DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, Zhaoqing; Khangaonkar, Tarang; Chase, Jared M.
2009-12-01
To support marine ecological resource management and emergency response and to enhance scientific understanding of physical and biogeochemical processes in Puget Sound, a real-time Puget Sound Operational Forecast System (PS-OFS) was developed by the Coastal Ocean Dynamics & Ecosystem Modeling group (CODEM) of Pacific Northwest National Laboratory (PNNL). PS-OFS employs the state-of-the-art three-dimensional coastal ocean model and closely follows the standards and procedures established by National Oceanic and Atmospheric Administration (NOAA) National Ocean Service (NOS). PS-OFS consists of four key components supporting the Puget Sound Circulation and Transport Model (PS-CTM): data acquisition, model execution and product archive, model skill assessment,more » and model results dissemination. This paper provides an overview of PS-OFS and its ability to provide vital real-time oceanographic information to the Puget Sound community. PS-OFS supports pacific northwest region’s growing need for a predictive tool to assist water quality management, fish stock recovery efforts, maritime emergency response, nearshore land-use planning, and the challenge of climate change and sea level rise impacts. The structure of PS-OFS and examples of the system inputs and outputs, forecast results are presented in details.« less
Effectiveness of early adalimumab therapy in psoriatic arthritis patients from Reuma.pt - EARLY PsA.
Santos, Helena; Eusébio, Mónica; Borges, Joana; Gonçalves, Diana; Ávila-Ribeiro, Pedro; Faria, Daniela Santos; Lopes, Carina; Rovisco, João; Águeda, Ana; Nero, Patrícia; Valente, Paula; Cravo, Ana Rita; Santos, Maria José
2017-01-01
Objective To compare outcomes in psoriatic arthritis (PsA) patients initiating adalimumab (ADA), with short- and long-term disease duration and to evaluate the potential effect of concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or glucocorticoids. Methods Analyses included adult PsA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) between June 2008-June 2016 who received ADA for ≥3 months. Psoriatic Arthritis Response Criteria (PsARC) response, tender and swollen joint count, inflammatory parameters, patient (PtGA) and physician global assessment (PhGA), Disease Activity Score-28 joints (DAS28), and Health Assessment Questionnaire Disability Index (HAQ-DI) were compared between patients with <5 years of disease (early PsA) and those with ≥5 years of disease duration (late PsA). Time to achieving PsARC response was estimated using the Kaplan-Meier method. Results Of 135 PsA patients treated with ADA, 126 had information on disease duration (earlyPsA, n=41). PsARC response was achieved by 72.9% of the patients (88.0% early PsA vs 62.2% late PsA; P=0.022) after 3 months and by 85.4% after 24 months (100% early PsA vs 75.9% late PsA; P=0.044). Early PsA patients achieved significantly less painful joints (2.7 vs 6.7, p=0.006), lower mean C-reactive protein (0.5 mg/dL vs 1.3 mg/dL; P=0.011), and PhGA (18.3 vs 28.1; P=0.020) at 3 months. In the long term, early PsA patients also had fewer swollen joints (0.3 vs 1.7; P=0.030) and lower PhGA (6.3 vs 21.9; P<0.001), C-reactive protein (0.4 mg/dL vs 1.0 mg/dL; P=0.026), and DAS28 (2.2 vs 3.2; P=0.030). HAQ-DI decreased in both groups reaching a mean value at 24 months of 0.4 and 0.8 (P=ns) in early and late PsA, respectively. Early PsA patients obtained PsARC response more rapidly than late PsA (3.8 and 7.4 months, respectively; P=0.008). Concomitant csDMARDs showed clinical benefit (2-year PsARC response, 88.3% vs 60.0%; P=0.044). Concomitant glucocorticoids had no effect on PsARC response over 2 years of follow-up. Persistence on ADA was similar in both groups. Conclusion Early PsA patients had a greater chance of improvement after ADA therapy and better functional outcome, and achieved PsARC response more rapidly than late PsA. In this cohort, comedication with csDMARDs was beneficial over 2 years.
Systems for measuring response statistics of gigahertz bandwidth photomultipliers
NASA Technical Reports Server (NTRS)
Abshire, J. B.; Rowe, H. E.
1977-01-01
New systems have been developed for measuring the average impulse response, the pulse-height spectrum, the transit-time statistics as a function of signal level, and the dark-count spectrum of gigahertz bandwidth photomultipliers. Measurements showed that the 0.53 microns pulse used as an optical test source had a 30 picoseconds and less than 70 ps pulse width. Calibration data showed the system resolution to be less than 20 ps for root mean square transit-time measurements. Test data for a static crossed-field photomultiplier showed 2-photoelectron resolution and less than 30-ps time jitter over the 1- to 100-photoelectron range.
Sulfide response analysis for sulfide control using a pS electrode in sulfate reducing bioreactors.
Villa-Gomez, D K; Cassidy, J; Keesman, K J; Sampaio, R; Lens, P N L
2014-03-01
Step changes in the organic loading rate (OLR) through variations in the influent chemical oxygen demand (CODin) concentration or in the hydraulic retention time (HRT) at constant COD/SO4(2-) ratio (0.67) were applied to create sulfide responses for the design of a sulfide control in sulfate reducing bioreactors. The sulfide was measured using a sulfide ion selective electrode (pS) and the values obtained were used to calculate proportional-integral-derivative (PID) controller parameters. The experiments were performed in an inverse fluidized bed bioreactor with automated operation using the LabVIEW software version 2009(®). A rapid response and high sulfide increment was obtained through a stepwise increase in the CODin concentration, while a stepwise decrease to the HRT exhibited a slower response with smaller sulfide increment. Irrespective of the way the OLR was decreased, the pS response showed a time-varying behavior due to sulfide accumulation (HRT change) or utilization of substrate sources that were not accounted for (CODin change). The pS electrode response, however, showed to be informative for applications in sulfate reducing bioreactors. Nevertheless, the recorded pS values need to be corrected for pH variations and high sulfide concentrations (>200 mg/L). Copyright © 2013 Elsevier Ltd. All rights reserved.
Zhang, Haiyan; Yu, Pengli; Zhao, Jiuhai; Jiang, Hongling; Wang, Haiyang; Zhu, Yingfang; Botella, Miguel A; Šamaj, Jozef; Li, Chuanyou; Lin, Jinxing
2018-01-01
Systemin (SYS), an octadecapeptide hormone processed from a 200-amino-acid precursor (prosystemin, PS), plays a central role in the systemic activation of defense genes in tomato in response to herbivore and pathogen attacks. However, whether PS mRNA is transferable and its role in systemic defense responses remain unknown. We created the transgenic tomato PS gene tagged with the green fluorescent protein (PS-GFP) using a shoot- or root-specific promoter, and the constitutive 35S promoter in Arabidopsis. Subcellular localization of PS-/SYS-GFP was observed using confocal laser scanning microscopy and gene transcripts were determined using quantitative real-time PCR. In Arabidopsis, PS protein can be processed and SYS is secreted. Shoot-/root-specific expression of PS-GFP in Arabidopsis, and grafting experiments, revealed that the PS mRNA moves in a bi-directional manner. We also found that ectopic expression of PS improves Arabidopsis resistance to the necrotrophic fungus Botrytis cinerea, consistent with substantial upregulation of the transcript levels of specific pathogen-responsive genes. Our results provide novel insights into the multifaceted mechanism of SYS signaling transport and its potential application in genetic engineering for increasing pathogen resistance across diverse plant families. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.
Time delay measurement in the frequency domain
Durbin, Stephen M.; Liu, Shih -Chieh; Dufresne, Eric M.; ...
2015-08-06
Pump–probe studies at synchrotrons using X-ray and laser pulses require accurate determination of the time delay between pulses. This becomes especially important when observing ultrafast responses with lifetimes approaching or even less than the X-ray pulse duration (~100 ps). The standard approach of inspecting the time response of a detector sensitive to both types of pulses can have limitations due to dissimilar pulse profiles and other experimental factors. Here, a simple alternative is presented, where the frequency response of the detector is monitored versus time delay. Measurements readily demonstrate a time resolution of ~1 ps. Improved precision is possible bymore » simply extending the data acquisition time.« less
Xu, J.; Stickrath, A. B.; Bhattacharya, P.; Nees, J.; Váró, G.; Hillebrecht, J. R.; Ren, L.; Birge, R. R.
2003-01-01
The photovoltaic signal associated with the primary photochemical event in an oriented bacteriorhodopsin film is measured by directly probing the electric field in the bacteriorhodopsin film using an ultrafast electro-optic sampling technique. The inherent response time is limited only by the laser pulse width of 500 fs, and permits a measurement of the photovoltage with a bandwidth of better than 350 GHz. All previous published studies have been carried out with bandwidths of 50 GHz or lower. We observe a charge buildup with an exponential formation time of 1.68 ± 0.05 ps and an initial decay time of 31.7 ps. Deconvolution with a 500-fs Gaussian excitation pulse reduces the exponential formation time to 1.61 ± 0.04 ps. The photovoltaic signal continues to rise for 4.5 ps after excitation, and the voltage profile corresponds well with the population dynamics of the K state. The origin of the fast photovoltage is assigned to the partial isomerization of the chromophore and the coupled motion of the Arg-82 residue during the primary event. PMID:12885657
Low-Timing-Jitter Near-Infrared Single-Photon-Sensitive 16-Channel Intensified-Photodiode Detector
NASA Technical Reports Server (NTRS)
Krainak, Michael A.; Lu, Wei; Yang, Guangning; Sun, Xiaoli; Sykora, Derek; Jurkovic, Mike; Aebi, Verle; Costello, Ken; Burns, Richard
2011-01-01
We developed a 16-channel InGaAsP photocathode intensified-photodiode (IPD) detector with 78 ps (1-sigma) timing-jitter, less than 500 ps FWHM impulse response, greater than 15% quantum efficiency at 1064 nm wavelength with 131 kcps dark counts at 15 C.
NASA Astrophysics Data System (ADS)
Li, Zhongyu; Jin, Zhaohui; Kasatani, Kazuo
2005-01-01
The third-order optical nonlinearities and responses of thin films containing the J-aggregates of a cyanine dye or a squarylium dye were measured using the degenerate four-wave mixing (DFWM) technique under resonant conditions. The sol-gel silica coating films containing the J-aggregates of the cyanine dye, NK-3261, are stable at room temperature and durable against laser beam irradiation. The temporal profiles of the DFWM signal were measured with a time resolution of 0.3 ps, and were found to consist of at least three components, i.e., the coherent instantaneous nonlinear response and the two slow responses with delay time constants of ca. 1.0 ps and ca. 5.6 ps. The contribution of the later was small. The electronic component of the effective third-order optical nonlinear susceptibility of the film had value of as high as ca. 3.0 x 10-7 esu. We also studied the neat film of a squarylium dye J-aggregates. The temporal profile of the DFWM signal of the neat film of squarylium dye was also found to consist of at least three components, the coherent instantaneous nonlinear response and the delayed response with decay time constants of ca. 0.6 ps and ca. 6.5 ps. The contribution of the slow tail was also very small. The electronic component of effective third-order optical nonlinear susceptibility of the neat film of squarylium dye had value of as high as ca. 3.6 x 10-8 esu.
