julilili42/papers huggingface dataset:
Abstract 5849: Exosomes promote survival and migration in squamous head and neck cancer cells after ionizing radiation: Evidence for a bystander effect
2017-07-01

Abstract Exosomes are important intercellular communicators in the acute radiation stress-response. Here we show that exosomes from head and neck tumor cells confer protective signals to their neighboring cells. This promotes the tumorigenic and radioresistant phenotype of head and neck cancer cells. Isolation of exosomes was performed by serial ultracentrifugation of conditioned medium collected from irradiated or non-irradiated head and neck cancer cell lines BHY and FaDu. Quantification by NanoSight technology indicated an increased exosome release from irradiated compared to non-irradiated cells 24 hours after treatment. To test whether the released exosomes influence the radiation response, exosomes isolated from non-irradiated and irradiated donor cells were transferred on non-irradiated and irradiated recipient cells. We found an enhanced uptake of exosomes, when transferred to irradiated recipient cells compared to the transfer to non-irradiated cells. Functional analyses indicate increased survival of irradiated recipient cells after exosome transfer. These findings mesh with increased DNA double strand break repair that we found after the transfer of exosomes isolated from irradiated cells. Moreover we observed an increased migration and enhanced chemotaxis induced motility after the transfer of exosomes isolated from irradiated cells. To investigate whether differential protein loading into exosomes is responsible for the functional differences we performed proteome analysis of the exosomes. We have identified 679 proteins, of which 39 were up- and 36 were downregulated by irradiation of the donor cells. In a good agreement with our functional assays, the proteome profiling showed that exosomal proteins were mainly involved in wound healing. Exosomes are functional components of the response of tumor cells to therapeutic radiation exposure. In a clinical context these results suggests that radiotherapy modified exosomes may influence the cancer progression, metastasis and therapeutic success. Citation Format: Lisa Mutschelknaus, Omid Azimzadeh, Theresa Heider, Klaudia Winkler, Marcus Vetter, Soile Tapio, Juliane Merl-Pham, Rosemarie Kell, Stephan Huber, Lena Edalat, Vanja Radulovic, Natasa Anastasov, Carsten Peters, Michael John Atkinson, Simone Moertl. Exosomes promote survival and migration in squamous head and neck cancer cells after ionizing radiation: Evidence for a bystander effect [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5849. doi:10.1158/1538-7445.AM2017-5849
XMCD going ultra-cold: Experiments at 100 mK and 7 T
2017-07-01

First experiments along with the general capabilities of the TTXMCD endstation at P04, PETRA III, DESY are presented. The TTXMCD endstation allows measuring the magnetic properties of solids, thin films, molecules or atomic adsorbates at ultra-cold temperatures in an element specific way. At such temperatures, electron-electron interaction phenomena are studied, such as the Kondo effect for Co on Cu(100).
[P4–248]: QUALITY ASSURANCE IN DELCODE: A MULTI‐CENTER NEUROIMAGING STUDY
2017-07-01

