Miracle-dz/UniFAR-FTUs huggingface dataset:
RipA, a Cytoplasmic Membrane Protein Conserved among Francisella Species, Is Required for Intracellular Survival

ABSTRACT Francisella tularensis is a highly virulent bacterial pathogen that invades and replicates within numerous host cell types, including macrophages and epithelial cells. In an effort to better understand this process, we screened a transposon insertion library of the F. tularensis live vaccine strain (LVS) for mutant strains that invaded but failed to replicate within alveolar epithelial cell lines. One such strain isolated from this screen contained an insertion in the gene FTL_1914, which is conserved among all sequenced Francisella species yet lacks significant homology to any gene with known function. A deletion strain lacking FTL_1914 was constructed. This strain did not replicate in either epithelial or macrophage-like cells, and intracellular replication was restored by the wild-type allele in trans. Based on the deletion mutant phenotype, FTL_1914 was termed ripA (required for intracellular proliferation, factor A). Following uptake by J774.A1 cells, F. tularensis LVS ΔripA colocalized with LAMP-1 then escaped the phagosome at the same rate and frequency as wild-type LVS-infected cells. Electron micrographs of the F. tularensis LVS ΔripA mutant demonstrated the reentry of the mutant bacteria into double membrane vacuoles characteristic of autophagosomes in a process that was not dependent on replication. The F. tularensis LVS ΔripA mutant was significantly impaired in its ability to persist in the lung and in its capacity to disseminate and colonize the liver and spleen in a mouse model of pulmonary tularemia. The RipA protein was expressed during growth in laboratory media and localized to the cytoplasmic membrane. Thus, RipA is a cytoplasmic membrane protein conserved among Francisella species that is required for intracellular replication within the host cell cytoplasm as well as disease progression, dissemination, and virulence.
Konzentrations- und Ungleichheitsindizes – ein Überblick am Beispiel der Textilindustrie

In empirischen Untersuchungen werden Konzentrations- und Ungleichheitsmase oftmals verwendet, um Informationen uber die raumliche Verteilung von Beschaftigung in einer Industrie zu komprimieren. Das sich aus einer Maszahl ergebende Bild uber das Ausmas an Konzentration (Ungleichheit) sowie die Veranderungen uber die Zeit hinweg konnen jedoch in Abhangigkeit des gewahlten Index divergieren. Grundsatzlich kann zwischen absoluten und relativen Indizes einerseits sowie zwischen Konzentrations- und Ungleichheitsindizes andererseits unterschieden werden. Das Papier geht auf die unterschiedlichen Charakteristika der einzelnen Indizes ein und zeigt auf, was bei der Wahl des Index fur empirische Studien zu beachten ist. Die Analyse zeigt zudem, dass es nicht einen Index gibt, der anderen Indizes uberlegen ist. Je nach Fragestellung sollte daher entschieden werden, welcher Index der geeignetste ist.
Motivation to Pursue Green Supply Chain Management

Green supply chain management (GSCM) is a highly discussed topic. However, not all companies deal with GSCM in the same way. The main aim of this paper to understand a company's GSCM motivation and how this motivation is linked to perceived stakeholder pressures, company's GSCM practices and performance. The authors report the findings of a survey on GSCM motivations of a sample of 101 manufacturing companies. We see clear differences in why companies are motivated to pursue GSCM. Based on these different motivations, we could explain differences in perceived stakeholder pressure and performance. Interestingly, only companies who are motivated by competitive and ecological motivators are able to green their supply chain in a sustainable way. GSCM motivation is a sensitive topic and as such might cause respondents to provide socially desired answers. However, our analyses show clear variances in the answers, indicating that our measures are valid. Our study shows that in order to achieve sustainable GSCM, companies should be convinced and support ecological responsibility and competitive motives for pursuing GSCM. Also stakeholders can learn from this study: they need to focus their attention towards companies whom they have the highest impact on. First, our study tests a framework for GSCM motivations and shows that there are different patterns in why companies pursue GSCM. Second, we show that these differences in motivation impact perceived stakeholder pressure, company characteristics and performance.
Transgenic Zebrafish as Sentinels for Aquatic Pollution