Fast Timing for High-Rate Environments with Micromegas
NASA Astrophysics Data System (ADS)
Papaevangelou, Thomas; Desforge, Daniel; Ferrer-Ribas, Esther; Giomataris, Ioannis; Godinot, Cyprien; Diaz, Diego Gonzalez; Gustavsson, Thomas; Kebbiri, Mariam; Oliveri, Eraldo; Resnati, Filippo; Ropelewski, Leszek; Tsiledakis, Georgios; Veenhof, Rob; White, Sebastian
2018-02-01
The current state of the art in fast timing resolution for existing experiments is of the order of 100 ps on the time of arrival of both charged particles and electromagnetic showers. Current R&D on charged particle timing is approaching the level of 10 ps but is not primarily directed at sustained performance at high rates and under high radiation (as would be needed for HL-LHC pileup mitigation). We demonstrate aMicromegas based solution to reach this level of performance. The Micromegas acts as a photomultiplier coupled to a Cerenkovradiator front window, which produces sufficient UV photons to convert the ˜100 ps single-photoelectron jitter into a timing response of the order of 10-20 ps per incident charged particle. A prototype has been built in order to demonstrate this performance. The first laboratory tests with a pico-second laser have shown a time resolution of the order of 27 ps for ˜50 primary photoelectrons, using a bulk Micromegas readout.
Lagutchev, Alexei S; Patterson, James E; Huang, Wentao; Dlott, Dana D
2005-03-24
Laser-driven approximately 1 GPa shock waves are used to dynamically compress self-assembled monolayers (SAMs) consisting of octadecanethiol (ODT) on Au and Ag, and pentanedecanethiol (PDT) and benzyl mercaptan (BMT) on Au. The SAM response to <4 ps shock loading and approximately 25 ps shock unloading is monitored by vibrational sum-frequency generation spectroscopy (SFG), which is sensitive to the instantaneous tilt angle of the SAM terminal group relative to the surface normal. Arrival of the shock front causes SFG signal loss in all SAMs with a material time constant <3.5 ps. Thermal desorption and shock recovery experiments show that SAMs remain adsorbed on the substrate, so signal loss is attributed to shock tilting of the methyl or phenyl groups to angles near 90 degrees. When the shock unloads, PDT/Au returns elastically to its native structure whereas ODT/Au does not. ODT evidences a complicated viscoelastic response that arises from at least two conformers, one that remains kinetically trapped in a large-tilt-angle conformation for times >250 ps and one that relaxes in approximately 30 ps to a nearly upright conformation. Although the shock responses of PDT/Au, ODT/Ag, and BMT/Au are primarily elastic, a small portion of the molecules, 10-20%, evidence viscoelastic response, either becoming kinetically trapped in large-tilt states or by relaxing in approximately 30 ps back to the native structure. The implications of the observed large-amplitude monolayer dynamics for lubrication under extreme conditions of high strain rates are discussed briefly.
NASA Astrophysics Data System (ADS)
Yuan, Lin; Hu, Ming; Wei, Yulong; Ma, Wenfeng
2016-12-01
The thorn-sphere-like tungsten oxide (WO3) made up by 1D nanorods has been successfully synthesized through hydrothermal method on the Au-modified porous silicon (PS) substrates with seed-layer induction. By using XRD, EDS, FESEM and TEM techniques, we tested and verified that the crystal structure and morphology evolution of WO3 hierarchical nanostructure on the Au-modified PS strongly depend on the Au-sputtering time and hydrothermal reaction time. In addition, by comparing the NO2-sensing properties of the prepared products, we found that the 10 s-Au decorated PS/WO3-3 h (sputtering Au for 10 s and hydrothermal reaction for 3 h) composites sensor behaving as a typical p-type semiconductor and operating at room temperature (RT) exhibits high sensitivity and response characteristics even to ppb-level NO2, which makes this kind of sensor a competitive candidate for NO2-sensing applications. Moreover, the enhanced response may not only due to the high specific surface area but the Au nanoparticles acting as promoters for the spillover effect and forming metal-semiconductor heterojunctions with the PS and WO3. The transmission of electrons and holes in the heterogeneous interface generated among PS, WO3 and Au is proposed to illustrate the p-type response mechanism.
Age-related variation in EEG complexity to photic stimulation: A multiscale entropy analysis
Takahashi, Tetsuya; Cho, Raymond Y.; Murata, Tetsuhito; Mizuno, Tomoyuki; Kikuchi, Mitsuru; Mizukami, Kimiko; Kosaka, Hirotaka; Takahashi, Koichi; Wada, Yuji
2010-01-01
Objective This study was intended to examine variations in electroencephalographic (EEG) complexity in response to photic stimulation (PS) during aging to test the hypothesis that the aging process reduces physiologic complexity and functional responsiveness. Methods Multiscale entropy (MSE), an estimate of time-series signal complexity associated with long-range temporal correlation, is used as a recently proposed method for quantifying EEG complexity with multiple coarse-grained sequences. We recorded EEG in 13 healthy elderly subjects and 12 healthy young subjects during pre-PS and post-PS conditions and estimated their respective MSE values. Results For the pre-PS condition, no significant complexity difference was found between the groups. However, a significant MSE change (complexity increase) was found post-PS only in young subjects, thereby revealing a power-law scaling property, which means long-range temporal correlation. Conclusions Enhancement of long-range temporal correlation in young subjects after PS might reflect a cortical response to stimuli, which was absent in elderly subjects. These results are consistent with the general “loss of complexity/diminished functional response to stimuli” theory of aging. Significance Our findings demonstrate that application of MSE analysis to EEG is a powerful approach for studying age-related changes in brain function. PMID:19231279
Miniaturized High Speed Controls for Turbine Engines (Fabrication and Test)
1974-08-01
Configuration) 43 ,AP!P Sensor Dynamic Response to Step 76 Inputs to Ps4 44 Radiation Pyrometer Assembly 80 45 Radiation Pyrometer Disassembled 81 Radiation...12.0 1 a Ŗ. 10.0~ 8.o /w I .4 4 .0 o/ /• 2 6.0 -, i-- 0 I 2.0 -- . ._ - -- 0 0.1 0.2 PT4 - PS4 W PT4 Figure 32. Estimated Performance of Fluidic LAP/P...time response obtained by ap- plying a step pressure change to Ps4 . Output of the linear volt- age transducer was recorded on a Visicorder with a
Readout Strategy of an Electro-optical Coupled PET Detector for Time-of-Flight PET/MRI
Bieniosek, M F; Olcott, P D; Levin, C S
2013-01-01
Combining PET with MRI in a single system provides clinicians with complementary molecular and anatomical information. However, existing integrated PET/MRI systems do not have time-of-flight PET capabilities. This work describes an MRI-compatible front-end electronic system with ToF capabilities. The approach employs a fast arrival-time pickoff comparator to digitize the timing information, and a laser diode to drive a 10m fiber-optic cable to optically transmit asynchronous timing information to a photodiode receiver readout system. The comparator and this electo-optical link show a combined 11.5ps fwhm jitter in response to a fast digital pulse. When configured with LYSO scintillation crystals and Hamamatsu MPPC silicon photo-multipliers the comparator and electro-optical link achieved a 511keV coincidence time resolution of 254.7ps +/− 8.0ps fwhm with 3×3×20mm crystals and 166.5 +/− 2.5ps fwhm with 3×3×5mm crystals. PMID:24061218
Vallejo, J G; Baker, C J; Edwards, M S
1996-01-01
Group B streptococci (GBS) are the major cause of sepsis and fatal shock in neonates in the United States. The precise role of tumor necrosis factor alpha (TNF-alpha) in the development of human GBS sepsis has not been defined; however, whole GBS have been shown to induce the production of this inflammatory cytokine. We sought to determine which bacterial cell wall components of GBS are responsible for triggering TNF-alpha production. Human cord blood monocytes were stimulated with encapsulated (COH1) or unencapsulated (COH1-13) whole type III GBS or with purified bacterial components, including type III capsular polysaccharide (III-PS), group B polysaccharide (GB-PS), lipoteichoic acid (LTA), or peptidoglycan (PG). Lipopolysaccharide from Escherichia coli served as a control. Supernatants were harvested at specific timed intervals, and TNF-alpha levels were measured by enzyme-linked immunosorbent assay. Monocytes exposed to COH1 and COH1-13 induced similar amounts of TNF-alpha. III-PS, GB-PS, LTA, and PG each induced TNF-alpha in a time- and concentration-dependent manner. However, TNF-alpha release was significantly greater after stimulation by the GB-PS or PG than after stimulation by III-PS or LTA (P < 0.05). Our findings indicate that GB-PS and PG are the bacterial cell wall components primarily evoking TNF-alpha release. These, alone or in concert with other factors, may be responsible for septic shock accompanying GBS sepsis. PMID:8945544
2017-09-30
AFRL-RD-PS- AFRL-RD-PS- TR-2017-0047 TR-2017-0047 TIME -DOMAIN FULL-WAVE MODELING OF NONLINEAR AIR BREAKDOWN IN HIGH-POWER MICROWAVE...Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions...TITLE AND SUBTITLE Time -Domain Full-Wave Modeling of Nonlinear Air Breakdown in High-Power Microwave Devices and Systems 5a. CONTRACT NUMBER 5b
Philp, Andrew; Schenk, Simon; Perez-Schindler, Joaquin; Hamilton, D Lee; Breen, Leigh; Laverone, Erin; Jeromson, Stewart; Phillips, Stuart M; Baar, Keith
2015-01-01
Abstract The present study aimed to investigate the role of the mechanistic target of rapamycin complex 1 (mTORC1) in the regulation of myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis following endurance exercise. Forty-two female C57BL/6 mice performed 1 h of treadmill running (18 m min−1; 5° grade), 1 h after i.p. administration of rapamycin (1.5 mg · kg−1) or vehicle. To quantify skeletal muscle protein fractional synthesis rates, a flooding dose (50 mg · kg−1) of l-[ring-13C6]phenylalanine was administered via i.p. injection. Blood and gastrocnemius muscle were collected in non-exercised control mice, as well as at 0.5, 3 and 6 h after completing exercise (n = 4 per time point). Skeletal muscle MyoPS and MitoPS were determined by measuring isotope incorporation in their respective protein pools. Activation of the mTORC1-signalling cascade was measured via direct kinase activity assay and immunoblotting, whereas genes related to mitochondrial biogenesis were measured via a quantitative RT-PCR. MyoPS increased rapidly in the vehicle group post-exercise and remained elevated for 6 h, whereas this response was transiently blunted (30 min post-exercise) by rapamycin. By contrast, MitoPS was unaffected by rapamycin, and was increased over the entire post-exercise recovery period in both groups (P < 0.05). Despite rapid increases in both MyoPS and MitoPS, mTORC1 activation was suppressed in both groups post-exercise for the entire 6 h recovery period. Peroxisome proliferator activated receptor-γ coactivator-1α, pyruvate dehydrogenase kinase 4 and mitochondrial transcription factor A mRNA increased post-exercise (P < 0.05) and this response was augmented by rapamycin (P < 0.05). Collectively, these data suggest that endurance exercise stimulates MyoPS and MitoPS in skeletal muscle independently of mTORC1 activation. Key points Previous studies have shown that endurance exercise increases myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis in skeletal muscle. The mechanistic target of rapamycin (mTOR) is considered to be a key intracellular nutrient-sensing protein complex, which activates MyoPS in response to anabolic stimuli. Little is known regarding the regulation of MyoPS and MitoPS in response to endurance exercise. In the present study, we show that MyoPS and MitoPS increase in skeletal muscle following endurance exercise, despite suppression of mTORC1 during the post-exercise recovery period. Our data suggests that mTORC1 independent processes regulate both MyoPS and MitoPS following acute endurance exercise. PMID:26227152
Epitaxial Ge2Sb2Te5 probed by single cycle THz pulses of coherent synchrotron radiation
NASA Astrophysics Data System (ADS)
Bragaglia, V.; Schnegg, A.; Calarco, R.; Holldack, K.
