julilili42/papers huggingface dataset:
Dermal Interleukin-1 Expression and Effective and Long-lasting Therapy with Interleukin-1 Receptor Antagonist Anakinra in Schnitzler Syndrome
2012-01-01

Schnitzler syndrome is a rare disease presenting with chronic urticaria and monoclonal gammopathy.Its pathogenesis is unclear and therapies effective in chronic urticaria remained without effect (1, 2).However, whether systemic or cutaneous IL-1 elicits urticaria in these patients is not known, because the source of IL-1 remained enigmatic.Here we demonstrate for the first time the presence of active IL-1β by immunohistochemistry in dermal cells of affected skin in a patient with Schnitzler syndrome.This not only underlines the rationale to treat Schnitzler syndrome with IL-1 blocking agents; it also demonstrates that immunoglobulin M (IgM), or yet unknown factors associated with monoclonal gammopathy in these patients, trigger IL-1 activation also in the skin, as gene defects do in patients with Muckle-Wells (MWS) or cryopyrin-associated periodic syndroms (CAPS) (3, 4).Consequently, treatment with the IL-1 receptor antagonist (IL-1RA) anakinra, initiated as first-line monotherapy, led to complete remission of symptoms within 2 days, and long-lasting remission for more than 3 years was achieved by daily administration of anakinra.
Interplay between Population Dynamics and Drug Tolerance of <b><i>Staphylococcus aureus</i></b> Persister Cells
2012-01-01

Population dynamics parameters of &lt;i&gt;Staphylococcus aureus&lt;/i&gt; strain SA113 were quantified based on growth and killing experiments with batch culture cells in rich medium. Eradication kinetics and the concomitant isolation of a subpopulation of drug-tolerant SA113 persisters upon treatment with super-minimal inhibitory concentrations of antibiotics such as ciprofloxacin, daptomycin, and tobramycin served as a basis for mathematical analyses. According to a two-state model for stochastic phenotype switching, levels of persister cells and their eradication rates were influenced by the antibiotics used for isolation, clearly indicating a heterogeneous pool of &lt;i&gt;S. aureus&lt;/i&gt; persisters. Judging from time-dependent experiments, the persisters’ degree of drug tolerance correlated with the duration of antibiotic challenge. Moreover, cross-tolerance experiments with cells consecutively treated with two different antibiotics revealed that multi-drug tolerance is not a necessary trait of &lt;i&gt;S. aureus&lt;/i&gt; persisters isolated by antibiotic challenge. In some cases, the results depended on the order of the two antibiotic treatments, suggesting that antibiotic tolerance may be achieved by a combination of preexisting persisters and an adaptive response to drug exposure. Counts of live cells which had endured drug treatment increased only after lag phases of at least 3 h after the shift to non-selective conditions. Thus, this study provides quantitative insights into population dynamics of &lt;i&gt;S. aureus&lt;/i&gt; persisters with regard to antibiotic challenge.
Late Miocene Palaeoclimate and Ecosystem Dynamics in Southwestern Bulgaria − A Study Based on Pollen Data from the Gotse-Delchev Basin
2012-01-01

A profile 63 m thick in the Late Miocene in the Gotse-Dechev Basin (SW Bulgaria) was sampled for pollen analysis in the Kanina opencast mine. The exposed sequence comprises a basal unit with brown coal-clay cycles and clayey/siliciclastic cover layers partly representing a lacustrine facies. A total of 60 pollen samples were analysed, but quantitative data are confined to 30 polleniferous samples. The palynological analysis carried out provides data about the composition and structure of the fossil vegetation. The main vegetation type was a mixed mesophytic forest dominated by Carya, Fagus, Betula, Quercus, and Ulmus. Accessory elements included Magnolia, Corylopsis, Liquidambar, Eucommia, Zelkova, Ulmus, Pterocarya, Juglans, Engelhardia, Platycarya, Symplocos, Araliaceae, Vitaceae, Hedera, Cornus, and Ilex. Mid- and high-altitude vegetation elements Tsuga, Abies, Keteleeria, Cathaya, Picea, Cedrus are also present. Swamp vegetation with high proportion of Alnus, and minor percentages of Taxodiaceae, Cyrillaceae, Myrica, Planera, some Poaceae, Cyperaceae, and some ferns also existed. Species of Platanus, Alnus, Pterocarya, Salix, Staphylea, and Liquidambar played important roles in the riparian vegetation. The aquatic vegetation consists of Butomus, Potamogeton, Menyanthes, Sparganium, Typha and Cyperaceae. Herbaceous palaeocoenoses had a limited distribution. The climatic data reconstructed by the Coexistence Approach indicate mean annual temperatures of ca. 15.6-17.1°C. For mean annual precipitation intervals from 1096 to 1347 mm are most common. The narrowest coexistence intervals for the mean of the coldest month are 5 to 7.5°C. Summer temperatures were mainly between 24.7 and 26.4°C. The curve obtained for the means of summer temperatures illustrates some cyclic changes, partly also observed for other temperature parameters. The dynamics of the reconstructed data indicate that the climatic changes were probably cyclical. However, the presence of several unconformities in the sampled section does not allow an unambiguous interpretation of these data.
Treatment Options in Cushing's Disease
2012-01-01

