julilili42/papers huggingface dataset:
Fluorodeoxyglucose positron emission tomography in Richardson's syndrome and progressive supranuclear palsy‐parkinsonism
2011-10-05

Abstract Background: We hypothesized that postural instability and cognitive decline in patients with Richardson's syndrome could be a consequence of reduced thalamic and frontal metabolism. Severe Parkinsonian signs in patients with progressive supranuclear palsy‐parkinsonism may be reflected by alterations in putaminal metabolism. Methods: Eleven patients with Richardson's syndrome, 8 patients with progressive supranuclear palsy‐parkinsonism, 12 with Parkinson's disease, and 10 controls underwent clinical assessment and fluorodeoxyglucose positron emission tomography (PET). Results: Richardson's syndrome patients showed pronounced thalamic hypometabolism, and patients with progressive supranuclear palsy‐parkinsonism pronounced putaminal hypometabolism, compared to all other investigated groups. The putamen/thalamus uptake ratio differentiated progressive supranuclear palsy‐parkinsonism from Richardson's syndrome (area under the curve = 0.86) and from Parkinson's disease (area under the curve = 0.80) with acceptable accuracy. Frontal hypometabolism was predominantly found in Richardson's syndrome patients. Conclusions: Richardson's syndrome, progressive supranuclear palsy‐parkinsonism and Parkinson's disease showed different metabolic patterns in fluorodeoxyglucose PET. © 2011 Movement Disorder Society
Mutations in the PDYN gene (SCA23) are not a frequent cause of dominant ataxia in Central Europe
2011-10-05

Supporting Information The following Supporting information is available for this article: Table S1. Polymerase chain reaction conditions and primer sequences of PDYN sequencing. Additional Supporting information may be found in the online version of this article. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Mechanical design of the WASA DIRC
2011-10-05

For precise measurements of the velocity of highly relativistic particles the detection of Cherenkov light is very promising. The Cherenkov rings can be reconstructed from the internally reflected Cherenkov photons detected with position sensitive photomultipliers. DIRC detectors (both in form of a barrel and in form of a disc) are planned to be used in the PANDA detector at FAIR. For the WASA-at-COSY experiment details of the DIRC elements manufacturing and their holding structure are discussed.
Impact of the 3d Electronic States of Cobalt and Manganese Phthalocyanines on the Electronic Structure at the Interface to Ag(111)
2011-10-06

X-ray absorption (XAS) and photoemission (XPS) spectroscopy revealed a strong interaction at the interface between transition-metal Cobalt phthalocyanine (CoPc) and single-crystalline Ag(111) substrate. According the Co L-edge absorption spectra of ultrathin CoPc films, charge transfer between the metal 3d electrons and the underlying metallic substrate occurs. Less intense but comparable effects are also observed at the MnPc/Ag(111) interface for partially filled d levels of Mn. The nature of interacting orbitals is also discussed by means of resonant photoemission spectroscopy (ResPES) as well as in comparison with the CoPc/Au(100) interface studied previously.
Coagulation Factor IX Mediates Serotype-Specific Binding of Species A Adenoviruses to Host Cells
2011-10-06

ABSTRACT Human species A adenoviruses (HAdVs) comprise three serotypes: HAdV-12, -18, and -31. These viruses are common pathogens and cause systemic infections that usually involve the airways and/or intestine. In immunocompromised individuals, species A adenoviruses in general, and HAdV-31 in particular, cause life-threatening infections. By combining binding and infection experiments, we demonstrate that coagulation factor IX (FIX) efficiently enhances binding and infection by HAdV-18 and HAdV-31, but not by HAdV-12, in epithelial cells originating from the airways or intestine. This is markedly different from the mechanism for HAdV-5 and other human adenoviruses, which utilize coagulation factor X (FX) for infection of host cells. Surface plasmon resonance experiments revealed that the affinity of the HAdV-31 hexon-FIX interaction is higher than that of the HAdV-5 hexon-FX interaction and that the half-lives of these interactions are profoundly different. Moreover, both HAdV-31–FIX and HAdV-5–FX complexes bind to heparan sulfate-containing glycosaminoglycans (GAGs) on target cells, but binding studies utilizing cells expressing specific GAGs and GAG-cleaving enzymes revealed differences in GAG dependence and specificity between these two complexes. These findings add to our understanding of the intricate infection pathways used by human adenoviruses, and they may contribute to better design of HAdV-based vectors for gene and cancer therapy. Furthermore, the interaction between the HAdV-31 hexon and FIX may also serve as a target for antiviral treatment.
Formation and Photocatalytic Decomposition of a Pellicle on Anatase Surfaces
2011-10-06