During the last years clinical multi-institutional studies are becoming more popular, since they offer neuroscientists the possibility of pooling larger datasets at the cost of strict data standardization and quality assessment rules. This work presents a set of rules and strategies, developed for the DELCODE study, designed to ensure data homogeneity across sites. DELCODE stands for: DZNE longitudinal cognitive impairment and dementia study. Starting in 2014, it is conducted over ten sites across Germany and currently contains about 1.350 scanning sessions from about 825 subjects. It aims to scan 1.000 subjects annually over a period of five years to establish the progression of dementia in the pre-clinical phase. Based on standard operating procedures designed for the study, every scan undergoes a quality check. Acquisition parameters, sequence- and protocol completeness are assessed automatically. Artifacts and coverage of the brain are evaluated manually, spatial orientation is inspected semi-automatically. The results are used as feedback in each center to minimize errors. Data is classified into three categories: A) Complete datasets without deviations from the protocol, B) deviations from the protocol but complete acquisition of scans e.g. suboptimal FoV positioning; and C) incomplete datasets e.g. only structural scans. In 2014, of 84 scans, 52,4% were of type A, 27,4% were of type B and 20,2% were classified as type C. In 2015, of 562 scans, 66,2% were type A, 17,3% were type B and 16,5% were type C. In 2016, of 683 scans, 68,8% were type A, 18,2% were type B and 13% were type C. This shows an increase of quality in data during the first year of feedback, followed by a steady quality assurance in the passing years with increased data acquisition. We were able to establish a harmonized scanning protocol for a multi-center study, assuring a steady monitoring of MRI data quality. Optimization is an ongoing process. The numbers above prove the usefulness of the proposed QA rules and effectiveness of regular feedback to sites. In the future, the currently manual/semi-automatic quality check information will be used to train an algorithm to assess the image quality automatically.
[P3–263]: MOTOR SYMPTOMS IN FAMILIAL ALZHEIMER's DISEASE: FREQUENCY, SEVERITY AND PREDICTIVE VALUE
2017-07-01

To evaluate motor dysfunction as a potential symptom of autosomal dominant Alzheimer's disease (ADAD). We utilized data from the Dominantly Inherited Alzheimer's Network (DIAN) observational study to assess motor dysfunction as determined by the Unified Parkinson Disease Rating Scale part-three (UPDRS-III). We analyzed UPDRS-III scores (0 (best) to 108 (worst)) at baseline for all 433 participants at data freeze 10. We compared the frequency (UPDRS-III 0 vs. >0) and severity (UPDRS-III scores) of motor symptoms between mutation carriers (MC) and non-carriers (NC). In MC, correlations of UPDRS-III scores with estimated years to symptom onset (EYO) and Clinical Dementia Rating Scale - Sum of Boxes (CDR-SOB) were analyzed. Fisher's exact test, Mann-Whitney U test, Spearman correlation and Holm-Bonferroni correction were used. MC exhibited a higher frequency (28.4% vs. 12.8%; p=0.0001) and severity (mean UPDRS-III scores 2.0 vs. 0.4; p=0.00007) of motor symptoms compared to NC. 13 out of 27 symptoms assessed in UPDRS-III were statistically more frequent in MC, with 7 symptoms surviving Holm-Bonferroni correction: finger taps right hand (6.9% vs. 0%; p=0.001), hand movements right hand (5.7% vs. 0%; p=0.0076) and left hand (6.1% vs. 0.6%; p=0.039), rapid alternating movements right hand (7.7% vs. 0%; p=0.0008) and left hand (9.6% vs. 0.6%; p=0.0005), leg agility right leg (4.6% vs. 0%; p=0.026), and gait (4.2% vs. 0%; p=0.039). In cognitively asymptomatic MC (CDR Global=0) rapid alternating movements right hand (3.8% vs. 0%; p=0.02) and left hand (4.4% vs. 0.6%; p=0.03) were more frequently impaired compared to NC after Holm-Bonferroni correction. The positive predictive value to predict MC status in cognitively asymptomatic persons with 50% a priori risk was 100% for right hand and 87.5% for left hand rapid alternating movements. In MC, highly significant positive correlations between UPDRS-III scores and EYO (rs=0.409; p=6.7597E-12) (increasing scores with disease duration) and CDR-SOB (rs=0.420; p=1.3918E-12) were found. In ADAD, motor symptoms occur more frequently and to a larger extend. Furthermore, their degree increases with disease progression and cognitive decline. Impairment in rapid alternating hand movements is a very strong predictor of mutation carrier status in cognitively asymptomatic ADAD family members.
[P4–532]: OBJECT AND SCENE MEMORY ARE DIFFERENTIALLY ASSOCIATED WITH CSF MARKERS OF ALZHEIMER's DISEASE AND MRI VOLUMETRY
2017-07-01