Endogenous Cushing's syndrome is a grave disease that requires a multidisciplinary and individualized treatment approach for each patient. Approximately 80% of all patients harbour a corticotroph pituitary adenoma (Cushing's disease) with excessive secretion of adrenocorticotropin-hormone (ACTH) and, consecutively, cortisol. The goals of treatment include normalization of hormone excess, long-term disease control and the reversal of comorbidities caused by the underlying pathology. The treatment of choice is neurosurgical tumour removal of the pituitary adenoma. Second-line treatments include medical therapy, bilateral adrenalectomy and radiation therapy. Drug treatment modalities target at the hypothalamic/pituitary level, the adrenal gland and at the glucocorticoid receptor level and are commonly used in patients in whom surgery has failed. Bilateral adrenalectomy is the second-line treatment for persistent hypercortisolism that offers immediate control of hypercortisolism. However, this treatment option requires a careful individualized evaluation, since it has the disadvantage of permanent hypoadrenalism which requires lifelong glucocorticoid and mineralocorticoid replacement therapy and bears the risk of developing Nelson's syndrome. Although there are some very promising medical therapy options it clearly remains a second-line treatment option. However, there are numerous circumstances where medical management of CD is indicated. Medical therapy is frequently used in cases with severe hypercortisolism before surgery in order to control the metabolic effects and help reduce the anestesiological risk. Additionally, it can help to bridge the time gap until radiotherapy takes effect. The aim of this review is to analyze and present current treatment options in Cushing's disease.
In vitro Study of Secreted Aspartyl Proteinases Sap1 to Sap3 and Sap4 to Sap6 Expression in Candida albicans Pleomorphic Forms
2012-01-01

Transition from round budding cells to long hyphal forms and production of secreted aspartic proteases (Saps) are considered virulence-associated factors of Candida albicans. Although plenty of data dealing with Saps involvement in the infection process have been published, Saps expression by the different pleomorphic forms as well as the capacity of C. albicans filaments to express Sap1-6 under serum influence are poorly investigated. In this study, we used immunofluorescence and immunoelectron microscopy for the detection of Sap1-6 isoenzymes in C. albicans pleomorphic cells (blastoconidia, germ tubes, pseudohyphae, true hyphae) grown in Sap-inductive human serum and Sap non-inductive medium - yeast extract-peptone-glucose (YEPD). Isoenzymes were below the detection level in all blastoconidial cells grown in YEPD for 18 h. Sap1-6 expression was hardly detected in C. albicans cells cultivated in serum for 20 min. Increasing level of Sap1-6 expression was observed when C. albicans was incubated for 2, 6 and 18 h in serum corresponding to the development of germ tubes, pseudohyphae and true hyphae. The expression of Sap1-3 in pseudohyphae and true hyphae was more intensive compared to Sap4-6. Thus, we could show that human serum induced hyphae formation and the expression of Sap1-6 were co-regulated.
Effect of Azathioprine on Na+/H+Exchanger Activity in Dendritic Cells
2012-01-01

