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Aims Patient‐performed lung ultrasound (LUS) in a heart failure (HF) telemedicine model may be used to monitor worsening pulmonary oedema and to titrate therapy, potentially reducing HF admission. The aim of the study was to assess the feasibility of training HF patients to perform a LUS self‐exam in a telemedicine model. Methods and results A pilot study was conducted at a public hospital involving subjects with a history of HF. After a 15 min training session involving a tutorial video, subjects performed a four‐zone LUS using a handheld ultrasound. Exams were saved on a remote server and independently reviewed by two LUS experts. Studies were determined interpretable according to a strict definition: the presence of an intercostal space, and the presence of A‐lines, B‐lines, or both. Subjects also answered a questionnaire to gather feedback and assess self‐efficacy. The median age of 44 subjects was 53 years (range, 36–64). Thirty (68%) were male. Last educational level attained was high school or below for 31 subjects (70%), and one‐third used Spanish as their preferred language. One hundred fifty of 175 lung zones (85%) were interpretable, with expert agreement of 87% and a kappa of 0.49. 98% of subjects reported that they could perform this LUS self‐exam at home. Conclusions This pilot study reports that training HF patients to perform a LUS self‐exam is feasible, with reported high self‐efficacy. This supports further investigation into a telemedicine model using LUS to reduce emergency department visits and hospitalizations associated with HF.

Optogenetic approaches for studying neuronal functions have proven their utility in the neurosciences. However, optogenetic tools capable of inducing synaptic plasticity at the level of single synapses have been lacking. Here, we engineered a photoactivatable (pa)CaMKII by fusing a light-sensitive domain, LOV2, to CaMKIIα. Blue light or two-photon excitation reversibly activated paCaMKII. Activation in single spines was sufficient to induce structural long-term potentiation (sLTP) in vitro and in vivo. paCaMKII activation was also sufficient for the recruitment of AMPA receptors and functional LTP in single spines. By combining paCaMKII with protein activity imaging by 2-photon FLIM-FRET, we demonstrate that paCaMKII activation in clustered spines induces robust sLTP via a mechanism that involves the actin-regulatory small GTPase, Cdc42. This optogenetic tool for dissecting the function of CaMKII activation (i.e., the sufficiency of CaMKII rather than necessity) and for manipulating synaptic plasticity will find many applications in neuroscience and other fields., Optogenetic control of molecules is important in cell biology and neuroscience. Here, the authors describe an optogenetic tool to control the Ca²+/calmodulin-dependent protein kinase II and use it to control plasticity at the single synapse level.

Using the ultrafast camera system and new theories for hop diffusion described in the companion paper, we for the first time demonstrated that membrane molecules undergo hop diffusion among the compartments in the bulk basal plasma membrane (PM), with virtually the same compartment sizes (108 nm) as those in the bulk apical PM and the same dwell lifetimes within a compartment (10 and 24 ms for the phospholipid and transferrin receptor, respectively), suggesting that the basic structures and molecular dynamics are very similar in the bulk regions of the apical and basal PMs. Ultrafast PALM and single-molecule imaging revealed that the focal adhesion (FA) is mostly a fluid membrane, partitioned into ∼74-nm compartments where transferrin receptor and β3 integrin undergo hop diffusion, and that the FA membrane is sparsely dotted with 51-nm diameter paxillin islands, where many other FA proteins probably assemble (compartmentalized archipelago model). β3 integrin intermittently associates with the paxillin islands, dynamically linking them to the extracellular matrix.SummaryAn ultrafast camera with single fluorescent-molecule sensitivities developed by Fujiwara et al. reveals that the focal adhesion membrane is dotted with protein islands and partitioned for molecular hop diffusion, and integrin β3 molecules become temporarily immobilized at the islands.

Climate change is threatening the availability, quality and quantity of water for basic human needs. In much of North America, showering is an activity that consumes significant water, as well as energy to heat the water. This study investigates the feasibility of an intervention that gradually decreases shower-water temperature to encourage shorter shower times, towards reduced water and energy usage. The two parts of this work were performed over two academic years. The first part explored user acceptance in 23 study participants who underwent a shower while manually decreasing their own water temperature, as prescribed by a protocol. Immediately following the temperature-decreasing shower, participants were asked questions to assess their attitudes and willingness to use or install such a shower concept. Participants also completed questionnaires determining their regulatory focus and environmental attitudes, the effects of which on their attitudes about the shower concept are discussed. Over 56% of participants were able to abide by the temperature-decreasing showering protocol. Out of 23 participants, only 3 found the temperature-decreasing shower experience to be negative, 12 were neutral, and the remaining 8 found the experience to be a positive one. Given this result, the second part of the work implemented a microcontroller-based system that automatically controls shower temperature, pressure, and duration. This system is described and simulations are used to project the resource-saving potential of the concept.