2016-10-01
A THz-probe spectroscopy scheme with laser-induced single cycle pulses of coherent synchrotron radiation is devised and adapted to reveal the dynamic THz transmittance response in epitaxially grown phase change materials upon 800 nm fs-laser excitation. Amorphous (a-) and crystalline (c-) films of the prototypical Ge2Sb2Te5 (GST) alloy are probed with single cycle THz pulses tuned to the spectral range of the highest absorption contrast at 2 THz. After an initial instantaneous sub-picosecond (ps) dynamic THz transmittance drop, the response of a-GST in that range is dominated only by a short recovery time τshort = 2 ps of the excited carriers. On the contrary, the behavior of the c-GST response displays a short decay of 0.85 ps followed by a long one τlong = 90 ps, suggesting that vacancy layers in an ordered c-GST play a role as dissipation channel for photo-induced free carriers.
Panek, Petr; Prochazka, Ivan
2007-09-01
This article deals with the time interval measurement device, which is based on a surface acoustic wave (SAW) filter as a time interpolator. The operating principle is based on the fact that a transversal SAW filter excited by a short pulse can generate a finite signal with highly suppressed spectra outside a narrow frequency band. If the responses to two excitations are sampled at clock ticks, they can be precisely reconstructed from a finite number of samples and then compared so as to determine the time interval between the two excitations. We have designed and constructed a two-channel time interval measurement device which allows independent timing of two events and evaluation of the time interval between them. The device has been constructed using commercially available components. The experimental results proved the concept. We have assessed the single-shot time interval measurement precision of 1.3 ps rms that corresponds to the time of arrival precision of 0.9 ps rms in each channel. The temperature drift of the measured time interval on temperature is lower than 0.5 ps/K, and the long term stability is better than +/-0.2 ps/h. These are to our knowledge the best values reported for the time interval measurement device. The results are in good agreement with the error budget based on the theoretical analysis.
Hosono, Hiroyuki; Homma, Masato; Ogasawara, Yoko; Makide, Kumiko; Aoki, Junken; Niwata, Hideaki; Watanabe, Machiko; Inoue, Keizo; Ohkohchi, Nobuhiro; Kohda, Yukinao
2010-01-01
The expression of phosphatidylserine-specific phospholipase A(1) (PS-PLA(1)) is most upregulated in the genes of peripheral blood cells from chronic rejection model rats bearing long-term surviving cardiac allografts. The expression profile of PS-PLA(1) in peripheral blood cells responsible for the immune response may indicate a possible biological marker for rejection episodes. In this study, PS-PLA(1) mRNA expression was examined in human THP-1-derived macrophages. The effects of several immunosuppressive agents on this expression were also examined in in vitro experiments. A real-time RT-PCR analysis revealed that PS-PLA(1) mRNA expression was found in human THP-1-derived macrophages. This expression was enhanced in the cells stimulated with lipopolysaccharide (LPS), a toll-like receptor (TLR) 4 ligand. Other TLR ligands (TLR2, 3, 5, 7, and 9) did not show a significant induction of PS-PLA(1) mRNA. The time course of the mRNA expression profiles was different between PS-PLA(1) and tumor necrosis factor-α (TNF-α), which showed a maximal expression at 12 and 1 h after LPS stimulation, respectively. Among the observed immunosuppressive agents, corticosteroids, prednisolone, 6α-methylprednisolone, dexamethasone, and beclomethasone inhibited PS-PLA(1) expression with half-maximal inhibitory concentrations less than 3.0 nM, while methotrexate, cyclosporine A, tacrolimus, 6-mercaptopurine, and mycophenoic acid showed either a weak or moderate inhibition. These results suggest that the expression of PS-PLA(1) mRNA in THP-1-derived macrophages is activated via TLR4 and it is inhibited by corticosteroids, which are used at high dosages to suppress chronic allograft rejection.
2007-04-01
for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data...Control Organization NRL Navy Research Laboratory nrtPS Non-real- time Polling Services OFDM Orthogonal frequency division multiplex OFDMA...Routeur IDentifier RTG RTO Task Group RTO Research & Technology Organization rtPS Real- time Polling Services SC Single-carrier modulation
Keszthelyi, D; Knol, D; Troost, F J; van Avesaat, M; Foltz, M; Masclee, A A M
2013-06-01
Plant sterol (PS)-enriched food products are known to reduce plasma cholesterol concentrations by inhibiting the absorption of dietary and biliary cholesterol. The physiological responses induced by food intake in the gastrointestinal tract are all important factors in determining the overall effect of PS. The aim of this study was therefore to assess the effect of timing of consumption of a plant sterol (PS)-containing yoghurt drink relative to meal ingestion on gastric emptying (GE) of the drink and gallbladder (GB) volume. This is a randomized, single-centre, controlled study with crossover design in 12 healthy male volunteers. Three treatments were tested; a 100 mL PS yoghurt drink (labeled with 1,000 mg acetaminophen) was consumed 45 min prior to, during and 45 min after a solid meal. Plasma samples were taken, and gallbladder volumes were measured at baseline and at regular intervals during a 6-h study period. When consumed before the consumption of a meal, the yoghurt drink exhibited fast GE. The solid meal intake caused a significant contraction of the gallbladder. Consumption of the PS drink before the meal had no significant effect on GB volume as compared to baseline and compared to during and after meal consumption. The PS-containing drink, which empties fast from the stomach, does not sufficiently trigger gallbladder contraction without co-ingestion of a solid meal and in consequence does not induce the necessary physiological changes needed to allow PS to exhibit their effect on inhibiting cholesterol absorption.
Aqueous solvation from the water perspective.
Ahmed, Saima; Pasti, Andrea; Fernández-Terán, Ricardo J; Ciardi, Gustavo; Shalit, Andrey; Hamm, Peter
2018-06-21
The response of water re-solvating a charge-transfer dye (deprotonated Coumarin 343) after photoexcitation has been measured by means of transient THz spectroscopy. Two steps of increasing THz absorption are observed, a first ∼10 ps step on the time scale of Debye relaxation of bulk water and a much slower step on a 3.9 ns time scale, the latter of which reflecting heating of the bulk solution upon electronic relaxation of the dye molecules from the S 1 back into the S 0 state. As an additional reference experiment, the hydroxyl vibration of water has been excited directly by a short IR pulse, establishing that the THz signal measures an elevated temperature within ∼1 ps. This result shows that the first step upon dye excitation (10 ps) is not limited by the response time of the THz signal; it rather reflects the reorientation of water molecules in the solvation layer. The apparent discrepancy between the relatively slow reorientation time and the general notion that water is among the fastest solvents with a solvation time in the sub-picosecond regime is discussed. Furthermore, non-equilibrium molecular dynamics simulations have been performed, revealing a close-to-quantitative agreement with experiment, which allows one to disentangle the contribution of heating to the overall THz response from that of water orientation.
Two-color short-pulse laser altimeter measurements of ocean surface backscatter
NASA Technical Reports Server (NTRS)
Abshire, James B.; Mcgarry, Jan F.
1987-01-01
The timing and correlation properties of pulsed laser backscatter from the ocean surface have been measured with a two-color short-pulse laser altimeter. The Nd:YAG laser transmitted 70- and 35-ps wide pulses simultaneously at 532 and 355 nm at nadir, and the time-resolved returns were recorded by a receiver with 800-ps response time. The time-resolved backscatter measured at both 330-m and 1291-m altitudes showed little pulse broadening due to the submeter laser spot size. The differential delay of the 355-nm and 532-nm backscattered waveforms were measured with a rms error of about 75 ps. The change in aircraft altitudes also permitted the change in atmospheric pressure to be estimated by using the two-color technique.
Characterization of gigahertz (GHz) bandwidth photomultipliers
NASA Technical Reports Server (NTRS)
Abshire, J. B.; Rowe, H. E.
1977-01-01
The average impulse response, root-mean-square times jitter as a function of signal level, single photoelectron distribution, and multiphotoelectron dark-count distribution have been measured for two static crossed-field and five electrostatic photomultipliers. The optical signal source for the first three of these tests was a 30 picosecond mode-locked laser pulse at 0.53 micron. The static crossed-field detectors had 2-photoelectron resolution, less than 200 ps rise times, and rms time jitters of 30 ps at the single photoelectron level. The electrostatic photomultipliers had rise times from 1 to 2.5 nanoseconds, and rms time jitters from 160 to 650 ps at the same signal level. The two static crossed-field photomultipliers had ion-feedback-generated dark pulses to the 50-photoelectron level, whereas one electrostatic photomultiplier had dark pulses to the 30-photoelectron level.
Just-in-time control of Spo0A synthesis in Bacillus subtilis by multiple regulatory mechanisms.
Chastanet, Arnaud; Losick, Richard
2011-11-01
The response regulator Spo0A governs multiple developmental processes in Bacillus subtilis, including most conspicuously sporulation. Spo0A is activated by phosphorylation via a multicomponent phosphorelay. Previous work has shown that the Spo0A protein is not rate limiting for sporulation. Rather, Spo0A is present at high levels in growing cells, rapidly rising to yet higher levels under sporulation-inducing conditions, suggesting that synthesis of the response regulator is subject to a just-in-time control mechanism. Transcription of spo0A is governed by a promoter switching mechanism, involving a vegetative, σ(A)-recognized promoter, P(v), and a sporulation σ(H)-recognized promoter, P(s), that is under phosphorylated Spo0A (Spo0A∼P) control. The spo0A regulatory region also contains four (including one identified in the present work) conserved elements that conform to the consensus binding site for Spo0A∼P binding sites. These are herein designated O(1), O(2), O(3), and O(4) in reverse order of their proximity to the coding sequence. Here we report that O(1) is responsible for repressing P(v) during the transition to stationary phase, that O(2) is responsible for repressing P(s) during growth, that O(3) is responsible for activating P(s) at the start of sporulation, and that O(4) is dispensable for promoter switching. We also report that Spo0A synthesis is subject to a posttranscriptional control mechanism such that translation of mRNAs originating from P(v) is impeded due to RNA secondary structure whereas mRNAs originating from P(s) are fully competent for protein synthesis. We propose that the opposing actions of O(2) and O(3) and the enhanced translatability of mRNAs originating from P(s) create a highly sensitive, self-reinforcing switch that is responsible for producing a burst of Spo0A synthesis at the start of sporulation.
