The cohesin ring concatenates sister DNA molecules

Sister chromatid cohesion, which is essential for mitosis, is mediated by a multi-subunit protein complex called cohesin whose Scc1, Smc1, and Smc3 subunits form a tripartite ring structure. It has been proposed that cohesin holds sister DNAs together by trapping them inside its ring. To test this, we used site-specific cross-linking to create chemical connections at the three interfaces between the ring’s three constituent polypeptides, thereby creating covalently closed cohesin rings. As predicted by the ring entrapment model, this procedure produces dimeric DNA/cohesin structures that are resistant to protein denaturation. We conclude that cohesin rings concatenate individual sister minichromosome DNAs

A framework for automatic semantic video annotation

The rapidly increasing quantity of publicly available videos has driven research into developing automatic tools for indexing, rating, searching and retrieval. Textual semantic representations, such as tagging, labelling and annotation, are often important factors in the process of indexing any video, because of their user-friendly way of representing the semantics appropriate for search and retrieval. Ideally, this annotation should be inspired by the human cognitive way of perceiving and of describing videos. The difference between the low-level visual contents and the corresponding human perception is referred to as the ‘semantic gap’. Tackling this gap is even harder in the case of unconstrained videos, mainly due to the lack of any previous information about the analyzed video on the one hand, and the huge amount of generic knowledge required on the other. This paper introduces a framework for the Automatic Semantic Annotation of unconstrained videos. The proposed framework utilizes two non-domain-specific layers: low-level visual similarity matching, and an annotation analysis that employs commonsense knowledgebases. Commonsense ontology is created by incorporating multiple-structured semantic relationships. Experiments and black-box tests are carried out on standard video databases for action recognition and video information retrieval. White-box tests examine the performance of the individual intermediate layers of the framework, and the evaluation of the results and the statistical analysis show that integrating visual similarity matching with commonsense semantic relationships provides an effective approach to automated video annotation

SCAMP: Rapid Focused Sonic Boom Waypoint Flight Planning Methods, Execution, and Results

Successful execution of the flight phase of the Superboom Caustic Analysis and Measurement Project (SCAMP) required accurate placement of focused sonic booms on an array of prepositioned ground sensors. While the array was spread over a 10,000-ft-long area, this is a relatively small region when considering the speed of a supersonic aircraft and sonic boom ray path variability due to shifting atmospheric conditions and aircraft trajectories. Another requirement of the project was to determine the proper position for a microphone-equipped motorized glider to intercept the sonic boom caustic, adding critical timing to the constraints. Variability in several inputs to these calculations caused some shifts of the focus away from the optimal location. Reports of the sonic booms heard by persons positioned amongst the array were used to shift the focus closer to the optimal location for subsequent passes. This paper describes the methods and computations used to place the focused sonic boom on the SCAMP array and gives recommendations for their accurate placement by future quiet supersonic aircraft. For the SCAMP flights, 67% of the foci were placed on the ground array with measured positions within a few thousand feet of computed positions. Among those foci with large caustic elevation angles, 96% of foci were placed on the array, and measured positions were within a few hundred feet of computed positions. The motorized glider captured sonic booms on 59% of the passes when the instrumentation was operating properly

Comparison of insulin glargine and liraglutide added to oral agents in patients with poorly controlled type 2 diabetes

Peer reviewe

Probing Mechanical Properties of Graphene with Raman Spectroscopy

The use of Raman scattering techniques to study the mechanical properties of graphene films is reviewed here. The determination of Gruneisen parameters of suspended graphene sheets under uni- and bi-axial strain is discussed and the values are compared to theoretical predictions. The effects of the graphene-substrate interaction on strain and to the temperature evolution of the graphene Raman spectra are discussed. Finally, the relation between mechanical and thermal properties is presented along with the characterization of thermal properties of graphene with Raman spectroscopy.Comment: To appear in the Journal of Materials Scienc

The Elg1 Clamp Loader Plays a Role in Sister Chromatid Cohesion

Mutations in the ELG1 gene of yeast lead to genomic instability, manifested in high levels of genetic recombination, chromosome loss, and gross chromosomal rearrangements. Elg1 shows similarity to the large subunit of the Replication Factor C clamp loader, and forms a RFC-like (RLC) complex in conjunction with the 4 small RFC subunits. Two additional RLCs exist in yeast: in one of them the large subunit is Ctf18, and in the other, Rad24. Ctf18 has been characterized as the RLC that functions in sister chromatid cohesion. Here we present evidence that the Elg1 RLC (but not Rad24) also plays an important role in this process. A genetic screen identified the cohesin subunit Mcd1/Scc1 and its loader Scc2 as suppressors of the synthetic lethality between elg1 and ctf4. We describe genetic interactions between ELG1 and genes encoding cohesin subunits and their accessory proteins. We also show that defects in Elg1 lead to higher precocious sister chromatid separation, and that Ctf18 and Elg1 affect cohesion via a joint pathway. Finally, we localize both Ctf18 and Elg1 to chromatin and show that Elg1 plays a role in the recruitment of Ctf18. Our results suggest that Elg1, Ctf4, and Ctf18 may coordinate the relative movement of the replication fork with respect to the cohesin ring