Fluorescence lifetime imaging microscopy (FLIM)-based Förster resonance energy transfer (FRET) measurement (FLIM-FRET) is one of the powerful methods for imaging of intracellular protein activities such as protein–protein interactions and conformational changes. Here, using saturation mutagenesis, we developed a dark yellow fluorescent protein named ShadowY that can serve as an acceptor for FLIM-FRET. ShadowY is spectrally similar to the previously reported dark YFP but has a much smaller quantum yield, greater extinction coefficient, and superior folding property. When ShadowY was paired with mEGFP or a Clover mutant (CloverT153M/F223R) and applied to a single-molecule FRET sensor to monitor a light-dependent conformational change of the light-oxygen-voltage domain 2 (LOV2) in HeLa cells, we observed a large FRET signal change with low cell-to-cell variability, allowing for precise measurement of individual cell responses. In addition, an application of ShadowY to a separate-type Ras FRET sensor revealed an EGF-dependent large FRET signal increase. Thus, ShadowY in combination with mEGFP or CloverT153M/F223R is a promising FLIM-FRET acceptor.

Uranus, together with Neptune in our Solar System, belongs to a class of planets called ice giants, which have never been explored using a dedicated mission. A mission to explore the ice giants is one of the highest priority missions of NASA. In this paper, we present a new and unique multi-probe, multi-planet spacecraft to explore two of the outer planets, Saturn and Uranus. The mission concept addresses the high-priority science goals of Saturn and Uranus as set forth by the National Research Council’s Planetary Sciences Decadal Survey: Visions and Voyages for Planetary Science in the Decade 2013–2022. The growing importance of understanding the evolution and role of ice giants in extra-solar planetary systems makes Uranus a pertinent scientific target. The mission concept employs the Space Launch System to deliver a 1700 kg orbiter to Uranus using a ballistic Saturn-Uranus trajectory with a time-of-flight of 11.5 years. The baseline mission concept includes two atmospheric entry probes: one deployed at Saturn and another at Uranus prior to an impulsive orbit capture. A payload of nine remote sensing and in situ plasma instruments onboard the orbiter support a broad array of investigations during the nominal 2-year science mission. In addition to the baseline concept, system trade studies were conducted to explore the advantages of aerocapture and use of the Space Launch System. Based on the results of these trade studies, a preferred point design within constraints of NASA’s Flagship program can be launched in the late 2020s. A neural network model using analogy-based data was developed to estimate the mission cost, which was found to be $1.9 billion in FY15$.

During development, neurons form synapses with their fate-determined targets. While we begin to elucidate the mechanisms by which extracellular ligand-receptor interactions enhance synapse specificity by inhibiting synaptogenesis, our knowledge about their intracellular mechanisms remains limited. Here we show that Rap2 GTPase (rap-2) and its effector, TNIK (mig-15), act genetically downstream of Plexin (plx-1) to restrict presynaptic assembly and to form tiled synaptic innervation in C. elegans. Both constitutively GTP- and GDP-forms of rap-2 mutants exhibit synaptic tiling defects as plx-1 mutants, suggesting that cycling of the RAP-2 nucleotide state is critical for synapse inhibition. Consistently, PLX-1 suppresses local RAP-2 activity. Excessive ectopic synapse formation in mig-15 mutants causes a severe synaptic tiling defect. Conversely, overexpression of mig-15 strongly inhibited synapse formation, suggesting that mig-15 is a negative regulator of synapse formation. These results reveal that subcellular regulation of small GTPase activity by Plexin shapes proper synapse patterning in vivo.

During development, neurons form extensive synaptic connectivity with their fate-determined targets. Ectopic synapse formation with aberrant targets underlie various neurological disorders including autism. While we are beginning to elucidate the underlying mechanisms by which extracellular ligand-receptor interactions enhance synapse specificity by inhibiting synaptogenesis, our knowledge about their intracellular mechanisms remains limited. Here we show that Rap2 GTPase (rap-2) and its effector, TNIK (mig-15), act downstream of Plexin (plx-1) signaling to restrict presynaptic assembly and to form tiled synaptic innervation of two cholinergic motor neurons (DA8 and DA9) in C. elegans. Both constitutively GTP- and GDP-forms of rap-2 mutants exhibit similar synaptic tiling defects as plx-1 mutants, suggesting that cycling of the RAP-2 nucleotide state is critical for synapse inhibition. Consistently, RAP-2 activity is suppressed in a short segment of axon lacking synapses where PLX-1 is enriched. Excessive ectopic synapse formation in mig-15 mutants causes expansion of the synaptic domains in DA8 and DA9, which induces a severe synaptic tiling defect. Conversely, overexpression of mig-15 strongly inhibited synapse formation, which suggests that mig-15 is a negative regulator of synapse formation. These results reveal that subcellular regulation of small GTPase activity by Plexin shapes proper synapse patterning in vivo.

