Maintaining Contour Trees of Dynamic Terrains

We study the problem of maintaining the contour tree T of a terrain Sigma, represented as a triangulated xy-monotone surface, as the heights of its vertices vary continuously with time. We characterize the combinatorial changes in T and how they relate to topological changes in Sigma. We present a kinetic data structure (KDS) for maintaining T efficiently. It maintains certificates that fail, i.e., an event occurs, only when the heights of two adjacent vertices become equal or two saddle vertices appear on the same contour. Assuming that the heights of two vertices of Sigma become equal only O(1) times and these instances can be computed in O(1) time, the KDS processes O(kappa + n) events, where n is the number of vertices in Sigma and kappa is the number of events at which the combinatorial structure of T changes, and processes each event in O(log n) time. The KDS can be extended to maintain an augmented contour tree and a join/split tree

Fibrillar form of α-synuclein-specific scFv antibody inhibits α-synuclein seeds induced aggregation and toxicity

Synucleinopathies including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are characterized by pathological accumulation of α-synuclein (α-syn). Amongst the various approaches attempting to tackle the pathological features of synucleinopathies, antibody-based immunotherapy holds much promise. However, the large size of antibodies and corresponding difficulty in crossing the blood-brain barrier has limited development in this area. To overcome this issue, we engineered single-chain variable fragments (scFvs) against fibrillar α-syn, a putative disease-relevant form of α-syn. The purified scFvs showed specific activity towards α-syn fibrils and oligomers in comparison to monomers and recognized intracellular inclusions in human post-mortem brain tissue of Lewy body disease cases, but not aged controls. In vitro studies indicated scFvs inhibit the seeding of α-syn aggregation in a time-dependent manner, decreased α-syn seed-induced toxicity in a cell model of PD, and reduced the production of insoluble α-syn phosphorylated at Ser-129 (pS129-α-syn). These results suggest that our α-syn fibril-specific scFvs recognize α-syn pathology and can inhibit the aggregation of α-syn in vitro and prevent seeding-dependent toxicity. Therefore, the scFvs described here have considerable potential to be utilized towards immunotherapy in synucleinopathies and may also have applications in ante-mortem imaging modalities.Dr. El-Agnaf’s laboratory was funded by Qatar Biomedical Research Institute under the Start-up Fund SF 2017– 007. The Newcastle Brain Tissue Resource is funded in part by a grant from the UK Medical Research Council, by NIHR Newcastle Biomedical Research Centre awarded to the Newcastle upon Tyne NHS Foundation Trust and Newcastle University, and by a grant from the Alzheimer’s Society and Alzheimer’s Research UK as part of the Brains for Dementia Research Project

A User Level Model for Artificial Internet Traffic Generation

vi LIST OF TABLES Table Page 1.1 1991 Application Breakdowns : : : : : : : : : : : : : : : : : : : : : : : : 8 1.2 1995 Application Packet Counts : : : : : : : : : : : : : : : : : : : : : : 9 1.3 1997 Application Breakdowns : : : : : : : : : : : : : : : : : : : : : : : : 9 3.1 conventions : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : 7 3.2 summary : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : 7 3.3 Correlation Values for OU Arti cial Timed Series : : : : : : : : : : : : : 8 3.4 Correlation Values for OU Arti cial Timed Series : : : : : : : : : : : : : 8 3.5 Correlation Values for NewWave Arti cial Timed Series : : : : : : : : : 9 3.6 Correlation for NewWave Arti cial Timed Series : : : : : : : : : : : : : 10 3.7 Correlation for NewWave Arti cial Timed Series : : : : : : : : : : : : : 10 3.8 Correlation for NewWave Arti cial Timed Series : : : : : : : : : : : : : 10 3.9 Correlation for NewWave Arti cial Timed Series : : : : : : : : : : : : : 11 3.10 Correlation for NewWave Arti cial Timed Series : : : : : : : : : : : : : 11 vii 3.12 tcplib Interpolation Results : : : : : : : : : : : : : : : : : : : : : : : : : 14 C.1 conventions : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : 63 C.2 Correlation Values for OU Arti cial Timed Series : : : : : : : : : : : : : 63 C.3 Correlation Values for OU Arti cial Timed Series : : : : : : : : : : : : : 64 C.4 Correlation for OU Arti cial Timed Series : : : : : : : : : : : : : : : : : 64 C.5 Correlation for OU Arti cial Timed Series : : : : : : : : : : : : : : : : : 64 C.6 Correlation for OU Arti cial Timed Series : : : : : : : : : : : : : : : : : 65 C.7 Correlation for OU Arti cial T..

Fibrillar form of α-synuclein-specific scFv antibody inhibits α-synuclein seeds induced aggregation and toxicity

Synucleinopathies including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are characterized by pathological accumulation of α-synuclein (α-syn). Amongst the various approaches attempting to tackle the pathological features of synucleinopathies, antibody-based immunotherapy holds much promise. However, the large size of antibodies and corresponding difficulty in crossing the blood-brain barrier has limited development in this area. To overcome this issue, we engineered single-chain variable fragments (scFvs) against fibrillar α-syn, a putative disease-relevant form of α-syn. The purified scFvs showed specific activity towards α-syn fibrils and oligomers in comparison to monomers and recognized intracellular inclusions in human post-mortem brain tissue of Lewy body disease cases, but not aged controls. In vitro studies indicated scFvs inhibit the seeding of α-syn aggregation in a time-dependent manner, decreased α-syn seed-induced toxicity in a cell model of PD, and reduced the production of insoluble α-syn phosphorylated at Ser-129 (pS129-α-syn). These results suggest that our α-syn fibril-specific scFvs recognize α-syn pathology and can inhibit the aggregation of α-syn in vitro and prevent seeding-dependent toxicity. Therefore, the scFvs described here have considerable potential to be utilized towards immunotherapy in synucleinopathies and may also have applications in ante-mortem imaging modalities.Other Information Published in: Scientific Reports License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41598-020-65035-8</p