julilili42/papers huggingface dataset:
7 Comparison of Efficacy and Safety of a Dipigmented Polymerized Allergen Extract of Grass and Birch with Placebo in Patients With Type-1 Allergic Rhinoconjunctivitis
2012-02-01

BACKGROUND: The safety and efficacy of specific immunotherapy (SIT) with depigmented and polymerized allergen extracts of pollen is well documented in several clinical trials. We investigated efficacy and safety of an extract containing 2 taxonomically non-related pollen species (birch and grasses) in a subcutaneous immunotherapy over 2 pollen seasons in co-sensitized allergic patients with rhinitis and/or rhinoconjunctivitis with or without allergic asthma. METHODS: 269 (ITT) patients with confirmed rhinitis and/or rhinoconjunctivitis were treated during 2009 and 2010 in Germany, Romania, Poland, Lithuania, and Bulgaria. For each patient a 1-day build-up phase applying 0.2 mL and 0.3 mL of 1000 DPP/mL allergen extract was applied. During the remaining 18-month period maintenance 500 DPP were administered in 4 to 6 weeks intervals. Patients were randomised to the treatment groups on a 2:1 basis (175 verum: 94 placebo). The main parameter in this study was the combined symptom and medication score during the birch and grass pollen season 2010 over 7 weeks. Secondary parameters were symptom score, medication score, IgE, IgG4 as well as quality of life. RESULTS: During the 2010 season a statistically significant difference (P = 0.0385) was observed between treatment groups: in patients treated with the allergen extract the median time weighted AUC of the combined symptom and medication score was 5.70, in patients treated with placebo 7.07. This effect was predominantly due to the reduction of symptom score by 21% over placebo. The intake of recue medication was very low during both seasons leading only to a 10% reduction (ns). Birch and phleum specific IgE did not change during the course of the study in both groups whereas respective IgG4 levels increased only in the verum group and remained nearly unchanged in the placebo group (P < 0.0001). Total QoL score was improved in verum patients (P = 0.0254). 5.4% of the patients in the verum group and 4.0% of the patients in the placebo group developed mild systemic reactions. CONCLUSIONS: The results show that specific immunotherapy with a depigmented polymerized extract of 2 taxonomically non-related pollen (birch and grass) was effective and safe demonstrated by clinical and immunological parameter.
Market Liberalization, Regulatory Uncertainty, and Firm Investment
2012-02-01

This paper analyzes the effects of regulatory uncertainty regarding labor costs on investment in a liberalized market. We distinguish between the external investment margin (market entry) and the internal investment margin (technology), and establish that regulatory uncertainty affects these margins differently, encouraging market entry, but discouraging technological investment. As a consequence, the impact of regulatory uncertainty on competition in liberalized markets is a combination of these two countervailing forces.
THE 2010 VERY HIGH ENERGY γ-RAY FLARE AND 10 YEARS OF MULTI-WAVELENGTH OBSERVATIONS OF M 87
2012-02-02

The giant radio galaxy M 87 with its proximity (16 Mpc), famous jet, and very massive black hole ((3 - 6) × 109 M ⊙) provides a unique opportunity to investigate the origin of very high energy (VHE; E &gt; 100 GeV) γ-ray emission generated in relativistic outflows and the surroundings of supermassive black holes. M 87 has been established as a VHE γ-ray emitter since 2006. The VHE γ-ray emission displays strong variability on timescales as short as a day. In this paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE was detected triggering further observations at VHE (H.E.S.S.), X-rays (Chandra), and radio (43 GHz Very Long Baseline Array, VLBA). The excellent sampling of the VHE γ-ray light curve enables one to derive a precise temporal characterization of the flare: the single, isolated flare is well described by a two-sided exponential function with significantly different flux rise and decay times of τrise d = (1.69 ± 0.30) days and τdecay d = (0.611 ± 0.080) days, respectively. While the overall variability pattern of the 2010 flare appears somewhat different from that of previous VHE flares in 2005 and 2008, they share very similar timescales (~day), peak fluxes (Φ&gt;0.35 TeV ~= (1-3) × 10-11 photons cm-2 s-1), and VHE spectra. VLBA radio observations of 43 GHz of the inner jet regions indicate no enhanced flux in 2010 in contrast to observations in 2008, where an increase of the radio flux of the innermost core regions coincided with a VHE flare. On the other hand, Chandra X-ray observations taken ~3 days after the peak of the VHE γ-ray emission reveal an enhanced flux from the core (flux increased by factor ~2; variability timescale &lt;2 days). The long-term (2001-2010) multi-wavelength (MWL) light curve of M 87, spanning from radio to VHE and including data from Hubble Space Telescope, Liverpool Telescope, Very Large Array, and European VLBI Network, is used to further investigate the origin of the VHE γ-ray emission. No unique, common MWL signature of the three VHE flares has been identified. In the outer kiloparsec jet region, in particular in HST-1, no enhanced MWL activity was detected in 2008 and 2010, disfavoring it as the origin of the VHE flares during these years. Shortly after two of the three flares (2008 and 2010), the X-ray core was observed to be at a higher flux level than its characteristic range (determined from more than 60 monitoring observations: 2002-2009). In 2005, the strong flux dominance of HST-1 could have suppressed the detection of such a feature. Published models for VHE γ-ray emission from M 87 are reviewed in the light of the new data.
Photoluminescence spectroscopy of pure pentacene, perfluoropentacene, and mixed thin films
2012-02-02

