julilili42/papers huggingface dataset:
Charcoal as evidence of palaeo‐wildfires in the Late Triassic of SW Germany
2010-06-18

Abstract So far only very few reports deal with Triassic (especially macro‐ or mesofossil) charcoal in detail. Here we present the first results of a detailed study of fossil charcoal from Late Triassic sandstones of the Tübingen Sandstein (Exter‐Formation, Rhaetian) in the vicinity of Tübingen in SW Germany. The discovery of charcoal at this locality can be regarded as direct evidence of wildfires in the hinterland of the Rhaetian sea and all charcoal fragments studied so far represent gymnosperm woods. At the moment nothing can be stated about the frequency and extent of such fires, although the occurrence of charcoal in different sandstone‐bodies points to more than one fire event. The charcoal content of the marginal marine deposit probably represents a larger region and not only the vegetation in the direct vicinity of the shore. A considerable amount of transport is indicated by abrasion of some of the charcoal fragments and the taphonomic sorting, leading to the selected accumulation of woody fragments. Some charcoal fragments are permineralized by goethite and we assume that in this case the goethite is the primary permineralization agent. Our data support the assumption that during the Late Triassic atmospheric oxygen concentrations were high enough to sustain larger wildfires. Copyright © 2010 John Wiley &amp; Sons, Ltd.
Involuntary eyelid closure after STN-DBS: evidence for different pathophysiological entities
2010-06-20

We identified two groups of IEC after STN-DBS based on clinical and EMG patterns: (1) STN-DBS induced IEC associated with tonic OO overactivity and (2) STN-DBS relieved IEC presenting with variable EMG patterns. Our findings provide relevant information on pathophysiology of STN-DBS related IEC and implications for its therapeutic management.
Spatial Modeling of a Soil Fertility Index using Visible–Near‐Infrared Spectra and Terrain Attributes
2010-06-20

Our objective was to develop a methodology to predict soil fertility using visible–near‐infrared (vis–NIR) diffuse reflectance spectra and terrain attributes derived from a digital elevation model (DEM). Specifically, our aims were to: (i) assemble a minimum data set to develop a soil fertility index for sugarcane ( Saccharum officinarum L.) (SFI‐SC) for biofuel production in tropical soils; (ii) construct a model to predict the SFI‐SC using soil vis–NIR spectra and terrain attributes; and (iii) produce a soil fertility map for our study area and assess it by comparing it with a green vegetation index (GVI). The study area was 185 ha located in São Paulo State, Brazil. In total, 184 soil samples were collected and analyzed for a range of soil chemical and physical properties. Their vis–NIR spectra were collected from 400 to 2500 nm. The Shuttle Radar Topographic Mission 3‐arcsec (90‐m resolution) DEM of the area was used to derive 17 terrain attributes. A minimum data set of soil properties was selected to develop the SFI‐SC. The SFI‐SC consisted of three classes: Class 1, the highly fertile soils; Class 2, the fertile soils; and Class 3, the least fertile soils. It was derived heuristically with conditionals and using expert knowledge. The index was modeled with the spectra and terrain data using cross‐validated decision trees. The cross‐validation of the model correctly predicted Class 1 in 75% of cases, Class 2 in 61%, and Class 3 in 65%. A fertility map was derived for the study area and compared with a map of the GVI. Our approach offers a methodology that incorporates expert knowledge to derive the SFI‐SC and uses a versatile spectro‐spatial methodology that may be implemented for rapid and accurate determination of soil fertility and better exploration of areas suitable for production.
Adjuvant therapy with pegylated interferon alfa-2b (36 months) versus low-dose interferon alfa-2b (18 months) in melanoma patients without macro-metastatic nodes: EADO trial.
2010-06-20