Alzheimer's Disease (AD) is characterized by progressive tau-pathology in perirhinal and entorhinal cortices (ErC), hippocampus, parahippocampal cortex and the retrosplenial/posterior cingulate region (RsC/PCC). The latter also shows early amyloid plaque accumulation. While these regions form a network for complex objects-in-scene memories, there is a segregation of object memory into a perirhinal-entorhinal and scene-layout memory into a RsC/PCC-parahippocampal-entorhinal pathway. Here we investigated whether complex objects-in-scene memory, as opposed to isolated object or scene-layout memory is correlated with CSF levels of Aß42 and phospho-tau and MR volume and thickness measures. 204 participants (cognitively healthy, subjective memory complaints, mild cognitive impairment or early AD) of the DELCODE study of the DZNE performed a complex scene recognition memory task. CSF samples were available from 80 participants. 78 participants also performed a second task on mnemonic discrimination of objects (in the absence of scenes) and scenes (in the absence of objects). Of these 28 CSF samples were available. MR thickness measures were obtained from T1 and T2-weighted images using Freesurfer 6. Objects-in-scene recognition memory correlated with right and left PCC volume (p=0.005; p=0.047), right and left hippocampal volume (p=0.002; p=0.001), Aß42, phospho-tau and their ratio (p=0.002; p=0.002; p=0.000). Isolated object and scene discrimination correlated with left and right hippocampal volume (Scene: p=0.039; p=0.006; Object: p=0.011; p=0.001); scene memory correlated with right and object memory with both left and right ErC thickness (Scene: p=0.027; Object: p=0.024; p=0.031). A scene-minus-object difference score correlated with Aß42 levels indicating that decreasing levels of Aß42 were associated with selective decline of scene discrimination (p=0.034). When considering only healthy older adults, object discrimination relatively selectively correlated with right and left hippocampal volume (n=57; rp=0.022; p=0.005), left entorhinal thickness (p=0.042) and with phospho-tau levels (n=19; p=0.052). These data suggest that complex object-in-scene recognition captures variance caused by both tau and amyloid pathology. A domain-specific breakdown, however, indicates that tau-related variance tends to be captured by object discrimination whereas amyloid pathology is captured by scene discrimination performance. The findings are compatible with the possibility that object and scene discrimination track different stages of disease progression in AD.
[P2–074]: MODELING OF HIDDEN CAUSES FOR DYNAMIC CHANGES IN STRUCTURAL INTEGRITY AND COGNITION IN SUBJECTIVE COGNITIVE DECLINE: A DELCODE PROJECT
2017-07-01

In the search for understanding the disease mechanism research is moving into the earlier phases of Alzheimer's disease (AD) (Scheltens et al., 2016). Subjective cognitive decline (SCD) with still normal cognitive performance might represent the first symptomatic representation of AD (Jessen et al., 2014). Proteins like Aβ are likely key initiators of a complex pathogenic cascade, involving tau aggregation, mediating neurodegeneration (Musiek et al., 2015). Although pathogenic effects on hippocampal circuit structure and function may occur early, there is still a controversy about the causal chain of effects during disease progression. Computational neuroimaging provides a promising path beyond statistical characterizations toward mechanistic explanations of image data (Stephan et al., 2015). The German multi-center DZNE Study DELCODE aims to follow 1000 participants with healthy aging, SCD, and clinically diagnosed MCI, AD and AD-relatives longitudinally for 5 years using sophisticated 3T multimodal imaging protocols including annual structural scans (T1, T2*, SWI, DTI), memory task-fMRI for functional phenotyping (Duzel et al., 2011), serum and CSF biomarkers. Our group uses ASHS (Yushkevich et al., 2015) to develop study-specific semi-automated segmentation protocols for subregions in the parahippocampal gyrus and hippocampal subfields. ROIs are used for characterization of macro-anatomical volumes and functional integrity during memory-related brain processes. A framework for multivariate mixed-effect dynamical systems is developed to model causal cascades of patient's impairments over study years. The states of structural and functional integrity evolve according to differential equations (a) accounting for individual differences and (b) potential interactions between modalities and brain regions. Bayesian model inversion involves estimation of forward models for multiple imaging modalities and behaviour within one generative model. Furthermore, we estimate hidden variables most likely to cause observed brain and behavioral changes on the individual level, e.g. protein load. Since this is an ongoing project over 5 years and no follow up MRI data is available yet, the longitudinal modelling framework including simulated longitudinal data will be presented. This multi-center longitudinal project aims at disease progression, stageing and predictions of patient's behavioural outcomes in subsequent years. Moreover, the framework might reveal quantitative evidence for competing hypotheses about mechanisms underlying early disease progression.
[P4–416]: GENETIC CHARACTERIZATION OF A TURKISH DEMENTIA COHORT: FOCUS ON TYROBP
2017-07-01

