julilili42/papers huggingface dataset:
Dark matter pair production in the MSSM and in simplified dark matter models at the LHC
2019-05-01

\\n We study the quantitative features of dark matter pair production at the LHC in simplified dark matter models and in the MSSM taking next-to-leading order QCD corrections and parton-shower effects fully into account. Among the large space of dark matter models, we focus on two particular models where a fermionic dark matter candidate interacts with the Standard Model via the exchange of either a vector mediator in the s-channel or coloured scalar mediators in the t-channel. We find that the simplified models are capable of reproducing the predictions of the MSSM to some extent in simplified supersymmetric scenarios, but lack the complexity to describe the complete theory over the full supersymmetric parameter space.\\n
Understanding the Sensing Mechanism of WO3 based Gas Sensors
2019-05-01

The first commercially available semiconducting metal oxide gas sensor, patented by Taguchi in the 1970s, was based on SnO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> . Even today, most commercially produced sensors are based on SnO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> . As computing power becomes more prevalent and metal oxide gas sensors are used in a broader range of applications, materials with complementary sensing characteristics will be needed. WO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> is a promising material that shows high responses to volatile organic compounds and NO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> . Interestingly, humidity is reported to have an oxidizing effect on the material, which is the opposite of what is commonly reported for SnO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> . Here the surface reaction which is responsible for the sensing mechanism of NO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> is examined using diffuse reflectance infrared Fourier transform spectroscopy. The effect of humidity on the sensor response is understood and a comparison to SnO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> is made.
Exercise improves brain insulin action in sedentary overweight and obese adults
2019-05-01

Exercise has beneficial effects on metabolism and brain function and is therefore recommended to prevent type 2 diabetes and support its treatment. However, little is known whether exercise can improve insulin sensitivity of the brain in overweight and obese individuals prone to brain insulin resistance.
Perspectives for CNO neutrino detection in Borexino
2019-05-01

Borexino measured with unprecedented accuracy the fluxes of solar neutrinos emitted at all the steps of the pp fusion chain. Still missing is the measurement of the flux of neutrinos produced in the CNO cycle. A positive measurement of the CNO neutrino flux is of fundamental importance for understanding the evolution of stars and addressing the unresolved controversy on the solar abundances. The measurement of the CNO neutrino flux in Borexino is challenging because of the low intensity of this component (CNO cycle accounts for about 1% of the energy emitted by Sun), the lack of prominent spectral features and the presence of background sources. The main background component is 210Bi decaying in the liquid scintillator of Borexino that creates events with an energy distribution very close to the one of CNO neutrino interactions. Since 2015 the collaboration undertook significant efforts to achieve an independent measurement of the background affecting a CNO measurement, whose impact on the sensitivity to a CNO signal will be discussed.
Ghrelin influences β-cell function by interference with KATP channels
2019-05-01

Ghrelin is well known as a hunger-inducing hormone which is mainly secreted from stomach cells. Meanwhile it has become evident, that ghrelin is produced in the pancreas as well and influences β-cell function. For many years it was well accepted, that ghrelin decreases glucose stimulated insulin secretion (GSIS) through the growth hormone secretagogue receptor 1a (GHS-R1a) coupled to Gαi/cAMP/TRPM2. This assumption was recently challenged by the discovery that the GHS-R1a is expressed in δ-cells. Accordingly, ghrelin may induce the secretion of somatostatin, which, in turn, acts in a paracrine manner on β-cells and inhibits GSIS.
Empagliflozin effectively reduces liver fat content in type 2 diabetes
2019-05-01