Abstract: Using the golden mutant zebrafish having a decrease in interfering pigmentation, we are developing transgenic lines in which DNA motifs that respond to selected environmental pollutants are capable of activating a reporter gene that can be easily assayed. We have begun with three response elements that recognize three important classes of foreign chemicals. Aromatic hydrocarbon response elements (AHREs) respond to numerous polycyclic hydrocarbons and halogenated coplanar molecules such as 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD; dioxin) and polychlorinated biphenyls. Electrophile response elements (EPREs) respond to quinones and numerous other potent electrophilic oxidants. Metal response elements (MREs) respond to heavy metal cations such as mercury, copper, nickel, cadmium, and zinc. Soon, we will include estrogen response elements (EREs) to detect the effects of environmental endocrine disruptors, and retinoic acid response elements (RARE, RXRE) to detect the effects of retinoids in the environment. Each of these substances is known to be bioconcentrated in fish to varying degrees; for example, 10−17 M TCDD in a body of water becomes concentrated to approximately 10−12 M TCDD in a fish, where it would act upon the AHRE motif and turn on the luciferase (LUC) reporter gene. The living fish as a sentinel will not only be assayed intact in the luminometer, but‐upon several days or weeks of depuration‐would be usable again. To date, we have established that zebrafish transcription factors are able to recognize both mammalian and trout AHRE, EPRE, and MRE sequences in a dose‐dependent and chemical‐class‐specific manner, and that expression of both the LUC and jellyfish green fluorescent protein (GFP) reporter genes is easily detected in zebrafish cell cultures and in the intact live zebrafish. Variations in sensitivity of this model system can be achieved by increasing the copy number of response elements and perhaps by altering the sequence of each core consensus response element and flanking regions. This transgenic technology should allow for a simple, exquisitely sensitive, and inexpensive assay for monitoring aquatic pollution. We have already initiated studies using sentinel zebrafish to monitor a public drinking water source.
Incidental findings of implant complications on postimplantation CBCTs: A cross‐sectional study

BACKGROUND Survival rates of dental implants are reported to be very high and seem to indicate minimal complications related to dental implants. PURPOSE The aim of this report was to evaluate in a cross-sectional study the prevalence of implant positioning complications as appears in postimplantation Cone-Beam Computerized Tomography (CBCT) in two of the major imaging facilities in Bucharest, Romania. METHODS Demographic and implant data was collected from two of the three main CBCT facilities in Bucharest, Romania. All postimplantation CBCT imaging were assessed and evaluated for the presence of different implant positioning related complications. Data were entered into Excel spreadsheet and analyzed statistically. RESULTS Of the 2323 CBCT's that were analyzed, a total of 160 (6.89%) presented with implant positioning related complications. Out of those, 62 cases revealed penetration of the implant to adjacent anatomic structure. More specifically, there were 21 instances of sinus penetration, 19 instances of nasal cavity penetration, 9 instances of inferior alveolar canal penetration, and 13 instances of lingual plate perforations. There were also 15 cases of adjacent tooth injury noted. CONCLUSIONS Despite the popularity of dental implants, the surgical placement of these implants is not a riskless procedure. Implant mal-positioning might be life-threatening and can lead to serious bleeding, airway obstruction, and unnecessary postoperative surgeries. Complications of dental implants are not obsolete and dental implant associated problems may not be apparent immediately. Surgeons must have proper training and use evidenced-based treatment planning in order to prevent dental implant complications.
Integrating Research on Temperament and Childhood Psychopathology: Its Pitfalls and Promise

This article discusses the promise and problems associated with integrating research on child temperament and research on childhood psychopathology. Unfortunately, these 2 extensive and influential areas of psychological research with children have largely been conducted independently of each other. This article provides a summary of the disciplinary, conceptual, and methodological issues that have hampered an integration of these 2 important bodies of research. It also highlights the great promise that such an integration could have for advancing causal theories of childhood disorders and for eventually improving the treatment provided to children with serious emotional and behavioral disturbances.
Cyclooxygenase-2 S-nitrosylation in salivary gland acinar cell inflammatory responses to Porphyromonas gingivalis: modulatory effect of ghrelin