LBA8506 Background: Adjuvant therapy with low-dose adjuvant interferon alfa-2b (IFN) as well as with pegylated interferon alfa-2b (PEG-IFN) were both shown to be superior to observation in melanoma (M) patients (pts) without macro-metastatic nodes. However, the two strategies have never been assessed head to head. Weekly injection of PEG-IFN facilitates a longer duration of treatment which may be critical for benefit. We thus compared adjuvant therapy of flat low-dose PEG-IFN (36 months) versus low-dose IFN (18 months) in intermediate-risk M pts without macro-metastatic nodes. Methods: In this multicenter, open-label, prospective randomized phase III trial, pts with resected M ≥ 1.5 mm in thickness and without clinically detectable nodes were randomized either to IFN (3 MU subcutaneously [sc] 3 times a week for 18 months) or to PEG-IFN (100 mcg sc once weekly for 36 months). Sentinel node procedure (SNP) was not a standard in 2003 and thus was optional. Approach was consistent by center. Randomization was stratified for centers and SNP procedure. Primary endpoint was relapse-free survival (RFS), and secondary were distant metastasis-free survival (DMFS), overall survival (OS), and grade 3-4 severe adverse events (SAE). Sample size (890 pts) was calculated to detect a 10% difference (power &gt;80%, type I error of 5%, 2-sided) for RFS. Analysis describes 5-year probability of survival. Comparisons were done by intent-to-treat using Cox proportional models. Results: Of 898 pts enrolled, 896 (443 PEG vs 453 IFN) were eligible for evaluation after a median follow-up of 4.7 years. SLNB was performed in 68.2% of pts. Neither RFS (PEG-IFN 66.2% vs IFN 64.8%, p=0.43; HR, 0.91; 95% CI, 0.73 to 1.15) nor DMFS (71.3% vs 72.6%, p=0.86; HR, 1.02; 95% CI, 0.80 to 1.32) or OS (77.0% vs 78.4%, p=0.55; HR, 1.09; 95% CI, 0.82 to 1.45) showed statistical difference. There was an excess of SAE grade 3-4 in PEG-IFN arm (44.6% vs 26.6% in the first 18 months) which impacted on median duration of treatment (17.8 months in IFN arm; 19.2 in PEG-IFN arm, with only 28% completing 36 months treatment). Conclusions: Flat low-dose PEG-IFN did not show superiority over conventional low dose IFN. Attempts to increase benefit by prolonging treatment with PEG-IFN over 3 years were hampered by a high rate of treatment discontinuation possibly linked to SAEs with PEG-IFN. [Table: see text]
Disruption of the olivo-cerebellar circuit by Purkinje neuron-specific ablation of BK channels
2010-06-21

The large-conductance voltage- and calcium-activated potassium (BK) channels are ubiquitously expressed in the brain and play an important role in the regulation of neuronal excitation. Previous work has shown that the total deletion of these channels causes an impaired motor behavior, consistent with a cerebellar dysfunction. Cellular analyses showed that a decrease in spike firing rate occurred in at least two types of cerebellar neurons, namely in Purkinje neurons (PNs) and in Golgi cells. To determine the relative role of PNs, we developed a cell-selective mouse mutant, which lacked functional BK channels exclusively in PNs. The behavioral analysis of these mice revealed clear symptoms of ataxia, indicating that the BK channels of PNs are of major importance for normal motor coordination. By using combined two-photon imaging and patch-clamp recordings in these mutant mice, we observed a unique type of synaptic dysfunction in vivo, namely a severe silencing of the climbing fiber–evoked complex spike activity. By performing targeted pharmacological manipulations combined with simultaneous patch-clamp recordings in PNs, we obtained direct evidence that this silencing of climbing fiber activity is due to a malfunction of the tripartite olivo-cerebellar feedback loop, consisting of the inhibitory synaptic connection of PNs to the deep cerebellar nuclei (DCN), followed by a projection of inhibitory DCN afferents to the inferior olive, the origin of climbing fibers. Taken together, our results establish an essential role of BK channels of PNs for both cerebellar motor coordination and feedback regulation in the olivo-cerebellar loop.
Serum and glucocorticoid‐inducible kinase 1 (SGK1) is necessary for vascular remodeling during angiogenesis
2010-06-21

Abstract The unquestionable importance of the cardiovascular system for pre‐ and postnatal life has prompted dissection of the molecular mechanisms underlying its development. Serum and glucocorticoid‐inducible kinase 1 (SGK1) is a serine/threonine kinase lying downstream of the phosphoinositide 3 (PI3) kinase pathway, whose embryonic function remains unknown. Here, we show that disruption of Sgk1 in the mouse C57BL/6J genetic background leads to embryonic lethality at embryonic day 10.5–11.5 due to severe embryonic and extraembryonic angiogenic defects and to impaired myocardial trabeculation. Absence of SGK1 results in increased apoptosis of endothelial cells, and of vascular smooth muscle cells highlighting a prosurvival role for SGK1 during angiogenesis. Sgk1 null embryos also display reduced expression levels of Notch signaling genes and decreased expression of the arterial markers Efnb2 and Nrp1 . These findings uncover a novel and essential function for SGK1 in cardiovascular development contributing to a better understanding of mammalian angiogenesis. Developmental Dynamics 239:2149–2160, 2010. © 2010 Wiley‐Liss, Inc.
Cream or foam in pedal skin care: towards the ideal vehicle for urea used against dry skin
2010-06-21