The acquired dental pellicle plays a critical role in the adhesion and detachment of dental plaque bacteria. It has been reported that titanium dioxide biomaterials decompose single-protein films by photocatalysis. However, it is not known whether this can also be achieved with complex structured pellicle films. This in vitro study investigated in real-time the formation and photocatalytic decomposition of human pellicle at anatase-saliva interfaces. Nanostructured polycrystalline anatase layers were deposited on titanium-coated quartz crystals by magnetron-sputtering, serving as a model for titanium implant surfaces. The quartz crystals were used as acoustic sensors in a quartz-crystal microbalance (QCM) system with dissipation. In situ UV irradiation of pellicle-covered anatase caused a statistically significant decrease of the adsorbed salivary mass. In contrast, photocatalytic decomposition of pellicle could not be observed on reference titanium surfaces. Wettability characterization revealed superhydrophilicity of anatase upon UV irradiation, whereas titanium was unaffected. XPS measurements provide further information concerning the decomposition of the salivary films. The results suggest that the photocatalytic activity of polycrystalline anatase-modified biomaterial surfaces is able to decompose complex structured macromolecular pellicle films. Therefore, this study opens the way to surface modifications supporting therapeutic approaches of biofilm removal.
Using real-time fMRI to learn voluntary regulation of the anterior insula in the presence of threat-related stimuli
2011-10-07

Previous studies have shown that healthy participants learn to control local brain activity with operant training by using real-time functional magnetic resonance imaging (rt-fMRI). Very little data exist, however, on the dynamics of interaction between critical brain regions during rt-fMRI-based training. Here, we examined self-regulation of stimulus-elicited insula activation and performed a psychophysiological interaction (PPI) analysis of real-time self-regulation data. During voluntary up-regulation of the left anterior insula in the presence of threat-related pictures, differential activations were observed in the ventrolateral prefrontal cortex, the frontal operculum, the middle cingulate cortex and the right insula. Down-regulation in comparison to no-regulation revealed additional activations in right superior temporal cortex, right inferior parietal cortex and right middle frontal cortex. There was a significant learning effect over sessions during up-regulation, documented by a significant improvement of anterior insula control over time. Connectivity analysis revealed that successful up-regulation of the activity in left anterior insula while viewing aversive pictures was directly modulated by dorsomedial and ventrolateral prefrontal cortex. Down-regulation of activity was more difficult to achieve and no learning effect was observed. More extensive training might be necessary for successful down-regulation. These findings illustrate the functional interactions between different brain areas during regulation of anterior insula activity in the presence of threat-related stimuli.
Human Hepatocytes: Isolation, Culture, and Quality Procedures
2011-10-07

The use of isolated human liver cells in research and development has gained increasing interest during the past years. The possible application may vary between elucidation of new biochemical pathways in liver diseases, drug development, safety issues, and new therapeutic strategies up to direct clinical translation for liver support. However, the isolation of human liver cells requires a well-developed logistic network among surgeons, biologists, and technicians to obtain a high quality of cells. Our laboratories have been involved in various applications of human liver cells and we have long-lasting experiences in human liver cell isolation and their application in R&D. We here summarize the present protocol of our laboratories for cell isolation from normal resected liver tissue, the most common tissue available. In addition, we discuss the necessary network in the clinic and quality controls to maintain human liver cells in culture and the effect of 3D extracellular matrix in cultured cells which results in preservation of hepatocyte epithelial polarity in the form of bile canaliculi and repression of epithelial to mesenchymal transitions occurring in 2D cultures.
High cytoplasmic expression of p27 Kip1 is associated with a worse cancer‐specific survival in clear cell renal cell carcinoma
2011-10-07