We report detailed temperature dependent photoluminescence (PL) spectra of pentacene (PEN), perfluoropentacene (PFP), and PEN:PFP mixed thin films grown on SiO2. PEN and PFP are particularly suitable for this study, since they are structurally compatible for good intermixing and form a model donor/acceptor system. The PL spectra of PEN are discussed in the context of existing literature and compared to the new findings for PFP. We analyze the optical transitions observed in the spectra of PEN and PFP using time-dependent density functional theory calculations. Importantly, for the mixed PEN:PFP film we observe an optical transition in PL at 1.4 eV providing evidence for coupling effects in the blend. We discuss a possible charge-transfer (CT) and provide a tentative scheme of the optical transitions in the blended films.
PCBs and OCPs on a East-to-West Transect: The Importance of Major Currents and Net Volatilization for PCBs in the Atlantic Ocean
2012-02-02

Air-water exchange gradients of selected polychlorinated biphenyl (PCB) congeners across a large section of the tropical Atlantic suggested net volatilization of PCBs to the atmosphere. Only for the higher chlorinated PCB 153 and hexachlorobenzene (HCB) were gradients near equilibrium detected. The use of passive samplers also enabled the detection of dichlorodiphenyltrichloroethane (DDT) and its transformation products across the tropical Atlantic, indicating net deposition. There were clear differences between the southern and northern hemisphere apparent in terms of atmospheric concentrations: Once the ship moved from the southern into the northern hemisphere air, concentrations of HCB and other organochlorine pesticides increased several-fold. For large swaths of the tropical Atlantic Ocean, neither PCB nor organochlorine pesticide dissolved concentrations varied much longitudinally, probably due to efficient mixing by ocean currents. In selected samples, dissolved concentrations reflected the influence of river plumes and major ocean currents far away from the continents. Dissolved concentrations of PCBs 28, 52, 101, 118, and HCB increased in the Amazon plume and the Gulf Stream. While the Amazon plume flushed only a few kg of PCBs and HCB, the Gulf Stream is potentially delivering tons of PCBs into the North Atlantic annually.
Visualization and Quantitative Analysis of Reconstituted Tight Junctions Using Localization Microscopy
2012-02-02

Tight Junctions (TJ) regulate paracellular permeability of tissue barriers. Claudins (Cld) form the backbone of TJ-strands. Pore-forming claudins determine the permeability for ions, whereas that for solutes and macromolecules is assumed to be crucially restricted by the strand morphology (i.e., density, branching and continuity). To investigate determinants of the morphology of TJ-strands we established a novel approach using localization microscopy.TJ-strands were reconstituted by stable transfection of HEK293 cells with the barrier-forming Cld3 or Cld5. Strands were investigated at cell-cell contacts by Spectral Position Determination Microscopy (SPDM), a method of localization microscopy using standard fluorophores. Extended TJ-networks of Cld3-YFP and Cld5-YFP were observed. For each network, 200,000 to 1,100,000 individual molecules were detected with a mean localization accuracy of ∼20 nm, yielding a mean structural resolution of ∼50 nm. Compared to conventional fluorescence microscopy, this strongly improved the visualization of strand networks and enabled quantitative morphometric analysis. Two populations of elliptic meshes (mean diameter <100 nm and 300-600 nm, respectively) were revealed. For Cld5 the two populations were more separated than for Cld3. Discrimination of non-polymeric molecules and molecules within polymeric strands was achieved. For both subtypes of claudins the mean density of detected molecules was similar and estimated to be ∼24 times higher within the strands than outside the strands.The morphometry and single molecule information provided advances the mechanistic analysis of paracellular barriers. Applying this novel method to different TJ-proteins is expected to significantly improve the understanding of TJ on the molecular level.
Lucinda Driving Too Fast Again--The Scalar Properties of Ambiguous Than-Clauses
2012-02-02

