julilili42/papers huggingface dataset:
Inhibitory Effect of NH4Cl Treatment on Renal Tgfß1 Signaling Following Unilateral Ureteral Obstruction
2015-01-01

Background/Aims: Consequences of obstructive nephropathy include tissue fibrosis, a major pathophysiological mechanism contributing to development of end-stage renal disease. Transforming growth factor β 1 (Tgfβ1) is involved in the progression of renal fibrosis. According to recent observations, ammonium chloride (NH4Cl) prevented phosphate-induced vascular remodeling, effects involving decrease of Tgfβ1 expression and inhibition of Tgfβ1-dependent signaling. The present study, thus, explored whether NH4Cl influences renal Tgfβ1-induced pro-fibrotic signaling in obstructive nephropathy induced by unilateral ureteral obstruction (UUO). Methods: UUO was induced for seven days in C57Bl6 mice with or without additional treatment with NH4Cl (0.28 M in drinking water). Transcript levels were determined by RT-PCR as well as protein abundance by Western blotting, blood pH was determined utilizing a blood gas and chemistry analyser. Results: UUO increased renal mRNA expression of Tgfb1, Tgfβ-activated kinase 1 (Tak1) protein abundance and Smad2 phosphorylation in the nuclear fraction of the obstructed kidney tissues, effects blunted in NH4Cl treated mice as compared to control treated mice. The mRNA levels of the transcription factors nuclear factor of activated T cells 5 (Nfat5) and SRY (sex determining region Y)-box 9 (Sox9) as well as of tumor necrosis factor α (Tnfα), interleukin 6 (Il6), plasminogen activator inhibitor 1 (Pai1) and Snai1 were up-regulated in the obstructed kidney tissues following UUO, effects again significantly ameliorated following NH4Cl treatment. Furthermore, the increased protein and mRNA expression of α-smooth muscle actin (α-Sma), fibronectin and collagen type I in the obstructed kidney tissues following UUO were significantly attenuated following NH4Cl treatment. Conclusion: NH4Cl treatment ameliorates Tgfβ1-dependent pro-fibrotic signaling and renal tissue fibrosis markers following obstructive nephropathy.
Synthesis and reactivity of an Ir(I) carbonyl complex bearing a carbazolide-bis(NHC) pincer ligand
2015-01-01

Abstract Synthesis of the new iridium NHC pincer complexes [Ir(bimca)(CO)] (3a) and [Ir(bimcaEt)(CO)] (3b) is realized by salt metathesis of in situ generated [Li(bimca)] (2) with Ir(I) carbonyl precursors. In the case of Vaskas complex [IrCl(CO)(PPh3)2] we isolated the Ir(III) hydrido complex (4). Reactivity studies of Ir complex 3a towards allyl halides show the ready formation of η1 coordinated allyl ligands at the Ir(III) center in all cases.
Virus-Induced Type I Interferon Deteriorates Control of Systemic Pseudomonas Aeruginosa Infection
2015-01-01

Background: Type I interferon (IFN-I) predisposes to bacterial superinfections, an important problem during viral infection or treatment with interferon-alpha (IFN-α). IFN-I-induced neutropenia is one reason for the impaired bacterial control; however there is evidence that more frequent bacterial infections during IFN-α-treatment occur independently of neutropenia. Methods: We analyzed in a mouse model, whether Pseudomonas aeruginosa control is influenced by co-infection with the lymphocytic choriomeningitis virus (LCMV). Bacterial titers, numbers of neutrophils and the gene-expression of liver-lysozyme-2 were determined during a 24 hours systemic infection with P. aeruginosa in wild-type and Ifnar-/- mice under the influence of LCMV or poly(I:C). Results: Virus-induced IFN-I impaired the control of Pseudomonas aeruginosa. This was associated with neutropenia and loss of lysozyme-2-expression in the liver, which had captured P. aeruginosa. A lower release of IFN-I by poly(I:C)-injection also impaired the bacterial control in the liver and reduced the expression of liver-lysozyme-2. Low concentration of IFN-I after infection with a virulent strain of P. aeruginosa alone impaired the bacterial control and reduced lysozyme-2-expression in the liver as well. Conclusion: We found that during systemic infection with P. aeruginosa Kupffer cells quickly controlled the bacteria in cooperation with neutrophils. Upon LCMV-infection this cooperation was disturbed.
Reverse-engineering Language: A Study on the Semantic Compositionality of German Compounds
2015-01-01

