Efficient Identification of Assembly Neurons within Massively Parallel Spike Trains

The chance of detecting assembly activity is expected to increase if the spiking activities of large numbers of neurons are recorded simultaneously. Although such massively parallel recordings are now becoming available, methods able to analyze such data for spike correlation are still rare, as a combinatorial explosion often makes it infeasible to extend methods developed for smaller data sets. By evaluating pattern complexity distributions the existence of correlated groups can be detected, but their member neurons cannot be identified. In this contribution, we present approaches to actually identify the individual neurons involved in assemblies. Our results may complement other methods and also provide a way to reduce data sets to the “relevant” neurons, thus allowing us to carry out a refined analysis of the detailed correlation structure due to reduced computation time

Late normal tissue response in the rat spinal cord after carbon ion irradiation

Background: The present work summarizes the research activities on radiation-induced late effects in the rat spinal cord carried out within the “clinical research group ion beam therapy” funded by the German Research Foundation (DFG, KFO 214). Methods and materials: Dose–response curves for the endpoint radiation-induced myelopathy were determined at 6 different positions (LET 16–99 keV/μm) within a 6 cm spread-out Bragg peak using either 1, 2 or 6 fractions of carbon ions. Based on the tolerance dose TD50 of carbon ions and photons, the relative biological effectiveness (RBE) was determined and compared with predictions of the local effect model (LEM I and IV). Within a longitudinal magnetic resonance imaging (MRI)-based study the temporal development of radiation-induced changes in the spinal cord was characterized. To test the protective potential of the ACE (angiotensin converting enzyme)-inhibitor ramipril™, an additional dose–response experiment was performed. Results: The RBE-values increased with LET and the increase was found to be larger for smaller fractional doses. Benchmarking the RBE-values as predicted by LEM I and LEM IV with the measured data revealed that LEM IV is more accurate in the high-LET, while LEM I is more accurate in the low-LET region. Characterization of the temporal development of radiation-induced changes with MRI demonstrated a shorter latency time for carbon ions, reflected on the histological level by an increased vessel perforation after carbon ion as compared to photon irradiations. For the ACE-inhibitor ramipril™, a mitigative rather than protective effect was found. Conclusions: This comprehensive study established a large and consistent RBE data base for late effects in the rat spinal cord after carbon ion irradiation which will be further extended in ongoing studies. Using MRI, an extensive characterization of the temporal development of radiation-induced alterations was obtained. The reduced latency time for carbon ions is expected to originate from a dynamic interaction of various complex pathological processes. A dominant observation after carbon ion irradiation was an increase in vessel perforation preferentially in the white matter. To enable a targeted pharmacological intervention more details of the molecular pathways, responsible for the development of radiation-induced myelopathy are required

68Ga-PSMA-PET/CT-based radiosurgery and stereotactic body radiotherapy for oligometastatic prostate cancer

Background: Androgen deprivation therapy (ADT) remains the standard therapy for patients with oligometastatic prostate cancer (OMPC). Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT)-based stereotactic body radiotherapy (SBRT) is emerging as an alternative option to postpone starting ADT and its associated side effects including the development of drug resistance. The aim of this study was to determine progression free-survival (PFS) and treatment failure free-survival (TFFS) after PSMA-PET/CT-based SBRT in OMPC patients. The efficacy and safety of single fraction radiosurgery (SFRS) and ADT delay were investigated. Methods: Patients with ≤ 5 metastases from OMPC, with/without ADT treated with PSMA-PET/CT-based SBRT were retrospectively analyzed. PFS and TFFS were primary endpoints. Secondary endpoints were local control (LC), overall survival (OS) and ADT-free survival (ADTFS). Results: Fifty patients with a total of 75 metastases detected by PSMA-PET/CT were analyzed. At the time of SBRT, 70% of patients were castration-sensitive. Overall, 80% of metastases were treated with SFRS (median dose 20 Gy, range: 16-25). After median follow-up of 34 months (range: 5-70) median PFS and TFFS were 12 months (range: 2-63) and 14 months (range: 2-70), respectively. Thirty-two (64%) patients had repeat oligometastatic disease. Twenty-four (48%) patients with progression underwent second SBRT course. Two-year LC after SFRS was 96%. Grade 1 and 2 toxicity occurred in 3 (6%) and 1 (2%) patients, respectively. ADTFS and OS rates at 2-years were 60.5% and 100%, respectively. In multivariate analysis, TFFS significantly improved in patients with time to first metastasis (TTM) >36 months (p = 0.01) and PSA before SBRT ≤ 1 ng/ml (p = 0.03). Conclusion: For patients with OMPC, SBRT might be used as an alternative to ADT. This way, the start/escalation of palliative ADT and its side effects can be deferred. Metastases treated with PSMA-PET/CT-based SFRS reached excellent LC with minimal toxicity. Low PSA levels and longer TTM predict elongated TFFS