Dementia represents a major public health problem in the elderly population. The most common form of dementia is Alzheimer's disease (AD). The majority of cases are sporadic, but familial cases of dementia have been reported, implying a genetic contribution in disease pathogenesis. Several genes have been identified to be causal or risk factors for different forms of dementia. In this study we aimed to genetically characterise a Turkish cohort of dementia patients by analysing known dementia genes and try to identify novel genetic causes of dementia. A cohort of 125 Turkish dementia cases including AD, frontotemporal dementia (FTD), mild cognitive impairment (MCI), and other forms of dementia was studied. We used: 1) whole genome genotyping (WGG) to detect large copy number variants and large tracts of homozygosity; 2) whole exome sequencing (WES) and Sanger sequencing to identify variants in known dementia genes; and 3) fragment analysis/Southern blot to detect C9ORF72 repeat expansions. We also used these techniques to identify novel genes and causative mutations within this dementia cohort. No CNVs expected to be pathogenic were found in this cohort. Six PSEN1 mutations were identified in five AD patients and in one case with atypical dementia. The c.708+6_708+9delTGAG in GRN was identified in a family with FTD. Another patient with FTD had the p.Pro618Leu in MAPT. In addition, hexanucleuotide expansions in C9ORF72 were identified in three FTD families. Exome sequencing analysis also identified the CADASIL-associated p.Arg1231Cys NOTCH3 mutation in an AD patient, and led to the discovery of homozygous TREM2 mutations in 3 patients with an atypical FTD phenotype. A full screen of TYROBP in the studied cohort did not identify any disease-associated variants. Integration of WES and WGG data allowed the identification of mutations in genes not previously associated with specific phenotypes. An example of this was the finding of bi-allelic TREM2 mutations in three patients not presenting with Nasu-Hakola disease, but manifesting an atypical FTD syndrome without osseous phenotypes. No disease-associated variants were identified in TYROBP in the studied cohort, a gene functionally associated with TREM2, and also known to cause Nasu-Hakola disease.
2017-07-01

We analyze fully implicit and linearly implicit backward difference formula (BDF) methods for quasilinear parabolic equations, without making any assumptions on the growth or decay of the coefficient functions.We combine maximal parabolic regularity and energy estimates to derive optimal-order error bounds for the time-discrete approximation to the solution and its gradient in the maximum norm and energy norm.
Building the Pamir‐Tibet Plateau—Crustal stacking, extensional collapse, and lateral extrusion in the Pamir: 3. Thermobarometry and petrochronology of deep Asian crust
2017-07-03