A Flight Research Overview of WSPR, a Pilot Project for Sonic Boom Community Response

In support of NASAs ongoing effort to bring supersonic commercial travel to the public, NASA Dryden Flight Research Center and NASA Langley Research Center, in cooperation with other industry organizations, conducted a flight research experiment to identify the methods, tools, and best practices for a large-scale quiet (or low) sonic boom community human response test. The name of the effort was Waveforms and Sonic boom Perception and Response. Such tests will go towards building a dataset that governing agencies like the Federal Aviation Administration and International Civil Aviation Organization will use to establish regulations for acceptable sound levels of overland sonic booms. Until WSPR, there had never been an effort that studied the response of people in their own homes and performing daily activities to non-traditional, low sonic booms.WSPR was a NASA collaborative effort with several industry partners, in response to a NASA Aeronautics Research Mission Directorate Research Opportunities in Aeronautics. The primary contractor was Wyle. Other partners included Gulfstream Aerospace Corporation, Pennsylvania State University, Tetra Tech, and Fidell Associates, Inc.A major objective of the effort included exposing a community with the sonic boom magnitudes and occurrences expected in high-air traffic regions with a network of supersonic commercial aircraft in place. Low-level sonic booms designed to simulate those produced by the next generation of commercial supersonic aircraft were generated over a small residential community. The sonic boom footprint was recorded with an autonomous wireless microphone array that spanned the entire community. Human response data was collected using multiple survey methods. The research focused on essential elements of community response testing including subject recruitment, survey methods, instrumentation systems, flight planning and operations, and data analysis methods.This paper focuses on NASAs role in the efforts logistics and operations including human response subject recruitment, the operational processes involved in implementing the surveys throughout the community, instrumentation systems, logistics, flight planning, and flight operations. Findings discussed in this paper include critical lessons learned in all of those areas. The paper also discusses flight operations results. Analysis of the accuracy and repeatability of planning and executing the unique aircraft maneuver used to generate low sonic booms concluded that the sonic booms had overpressures within 0.15 pounds-per-square-feet of the planned values for 76 of t he attempts. Similarly, 90 of the attempts to generate low sonic booms within the community were successful

Centromere-associated topoisomerase activity in bloodstream form Trypanosoma brucei

Topoisomerase-II accumulates at centromeres during prometaphase, where it resolves the DNA catenations that represent the last link between sister chromatids. Previously, using approaches including etoposide-mediated topoisomerase-II cleavage, we mapped centromeric domains in trypanosomes, early branching eukaryotes in which chromosome segregation is poorly understood. Here, we show that in bloodstream form Trypanosoma brucei, RNAi-mediated depletion of topoisomerase-IIα, but not topoisomerase-IIβ, results in the abolition of centromere-localized activity and is lethal. Both phenotypes can be rescued by expression of the corresponding enzyme from T. cruzi. Therefore, processes which govern centromere-specific topoisomerase-II accumulation/activation have been functionally conserved within trypanosomes, despite the long evolutionary separation of these species and differences in centromeric DNA organization. The variable carboxyl terminal region of topoisomerase-II has a major role in regulating biological function. We therefore generated T. brucei lines expressing T. cruzi topoisomerase-II truncated at the carboxyl terminus and examined activity at centromeres after the RNAi-mediated depletion of the endogenous enzyme. A region necessary for nuclear localization was delineated to six residues. In other organisms, sumoylation of topoisomerase-II has been shown to be necessary for regulated chromosome segregation. Evidence that we present here suggests that sumoylation of the T. brucei enzyme is not required for centromere-specific cleavage activity

Distinct Roles for Condensin's Two ATPase Sites in Chromosome Condensation

Condensin is a conserved SMC complex that uses its ATPase machinery to structure genomes, but how it does so is largely unknown. We show that condensin's ATPase has a dual role in chromosome condensation. Mutation of one ATPase site impairs condensation, while mutating the second site results in hyperactive condensin that compacts DNA faster than wild-type, both in vivo and in vitro. Whereas one site drives loop formation, the second site is involved in the formation of more stable higher-order Z loop structures. Using hyperactive condensin I, we reveal that condensin II is not intrinsically needed for the shortening of mitotic chromosomes. Condensin II rather is required for a straight chromosomal axis and enables faithful chromosome segregation by counteracting the formation of ultrafine DNA bridges. SMC complexes with distinct roles for each ATPase site likely reflect a universal principle that enables these molecular machines to intricately control chromosome architecture