Synopsis The aim of this study was to evaluate different urea‐containing cosmetic preparations designed for foot care regarding skin occlusion. The primary aim was therefore to screen the short‐term transepidermal water loss (TEWL) as a parameter for skin barrier function and skin occlusion and to characterize the relative role of the vehicle, i.e. cream or foam in the context of cosmetics containing urea in the 2–10% range addressing the cosmetic products urea 2% cream (GEHWOL FUSSKRAFT blau), petrolatum containing cream (GEHWOL med Schrundensalbe), urea 10% cream (GEHWOL med Lipidro‐Crème), urea 10% foam (Allpresan Fuss Schaum) and vaseline (positive control) compared with an untreated area on the volar forearms of volunteers. Moreover, the short time (24 h) kinetics regarding the moisturizing effect of cream and foam formulations in diabetic patients were compared. The efficacy of a cream on reduction of skin thickness of hyperkeratotic skin in the heel region before and after a period of product application was also evaluated. In some of the trials, healthy individuals and in others, diabetic patients (type I and II) were enrolled. TEWL was determined before product application, as well as at given points of time thereafter. In this study, no excessive occlusion effects comparable with a blockage of the skin’s natural water evaporation could be observed for any of the test products. To the extent to be expected, this was found neither for the cream products nor for the foam product. Slightly lowered TEWL values after application of the 10% urea cream can be interpreted as a beneficial effect in terms of an improved barrier function. Regarding skin moisture, the urea‐containing cream formulation appeared equal or slightly superior to the foam formulation. The thickness of the horny layer was found reduced after application of 10 % urea‐containing cream. At present it looks as if cream vehicles would still be vehicles of choice in general, when it comes to the formulation of skin care preparations for not only dry skin but also in the context of pedal skin care.
The 5‐lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages
2010-06-22

BACKGROUND AND PURPOSE Zileuton is the only 5‐lipoxygenase (5‐LOX) inhibitor marketed as a treatment for asthma, and is often utilized as a selective tool to evaluate the role of 5‐LOX and leukotrienes. The aim of this study was to investigate the effect of zileuton on prostaglandin (PG) production in vitro and in vivo . EXPERIMENTAL APPROACH Peritoneal macrophages activated with lipopolysaccharide (LPS)/interferon γ (LPS/IFNγ), J774 macrophages and human whole blood stimulated with LPS were used as in vitro models and rat carrageenan‐induced pleurisy as an in vivo model. KEY RESULTS Zileuton suppressed PG biosynthesis by interference with arachidonic acid (AA) release in macrophages. We found that zileuton significantly reduced PGE2 and 6‐keto prostaglandin F1α (PGF1α) levels in activated mouse peritoneal macrophages and in J774 macrophages. This effect was not related to 5‐LOX inhibition, because it was also observed in macrophages from 5‐LOX knockout mice. Notably, zileuton inhibited PGE2 production in LPS‐stimulated human whole blood and suppressed PGE2 and 6‐keto PGF1α pleural levels in rat carrageenan‐induced pleurisy. Interestingly, zileuton failed to inhibit the activity of microsomal PGE2 synthase1 and of cyclooxygenase (COX)‐2 and did not affect COX‐2 expression. However, zileuton significantly decreased AA release in macrophages accompanied by inhibition of phospholipase A2 translocation to cellular membranes. CONCLUSIONS AND IMPLICATION Zileuton inhibited PG production by interfering at the level of AA release. Its mechanism of action, as well as its use as a pharmacological tool, in experimental models of inflammation should be reassessed.
Silver-Russell syndrome: genetic basis and molecular genetic testing
2010-06-23

