Miracle-dz/UniFAR-FTUs huggingface dataset:
Bone morphogenetic protein 4 expressed in esophagitis induces a columnar phenotype in esophageal squamous cells.

BACKGROUND & AIMS Barrett's esophagus (BE) is a metaplastic condition in which normal squamous esophageal epithelium is replaced by columnar epithelium. It is proposed that one of the possible mechanisms is dedifferentiation of squamous epithelium into columnar epithelium. The pathophysiology through which this metaplasia occurs is unknown. A recent study by serial analysis of gene expression showed that bone morphogenetic protein 4 (BMP-4) is uniquely expressed in BE. In this study, the role of the BMP pathway in the metaplastic transformation of normal squamous cells into columnar cells was examined. METHODS Tissues from patients with esophagitis and BE and in an esophagitis-BE rat model were examined for the activation of the BMP pathway. Short-term cultures of primary normal squamous esophageal cells were treated with BMP-4, and cell biological changes were examined by Western blot analysis, immunohistochemistry, and microarrays. RESULTS In both human and rat tissues, the BMP pathway proved to be activated in esophagitis and BE. Upon incubation of squamous cell cultures with BMP-4, the cytokeratin expression pattern showed a shift that was consistent with columnar epithelium. Involvement of the BMP pathway was suggested by up-regulation of Phosphorylated-Smad 1/5/8 (P-Smad 1/5/8) that was effectively blocked by Noggin, a BMP antagonist. Comparison of the gene expression profiles of squamous cells, BMP-4-treated squamous cells, and BE cells showed a significant shift in the profile of the BMP-4-treated squamous cells toward that of the cultured BE cells. CONCLUSIONS These results suggest that the BMP pathway could play a role in the transformation of normal esophageal squamous cells into columnar cells.
Compromised blood-nerve barrier, astrogliosis, and myelin disruption in optic nerves during fatal murine cerebral malaria.

We examined the optic nerve, as an analogous tissue to brain white matter, to assess possible relationships between changes in the blood-nerve barrier, axonal integrity, and astrocyte morphology in the central nervous system during fatal murine cerebral malaria (FMCM). In the FMCM model, namely, CBA mice infected with Plasmodium berghei ANKA, neurological symptoms begin around day 5 post-inoculation (p.i.) and mice become increasingly ill by day 7 p.i. , at which time they lapse into coma and die. Using intravascular perfusion with horseradish peroxidase combined with light and electron microscopy, and GFAP immunohistochemistry, the optic nerves in malaria-infected mice were found to display i) breakdown of the blood-nerve barrier, detectable as early as day 3 p.i. (about 2 days before the onset of neurological symptoms) increasing to peak severity by day 7 p.i. ; ii) monocytosis, vascular congestion, and monocyte adherence to the endothelium in the microvasculature during the later stages of the disease process; iii) an increased incidence of patchy axonal demyelination and degeneration, mostly associated with vascular changes and astrogliosis, beginning at day 5 p.i. and more evident by day 7 p.i. ; and iv) an increased intensity of GFAP immunostaining, detectable from day 3 p.i. and peaking at day 7 p.i. These optic nerve changes were always seen in the infected individuals, though they varied in intensity. The temporal and anatomical coincidence between the compromised blood-nerve barrier, monocyte adherence to the vascular endothelium, astrocyte changes, neuronal degeneration, and demyelination in the optic nerve in FMCM suggests that these factors are mechanistically inter-related. These findings are consistent with the proposed immunopathological nature of FMCM and provide further evidence for the pivotal role of the CNS microvasculature in the disease process. This is the first investigation of involvement of the optic nerve in FMCM and the first demonstration, to our knowledge, of loss of axonal viability in this condition in any CNS tissue. The observed demyelination is consistent with reports by other workers on such changes in the brain in human cerebral malaria.
Fetuin A as a new marker of inflammation in Hashimoto thyroiditis.

AIM Fetuin-A levels are reported to be low as a negative acute phase reactant in systemical inflammatory situations. Hashimoto thyroiditis is characterized with inflammation. In this study, we hypothesised that the serum fetuin A levels could be found to be low due to inflammation in patients with Hashimoto thyroiditis. For this purpose, serum fetuin A levels in patients with Hashimoto thyroiditis were compared with those in healthy subjects. METHODS A total of 85 participants (11 male, 74 female, mean age: 38.60±10.14 years) were included. The patient group consisted of 44 Hashimoto thyroiditis patients with subclinical hypothyroidism (7 male, 37 female) and the control group consisted of 41 healthy subjects (4 male, 37 female). Groups were compared according to their demographic, anthropometric and biochemical data and serum fetuin-A levels. Correlation analysis was used for determining the relation between fetuin A levels and clinical parameters. RESULTS Fetuin-A levels of the patient group were found lower than those of the control group (0.58±0.50 g/L versus 1.53±1.60 g/L, P=0.001). Fetuin-A levels were not correlated with clinical parameters such as TSH, C-reactive protein, body mass index, waist circumference, blood pressure, glucose, and lipids. CONCLUSION These findings supported the hypothesis that serum fetuin A levels could be found to be low as a negative acute phase reactant in patients with Hashimoto thyroiditis. Fetuin A can be considered as an indicator of inflammation in Hashimoto thyroiditis.
Simultaneous mobile robot localization and mapping using an adaptive curvature-based environment description