NASA Astrophysics Data System (ADS)
Lin, Gong-Ru
2002-12-01
We develop a delay-line-free and frequency traceable electro-optic sampling oscilloscope by use of a digital phase-locked loop phase shifter (PLL-PS) controlled delay-time-tunable gain-switched laser diode (GSLD). The home-made voltage-controllable PLL-PS exhibits a linear transfer function with ultra-wide phase shifting range of ±350° and tuning error of <±5%, which benefits the advantages of frequency tracking to free-running signals with suppressed timing-jitter. The maximum delay-time of PLL-PS controlled GSLD is up to 1.95 periods by changing the controlling voltage ( VREF) from -3.5 to 3.5 V, which corresponds to 3.9 ns at repetition frequency of 500 MHz. The tuning responsivity and resolution are about 0.56 ns/V and 0.15˜0.2 ps, respectively. The maximum delay-time switching bandwidth of 100 Hz is determined under the control of a saw-tooth modulated VREF function. The waveform sampling of microwave PECL signals generated from a free-running digital frequency divider is performed with acceptable measuring deviation.
Addressing Passive Smoking in Children
Hutchinson, Sasha G.; Kuijlaars, Jennifer S.; Mesters, Ilse; Muris, Jean W. M.; van Schayck, Constant P.; Dompeling, Edward; Feron, Frans J. M.
2014-01-01
Background A significant number of parents are unaware or unconvinced of the health consequences of passive smoking (PS) in children. Physicians could increase parental awareness by giving personal advice. Aim To evaluate the current practices of three Dutch health professions (paediatricians, youth health care physicians, and family physicians) regarding parental counselling for passive smoking (PS) in children. Methods All physicians (n = 720) representing the three health professions in Limburg, the Netherlands, received an invitation to complete a self-administered electronic questionnaire including questions on their: sex, work experience, personal smoking habits, counselling practices and education regarding PS in children. Results The response rate was 34%. One tenth (11%) of the responding physicians always addressed PS in children, 32% often, 54% occasionally and 4% reported to never attend to it. The three health professions appeared comparable regarding their frequency of parental counselling for PS in children. Addressing PS was more likely when children had respiratory problems. Lack of time was the most frequently mentioned barrier, being very and somewhat applicable for respectively 14% and 43% of the physicians. One fourth of the responders had received postgraduate education about PS. Additionally, 49% of the responders who did not have any education about PS were interested in receiving it. Conclusions Physicians working in the paediatric field in Limburg, the Netherlands, could more frequently address PS in children with parents. Lack of time appeared to be the most mentioned barrier and physicians were more likely to counsel parents for PS in children with respiratory complaints/diseases. Finally, a need for more education on parental counselling for PS was expressed. PMID:24809443
Femtosecond/picosecond time-resolved fluorescence study of hydrophilic polymer fine particles.
Nanjo, Daisuke; Hosoi, Haruko; Fujino, Tatsuya; Tahara, Tahei; Korenaga, Takashi
2007-03-22
Femtosecond/picosecond time-resolved fluorescence study of hydrophilic polymer fine particles (polyacrylamide, PAAm) was reported. Ultrafast fluorescence dynamics of polymer/water solution was monitored using a fluorescent probe molecule (C153). In the femtosecond time-resolved fluorescence measurement at 480 nm, slowly decay components having lifetimes of tau(1) approximately 53 ps and tau(2) approximately 5 ns were observed in addition to rapid fluorescence decay. Picosecond time-resolved fluorescence spectra of C153/PAAm/H2O solution were also measured. In the time-resolved fluorescence spectra of C153/PAAm/H2O, a peak shift from 490 to 515 nm was measured, which can be assigned to the solvation dynamics of polymer fine particles. The fluorescence peak shift was related to the solvation response function and two time constants were determined (tau(3) approximately 50 ps and tau(4) approximately 467 ps). Therefore, the tau(1) component observed in the femtosecond time-resolved fluorescence measurement was assigned to the solvation dynamics that was observed only in the presence of polymer fine particles. Rotational diffusion measurements were also carried out on the basis of the picosecond time-resolved fluorescence spectra. In the C153/PAAm/H2O solution, anisotropy decay having two different time constants was also derived (tau(6) approximately 76 ps and tau(7) approximately 676 ps), indicating the presence of two different microscopic molecular environments around the polymer surface. Using the Stokes-Einstein-Debye (SED) equation, microscopic viscosity around the polymer surface was evaluated. For the area that gave a rotational diffusion time of tau(6) approximately 76 ps, the calculated viscosity is approximately 1.1 cP and for tau(7) approximately 676 ps, it is approximately 10 cP. The calculated viscosity values clearly revealed that there are two different molecular environments around the polyacrylamide fine particles.
Body temperature and respiratory dynamics in un-shaded beef cattle
NASA Astrophysics Data System (ADS)
Gaughan, J. B.; Mader, T. L.
2014-09-01
In this study body temperature (BT, °C) and panting score (PS, 0-4.5; where 0 = no panting/no stress and 4.5 = catastrophic stress) data were obtained from 30 Angus steers housed outside over 120 days Steers were implanted with a BT transmitter on day -31, BT was recorded at 30-min intervals to a data logger and downloaded each day to a database. The cattle were housed in ten outdoor un-shaded pens with an earthen floor, eight of which had a pen floor area of 144 m2 (three transmitter steers plus five non-transmitter steers; 18 m2/steer) and two had an area of 168 m2 (three transmitter steers and six non-transmitter steers; 18.7 m2/steer). Only data from the transmitter steers were used in this study. The PS of the steers was obtained daily (± 15 min) at 0600 hours (AM), 1200 hours (MD) and 1600 hours (PM). At the same times climate variables (ambient temperature, black globe temperature, solar radiation, relative humidity, wind speed and rainfall) were obtained from an on-site weather station. PS observations were made from outside the pens so as not to influence cattle responses. The two closest BT values to the time when PS was obtained were downloaded retrospectively from a logger and averaged. A total of 8,352 observations were used to generate second order polynomial response curves: (AM) y = 39.08 + 0.009 x + 0.137 x 2 ( R 2 = 0.94; P < 0.001) (MD) y = 39.09 + 0.914 x - 0.080 x 2 ( R 2 = 0.89; P < 0.001) and (PM) y = 39.52 + 0.790 x - 0.068 x 2 ( R 2 = 0.83; P < 0.001) where y = BT (°C) and x PS. These data suggest that PS is a good indicator of body temperature. The BT at MD corresponded to slightly lower PS compared with PM, e.g., for PS 1; BT at MD = 39.1 ± 0.05 °C whereas BT at PM = 39.5 ± 0.05 °C. However during AM, BT was lower ( P < 0.05) at PS 1, 2 and 2.5 compared with MD and PM. For example, when PS was 2.5 the BT at AM was 40.2 ± 0.04 °C, at MD it was 40.9 ± 0.04 °C and at PM BT was 41.1 ± 0.04 °C. When PS was 0 the BT at AM and MD were similar. The AM response curve suggests animals attempt to increase heat dissipation during the cooler AM period relative to MD and PM. Morning observation of cattle (before feeding) are crucial for effective heat load management especially on days when high heat load is expected. The MD and PM observations provide a good indication of the impact of high environmental heat load on cattle. Differences in PS between AM and PM observations suggest that more research is needed to determine the effect of night time conditions on BT, PS and overall respiratory dynamics of cattle during periods of hot weather.
Mallidi, Srivalleesha; Anbil, Sriram; Lee, Seonkyung; Manstein, Dieter; Elrington, Stefan; Kositratna, Garuna; Schoenfeld, David; Pogue, Brian; Davis, Steven J; Hasan, Tayyaba
2014-02-01
The need for patient-specific photodynamic therapy (PDT) in dermatologic and oncologic applications has triggered several studies that explore the utility of surrogate parameters as predictive reporters of treatment outcome. Although photosensitizer (PS) fluorescence, a widely used parameter, can be viewed as emission from several fluorescent states of the PS (e.g., minimally aggregated and monomeric), we suggest that singlet oxygen luminescence (SOL) indicates only the active PS component responsible for the PDT. Here, the ability of discrete PS fluorescence-based metrics (absolute and percent PS photobleaching and PS re-accumulation post-PDT) to predict the clinical phototoxic response (erythema) resulting from 5-aminolevulinic acid PDT was compared with discrete SOL (DSOL)-based metrics (DSOL counts pre-PDT and change in DSOL counts pre/post-PDT) in healthy human skin. Receiver operating characteristic curve (ROC) analyses demonstrated that absolute fluorescence photobleaching metric (AFPM) exhibited the highest area under the curve (AUC) of all tested parameters, including DSOL based metrics. The combination of dose-metrics did not yield better AUC than AFPM alone. Although sophisticated real-time SOL measurements may improve the clinical utility of SOL-based dosimetry, discrete PS fluorescence-based metrics are easy to implement, and our results suggest that AFPM may sufficiently predict the PDT outcomes and identify treatment nonresponders with high specificity in clinical contexts.
Sun, ZhengWang; Du, Juan; Hwang, Eunson; Yi, Tae-Hoo
2018-05-10
Paeonia suffruticosa Andr. (PS) has been used in traditional Chinese medicine for a long time. However, there are no studies that investigate the preventive effects of PS on ultraviolet B (UVB)-induced photoaging. In this study, paeonol (PA) was detected the main compound in PS root. In vitro, PS and PA significantly inhibited UVB-induced phosphorylation of mitogen-activated protein kinase and activator protein 1 in keratinocytes, which consequently led to degradation of procollagen type I. On the other hand, PS and PA increased NAD(P)H:quinone oxidoreductase 1 and heme oxygenase-1 expression, confirmed by greater nuclear accumulation of nuclear factor E2-releated factor 2 (Nrf2). Furthermore, this study proved that the endogenous antioxidant system Nrf2/antioxidant response element was regulated by dihydrolipoamide dehydrogenase, a tricarboxylic acid (TCA) cycle-associated protein whose level was decreased after UVB exposure. PS and PA promoted the production of dihydrolipoamide dehydrogenase, as well as the activation of Nrf2 and antioxidant response element, resulting in preventing procollagen type I ruined caused by UVB. In vivo, topical application of PS and PA attenuated UVB-induced matrix metalloproteinase-1 production and promoted procollagen type I in hairless mice. These results suggested PA a promising botanical in protecting skin from UVB-induced photoaging. Copyright © 2018 John Wiley & Sons, Ltd.