Investigations of graphene nanosheets and oxidized graphene nanosheets were carried out using X-rayphotoelectron spectroscopy. Scanning and transmission electron microscopy investigations were used in additionto X-ray photoelectron spectroscopy. It was found that functional carboxyl and epoxide groups were removedfrom samples due to argon bombardment in studies of oxidized graphene nanosheets with X-ray photoelectronspectroscopy. Thus the ОKα-band was not revealed in oxidized graphene nanosheets owing to oxygen removaldue to electron bombardment with the use of. ultra-soft X-ray emission spectroscopy. Keywords: X-ray photoelectron spectroscopy, electronic structure, graphene nanosheets, oxidized graphenenanosheets.

Measurement of Förster resonance energy transfer by fluorescence lifetime imaging microscopy (FLIM-FRET) is a powerful method for visualization of intracellular signaling activities such as protein-protein interactions and conformational changes of proteins. Here, we developed a dark green fluorescent protein (ShadowG) that can serve as an acceptor for FLIM-FRET. ShadowG is spectrally similar to monomeric enhanced green fluorescent protein (mEGFP) and has a 120-fold smaller quantum yield. When FRET from mEGFP to ShadowG was measured using an mEGFP-ShadowG tandem construct with 2-photon FLIM-FRET, we observed a strong FRET signal with low cell-to-cell variability. Furthermore, ShadowG was applied to a single-molecule FRET sensor to monitor a conformational change of CaMKII and of the light oxygen voltage (LOV) domain in HeLa cells. These sensors showed reduced cell-to-cell variability of both the basal fluorescence lifetime and response signal. In contrast to mCherry- or dark-YFP-based sensors, our sensor allowed for precise measurement of individual cell responses. When ShadowG was applied to a separate-type Ras FRET sensor, it showed a greater response signal than did the mCherry-based sensor. Furthermore, Ras activation and translocation of its effector ERK2 into the nucleus could be observed simultaneously. Thus, ShadowG is a promising FLIM-FRET acceptor.

The focal adhesion (FA) is an integrin-based structure built in/on the plasma membrane (PM), linking the extracellular matrix to the actin stress-fibers, working as cell migration scaffolds. Previously, we proposed the archipelago architecture of the FA, in which FA largely consists of fluid membrane, dotted with small islands accumulating FA proteins: membrane molecules enter the inter-island channels in the FA zone rather freely, and the integrins in the FA-protein islands rapidly exchanges with those in the bulk membrane. Here, we examined how Rac1, a small G-protein regulating FA formation, and its activators αPIX and βPIX, are recruited to the FA zones. PIX molecules are recruited from the cytoplasm to the FA zones directly. In contrast, majorities of Rac1 molecules first arrive from the cytoplasm on the general inner PM surface, and then enter the FA zones via lateral diffusion on the PM, which is possible due to rapid Rac1 diffusion even within the FA zones, slowed only by a factor of two to four compared with that outside. The constitutively-active Rac1 mutant exhibited temporary and all-time immobilizations in the FA zone, suggesting that upon PIX-induced Rac1 activation at the FA-protein islands, Rac1 tends to be immobilized at the FA-protein islands. © 2013 Wiley Periodicals, Inc

Author, This study investigated the possible relationships between exposures to mite allergen and airborne fungi with sick building syndrome (SBS) symptoms for residents living in newly built dwellings. We randomly sampled 5709 newly built dwellings in six prefectures from northern to southern Japan. A total of 1479 residents in 425 households participated in the study by completing questionnaire surveys and agreeing to environmental monitoring for mite allergen (Der 1), airborne fungi, aldehydes, and volatile organic compounds. Stepwise logistic regression analyses adjusted for confounders were used to obtain odds ratios (OR) of mite allergen and fungi for SBS symptoms. Der 1 had a significantly high OR for nose symptoms. Rhodotorula had a significantly high OR for any symptoms, and Aspergillus had significantly high OR for eye symptoms. However, the total colony-forming units had a significantly low OR for throat and respiratory symptoms. Eurotium had a significantly low OR for skin symptoms. In conclusion, dust-mite allergen levels and indoor airborne Rhodotorula and Aspergillus concentrations may result in SBS symptoms in newly built dwellings. PRACTICAL IMPLICATIONS: Various factors can cause sick building syndrome symptoms. This study focused on biologic factors such as dust-mite allergen and airborne fungi in newly built dwellings in Japan. Dust-mite allergen levels were significantly associated with higher rates of nose symptoms, airborne Rhodotorula concentrations were significantly associated with higher rates of any symptoms, and Aspergillus concentrations were significantly associated with higher rates of eye symptoms. Measures should be taken to reduce mite allergen levels and fungal concentrations in these dwellings.