This paper presents an algorithm for simultaneous localization and mapping (SLAM) of office-like environments to use with conventional 2D laser range finders which is based on the extended Kalman filter (EKF) approach. This system employs the set of landmarks extracted from a novel curvature-based environment description. Landmarks include straight-line segments and corners, defined as the intersection of previously detected line segments. Therefore, these corners can be associated to real features of the environment or to virtual ones. In order to provide precise feature estimation, uncertainties will be represented and propagated from single range reading measurements to all stages involved in the feature estimation process. Experimental results provided by the EKF-SLAM algorithm show the ability of the proposed set of landmarks to correctly characterize structured environments.
Peter W. Graham, Jane Austen and Charles Darwin: Naturalists and Novelists

Peter Graham explains in his introduction that his book evolved from ‘‘two long-cherished, initially distinct interests that eventually converged’’ (xi). After years of appreciating the novels of Jane Austen and the works of Charles Darwin, he came to believe that underlying similarities between these figures informed his interest in both, and the present book explores these similarities. Graham admits that his project is not a conventional study of two writers who influenced one another or even shared the same historical period and intellectual milieu—though they were only thirty-four years apart in age, both came from large families among the provincial gentry in the south of England, and Darwin and his family knew Austen’s novels. Graham calls his comparative study ‘‘suggestive rather than definitive, eclectic rather than rigorous’’ (134); classifies his approach as that of an essayist in the manner of Montaigne, ‘‘trying out ideas in a highly personal thought experiment’’ (xvi); and says his book is composed of a ‘‘series of interlocking essays’’ (133) rather than tightly organized, sequential chapters. Having made these disclaimers, alerting the reader what not to expect, Graham commences his study, which if not systematic and historicist in a conventional sense provides many flashes of illumination about its subjects. The book, moreover, is well written and sustains the reader’s interest throughout. The first chapter, ‘‘‘3 or 4 Families in a Country Village,’ or Naturalists, Novelists, Empiricists, and Serendipidists,’’ establishes some of the major parallels between Austen and Darwin. These figures ‘‘possessed congenial temperaments and analogous talents’’; in particular, both ‘‘were keen observers of the world before them, observers who excelled both in notic-
Impacts of Trunk and Soil Injections of Low Rates of Imidacloprid on Hemlock Woolly Adelgid (Hemiptera: Adelgidae) and Eastern Hemlock (Pinales: Pinaceae) Health

ABSTRACT Eastern hemlocks (Tsuga canadensis Carrière) at two sites in southwestern Virginia were treated by trunk and soil injections of imidacloprid to determine the insecticide's impact on hemlock woolly adelgid, Adelges tsugae Annand. Treatments were 25, 50, and 100% of the highest labeled dosage rates for both stem and soil injection. Three and 4 yr after treatment, the half and full rates had significantly reduced A. tsugae populations, which were accompanied by increased new hemlock shoot growth and higher hemlock health scores on a visual rating of tree appearance. Imidacloprid and metabolite concentrations in tissue of treated trees were determined by liquid chromatography—tandem mass spectrometry, and A. tsugae density decreased as imidacloprid concentrations increased in wood tissue. There were no observed A. tsugae populations in all trees with imidacloprid tissue concentrations >413 ppb. Olefin, di-hydroxy, and 6-chloro-nicotinic-acid metabolites were the imidacloprid metabolites recovered in the highest concentrations. This suggests that hemlock metabolism of imidacloprid may increase efficacy of the parent compound. Stem and soil treatments of low rates of systemic imidacloprid reduce adelgid populations and promote hemlock health, but still may provide a remnant food source for beneficial predators.
Organizing and managing care in a changing health system.