Journal Article Lucinda Driving Too Fast Again—The Scalar Properties of Ambiguous Than-Clauses Get access Sigrid Beck Sigrid Beck Universität Tübingen SIGRID BECK Universität Tübingen Wilhelmstr. 50 72074 Tübingen, Germany sigrid.beck@uni-tuebingen.de Search for other works by this author on: Oxford Academic Google Scholar Journal of Semantics, Volume 30, Issue 1, February 2013, Pages 1–63, https://doi.org/10.1093/jos/ffr011 Published: 02 February 2012 Article history Received: 20 December 2010 Revision received: 11 August 2011 Accepted: 27 September 2011 Published: 02 February 2012
Persistence versus Escape: Aspergillus terreus and Aspergillus fumigatus Employ Different Strategies during Interactions with Macrophages
2012-02-03

Invasive bronchopulmonary aspergillosis (IBPA) is a life-threatening disease in immunocompromised patients. Although Aspergillus terreus is frequently found in the environment, A. fumigatus is by far the main cause of IBPA. However, once A. terreus establishes infection in the host, disease is as fatal as A. fumigatus infections. Thus, we hypothesized that the initial steps of disease establishment might be fundamentally different between these two species. Since alveolar macrophages represent one of the first phagocytes facing inhaled conidia, we compared the interaction of A. terreus and A. fumigatus conidia with alveolar macrophages. A. terreus conidia were phagocytosed more rapidly than A. fumigatus conidia, possibly due to higher exposure of β-1,3-glucan and galactomannan on the surface. In agreement, blocking of dectin-1 and mannose receptors significantly reduced phagocytosis of A. terreus, but had only a moderate effect on phagocytosis of A. fumigatus. Once phagocytosed, and in contrast to A. fumigatus, A. terreus did not inhibit acidification of phagolysosomes, but remained viable without signs of germination both in vitro and in immunocompetent mice. The inability of A. terreus to germinate and pierce macrophages resulted in significantly lower cytotoxicity compared to A. fumigatus. Blocking phagolysosome acidification by the v-ATPase inhibitor bafilomycin increased A. terreus germination rates and cytotoxicity. Recombinant expression of the A. nidulans wA naphthopyrone synthase, a homologue of A. fumigatus PksP, inhibited phagolysosome acidification and resulted in increased germination, macrophage damage and virulence in corticosteroid-treated mice. In summary, we show that A. terreus and A. fumigatus have evolved significantly different strategies to survive the attack of host immune cells. While A. fumigatus prevents phagocytosis and phagolysosome acidification and escapes from macrophages by germination, A. terreus is rapidly phagocytosed, but conidia show long-term persistence in macrophages even in immunocompetent hosts.
A novel GlnR target gene, nnaR, is involved in nitrate/nitrite assimilation in Streptomyces coelicolor
2012-02-03

GlnR is the global transcriptional regulator of nitrogen assimilation in Streptomyces coelicolor. Under nitrogen starvation, GlnR controls the transcription of at least nine genes associated with nitrogen metabolism. In this study, we identified a new GlnR target gene, SCO2958, named nnaR (nitrate/nitrite assimilation regulator). In silico analysis of NnaR revealed the presence of two distinct domains: an N-terminal uroporphyrinogen-III synthase (HemD)-like enzymatic domain and a C-terminal DNA binding domain. Complementation experiments with a haemin auxotroph Escherichia coli ΔhemD mutant strain revealed that NnaR has no HemD activity. Physiological studies of an S. coelicolor nnaR : : Tn5062 mutant showed that NnaR is involved in regulating nitrite reduction. By electrophoretic mobility shift assays the functionality of the NnaR DNA binding domain was confirmed, and it was found that NnaR binds in front of the genes narK (putative nitrate extrusion protein), nirB (nitrite reductase), nirA (putative nitrite/sulphite reductase) and nasA (putative nitrate reductase), which are associated with nitrate/nitrite assimilation. Furthermore, a cooperative binding of NnaR together with GlnR to the nirB promoter was observed, suggesting that NnaR may act as a GlnR co-activator.
Immunotherapy of Renal Cell Carcinoma – From Antigen Identification to Patient Treatment
2012-02-03

