Is Tricistronic, Encoding NS2, VP1, and VP2

ABSTRACT The abundant R2 mRNA encoded by the single left-end promoter of Aleutian mink disease parvovirus is tricistronic; it not only expresses the capsid proteins VP1 and VP2 but is also the major source for the nonstructural protein NS2. A cis-acting sequence within the NS2 gene was shown to be required for efficient capsid protein production, and its effect displayed a distinct location dependence. Ribosome transit through the upstream NS2 gene region was necessary for efficient VP1 and VP2 expression; however, neither ablation nor improvement of the NS2 initiating AUG had an effect on capsid protein production, suggesting that the translation of the NS2 protein per se had little influence on VP1 and VP2 expression. Thus, proper control of the alternative translation of the tricistronic R2 mRNA, a process critical for viral replication, is governed in a complex manner.
Interference effects on wireless link availability

Interference effects on a 2.4 GHz wireless local area network (WLAN) link with regard to using or manipulating personal media, including video, music, and online gaming, have been minimally addressed by prior research. Many consumer and business applications recommend a minimum bandwidth that must be adhered to for performance expectations to be in-line with specified capabilities. Users should be able to judge if link availability will be impacted when using wirelessly enabled mobile devices. The research performed identified sources of interference and their affect on a 2.4 GHz 802.11b WLAN network link. The test environment mirrored a wireless hotspot with additional users present. It was found that each interference source had a varying degradation effect on wireless link availability.
Carbapenemase-Producing Klebsiella pneumoniae Bloodstream Infections: Lowering Mortality by Antibiotic Combination Schemes and the Role of Carbapenems

ABSTRACT Carbapenemase-producing Klebsiella pneumoniae strains (CP-Kps) are currently among the most important nosocomial pathogens. An observational study was conducted during 2009 to 2010 in two hospitals located in a high-prevalence area (Athens, Greece). The aims were (i) to evaluate the clinical outcome of patients with CP-Kp bloodstream infections (BSIs), (ii) to identify predictors of mortality, and (iii) to evaluate the various antibiotic schemes employed. A total of 205 patients with CP-Kp BSIs were identified: 163 (79.5%) were infected with KPC or KPC and VIM, and 42 were infected with VIM producers. For definitive treatment, 103 patients received combination therapy (two or more active drugs), 72 received monotherapy (one active drug), and 12 received therapy with no active drug. The remaining 18 patients died within 48 h after the onset of bacteremia. The all-cause 28-day mortality was 40%. A significantly higher mortality rate was observed in patients treated with monotherapy than in those treated with combination therapy (44.4% versus 27.2%; P = 0.018). The lowest mortality rate (19.3%) was observed in patients treated with carbapenem-containing combinations. In the Cox proportion hazards model, ultimately fatal disease (hazards ratio [HR], 3.25; 95% confidence interval [CI], 1.51 to 7.03; P = 0.003), the presence of rapidly fatal underlying diseases (HR, 4.20; 95% CI, 2.19 to 8.08; P < 0.001), and septic shock (HR, 2.15; 95% CI, 1.16 to 3.96; P = 0.015) were independent predictors of death. Combination therapy was strongly associated with survival (HR of death for monotherapy versus combination, 2.08; 95% CI, 1.23 to 3.51; P = 0.006), mostly due to the effectiveness of the carbapenem-containing regimens.
Skin‐sensitization structure‐activity relationships for aldehydes

A selection of 17 aldehydes (13 sensitizing and 4 non‐sensitizing), all of which possessed a benzene ring, were evaluated using structure‐activity relationships (SARs). The sensitizing compounds were classified as strong, moderate or weak skin sensitizers on the basis of in vivo data. The aldehydes were grouped into 4 distinct subcategories of functionally related aldehydes that were termed aryl‐substituted aliphatic, aryl, aryl with special features (that can undergo metabolism) and α,β‐unsaturated aldehydes. It was observed that a structure‐activity relationship could be derived for a subset of aldehydes that could react via the same chemical mechanism. This further supports the view that applying knowledge on reaction mechanisms to develop SAR models can provide a more accurate means of investigating and predicting the sensitization potential of structurally and functionally related chemicals.
[Construction of enterohemorrhagic Escherichia coli O157:H7 strains with espF gene deletion and complementation].