Imprinted genes with a parent-of-origin specific expression are involved in various aspects of growth that are rooted in the prenatal period. Therefore it is predictable that many of the so far known congenital imprinting disorders (IDs) are clinically characterised by growth disturbances. A noteable imprinting disorder is Silver-Russell syndrome (SRS), a congenital disease characterised by intrauterine and postnatal growth retardation, relative macrocephaly, a typical triangular face, asymmetry and further less characteristic features. However, the clinical spectrum is broad and the clinical diagnosis often subjective. Genetic and epigenetic disturbances can meanwhile be detected in approximately 50% of patients with typical SRS features. Nearly one tenth of patients carry a maternal uniparental disomy of chromosome 7 (UPD(7)mat), more than 38% show a hypomethylation in the imprinting control region 1 in 11p15. More than 1% of patients show (sub)microscopic chromosomal aberrations. Interestingly, in approximately 7% of 11p15 hypomethylation carriers, demethylation of other imprinted loci can be detected. Clinically, these patients do not differ from those with isolated 11p15 hypomethylation whereas the UPD(7)mat patients generally show a milder phenotype. However, an unambiguous (epi)genotype-phenotype correlation can not be delineated.We therefore suggest a diagnostic algorithm focused on the 11p15 hypomethylation, UPD(7)mat and cryptic chromosomal imbalances for patients with typical SRS phenotype, but also with milder clinical signs only reminiscent for the disease.
Heterologous expression of the biosynthetic gene clusters of coumermycin A1, clorobiocin and caprazamycins in genetically modified Streptomyces coelicolor strains
2010-06-23

Abstract The biosynthetic gene clusters of the aminocoumarin antibiotics clorobiocin and coumermycin A 1 and of the liponucleoside antibiotic caprazamycin were stably integrated into the genomes of different host strains derived from Streptomyces coelicolor A3(2). For the heterologous expression of clorobiocin derivatives in a chemically defined medium, inclusion of 0.6% of the siloxylated ethylene oxide/propylene oxide copolymer Q2‐5247 into the growth medium proved to result in a 4.8‐fold increase of productivity. Presumably, this copolymer acts as an oxygen carrier. The additional inclusion of cobalt chloride (0.2–2 mg l −1 ) dramatically increased the percentage of the desired compound clorobiocin within the total produced clorobiocin derivatives. This is very likely due to a stimulation of a cobalamin‐dependent methylation reaction catalyzed by the enzyme CloN6 of clorobiocin biosynthesis. All three investigated host strains ( S. coelicolor M512, M1146 and M1154) gave similar production rates of total clorobiocin derivatives (on average, 158 mg l −1 in the presence of 0.6% Q2‐5247 and 0.2 mg l −1 CoCl 2 ). In contrast, heterologous production of caprazamycin derivatives was optimal in strain M1154 (amounts of 152 mg l −1 on average). © 2010 Wiley Periodicals, Inc. Biopolymers 93: 823–832, 2010.
A self-consistent approach to the hard and soft states of 4U 1705-44
2010-06-23

Context. High-resolution spectroscopy has recently revealed in many low-mass X-ray binaries hosting a neutron star that the shape of the broad iron line observed in the 6.4–6.97 keV range is consistently well-fitted by a relativistically smeared line profile. Aims. The presence of other broad features, besides the iron line, together with a high S/N of the spectra offer the possibility of testing a self-consistent approach to the overall broadband reflection spectrum and evaluating the impact of the reflection component in the formation of the broadband X-ray spectra. Methods. We analyzed two XMM-Newton observations of the bright atoll source 4U 1705-44, which can be considered a prototype of the class of the persistent NS LMXBs showing both hard and soft states. The first observation was performed when the source was in a hard low flux state, the second during a soft, high-flux state. Both the spectra show broad iron emission lines. We fit the spectra using a two-component model, together with a reflection model specifically suited to the case of a neutron star, where the incident spectrum has a blackbody shape. Results. In the soft state, the reflection model, convolved with a relativistic smearing component, consistently describes the broad features present in the spectrum, and we find a clear relation between the temperature of the incident flux and the temperature of the harder X-ray component that we interpret as the boundary layer emission. In this state we find converging evidence that the boundary layer outer radius is ~2 times the neutron star radius. In the low flux state, we observe a change in the continuum shape of the spectrum with respect to the soft state. Still, the broad local emission features can be associated with a disk reflecting matter, but in a lower ionization state, and possibly produced in an accretion disk truncated at greater distance. Conclusions. Our analysis provides strong evidence that the reflection component in soft states of LMXBs comes from to hard X-ray thermal irradiation, which we identify with the boundary layer emission, also present in the continuum model. In the hard state, the broad iron line if also produced by reflection, and the continuum disk emission can be self-consistently accounted if the disk is truncated at a greater distance than the soft state.
Inhibition of Eimeria tenella CDK‐Related Kinase 2: From Target Identification to Lead Compounds
2010-06-23