Immunotherapy of Renal Cell Carcinoma -From Antigen Identification to Patient Treatment 195In some cases systemic application of high dose cytokines can however also lead to serious and life-threatening side effects.These symptoms have been known for a long time to also occur under cytokine monotherapy and are therefore not directly associated with the vaccine. www.intechopen.comEmerging Research and Treatments in Renal Cell Carcinoma 196 *Number of patients treated versus number of patients in control group in brackets.mRCC: metastatic renal cell carcinoma, ccRCC: clear cell renal cell
Bone Marrow-Derived Human Mesenchymal Stem Cells Express Cardiomyogenic Proteins But Do Not Exhibit Functional Cardiomyogenic Differentiation Potential
2012-02-06

Despite their paracrine activites, cardiomyogenic differentiation of bone marrow (BM)-derived mesenchymal stem cells (MSCs) is thought to contribute to cardiac regeneration. To systematically evaluate the role of differentiation in MSC-mediated cardiac regeneration, the cardiomyogenic differentiation potential of human MSCs (hMSCs) and murine MSCs (mMSCs) was investigated in vitro and in vivo by inducing cardiomyogenic and noncardiomyogenic differentiation. Untreated hMSCs showed upregulation of cardiac tropopin I, cardiac actin, and myosin light chain mRNA and protein, and treatment of hMSCs with various cardiomyogenic differentiation media led to an enhanced expression of cardiomyogenic genes and proteins; however, no functional cardiomyogenic differentiation of hMSCs was observed. Moreover, co-culturing of hMSCs with cardiomyocytes derived from murine pluripotent cells (mcP19) or with murine fetal cardiomyocytes (mfCMCs) did not result in functional cardiomyogenic differentiation of hMSCs. Despite direct contact to beating mfCMCs, hMSCs could be effectively differentiated into cells of only the adipogenic and osteogenic lineage. After intramyocardial transplantation into a mouse model of myocardial infarction, Sca-1(+) mMSCs migrated to the infarcted area and survived at least 14 days but showed inconsistent evidence of functional cardiomyogenic differentiation. Neither in vitro treatment nor intramyocardial transplantation of MSCs reliably generated MSC-derived cardiomyocytes, indicating that functional cardiomyogenic differentiation of BM-derived MSCs is a rare event and, therefore, may not be the main contributor to cardiac regeneration.
Micropollutants in three tributaries of Lake Constance, Argen, Schussen and Seefelder Aach: a literature review
2012-02-06

A literature review made evident that in three tributaries of Lake Constance, Argen, Schussen and Seefelder Aach 82 micropollutants (including 3 metabolites of pesticides) were detected in at least one of the streams. Quality standards according to the EU Water Frame Directive (which however comprises only 16 of the detected chemicals) are not exceeded in any of the streams. The comparison of maximal values with existing threshold values and effect concentrations obtained in ecotoxicological analyses and biomarker studies revealed 35 substances to be of relevance in at least one of the three waters. These were 5 chemicals in the Argen, 31 chemicals in the Schussen, and 17 chemicals in the Seefelder Aach, for which effects on mortality, development, health or reproduction in aquatic organisms cannot be excluded.
Abstract C27: Whole-exome sequencing identifies potential therapeutic targets for castration-resistant prostate cancer
2012-02-06