Measurement of Förster resonance energy transfer by fluorescence lifetime imaging microscopy (FLIM-FRET) is a powerful method for visualization of intracellular signaling activities such as protein-protein interactions and conformational changes of proteins. Here, we developed a dark green fluorescent protein (ShadowG) that can serve as an acceptor for FLIM-FRET. ShadowG is spectrally similar to monomeric enhanced green fluorescent protein (mEGFP) and has a 120-fold smaller quantum yield. When FRET from mEGFP to ShadowG was measured using an mEGFP-ShadowG tandem construct with 2-photon FLIM-FRET, we observed a strong FRET signal with low cell-to-cell variability. Furthermore, ShadowG was applied to a single-molecule FRET sensor to monitor a conformational change of CaMKII and of the light oxygen voltage (LOV) domain in HeLa cells. These sensors showed reduced cell-to-cell variability of both the basal fluorescence lifetime and response signal. In contrast to mCherry- or dark-YFP-based sensors, our sensor allowed for precise measurement of individual cell responses. When ShadowG was applied to a separate-type Ras FRET sensor, it showed a greater response signal than did the mCherry-based sensor. Furthermore, Ras activation and translocation of its effector ERK2 into the nucleus could be observed simultaneously. Thus, ShadowG is a promising FLIM-FRET acceptor.

Elucidating the spatiotemporal dynamics of proteins in living cells, including protein–protein interactions and conformational changes, is essential for understanding the mechanisms of intracellular signal transduction and cellular functions such as synaptic plasticity, cell motility, and cell division. One of the best ways to visualize protein activity with high spatiotemporal resolution is to utilize optogenetic probes, such as green fluorescent protein, in combination with fluorescence resonance energy transfer (FRET) techniques, which enable us to measure the distance between donor and acceptor fluorescent proteins fused to the signaling proteins. Among the various FRET detection methods, 2-photon fluorescence lifetime imaging microscopy (2pFLIM) is the ideal method to monitor FRET in subcellular compartments of living cells located deep within tissues, such as in brain slices. This review introduces the principle of the 2pFLIM-FRET for monitoring intracellular protein activities and protein–protein interactions using two examples: detecting small GTPase activity and monitoring actin polymerization in dendrites and synapses of hippocampal neurons in brain slices.

植生がニホンジカの採食下にある大台ヶ原では, その採食から樹木を保護するために防鹿柵が設置されている。この点に着目し, ササの形態特性とネズミ類の生息状況との関係を明らかにすることを本研究の目的とした。ササの繁殖状態の相違に基づき6プロットを設定し, 各プロットでミヤコザサの形態特性などを調べた。同時にネズミ類の捕獲調査を行い, 100トラップ・ナイト当たりのネズミ類各種の捕獲個体数を算出した。捕獲されたネズミ類は, アカネズミ, ヒメネズミ, およびスミスネズミであった。ニホンジカ個体群密度のより高い地域では, 防鹿柵内外でアカネズミおよびヒメネズミの捕獲個体数が異なり, 柵内で多く捕獲された。一方, スミスネズミは柵内でのみ捕獲された。防鹿柵内のミヤコザサは柵外よりも稈高が高く, 稈密度が低く, 乾燥重量が大きかったことから, これらがカバー (避難所) として作用し, ネズミ類の活動に有利に働いていると推察された。

Summary Elucidating temporal windows of signaling activity required for synaptic and behavioral plasticity is crucial for understanding molecular mechanisms underlying these phenomena. Here, we developed photoactivatable autocamtide inhibitory peptide 2 (paAIP2), a genetically encoded, light-inducible inhibitor of CaMKII activity. The photoactivation of paAIP2 in neurons for 1–2 min during the induction of LTP and structural LTP (sLTP) of dendritic spines inhibited these forms of plasticity in hippocampal slices of rodents. However, photoactivation ∼1 min after the induction did not affect them, suggesting that the initial 1 min of CaMKII activation is sufficient for inducing LTP and sLTP. Furthermore, the photoactivation of paAIP2 expressed in amygdalar neurons of mice during an inhibitory avoidance task revealed that CaMKII activity during, but not after, training is required for the memory formation. Thus, we demonstrated that paAIP2 is useful to elucidate the temporal window of CaMKII activation required for synaptic plasticity and learning.

Electron tomography of the plasma membrane (PM) identified several layers of cortical actin meshwork running parallel to the PM cytoplasmic surface throughout the PM. Here, cortical actin structures and dynamics were examined in living cells, using super-resolution microscopy, with (x,y)- and z-resolutions of ~140 and ~400 nm, respectively, and single-molecule imaging. The super-resolution microscopy identified sub-micron-sized actin clusters that appeared identical by both phalloidin post-fixation staining and Lifeact-mGFP expression followed by fixation, and therefore, these actin clusters were named "actin-pl-clusters". In live cells, the actin-pl-clusters visualized by Lifeact-mGFP linked two or more actin filaments in the fine actin meshwork, acting as a node of the meshwork, and dynamically moved on/along the meshwork in a myosin II-dependent manner. Their formation depended on the Arp2/3 activities, suggesting that the movements could involve both the myosin motor activity and actin polymerization-depolymerization. The actin-pl-clusters differ from the actin nodes/asters found previously after latrunculin treatments, since myosin II and filamin A were not colocalized with the actin-pl-clusters, and the actin-pl-clusters were much smaller than the previously reported nodes/asters. The Lifeact linked to a fluorescently-labeled transmembrane peptide from syntaxin4 (Lifeact-TM) expressed in the PM exhibited temporary immobilization in the PM regions on which actin-pl-clusters and stress fibers were projected, showing that ≥66% of actin-pl-clusters and 89% of stress fibers were located in close proximity (within 3.5 nm) to the PM cytoplasmic surface. Podosome-associated cytoplasmic proteins, Tks4, Tks5, cortactin, and N-WASP, were transiently recruited to actin-pl-clusters, and thus, we propose that actin-pl-clusters also represent "actin podosome-like clusters".