In this paper we analyze the performance of different composition models on a large dataset of German compound nouns.Given a vector space model for the German language, we try to reconstruct the observed representation (the corpusestimated vector) of a compound by composing the observed representations of its two immediate constituents.We explore the composition models proposed in the literature and also present a new, simple model that achieves the best performance on our dataset.
Different Effects of Ranibizumab and Bevacizumab on Platelet Activation Profile
2015-01-01

&lt;b&gt;&lt;i&gt;Purpose:&lt;/i&gt;&lt;/b&gt; The aim of the study was to evaluate the potential influence of ranibizumab and bevacizumab on platelet activation and aggregation, which are critical processes in the pathogenesis of arterial thromboembolic events (ATEs). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; For the assessment of platelet function, flow cytometry and aggregometry were employed. Platelets were isolated from healthy volunteers and exposed to ranibizumab (1 mg/ml and 150 ng/ml) and bevacizumab (2.5 mg/ml and 3 μg/ml) or their solvents for 10 and 30 min prior to the addition of TRAP (25 μ&lt;smlcap&gt;M&lt;/smlcap&gt;), PAR-4-AP (25 μ&lt;smlcap&gt;M&lt;/smlcap&gt;) or thrombin (0.02 U/ml). The surface expression of activated GP IIb/IIIa, P-selectin (CD62P) and platelet-bound stromal cell-derived factor-1 (SDF-1) was measured on resting (nonactivated) and activated platelets by flow cytometry. The platelet aggregation capacity was examined using light transmission aggregometry. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The expression of surface activation markers did not differ significantly between nonstimulated and TRAP-, PAR-4-AP- or thrombin-activated platelets after incubating with ranibizumab. However, GP IIb/IIIa, CD62P and SDF-1 were significantly downregulated in PAR-4-AP- and thrombin-activated platelets after exposure to bevacizumab 2.5 mg/ml. In addition, ranibizumab- and bevacizumab-FITC were significantly increased in all activated platelets. No significant differences were observed in the aggregation of activated platelets after incubation with ranibizumab or bevacizumab. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; All ranibizumab concentrations as well as the bevacizumab concentration of 3 μg/ml had no influence on platelet activation and aggregation. Therefore, this in vitro study did not show any relationship between the exposition of activated platelets to ranibizumab or bevacizumab and the development of ATEs. However, the highest level of bevacizumab interfered with platelet activation, leading to downregulation of platelet activation markers. This observation might explain why the systemic treatment with high-dose bevacizumab could be associated with an increased risk of bleeding. Regarding the use of lower intravitreal dosages, further research should focus on the complex interactions between platelets and other cells, such as endothelial cells, which might stronger relate to a potentially increased risk of ATEs and depend on systemic vascular endothelial growth factor levels. Facing the different activation profiles, the diverse effects of the drugs on the cellular level have to be critically scrutinized for their clinical relevance.
Introduction of Auricular Acupuncture in Elderly Patients Suffering from Major Depression: Protocol of a Mixed Methods Feasibility Study
2015-01-01

Background . Due to an increasing number of elderly people suffering from major depression and potential side effects of the prescribed drugs, the introduction of new therapeutic approaches is needed. Currently, in Germany, auricular acupuncture is no part of clinical care for gerontopsychiatric patients. Based on promising clinical experiences and existing evidence for treating addiction and trauma, a benefit of auricular acupuncture integrated in existing treatment programs in elderly patients may be hypothesized. Within this project auricular acupuncture according to the National Acupuncture Detoxification Association (NADA) will be integrated in the multimodal treatment regime for elderly patients with major depression in a daytime ward setting. Methods/Design . To evaluate the feasibility and acceptance a mixed method approach is used. In a day clinic, a sample of 20 psychogeriatric patients with the diagnosis of major depression will be enrolled. The patients will receive a total of nine auricular acupuncture treatments according to the standardized NADA protocol in a group setting. The therapeutic process, its organization, the experience, and the willingness of patients to participate will be evaluated by interviews with patients and the therapeutic team. Data will be analyzed qualitatively using content analysis. Additionally, quantitative outcome parameters will be measured by standardized questionnaires.
In vivo Optical Imaging of Matrix Metalloproteinase Activity Detects Acute and Chronic Contact Hypersensitivity Reactions and Enables Monitoring of the Antiinflammatory Effects ofN-Acetylcysteine
2015-01-01

