Biomass burning emission disturbances of isoprene oxidation in a tropical forest

We present a characterization of the chemical composition of the atmosphere of the Brazilian Amazon rainforest based on trace gas measurements carried out during the South AMerican Biomass Burning Analysis (SAMBBA) airborne experiment in September 2012. We analyzed the observations of primary biomass burning emission tracers, i.e., carbon monoxide (CO), nitrogen oxides (NOx), ozone (O3), isoprene, and its main oxidation products, methyl vinyl ketone (MVK), methacrolein (MACR), and isoprene hydroxy hydroperoxide (ISOPOOH). The focus of SAMBBA was primarily on biomass burning emissions, but there were also several flights in areas of the Amazon forest not directly affected by biomass burning, revealing a background with a signature of biomass burning in the chemical composition due to long-range transport of biomass burning tracers from both Africa and the eastern part of Amazonia. We used the [MVK+MACR+ISOPOOH]∕[isoprene] ratio and the hydroxyl radical (OH) indirect calculation to assess the oxidative capacity of the Amazon forest atmosphere. We compared the background regions (CO<150ppbv), fresh and aged smoke plumes classified according to their photochemical age ([O3]∕[CO]), to evaluate the impact of biomass burning emissions on the oxidative capacity of the Amazon forest atmosphere. We observed that biomass burning emissions disturb the isoprene oxidation reactions, especially for fresh plumes ([MVK+MACR+ISOPOOH]∕[isoprene] = 7) downwind. The oxidation of isoprene is higher in fresh smoke plumes at lower altitudes (∼500m) than in aged smoke plumes, anticipating near the surface a complex chain of oxidation reactions which may be related to secondary organic aerosol (SOA) formation. We proposed a refinement of the OH calculation based on the sequential reaction model, which considers vertical and horizontal transport for both biomass burning regimes and background environment. Our approach for the [OH] estimation resulted in values on the same order of magnitude of a recent observation in the Amazon rainforest [OH]≅106 (moleculescm−3). During the fresh plume regime, the vertical profile of [OH] and the [MVK+MACR+ISOPOOH]∕[isoprene] ratio showed evidence of an increase in the oxidizing power in the transition from planetary boundary layer to cloud layer (1000–1500m). These high values of [OH] (1.5×106moleculescm−3) and [MVK+MACR+ISOPOOH]∕[isoprene] (7.5) indicate a significant change above and inside the cloud decks due to cloud edge effects on photolysis rates, which have a major impact on OH production rates

Pegvaliase for the treatment of phenylketonuria: A pivotal, double-blind randomized discontinuation Phase 3 clinical trial

Introduction Pegvaliase is a recombinant Anabaena variabilis phenylalanine ammonia lyase (PAL) enzyme under investigation for treatment of adult phenylketonuria (PKU). This manuscript describes results of a randomized discontinuation trial (RDT) designed to evaluate the effects of pegvaliase treatment on blood phenylalanine (Phe) and neuropsychiatric outcomes in adults with PKU. Methods PRISM-2 is a 4-part, Phase 3 study that enrolled adults with PKU receiving pegvaliase treatment (initiated in a prior Phase 2 or Phase 3 study). The RDT, Part 2 of PRISM-2, was an 8-week trial that evaluated change in blood Phe concentrations, neuropsychiatric and neurocognitive measures, and safety outcomes in PRISM-2 participants who had achieved at least a 20% blood Phe reduction from pre-treatment baseline with pegvaliase treatment. Participants were randomized 2:1 to either continue pegvaliase (20 mg/day or 40 mg/day) or switch to matching placebo. Results The pooled pegvaliase group enrolled 66 participants and each placebo group enrolled 14 participants. The primary endpoint of change in blood Phe concentration from RDT entry to RDT Week 8 was met with clinically meaningful and statistically significant differences between the pegvaliase and placebo groups. Mean (SD) blood Phe at the beginning of the RDT when all participants were receiving pegvaliase was 563.9 μM (504.6) in the group assigned to the 20 mg/day placebo group (n = 14), 508.2 μM (363.7) in those assigned to the 40 mg/day placebo group (n = 14), and 503.9 μM (520.3) in those assigned to continue pegvaliase treatment (n = 58). At Week 8 of the RDT, the least squares mean change (95% confidence interval) in blood Phe was 949.8 μM (760.4 to 1139.1) for the 20 mg/day placebo group and 664.8 μM (465.5 to 864.1) for the 40 mg/day placebo group in comparison to 26.5 μM (−68.3 to 121.3) for the pooled (20 mg/day and 40 mg/day) pegvaliase group (P < 0.0001 for pooled pegvaliase group vs each placebo group). Adverse events (AEs) were usually lower in the pooled placebo group when compared to the pooled pegvaliase group. The most common AEs for the pooled pegvaliase and pooled placebo groups were arthralgia (13.6% and 10.3%, respectively), headache (12.1% and 24.1%), anxiety (10.6% and 6.9%), fatigue (10.6% and 10.3%), and upper respiratory tract infection (1.5% and 17.2%). Conclusion Mean blood Phe reduction was sustained in the pegvaliase group, while placebo groups had mean blood Phe concentration increase toward pre-treatment baseline levels. Results from this study confirmed the efficacy of pegvaliase in maintaining reduced blood Phe concentrations with a manageable safety profile for most participants