We have studied inclusive muon events using all the data collected by the TOPAZ detector at sqrt(s)=58 GeV with an integrated luminosity of 273pb-1. From 1328 inclusive muon events, we measured the ratio R_qq of the cross section for qq-bar production to the total hadronic cross section and forward-backward asymmetry A^q_FB for b and c quarks. The obtained results are R_bb = 0.13+-0.02(stat)+-0.01(syst), R_cc = 0.36+-0.05(stat)+-0.05(syst), A^b_FB = -0.20+-0.16(stat)+-0.01(syst) and A^c_FB = -0.17+-0.14(stat)+-0.02(syst), in fair agreement with a prediction of the standard model., Comment: To be published in EPJ C. 24 pages, 12 figures

The Bonin (Ogasawara) Islands are oceanic islands located in the northwest Pacific, and have ten native (nine endemic) bee species, all of which are nonsocial. The European honeybee (Apis mellifera), which was introduced to the islands for apiculture in the 1880s, became naturalized in a few islands shortly after introduction. To detect the impact of the honeybees upon native bee diversity, we analyzed pollen harvest by honeybees and surveyed the relative abundance of honeybees and native bees on flowers on several islands. Both hived and feral honeybee colonies were active throughout the year, harvesting pollen of both native and alien flowers and from both entomophilous and anemophilous flowers. Honeybees strongly depended on the alien plants, especially during winter to spring when native melittophilous flowers were rare. From June to November, honeybees exhaustively utilized native flowers, which had originally been utilized and pollinated by native bees. On Chichi and Haha Islands, where human disturbance of forests has been severe, both native and alien flowers were dominated by honeybees, and native bees were rare or extinct even in well-conserved forests. In contrast, on Ani Island and Haha's satellite islands where primary forests were well conserved and honeybees were still uncommon or absent, native bees remained dominant. These results suggest that competition for nectar and pollen of the native flowers between honeybees and native bees favors honeybees on the disturbed islands, which are thoroughly invaded by alien nectariferous, sometimes aggressive, weedy plants.

The shape of jets produced in (quasi-) real photon-photon collisions as well as in e^+e^- annihilation process has been studied with a cone jet finding algorithm, using the data taken with the TOPAZ detector at the TRISTAN e^+e^- collider at an average center-of-mass energy of 58 GeV. The results are presented in terms of the jet width as a function of the jet transverse energy(E^{jet}_T) as well as a scaled transverse jet energy, x_T(=2E^{jet}_T/root(s)). The jet width narrows as E^{jet}_T increases; however, at the same value of E^{jet}_T the jet width in gamma-gamma collisions at TRISTAN is significantly narrower than that in gamma p collisions at HERA. By comparing our results with the data in other reactions, it has been shown that the jet width in gamma-gamma, gamma p, p\bar{p} collisions as well as the e^+e^- annihilation process has an approximate scaling behavior as a function of x_T.

The mechanism of baryon-anti-baryon pair production in e + e − annihilation into hadrons has been studied using the TOPAZ detector at the TRISTAN e + e − collider at an average center-of-mass energy of 58 GeV. The distributions of various p p correlations were compared with two prominent models: the cluster-fragmentation model and the string-fragmentation model. We rejected the cluster-fragmentation model at the 90% C.L. Furthermore, in the context of the string-fragmentation model, we favor the “popcorn” model, rejecting the “diquark” model, where a diquark is considered to be a fundamental entity, at the 95% C.L.

We report the first purely electroweak measurement of the strengthening of the electromagnetic coupling, {alpha}{sub QED} with increasing momentum transfer Q{sup 2}, by comparing the process e{sup +}e{sup -}{r_arrow}{mu}{sup +}{mu}{sup -} with the process e{sup +}e{sup -}{r_arrow}e{sup +}e{sup -}{mu}{sup +}{mu}{sup -}. The data were accumulated at an average center-of-mass energy {l_angle}{radical}(s){r_angle}=57.77GeV using the TOPAZ detector at the TRISTAN e{sup +}e{sup -} collider. We measure {alpha}{sup -1}{sub QED}(Q{sup 2}) to change from its known value of {alpha}{sup -1}{sub QED}{congruent} 137.0 at Q{sup 2}=0to1 28.5{plus_minus}1.8(stat){plus_minus}0.7(syst) at Q{sup 2}=(57.77GeV/c){sup 2}. This result agrees with electroweak predictions. {copyright} {ital 1997} {ital The American Physical Society}

We report a study of single photon production in e+e− collisions at s =58 GeV with the TOPAZ detector at TRISTAN. From data corresponding to an integrated luminosity of 213 pb−1, 5 single photon candidates remained after event selection, which can be compared with the expected 3.1 ν ν γ and 2.8 background events. These results exclude the selectron mass below 47.2 GeV at the 90% confidence level, if e L and e R are mass-degenerate and the photino is massless. When combined with results from other experiments, this limit improves to 75.0 GeV.