The aim of this study was to determine whether the severity of contact hypersensitivity reactions (CHSRs) can be observed by noninvasive in vivo optical imaging of matrix metalloproteinase (MMP) activity and whether this is an appropriate tool for monitoring an antiinflammatory effect. Acute and chronic CHSRs were elicited by application of a 1% trinitrochlorobenzene (TNCB) solution for up to five times on the right ear of TNCB-sensitized mice. N-Acetylcysteine (NAC)-treated and sham-treated mice were monitored by measuring ear swelling and optical imaging of MMP activity. In addition, we performed hematoxylin-eosin staining and CD31 immunohistochemistry for histopathologic analysis of the antiinflammatory effects of NAC. The ear thickness and the MMP activity increased in line with the increasing severity of the CHSR. MMP activity was enhanced 2.5- to 2.7-fold during acute CHSR and 3.1- to 4.1-fold during chronic CHSR. NAC suppressed ear swelling and MMP signal intensity in mice with acute and chronic CHSR. During chronic CHSR, the vessel density was significantly reduced in ear sections derived from NAC-treated compared to sham-treated mice. In vivo optical imaging of MMP activity measures acute and chronic CHSR and is useful to monitor antiinflammatory effects.
Up-Regulation of Voltage Gated K+ Channels Kv1.3 and Kv1.5 by Protein Kinase PKB/Akt
2015-01-01

Background: The voltage gated K+ channels Kv1.3 and Kv1.5 contribute to the orchestration of cell proliferation. Kinases participating in the regulation of cell proliferation include protein kinase B (PKB/Akt). The present study thus explored whether PKB/Akt modifies the abundance and function of Kv1.3 and Kv1.5. Methods: Kv1.3 or Kv1.5 was expressed in Xenopus laevis oocytes with or without wild-type PKB/Akt, constitutively active T308D/S473DPKB/Akt or inactive T308A/S473APKB/Akt. The channel activity was quantified utilizing dual electrode voltage clamp. Moreover, HA-tagged Kv1.5 protein was determined utilizing chemiluminescence. Results: Voltage gated K+ currents were observed in Kv1.3 or Kv1.5 expressing oocytes but not in water-injected oocytes or in oocytes expressing PKB/Akt alone. Co-expression of PKB/Akt or T308D/S473DPKB/Akt, but not co-expression of T308A/S473APKB/Akt significantly increased the voltage gated current in both Kv1.3 and Kv1.5 expressing oocytes. As shown for Kv1.5, co-expression of PKB/Akt enhanced the channel protein abundance in the cell membrane. In Kv1.5 expressing oocytes voltage gated current decreased following inhibition of carrier insertion by brefeldin A (5 μM) to similarly low values in the absence and presence of PKB/Akt, suggesting that PKB/Akt stimulated carrier insertion into rather than inhibiting carrier retrieval from the cell membrane. Conclusion: PKB/Akt up-regulates both, Kv1.3 and Kv1.5 K+ channels.
Rapid Upregulation of Orai1 Abundance in the Plasma Membrane of Platelets Following Activation with Thrombin and Collagen Related Peptide
2015-01-01

Background: Blood platelets accomplish primary hemostasis following vascular injury and contribute to the orchestration of occlusive vascular disease. Platelets are activated by an increase of cytosolic Ca2+-activity ([Ca2+]i), which is accomplished by Ca2+-release from intracellular stores and subsequent store operated Ca2+ entry (SOCE) through Ca2+ release activated Ca2+ channel moiety Orai1. Powerful activators of platelets include thrombin and collagen related peptide (CRP), which are in part effective by activation of small G- protein Rac1. The present study explored the influence of thrombin and CRP on Orai1 protein abundance and cytosolic Ca2+-activity ([Ca2+]i) in platelets drawn from wild type mice. Methods: Orai1 protein surface abundance was quantified utilizing CFTM488A conjugated antibodies, and [Ca2+]i was determined with Fluo3-fluorescence. Results: In resting platelets, Orai1 protein abundance and [Ca2+]i were low. Thrombin (0.02 U/ml) and CRP (5ug/ml) within 2 min increased [Ca2+]i and Orai1 protein abundance at the platelet surface. [Ca2+]i was further increased by Ca2+ ionophore ionomycin (1 μM) and by store depletion with the sarcoendoplasmatic Ca2+ ATPase inhibitor thapsigargin (1 μM). However, Orai1 protein abundance at the platelet surface was not significantly affected by ionomycin and only slightly increased by thapsigargin. The effect of thrombin and CRP on Orai1 abundance and [Ca2+]i was significantly blunted by Rac1 inhibitor NSC23766 (50 μM). Conclusion: The increase of [Ca2+]i following stimulation of platelets with thrombin and collagen related peptide is potentiated by ultrarapid Rac1 sensitive translocation of Orai1 into the cell membrane.
Embedding lanthanide-functionalized polymers into hollow mesoporous silica spheres: a ship-in-a-bottle approach to luminescent hybrid materials
2015-01-01