Experimental and Theoretical Study of Molecular Response of Amine Bases in Organic Solvents
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kathmann, Shawn M.; Cho, Herman M.; Chang, Tsun-Mei
2014-05-08
Reorientational correlation times of various amine bases (viz., pyridine, 2,6-lutidene, 2,2,6,6-tetramethylpiperidine) and organic solvents (dichloromethane, toluene) were determined by solution-state NMR relaxation time measurements and compared with predictions from molecular dynamics (MD) simulations. The bases and solvents are reagents in complex reactions involving Frustrated Lewis Pairs (FLP), which display remarkable catalytic activity in metal-free H2 scission. The comparison of measured and simulated correlation times is a key test of the ability of recent MD and quantum electronic structure calculations to elucidate the mechanism of FLP activity. Correla- tion times were found to be in the range 1.4-3.4 ps (NMR) andmore » 1.23-5.28 ps (MD) for the amines, and 0.9-2.3 ps (NMR) and 0.2-1.7 ps (MD) for the solvent molecules. This work was supported by the U.S. Department of Energy, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences. Pacic Northwest National Laboratory (PNNL) is a multiprogram national laboratory operated for DOE by Battelle.« less
2014-01-01
Introduction The novel arthritis-specific Work Productivity Survey (WPS) was developed to estimate patient productivity limitations associated with arthritis within and outside the home, which is an unmet need in psoriatic arthritis (PsA). The WPS has been validated in rheumatoid arthritis. This report assesses the discriminant validity, responsiveness and reliability of the WPS in adult-onset PsA. Methods Psychometric properties were assessed using data from the RAPID-PsA trial (NCT01087788) investigating certolizumab pegol (CZP) efficacy and safety in PsA. WPS was completed at baseline and every 4 weeks until Week 24. Validity was evaluated at baseline via known-groups defined using first and third quartiles of patients’ Disease Activity Score 28 based on C-reactive protein (DAS28(CRP)), Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 (SF-36) items and PsA Quality of Life (PsAQoL) scores. Responsiveness and reliability were assessed by comparing WPS mean changes at Week 12 in American College of Rheumatology 20% improvement criteria (ACR20) or HAQ-DI Minimal Clinically Important Difference (MCID) 0.3 responders versus non-responders, as well as using standardized response means (SRM). All comparisons were conducted on the observed cases in the Randomized Set, regardless of the randomization group, using a non-parametric bootstrap-t method. Results Compared with patients with a better health state, patients with a worse health state had on average 2 to 6 times more household work days lost, more days with reduced household productivity, more days missed of family/social/leisure activities, more days with outside help hired and a significantly higher interference of arthritis per month. Among employed patients, those with a worse health state had 2 to 4 times more workplace days lost, more days with patient workplace productivity reduced, and a significantly higher interference of arthritis on patient workplace productivity versus patients with a better health state. WPS was also responsive to clinical changes, with responders having significantly larger improvements at Week 12 in WPS scores versus non-responders. The effect sizes for changes in productivity in ACR20 or HAQ-DI MCID responders were moderate (0.5 < SRM < 0.8) or small. Conclusions These analyses demonstrate the validity, responsiveness and reliability of the WPS, as an instrument for the measurement of patient productivity within and outside the home in an adult-onset PsA population. PMID:24996416
Cao, Yixiang; Hughes, Thomas; Giesen, Dave; Halls, Mathew D; Goldberg, Alexander; Vadicherla, Tati Reddy; Sastry, Madhavi; Patel, Bhargav; Sherman, Woody; Weisman, Andrew L; Friesner, Richard A
2016-06-15
We have developed and implemented pseudospectral time-dependent density-functional theory (TDDFT) in the quantum mechanics package Jaguar to calculate restricted singlet and restricted triplet, as well as unrestricted excitation energies with either full linear response (FLR) or the Tamm-Dancoff approximation (TDA) with the pseudospectral length scales, pseudospectral atomic corrections, and pseudospectral multigrid strategy included in the implementations to improve the chemical accuracy and to speed the pseudospectral calculations. The calculations based on pseudospectral time-dependent density-functional theory with full linear response (PS-FLR-TDDFT) and within the Tamm-Dancoff approximation (PS-TDA-TDDFT) for G2 set molecules using B3LYP/6-31G*(*) show mean and maximum absolute deviations of 0.0015 eV and 0.0081 eV, 0.0007 eV and 0.0064 eV, 0.0004 eV and 0.0022 eV for restricted singlet excitation energies, restricted triplet excitation energies, and unrestricted excitation energies, respectively; compared with the results calculated from the conventional spectral method. The application of PS-FLR-TDDFT to OLED molecules and organic dyes, as well as the comparisons for results calculated from PS-FLR-TDDFT and best estimations demonstrate that the accuracy of both PS-FLR-TDDFT and PS-TDA-TDDFT. Calculations for a set of medium-sized molecules, including Cn fullerenes and nanotubes, using the B3LYP functional and 6-31G(**) basis set show PS-TDA-TDDFT provides 19- to 34-fold speedups for Cn fullerenes with 450-1470 basis functions, 11- to 32-fold speedups for nanotubes with 660-3180 basis functions, and 9- to 16-fold speedups for organic molecules with 540-1340 basis functions compared to fully analytic calculations without sacrificing chemical accuracy. The calculations on a set of larger molecules, including the antibiotic drug Ramoplanin, the 46-residue crambin protein, fullerenes up to C540 and nanotubes up to 14×(6,6), using the B3LYP functional and 6-31G(**) basis set with up to 8100 basis functions show that PS-FLR-TDDFT CPU time scales as N(2.05) with the number of basis functions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Zhang, Xiao-yan; Peng, Yong; Su, Zhong-rui; Chen, Qi-he; Ruan, Hui; He, Guo-qing
2013-02-01
Biotransformation of phytosterol (PS) by a newly isolated mutant Mycobacterium neoaurum ZJUVN-08 to produce androstenedione has been investigated in this paper. The parameters of the biotransformation process were optimized using fractional factorial design and response surface methodology. Androstenedione was the sole product in the fermentation broth catalyzed by the mutant M. neoaurum ZJUVN-08 strain. Results showed that molar ratio of hydroxypropyl-β-cyclodextrin (HP-β-CD) to PS and substrate concentrations were the two most significant factors affecting androstenedione production. By analyzing the statistical model of three-dimensional surface plot, the optimal process conditions were observed at 0.1 g/L inducer, pH 7.0, molar ratio of HP-β-CD to PS 1.92:1, 8.98 g/L PS, and at 120 h of incubation time. Under these conditions, the maximum androstenedione yield was 5.96 g/L and nearly the same with the non-optimized (5.99 g/L), while the maximum PS conversion rate was 94.69% which increased by 10.66% compared with the non-optimized (84.03%). The predicted optimum conditions from the mathematical model were in agreement with the verification experimental results. It is considered that response surface methodology was a powerful and efficient method to optimize the parameters of PS biotransformation process.
Zhang, Xiao-yan; Peng, Yong; Su, Zhong-rui; Chen, Qi-he; Ruan, Hui; He, Guo-qing
2013-01-01
Biotransformation of phytosterol (PS) by a newly isolated mutant Mycobacterium neoaurum ZJUVN-08 to produce androstenedione has been investigated in this paper. The parameters of the biotransformation process were optimized using fractional factorial design and response surface methodology. Androstenedione was the sole product in the fermentation broth catalyzed by the mutant M. neoaurum ZJUVN-08 strain. Results showed that molar ratio of hydroxypropyl-β-cyclodextrin (HP-β-CD) to PS and substrate concentrations were the two most significant factors affecting androstenedione production. By analyzing the statistical model of three-dimensional surface plot, the optimal process conditions were observed at 0.1 g/L inducer, pH 7.0, molar ratio of HP-β-CD to PS 1.92:1, 8.98 g/L PS, and at 120 h of incubation time. Under these conditions, the maximum androstenedione yield was 5.96 g/L and nearly the same with the non-optimized (5.99 g/L), while the maximum PS conversion rate was 94.69% which increased by 10.66% compared with the non-optimized (84.03%). The predicted optimum conditions from the mathematical model were in agreement with the verification experimental results. It is considered that response surface methodology was a powerful and efficient method to optimize the parameters of PS biotransformation process. PMID:23365012
Erlotinib as a single agent in select subsets of patients with advanced non-small-cell lung cancer.
Carrión, Ramón Pérez; Gracián, Antonio Cubillo; Hernandez, Pedro Salinas
2007-07-01
Erlotinib is an orally active inhibitor of the epidermal growth factor receptor that is effective for the treatment of non-small-cell lung cancer (NSCLC). Patients with a poor performance status (PS) of 2 constitute up to 40% of advanced NSCLC. This group of patients have a lower life expectancy and are thought to have a greater degree of treatment-related toxicity. The clinical benefit on 238 patients with poor PS included in an open-label, nonrandomized, phase II trial of erlotinib in advanced/metastatic NSCLC was 57.58% defined as complete response plus partial response plus stable disease. Median time to progression was 2.9 months. This review will summarize available data about erlotinib on patients with a PS of 2.
Studies of uniformity of 50 μm low-gain avalanche detectors at the Fermilab test beam
NASA Astrophysics Data System (ADS)
Apresyan, A.; Xie, S.; Pena, C.; Arcidiacono, R.; Cartiglia, N.; Carulla, M.; Derylo, G.; Ferrero, M.; Flores, D.; Freeman, P.; Galloway, Z.; Ghassemi, A.; Al Ghoul, H.; Gray, L.; Hidalgo, S.; Kamada, S.; Los, S.; Mandurrino, M.; Merlos, A.; Minafra, N.; Pellegrini, G.; Quirion, D.; Ronzhin, A.; Royon, C.; Sadrozinski, H.; Seiden, A.; Sola, V.; Spiropulu, M.; Staiano, A.; Uplegger, L.; Yamamoto, K.; Yamamura, K.
2018-07-01
In this paper we report measurements of the uniformity of time resolution, signal amplitude, and charged particle detection efficiency across the sensor surface of low-gain avalanche detectors (LGAD). Comparisons of the performance of sensors with different doping concentrations and different active thicknesses are presented, as well as their temperature dependence and radiation tolerance up to 6 × 1014 n/cm2. Results were obtained at the Fermilab test beam facility using 120 GeV proton beams, and a high precision pixel tracking detector. LGAD sensors manufactured by the Centro Nacional de Microelectrónica (CNM) and Hamamatsu Photonics (HPK) were studied. The uniformity of the sensor response in pulse height before irradiation was found to have a 2% spread. The signal detection efficiency and timing resolution in the sensitive areas before irradiation were found to be 100% and 30-40 ps, respectively. A "no-response" area between pads was measured to be about 130 μm for CNM and 170 μm for HPK sensors. After a neutron fluence of 6 × 1014 n/cm2 the CNM sensor exhibits a large gain variation of up to a factor of 2.5 when comparing metalized and non-metalized sensor areas. An irradiated CNM sensor achieved a time resolution of 30 ps for the metalized area and 40 ps for the non-metalized area, while a HPK sensor irradiated to the same fluence achieved a 30 ps time resolution.
Prognostic impact of paraneoplastic cushing's syndrome in small-cell lung cancer.