OBJECTIVE To construct enterohemorrhagic Escherichia coli (EHEC) O157:H7 strains with delection espF gene and its nucleotide fragment and with espF gene complementation. METHODS A pair of homologous arm primers was designed to amplify the gene fragment of kanamycin resistance, which was transformed into EHEC O157:H7 EDL933w strain via the PKD46 plasmid by electroporation. The replacement of the espF gene by kanamycin resistance gene through the PKD46-mediated red recombination system was confirmed by PCR and sequencing. The entire coding region of espF along with its nucleotide fragment was amplified by PCR and cloned into pBAD33 plasmid, which was transformed into a mutant strain to construct the strain with espF complementation. RT-PCR was used to verify the transcription of espF and its nucleotide fragment in the complemented mutant strain. RESULTS AND CONCLUSION We established EHEC O157:H7 EDL933w strains with espF gene deletion and with espF gene complementation. Both espF and its nucleotide fragment were transcribed in the complemented mutant strain. The two strains provide a basis for further study of the regulatory mechanism of espF.
Cartographie in vivo des remaniements anatomo-fonctionnels de l’architecture des réseaux neuronaux dans le système nerveux central au cours du développement par Imagerie du Tenseur de Diffusion et Imagerie renforcée par le manganèse

L’objectif de cette these est de developper des methodes IRM permettant d’etudier l’impact d’une ischemie focale transitoire sur le cerveau de rat nouveau-ne. Les techniques utilisees sont l’imagerie a contraste renforce par le manganese (MEMRI), l’imagerie du tenseur de diffusion (DTI) ainsi que de facon preliminaire l’imagerie Q-ball (QBI). Le MEMRI apres injection intra cerebrale a ete utilise afin d’etudier de maniere dynamique le tractus cortico-thalamique, en parallele le DTI a servi de marqueur de la structuration cerebrale. Les resultats ont montre une atteinte du tractus cortico-thalamique ipsi-lateral, sept et quatorze jours apres ischemie. De maniere generale le DTI a montre une structuration ralentie a la suite de l’ischemie. A partir de ces resultats la faisabilite d’une methode d’acquisition rapide et de traitement de donnees Q-ball a ete etablie puis testee sur un animal immature. Les methodes mises en place se sont revelees efficaces dans le suivi de la maturation cerebrale dans des conditions normales ainsi que pathologiques, ouvrant des perspectives d’etudes liees au developpement cerebral.
Expanding the Ig Superfamily Code for Laminar Specificity in Retina: Expression and Role of Contactins

Bipolar, amacrine, and retinal ganglion cells elaborate arbors and form synapses within the inner plexiform layer (IPL) of the vertebrate retina. Specific subsets of these neuronal types synapse in one or a few of the ≥10 sublaminae of the IPL. Four closely related Ig superfamily transmembrane adhesion molecules—Sidekick1 (Sdk1), Sdk2, Dscam, and DscamL—are expressed by non-overlapping subsets of chick retinal neurons and promote their lamina-specific arborization (Yamagata and Sanes, 2008). Here, we asked whether contactins (Cntns), six homologs of Sdks and Dscams, are expressed by and play roles in other subsets. In situ hybridization showed that cntn1–5 were differentially expressed by subsets of amacrine cells. Immunohistochemistry showed that each Cntn protein was concentrated in a subset of IPL sublaminae. To assess roles of Cntns in retinal development, we focused on Cntn2. Depletion of Cntn2 by RNA interference markedly reduced the ability of Cntn2-positive cells to restrict their arbors to appropriate sublaminae. Conversely, ectopic expression of cntn2 redirected neurites of transduced neurons to the Cntn2-positive sublaminae. Thus, both loss- and gain-of-function strategies implicate Cntn2 in lamina-specific neurite targeting. Studies in heterologous cells showed that Cntn2 mediates homophilic adhesion, but does not bind detectably to Sdks, Dscams, or other Cntns. Overexpression analysis showed that Cntns1 and 3 can also redirect neurites to appropriate sublaminae. We propose that Cntns, Sdks, and Dscams comprise an Ig superfamily code that uses homophilic interactions to promote lamina-specific targeting of retinal dendrites in IPL.
The Ubiquitous Pharmacogenomics consortium: making effective treatment optimization accessible to every European citizen.