Abstract Apicomplexan parasites encompass several human‐ and animal‐pathogenic protozoans such as Plasmodium falciparum , Toxoplasma gondii , and Eimeria tenella . E. tenella causes coccidiosis, a disease that afflicts chickens, leading to tremendous economic losses to the global poultry industry. The considerable increase in drug resistance makes it necessary to develop new therapeutic strategies against this parasite. Cyclin‐dependent kinases (CDKs) are key molecules in cell‐cycle regulation and are therefore prominent target proteins in parasitic diseases. Bioinformatics analysis revealed four potential CDK‐like proteins, of which one— E. tenella CDK‐related kinase 2 (EtCRK2)—has already been characterized by gene cloning and expression. By using the CDK‐specific inhibitor flavopiridol in EtCRK2 enzyme assays and schizont maturation assays (SMA), we could chemically validate CDK‐like proteins as potential drug targets. An X‐ray crystal structure of human CDK2 (HsCDK2) served as a template to build protein models of EtCRK2 by comparative homology modeling. Structural differences in the ATP binding site between EtCRK2 and HsCDK2, as well as chicken CDK3, were addressed for the optimization of selective ATP‐competitive inhibitors. Virtual screening and “wet‐bench” high‐throughput screening campaigns on large compound libraries resulted in an initial set of hit compounds. These compounds were further analyzed and characterized, leading to a set of four promising lead compounds for development as EtCRK2 inhibitors.
A novel gelatin sponge for accelerated hemostasis
2010-06-24

Abstract To more effectively manage the substantial bleeding encountered during surgical procedures in oto‐rhino‐laryngology, we developed a novel hemostatic sponge made of pharmaceutical grade, chemically cross‐linked gelatin. The sponge is characterized by a high pore density, reduced ligaments, and a high nanoscale roughness of lamella surfaces in the matrix. In vitro blood uptake assays revealed a very rapid absorption of human blood, which was two to three times faster than that measured with comparative hemostyptic devices. In an in vitro hemorrhage model using human veins, the novel gelatin sponge matrix induced hemostasis less than a minute after bleeding was induced. The sponge was shown to bring about rapid hemostasis when it was administered in a young patient suffering from acute bleeding of a pharyngeal angiofibroma, even though the patient had been treated with an anticoagulant because of a transient ischemic attack. As the gelatin matrix of the sponge is biocompatible and resorbable, the hemostyptic device could be left in place and was shown to be resorbed within 2 weeks. We hypothesize that the excellent hemostatic performance of the sponge might be linked to enhanced capillary effects in conjunction with optimized anchoring of fibrinogen on the nano‐rough material surface, as suggested by scanning electron microscopy. The novel gelatin sponge appears to be a promising hemostatic matrix, which could be of great benefit for patients suffering from epistaxis and other acute injuries resulting in severe bleeding. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010.
Real-Time Changes in the Optical Spectrum of Organic Semiconducting Films and Their Thickness Regimes during Growth
2010-06-24

We present real-time in situ studies of optical spectra during thin film growth of several prototype organic semiconductors (pentacene, perfluoropentacene, and diindenoperylene) on SiO2. These data provide insight into surface and interface effects that are of fundamental importance and of relevance for applications in organic electronics. With respect to the bulk, the different molecular environment and structural changes within the first few monolayers can give rise to significant optical changes. Similar to interface-driven phenomena in, e.g., magnetism, spectral changes as a function of thickness d are a very general effect, decaying as 1/d in the simplest approximation. We observe energy shifts of 50-100 meV, rather small changes of the exciton-phonon coupling, and new transitions in specific systems, which should be considered as general features of the growth of organics.
Phototherapy and photochemotherapy
2010-06-24

Summary The treatment of skin diseases with ultraviolet radiation represents an important therapeutic modality in clinical dermatology, and the number of skin diseases that improve under the phototherapeutic modalities of today is still growing. While clinical phototherapy was originally based on empirical observations, our present understanding of the underlying mechanisms has improved substantially due to important progress in photobiological science. The better understanding of this scientific basis of treatment allows to both choose the correct phototherapeutic modality and determine the most effective treatment regimen. The aim of this article is to discuss the appropriate indications for phototherapy as well as its safe and effective employment, providing practical help in daily clinical phototherapeutic practice.