Trackers based on scintillating-fiber technology are being considered by the Solenoidal Detector Collaboration at SSC and the DO collaboration at Fermilab. Some 600 fibers in the Fermilab Tevatron CO area were irradiated, thereby obtaining a hadronic irradiation at realistic rates. Four-meter-long samples of ten Bicron polystyrene-based fibre types, maintained in air, dry nitrogen, argon, and vacuum atmospheres within stainless-steel tubes, were irradiated for seven weeks at various distances from the accelerator beam pipes. Maximum doses, measured by thermoluminescence detectors, were about 80 krad. Fiber properties, particularly light yield and attenuation length, were measured over a one-year period. A description of the work together with the results is presented. At the doses achieved, corresponding to a few years of actual fiber-tracking detector operation, little degradation was observed. Recovery after several days' exposure to air was noted. Properties of unirradiated samples kept in darkness show no changes after one year. >

We used capacitance-voltage (C-V) and capacitance deep-level transient spectroscopy (C-DLTS) methods to study the electrical properties of GaN metal-insulator-semiconductor (MIS) capacitors. The MIS capacitors consisted of SiO2/GaN, SiN/GaN, or SiO2/SiN/GaN, respectively, and annealing temperature was varied. From the C-V characteristics, samples annealed at 400 °C had a large hysteresis, an insufficient accumulation in the measured bias range, and a specific ledge. These features relate with traps and fixed charge. For the SiO2/GaN and the SiO2/SiN/GaN interface, these features improved when the annealing temperature exceeded 600 °C. On the other hand, it is confirmed that the annealing treatment up to 800 °C was insufficient in the SiN/GaN interface. From the C-DLTS analysis, a common trap with an activation energy of 0.7-0.8 eV was observed from all the MIS capacitors, suggesting the existence of complexes of Si and surface defect on GaN. In the SiO2/GaN MIS capacitor annealed above 600 °C, traps with an activation energy of 50, 150, 180, and 630 meV were observed. The intensities of these peaks decreased with increasing annealing temperature and it is considered that they correlate with the improvement of depletion behavior. A specific trap with an activation energy of 0.32 eV was observed from SiN/GaN MIS capacitor and it agreed with that of the trap related to ledge estimated from the C-V characteristics. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

We have estimated changes in surface solar ultraviolet (UV) radiation under cloud free conditions in the 21st century based on simulations of 11 coupled Chemistry-Climate Models (CCMs). The total ozone columns and vertical profiles of ozone and temperature projected from CCMs were used as input to a radiative transfer model in order to calculate the corresponding erythemal irradiance levels. Time series of monthly erythemal irradiance received at the surface during local noon are presented for the period 1960 to 2100. Starting from the first decade of the 21st century, the surface erythemal irradiance decreases globally as a result of the projected stratospheric ozone recovery at rates that are larger in the first half of the 21st century and smaller towards its end. This decreasing tendency varies with latitude, being more pronounced over areas where stratospheric ozone.

A test facility to study the light-transmission properties of scintillating fiber waveguides for tracking applications in high-energy physics is being developed. A light-tight box 2 m in length has been built, and data acquisition hardware and software is in place for testing various aspects of scintillating fibers and waveguides. Scintillating fibers have been excited with radioactive sources, ultraviolet light sources, and light-emitting diodes. Various photodetectors such as photomultiplier tubes, photodiodes, charge-coupled devices and solid-state photomultipliers have been utilized to detect the transmitted light. Studies of attenuation length and transmission through splices are presented. >

We have proposed a novel etching gas C5F10O of which global warming potential would be less than 50, for the plasma etching of SiOCH. The etching was performed using a dual frequency capacitively coupled plasma (CCP). The high performances of a high etching rate and a high selectivity over resist films were obtained. The C5F10O gas produced many CF3 + ions which have a large etching yield due to its special molecular structure and the deposition of polymers was decreased by addition of the N2 gas. Consequentially, the Ar/C5F10O/N2 plasmas have a great potential for realizing a higher etch rate of 980 nm/min and a high etching selectivity over resist of about 7 than the Ar/C4F8/N2 plasmas.

