Controlling Hazardous Noise and Dust within the Industrial Workforce Using a Simple Barrier

The United States Air Force (USAF) has experienced a dramatic increase in hearing loss claims since 2001. Additionally, many operations within the USAF expose personnel to hazardous dust levels. Likewise, the US mining industry has difficulties controlling hazardous noise and dust exposures in underground mining. Specifically, studies have shown that coal mine longwall shearer operators are routinely exposed to noise levels at 151 percent of the allowable dose and approximately 20 percent exceed regulatory dust levels. An above ground full scale model of the underground shearing operation was developed to test the feasibility of mounting a permanent partial barrier on the longwall shearer. The barrier was constructed and tested at the National Institute for Occupational Safety and Health Pittsburgh Research Laboratory (NIOSH-PRL) longwall test facility. The barrier achieved as high as a 7.3 dB(A) reduction in noise levels and a 96 percent reduction in respirable dust. Several predictive models were tested and compared to measured noise reduction results. A final spreadsheet was developed as a tool for base level Bioenvironmental Engineers to determine when a partial barrier may be an effective engineered solution for controlling hazardous noise or dust within USAF industrial operations

Serendipitous Discovery of Light-Induced \u3cem\u3e(In Situ)\u3c/em\u3e Formation of An Azo-Bridged Dimeric Sulfonated Naphthol as a Potent PTP1B Inhibito

Background Protein tyrosine phosphatases (PTPs) like dual specificity phosphatase 5 (DUSP5) and protein tyrosine phosphatase 1B (PTP1B) are drug targets for diseases that include cancer, diabetes, and vascular disorders such as hemangiomas. The PTPs are also known to be notoriously difficult targets for designing inihibitors that become viable drug leads. Therefore, the pipeline for approved drugs in this class is minimal. Furthermore, drug screening for targets like PTPs often produce false positive and false negative results. Results Studies presented herein provide important insights into: (a) how to detect such artifacts, (b) the importance of compound re-synthesis and verification, and (c) how in situ chemical reactivity of compounds, when diagnosed and characterized, can actually lead to serendipitous discovery of valuable new lead molecules. Initial docking of compounds from the National Cancer Institute (NCI), followed by experimental testing in enzyme inhibition assays, identified an inhibitor of DUSP5. Subsequent control experiments revealed that this compound demonstrated time-dependent inhibition, and also a time-dependent change in color of the inhibitor that correlated with potency of inhibition. In addition, the compound activity varied depending on vendor source. We hypothesized, and then confirmed by synthesis of the compound, that the actual inhibitor of DUSP5 was a dimeric form of the original inhibitor compound, formed upon exposure to light and oxygen. This compound has an IC50 of 36 μM for DUSP5, and is a competitive inhibitor. Testing against PTP1B, for selectivity, demonstrated the dimeric compound was actually a more potent inhibitor of PTP1B, with an IC50 of 2.1 μM. The compound, an azo-bridged dimer of sulfonated naphthol rings, resembles previously reported PTP inhibitors, but with 18-fold selectivity for PTP1B versus DUSP5. Conclusion We report the identification of a potent PTP1B inhibitor that was initially identified in a screen for DUSP5, implying common mechanism of inhibitory action for these scaffolds

Saccharomyces cerevisiae Rad9 Acts as a Mec1 Adaptor to Allow Rad53 Activation

SummaryBackground: The DNA damage checkpoint is a protein kinase-based signaling system that detects and signals physical alterations in DNA. Despite having identified many components of this signaling cascade, the exact mechanisms by which checkpoint kinases are activated after DNA damage, as well as the role of the checkpoint mediators, remain poorly understood.Results: To elucidate the mechanisms that underlie the MEC1 and RAD9-dependent activation of Rad53, the Saccharomyces cerevisiae ortholog of Chk2, we mapped and characterized in vivo phosphorylation sites present on Rad53 after DNA damage by mass spectrometry. We find that Rad53 requires for its activation multisite phosphorylation on a number of typical and atypical Mec1 phosphorylation sites, thus confirming that Rad53 is a direct target of Mec1, the mammalian ATR homolog. Moreover, by using biochemical reconstitution experiments, we demonstrate that efficient and direct phosphorylation of Rad53 by Mec1 is only observed in the presence of purified Rad9, the archetypal checkpoint mediator. We find that the stimulatory activity of Rad9 requires a phospho- and FHA-dependent interaction with Rad53, which allows Rad53 to be recognized as a substrate for Mec1.Conclusions: Our results indicate that Rad9 acts as a bona fide signaling adaptor that enables Rad53 phosphorylation by Mec1. Given the high degree of conservation of checkpoint signaling in eukaryotes, we propose that one of the critical functions of checkpoint mediators such as MDC1, 53BP1, or Brca1 is to act as PIKK adaptors during the DNA damage response

CDC5 Inhibits the Hyperphosphorylation of the Checkpoint Kinase Rad53, Leading to Checkpoint Adaptation

The mechanistic role of the yeast kinase CDC5, in allowing cells to adapt to the presence of irreparable DNA damage and continue to divide, is revealed

Characterizing the impacts of multi-scale heterogeneity on solute transport in fracture networks

