Going the distance for protein function prediction: a new distance metric for protein interaction networks

Due to an error introduced in the production process, the x-axes in the first panels of Figure 1 and Figure 7 are not formatted correctly. The correct Figure 1 can be viewed here: http://dx.doi.org/10.1371/annotation/343bf260-f6ff-48a2-93b2-3cc79af518a9In protein-protein interaction (PPI) networks, functional similarity is often inferred based on the function of directly interacting proteins, or more generally, some notion of interaction network proximity among proteins in a local neighborhood. Prior methods typically measure proximity as the shortest-path distance in the network, but this has only a limited ability to capture fine-grained neighborhood distinctions, because most proteins are close to each other, and there are many ties in proximity. We introduce diffusion state distance (DSD), a new metric based on a graph diffusion property, designed to capture finer-grained distinctions in proximity for transfer of functional annotation in PPI networks. We present a tool that, when input a PPI network, will output the DSD distances between every pair of proteins. We show that replacing the shortest-path metric by DSD improves the performance of classical function prediction methods across the board.MC, HZ, NMD and LJC were supported in part by National Institutes of Health (NIH) R01 grant GM080330. JP was supported in part by NIH grant R01 HD058880. This material is based upon work supported by the National Science Foundation under grant numbers CNS-0905565, CNS-1018266, CNS-1012910, and CNS-1117039, and supported by the Army Research Office under grant W911NF-11-1-0227 (to MEC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Tropospheric Airborne Meteorological Data Reporting (TAMDAR) Sensor Validation and Verification on National Oceanographic and Atmospheric Administration (NOAA) Lockheed WP-3D Aircraft

As part of the National Aeronautics and Space Administration's Aviation Safety and Security Program, the Tropospheric Airborne Meteorological Data Reporting project (TAMDAR) developed a low-cost sensor for aircraft flying in the lower troposphere. This activity was a joint effort with support from Federal Aviation Administration, National Oceanic and Atmospheric Administration, and industry. This paper reports the TAMDAR sensor performance validation and verification, as flown on board NOAA Lockheed WP-3D aircraft. These flight tests were conducted to assess the performance of the TAMDAR sensor for measurements of temperature, relative humidity, and wind parameters. The ultimate goal was to develop a small low-cost sensor, collect useful meteorological data, downlink the data in near real time, and use the data to improve weather forecasts. The envisioned system will initially be used on regional and package carrier aircraft. The ultimate users of the data are National Centers for Environmental Prediction forecast modelers. Other users include air traffic controllers, flight service stations, and airline weather centers. NASA worked with an industry partner to develop the sensor. Prototype sensors were subjected to numerous tests in ground and flight facilities. As a result of these earlier tests, many design improvements were made to the sensor. The results of tests on a final version of the sensor are the subject of this report. The sensor is capable of measuring temperature, relative humidity, pressure, and icing. It can compute pressure altitude, indicated air speed, true air speed, ice presence, wind speed and direction, and eddy dissipation rate. Summary results from the flight test are presented along with corroborative data from aircraft instruments

Interplay of Inflammatory, Antigen and Tissue-Derived Signals in the Development of Resident CD8 Memory T Cells

CD8 positive, tissue resident memory T cells (TRM) are a specialized subset of CD8 memory T cells that surveil tissues and provide critical first-line protection against tumors and pathogen re-infection. Recently, much effort has been dedicated to understanding the function, phenotype and development of TRM. A myriad of signals is involved in the development and maintenance of resident memory T cells in tissue. Much of the initial research focused on the roles tissue-derived signals play in the development of TRM, including TGFß and IL-33 which are critical for the upregulation of CD69 and CD103. However, more recent data suggest further roles for antigenic and pro-inflammatory cytokines. This review will focus on the interplay of pro-inflammatory, tissue and antigenic signals in the establishment of resident memory T cells

Can Biomechanical Testing After Anterior Cruciate Ligament Reconstruction Identify Athletes at Risk for Subsequent ACL Injury to the Contralateral Uninjured Limb?