Azathioprine is a powerful immunosuppressive drug, which is partially effective by interfering with the maturation and function of dendritic cells (DCs), antigen-presenting cells linking innate and adaptive immunity. DCs are stimulated by bacterial lipopolysaccharides (LPS), which trigger the formation of reactive oxygen species (ROS), paralleled by activation of the Na(+)/H(+) exchanger. The carrier is involved in the regulation of cytosolic pH, cell volume and migration. The present study explored whether azathioprine influences Na(+)/H(+) exchanger activity in DCs. DCs were isolated from murine bone marrow, cytosolic pH (pH(i)) was estimated utilizing 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF-AM) fluorescence, Na(+)/H(+) exchanger activity from the Na(+)-dependent realkalinization following an ammonium pulse, cell volume from forward scatter in FACS analysis, ROS production from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, TNFα release utilizing ELISA, and migration utilizing transwell migration assays. Exposure of DCs to lipopolysaccharide (LPS, 1 μg/ml) led to a transient increase of Na(+)/H(+) exchanger activity, an effect paralleled by ROS formation, increased cell volume, TNFα production and stimulated migration. Azathioprine (10 μM) did not significantly alter the Na(+)/H(+) exchanger activity, cell volume and ROS formation prior to LPS exposure but significantly blunted the LPS-induced stimulation of Na(+)/H(+) exchanger activity, ROS formation, cell swelling, TNFα production and cell migration. In conclusion, azathioprine interferes with the activation of dendritic cell Na(+)/H(+) exchanger by bacterial lipopolysaccharides, an effect likely participating in the anti-inflammatory action of the drug.
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Where are we?
2012-01-01

Peritoneal surface malignancies are generally associated with poor prognosis. In daily clinical routine, systemic chemotherapy is still considered the only reasonable therapy despite of encouraging results of cytoreductive surgery (CRS) along with intraperitoneal hyperthermic chemotherapy (HIPEC). The Achilles heel of CRS and HIPEC is appropriate patient selection and precise surgical technique preventing patients from excessive morbidity and mortality. Given these findings, new concepts of second look surgery for high risk patients allow detection of peritoneal spread ahead of clinical symptoms or presence of peritoneal masses reducing perioperative morbidity. In addition, personalized intraperitoneal chemotherapy might further improve outcome by appreciating individual tumor biology. These days, every physician should be aware of CRS and HIPEC for treatment of peritoneal surface malignancies. Since there is now sufficient data for the superiority of CRS and HIPEC to systemic chemotherapy in selected patients, our next goal should be providing this strategy with minimal morbidity and mortality even in the presence of higher tumor load.
Anger Elicitation in Tonga and Germany: The Impact of Culture on Cognitive Determinants of Emotions
2012-01-01

The cognitive appraisal of an event is crucial for the elicitation and differentiation of emotions, and causal attributions are an integral part of this process. In an interdisciplinary project comparing Tonga and Germany, we examined how cultural differences in attribution tendencies affect emotion assessment and elicitation. Data on appraising causality and responsibility and on emotional responses were collected through questionnaires based on experimentally designed vignettes, and were related to culture-specific values, norms, and the prevailing self-concept. The experimental data support our hypothesis that - driven by culturally defined self-concepts and corresponding attribution tendencies - members of the two cultures cognitively appraise events in diverging manners and consequently differ in their emotional responses. Ascription of responsibility to self and/or circumstances, in line with a more interdependent self-concept, co-varies with higher ratings of shame, guilt, and sadness, whereas ascription of responsibility to others, in line with a less interdependent self-concept, co-varies with higher ratings of anger. These findings support the universal contingency hypothesis and help to explain cultural differences in this domain on a fine-grained level.
Working Around HTS Thickness Limitations–towards 1000+A/cm–Class Coated Conductors
2012-01-01

Increasing the HTS film thickness would be the straightforward route to enhance the current transport capacity of coated conductors. Usually, however, growth defects lead to a strong deterioration of the critical current density with thickness. The unique growth mode of HTS films on graded and tilted MgO buffer layers grown by inclined substrate deposition (ISD) paves the way to overcome this limit. This contribution presents micro-structural and performance data of coated conductors with monolithic REBCO-films up to 7.5 μm thickness exhibiting perfect crystallinity and critical currents in excess of 1000 A/cm-width.
Linguistic Tests for Discourse Relations in the TüBa-D/Z Corpus of Written German
2012-01-01