What's known on the subject? and What does the study add? The loss of p27 Kip1 correlates with poor prognosis in various human cancers, and was postulated as a biomarker in RCC. Up to now p27 Kip1 analysis in RCC was focused on its nuclear localization. We confirmed higher p27 Kip1 expression in the nucleus and cytoplasm of RCC and correlated high cytoplasmic p27 Kip1 with an unfavourable clinic and a reduced survival. OBJECTIVES To analyse the cytoplasmic and nuclear differences of p27 Kip1 expression and localization in benign and clear cell renal cell carcinoma (ccRCC) with regard to overall survival (OS) and cancer‐specific survival (CSS). p27 Kip1 is considered to contribute to the progression of ccRCC and is targeted by next generation dual‐therapies. PATIENTS AND METHODS In 140 patients, ccRCC and corresponding benign kidney tissue were analyzed for nuclear and cytoplasmic staining of p27 Kip1 by immunohistochemistry using a tissue microarray technique. Staining intensity and percentage of positive stained cells are given as expression scores. p27 Kip1 expression was categorized as high if ccRCC tissue stained stronger than the respective level of the corresponding benign tissue and categorized as low if ccRCC tissue stained less than or equal to the corresponding benign tissue. Differences in OS and CSS were analyzed by log‐rank analysis and expression levels were correlated with tumour and patient characteristics using Fisher's exact test. RESULTS Cytoplasmatic (mean [ sd ]: 13.8% [1.2%] vs 10.7% [1.7%]; P = 0.04) and nuclear (mean [ sd ]: 75.6% [2.7%] vs 13.6% [2.1%]; P &lt; 0.001) staining of p27 Kip1 were significantly stronger in ccRCC tissues compared to benign tissue. High cytoplasmic p27 Kip1 expression was significantly associated with a higher T and N stage, Fuhrman grade and the presence of metastatic disease ( P &lt; 0.001). The median follow‐up time was 38.2 months. There was no difference in OS between the low and high expression groups, although CSS was significantly lower in patients with high cytoplasmic p27 Kip1 ( P &lt; 0.001) and CSS heavily tended to be lower in the nuclear low expression group ( P = 0.069). CONCLUSIONS High cytoplasmic p27 Kip1 levels in renal cancer tissues are associated with advanced disease and reduced cancer specific survival, whereas low nuclear expression levels appear to be beneficial. The present study corroborates the consideration of cytoplasmic p27 Kip1 for future diagnostic and targeted therapeutic approaches in RCC establishing a potential protective shift of p27 Kip1 from the cytoplasm to the nucleus.
Alterations in expression levels of deafness dystonia protein 1 affect mitochondrial morphology
2011-10-07

Deafness-Dystonia-Optic Neuropathy (DDON) Syndrome is a rare X-linked progressive neurodegenerative disorder resulting from mutations in the TIMM8A gene encoding for the deafness dystonia protein 1 (DDP1). Despite important progress in identifying and characterizing novel mutations in this gene, little is known about the underlying pathomechanisms. Deficiencies in the biogenesis of hTim23 and consecutive alterations in biogenesis of inner membrane and matrix proteins have been proposed to serve as one possible mechanistic explanation. To shed new light on the role of DDP1 in the biogenesis of mammalian mitochondria, we investigated the effects of reduced or elevated DDP1 levels on mitochondrial dynamics and function. Our results show a reduction in the import of β-barrel proteins into mitochondria from cells overexpressing DDP1. This effect was not observed when the DDON-related mutant form DDP1-C66W was overexpressed. Live cell microscopy of primary fibroblasts derived from DDON patients and of DDP1 downregulated HeLa cells displayed alterations of mitochondrial morphology with notable extensions in the length of mitochondrial tubules, whereas overexpression of DDP1 induced the formation of hollow spherical mitochondria. Of note, knockdown of the TIMM8A gene by RNA interference did not show an influence on the oxygen respiration rate and the mitochondrial membrane potential. Taken together, these results suggest that alterations in the levels of DDP1 can affect the morphology of mitochondria and thus shed new light on the pathogenic mechanisms of DDON.
Novel Role for SGK3 in Glucose Homeostasis Revealed in SGK3/Akt2 Double-Null Mice
2011-10-07