Type 2 diabetes (T2D) associates with non-alcoholic fatty liver disease (NAFLD), which contributes to insulin resistance and cardiovascular risk of diabetes. Currently, there is no established therapy for NAFLD in T2D. This trial examined whether treatment with the sodium glucose transporter 2 inhibitor empagliflozin (EMPA) reduces liver fat content (HCL, primary outcome). T2D patients (n = 84; BMI 32.2 ± 4.5 kg/m2; HbA1c 6.6 ± 0.5%) were randomly assigned to 24-week treatment with either EMPA 25 mg per day or placebo (PLAC). HCL was measured by magnetic resonance (MR) methods (1 H-MR spectroscopy, STEAM); MR imaging, IDEAL). Statistical analysis was done by ANCOVA adjusted for the respective baseline value, age, sex and BMI. After treatment, HCL was reduced compared to baseline (relative change, RC: EMPA -33%[95% confidence interval -43;-23], p < 0.0001; PLAC -14[-23;-3]%, p = 0.014) and different between the two interventions (p = 0.007). Body weight decreased with EMPA, but not with PLAC (least square means (LSM): -2.7 ± 0.4 kg, p < 0.0001, vs. 0.06 ± 0.5 kg) and contributed to reduction of HCL as shown by causal mediation analysis. Serum uric acid decreased (LSM: -81 ± 13 mmol/l, p < 0.0001, vs. -4 ± 11 mmol/l), while serum adiponectin rose with EMPA only (RC: 27[15;40]%, p < 0.0001, vs. -5[-16;9]%) and correlated only in EMPA (p = 0.038). Furthermore, the changes in adiponectin inversely associated with changes in serum cytokeratin-18 M30 fragment in the EMPA group only (p = 0.005). In conclusion, empagliflozin effectively reduces HCL in well-controlled T2D patients and increases serum adiponectin with beneficial effects on hepatocellular integrity. Thus, empagliflozin may improve NAFLD via distinct different mechanisms.
Downstream effect of CSF3R and RUNX1 mutations that underlie leukemic transformations in congenital neutropenia (CN)
2019-05-01

Ca. 70% of CN patients with AML carry CSF3R and RUNX1 mutations (Skokowa et al 2014). We established an in vitro model utilizing lin- bone marrow cells from C57BL/6 – 1d715csf3r mice (with homozygous d715G CSF3R mutations) transduced with lentivirus vectors carrying RUNX1 wildtype or RUNX1 missense mutations. Cells transduced with RUNX1 mutants showed diminished in vitro myeloid differentiation and elevated replating capacity, compared to WT. mRNA expression analysis of transduced cells using Pathway analysis (IPA) and Motif activity response analysis (using ISMARA) revealed that the highest activated motif in RUNX1-Mutants was Irf2_Irf1_Irf8_Irf9_Irf7 motif. Correspondingly, IPA Pathway analysis showed that Interferon Signaling was highly upregulated in cells transduced with RUNX1 mutants, compared to WT RUNX1. Additionally, pathway analysis showed the upregulation and activation of IL-6, IL-8-, Toll like Receptor- and TREM1 signaling pathways. This data suggests that the mutated RUNX1 may cause activation of the pro-inflammatory cell state propagating proliferation, which may be emerging as a cause of clonal hematopoiesis and consequently may lead to MDS/AML.
The Influence of MAP4K4 on the beneficial effects of exercise on skeletal muscle, substrate oxidation and insulin signaling
2019-05-01

The mitogen-activated kinase kinase kinase kinase 4 (MAP4K4) is a ubiquitously expressed serine/threonine kinase. Its stimulation induces insulin resistance and specific gene polymorphisms are associated with prediabetes and insulin resistance. Moreover, MAP4K4 activity is increased in Exercise Non-Responders (NREs) failing to improve their insulin sensitivity after an exercise intervention.
GADD45b plays an essential role in the G-CSF triggered granulocytic differentiation of human hematopoietic cells
2019-05-01