Disturbances in nitric oxide synthase (NOS) system and the excessive prostaglandin (PGE2) generation are well-recognized features of oral mucosal inflammatory responses to periodontopathic bacterium, P. gingivalis. Employing rat sublingual gland acinar cells, we show that P. gingivalis LPS-induced up-regulation in PGE2 generation and the enhancement in inducible (i) iNOS activity was associated with COX-2 activation through S-nitrosylation, and accompanied by the suppression in cSrc activity and the impairment in constitutive (c) cNOS phosphorylation. Further, we demonstrate that the countering effect of peptide hormone, ghrelin, on the LPS-induced changes was reflected in the increased cNOS activation through phosphorylation, repression in iNOS induction, and the reduction in PGE2 generation associated with the loss of COX-2 protein S-nitrosylation. Moreover, the effect of ghrelin on cNOS phosphorylation and the LPS-induced COX-2 S-nitrosylation was susceptible to the blockage by cSrc inhibition. Our findings suggest that P. gingivalis-induced up-regulation in iNOS leads to COX-2 S-nitrosylation and up-regulation in PGE2 generation, and that the countering effect of ghrelin is mediated through Src-dependent cNOS activation that is obligatory for the maintenance of iNOS gene suppression.
Prise en charge de l'insomnie chronique primaire par les médecins généralistes ambulatoires de l'arc alpin : exploration des difficultés ressenties

Objectif : Quelles sont les difficultes ressenties par les medecins generalistes dans la prise en charge de l'insomnie chronique primaire ? Methode : Une etude qualitative a ete menee aupres de 13 medecins generalistes volontaires de l'arc Alpin francais. Un echantillon aleatoire en recherche de variation maximale a ete choisi. Les entretiens ont ete diriges entre janvier et aout 2012 par une moderatrice independante grâce a un questionnaire semi-structure, et effectues jusqu'a saturation des donnees. Une analyse thematique des donnees a ete realisee par 2 enquetrices. Resultats : Des difficultes existent dans la prise en charge diagnostique. L'insomnie ne motive pas a elle seule une consultation. Elle est evoquee en fin de consultation, lors du renouvellement ce qui est un frein a la prise en charge du fait du manque de disponibilite et de temps du medecin. C'est un probleme chronique souvent banalise et peu aborde par le patient, entrainant un sous-diagnostic de cette pathologie. Lors de la prise en charge therapeutique les medecins soulignent la difficulte de ne pas ceder au renouvellement d'hypnotique par manque de temps et de motivation mais aussi face a la pression des patients. Ils expriment des difficultes a convaincre les patients et a leur faire changer de mode de vie. Le sevrage est aussi problematique : les difficultes dependent de la duree de prise et du type de traitement, de la dependance, du type de patient et de la peur d'arreter ce traitement. Les medecins evoquent un sentiment d'insatisfaction face au sevrage. Conclusion : Les medecins generalistes rencontrent des difficultes lors de la prise en charge diagnostique, therapeutique et sevrage medicamenteux.
Quantification of Insulin-Like Growth Factor I (IGF-I) Without Interference by IGF Binding Proteins.

A chemiluminescent dot blot assay has been developed by our laboratory for rapid determinations of IGF-I in serum-free conditioned media (CM) collected from cultured cells. In contrast to IGF-I radioimmunoassays (RIAs), the IGF binding proteins (IGFBPs) did not interfere with the dot blot assay and did not require the laborious (and sometimes ineffective) removal of IGFBPs. Although all six IGFBPs were shown to bind to 125I IGF-I, none interfered with IGF-I detection on nitrocellulose dot blots. In contrast, an RIA using the same Oncogene monoclonal antibody (clone 82-9A) showed interference by IGFBP-1, IGFBP-2, and IGFBP-4. The IGF-I dot blot assay was sensitive (0.125 − 8.0 ng IGF-I), specific (assay crossreactivity with IGF-II is less than 1%), and reproducible (intra-assay variance≤ 6%; inter-assay variance <12%) when chemiluminescence was quantified by phosphorimager and Molecular Analyst software (BioRad). The apparent sensitivity of the enhanced chemiluminescence (ECL) reagent to serum, precludes t.
Apoproteínas A1 y B: valores de referencia para la población de manizales