Genetically encoded fluorescence resonance energy transfer (FRET) biosensors have been successfully used to visualize protein activity in living cells. The sensitivity and accuracy of FRET measurements directly depend on biosensor folding efficiency, expression pattern, sensitivity, and dynamic range. Here, to improve the folding efficiency of the Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIα) FRET biosensor, we amplified the association domain of the CaMKIIα gene using error-prone polymerase chain reaction (PCR) and fused it to the N-terminus of mCherry in a bacterial expression vector. We also created an Escherichia coli expression library based on a previously reported fluorescent protein folding reporter method, and found a bright red fluorescent colony that contained the association domain with four mutations (F394L, I419V, A430T, and I434T). In vitro assays using the purified mutant protein confirmed improved folding kinetics of the downstream fluorescent protein, but not of the association domain itself. Furthermore, we introduced these mutations into the previously reported CaMKIIα FRET sensor and monitored its Ca2+/calmodulin-dependent activation in HeLa cells using 2-photon fluorescence lifetime imaging microscopy (2pFLIM), and found that the expression pattern and signal reproducibility of the mutant sensor were greatly improved without affecting the autophosphorylation function and incorporation into oligomeric CaMKIIα. We believe that our improved CaMKIIα FRET sensor would be useful in various types of cells and tissues, providing data with high accuracy and reproducibility. In addition, the method described here may also be applicable for improving the performance of all currently available FRET sensors.

A growing body of evidence indicates that the pathogenesis of pre-eclampsia is closely associated with oxidative stress occurring in mitochondria. In the present study, we evaluated the degree of mitochondrial lipid peroxidation by assessing the accumulation of 4-hydroxy-2-nonenal (HNE)-modified proteins and examined the expression of mitochondrial antioxidant protein peroxiredoxin III/SP-22 in normal and pre-eclamptic human placentae. The accumulation of HNE-modified proteins increased to a greater extent in both the mitochondria and cytosol of pre-eclamptic placentae than in those of normal placentae. Moreover, the accumulation of HNE-modified proteins was much more evident in the mitochondria than in the cytosol, indicating that lipid peroxidation occurred mainly in the mitochondria of pre-eclamptic placentae. The mRNA expression of peroxiredoxin III/SP-22 was increased about 2-fold in pre-eclamptic placentae compared to normal placentae. The protein levels of peroxiredoxin III/SP-22 were approximately 4-fold higher in pre-eclamptic placentae than in normal placentae. Immunohistochemistry of placental tissues showed that the levels of peroxiredoxin III/SP-22 protein were increased in the trophoblasts of floating villi, stromal cells of stem villi, and decidual cells in pre-eclamptic placentae. These results indicate that peroxiredoxin III/SP-22 plays a crucial role in the protection of placental function from oxidative stress occurring in mitochondria of pre-eclamptic placentae.

Scintillating fiber tracking detectors are being developed for the SDC experiment at Superconducting Super Collider (SSC) and the upgrade of the D0 detector at the Fermilab Tevatron. The many attractive features of a fiber tracker include good position resolution, low occupancy, low mass in the active volume, and excellent resistance to radiation damage. An additional important feature, especially at the SSC, is the intrinsically prompt response time of a scintillating fiber. The photodetector of choice is the visible light phonon counter (VLPC), a device which combines high rate capability with high quantum efficiency at visible wavelengths. To realize the high rate capability of the VLPC requires the implementation of a suitable, fast preamplifier. Until recently, studies of fibers and VLPCs with radioactive sources and cosmic rays have been performed under low rate conditions using transimpedance amplifiers (TIAs). The authors report on the response characteristics of a fiber-VLPC system coupled to a variety of fast preamplifiers, including QPA02, VTX, and TVC devices. Their performance is compared with that of a transimpedance amplifier. >

Female transgenic mice that express SV40 T/t antigens under the regulatory control of the rat C3(1) gene spontaneously develop multifocal mammary lesions that predictably evolve into invasive, hormone-independent carcinomas, whereas male mice are prone to develop prostate cancer. Chemopreventive agents were administered to female C3(1)/SV40 large T-antigen mice from 7 to 19 weeks of age, during which time the mammary lesions developed and progressed to invasive carcinomas. No significant differences in the numbers of preinvasive mammary intraepithelial neoplasia lesions (histologically similar to human ductal carcinoma in situ) were observed after 2 or 8 weeks of treatment between mice receiving either vehicle alone, dehydroepiandrosterone (DHEA), or 2-difluoromethylornithine (DFMO). However, a dose-response reduction in invasive carcinoma growth was observed for both DFMO, an inhibitor of ornithine decarboxylase, and DHEA, the primary steroid precursor to both androgens and estrogens in primates. Despite unaltered expression of the transgene, tumor incidence was reduced approximately 20% by DFMO (8000 mg/kg) and 30% by DHEA (4000 mg/kg; P0.05). Tumor multiplicity was reduced by approximately 50% by both DFMO and DHEA (P0.05). DFMO had a dose-dependent effect on total tumor burden, which was reduced by 25% at low doses (4000 mg/kg) and 70% at high doses (8000 mg/kg). DHEA reduced tumor burden by 50% and 66% at low (2000 mg/kg) and high (4000 mg/kg) doses, respectively. Interestingly, despite its inhibitory effects on tumor development, DHEA caused a dose-dependent increase of serum estradiol levels that we have previously shown to increase mammary tumor formation in this model. No effect on the development of the prostate cancer precursor lesions (prostate intraepithelial neoplasia) was observed when mice were treated with DHEA, DFMO, tocopherol acetate, selenomethionine, or 9-cis-retinoic acid, although the effects on late-stage prostate cancer development were not determined. These results demonstrate that despite the expression of the highly transforming C3(1)/SV40 large T-antigen transgene, this transgenic model can be used to study the effects of chemopreventive agents on mammary cancer progression. The tumor-inhibitory effects of DHEA and DFMO on mammary cancer growth appear to occur after the development of preinvasive lesions, suggesting that these agents inhibit tumor progression but not initiation.