The mechanism of maturation arrest of granulopoiesis in congenital neutropenia (CN) is not fully elucidated. We found that GADD45b is induced by G-CSF in healthy HSPCs, but not in CN cells. We inhibited GADD45b expression in CD34+ cells and iPSCs by CRISPR/Cas9 RNP and found markedly diminished granulocytic differentiation in GADD45b knockout iPSCs and CD34+ cells. Transduction of CN patient HSPCs with GADD45B cDNA restored granulocytic differentiation. In silico analysis of GADD45B promoter, reporter gene and ChIP assays revealed CEBPA-mediated activation of GADD45b. GADD45b is regulating active DNA demethylation by promoting the recruiting of DNA demethylation machineries to specific genomic loci. Therefore, we investigated whether G-CSF-triggered granulocytic differentiation of HSPCs requires regulation of active gene demethylation by GADD45b using RNA sequencing and the Infinium methylation EPIC array of WT or GADD45b-edited CD34+ HSPCs treated or not with G-CSF. G-CSF treatment of HSPCs resulted in the robust changes of DNA methylation that was markedly reduced in GADD45b KO cells. We identified several signaling pathways that are regulated by GADD45b-mediated demethylation.
Urinary fetuin-A peptides as new markers for kidney damage in type-2 diabetes patients
2019-05-01

The hepatokine fetuin-A, which is released by fatty liver, promotes the proinflammatory effects of perivascular fat. The involvement of inflammation in type-2 diabetes can affect the kidney and cause diabetic nephropathy. Therefore, we examined the association of urinary fetuin-A protein fragments with renal damage in diabetes type-2 patients.
Diabetic conditions alter immune cells and are partially responsible for a delayed fracture healing
2019-05-01

Objectives: The overall immunogenic state and the cytokine secretion of immune cells after fracture are proposed to have a large impact on the start and process of the fracture healing process. Aim of this study was to investigate if an altered immune status of type 2 diabetics has a direct impact on impaired fracture and wound healing.
iPSC Model of Stepwise Leukemia Development in Congenital Neutropenia Reveals BAALC as a Key Mediator of Leukemogenesis
2019-05-01

Recently, we reported a high frequency of cooperating RUNX1 and CSF3R mutations in CN patients that developed AML or MDS. We established a model for step-wise leukemia progression in CN using iPSC-based hematopoietic differentiation in combination with CRISPR/Cas9-mediated gene editing of iPSCs. Using this model, we confirmed that co-acquisition of CSF3R and RUNX1 mutations is sufficient to induce leukemia in CN. In addition, we identified BAALC (brain and acute leukemia, cytoplasmic) upregulation as a key leukemogenic event downstream of RUNX1 and CSF3R mutations. BAALC mRNA was upregulated in primary CN/AML blasts (n = 5) and in CD34+ HSPCs generated from CN/AML iPSCs of two patients. Importantly, CRISPR/Cas9-mediated knockout of BAALC in CN/AML-iPSCs inhibited proliferation and induced myeloid differentiation of CN/AML blasts. Using connectivity Map analysis of RNA-Seq data of iPSC-derived CD34+ cells, we identified a p38 MAPK/MK2 inhibitor that could possibly reverse BAALC-mediated leukemogenic gene expression signature. Proliferation of primary CN/AML blasts, CN/AML-iPSC-derived CD34+ cells and BAALC-expressing de novo AML blasts was decreased upon treatment with this inhibitor.
BOOTABLE: Bioinformatics Benchmark Tool Suite
2019-05-01

The interest in analyzing biological data on a large scale has grown over the last years. Bioinformatic applications play an important role when it comes to the analysis of huge amounts of data. Due to the large amount of biological data and/or large problem spaces a considerable amount of computing resources is required to answer the raised research questions. In order to estimate which underlying hardware might be the most suitable for the bioinformatic tools applied, a well-defined benchmark suite is required. Such a benchmark suite can get useful in the case of purchasing hardware and even further for larger projects with the goal to establish a bioinformatics compute infrastructure. With this paper we present BOOTABLE, our bioinformatic benchmark suite. BOOTABLE currently contains six popular and widely used bioinformatic applications representing a broad spectrum of usage characteristics. It further includes an automated installation procedure and all required datasets. BOOTABLE is available from our Github repository (https://github.com/MaximilianHanussek/BOOTABLE) in various formats.
Paul Silas Peterson: Romano Guardini in the Weimar Republic and in National Socialist Germany: With a brief look into the National Socialist correspondences on Guardini in the early 1940s
2019-05-01