Se determinaron los valores de refernecia de apoproteinas A1 (apo A1) y B (apo B) para la poblacion de Manizales. Para tal efecto fue realizado un muestreo estratificado proporcional de conglomerados. Sobre un total de 186 pacientes se realizaron cuantificaciones de lipidos sericos y apo A1 y apo B, y se calcularon los promedios poblacionales mediante un analisis de distribucion 2 parametrica log-normal. Sobre los datos obtenidos se calcularon los coeficientes de correlacion (r), significancia estadistica de tales coeficientes y analisis de regresion de los valores de aoproteinas con los lipidos sericos, edad y sexo. Los resulatdos obtenidos muestran diferencias en los niveles de apoproteinas por grupos de edad observandose valores inferiores de apo A1 y B en el grupo de personas de 15 a 24 anos. los valores de apo A1 se incrementan hasta los 44 anos en los hombres y van disminuyendo paulatinamente; en las mujeres el incremento se presenta hasta los 59 anos y disminuye ligeramente despues de los 60 anos. Respecto a los valores de apo B se observa el mismo comportamiento. Sin embargo, la correlacion apo A1 y B con edad es muy baja. Se presentaron diferencias estadisticamente significativas entre los promedios de apo A 1 y B por grupos de edad y segun el sexo. Realizadas las correlaciones con los diferentes lipidos sericos los valores mas altos observados fueron A1 con C-HDL (0.38) y de apo B con colesterol total (0.45), con C-LDL (0.34). La significancia de estas correlaciones es de P
[Biotransformation of taxanes].

Enzymes are being used increasingly widely in industrial synthetic chemistry as excellent catalysts. They are capable of catalyzing reactions exhibiting strict enantioselectivity, regioselectivity, or both, under benign conditions. With the use of enzymes, we can avoid not only the tedious blocking and deblocking steps that are common in enantioselective and regioselective organic synthesis, but also the wasting of fossil fuels required for preparing high-temperature and high-pressure conditions. Thus, enzymes are considered to be more satisfactory catalysts than conventional chemical ones from economical and environmental points of view . Microbial cells play a leading role in chemo-enzymatic synthesis because of their great diversity. In an attempt to search for new potent anticancer agents, various microorganisms were used for the transformation of taxanes. Microbial reduction was useful during the preparation of a taxol side-chain synthon, and several microorganisms can reduce the 2-keto-3-(N-benzoylamino)-3-phenyl propionic acid ethyl ester (1) to (2R, 3S)-(-)-N-benzoyl-3-phenyl isoserine ethyl ester (2) in yields as high as 85% with an optical purity of 99% . The endophytic fungi Aspergillus niger 3.4523 [3] and
Changes in the Structure of Wages During the 1980&Apos;S: an Evaluation of Alternative Explanations

During the 1980's, a period in which the average level of real wage rates was roughly stagnant, there were large changes in the structure of relative wages, most notably a huge increase in the relative wages of highly educated workers. This paper attempts to assess the power of several alternative explanations of the observed relative wage changes in the context of a theoretical framework that nests all of these explanations. Our conclusion is that their major cause was a shift in the skill structure of labor demand brought about by biased technological change.
Diabetes of Anterior Pituitary and Adrenal Cortical Origin

In recent years it has become increasingly clear that diabetes mellitus, once considered a disease entity, must in the future be looked upon as a group of diseases which have one common feature—hyperglycemia. Disorders which cause hyperglycemia vary greatly and in essential ways. Although it is possible in some instances to point to reversal of diabetes to a state of cure even after it has persisted for a long time, it must also be recognized that long-sustained hyperglycemia, regardless of its cause, may in itself be sufficient in some individuals to precipitate lasting pancreatic diabetes. The various forms of diabetes which are emerging most clearly (to be added to pure beta cell failure) include pituitary diabetes due to excess of growth hormone, diabetes due to excess of corticotropin (ACTH), and diabetes due to excess of adrenocortical steroids of the 11-oxysteroid type.
Single Doses up to 800 mg of E-52862 Do Not Prolong the QTc Interval – A Retrospective Validation by Pharmacokinetic-Pharmacodynamic Modelling of Electrocardiography Data Utilising the Effects of a Meal on QTc to Demonstrate ECG Assay Sensitivity

