Miracle-dz/UniFAR-FTUs huggingface dataset:
Endobronchial ultrasound with transbronchial needle aspiration for restaging the mediastinum in lung cancer.

PURPOSE To investigate the sensitivity and accuracy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for restaging the mediastinum after induction chemotherapy in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS One hundred twenty-four consecutive patients with tissue-proven stage IIIA-N2 disease who were treated with induction chemotherapy and who had undergone mediastinal restaging by EBUS-TBNA were reviewed. On the basis of computed tomography, 58 patients were classified as having stable disease and 66 were judged to have had a partial response. All patients subsequently underwent thoracotomy with attempted curative resection and a lymph node dissection regardless of EBUS-TBNA findings. RESULTS Persistent nodal metastases were detected by using EBUS-TBNA in 89 patients (72%). Of the 35 patients in whom no metastases were assessed by EBUS-TBNA, 28 were found to have residual stage IIIA-N2 disease at thoracotomy. The majority (91%) of these false negative results were due to nodal sampling error rather than detection error. Overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of EBUS-TBNA for mediastinal restaging after induction chemotherapy were 76%, 100%, 100%, 20%, and 77%, respectively. CONCLUSION EBUS-TBNA is a sensitive, specific, accurate, and minimally invasive test for mediastinal restaging of patients with NSCLC. However, because of the low negative predictive value, tumor-negative findings should be confirmed by surgical staging before thoracotomy.
The FEN‐1 family of structure‐specific nucleases in eukaryotic dna replication, recombination and repair

Unlike the most well‐characterized prokaryotic polymerase, E. Coli DNA pol I, none of the eukaryotic polymerases have their own 5′ to 3′ exonuclease domain for nick translation and Okazaki fragment processing. In eukaryotes, FEN‐1 is an endo‐and exonuclease that carries out this function independently of the polymerase molecules. Only seven nucleases have been cloned from multicellular eukaryotic cells. Among these, FEN‐1 is intriguing because it has complex structural preferences; specifically, it cleaves at branched DNA structures. The cloning of FEN‐1 permitted establishment of the first eukaryotic nuclease family, predicting that S. cerevisiae RAD2 (S. pombe Rad13) and its mammalian homolog, XPG, would have similar structural specficity. The FEN‐1 nuclease family includes several similar enzymes encoded by bacteriophages. The crystal structures of two enzymes in the FEN‐1 nuclease family have been solved and they provide a structural basis for the interesting steric requirements of FEN‐1 substrates. Because of their unique structural specificities, FEN‐1 and its family members have important roles in DNA replication, repair and, potentially, recombination. Recently, FEN‐1 was found to specifically associate with PCNA, explaining some aspects of FEN‐1 function during DNA replication and potentially in DNA repair.
Complex Formation with Rev1 Enhances the Proficiency of Saccharomyces cerevisiae DNA Polymerase ζ for Mismatch Extension and for Extension Opposite from DNA Lesions

ABSTRACT Rev1, a Y family DNA polymerase (Pol) functions together with Polζ, a B family Pol comprised of the Rev3 catalytic subunit and Rev7 accessory subunit, in promoting translesion DNA synthesis (TLS). Extensive genetic studies with Saccharomyces cerevisiae have indicated a requirement of both Polζ and Rev1 for damage-induced mutagenesis, implicating their involvement in mutagenic TLS. Polζ is specifically adapted to promote the extension step of lesion bypass, as it proficiently extends primer termini opposite DNA lesions, and it is also a proficient extender of mismatched primer termini on undamaged DNAs. Since TLS through UV-induced lesions and various other DNA lesions does not depend upon the DNA-synthetic activity of Rev1, Rev1 must contribute to Polζ-dependent TLS in a nonenzymatic way. Here, we provide evidence for the physical association of Rev1 with Polζ and show that this binding is mediated through the C terminus of Rev1 and the polymerase domain of Rev3. Importantly, a rev1 mutant that lacks the C-terminal 72 residues which inactivate interaction with Rev3 exhibits the same high degree of UV sensitivity and defectiveness in UV-induced mutagenesis as that conferred by the rev1Δ mutation. We propose that Rev1 binding to Polζ is indispensable for the targeting of Polζ to the replication fork stalled at a DNA lesion. In addition to this structural role, Rev1 binding enhances the proficiency of Polζ for the extension of mismatched primer termini on undamaged DNAs and for the extension of primer termini opposite DNA lesions.
On the evolutionary origins of the bacterial phosphoenolpyruvate:sugar phosphotransferase system