Search for the Lepton-Number-Violating Decay Ξ−→pμ−μ−\Xi^- \to p \mu^- \mu^-

A sensitive search for the lepton-number-violating decay $\Xi^-\to p \mu^-\mu^-$ has been performed using a sample of $\sim10^9$ $\Xi^-$ hyperons produced in 800 GeV/$c$ $p$-Cu collisions. We obtain $\mathcal{B}(\Xi^-\to p \mu^-\mu^-)< 4.0\times 10^{-8}$ at 90% confidence, improving on the best previous limit by four orders of magnitude.Comment: 9 pages, 5 figures, to be published in Phys. Rev. Let

Measurement of the Alpha Asymmetry Parameter for the Omega- to Lambda K- Decay

We have measured the alpha parameter of the Omega- to Lambda K- decay using data collected with the HyperCP spectrometer during the 1997 fixed-target run at Fermilab. Analyzing a sample of 0.96 million Omega- to Lambda K^-, Lambda to p pi- decays, we obtain alpha_Omega*alpha_Lambda = [1.33+/-0.33(stat)+/-0.52(syst)] x 10^{-2}. With the accepted value of alpha_Lambda, alpha_Omega is found to be [2.07+/-0.51(stat)+/-0.81(syst)] x 10^{-2}.Comment: 5 pages, 4 figures, to be appeared as a Rapid Communication in Phys. Rev.

HyperCP: A high-rate spectrometer for the study of charged hyperon and kaon decays

The HyperCP experiment (Fermilab E871) was designed to search for rare phenomena in the decays of charged strange particles, in particular CP violation in $\Xi$ and $\Lambda$ hyperon decays with a sensitivity of $10^{-4}$. Intense charged secondary beams were produced by 800 GeV/c protons and momentum-selected by a magnetic channel. Decay products were detected in a large-acceptance, high-rate magnetic spectrometer using multiwire proportional chambers, trigger hodoscopes, a hadronic calorimeter, and a muon-detection system. Nearly identical acceptances and efficiencies for hyperons and antihyperons decaying within an evacuated volume were achieved by reversing the polarities of the channel and spectrometer magnets. A high-rate data-acquisition system enabled 231 billion events to be recorded in twelve months of data-taking.Comment: 107 pages, 45 Postscript figures, 14 tables, Elsevier LaTeX, submitted to Nucl. Instrum. Meth.

PAK6 phosphorylates 14-3-3γ to regulate steady state phosphorylation of LRRK2

Mutations in Leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease (PD) and, as such, LRRK2 is considered a promising therapeutic target for age-related neurodegeneration. Although the cellular functions of LRRK2 in health and disease are incompletely understood, robust evidence indicates that PD-associated mutations alter LRRK2 kinase and GTPase activities with consequent deregulation of the downstream signaling pathways. We have previously demonstrated that one LRRK2 binding partner is P21 (RAC1) Activated Kinase 6 (PAK6). Here, we interrogate the PAK6 interactome and find that PAK6 binds a subset of 14-3-3 proteins in a kinase dependent manner. Furthermore, PAK6 efficiently phosphorylates 14-3-3γ at Ser59 and this phosphorylation serves as a switch to dissociate the chaperone from client proteins including LRRK2, a well-established 14-3-3 binding partner. We found that 14-3-3γ phosphorylated by PAK6 is no longer competent to bind LRRK2 at phospho-Ser935, causing LRRK2 dephosphorylation. To address whether these interactions are relevant in a neuronal context, we demonstrate that a constitutively active form of PAK6 rescues the G2019S LRRK2-associated neurite shortening through phosphorylation of 14-3-3γ. Our results identify PAK6 as the kinase for 14-3-3γ and reveal a novel regulatory mechanism of 14-3-3/LRRK2 complex in the brain