The phosphatidylinositol-3-kinase-dependent kinase, Akt2, plays a central role in mediating insulin effects in glucose-metabolizing tissues. Akt2 knockout mice display insulin resistance with a reactive increase in pancreatic islet mass and hyperinsulinemia. The related phosphatidylinositol-3-kinase-dependent kinase, serum- and glucocorticoid-regulated kinase 3 (SGK3), is essential for normal postnatal hair follicle development but plays no apparent role in glucose homeostasis. We report here an unexpected role of SGK3 in islet β-cell function, which is revealed in Akt2/SGK3 double-knockout (DKO) mice. DKO mice have markedly worse glucose homeostasis than Akt2 single-null animals, including greater baseline glucose, and greater rise in blood glucose after glucose challenge. However, surprisingly, our data strongly support the idea that this exacerbation of the glucose-handling defect is due to impaired β-cell function, rather than increased insulin resistance in peripheral tissues. DKO mice had lower plasma insulin and C-peptide levels, lower β-cell mass, reduced glucose-stimulated insulin secretion, and greater sensitivity to exogenous insulin than Akt2 single nulls. We further demonstrated that SGK3 is strongly expressed in normal mouse islets and, interestingly, that β-catenin expression is dramatically lower in the islets of DKO mice than in those of Akt2(-/-)/SGK3(+/+) or Akt2(-/-)/SGK3(+/-) mice. Taken together, these data strongly suggest that SGK3 plays a previously unappreciated role in glucose homeostasis, likely through direct effects within β-cells, to stimulate proliferation and insulin release, at least in part by controlling the expression and activity of β-catenin.
Preclinical Testing of Virotherapeutics for Primary and Secondary Tumors of the Liver
2011-10-07

Virotherapy offers a new treatment strategy using oncolytic viruses as self-replicating, tumor-specific agents, which destroy tumors during their natural lytic replication process. To study potential oncolytic viruses, cell culture experiments give basic information about the lytic potential of a virus, measured as cell lysis or decreased viability. For further analysis, animal models are usually employed. As these in vivo experiments are often performed in immunocompromised animals, results have to be interpreted with caution. Therefore, to obtain deeper information of the oncolytic action of specific viruses in a patient's individual context we established a test platform based on human primary tissue slices. In this three-dimensional model, we observed a preferential tumor infection and the penetration of oncolytic measles vaccine virus into deeper cell layers of tumor tissues, which is an essential feature of an effective oncolytic virus.
Pyronaridine–artesunate combination therapy for the treatment of malaria
2011-10-08

Pyronaridine-artesunate - currently under evaluation by the European Medicines Agency - may become a preferred choice as first-line therapy in malaria endemic regions based on its low cost, long shelf-life, simplified once-daily dosing regimen, proven efficacy against falciparum and vivax malaria, and the parallel clinical development of a paediatric drug formulation.
Design and architectures for dependable embedded systems
2011-10-09

The paper presents an overview of a major research project on dependable embedded systems that has started in Fall 2010 and is running for a projected duration of six years. Aim is a 'dependability co-design' that spans various levels of abstraction in the design process of embedded systems starting from gate level through operating system, applications software to system architecture. In addition, we present a new classification on faults, errors, and failures.
Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells
2011-10-10

Fumarates improve multiple sclerosis (MS) and psoriasis, two diseases in which both IL-12 and IL-23 promote pathogenic T helper (Th) cell differentiation. However, both diseases show opposing responses to most established therapies. First, we show in humans that fumarate treatment induces IL-4–producing Th2 cells in vivo and generates type II dendritic cells (DCs) that produce IL-10 instead of IL-12 and IL-23. In mice, fumarates also generate type II DCs that induce IL-4–producing Th2 cells in vitro and in vivo and protect mice from experimental autoimmune encephalomyelitis. Type II DCs result from fumarate-induced glutathione (GSH) depletion, followed by increased hemoxygenase-1 (HO-1) expression and impaired STAT1 phosphorylation. Induced HO-1 is cleaved, whereupon the N-terminal fragment of HO-1 translocates into the nucleus and interacts with AP-1 and NF-κB sites of the IL-23p19 promoter. This interaction prevents IL-23p19 transcription without affecting IL-12p35, whereas STAT1 inactivation prevents IL-12p35 transcription without affecting IL-23p19. As a consequence, GSH depletion by small molecules such as fumarates induces type II DCs in mice and in humans that ameliorate inflammatory autoimmune diseases. This therapeutic approach improves Th1- and Th17-mediated autoimmune diseases such as psoriasis and MS by interfering with IL-12 and IL-23 production.
Prospective detection of open spina bifida at 11–13 weeks by assessing intracranial translucency and posterior brain
2011-10-10