The genes encoding the proteins of the fructose‐specific phosphotransferase system (PTS) of Rhodobacter capsulatus were sequenced, and the deduced amino acyl sequences of the energy‐coupling protein, Enzyme I, and the transport protein, Enzyme IItru, were compared with published sequences. Enzyme I was found to be homologous to pyruvate: phosphate dikinase of plants, while Enzyme IIfru was found to be homologous to the insulin‐responsive glucose facilitator of mammals. The evolutionary and functional implications of these findings are discussed.
Formation of Giant Planets by Fragmentation of Protoplanetary Disks

The evolution of gravitationally unstable protoplanetary gaseous disks has been studied with the use of three-dimensional smoothed particle hydrodynamics simulations with unprecedented resolution. We have considered disks with initial masses and temperature profiles consistent with those inferred for the protosolar nebula and for other protoplanetary disks. We show that long-lasting, self-gravitating protoplanets arise after a few disk orbital periods if cooling is efficient enough to maintain the temperature close to 50 K. The resulting bodies have masses and orbital eccentricities similar to those of detected extrasolar planets.
Inhibition by sugars of Candida albicans adherence to human buccal mucosal cells and corneocytes in vitro

The adherence and inhibition of adherence of Candida albicans to epithelial cells was studied for human cells obtained from skin (corneocytes) and buccal mucosa. The yeast adhered to both kinds of cells, although in somewhat greater numbers to buccal mucosal cells. Adherence to the cells of different individuals was variable, but the ratios of values for the two kinds of cells from a single subject were quite constant. Inhibition of adherence was produced by several sugars, including the aminosugars mannosamine, glucosamine, and galactosamine. The pattern of inhibition produced by the sugars was similar for the two types of cells. Pretreatment of the yeast with mannosamine, followed by dilution to a subinhibitory concentration, produced some inhibition of yeast-buccal mucosal cell attachment, indicating some direct interaction between the sugar and the fungal cell. These data suggest that the mechanisms whereby C. albicans attaches to corneocytes and to buccal mucosal cells are probably similar.
A Review of Epidemiologic Studies of Nonnarcotic Analgesics and Chronic Renal Disease

&NA; Abbreviations used in this article: AN, analgesic nephropathy; CI, confidence interval; CRD, chronic renal disease; ESRD, end‐stage renal disease; NAPAP, N‐acetyl‐p‐aminophenol; NSAIDs, nonsteroidal antiinflammatory drugs; RPN, renal papillary necrosis; RR, risk ratio.
Loss of endosomal/lysosomal membrane impermeability is an early event in amyloid Aβ1‐42 pathogenesis

Previous studies have implicated the failure to degrade aggregated Aβ1‐42 in late endosomes or secondary lysosomes as a mechanism for the accumulation of β‐amyloid in Alzheimer's disease. We examined the consequences of intracellular accumulation of Aβ1‐42 on the integrity of the endosomal/lysosomal compartment by monitoring Lucifer Yellow fluorescence and the release of lysosomal hydrolases into the soluble, cytosolic fraction. In control cells, the Lucifer Yellow fluorescence is observed as punctate staining in a perinuclear distribution with no apparent cytoplasmic fluorescence, consistent with its localization in late endosomes or secondary lysosomes. After incubation with Aβ1‐42 for 6 hr, a loss of lysosomal membrane impermeability is observed as evidenced by redistribution of the fluorescence to a diffuse, cytoplasmic pattern. The loss of lysosomal membrane impermeability is correlated with Aβ1‐42 accumulation, since incubation of the cells with the nonaccumulating isoform of amyloid, Aβ1‐40, does not induce leakage. The same results were obtained using the release of soluble lysosomal hydrolases, cathepsin D and β‐hexosaminidase, into the cytosol as an assay for the leakage of lysosomal contents. Together, our results suggest that the loss of lysosomal membrane impermeability may be an early event in Aβ pathogenesis, and provide an explanation for the miscompartmentalization of extracellular and cytoplasmic components observed in Alzheimer's disease (AD). The release of hydrolases may further cause the breakdown of the cytoskeleton and the blebbing of the plasma membrane, and the leakage of heparan sulfate glycosaminoglycans from the lysosome may ultimately promote the assembly of tau into neurofibrillary tangles (NFT). J. Neurosci. Res. 52:691–698, 1998. © 1998 Wiley‐Liss, Inc.
Exposure-affecting factors of dairy farmers' exposure to inhalable dust and endotoxin.