Recent studies have indicated that pre-eclampsia is closely associated with oxidative stress both in maternal circulation and in the placenta. Protein thiol/disulphide oxidoreductases, such as thioredoxin, glutaredoxin, and protein disulphide isomerase have recently been found to eliminate reactive oxygen species (ROS) and regenerate oxidatively damaged proteins. Protein thiol/disulphide oxidoreductases may also play a role in combating pre-eclampsia. In this study, we examined the accumulation of 4-hydroxy-2-nonenal (HNE)-modified proteins, which are markers of lipid peroxidation, in human placentae of normal and pre-eclamptic subjects. We also examined the protein levels of thioredoxin, glutaredoxin, and protein disulphide isomerase in placentae. Immunoblotting and immunohistochemistry showed that HNE-modified proteins accumulated to a greater extent in pre-eclamptic placentae than in normal placentae. In both normal and pre-eclamptic placentae, thioredoxin, glutaredoxin, and protein disulphide isomerase were detected in the trophoblasts of the floating villi. The levels of these proteins were increased approximately 2- to 3-fold in the pre-eclamptic placentae compared to the normal placentae. These results indicated that the pre-eclamptic placentae were exposed to oxidative stress and that the protein thiol/disulphide oxidoreductases were adaptively induced in pre-eclamptic placentae, suggesting possible roles for thioredoxin, glutaredoxin, and protein disulphide isomerase in protecting placental functions against oxidative stress caused by pre-eclampsia.

The aim of this study was to elucidate whether a novel mitochondrial antioxidant protein, SP-22, is localized in placenta and whether its expression is induced in placenta of lipopolysaccharide (LPS)-exposed mouse. Western blot analysis of normal human placenta indicated that the SP-22 protein was located in the mitochondrial fraction. Immunohistochemical analysis of SP-22 in normal placenta showed that immunoreactive SP-22 was distributed mostly in cytotrophoblastic cells but with almost no signal in syncytiotrophoblasts. The positive signals were also detected in the decidual cells and stromal cells in stem villi of normal placenta. We also examined LPS-mediated inflammatory placenta on day 13 of pregnancy at various time points after LPS injection (50 microg/kg, intraperitoneally). Western blot analysis indicated that LPS approximately quadrupled the expression of SP-22 in placenta of LPS-exposed mouse. When the SP-22 protein was localized immunohistochemically, the decidua and the diploid trophoblasts in the basal zone were intensively stained in placenta of LPS-exposed mouse compared to the control. The localization and inducible expression of SP-22 protein in placenta suggest a possible role in antioxidant system in mitochondria of normal and inflammatory placentae.

The objective of this study was to estimate the types and origin of the mineral fibers in the lungs of residents in the urban area.Mineral fibers in the atmosphere from 21 urban areas were analyzed by direct transfer-analytical transmission electron microscopy (ATEM). Lung tissues of 36 urban residents without occupational asbestos exposure were also analyzed by ATEM after low temperature ashing. Measurement of dimensions of all types of mineral fibers, identification of asbestos, and classification of nonasbestos fibers according to the combination of main elements were carried out.1. Chrysotile, amosite, actinolite, tremolite and 11 types of nonasbestos fibers were found in both the lung tissues and the atmospheric samples. The fibers, mainly composed of Al and Si, contributed 16.3% and 62.3% of the atmospheric samples and lung tissues respectively. On the other hand, the proportion of the fibers mainly composed of S and Ca were 43.7% and 0.0% in the atmosphere and lung tissues respectively. Those fibers mainly composed of P and Fe were 0.4% and 18.4% in the atmosphere and lung tissues respectively. 2. Fifteen types of nonasbestos fibers were found exclusively in the atmosphere. The average proportions for ten of these were less than 0.5% each. 3. Crocidolite was found exclusively in the lung tissues. 4. No significant difference in the geometric mean of length and diameter of asbestos was found between the atmospheric samples and lung tissues. Some types of nonasbestos fibers had significantly larger length and diameter in the atmospheres than in the lung tissues (p0.01).The results suggest that mineral fibers found in lung tissues could be classified into three groups on the basis of their behavior. 1) Some fibers, such as amphibole asbestos and fibers composed of Al and Si, are inhaled from the atmosphere and remain in the lung tissues for a long time. 2) Some fibers, such as those composed of S and Ca, are inhaled from the atmosphere and eliminated from the lung tissues within a relatively short time. 3) Some fibers found more in the lung tissues than in the atmospheres, such as those composed of P and Fe, are suspected to be generated in the lungs.