Background E-52862 is a Sigma-1 receptor antagonist (S1RA) currently under investigation as a potential analgesic medicine. We successfully applied a concentration-effect model retrospectively to a four-way crossover Phase I single ascending dose study and utilized the QTc shortening effects of a meal to demonstrate assay sensitivity by establishing the time course effects from baseline in all four periods, independently from any potential drug effects. Methods Thirty two healthy male and female subjects were included in four treatment periods to receive single ascending doses of 500 mg, 600 mg or 800 mg of E-52862 or placebo. PK was linear over the dose range investigated and doses up to 600 mg were well tolerated. The baseline electrocardiography (ECG) measurements on Day-1 were time-matched with ECG and pharmacokinetic (PK) samples on Day 1 (dosing day). Results In this conventional mean change to time-matched placebo analysis, the largest time-matched difference to placebo QTcI was 1.44 ms (90% CI: -4.04, 6.93 ms) for 500 mg; -0.39 ms (90% CI: -3.91, 3.13 ms) for 600 mg and 1.32 ms (90% CI: -1.89, 4.53 ms) for 800 mg of E-52862, thereby showing the absence of any QTc prolonging effect at the doses tested. In addition concentration-effect models, one based on the placebo corrected change from baseline and one for the change of QTcI from average baseline with time as fixed effect were fitted to the data confirming the results of the time course analysis. Conclusion The sensitivity of this study to detect small changes in the QTc interval was confirmed by demonstrating a shortening of QTcF of -8.1 (90% CI: -10.4, -5.9) one hour and -7.2 (90% CI: -9.4, -5.0) three hours after a standardised meal. Trial Registration EU Clinical Trials Register EudraCT 2010 020343 13
Molecular characterization of human immunodeficiency virus type 1 cloned directly from uncultured human brain tissue: identification of replication-competent and -defective viral genomes

All presently available replication-competent proviral clones of human immunodeficiency virus type 1 (HIV-1) are derived from cell culture-amplified virus. Since tissue culture is highly selective for viral strains with an in vitro growth advantage, such clones may not be representative of the biologically relevant virus present in vivo. In this study, we report the molecular cloning and genotypic characterization of 10 HIV-1 genomes directly from uncultured brain tissue of a patient with AIDS dementia complex. Targeting unintegrated circular HIV-1 molecules for recombinant lambda phage cloning, we obtained four full-length genomes with one or two long terminal repeats (LTRs), three defective genomes with internal deletions, two rearranged genomes with inverted LTR sequences, and one integrated proviral half with flanking cellular sequences. Nucleotide sequence analysis of these clones demonstrated chromosomal integration, circle formation, genomic inversion, and LTR-mediated autointegration of HIV-1 genomes in vivo. Comparison of a 510-bp hypervariable envelope region among 8 lambda phage-derived and 12 polymerase chain reaction-derived clones from the same brain specimen identified a predominant viral form as well as genetically divergent variants. Variability among 19 of 20 clones ranged between 0.2 and 1.2%. One clone exhibited 8.2% nucleotide sequence differences consisting almost exclusively of G-to-A changes. Transfection of the four full-length HIV-1 genomes identified one clone (YU-2) as replication competent and exhibiting growth characteristics similar to those of tissue culture-derived macrophage tropic strains of HIV-1. These results demonstrate, for the first time, that replication-competent HIV-1 genomes, complex mixtures of defective viral forms, and chromosomally integrated provirus persist in vivo. In addition, the brain-derived viral clones are expected to prove valuable for future studies of macrophage and neurotropism as well as for the analysis of other viral properties that are subject to in vitro selection pressures.
Performance Evaluation of WDM Systems Through Multicanonical Monte Carlo Simulations

In wavelength-division-multiplexed (WDM) systems, performance is affected by the bit patterns on the various channels and, in order to account for this pattern dependence, one should perform a large number of simulations, each by using different patterns of suitable length in all channels and then average all results. However, since the number of patterns to be considered for averaging could be considerable, this approach would be very demanding from a computational point of view, even using multicanonical Monte Carlo (MMC) simulations. In single-channel systems, pattern dependence can be accounted for through the pattern perturbation method, a computationally efficient way for performing a random walk over an extended state space, which includes, in addition to noise components, also the transmitted bit pattern. In this way, not only the most relevant noise configurations but also the most relevant bit patterns (those having a major impact on the error events) are sampled more frequently by the MMC simulation, leading to enhanced efficiency in estimating the error probability. Here, the pattern perturbation method is extended to the WDM case, and simulations results are reported to show the effectiveness of the proposed approach.