INTRODUCTION Studies on determinants of dairy farmers' exposure to dust and endotoxin have been sparse and so far none has addressed the combined effect of tasks and farm characteristics. OBJECTIVE To study whether and how work tasks and specific stable characteristics influence the level of dairy farmers' personal exposure to inhalable dust and endotoxin. METHODS We applied an observational design involving full-shift repeated personal measurements of inhalable dust and endotoxin exposure among 77 subjects (owners and farm workers) from 26 dairy farms. Performed tasks were self-registered in activity diaries, and information on stable characteristics was collected through personal interviews and walk-through surveys. Associations between exposure, tasks, and stable characteristics were examined in linear mixed-effect models with individual and farm treated as random effects. Separate as well as combined models for tasks and stable characteristics were elaborated. RESULTS The 124 personal samples collected had a geometric mean level (geometric standard deviation) of 360 EU m(-3) (3.8) for endotoxin exposure and of 1.0mg m(-3) (2.7) for dust exposure. Identified factors that increased endotoxin exposure included a lower outdoor temperature and use of slope-based or back-flushed slurry systems along with milking, distribution of bedding, and handling of feed and seeds in barns. For dust, exposure was higher when fully automatic (robotic) milking was used and during re-penning of animals, handling of feed and seeds, handling of silos and when distributing bedding. Dust exposure increased also as a result of use of rail feed dispensers in a model without fully automatic milking. CONCLUSIONS The current exposure to dust and in particular endotoxin among Danish dairy farmers demand effective strategies to reduce their exposure. The present findings suggest that future interventions should focus on feeding and manure handling systems. Use of respirators during handling of feed and distribution of bedding should be advised until adequate risk management measures have been established. The expected increased use of fully automatic milking in the future might increase dust exposure of dairy farmers.
An Association Study of Polymorphisms in JAK3 Gene with Lung Cancer in the Korean Population

Purpose The genetic alteration of the janus kinases (JAKs), non-receptor tyrosine kinase, is related to the development of human cancers. However, little is known about how the sequence variation of JAK3 contributes to the development of lung cancer. This study investigated whether polymorphisms at the promoter region of the JAK3 gene are associated with the risk of lung cancer in the Korean population. Materials and Methods A total of 819 subjects, including 409 lung cancer patients and 410 healthy controls were recruited. The SNaPshot assay and polymerase chain reaction-restriction fragment length polymorphism analysis were used, and logistic regression analyses were performed to characterize the association between polymorphisms of JAK3 and lung cancer risk. Results Three polymorphisms (-672 G>A, +64 A>G and +227 G>A) of JAK3 were analyzed for large-scale genotyping (n=819). Statistical analyses revealed that polymorphisms and haplotypes in the JAK3 gene were not significantly associated with lung cancer. Conclusion JAK3 gene was not significantly associated with the risk of lung cancer in the Korean population.
Un test statistique pour la détection d'anomalies basé sur l'erreur de reconstruction de l'ACP à noyau

La detection d'anomalies concerne l'identification de points dont le comportement devie d'un modele dit nominal. On presente ici un test statistique non parametrique pour la detection d'anomalies dont la statistique de test est basee sur la distance entre un point a tester, represente dans un espace de redescription, et sa projection sur l'espace genere par une Analyse en Composantes Principales a noyau realisee sur un echantillon tire d'une loi de probabilite nominale. La methode est testee sur des donnees reelles et artificielles, et montre de bonnes performances en ce qui concerne a la fois de l'erreur de type-I et de type-II par rapport a des methodes usuelles de detection d'anomalies. Cette communication est basee sur un article recemment publie par les memes auteurs.
Achilles, a New Family of Transcriptionally Active Retrotransposons from the Olive Fruit Fly, with Y Chromosome Preferential Distribution