Nagy-Mignotte, Hélène; Shestaeva, Oxana; Vignoud, Lucile; Guillem, Pascale; Ruckly, Stéphane; Chabre, Olivier; Sakhri, Linda; Duruisseaux, Michael; Mousseau, Mireille; Timsit, Jean-François; Moro-Sibilot, Denis
2014-04-01
Paraneoplastic Cushing's syndrome (CushingPS) in small-cell lung cancer is rare but severe. We studied 383 patients with small-cell lung cancer diagnosed between 1998 and 2012. Among them, 23 patients had CushingPS, 56 had other paraneoplastic syndrome (OtherPS), and 304 had no paraneoplastic syndrome (NoPS). After comparison of the three groups, we observed that CushingPS patients had more extensive disease: 82.6% versus 67.8% versus 53.3% (p = 0.005), respectively, with more than two metastatic sites: 63.2% versus 15.8% and 24.1% (p ≤ 0.001), a higher World Health Organization performance status (2-4): 73.9% versus 57.1% versus 43.7% (p = 0.006), greater weight loss (≥10%): 47.8% versus 33.9% versus 16.4% (p ≤ 0.001), reduced objective response to first-line treatment: 47.6% versus 74.1% versus 71.1% (p = 0.04), and poorer sensitivity to first-line treatment: 19% versus 38.9% versus 48.6% (p = 0.01). NoPS patients, with World Health Organization performance status of 3-4, had extensive disease at diagnosis, with response, sensitivity to first-line treatment, and survival similar to the CushingPS group. At relapse, the CushingPS group had no objective response to second-line treatment versus 25% versus 42.8% in OtherPS and NoPS groups, respectively (p = 0.005). The median survival of CushingPS patients was 6.6 months versus 9.2 months for OtherPS and 13.1 months for NoPS patients (p ≤ 0.001). CushingPS is a prognostic factor of death (hazard ratio, 2.31; p ≤ 0.001). CushingPS is the worst form of the paraneoplastic syndromes with particularly extensive tumors. Reduced objective response and sensitivity to first-line treatment and no response to second-line treatment suggest starting palliative care early at first line and exclusively at relapse.
Body temperature and respiratory dynamics in un-shaded beef cattle.
Gaughan, J B; Mader, T L
2014-09-01
In this study body temperature (BT, °C) and panting score (PS, 0-4.5; where 0 = no panting/no stress and 4.5 = catastrophic stress) data were obtained from 30 Angus steers housed outside over 120 days Steers were implanted with a BT transmitter on day -31, BT was recorded at 30-min intervals to a data logger and downloaded each day to a database. The cattle were housed in ten outdoor un-shaded pens with an earthen floor, eight of which had a pen floor area of 144 m2 (three transmitter steers plus five non-transmitter steers; 18 m2/steer) and two had an area of 168 m2 (three transmitter steers and six non-transmitter steers; 18.7 m2/steer). Only data from the transmitter steers were used in this study. The PS of the steers was obtained daily (± 15 min) at 0600 hours (AM), 1200 hours (MD) and 1600 hours (PM). At the same times climate variables (ambient temperature, black globe temperature, solar radiation, relative humidity, wind speed and rainfall) were obtained from an on-site weather station. PS observations were made from outside the pens so as not to influence cattle responses. The two closest BT values to the time when PS was obtained were downloaded retrospectively from a logger and averaged. A total of 8,352 observations were used to generate second order polynomial response curves: (AM) y = 39.08 + 0.009 x + 0.137x2 (R2 = 0.94; P < 0.001) (MD) y = 39.09 + 0.914x − 0.080x2 (R2 = 0.89; P < 0.001) and (PM) y = 39.52 + 0.790x − 0.068x2 (R2 = 0.83; P < 0.001) where y = BT (°C) and x PS. These data suggest that PS is a good indicator of body temperature. The BT at MD corresponded to slightly lower PS compared with PM, e.g., for PS 1; BT at MD = 39.1 ± 0.05 °C whereas BT at PM = 39.5 ± 0.05 °C. However during AM, BT was lower (P < 0.05) at PS 1, 2 and 2.5 compared with MD and PM. For example, when PS was 2.5 the BT at AM was 40.2 ± 0.04 °C, at MD it was 40.9 ± 0.04 °C and at PM BT was 41.1 ± 0.04 °C. When PS was 0 the BT at AM and MD were similar. The AM response curve suggests animals attempt to increase heat dissipation during the cooler AM period relative to MD and PM. Morning observation of cattle (before feeding) are crucial for effective heat load management especially on days when high heat load is expected. The MD and PM observations provide a good indication of the impact of high environmental heat load on cattle. Differences in PS between AM and PM observations suggest that more research is needed to determine the effect of night time conditions on BT, PS and overall respiratory dynamics of cattle during periods of hot weather.
Zamboni, Anita; Zanin, Laura; Tomasi, Nicola; Avesani, Linda; Pinton, Roberto; Varanini, Zeno; Cesco, Stefano
2016-01-07
It is well known that in the rhizosphere soluble Fe sources available for plants are mainly represented by a mixture of complexes between the micronutrient and organic ligands such as carboxylates and phytosiderophores (PS) released by roots, as well as fractions of humified organic matter. The use by roots of these three natural Fe sources (Fe-citrate, Fe-PS and Fe complexed to water-extractable humic substances, Fe-WEHS) have been already studied at physiological level but the knowledge about the transcriptomic aspects is still lacking. The (59)Fe concentration recorded after 24 h in tissues of tomato Fe-deficient plants supplied with (59)Fe complexed to WEHS reached values about 2 times higher than those measured in response to the supply with Fe-citrate and Fe-PS. However, after 1 h no differences among the three Fe-chelates were observed considering the (59)Fe concentration and the root Fe(III) reduction activity. A large-scale transcriptional analysis of root tissue after 1 h of Fe supply showed that Fe-WEHS modulated only two transcripts leaving the transcriptome substantially identical to Fe-deficient plants. On the other hand, Fe-citrate and Fe-PS affected 728 and 408 transcripts, respectively, having 289 a similar transcriptional behaviour in response to both Fe sources. The root transcriptional response to the Fe supply depends on the nature of chelating agents (WEHS, citrate and PS). The supply of Fe-citrate and Fe-PS showed not only a fast back regulation of molecular mechanisms modulated by Fe deficiency but also specific responses due to the uptake of the chelating molecule. Plants fed with Fe-WEHS did not show relevant changes in the root transcriptome with respect to the Fe-deficient plants, indicating that roots did not sense the restored cellular Fe accumulation.
Mizukami, Yoshihisa; Abe, Tomoyuki; Shibata, Hiroaki; Makimura, Yukitoshi; Fujishiro, Shuh-hei; Yanase, Kimihide; Hishikawa, Shuji; Kobayashi, Eiji; Hanazono, Yutaka
2014-01-01
Recent studies have revealed negligible immunogenicity of induced pluripotent stem (iPS) cells in syngeneic mice and in autologous monkeys. Therefore, human iPS cells would not elicit immune responses in the autologous setting. However, given that human leukocyte antigen (HLA)-matched allogeneic iPS cells would likely be used for medical applications, a more faithful model system is needed to reflect HLA-matched allogeneic settings. Here we examined whether iPS cells induce immune responses in the swine leukocyte antigen (SLA)-matched setting. iPS cells were generated from the SLA-defined C1 strain of Clawn miniature swine, which were confirmed to develop teratomas in mice, and transplanted into the testes (n = 4) and ovary (n = 1) of C1 pigs. No teratomas were found in pigs on 47 to 125 days after transplantation. A Mixed lymphocyte reaction revealed that T-cell responses to the transplanted MHC-matched (C1) iPS cells were significantly lower compared to allogeneic cells. The humoral immune responses were also attenuated in the C1-to-C1 setting. More importantly, even MHC-matched iPS cells were susceptible to innate immunity, NK cells and serum complement. iPS cells lacked the expression of SLA class I and sialic acids. The in vitro cytotoxic assay showed that C1 iPS cells were targeted by NK cells and serum complement of C1. In vivo, the C1 iPS cells developed larger teratomas in NK-deficient NOG (T-B-NK-) mice (n = 10) than in NK-competent NOD/SCID (T-B-NK+) mice (n = 8) (p<0.01). In addition, C1 iPS cell failed to form teratomas after incubation with the porcine complement-active serum. Taken together, MHC-matched iPS cells can attenuate cellular and humoral immune responses, but still susceptible to innate immunity in pigs.
In-depth study of single photon time resolution for the Philips digital silicon photomultiplier
NASA Astrophysics Data System (ADS)
Liu, Z.; Gundacker, S.; Pizzichemi, M.; Ghezzi, A.; Auffray, E.; Lecoq, P.; Paganoni, M.
2016-06-01
The digital silicon photomultiplier (SiPM) has been commercialised by Philips as an innovative technology compared to analog silicon photomultiplier devices. The Philips digital SiPM, has a pair of time to digital converters (TDCs) connected to 12800 single photon avalanche diodes (SPADs). Detailed measurements were performed to understand the low photon time response of the Philips digital SiPM. The single photon time resolution (SPTR) of every single SPAD in a pixel consisting of 3200 SPADs was measured and an average value of 85 ps full width at half maximum (FWHM) was observed. Each SPAD sends the signal to the TDC with different signal propagation time, resulting in a so called trigger network skew. This distribution of the trigger network skew for a pixel (3200 SPADs) has been measured and a variation of 50 ps FWHM was extracted. The SPTR of the whole pixel is the combination of SPAD jitter, trigger network skew, and the SPAD non-uniformity. The SPTR of a complete pixel was 103 ps FWHM at 3.3 V above breakdown voltage. Further, the effect of the crosstalk at a low photon level has been studied, with the two photon time resolution degrading if the events are a combination of detected (true) photons and crosstalk events. Finally, the time response to multiple photons was investigated.
Superconducting flux flow digital circuits
DOE Office of Scientific and Technical Information (OSTI.GOV)
Martens, J.S.; Zipperian, T.E.; Hietala, V.M.
1993-03-01
The authors have developed a family of digital logic circuits based on superconducting flux flow transistors that show high speed, reasonable signal levels, large fan-out, and large noise margins. The circuits are made from high-temperature superconductors (HTS) and have been shown to operate at over 90 K. NOR gates have been demonstrated with fan-outs of more than 5 and fully loaded switching times less than a fixture-limited 50 ps. Ring-oscillator data suggest inverter delay times of about 40ps when using a 3-[mu]m linewidths. Simple flip-flops have also been demonstrated showing large noise margins, response times of less than 30 ps,more » and static power dissipation on the order of 30 nW. Among other uses, this logic family is appropriate as an interface between logic families such as single flux quantum and conventional semiconductor logic.« less
Joy, R M; Walby, W F; Stark, L G; Albertson, T E
1995-01-01
An in vitro paired-pulse orthodromic stimulation technique was used to examine the effects of lindane on excitatory afferent terminals, CA1 pyramidal cells and recurrent collateral evoked inhibition in the rat hippocampal slice. This was done to establish simultaneous effects on a simple neural network and to develop procedures for more detailed analyses of the effects of lindane. Hippocampal slices 400 microns thick were perfused with oxygenated artificial cerebrospinal fluid. Electrodes were placed in the CA1 region to record extracellular population spike (PS) or excitatory postsynaptic potential (EPSP) responses to stimulation of Schaffer collateral/commissural (SC/C) fibers. Gamma-aminobutyric acid (GABA)-mediated recurrent inhibition was measured using a paired-pulse technique. Perfusion with lindane produced both time and dose dependent changes in a number of the responses measured. The most striking effect produced by lindane was the loss of GABAA-mediated recurrent collateral inhibition. This tended to occur rapidly, often before changes in EPSP or PS responses could be detected. With longer exposures to lindane, repetitive discharge of pyramidal cells developed resulting in multiple PSs to single stimuli. Lindane (50 microM) also completely reversed the effects of the injectable anesthetic, propofol, a compound known to potentiate GABAA-mediated inhibition via a direct action on the GABAA receptor-chloride channel complex. An analysis of input/output relationships at varying stimulus intensities showed that lindane increased EPSP and PS response amplitudes at any given stimulus intensity resulting in a leftward shift in the EPSP amplitude/stimulus intensity, PS amplitude/stimulus intensity and PS amplitude/EPSP amplitude relationships. This effect was most noticeable with low intensity stimuli and became progressively less so as stimulus intensities approached those yielding maximal responses. In addition lindane significantly increased paired pulse facilitation of EPSPs during paired stimulus presentation.