Abstract Aim: Castration resistant prostate cancer (CR-PCa) is the most aggresive form of prostate cancer (PCa) having a poor prognosis, and is a significant therapeutic challenge. The key to the development of novel therapeutic targets for CR-PCa is to decipher the molecular alterations underlying this lethal disease. The aim of our study was to perform whole exome sequencing and gene copy number analysis on 5 CR-PCa/normal paired formalin fixed paraffin embedded (FFPE) samples using the SOLiD4 next generation sequencing platform. Methods: Genomic DNA was extracted from 5 CR-PCa/normal paired FFPE samples. The DNA was subjected to targeted exon capture using the Agilent Sure Select kit. The captured DNA was sequenced using the SOLiD4 next generation sequencing platform. The sequencing output was mapped, sorted, filtered and annotated using well-known human genome databases. The results were further analyzed for SNPs and copy number variations. A set of amplified/deleted genes were validated using fluorescence in-situ hybridization (FISH) assays with a PCa progression cohort. The cohort consisted of 138 cases for localized cancer, 105 patients with primary PCa and corresponding LN metastasis, and 39 samples for castration resistant tumors. Results: Whole exome sequencing analysis identified focal regions of deletion, which included well-known tumor suppressors such as NKX3.1 and PTEN. Focal regions of amplification included well-known genes such as CMYC and AR that are known to play a role in PCa. Furthermore, we identified several amplified genes as druggable targets e.g. HDAC6, NTRK1, PLD1, SPHK1, and SIRT7. NTRK1 is a kinase that plays an active role in cell proliferation. HDAC6, PLD1, SPHK1 and SIRT7 regulate numerous complex cellular processes including signal transduction, transcription and apoptosis. Conclusions: This is the first study to use whole exome sequencing approaches on FFPE CR-PCa material to identity novel therapeutic targets. Validation studies would further shed light into the biological understanding of the disease and its plausible treatment options. Citation Format: Roopika Menon, Mario Deng, Diana Boehm, Falko Fend, Detlef Boehm, Saskia Biskup, Sven Perner. Whole-exome sequencing identifies potential therapeutic targets for castration-resistant prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C27.
Spinocerebellar ataxia type 1 (SCA1): new pathoanatomical and clinico‐pathological insights
2012-02-07

U. Rüb, K. Bürk, D. Timmann, W. den Dunnen, K. Seidel, K. Farrag, E. Brunt, H. Heinsen, R. Egensperger, A. Bornemann, S. Schwarzacher, H.‐W. Korf, L. Schöls, J. Bohl and T. Deller (2012) Neuropathology and Applied Neurobiology 38, 665–680 Spinocerebellar ataxia type 1 (SCA1): new pathoanatomical and clinico‐pathological insights Aims: Spinocerebellar ataxia type 1 (SCA1) represents the first molecular genetically characterized autosomal dominantly inherited cerebellar ataxia and is assigned to the CAG‐repeat or polyglutamine diseases. Owing to limited knowledge about SCA1 neuropathology, appropriate pathoanatomical correlates of a large variety of SCA1 disease symptoms are missing and the neuropathological basis for further morphological and experimental SCA1 studies is still fragmentary. Methods: In the present study, we investigated for the first time serial tissue sections through the complete brains of clinically diagnosed and genetically confirmed SCA1 patients. Results: Brain damage in the three SCA1 patients studied went beyond the well‐known brain predilection sites of the underlying pathological process. Along with neuronal loss in the primary motor cortex, it included widespread degeneration of gray components of the basal forebrain, thalamus, brainstem and cerebellum, as well as of white matter components in the cerebellum and brainstem. It involved the motor cerebellothalamocortical and basal ganglia‐thalamocortical circuits, the visual, auditory, somatosensory, oculomotor, vestibular, ingestion‐related, precerebellar, basal forebrain cholinergic and midbrain dopaminergic systems. Conclusions: These findings show for the first time that the extent and severity of brain damage in SCA1 is very similar to that of clinically closely related spinocerebellar ataxias (that is, SCA2, SCA3 and SCA7). They offer suitable explanations for poorly understood SCA1 disease symptoms and will facilitate the interpretation of further morphological and experimental SCA1 studies.
The impact of cyclin D1 mRNA isoforms, morphology and p53 in mantle cell lymphoma: p53 alterations and blastoid morphology are strong predictors of a high proliferation index
2012-02-07

TP53 alterations are strongly associated with a high proliferation index and aggressive behavior in mantle cell lymphoma. Predominance of the 3'UTR-deficient transcript correlates with higher cyclin D1 levels and may be a secondary contributing factor to high proliferation, but failed to reach prognostic significance in this study.