We model flow and transport in three-dimensional fracture networks with varying degrees of fracture-to-fracture aperture/permeability heterogeneity and network density to show how changes in these properties can cause the emergence of anomalous flow and transport behavior. If fracture-to-fracture aperture heterogeneity is increased in sparse networks, velocity fluctuations can inhibit high flow rates and solute transport can be delayed, even in cases where hydraulic aperture is monotonically increased. As the density of the networks is increased, more connected pathways allow for particles to bypass these effects. We discover transition behavior where with relatively few connected pathways in a network from inflow to outflow boundaries, the first arrival times of particles are not heavily affected by fracture-to-fracture aperture heterogeneity, but the scaling behavior of the tails is strongly influenced due to the particles being forced to sample some of the heterogeneity in the velocity field caused by aperture differences. These results reinforce the importance of considering multi-scale effects in fractured systems and can inform flow and transport processes in both natural and engineered fracture systems, especially the latter where high aperture fractures are often stimulated and connect to existing fracture networks with smaller apertures

Foreign Intravascular Object Embolization and Migration: Bullets, Catheters, Wires, Stents, Filters, and More

Foreign intravascular object embolization (FIOE) is an important, yet underreported occurrence that has been described in a variety of settings, from penetrating trauma to intravascular procedures. In this chapter, the authors will review the most common types of FIOEs, including bullet or “projectile” embolism (BPE), followed by intravascular catheter or wire embolization (ICWE), and conclude with intravascular noncatheter object (e.g., coil, gelatin, stent, and venous filter) migration (INCOM). In addition to detailed topic-based summaries, tables highlighting selected references and case scenarios are also presented to provide the reader with a resource for future research in this clinical area

One-pot hydrogen peroxide and hydrohalic acid induced ring closure and selective aromatic halogenation to give new ring-fused benzimidazoles

A new series of selectively dichlorinated and dibrominated five to eight-membered ring [1,2-a] fused benzimidazoles and [1,4]oxazino[4,3-a]benzimidazoles are synthesized in mostly high yields of >80% using the reaction of hydrogen peroxide and hydrohalic acid with commercially available o-cyclic amine substituted anilines. Domestic bleach with HCl is also capable of a one-pot ring-closure and chlorination

The Pan-STARRS Moving Object Processing System

We describe the Pan-STARRS Moving Object Processing System (MOPS), a modern software package that produces automatic asteroid discoveries and identifications from catalogs of transient detections from next-generation astronomical survey telescopes. MOPS achieves > 99.5% efficiency in producing orbits from a synthetic but realistic population of asteroids whose measurements were simulated for a Pan-STARRS4-class telescope. Additionally, using a non-physical grid population, we demonstrate that MOPS can detect populations of currently unknown objects such as interstellar asteroids. MOPS has been adapted successfully to the prototype Pan-STARRS1 telescope despite differences in expected false detection rates, fill-factor loss and relatively sparse observing cadence compared to a hypothetical Pan-STARRS4 telescope and survey. MOPS remains >99.5% efficient at detecting objects on a single night but drops to 80% efficiency at producing orbits for objects detected on multiple nights. This loss is primarily due to configurable MOPS processing limits that are not yet tuned for the Pan-STARRS1 mission. The core MOPS software package is the product of more than 15 person-years of software development and incorporates countless additional years of effort in third-party software to perform lower-level functions such as spatial searching or orbit determination. We describe the high-level design of MOPS and essential subcomponents, the suitability of MOPS for other survey programs, and suggest a road map for future MOPS development.Comment: 57 Pages, 26 Figures, 13 Table

Changes in reflectin protein phosphorylation are associated with dynamic iridescence in squid

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of The Royal Society for personal use, not for redistribution. The definitive version was published in Journal of The Royal Society Interface 6 (2010): 549-560, doi:10.1098/rsif.2009.0299.Many cephalopods exhibit remarkable dermal iridescence, a component of their complex, dynamic camouflage and communication. In the species Euprymna scolopes, the light-organ iridescence is static and is due to reflectin protein-based platelets assembled into lamellar thin-film reflectors called iridosomes, contained within iridescent cells called iridocytes. Squid in the family Loliginidae appear to be unique in that the dermis possesses a dynamic iridescent component, with reflective, colored structures that are assembled and disassembled under the control of the muscarinic cholinergic system and the associated neurotransmitter acetylcholine (Mathger et al. 2004). Here we present the sequences and characterization of three new members of the reflectin family associated with the dynamically changeable iridescence in Loligo and not found in static Euprymna iridophores. In addition, we show that application of genistein, a protein tyrosine kinase inhibitor, suppresses acetylcholine- and calcium-induced iridescence in Loligo. We further demonstrate that two of these novel reflectins are extensively phosphorylated in concert with the activation of iridescence by exogenous acetylcholine. This phosphorylation and the correlated iridescence can be blocked with genistein. Our results suggest that tyrosine phosphorylation of reflectin proteins is involved in the regulation of dynamic iridescence in Loligo.We gratefully acknowledge support from Anteon contract F33615-03-D-5408 to the Marine Biological Laboratory, Woods Hole, MA and grant # W911NF-06-1-0285 from the Army Research Office to D.E.M

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500