Sex chromosomes have many unusual features relative to autosomes. The in depth exploration of their structure will improve our understanding of their origin and divergence (degeneration) as well as the evolution of genetic sex determination pathways which, most often are attributed to them. In Tephritids, the structure of Y chromosome, where the male-determining factor M is localized, is largely unexplored and limited data concerning its sequence content and evolution are available. In order to get insight into the structure and organization of the Y chromosome of the major olive insect pest, the olive fly Bactrocera oleae, we characterized sequences from a Pulse Field Gel Electrophoresis (PFGE)-isolated Y chromosome. Here, we report the discovery of the first olive fly LTR retrotransposon with increased presence on the Y chromosome. The element belongs to the BEL-Pao superfamily, however, its sequence comparison with the other members of the superfamily suggests that it constitutes a new family that we termed Achilles. Its ~7.5 kb sequence consists of the 5’LTR, the 5’non-coding sequence and the open reading frame (ORF), which encodes the polyprotein Gag-Pol. In situ hybridization to the B. oleae polytene chromosomes showed that Achilles is distributed in discrete bands dispersed on all five autosomes, in all centromeric regions and in the granular heterochromatic network corresponding to the mitotic sex chromosomes. The between sexes comparison revealed a variation in Achilles copy number, with male flies possessing 5–10 copies more than female (CI range: 18–38 and 12–33 copies respectively per genome). The examination of its transcriptional activity demonstrated the presence of at least one intact active copy in the genome, showing a differential level of expression between sexes as well as during embryonic development. The higher expression was detected in male germline tissues (testes). Moreover, the presence of Achilles-like elements in different species of the Tephritidae family suggests an ancient origin of this element.
Ermittlung repräsentativer Lastkollektive zur Betriebsfestigkeit von Ackerschleppern

Bei der Entwicklung moderner Landmaschinen besteht der Zielkonflikt zwischen Zuverlassigkeit und Dauerhaltbarkeit auf der einen Seite und Kosten- und Fahrzeugeffizienz auf der anderen Seite. Reprasentative Lastkollektive zur Beschreibung der Betriebsbelastungen im Nutzungsbetrieb sind dabei eine zentrale Forderung zur Dimensionierung von Bauteilen. Eine grose Herausforderung besteht in der adaquaten Beschreibung der Nutzungsvariabilitat einer Kundenpopulation und der Identifikation der kritischsten Kombination der Lastfalle. Ziel der vorliegenden Arbeit ist die Ermittlung und Erprobung eines Verfahrens zur Beschreibung der wirkenden Belastungen von Traktoren im Anwendungsbetrieb. Im Fokus steht die Ableitung reprasentativer Lastkollektive, die als Grundlage fur Betriebsfestigkeitsprufungen dienen. Inhaltlich basiert das eingesetzte Verfahren auf der systematischen Trennung der auftretenden Betriebszustande (Faktormodell) und deren Einsatzverteilung im Kundenbetrieb (Nutzungsmodell). Die im Faktormodell identifizierten Betriebszustande werden dabei durch reprasentative Lastmessungen im Kundenbetrieb beschrieben. Mittels Monte-Carlo-Simulation erfolgt die Erzeugung einer beliebigen Anzahl virtueller Nutzer auf Basis der definierten Randbedingungen des Nutzungsmodells. Die erzeugten Nutzer besitzen jeweils eine individuelle Einsatzverteilung und das Verfahren ordnet ihnen abhangig von der vorgegebenen Nutzungsdauer die Lastdaten der korrespondierenden Betriebszustande zu. Die ausgewahlten Lastdaten werden entsprechend der spezifischen Einsatzverteilung in Form von Pseudo-Schadigungszahlen fur die Ziellebensdauer des Fahrzeugs aufsummiert. Die ermittelten Gesamtschadigungen sind dabei als Mas fur die Harte der Belastungen im Anwendungsbetrieb zu verstehen. Auf Basis der Verteilung der Gesamtschadigungen einer Nutzerpopulation erfolgt die Identifikation des Referenz- oder Auslegungsnutzers (z. B.: 95% oder 99% Quantil). Die hinter dem ausgewahlten Nutzer steckende Kombination der Lastfalle ermoglicht die Berechnung von reprasentativen Lastkollektiven. Das Verfahren ist zur Ermittlung von Eingangsbelastungen fur Prufprozeduren und die numerische Betriebsfestigkeitssimulation nutzbar. Es eignet sich weiterhin zur Durchfuhrung von Sensitivitatsstudien bei der Entwicklung neuer Fahrzeuge wie auch zur Identifikation von marktspezifischem Kostenreduzierungspotential.
Cardiac Disease in Chronic Kidney Disease: Current Understandings and Opportunities for Change