Using hollow mesoporous silica spheres (HMSS) as host (“bottle”) and 4-vinylpyridine (4VP), Ln(<sc>iii</sc>) chlorides (Ln = Eu, Tb), and 1,10-phenanthroline (Phen) as “ship” components gives facile access to luminescent hybrid materials.
Novel C8orf37 mutations cause retinitis pigmentosa in consanguineous families of Pakistani origin.
2015-01-01

In this report, we describe C8orf37 mutations that cause retinal dystrophy in two families of Pakistani origin, contributing further data on the phenotype and the spectrum of mutations in this form of retinitis pigmentosa.
Genetic Deletion and Pharmacological Inhibition of PI3Kγ Reduces Neutrophilic Airway Inflammation and Lung Damage in Mice with Cystic Fibrosis‐Like Lung Disease
2015-01-01

Purpose . Neutrophil‐dominated airway inflammation is a key feature of progressive lung damage in cystic fibrosis (CF). Thus, reducing airway inflammation is a major goal to prevent lung damage in CF. However, current anti‐inflammatory drugs have shown several limits. PI3K γ plays a pivotal role in leukocyte recruitment and activation; in the present study we determined the effects of genetic deletion and pharmacologic inhibition of PI3K γ on airway inflammation and structural lung damage in a mouse model of CF lung disease. Methods . β ENaC overexpressing mice ( β ENaC‐Tg) were backcrossed with PI3K γ ‐deficient (PI3K γ KO ) mice. Tissue damage was assessed by histology and morphometry and inflammatory cell number was evaluated in bronchoalveolar lavage fluid (BALF). Furthermore, we assessed the effect of a specific PI3K γ inhibitor (AS‐605240) on inflammatory cell number in BALF. Results . Genetic deletion of PI3K γ decreased neutrophil numbers in BALF of PI3K γ KO / β ENaC‐Tg mice, and this was associated with reduced emphysematous changes. Treatment with the PI3K γ inhibitor AS‐605240 decreased the number of neutrophils in BALF of β ENaC‐Tg mice, reproducing the effect observed with genetic deletion of the enzyme. Conclusions . These results demonstrate the biological efficacy of both genetic deletion and pharmacological inhibition of PI3K γ in reducing chronic neutrophilic inflammation in CF‐like lung disease in vivo .
Validation of the Tuebingen CD-25 Inventory as a Measure of Postoperative Health-Related Quality of Life in Patients Treated for Cushing's Disease
2015-01-01

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; To evaluate the construct and criterion validity of the Tuebingen Cushing's disease quality of life inventory (Tuebingen CD-25) for application in patients treated for Cushing's disease (CD). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A total of 176 patients with adrenocorticotropin hormone-dependent CD (144 of them female, overall mean age 46.1 ± 13.7 years) treated at 3 large tertiary referral centers in Germany were studied. Construct validity was assessed by hypothesis testing (self-perceived symptom reduction assessment) and contrasted groups (patients with vs. without hypercorticolism). For this purpose, already existing data from 55 CD patients was used, representing the hypercortisolemic group. Criterion validity (concurrent validity) was assessed in relation to the Cushing's quality of life questionnaire (CushingQoL), the Short Form 36 health survey (SF-36), and the body mass index (BMI). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Patients with self-perceived remarkable symptom reduction had significant lower Tuebingen CD-25 scores (i.e. better health-related quality of life) than patients with self-perceived insufficient symptom reduction (p &lt; 0.05). Similarly, the mean scores of the Tuebingen CD-25 scales were lower in patients without hypercortisolism (total score 27.0 ± 17.2) compared to those with hypercortisolism (total score 45.3 ± 22.1; each p &lt; 0.05), providing evidence for construct validity. Criterion validity was confirmed by the correlations between the Tuebingen CD-25 total score and the CushingQoL (Spearman's coefficient -0.733), as well as all scales of the SF-36 (Spearman's coefficient between -0.447 and -0.700). &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; The analyses presented in this large-sample study provide robust evidence for the construct and criterion validity of the Tuebingen CD-25.
Regulation of Na+/H+ Exchanger in Dendritic Cells by Akt1
2015-01-01