OBJECTIVE To examine ways in which the management and organization of medical care is changing in response to the shifting incentives created by managed care. DATA SOURCES Site visits conducted in 12 randomly selected communities in 1996/ 1997. STUDY DESIGN Approximately 35-60 interviews were conducted per site with key informants in healthcare and community organizations; about half were with providers. DATA COLLECTION A standardized interview protocol was implemented across all sites, enabling cross-site comparisons. Multiple respondents were interviewed on each issue. PRINCIPAL FINDINGS A great deal of experimentation and apparent duplication exist in efforts to develop programs to influence physician practice patterns. Responsibility for managing care is being contested by health plans, medical groups and hospitals, as each seeks to accrue the savings that can result from the more efficient delivery of care. To manage the financial and clinical risk, providers are aggressively consolidating and reorganizing. Most significant was the rapid formation of intermediary organizations, such as independent practice arrangements (IPAs), physician-hospital organizations (PHOs), or management services organizations (MSOs), for contracting with managed care organizations. CONCLUSIONS Managed care appears to have only a modest effect on how healthcare organizations deliver medical care, despite the profound effect that managed care has on how providers are organized. Rather than improving the efficiency of healthcare organizations, provider efforts to build large systems and become indispensable to health plans are exacerbating problems of excess capacity. It is not clear if new organizational arrangements will help providers manage the changing incentives they face, or if their intent is to blunt the effects of the incentives by forming larger organizations to improve their bargaining power and resist change.
Childhood and adolescent resiliency, regulation, and executive functioning in relation to adolescent problems and competence in a high-risk sample

This study first examined the respective relations of resiliency and reactive control with executive functioning. It then examined the relationship of these different domains to the development of academic and social outcomes, and to the emergence of internalizing and externalizing problem behavior in adolescence. Resiliency and reactive control were assessed from preschool to adolescence in a high-risk sample of boys and girls (n = 498) and then linked to component operations of neuropsychological executive functioning (i.e., response inhibition, interference control, fluency, working memory/set-shifting, planning, and alertness), assessed in early and late adolescence. Consistent, linear relations were found between resiliency and executive functions (average r = .17). A curvilinear relationship was observed between reactive control and resiliency, such that resiliency was weaker when reactive control was either very high or very low. In multivariate, multilevel models, executive functions contributed to academic competence, whereas resiliency and interference control jointly predicted social competence. Low resiliency, low reactive control, and poor response inhibition uniquely and additively predicted internalizing problem behavior, whereas low reactive control and poor response inhibition uniquely predicted externalizing problem behavior. Results are discussed in relation to recent trait models of regulation and the scaffolded development of competence and problems in childhood and adolescence.This work was supported by NIAAA Grant R01-AA12217 to Robert Zucker and Joel Nigg, NIAAA Grant R37-AA07065 to Robert Zucker and Hiram Fitzgerald, and NIMH Grant R01-MH59105 to Joel Nigg. We are indebted to the families and staff who made the study possible.
Acquisition of EGFR TKI resistance and EMT phenotype is linked with activation of IGF1R/NF-κB pathway in EGFR-mutant NSCLC

Epithelial-mesenchymal transition (EMT) is clinically associated with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in non-small cell lung cancers (NSCLC). However, the mechanisms promoting EMT in EGFR TKI-resistant NSCLC have not been fully elucidated. Previous studies have suggested that IGF1R signaling is involved in both acquired EGFR TKI resistance in NSCLC and induction of EMT in some types of tumor. In this study, we further explored the role of the IGF1R signaling in the acquisition of EMT phenotype associated with EGFR TKI resistance in mutant-EGFR NSCLC. Compared to gefitinib-sensitive parental cells, gefitinib-resistant (GR) cells displayed an EMT phenotype associated with increased migration and invasion abilities with the concomitant activation of IGF1R and NF-κB p65 signaling. Inhibition of IGF1R or p65 using pharmacological inhibitor or specific siRNA partially restored sensitivity to gefitinib with the concomitant reversal of EMT in GR cells. Conversely, exogenous IGF1 induced both gefitinib resistance and accompanying EMT in parental cells. We also demonstrated that IGF1R could phosphorylate downstream Akt and Erk to activate NF-κB p65. Taken together, our findings indicate that activation of IGF1R/Akt/Erk/NF-κB signaling is linked to the acquisition of EGFR TKI resistance and EMT phenotype in EGFR-mutant NSCLC and could be a novel therapeutic target for advanced NSCLC.
Motor, affective and cognitive empathy in adolescence: Interrelations between facial electromyography and self-reported trait and state measures

This study examined interrelations of trait and state empathy in an adolescent sample. Self-reported affective trait empathy and cognitive trait empathy were assessed during a home visit. During a test session at the university, motor empathy (facial electromyography), and self-reported affective and cognitive state empathy were assessed in response to empathy-inducing film clips portraying happiness and sadness. Adolescents who responded with stronger motor empathy consistently reported higher affective state empathy. Adolescents' motor empathy was also positively related to cognitive state empathy, either directly or indirectly via affective state empathy. Whereas trait empathy was consistently, but modestly, related to state empathy with sadness, for state empathy with happiness few trait–state associations were found. Together, the findings provide support for the notion that empathy is a multi-faceted phenomenon. Motor, affective and cognitive empathy seem to be related processes, each playing a different role in the ability to understand and share others' feelings.
The Leukemic Stem Cell Niche: Adaptation to “Hypoxia” versus Oncogene Addiction