Discourse structure and discourse relations are an important ingredient in systems for the analysis of text that go beyond the boundary of single clauses. Discourse relations often indicate important additional information about the connection between two clauses, such as causality, and are widely believed to have an influence on aspects of reference resolution. More so than for referential annotation, discourse relation annotation is rendered difficult by the absence of a general consensus on the underlying linguistic phenomena that should be targeted, as well as by a lack of strong predictions on the possible or permissible interactions between these phenomena. While it is sometimes claimed that the structuring of discourse is only weakly constrained and as a result capturing discourse structure and discourse relations will always result in poor reproducibility of the annotation task, we want to argue in this paper that an explicit notion of the relata of discourse relations allows to delimit annotation scope and to make use of theoretical accounts of the linguistic phenomena involved without giving up the goal of theory-neutrality that is essential in making sure that a given resource stays useful to a large community of users. In this article, we first present the general design choices that are to be made in the design of
Island shapes and aggregation steered by the geometry of the substrate lattice
2012-01-01

We find that island shapes and aggregation in diindenoperylene deposited on Au(100), Au(110), and Au(111) single crystals are steered by the anisotropy due to the lattice geometry of the substrate. This phenomenon may be exploited as a tool for molecular patterning of surfaces.
Regulation of KCNQ1/KCNE1 by β-catenin
2012-01-01

β-catenin, a multifunctional protein expressed in all tissues including the heart stimulates the expression of several genes important for cell proliferation. Signaling involving ß-catenin participates in directing cardiac development and in the pathophysiology of cardiac hypertrophy. Nothing is known, however, on the role of β-catenin in the regulation of cardiac ion channels. The present study explored the functional interaction of β-catenin and KCNE1/KCNQ1, the K+ channel complex underlying the slowly activating outwardly rectifying K+ current. To this end, KCNE1/KCNQ1 was expressed in Xenopus oocytes with and without β-catenin and the depolarization (up to + 80 mV) induced current (I(Ks)) was determined using the two-electrode voltage clamp. As a result, β-catenin enhanced I(Ks) by 30%. The effect of β-catenin on I(Ks) was not affected by actinomycin D (10 μM), an inhibitor of transcription, indicating that β-catenin was not effective as transcription factor. Confocal microscopy revealed that β-catenin enhanced the KCNE1/KCNQ1 protein abundance in the cell membrane. Exposure of the oocytes to brefeldin A (5 μM), an inhibitor of vesicle insertion, was followed by a decline of I(Ks), which was then similar in oocytes expressing KCNE1/KCNQ1 together with β-catenin and in oocytes expressing KCNE1/KCNQ1 alone. In conclusion, β-catenin enhances I(Ks) by increasing the KCNE1/KCNQ1 protein abundance in the cell membrane, an effect requiring vesicle insertion into the cell membrane.
Parental Origin of de novo Cytogenetically Balanced Reciprocal Non-Robertsonian Translocations
2012-01-01

De novo cytogenetically balanced reciprocal non-Robertsonian translocations are rare findings in clinical cytogenetics and might be associated with an abnormal phenotype. Knowledge of the parental origin and mechanisms of formation is still limited. By microdissection of the derivative chromosomes and their normal homologs from metaphases followed by microsatellite-mediated marker analysis we identified 7 cases of paternal and 3 cases of maternal origin in a cohort of 10 patients with de novo cytogenetically balanced reciprocal non-Robertsonian translocations. Neither in the maternal nor in the paternal group of our study parental age seems to be increased. Together with the data from the literature our results confirm that the majority of de novo cytogenetically balanced reciprocal translocations are of paternal origin, but the preponderance does not appear to be as distinct as previously thought and the paternal age does not seem to be necessarily a major contributing factor.
What’s in a Name: A Bayesian Hierarchical Analysis of the Name-Letter Effect
2012-01-01

People generally prefer their initials to the other letters of the alphabet, a phenomenon known as the name-letter effect. This effect, researchers have argued, makes people move to certain cities, buy particular brands of consumer products, and choose particular professions (e.g., Angela moves to Los Angeles, Phil buys a Philips TV, and Dennis becomes a dentist). In order to establish such associations between people's initials and their behavior, researchers typically carry out statistical analyses of large databases. Current methods of analysis ignore the hierarchical structure of the data, do not naturally handle order-restrictions, and are fundamentally incapable of confirming the null hypothesis. Here we outline a Bayesian hierarchical analysis that avoids these limitations and allows coherent inference both on the level of the individual and on the level of the group. To illustrate our method, we re-analyze two data sets that address the question of whether people are disproportionately likely to live in cities that resemble their name.
Activation of a silent phenazine biosynthetic gene cluster reveals a novel natural product and a new resistance mechanism against phenazines
2012-01-01