Abstract Romano Guardini was one of the most important intellectuals of German Catholicism in the twentieth century. He influenced nearly an entire generation of German Catholic theologians and was the leading figure of the German Catholic youth movement as it grew exponentially in the 1920s. Yet there are many open questions about his early intellectual development and his academic contribution to religious, cultural, social and political questions in the Weimar Republic and in National Socialist Germany. This article draws upon Guardini’s publications, the secondary literature on Guardini and on some archival material, seeking to outline his early development and his engagement with the ideological context following World War I and in National Socialist Germany. Here Guardini’s criticisms of the modern age are presented. Besides this many other issues are addressed, such as his criticism of the women’s movement, his understanding of the youth movement, reception of Carl Schmitt, views of race, interpretation of the controversial Volk -concept, contribution to a Jewish journal in 1933, and his basic positions on the issues of obedience, order and authority. While Guardini was viewed critically by some National Socialists in the Third Reich, the administrative correspondences on him in the 1940s actually show that there was an internal debate about him among the National Socialist officials. This involved different figures, including a diplomat who came to Guardini’s defense. The internal disagreements were made more complicated because Guardini’s brothers were apparently members of the Fascist Party in Italy at this time.
C-11-Raclopride-displacement and altered functional connectivity after intranasal application of insulin in humans. A PET/MRI study.
2019-05-01

390 Objectives: Animal studies provided evidence that effects from insulin on food intake are at least in part mediated by central dopaminergic activity. Specifically, insulin inhibits excitatory synaptic transmission in the ventral tegmental area and reduces dopamine release in the nucleus accumbens. fMRI studies showed that insulin decreases striatal activation. No study so far has investigated the effect of central insulin action on central dopaminergic activity in humans. Hence, we investigated whether centrally/intranasally administered insulin influences dopaminergic activity in striatal regions and resting-state functional connectivity. Methods: 10 healthy normal weight men (age 27±3 years, BMI 23.6±2.3 kg/m2) underwent two dynamic C-11-raclopride-PET/MRI (376±79 MBq) including resting-state fMRI after intranasal application of insulin or placebo (randomized order). Binding potential (BPnd) was estimated in regions of interest (ROIs) using the multilinear reference tissue model MRTM2 (t[asterisk]=10 min, cerebellum as reference region). ROIs were defined according to the label atlas from Neuromorphometrics, Inc.: ventral striatum, dorsal striatum, caudate and putamen. BPnd (insulin vs. placebo) in striatal subregions were compared using one-sided paired t-tests. Functional connectivity (FC) was calculated voxelwise using the ventral striatum as seed. Results: After intranasal insulin administration, BPndincreased significantly in all striatal subregions (p<0.05), most significantly in the ventral striatum (p=0.02). Insulin induced changes of FC between the ventral striatum and VTA correlated significantly with the increase of BPnd in the ventral striatum (p=0.02). Conclusions: This is the first study in humans showing that central insulin action modulates dopaminergic activity and functional connectivity in the striatum. C-11-raclopride-PET/MRI may help to understand the role of central insulin action in obesity.
FDG-PET/MRI combined with SPECT/CT guided sentinel lymph node mapping for lymph node staging in patients with early stage cervical and endometrial carcinoma: a prospective study.
2019-05-01