Abstract Large domes of crystalline, middle to deep crustal rocks of Asian provenance make the Pamir a unique part of the India‐Asia collision. Combined major‐element and trace element thermobarometry, pseudosections, garnet‐zoning deconstruction, and geochronology are used to assess the burial and exhumation history of five of these domes. All domes were buried and heated sufficiently to initiate garnet growth at depths of 15–20 km at 37–27 Ma. The Central Pamir was then heated at ~10–20°C/Myr and buried at 1–2 km/Myr to 600–675°C at depths of 25–35 km by 22–19 Ma. The Shakhdara Dome in the South Pamir was heated at ~20°C/Myr and buried at 2–8 km/Myr to reach 750–800°C at depths of ≥50 km by ~20 Ma. All domes were exhumed at &gt;3 km/Myr to 5–10 km depths and ~300°C by 17–15 Ma. The pressures, temperatures, burial rates, and heating rates are typical of continental collision. Decompression during exhumation outpaced cooling, compatible with tectonic unroofing along mapped large‐scale, normal‐sense shear zones, and with advection of near‐solidus or suprasolidus temperatures into the upper crust, triggering exhumation‐related magmatism. The Shakhdara Dome was exhumed from greater depth than the Central Pamir domes perhaps due to its position farther in the hinterland of the Paleogene retrowedge and to higher heat input following Indian slab breakoff. The large‐scale thickening and coincident ~20 Ma switch to extension throughout a huge area encompassing the Pamir and Karakorum strengthens the idea that the evolution of orogenic plateaux is governed by catastrophic plate‐scale events.
Meat allergy associated with galactosyl‐α‐(1,3)‐galactose (α‐Gal)—Closing diagnostic gaps by anti‐α‐Gal IgE immune profiling
2017-07-03

Abstract Background Glycoproteins and glycolipids of some mammalian species contain the disaccharide galactosyl‐α‐(1,3)‐galactose (α‐Gal). It is known that α‐Gal is immunogenic in humans and causes glycan‐specific IgG and also IgE responses with clinical relevance. α‐Gal is part of the IgE‐reactive monoclonal therapeutic antibody cetuximab (CTX) and is associated with delayed anaphylaxis to red meat. In this study, different α‐Gal‐containing analytes are examined in singleplex and multiplex assays to resolve individual sensitization patterns with IgE against α‐Gal. Methods Three serum groups, α‐Gal‐associated meat allergy ( MA ) patients, idiopathic anaphylaxis ( IA ) patients with suspected MA, and non‐meat‐allergic healthy control individuals ( HC ), were analyzed via singleplex allergy diagnostics and a newly established immunoblot diagnostic system. The new dot blot detection system resolved individual IgE sensitization profiles for α‐Gal‐containing analytes CTX, bovine thyroglobulin (Bos d TG), and human serum albumin ( HSA )‐conjugated α‐Gal. Results Singleplex allergy diagnostics using the α‐Gal analytes CTX and Bos d TG confirms the history of MA patients in 91% and 88% of the cases, respectively. A novel dot blot‐based assay system for the detection of IgE against α‐Gal reveals individual IgE sensitization profiles for α‐Gal‐containing analytes. An α‐Gal‐associated IgE cross‐reactivity profile (IgE against CTX, Bos d TG, and HSA ‐α‐Gal) was identified, which is associated with MA. Conclusions Detection of individual sensitization patterns with different α‐Gal‐containing analytes provides the basis for an individual allergy diagnosis for α‐Gal‐sensitized patients. Higher amounts of α‐Gal in pork and beef innards compared to muscle meat as indicated by a higher staining intensity are a plausible explanation for the difference in allergic symptom severity.
Cerium(IV) Neopentoxide Complexes
2017-07-03

