Christopher Dobson

2017-04-07 Assigned to PRESIDENT AND FELLOWS OF HARVARD COLLEGE reassignment PRESIDENT AND FELLOWS OF HARVARD COLLEGE ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: Weitz, David A.

Flow apparatuses comprising a separation channel, a downstream flow separator, a detection zone, an observation zone, and a waste channel. The separation channel has first and second flows in contact and allows lateral movement of components between contacting first and second flows. The downstream flow separator is in communication with the separation channel and diverts a part of the first fluid flow, the second fluid flow, or both, from the separation channel. The detection zone comprises a detection channel downstream of and in communication with the flow separator and configured to receive a plurality of diverted flows from the flow separator and a label channel configured to label the diverted flows from the flow separator. The observation zone is configured to record an analytical signal indicative of the quantity and the electrical properties of the component. The waste channel is at the downstream …

The aberrant aggregation of α-synuclein (αS) into amyloid fibrils is associated with a range of highly debilitating neurodegenerative conditions, including Parkinson’s disease. Although the structural properties of mature amyloids of αS are currently understood, the nature of transient protofilaments and fibrils that appear during αS aggregation remains elusive. Using solid-state nuclear magnetic resonance (ssNMR), cryogenic electron microscopy (cryo-EM), and biophysical methods, we here characterized intermediate amyloid fibrils of αS forming during the aggregation from liquid-like spherical condensates to mature amyloids adopting the structure of pathologically observed aggregates. These transient amyloid intermediates, which induce significant levels of cytotoxicity when incubated with neuronal cells, were found to be stabilized by a small core in an antiparallel β-sheet conformation, with a disordered N …

Neurodegenerative diseases, such as Alzheimer’s disease (AD), are associated with protein misfolding and aggregation into amyloid fibrils. Increasing evidence suggests that soluble, low-molecular-weight aggregates play a key role in disease-associated toxicity. Within this population of aggregates, closed-loop pore-like structures have been observed for a variety of amyloid systems, and their presence in brain tissues is associated with high levels of neuropathology. However, their mechanism of formation and relationship with mature fibrils have largely remained challenging to elucidate. Here, we use atomic force microscopy and statistical theory of biopolymers to characterize amyloid ring structures derived from the brains of AD patients. We analyze the bending fluctuations of protofibrils and show that the process of loop formation is governed by the mechanical properties of their chains. We conclude that ex …

CN1242262C (zh)* 2002-08-21 2006-02-15 中国科学院大连化学物理研究所 二维或多维毛细管电泳分离生物大分子的方法

CN1242262C (zh)* 2002-08-21 2006-02-15 中国科学院大连化学物理研究所 二维或多维毛细管电泳分离生物大分子的方法

Antibody profiling is a fundamental component of understanding the humoral response in a wide range of disease areas. Most currently used approaches operate by capturing antibodies onto functionalised surfaces. Such measurements of surface binding are governed by an overall antibody titre, while the two fundamental molecular parameters, antibody affinity and antibody concentration, are challenging to determine individually from such approaches. Here, by applying microfluidic diffusional sizing (MDS), we show how we can overcome this challenge and demonstrate reliable quantification of alloantibody binding affinity and concentration of alloantibodies binding to Human Leukocyte Antigens (HLA), an extensively used clinical biomarker in organ transplantation, both in buffer and in crude human serum. Capitalising on the ability to vary both serum and HLA concentrations during MDS, we show that both …

NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C (= O) C (NC (= O) C (CCC (N)= O) NC (= O) C (CCC (O)= O) NC (= O) C (C (C) C) NC (= O) C (NC (= O) CN) C (C) CC) CSSCC (C (NC (CO) C (= O) NC (CC (C) C) C (= O) NC (CC= 2C= CC (O)= CC= 2) C (= O) NC (CCC (N)= O) C (= O) NC (CC (C) C) C (= O) NC (CCC (O)= O) C (= O) NC (CC (N)= O) C (= O) NC (CC= 2C= CC (O)= CC= 2) C (= O) NC (CSSCC (NC (= O) C (C (C) C) NC (= O) C (CC (C) C) NC (= O) C (CC= 2C= CC (O)= CC= 2) NC (= O) C (CC (C) C) NC (= O) C (C) NC (= O) C (CCC (O)= O) NC (= O) C (C (C) C) NC (= O) C (CC (C) C) NC (= O) C (CC= 2NC= NC= 2) NC (= O) C (CO) NC (= O) CNC2= O) C (= O) NCC (= O) NC (CCC (O)= O) C (= O) NC (CCCNC (N)= N) C (= O) NCC (= O) NC (CC= 3C= CC= CC= 3) C (= O) NC (CC= 3C= CC= CC= 3) C (= O) NC (CC= 3C= CC (O)= CC= 3) C (= O) NC (C (C) O) C (= O) N3C …