NASA Astrophysics Data System (ADS)
Ali, Hiba M.; Makki, Sameer A.; Abd, Ahmed N.
2018-05-01
Porous silicon (n-PS) films can be prepared by photoelectochemical etching (PECE) Silicon chips n - types with 15 (mA / cm2), in 15 minutes etching time on the fabrication nano-sized pore arrangement. By using X-ray diffraction measurement and atomic power microscopy characteristics (AFM), PS was investigated. It was also evaluated the crystallites size from (XRD) for the PS nanoscale. The atomic force microscopy confirmed the nano-metric size chemical fictionalization through the electrochemical etching that was shown on the PS surface chemical composition. The atomic power microscopy checks showed the roughness of the silicon surface. It is also notified (TiO2) preparation nano-particles that were prepared by pulse laser eradication in ethanol (PLAL) technique through irradiation with a Nd:YAG laser pulses TiO2 target that is sunk in methanol using 400 mJ of laser energy. It has been studied the structural, optical and morphological of TiO2NPs. It has been detected that through XRD measurement, (TiO2) NPs have been Tetragonal crystal structure. While with AFM measurements, it has been realized that the synthesized TiO2 particles are spherical with an average particle size in the (82 nm) range. It has been determined that the energy band gap of TiO2 NPs from optical properties and set to be in (5eV) range.The transmittance and reflectance spectra have determined the TiO2 NPs optical constants. It was reported the effectiveness of TiO2 NPs expansion on the PS Photodetector properties which exposes the benefits in (Al/PS/Si/Al). The built-in tension values depend on the etching time current density and laser flounce. Al/TiO2/PS/Si/Al photo-detector heterojunction have two response peaks that are situated at 350 nm and (700 -800nm) with max sensitivity ≈ 0.7 A/W. The maximum given detectivity is 9.38at ≈ 780 nm wavelength.
Response Time Measurements of the NIF DANTE XRD-31 X-Ray Diodes (Pre-print)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Don Pellinen and Michael Griffin
2009-01-23
The XRD-31 is a fast, windowless X-ray vacuum photodiode developed by EG&G. It is currently the primary fast X-ray detector used to diagnose the X-rays on NIF and OMEGA on the multichannel DANTE spectrometer. The XRD-31 has a dynamic range of less than 1e-12 amps to more than 10 amps. A technique is described to measure the impulse response of the diodes to a 150 fs pulse of 200 nm laser light and a method to calculate the “risetime” for a square pulse and compare it with the computed electron transit time from the photocathode to the anode. Measured responsemore » time for 5 XRD-31s assembled in early 2004 was 149.7 ps +-2.75 ps.« less
Study on the Curcumin dynamics and distribution through living biofilms
NASA Astrophysics Data System (ADS)
Carvalho, Mariana T.; Dovigo, Lívia N.; Rastelli, Alessandra N. S.; Bagnato, Vanderlei S.
2013-03-01
Human oral cavity is colonized by a wide range of microorganisms, often organized in biofilms. These biofilms are responsible for the pathogenesis of caries and most periodontal diseases. A possible alternative to reduce biofilms is the photodynamic inactivation (PDI). The success of the PDI depends on different factors. The time required by the PS to remain in contact with the target cells prior to illumination is determinant for the technique's efficacy. This study aimed to assess the interaction between the PS and the biofilm prior to the PDI. We used confocal microscopy and FLIM to evaluate the interaction between the PS and the biofilm's microorganism during the pre-irradiation time (PIT). The study of this dynamics can lead to the understanding of why only some PSs are effective and why is necessary a long PIT for some microorganisms. Our results showed that are differences for each PIT. These differences can be the determinate for the efficacy of the PDI. We observed that the microorganism needs time to concentrate and/or transport the PS within the biofilm. We presented preliminary results for biofilms of Candida albicans and Streptococcus mutans in the presence of Curcumin and compared it with the literature. We observed that the effectiveness of the PDI might be directly correlated to the position of the PS with the biofilm. Further analyses will be conducted in order to confirm the potential of FLIM to assess the PS dynamics within the biofilms.
Holme, Daniel; Findlow, Helen; Sow, Samba O.; Idoko, Olubukola T.; Preziosi, Marie-Pierre; Carlone, George; Plikaytis, Brian D.; Borrow, Ray
2015-01-01
Background. A group A meningococcal conjugate vaccine, PsA-TT, was licensed in 2010 and was previously studied in a phase 2 clinical trial to evaluate its safety and immunogenicity in African children 12–23 months of age. Methods. Subjects received either PsA-TT; meningococcal group A, C, W, Y polysaccharide vaccine (PsACWY); or Haemophilus influenzae type b conjugate vaccine (Hib-TT). Forty weeks following primary vaccination, the 3 groups were further randomized to receive either PsA-TT, one-fifth dose of PsACWY, or Hib-TT. Group A–specific immunoglobulin G (IgG) subclass response was characterized using an enzyme-linked immunosorbent assay. Results. The predominant IgG subclass response, regardless of vaccine, was IgG1. One month following primary vaccination, the geometric mean concentrations (GMCs) of IgG1 and IgG2 in the PsA-TT group were 21.73 µg/mL and 6.27 µg/mL, whereas in the PsACWY group the mean GMCs were 2.01 µg/mL and 0.97 µg/mL, respectively (P < .0001). Group A–specific IgG1 and IgG2 GMCs remained greater in the PsA-TT group than in the PsACWY group 40 weeks following primary vaccination (P < .0001). One week following revaccination, those given 2 doses of PsA-TT had the greatest IgG1 and IgG2 GMCs of 125.23 µg/mL and 36.12 µg/mL, respectively (P = .0008), and demonstrated a significant increase in IgG1:IgG2 mean ratio, indicative of the T-cell–dependent response associated with conjugate vaccines. Conclusions. Vaccination of African children aged 12–24 months with either PsA-TT or PsACWY elicited a predominantly IgG1 response. The IgG1:IgG2 mean ratio decreased following successive vaccination with PsACWY, indicating a shift toward IgG2, suggestive of the T-cell–independent immune response commonly associated with polysaccharide antigens. Clinical Trials Registration. SRCTN78147026. PMID:26553689
Gao, Shuibo; Suenaga, Toshiko; Oki, Yutaka; Yukie, Masao; Nakahara, Daiichiro
2011-10-01
The present experiment assessed whether prenatal stress (PS) can alter the ability of acute and chronic cocaine administration to increase and decrease the rewarding effectiveness of the medial forebrain bundle (MFB) using intracranial self-stimulation (ICSS), and also whether PS can affect the extinction of the MFB stimulation response. Adult male offspring of female rats that received PS or no PS (nPS) were implanted with MFB stimulating electrodes, and were then tested in ICSS paradigms. In both nPS and PS offspring, acute cocaine injection decreased ICSS thresholds dose-dependently. However, the threshold-lowering effects at any dose were not significantly different between groups. There was also no group-difference in the threshold-elevating effects of chronic cocaine administration. Nevertheless, chronically drug-administered PS rats exhibited a resistance to the extinguishing of the response for brain-stimulation reward when acutely treated with cocaine, as compared to extinction without cocaine treatment. The results suggest that PS may weaken the ability for response inhibition under cocaine loading in male adult offspring. Copyright © 2011 Elsevier B.V. All rights reserved.
MenAfriVac as an Antitetanus Vaccine
Borrow, Ray; Tang, Yuxiao; Yakubu, Ahmadu; Kulkarni, Prasad S.; LaForce, F. Marc
2015-01-01
Background. The group A meningococcal conjugate vaccine, PsA-TT, uses tetanus toxoid (TT) as a carrier protein (PsA-TT). TT as a carrier protein in other conjugate vaccines is known to be immunogenic and generates a robust anti-TT response. Methods. Clinical studies in Africa assessed whether PsA-TT generated tetanus serologic responses when tested in African populations (toddlers to adults). Second, the high acceptance of PsA-TT mass immunization campaigns in the 1- to 29-year age group meant that a sizeable fraction of women of reproductive age received PsA-TT. Incidence data for neonatal tetanus were reviewed for countries with and without PsA-TT campaigns to check whether this had any impact on the incidence. Results. PsA-TT generated robust tetanus serologic responses in 1- to 29-year-olds, similar to those expected after a booster dose of TT. Neonatal cases of tetanus fell by 25% in countries that completed PsA-TT campaigns in 1- to 29-year-olds. Conclusions. Although these data are not yet definitive, they are consistent with the hypothesis that improved community immunity to tetanus as a result of the PsA-TT campaigns may be having an impact on the incidence of neonatal tetanus in sub-Saharan Africa. Clinical Trials Registration. ISRCTN17662153 (PsA-TT 001); ISRTCN78147026 (PsA-TT 002); ISRCTN87739946 (PsA-TT 003); ISRCTN46335400 (PsA-TT 003a); ISRCTN82484612 (PsA-TT 004); CTRI/2009/091/000368 (PsA-TT 005); PACTR ATMR2010030001913177 (PsA-TT 006); and PACTR201110000328305 (PsA-TT 007). PMID:26553690
Transient photoconductivity in the ferromagnetic semiconductor CdCr2Se4
NASA Technical Reports Server (NTRS)
Walser, A. D.; Alfano, R. R.
1988-01-01
The transient photoconductive response time of the ferromagnetic semiconductor CdCr2Se4 was measured to be smaller than 90 ps, the response time of the scope. The measurements were performed at room temperature (300 K) for 0.53 and 1.06 microns excitations using a mode locked frequency-doubled YAG laser.
NASA Astrophysics Data System (ADS)
Gundacker, S.; Turtos, R. M.; Auffray, E.; Lecoq, P.
2018-05-01
The emergence of new solid-state avalanche photodetectors, e.g. SiPMs, with unprecedented timing capabilities opens new ways to profit from ultrafast and prompt photon emission in scintillators. In time of flight positron emission tomography (TOF-PET) and high energy timing detectors based on scintillators the ultimate coincidence time resolution (CTR) achievable is proportional to the square root of the scintillation rise time, decay time and the reciprocal light yield, CTR ∝√{τrτd / LY }. Hence, the precise study of light emission in the very first tens of picoseconds is indispensable to understand time resolution limitations imposed by the scintillator. We developed a time correlated single photon counting setup having a Gaussian impulse response function (IRF) of 63ps sigma, allowing to precisely measure the scintillation rise time of various materials with 511keV excitation. In L(Y)SO:Ce we found two rise time components, the first below the resolution of our setup <10 ps and a second component being ∼380 ps. Co-doping with Ca2+ completely suppresses the slow rise component leading to a very fast initial scintillation emission with a rise time of <10ps. A very similar behavior is observed in LGSO:Ce crystals. The results are further confirmed by complementary measurements using a streak-camera system with pulsed X-ray excitation and additional 511 keV excited measurements of Mg2+ co-doped LuAG:Ce, YAG:Ce and GAGG:Ce samples.