551 Aim: Lymph node metastases (LNM) are rare in early stage endometrial and cervical carcinomas. Thus, minimal invasive lymph node staging is desirable to prevent from complications associated with a full lymphadenectomy for diagnostic purpose. Aim of this prospective study was to analyze the impact of a combined protocol including FDG-PET/MRI followed by SPECT/CT guided sentinel lymph node (SLN) biopsy. Methods: 53 women with initial diagnosis of Figo IA-IIB endometrial and cervical carcinomas were assessed. All patients received preoperative whole body FDG-PET/MRI (Siemens Biograph mMR®) as well as SPECT/CT (GE Discovery 670 Pro®) after intracervical Tc-99m Nanocoll injection performed on the day before surgery. Intraoperative lymph node (LN) mapping was conducted using a laparoscopic gamma probe. LN status was validated by histology. Results: One patient was excluded from lymphadenectomy due to liver metastases on PET/MRI. 10/52 patients (19%) presented with LNM in 13/104 hemiplevis (13%). Interestingly, there were no LNM in patients with endometrial carcinoma (0/18), whereas the prevalence for LNM in patients with cervical carcinoma was higher than expected (10/34 patients = 29%; literature 14-26%). 4/10 patient with LNM solely had lesions with a diameter ≤5mm. PET/MRI demonstrated an excellent specificity for LNM staging (100% per patient / 100% per hemipelvis), with a good accuracy (90%/92%), but low sensitivity (50%/43%). The size of LNM was found to be the most important factor on PET/MRI sensitivity with a sharp drop in detectability of metastases ≤5mm (LN ≤5mm: 0%; >5mm: 83%). Paraaortal LNM were evaluated accurately by PET/MRI in all 3 cases (LNM in 3/26 patients with paraaortal LN sampling). Detection rate of SLN in SPECT/CT was 82% per patient, 70% for hemipelvis and 32% for paraaortal LN. However, the presence of malignancy in patients with SLN was lower (16% per patient/12% per hemipelvis) than in patients without detected SLN (33%/16%). Only 1/3 patients with paraaortal LNM showed corresponding SLNs in SPECT/CT. The combination of both methods improved the detection rate of LNM significantly to 78% (PET/MRI alone 43%, SLN alone: 64%). Conclusion: FDG-PET/MRI is a highly specific imaging method in lymph node staging and can detect paraaortal and distant lymph node metastases sufficiently but has a limited sensitivity in small metastases ≤5mm. However, the combination of PET/MRI and SPECT/CT guided SLN biopsy increases the sensitivity and might have the potential to replace full lymphadenectomies in early tumor stages.
Favorable outcome of patients treated by radioembolization of liver metastasis from uveal melanoma
2019-05-01

432 Aim: Hepatic metastasis is the most frequent and prognostically relevant spread in uveal melanoma. At diagnosis, hepatic lesions are typically to wide-spread to be removed by surgery. Median survival has been reported to be only 4-15 month from first diagnosis of liver involvement. Radioembolization (RE), also referred to as selective internal radiotherapy (SIRT), may be considered as a palliative treatment. However, because uveal melanoma is a rare disease, scientific knowledge on the role of RE is still limited in this entity. We thus conceived this study to analyze feasibility and longtime outcome of RE. Methods: 27 consecutive patients with known hepatic metastasis from uveal melanoma (mean age 69 y, range 52-83) were included into this study between 1/2014 and 4/2018. Decision to evaluate RE was made by the local multidisciplinary tumor board for management of cutaneous malignancies. In the majority of patients (74%), RE was considered as first-line treatment of liver metastases. The other patients had previously been treated by RFA/TACE (n=2), chemo- or immunotherapy (n=3) or by combined locoregional and systemic therapy (n=2). Overall survival was measured using the Kaplan-Meier estimator. Results: As based on hepatic angiography and simulation of sphere distribution using MAA-SPECT/CT, 23/27 individuals were deemed to qualify for RE. In 4 patients RE was considered not feasible due to either insufficient targeting of tumor lesions (n=2) or non-correctable gastrointestinal shunting (n=2). 19/23 patients received RE of the whole liver, while RE could be restricted to a single liver lobe in 4 individuals. The mean hepatic tumor load accounted for 19% of the total liver volume (range 5-44%). RE was predominantly performed as a single time point intervention (n=17) while two procedures with approx. 6-week interval were applied in the remainder. Median overall survival was 14.8 month from RE and 20.7 month from the first diagnosis of hepatic metastases. In 3 cases RE was repeated after 11, 12 or 27 month due to progression after initial response. Conclusions: Despite advanced hepatic metastatic spread, favorable survival can be achieved after RE in patients with uveal melanoma. In the view of other evolving treatment options (immunotherapy, chemosaturation) prognostic factors as well as treatment sequence and combination are to be evaluated.