Treatment of ceric ammonium nitrate (CAN) with varying amounts of sodium neopentoxide led to the isolation of crystalline cerium(IV) complexes [Ce(OCH<sub>2</sub>tBu)<sub>2</sub>(NO<sub>3</sub>)<sub>2</sub>(HOCH<sub>2</sub>tBu)<sub>2</sub>], [Ce(OCH<sub>2</sub>tBu)<sub>3</sub>(NO<sub>3</sub>)-(NCCH<sub>3</sub>)]<sub>2</sub>, [Ce<sub>2</sub>(OCH<sub>2</sub>tBu)<sub>7</sub>(NO<sub>3</sub>)]<sub>2</sub>, and [Ce<sub>2</sub>(OCH<sub>2</sub>tBu)<sub>9</sub>Na-(THF)] featuring Ce<sup>IV</sup>/(OR) ratios of 1:2, 1:3, 1:3.5, and 1:4.5, respectively. The complexes are light-sensitive and prone to ligand redistribution as evidenced by multicomponent NMR spectra as well as the formation of [{Ce(OCH<sub>2</sub>tBu)<sub>4</sub>}<sub>2</sub>(THF)] and the mixed-valent complex [Ce<sub>3</sub>(OCH<sub>2</sub>tBu)<sub>9</sub>(NO<sub>3</sub>)<sub>2</sub>]. The CAN protocol also gave access to the isopropoxide derivative [Ce(OiPr)<sub>3</sub>(NO<sub>3</sub>)(THF)]<sub>2</sub>. The reaction of [Et<sub>4</sub>N]<sub>2</sub>[CeCl<sub>6</sub>] (CAC, ceric organoammonium chloride) with different equivalents of Na(OCH<sub>2</sub>tBu) was also impaired by ligand reorganization and ate complexation as detected for the tetravalent cerium complex [Ce<sub>2</sub>(OCH<sub>2</sub>tBu)<sub>7</sub>Cl<sub>2</sub>][Et<sub>4</sub>N]. Protonolysis of [Ce{N(SiHMe<sub>2</sub>)<sub>2</sub>}<sub>4</sub>] with 4 equiv of HOCH<sub>2</sub>tBu afforded donor-free homoleptic [Ce(OCH<sub>2</sub>tBu)<sub>4</sub>]<sub>3</sub> in quantitative yield. All complexes were characterized by NMR, DRIFT, and UV-vis spectroscopy, as well as paramagnetic susceptibility measurements, X-ray structure analysis, and elemental analysis.
Gene–environment interactions involving functional variants: Results from the Breast Cancer Association Consortium
2017-07-03

Investigating the most likely causal variants identified by fine‐mapping analyses may improve the power to detect gene–environment interactions. We assessed the interplay between 70 single nucleotide polymorphisms identified by genetic fine‐scale mapping of susceptibility loci and 11 epidemiological breast cancer risk factors in relation to breast cancer. Analyses were conducted on up to 58,573 subjects (26,968 cases and 31,605 controls) from the Breast Cancer Association Consortium, in one of the largest studies of its kind. Analyses were carried out separately for estrogen receptor (ER) positive (ER+) and ER negative (ER–) disease. The Bayesian False Discovery Probability (BFDP) was computed to assess the noteworthiness of the results. Four potential gene–environment interactions were identified as noteworthy (BFDP &lt; 0.80) when assuming a true prior interaction probability of 0.01. The strongest interaction result in relation to overall breast cancer risk was found between CFLAR ‐rs7558475 and current smoking (OR int = 0.77, 95% CI: 0.67–0.88, p int = 1.8 × 10 −4 ). The interaction with the strongest statistical evidence was found between 5q14‐rs7707921 and alcohol consumption (OR int =1.36, 95% CI: 1.16–1.59, p int = 1.9 × 10 −5 ) in relation to ER– disease risk. The remaining two gene–environment interactions were also identified in relation to ER– breast cancer risk and were found between 3p21‐rs6796502 and age at menarche (OR int = 1.26, 95% CI: 1.12–1.43, p int =1.8 × 10 −4 ) and between 8q23‐rs13267382 and age at first full‐term pregnancy (OR int = 0.89, 95% CI: 0.83–0.95, p int = 5.2 × 10 −4 ). While these results do not suggest any strong gene–environment interactions, our results may still be useful to inform experimental studies. These may in turn, shed light on the potential interactions observed.