Determining Protein Complex Connectivity Using a Probabilistic Deletion Network Derived from Quantitative Proteomics

Protein complexes are key molecular machines executing a variety of essential cellular processes. Despite the availability of genome-wide protein-protein interaction studies, determining the connectivity between proteins within a complex remains a major challenge. Here we demonstrate a method that is able to predict the relationship of proteins within a stable protein complex. We employed a combination of computational approaches and a systematic collection of quantitative proteomics data from wild-type and deletion strain purifications to build a quantitative deletion-interaction network map and subsequently convert the resulting data into an interdependency-interaction model of a complex. We applied this approach to a data set generated from components of the Saccharomyces cerevisiae Rpd3 histone deacetylase complexes, which consists of two distinct small and large complexes that are held together by a module consisting of Rpd3, Sin3 and Ume1. The resulting representation reveals new protein-protein interactions and new submodule relationships, providing novel information for mapping the functional organization of a complex

The Hubble Deep Field South Flanking Fields

As part of the Hubble Deep Field South program, a set of shorter 2-orbit observations were obtained of the area adjacent to the deep fields. The WFPC2 flanking fields cover a contiguous solid angle of 48 square arcminutes. Parallel observations with the STIS and NICMOS instruments produce a patchwork of additional fields with optical and near-infrared (1.6 micron) response. Deeper parallel exposures with WFPC2 and NICMOS were obtained when STIS observed the NICMOS deep field. These deeper fields are offset from the rest, and an extended low surface brightness object is visible in the deeper WFPC2 flanking field. In this data paper, which serves as an archival record of the project, we discuss the observations and data reduction, and present SExtractor source catalogs and number counts derived from the data. Number counts are broadly consistent with previous surveys from both ground and space. Among other things, these flanking field observations are useful for defining slit masks for spectroscopic follow-up over a wider area around the deep fields, for studying large-scale structure that extends beyond the deep fields, for future supernova searches, and for number counts and morphological studies, but their ultimate utility will be defined by the astronomical community.Comment: 46 pages, 15 figures. Images and full catalogs available via the HDF-S at http://www.stsci.edu/ftp/science/hdfsouth/hdfs.html at present. The paper is accepted for the February 2003 Astronomical Journal. Full versions of the catalogs will also be available on-line from AJ after publicatio

Combinatorial depletion analysis to assemble the network architecture of the SAGA and ADA chromatin remodeling complexes

A combinatorial depletion strategy is combined with biochemistry, quantitative proteomics and computational approaches to elucidate the structure of the SAGA/ADA complexes. The analysis reveals five connected functional modules capable of independent assembly

Proof of principle for a high sensitivity search for the electric dipole moment of the electron using the metastable a(1)[^3\Sigma^+] state of PbO

The metastable a(1)[^3\Sigma^+] state of PbO has been suggested as a suitable system in which to search for the electric dipole moment (EDM) of the electron. We report here the development of experimental techniques allowing high-sensitivity measurements of Zeeman and Stark effects in this system, similar to those required for an EDM search. We observe Zeeman quantum beats in fluorescence from a vapor cell, with shot-noise limited extraction of the quantum beat frequencies, high counting rates, and long coherence times. We argue that improvement in sensitvity to the electron EDM by at least two orders of magnitude appears possible using these techniques.Comment: 5 pages, 3 figure

The effect of intervertebral cartilage on neutral posture and range of motion in the necks of sauropod dinosaurs

The necks of sauropod dinosaurs were a key factor in their evolution. The habitual posture and range of motion of these necks has been controversial, and computer-aided studies have argued for an obligatory sub-horizontal pose. However, such studies are compromised by their failure to take into account the important role of intervertebral cartilage. This cartilage takes very different forms in different animals. Mammals and crocodilians have intervertebral discs, while birds have synovial joints in their necks. The form and thickness of cartilage varies significantly even among closely related taxa. We cannot yet tell whether the neck joints of sauropods more closely resembled those of birds or mammals. Inspection of CT scans showed cartilage:bone ratios of 4.5% for Sauroposeidon and about 20% and 15% for two juvenile Apatosaurus individuals. In extant animals, this ratio varied from 2.59% for the rhea to 24% for a juvenile giraffe. It is not yet possible to disentangle ontogenetic and taxonomic signals, but mammal cartilage is generally three times as thick as that of birds. Our most detailed work, on a turkey, yielded a cartilage:bone ratio of 4.56%. Articular cartilage also added 11% to the length of the turkey's zygapophyseal facets. Simple image manipulation suggests that incorporating 4.56% of neck cartilage into an intervertebral joint of a turkey raises neutral posture by 15°. If this were also true of sauropods, the true neutral pose of the neck would be much higher than has been depicted. An additional 11% of zygapophyseal facet length translates to 11% more range of motion at each joint. More precise quantitative results must await detailed modelling. In summary, including cartilage in our models of sauropod necks shows that they were longer, more elevated and more flexible than previously recognised

Multihospital Outbreak of Clostridium difficile Ribotype 027 Infection: Epidemiology and Analysis of Control Measures

Objective. To report a large outbreak of Clostridium difficile infection (CDI; ribotype 027) between June 2007 and August 2008, describe infection control measures, and evaluate the impact of restricting the use of fluoroquinolones in controlling the outbreak. Design. Outbreak investigation in 3 acute care hospitals of the Northern Health and Social Care Trust in Northern Ireland. Interventions. Implementation of a series of CDI control measures that targeted high-risk antibiotic agents (ie, restriction of fluoroquinolones), infection control practices, and environmental hygiene. Results. A total of 318 cases of CDI were identified during the outbreak, which was the result of the interaction between C. difficile ribotype 027 being introduced into the affected hospitals for the first time and other predisposing risk factors (ranging from host factors to suboptimal compliance with antibiotic guidelines and infection control policies). The 30-day all-cause mortality rate was 24.5%; however, CDI was the attributable cause of death for only 2.5% of the infected patients. Time series analysis showed that restricting the use of fluoroquinolones was associated with a significant reduction in the incidence of CDI (coefficient, —0.054; lag time, 4 months; P = .003). Conclusion. These findings provide additional evidence to support the value of antimicrobial stewardship as an essential element of multifaceted interventions to control CDI outbreaks. The present CDI outbreak was ended following the implementation of an action plan improving communication, antibiotic stewardship, infection control practices, environmental hygiene, and surveillanc

Squeezed States for General Systems

We propose a ladder-operator method for obtaining the squeezed states of general symmetry systems. It is a generalization of the annihilation-operator technique for obtaining the coherent states of symmetry systems. We connect this method with the minimum-uncertainty method for obtaining the squeezed and coherent states of general potential systems, and comment on the distinctions between these two methods and the displacement-operator method.Comment: 8 pages, LAUR-93-1721, LaTe