Background: Athletes are twice as likely to rupture the anterior cruciate ligament (ACL) on their healthy contralateral knee than the reconstructed graft after ACL reconstruction (ACLR). Although physical testing is commonly used after ACLR to assess injury risk to the operated knee, strength, jump, and change-of-direction performance and biomechanical measures have not been examined in those who go on to experience a contralateral ACL injury, to identify factors that may be associated with injury risk. Purpose: To prospectively examine differences in biomechanical and clinical performance measures in male athletes 9 months after ACLR between those who ruptured their previously uninjured contralateral ACL and those who did not at 2-year follow-up and to examine the ability of these differences to predict contralateral ACL injury. Study Design: Case-control study; Level of evidence, 3. Methods: A cohort of male athletes returning to level 1 sports after ACLR (N = 1045) underwent isokinetic strength testing and 3-dimensional biomechanical analysis of jump and change-of-direction tests 9 months after surgery. Participants were followed up at 2 years regarding return to play or at second ACL injury. Between-group differences were analyzed in patient-reported outcomes, performance measures, and 3-dimensional biomechanics for the contralateral limb and asymmetry. Logistic regression was applied to determine the ability of identified differences to predict contralateral ACL injury. Results: Of the cohort, 993 had follow-up at 2 years (95%), with 67 experiencing a contralateral ACL injury and 38 an ipsilateral injury. Male athletes who had a contralateral ACL injury had lower quadriceps strength and biomechanical differences on the contralateral limb during double- and single-leg drop jump tests as compared with those who did not experience an injury. Differences were related primarily to deficits in sagittal plane mechanics and plyometric ability on the contralateral side. These variables could explain group membership with fair to good ability (area under the curve, 0.74-0.80). Patient-reported outcomes, limb symmetry of clinical performance measures, and biomechanical measures in change-of-direction tasks did not differentiate those at risk for contralateral injury. Conclusion: This study highlights the importance of sagittal plane control during drop jump tasks and the limited utility of limb symmetry in performance and biomechanical measures when assessing future contralateral ACL injury risk in male athletes. Targeting the identified differences in quadriceps strength and plyometric ability during late-stage rehabilitation and testing may reduce ACL injury risk in healthy limbs in male athletes playing level 1 sports. Clinical Relevance: This study highlights the importance of assessing the contralateral limb after ACLR and identifies biomechanical differences, particularly in the sagittal plane in drop jump tasks, that may be associated with injury to this limb. These factors could be targeted during assessment and rehabilitation with additional quadriceps strengthening and plyometric exercises after ACLR to potentially reduce the high risk of injury to the previously healthy knee

The EVERSHED receptor-like kinase modulates floral organ shedding in Arabidopsis

Plant cell signaling triggers the abscission of entire organs, such as fruit, leaves and flowers. Previously, we characterized an ADP-ribosylation factor GTPase-activating protein, NEVERSHED (NEV), that regulates membrane trafficking and is essential for floral organ shedding in Arabidopsis. Through a screen for mutations that restore organ separation in nev flowers, we have identified a leucine-rich repeat receptor-like kinase, EVERSHED (EVR), that functions as an inhibitor of abscission. Defects in the Golgi structure and location of the trans-Golgi network in nev abscission zone cells are rescued by a mutation in EVR, suggesting that EVR might regulate membrane trafficking during abscission. In addition to shedding their floral organs prematurely, nev evr flowers show enlarged abscission zones. A similar phenotype was reported for plants ectopically expressing INFLORESCENCE DEFICIENT IN ABSCISSION, a predicted signaling ligand for the HAESA/HAESA-LIKE2 receptor-like kinases, indicating that this signaling pathway may be constitutively active in nev evr flowers. We present a model in which EVR modulates the timing and region of abscission by promoting the internalization of other receptor-like kinases from the plasma membrane

Bostonia: 1998-1999, no. 1, 3-4

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Improving Colorectal Cancer Screening Decision Making Processes

Introduction: Although shared decision making is recommended for cancer screening, it is not routinely completed in practice because of time constraints. We evaluated a process for improving decision making about colorectal cancer (CRC) screening using mailed decision aids (DA) with follow-up telephone support in primary care practices. Methods: We identified patients aged 50-75 who were not up to date with CRC screening in three primary care practices. DA were distributed via mail with telephone follow-up to eligible patients, and charts were reviewed six months later for CRC screening completion. Results: Among 1,064 eligible patients who received the mailed DA, 513 (48.2%) were reached by phone. During the six months after the intervention, 148/1064 (13.9%) patients were screened for CRC (4.8% underwent FIT, 9.1% underwent colonoscopy). Younger patients (aged 50-54) had higher rates of any screening (32.4%) compared with all other age groups (range 12.8%-19.6%), p=0.026, while Medicaid patients had the lowest rates of screening (4.0%), and insured patients had the highest rates (45.3%), p=0.003. Overall, 113/513 (22.0%) who were reached by phone went on to complete screening within 6 months, compared with 35/551 (6.4%) of patients who were not reached by phone (p Conclusion: A standard process for identifying patients unscreened for CRC and DA distribution via mail with telephone decision support modestly increased CRC screening and is consistent with the goal of providing preference-sensitive care and informed decision making. Improving care processes to include decision support outside of office visits is possible in primary care practices

Tropospheric Airborne Meteorological Data and Reporting (TAMDAR) Icing Sensor Performance during the 2003/2004 Alliance Icing Research Study (AIRS II)

NASA Langley Research Center and its research partners from the University of North Dakota (UND) and the National Center for Atmospheric Research (NCAR) participated in the AIRS II campaign from November 17 to December 17, 2003. AIRS II provided the opportunity to compare TAMDAR in situ in-flight icing condition assessments with in situ data from the UND Citation II aircraft's Rosemont system. TAMDAR is designed to provide a general warning of ice accretion and to report it directly into the Meteorological Data Communications and Reporting System (MDCRS). In addition to evaluating TAMDAR with microphysical data obtained by the Citation II, this study also compares these data to the NWS operational in-flight icing Current Icing Potential (CIP) graphic product and with the NASA Advanced Satellite Aviation-weather Products (ASAP) Icing Severity product. The CIP and ASAP graphics are also examined in this study to provide a context for the Citation II's sorties in AIRS II