The activation of silent biosynthetic gene clusters is a principal challenge for genome mining strategies in drug discovery. In the present study, a phenazine biosynthetic gene cluster was discovered in the Gram-positive bacterium Streptomyces tendae Tü1028. This gene cluster remained silent under a multitude of cultivation conditions, both in the genuine producer strain and in a heterologous expression strain. However, introduction of a constitutive promoter upstream of the phenazine biosynthesis genes led to the production of phenazine-1-carboxylic acid (PCA) and of a new derivative thereof, i.e. a conjugate of PCA and L-glutamine. The linkage of PCA to L-glutamine by amide bond formation was catalyzed by enzymes of the heterologous expression host Streptomyces coelicolor M512. PCA showed a strong antibiotic effect, but PCA-Gln did not. Glutamination of PCA therefore appears to represent a resistance mechanism against the antibiotic PCA, which can be produced in significant quantities in soil by Pseudomonas strains. The gene cluster also contained genes for all enzymes of the mevalonate pathway and for an aromatic prenyltransferase, thereby resembling gene clusters for prenylated phenazines. However, purification and biochemical investigation of the prenyltransferase proved that it does not prenylate phenazines but hydroxynaphthalene substrates, showing very similar properties as NphB of naphterpin biosynthesis (Kuzuyma et al., Nature, 2005, 435, 983–987.).
The Role of Environmental Heterogeneity in Maintaining Reproductive Isolation between HybridizingPasserina(Aves: Cardinalidae) Buntings
2012-01-01

Hybrid zones are useful systems in which to investigate processes important in creating and maintaining biological diversity. As they are often located in ecotones, patterns of environmental heterogeneity may influence hybridization, and may also influence the maintenance of reproductive isolation between hybridizing species. Focusing on the hybrid zone between Passerina amoena (Lazuli Bunting) and Passerina cyanea (Indigo Bunting), located in the eastern Rocky Mountain/western Great Plains ecotone, we examined the relationship between population-pairwise differences in the proportion of hybrids and environmental variation. Models including environmental variables explained more of the variation in hybridization rates across the ecotone than did models that only included the geographic distance between sampling localities as predictor variables (63.9% and 58.9% versus 38.8% and 39.9%, depending on how hybridization was quantified). In the models including environmental variables, the amount of rainfall during the warmest quarter had the greatest explanatory power, consistent with a hypothesis that P. cyanea is better adapted to the mesic environments of eastern North America and P. amoena is better adapted to the xeric habitats of western North America. These results suggest that continued reproductive isolation between these species is mediated, at least partially, by differential adaptations to local environmental conditions.
Antimicrobial peptides in the brain neuropeptides and amyloid
2012-01-01

Antimicrobial peptides (AMPs) are ancient defense molecules of the innate immune system. Similarly, neuropeptides are ancient signaling molecules. Similarities in size, cationic charge or amphipatic design between some neuropeptides and AMPs suggest that they might serve an additional function in antimicrobial immunity. This hypothesis, supported by experimental evidence, adds another level of understanding to the intricate crosstalk between the nervous system and the immune system. The recent observation, that another brain protein, amyloid-beta, has antimicrobial activities, suggests that this peptide, prominently known as an accumulating toxic waste material, might have a physiologic function as anti-infective agent.
Evaluation of objectivity, reliability and criterion validity of the Key Indicator Method for Manual Handling Operations (KIM-MHO), draft 2007
2012-01-01

Upper extremity musculoskeletal symptoms and disorders are common in the working population. The economic and social impact of such disorders is considerable. Long-time, dynamic repetitive exposure of the hand-arm system during manual handling operations (MHO) alone or in combination with static and postural effort are recognised as causes of musculoskeletal symptoms and disorders. The assessment of these manual work tasks is crucial to estimate health risks of exposed employees. For these work tasks, a new method for the assessment of the working conditions was developed and a validation study was performed. The results suggest satisfying criterion validity and moderate objectivity of the KIM-MHO draft 2007. The method was modified and evaluated again. It is planned to release a new version of KIM-MHO in spring 2012.