Cardiovascular disease (CVD) is prevalent in patients with kidney disease: in populations prior to dialysis, on dialysis and after transplantation. Publications over the last decade have focused on this, and more recently, patients with cardiac disease are now recognized as being at increased risk in the presence of even mild kidney dysfunction. The presence of both traditional and non-traditional risk factors contributes to this overwhelming burden of cardiovascular disease in patients with chronic kidney disease (CKD). Recent studies have focused on the impact of anemia and disorders of mineral metabolism on CVD outcomes, in the context of inflammation and evidence of cytokine activation. Cross-sectional and prospective observational studies have led to improved understanding, and generated novel hypotheses. To date, no clinical trial has determined the positive impact of interventions targeted at these novel risk factors. This overview describes the current state of knowledge and emphasizes the interplay between CVD and CKD as two aspects of a set of pathophysiological processes, which impact on patient outcomes.
Pervasive Healthcare

Summary Objectives: The aging of the population creates pressure on the healthcare systems in various ways. A massive increase of chronic disease conditions and age-related illness are predicted as the dominant forces driving the future health care. The objective of this paper is to present future research demands in pervasive healthcare with the goal to meet the healthcare challenges by paving the way for a pervasive, user-centered and preventive healthcare model. Methods: This paper presents recent methodological approaches and proposes future research topics in three areas: i) pervasive, continuous and reliable long-term monitoring systems; ii) prevention through pervasive technology as a key element to maintain lifelong wellness; and iii) design and evaluation methods for ubiquitous, patient-centric technologies. Results: Pervasive technology has been identified as a strong asset for achieving the vision of user-centered preventive healthcare. In order to make this vision a reality, new strategies for design, development and evaluation of technology have to find a common denominator and consequently interoperate. Moreover, the potential of pervasive health-care technologies offers new opportunities beyond traditional disease treatment and may play a major role in prevention, e.g. motivate healthy behavior and disease prevention throughout all stages of life. In this sense, open challenges in future research have to be addressed such as the variability of health indicators between individuals and the manner in which relevant health indicators are provided to the users in order to maximize their motivation to mitigate or prevent unhealthy behaviors. Additionally, collecting evidence that pervasive technology improves health is seen as one of the toughest challenges. Promising approaches are recently introduced, such as “clinical proof-of-concept” and balanced observational studies. Conclusions: The paper concludes that pervasive healthcare will enable a paradigm shift from the established centralized healthcare model to a pervasive, user-centered and preventive overall lifestyle health management. In order to provide these new opportunities everywhere, anytime and to anyone, future research in the fields of pervasive sensing, pervasive prevention and evaluation of pervasive technology is inevitably needed.
Difusão singular em um sistema confinado

Padroes de invariância de escala, associados a leis de potencia, sao frequentemente observados na natureza. Alguns exemplos sao: flutuacoes em precos de itens de bolsa de valores e outros investimentos, alem do espectro de energia em sistemas turbulentos. Esses dois sistemas e varios outros que exibem invariância de escala tem propriedades em comum: compoem-se de varios elementos que interagem de forma nao linear, estao fora do equilibrio e exibem auto-organizacao. Invariância de escala tambem e encontrada nas correlacoes observadas no ponto critico de sistemas que apresentam transicoes de fase. O conceito de criticalidade auto-organizada sugere que as propriedades de invariância emergem espontaneamente em sistema complexos. Varios modelos exibem propriedades criticamente auto-organizadas, entre eles percolacao invasiva, pilhas de areia e o modelo de desniveis, no entanto, nao se sabe ao certo quais os ingredientes necessarios para criticalidade emergir. Sabe-se que essa propriedade se manifesta em alguns sistemas difusivos nao lineares. Nesse trabalho, introduzimos um potencial confinante em um modelo de difusao unidimensional com uma nao linearidade singular no coeficiente de difusao e analisamos a influencia dessa mudanca no estado estacionario do sistema. Conseguimos, entao, derivar uma equacao de difusao do modelo e obtemos uma solucao para o perfil de densidade. Nossa solucao analitica concorda perfeitamente com os resultados numericos. Fizemos, ainda, um estudo estatistico do perfil de avalanches do modelo, e obtemos perfis de avalanche em leis de potencia, o que normalmente nao e observado em outros sistemas unidimensionais. Analisamos, ainda, como esses perfis variam na medida que se aumenta o confinamento, e usando transformacoes de escala encontramos uma curva universal para os perfis de distribuicao de tamanhos de avalanche. Nossos resultados demonstram que a acao do confinamento em um sistema unidimensional pode levar ao surgimento da invariância de escala.