Down-regulation of TM4SF is associated with the metastatic potential of gastric carcinoma TM4SF members in gastric carcinoma

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to clarify the clinical significance of TM4SF members CD9, CD63 and CD82 in human gastric carcinoma.</p> <p>Methods</p> <p>By employing RT-PCR and immunohistochemistry, we studied the expression of CD9, CD63 and CD82 in 49 paired tissue specimens of normal gastric mucosa and carcinoma. All tissues were obtained from patients who underwent curative surgery.</p> <p>Results</p> <p>All normal gastric epithelium and gastric ulcer tissues strongly expressed transcripts and proteins of CD9, CD63 and CD82 as compared with corresponding controls. We found a significant correlation between CD63 mRNA level and different pM statuses (P = 0.036). Carcinomas in M0 stage revealed a stronger expression of CD63 than carcinomas in M1 stage. Expression of CD9 protein was found significantly stronger in pN0, pM0 than in advanced pN stages (P = 0.03), pM1 (P = 0.013), respectively. We found the relationship between CD63 expression, gender (p = 0.09) and nodal status (p = 0.028), respectively. Additionally, advanced and metastasized tumor tissues revealed significantly down-regulated CD82 protein expression (p = 0.033 and p = 0, respectively), which correlated with the tumor pTNM stage (p = 0.001).</p> <p>Conclusion</p> <p>The reduction of CD9, CD63 and CD82 expression are indicators for the metastatic potential of gastric carcinoma cells. Unlike their expression in other tumor types, the constitutive expression of CD63 may indicate that this factor does play a direct role in human gastric carcinogenesis.</p

CP Violation in Hyperon and Charged Kaon Decays

The primary purpose of the HyperCP experiment at Fermilab is to test CP in hyperon decays by comparing the decay distributions for Ξ− (“cascade”) decays in the decay sequence: Ξ− → π− + Λ0, Λ0 → π− + p, with those for the antiparticle Ξ̄+. In addition, we can test CP in charged kaon decays by comparing the slopes of the Dalitz plot for Κ+ and Κ− decays. We are also looking at rare decay modes of charged kaons and hyperons, particularly those involving muons. In two runs in 1997 and 1999, we collected approx. 500 millon charged kaon decays, 2.5 billion Ξ− and Ξ̄+ decays, and 19 million Ω− and Ω̄+ decays. This is the largest sample of fully reconstructed particle decays ever collected. © 2002 American Institute of PhysicsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87464/2/298_1.pd

Heartfelt embodiment: Changes in body-ownership and self-identification produce distinct changes in interoceptive accuracy

Interoceptive and exteroceptive information are both essential for the construction and update of self-awareness. Whereas several studies have shown how interoceptive accuracy or cardiac feedback influences body-awareness, no studies have looked at the reverse effect, namely how exteroceptively-driven changes in body-ownership and self-identification can influence individuals’ ability to detect internal bodily signals. We exposed participants to the Rubber Hand Illusion (Experiment 1) and to the Enfacement Illusion (Experiment 2), and tested how this change in the sense of body-ownership and self-identification affected their interoceptive accuracy (IAcc). The heartbeat-counting task was used to measure IAcc before the bodily illusions, and then the same task was interleaved with periods of visuo-tactile stimulation, during which synchronous and asynchronous multisensory stimulation was applied. We found that a change in body-ownership significantly improved performance of participants with lower interoceptive accuracy. In contrast, a change in self-identification significantly decreased performance of participants with higher interoceptive accuracy. These results suggest that changes in different domains of self-awareness can differentially impact individuals’ ability to accurately detect signals arising from within the body, highlighting the distinct role that interoceptive signals play for different facets of bodily self-consciousness