Previous studies based on low oxygen concentrations in the incubation atmosphere revealed that metabolic factors govern the maintenance of normal hematopoietic or leukemic stem cells (HSC and LSC). The physiological oxygen concentration in tissues ranges between 0.1 and 5.0%. Stem cell niches (SCN) are placed in tissue areas at the lower end of this range (“hypoxic” SCN), to which stem cells are metabolically adapted and where they are selectively hosted. The data reported here indicated that driver oncogenic proteins of several leukemias are suppressed following cell incubation at oxygen concentration compatible with SCN physiology. This suppression is likely to represent a key positive regulator of LSC survival and maintenance (self-renewal) within the SCN. On the other hand, LSC committed to differentiation, unable to stand suppression because of addiction to oncogenic signalling, would be unfit to home in SCN. The loss of oncogene addiction in SCN-adapted LSC has a consequence of crucial practical relevance: the refractoriness to inhibitors of the biological activity of oncogenic protein due to the lack of their molecular target. Thus, LSC hosted in SCN are suited to sustain the long-term maintenance of therapy-resistant minimal residual disease.
Regulation of the immune system by biodiversity from the natural environment: An ecosystem service essential to health

Epidemiological studies suggest that living close to the natural environment is associated with long-term health benefits including reduced death rates, reduced cardiovascular disease, and reduced psychiatric problems. This is often attributed to psychological mechanisms, boosted by exercise, social interactions, and sunlight. Compared with urban environments, exposure to green spaces does indeed trigger rapid psychological, physiological, and endocrinological effects. However, there is little evidence that these rapid transient effects cause long-term health benefits or even that they are a specific property of natural environments. Meanwhile, the illnesses that are increasing in high-income countries are associated with failing immunoregulation and poorly regulated inflammatory responses, manifested as chronically raised C-reactive protein and proinflammatory cytokines. This failure of immunoregulation is partly attributable to a lack of exposure to organisms (“Old Friends”) from mankind’s evolutionary past that needed to be tolerated and therefore evolved roles in driving immunoregulatory mechanisms. Some Old Friends (such as helminths and infections picked up at birth that established carrier states) are almost eliminated from the urban environment. This increases our dependence on Old Friends derived from our mothers, other people, animals, and the environment. It is suggested that the requirement for microbial input from the environment to drive immunoregulation is a major component of the beneficial effect of green space, and a neglected ecosystem service that is essential for our well-being. This insight will allow green spaces to be designed to optimize health benefits and will provide impetus from health systems for the preservation of ecosystem biodiversity.
Methodology for Droop Control Dynamic Analysis of Multiterminal VSC-HVDC Grids for Offshore Wind Farms

This paper addresses the control of multiterminal voltage-source converters at high-voltage direct current in the context of offshore wind farms. Droop control is commonly used to regulate the dc voltage in this kind of grid, and droop parameters are selected on the basis of steady-state analyses. Here, a control design methodology is proposed based on the frequency-response analysis. This methodology provides a criterion to select the droop gains, taking into account the performance specifications [i.e., the desired voltage errors and the maximum control inputs (currents)]. The application of the methodology is illustrated with a four-terminal grid.
Ultrastructural organization of medial prefrontal inputs to the rhinal cortices

Accumulating evidence suggests that the medial prefrontal cortex (mPFC) plays a critical role in the formation, retrieval and long‐term storage of hippocampal‐dependent memories. Consistent with this, there are direct hippocampal projections to the mPFC. Moreover, the mPFC sends robust projections to the perirhinal and entorhinal cortices, two interconnected cortical fields that funnel information into and out of the hippocampus. However, the significance of the latter projection remains unclear because no data are available regarding the rhinal targets of mPFC axons. This question was examined in the present study using a combination of anterograde tracing with Phaseolus vulgaris leucoagglutinin and pre‐embedding γ‐aminobutyric acid (GABA) immunocytochemistry in guinea pigs. Following Phaseolus vulgaris leucoagglutinin injections in the mPFC, anterogradely labeled axons were seen in the perirhinal (mainly superficial layers) and lateral entorhinal (mainly deep layers) cortices. In the electron microscope, the synaptic articulation of anterogradely labeled mPFC axon terminals with perirhinal and entorhinal neurons was found to be nearly identical. In these two rhinal fields, mPFC axon terminals only formed asymmetric synapses, typically with GABA‐immunonegative spines (≈70%) but occasionally with dendritic profiles (≈30%), half of which were GABA immunopositive. In the light of earlier observations, these findings indicate that mPFC inputs exert mainly excitatory effects in the rhinal cortices, prevalently on principal neurons. Thus, these results suggest that the mPFC may affect hippocampal‐dependent memories by enhancing impulse traffic into and out of the hippocampus at the level of the rhinal cortices.