Arginase Inhibition Reverses Monocrotaline-Induced Pulmonary Hypertension

Pulmonary hypertension (PH) is a heterogeneous disorder associated with a poor prognosis. Thus, the development of novel treatment strategies is of great interest. The enzyme arginase (Arg) is emerging as important player in PH development. The aim of the current study was to determine the expression of ArgI and ArgII as well as the effects of Arg inhibition in a rat model of PH. PH was induced in 35 Sprague–Dawley rats by monocrotaline (MCT, 60 mg/kg as single-dose). There were three experimental groups: sham-treated controls (control group, n = 11), MCT-induced PH (MCT group, n = 11) and MCT-induced PH treated with the Arg inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA; MCT/NorNoha group, n = 13). ArgI and ArgII expression was determined by immunohistochemistry and Western blot. Right ventricular systolic pressure (RVPsys) was measured and lung tissue remodeling was determined. Induction of PH resulted in an increase in RVPsys (81 ± 16 mmHg) compared to the control group (41 ± 15 mmHg, p = 0.002) accompanied by a significant elevation of histological sum-score (8.2 ± 2.4 in the MCT compared to 1.6 ± 1.6 in the control group, p < 0.001). Both, ArgI and ArgII were relevantly expressed in lung tissue and there was a significant increase in the MCT compared to the control group (p < 0.01). Arg inhibition resulted in a significant reduction of RVPsys to 52 ± 19 mmHg (p = 0.006) and histological sum-score to 5.8 ± 1.4 compared to the MCT group (p = 0.022). PH leads to increased expression of Arg. Arg inhibition leads to reduction of RVPsys and diminished lung tissue remodeling and therefore represents a potential treatment strategy in PH

Discovering Mathematical Objects of Interest -- A Study of Mathematical Notations

Mathematical notation, i.e., the writing system used to communicate concepts in mathematics, encodes valuable information for a variety of information search and retrieval systems. Yet, mathematical notations remain mostly unutilized by today's systems. In this paper, we present the first in-depth study on the distributions of mathematical notation in two large scientific corpora: the open access arXiv (2.5B mathematical objects) and the mathematical reviewing service for pure and applied mathematics zbMATH (61M mathematical objects). Our study lays a foundation for future research projects on mathematical information retrieval for large scientific corpora. Further, we demonstrate the relevance of our results to a variety of use-cases. For example, to assist semantic extraction systems, to improve scientific search engines, and to facilitate specialized math recommendation systems. The contributions of our presented research are as follows: (1) we present the first distributional analysis of mathematical formulae on arXiv and zbMATH; (2) we retrieve relevant mathematical objects for given textual search queries (e.g., linking $P_{n}^{(\alpha, \beta)}\!\left(x\right)$ with `Jacobi polynomial'); (3) we extend zbMATH's search engine by providing relevant mathematical formulae; and (4) we exemplify the applicability of the results by presenting auto-completion for math inputs as the first contribution to math recommendation systems. To expedite future research projects, we have made available our source code and data.Comment: Proceedings of The Web Conference 2020 (WWW'20), April 20--24, 2020, Taipei, Taiwa