Background/Aims: Dendritic cells (DCs), antigen-presenting cells critically important for primary immune response and establishment of immunological memory, are activated by bacterial lipopolysaccharides (LPS) resulting in stimulation of Na+/H+ exchanger, ROS formation and migration. The effects are dependent on phosphoinositide 3 (PI3) kinase and paralleled by Akt phosphorylation. The present study explored the contribution of the Akt isoform Akt1. Methods: Cytosolic pH (pHi) (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein [BCECF] fluorescence), Na+/H+ exchanger activity (Na+ dependent realkalinization after an ammonium pulse), cell volume (forward scatter in FACS analysis), and ROS production (2′,7′-dichlorodihydrofluorescein diacetate [DCFDA] fluorescence) were determined in DCs isolated from bone marrow of mice lacking functional Akt1/PKBα (akt1-/-) and their wild type littermates (akt1+/+). Results: Forward scatter was lower in akt1-/- than in akt1+/+ DCs, whereas pHi, Na+/H+ exchanger activity and ROS formation were less in untreated akt1-/- and akt1+/+ DCs. Exposure of DCs to LPS was followed by increase of forward scatter and ROS formation to a similar extent in akt1-/- and in akt1+/+ DCs. A 4 hours treatment with either LPS (1μg/ml) or tert-butylhydroperoxide (tBOOH, 5 μM) significantly stimulated Na+/H+ exchanger activity in both genotypes, effects, however, significantly blunted in akt1-/- DCs. Conclusion: The present observations demonstrate that Akt1 is required for the full stimulation of Na+/H+ exchanger activity by LPS or oxidative stress in dendritic cells.
Medical Therapy of Perianal Crohn's Disease
2015-01-01

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Development of perianal fistulas are a common feature of Crohn's disease (CD). Consequences are severe impairment of quality of life as well as potentially life-threatening complications like abscess formation or bacterial sepsis. Therefore, appropriate treatment is an important task in the management of CD. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; This review describes the epidemiology, pathogenesis, diagnosis, and conservative medical treatment of perianal CD with regard to the available literature. In February 2015, a PubMed search was performed with the following terms (combined and separate): ‘Crohn's disease management', ‘Crohn's disease complications', ‘perianal Crohn's disease', ‘fistulizing Crohn's disease', ‘perianal fistulas', ‘fistula healing', ‘fistula closure'. From the search results, 36 articles were chosen as core elements of this review. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Pelvic magnetic resonance imaging and rectal endosonography are established diagnostic approaches to evaluate perianal fistulas in conjunction with endoscopy. Antibiotics, thiopurines, and calcineurin inhibitors are useful agents in the management of perianal CD. The availability of anti-TNF-alpha therapies has substantially changed the prospects and goals of medical treatment, and fistula healing seems to be possible in a substantial proportion of patients. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Antibiotics and several immunosuppressive drugs have improved the treatment of fistulizing CD and should be combined with surgical measures.
A software package for Mori dream spaces
2015-01-01

Mori dream spaces form a large example class of algebraic varieties, comprising the well-known toric varieties. We provide a first software package for the explicit treatment of Mori dream spaces and demonstrate its use by presenting basic sample computations. The software package is accompanied by a Cox ring database which delivers defining data for Cox rings and Mori dream spaces in a suitable format. As an application of the package, we determine the common Cox ring for the symplectic resolutions of a certain quotient singularity investigated by Bellamy–Schedler and Donten-Bury–Wiśniewski.
The effects of wage subsidies for older workers
2015-01-01

Population aging in many developed countries has motivated some governments to provide wage subsidies to employers for hiring or retaining older workers. The subsidies are intended to compensate for the gap between the pay and productivity of older workers, which may discourage their hiring. A number of empirical studies have investigated how wage subsidies influence employers’ hiring and employment decisions and whether the subsidies are likely to be efficient. To which groups subsidies should be targeted and how the wage subsidy programs interact with incentives for early retirement are open questions.
UV photoexcitation of a dissolved metalloid Ge9 cluster compound and its extensive ultrafast response
2015-01-01

Femtosecond pump–probe absorption spectroscopy in tetrahydrofuran solution has been used to investigate the dynamics of a metalloid cluster compound {Ge<sub>9</sub>[Si(SiMe<sub>3</sub>)<sub>3</sub>]<sub>3</sub>}<sup>−</sup><bold>1</bold>.