Abstract We describe a case series of six fetuses with open spina bifida (OSB) from four different prenatal units, where the anomaly was detected at the routine 11–13‐week ultrasound examination. Crown–rump length ranged from 49 to 78 mm. All cases were first suspected during nuchal translucency thickness measurement in the mid‐sagittal plane of the face. OSB was lumbosacral in five fetuses and cervical in one. The intracranial translucency (IT) was obliterated in two cases, but some fluid was found in the other four cases. However, in all cases the typical landmarks of a normal posterior brain and normal IT were absent. In all six cases the ratio of brainstem diameter to brainstem–occipital bone distance was increased (≥ 1). This detection of an abnormal posterior brain led to a targeted examination and detection of the spinal lesion during the same examination in five cases, whereas in one suspicious case the patient was recalled at 17 weeks, when the abnormality was detected. Two fetuses had both multiple anomalies and trisomy 18. These prospective cases demonstrate the feasibility of using the standard mid‐sagittal plane commonly used for NT measurement to assess the IT and the posterior brain and to determine the presence of OSB during NT screening. Copyright © 2011 ISUOG. Published by John Wiley &amp; Sons, Ltd.
Macrocyclic Proteasome Inhibitors
2011-10-10

Proteasome inhibitors have proven to be effective anticancer agents. Despite the success of the first on the market proteasome inhibitor bortezomib in chemotherapy, alternative clinically useful proteasome inhibitors are still urgently needed as bortezomib therapy causes severe side effects and is limited by arising drug resistance. Experience from previous proteasome inhibitor studies has thereby demonstrated that the identification of proteasome inhibitor structures with suitable pharmacological properties is a key factor for a successful development of clinically useful proteasome inhibitors. Macrocycles often show distinct and in comparison to linear small molecules superior pharmacological properties. Consequently, macrocyclic proteasome inhibitors might represent promising small molecules for drug development. Here, we want to highlight the current state of the art of macrocyclic proteasome inhibitor research. To this end, we give an overview and critically discuss currently known classes of macrocyclic proteasome inhibitors.
Platelet and Soluble Glycoprotein VI - Novel Applications in Diagnosis and Therapy
2011-10-10

One of the key receptors involved in the prothrombotic stage of an acute coronary syndrome (ACS) is platelet glycoprotein VI (GPVI). This constitutively expressed collagen receptor is platelet-specific and has shown to be a useful biomarker tool for the early detection of atheroslerotic diseases such as ACS and ischemic stroke. In a multimarker panel of several biomarkers, platelet GPVI may contribute to risk stratification and prediction of clinical outcome in patients with symptomatic atherosclerotic diseases. Moreover, the soluble receptor of GPVI may also be an interesting and prospective target for molecular imaging to identify sites of vulnerable plaques as the results of preclinical studies suggest. Apart from the diagnostic use of platelet as well as soluble, plasmatic GPVI, therapeutical implications may be the blockade of collagen binding sides of GPVI, as platelet GPVI is not able to bind to collagen where the binding sides were already saturated with soluble GPVI. This therapeutic aspect could serve as a promising strategy for antithrombotic and antiatherosclerotic therapy in future.
Numerical approximations of the Mumford–Shah functional for unit vector fields
2011-10-10

Two numerical approximation schemes for minimising the Mumford–Shah functional for unit vector fields are proposed, analysed, and compared. The first uses a projection strategy, the second a penalisation strategy to enforce the sphere constraint. Both schemes are then applied to the segmentation of colour images using the Chromaticity and Brightness colour model.