Physicians and pharmacists increasingly recognize that pharmacogenomics (PGx)-informed prescribing and dispensing improves both the efficacy and safety of drug treatment [1,2]. An estimated 15% of the medicines recently evaluated by the EMA contain PGx information in the label that directly impacts patient treatment and this percentage will increase in the near future [3]. Several randomized controlled trials have shown the clinical utility of single drug–gene pre-emptive PGx testing. Examples include PGx testing to guide dosing of thiopurines, acenocoumarol and warfarin [4,5,6], and PGx testing to guide drug selection for carbamazepine and abacavir [7,8]. Interestingly, this gold-standard evidence has focused on individual single gene–drug pair(s). Pre-emptive PGx testing for a panel of relevant pharmacogenes may be even more informative and clinically relevant than testing for individual gene–drug pairs. Reasons for this being threefold. First, PGx test results are static and can, therefore, be utilized lifelong. Second, over the course of their lifespan most patients will likely use multiple drugs of which multiple may benefit from PGx-informed prescribing [9]. Third, actionable PGx variants are highly common in the population and recent studies show that more than 95% of the population carry at least one actionable PGx variant when tested for a panel of six to eight well-recognized pharmacogenes [10,11,12,13]. Indeed, the positive effects of pre-emptive PGx testing for a panel of genes have recently been demonstrated in several small studies [14,15,16]. Nevertheless, convincing evidence from well-designed, sufficiently powered prospective studies is needed. To fill this unmet need and to achieve implementation of PGxguided prescribing in Europe, the Ubiquitous Pharmacogenomics (U-PGx) consortium was founded.
Natural Language Interaction with Semantic Web Knowledge Bases and LOD

Cultural heritage appears to be a very useful use case for Semantic Web technologies. The domain provides with plenty of circumstances where linkages between different knowledge sources are required to ensure access to rich information and respond to the needs of professionals dealing with cultural heritage content. Semantic Web technologies offer the technological backbone to meet the requirement of integrating heterogeneous data easily, but they are still more adapted to be consumed by computers than by humans, especially non-engineers or developers. This chapter is about a technique which allows interaction in natural language with semantic knowledge bases. The proposed technique offers a method that allows querying a semantic repository in natural language and obtaining results from it as a coherent text. This unique solution includes several steps of transition from natural language to SPARQL and from RDF to coherent multilingual descriptions, using the Grammatical Framework, GF. The approach builds on a semantic knowledge infrastructure in RDF, it is based on OWLIM-SE and the data integration method Reason-able View supplied with an ontological reference layer. The latter is connected via formal rules with abstract representations derived from the syntactic trees of natural language input using the GF resource grammar library.
Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs.

1 The serum concentration profile of paracetamol has been determined after administration of single 1000 mg intravenous and oral doses in six normal subjects and six epileptic patients on chronic antiepileptic drug therapy. The urinary excretion of free and conjugated paracetamol has also been determined. 2 Following intravenous administration, serum paracetamol concentration declined with first-order kinetics. Both elimination rate and total body clearance were higher in the epileptic patients, although in neither case was the difference statistically significant. 3 The oral bioavailability (mean +/- s.e. mean) was significantly lower in the epileptic patients than in the normal subjects (0.77 +/- 0.03 and 0.89 +/- 0.02 respectively, P less than 0.01), whereas the urinary excretion total (free+conjugated) paracetamol was almost identical in the two groups. 4 It is suggested that the lower bioavailability of paracetamol in the epileptic patients results from enhancement of first-pass metabolism, secondary to enzyme induction.