Kar, Swagata; Arjunaraja, Swadhinya; Akkoyunlu, Mustafa; Pier, Gerald B; Snapper, Clifford M
2016-06-01
Priming of mice with intact, heat-killed cells of Gram-negative Neisseria meningitidis, capsular serogroup C (MenC) or Gram-positive group B Streptococcus, capsular type III (GBS-III) bacteria resulted in augmented serum polysaccharide (PS)-specific IgG titers following booster immunization. Induction of memory required CD4(+) T cells during primary immunization. We determined whether PS-specific memory for IgG production was contained within the B cell and/or T cell populations, and whether augmented IgG responses following booster immunization were also dependent on CD4(+) T cells. Adoptive transfer of purified B cells from MenC- or GBS-III-primed, but not naive mice resulted in augmented PS-specific IgG responses following booster immunization. Similar responses were observed when cotransferred CD4(+) T cells were from primed or naive mice. Similarly, primary immunization with unencapsulated MenC or GBS-III, to potentially prime CD4(+) T cells, failed to enhance PS-specific IgG responses following booster immunization with their encapsulated isogenic partners. Furthermore, in contrast to GBS-III, depletion of CD4(+) T cells during secondary immunization with MenC or another Gram-negative bacteria, Acinetobacter baumannii, did not inhibit augmented PS-specific IgG booster responses of mice primed with heat-killed cells. Also, in contrast with GBS-III, booster immunization of MenC-primed mice with isolated MenC-PS, a TI Ag, or a conjugate of MenC-PS and tetanus toxoid elicited an augmented PS-specific IgG response similar to booster immunization with intact MenC. These data demonstrate that memory for augmented PS-specific IgG booster responses to Gram-negative and Gram-positive bacteria is contained solely within the B cell compartment, with a differential requirement for CD4(+) T cells for augmented IgG responses following booster immunization. Copyright © 2016 by The American Association of Immunologists, Inc.
Ivanova, Kira A; Tsyganova, Anna V; Brewin, Nicholas J; Tikhonovich, Igor A; Tsyganov, Viktor E
2015-11-01
Rhizobia are able to establish a beneficial interaction with legumes by forming a new organ, called the symbiotic root nodule, which is a unique ecological niche for rhizobial nitrogen fixation. Rhizobial infection has many similarities with pathogenic infection and induction of defence responses accompanies both interactions, but defence responses are induced to a lesser extent during rhizobial infection. However, strong defence responses may result from incompatible interactions between legumes and rhizobia due to a mutation in either macro- or microsymbiont. The aim of this research was to analyse different plant defence reactions in response to Rhizobium infection for several pea (Pisum sativum) mutants that result in ineffective symbiosis. Pea mutants were examined by histochemical and immunocytochemical analyses, light, fluorescence and transmission electron microscopy and quantitative real-time PCR gene expression analysis. It was observed that mutations in pea symbiotic genes sym33 (PsIPD3/PsCYCLOPS encoding a transcriptional factor) and sym40 (PsEFD encoding a putative negative regulator of the cytokinin response) led to suberin depositions in ineffective nodules, and in the sym42 there were callose depositions in infection thread (IT) and host cell walls. The increase in deposition of unesterified pectin in IT walls was observed for mutants in the sym33 and sym42; for mutant in the sym42, unesterified pectin was also found around degrading bacteroids. In mutants in the genes sym33 and sym40, an increase in the expression level of a gene encoding peroxidase was observed. In the genes sym40 and sym42, an increase in the expression levels of genes encoding a marker of hypersensitive reaction and PR10 protein was demonstrated. Thus, a range of plant defence responses like suberisation, callose and unesterified pectin deposition as well as activation of defence genes can be triggered by different pea single mutations that cause perception of an otherwise beneficial strain of Rhizobium as a pathogen.
Scanning SQUID sampler with 40-ps time resolution
NASA Astrophysics Data System (ADS)
Cui, Zheng; Kirtley, John R.; Wang, Yihua; Kratz, Philip A.; Rosenberg, Aaron J.; Watson, Christopher A.; Gibson, Gerald W.; Ketchen, Mark B.; Moler, Kathryn. A.
2017-08-01
Scanning Superconducting QUantum Interference Device (SQUID) microscopy provides valuable information about magnetic properties of materials and devices. The magnetic flux response of the SQUID is often linearized with a flux-locked feedback loop, which limits the response time to microseconds or longer. In this work, we present the design, fabrication, and characterization of a novel scanning SQUID sampler with a 40-ps time resolution and linearized response to periodically triggered signals. Other design features include a micron-scale pickup loop for the detection of local magnetic flux, a field coil to apply a local magnetic field to the sample, and a modulation coil to operate the SQUID sampler in a flux-locked loop to linearize the flux response. The entire sampler device is fabricated on a 2 mm × 2 mm chip and can be scanned over macroscopic planar samples. The flux noise at 4.2 K with 100 kHz repetition rate and 1 s of averaging is of order 1 mΦ0. This SQUID sampler will be useful for imaging dynamics in magnetic and superconducting materials and devices.
Scanning SQUID sampler with 40-ps time resolution.
Cui, Zheng; Kirtley, John R; Wang, Yihua; Kratz, Philip A; Rosenberg, Aaron J; Watson, Christopher A; Gibson, Gerald W; Ketchen, Mark B; Moler, Kathryn A
2017-08-01
Scanning Superconducting QUantum Interference Device (SQUID) microscopy provides valuable information about magnetic properties of materials and devices. The magnetic flux response of the SQUID is often linearized with a flux-locked feedback loop, which limits the response time to microseconds or longer. In this work, we present the design, fabrication, and characterization of a novel scanning SQUID sampler with a 40-ps time resolution and linearized response to periodically triggered signals. Other design features include a micron-scale pickup loop for the detection of local magnetic flux, a field coil to apply a local magnetic field to the sample, and a modulation coil to operate the SQUID sampler in a flux-locked loop to linearize the flux response. The entire sampler device is fabricated on a 2 mm × 2 mm chip and can be scanned over macroscopic planar samples. The flux noise at 4.2 K with 100 kHz repetition rate and 1 s of averaging is of order 1 mΦ 0 . This SQUID sampler will be useful for imaging dynamics in magnetic and superconducting materials and devices.
Ruyssen-Witrand, A; Fernandez-Lopez, C J; Gossec, L; Anract, P; Courpied, J P; Dougados, M
2011-01-01
To evaluate the psychometric properties of the OARSI-OMERACT questionnaires in comparison to the existing validated scales. Consecutive hip or knee osteoarthritis patients consulting in an orthopedic department were enrolled in the study. Data collected were pain using the Intermittent and Constant Osteoarthritis Pain (ICOAP), a Numeric Rating Scale (NRS), the Western Ontario McMaster Universities' Osteoarthritis Index (WOMAC) pain subscale, the Lequesne pain subscale; functional impairment using the Knee disability and Osteoarthritis Outcome Score-Physical Function Shortform (KOOS-PS), the Hip disability and Osteoarthritis Outcome Score-Physical Function Shortform (HOOS-PS), a NRS, the WOMAC function sub-scale, the Lequesne function subscale. Validity was assessed by calculating the Spearman's correlation coefficient between all the scales. Reliability was assessed in out-patients with stable disease comparing the data collected within 2 weeks using the intra-class correlation coefficient (ICC). Responsiveness was assessed on the data from hospitalised patients prior to and 12 weeks after a total joint replacement (TJR) using the standardised response mean. Three hundred patients (mean age=68 years, females=62%, hip OA=57%) were included. There was a moderate to good correlation between ICOAP, KOOS-PS, HOOS-PS and the WOMAC, NRS and Lequesne scales. Reliability of the ICOAP hip OA HOOS-PS and KOOS-PS was good (ICC range 0.80-0.81) whereas it was moderate for knee ICOAP (ICC=0.65). Responsiveness of the ICOAP, KOOS-PS and HOOS-PS 12 weeks after TJR was comparable to responsiveness of other scales (SRM range: 0.54-1.82). The psychometric properties of the ICOAP, KOOS-PS and HOOS-PS were comparable to those of the WOMAC, Lequesne and NRS.
NASA Astrophysics Data System (ADS)
Kasatani, Kazuo; Okamoto, Hiroaki; Takenaka, Shunsuke
2003-11-01
Third-order optical nonlinearities of sol-gel silica coating films containing metal porphyrin derivatives were measured under resonant conditions by the femtosecond degenerate four-wave mixing (DFWM) technique. Temporal profiles of the DFWM signal were measured with a time resolution of 0.3 ps, and were found to consist of two components, the coherent instantaneous nonlinear response and the delayed response with a decay time constant of several to several hundred ps. The latter can be attributed to population grating of an excited state, and contribution of slow component was very little for a zinc porphyrin derivative. The values of electronic component of the optical nonlinear susceptibility, χ(3) xxxx, for these films were ca. 2 x 10-10 esu.
Ultra-fast switching blue phase liquid crystals diffraction grating stabilized by chiral monomer
NASA Astrophysics Data System (ADS)
Manda, Ramesh; Pagidi, Srinivas; Sarathi Bhattacharya, Surjya; Yoo, Hyesun; T, Arun Kumar; Lim, Young Jin; Lee, Seung Hee
2018-05-01
We have demonstrated an ultra-fast switching and efficient polymer stabilized blue phase liquid crystal (PS-BPLC) diffraction grating utilizing a chiral monomer. We have obtained a 0.5 ms response time by a novel polymer stabilization method which is three times faster than conventional PS-BPLC. In addition, the diffraction efficiency was improved 2% with a much wider phase range and the driving voltage to switch the device is reduced. The polarization properties of the diffracted beam are unaffected by this novel polymer stabilization. This device can be useful for future photonic applications.
Hamm, Jordan P; Ethridge, Lauren E; Boutros, Nashaat N; Keshavan, Matcheri S; Sweeney, John A; Pearlson, Godfrey D; Tamminga, Carol A; Clementz, Brett A
2014-04-01
Disrupted sensory processing is a core feature of psychotic disorders. Auditory paired stimuli (PS) evoke a complex neural response, but it is uncertain which aspects reflect shared and/or distinct liability for the most common severe psychoses, schizophrenia (SZ) and psychotic bipolar disorder (BDP). Evoked time-voltage/time-frequency domain responses quantified with EEG during a typical PS paradigm (S1-S2) were compared among proband groups (SZ [n = 232], BDP [181]), their relatives (SZrel [259], BDPrel [220]), and healthy participants (H [228]). Early S1-evoked responses were reduced in SZ and BDP, while later/S2 abnormalities showed SZ/SZrel and BDP/BDPrel specificity. Relatives' effects were absent/small despite significant familiality of the entire auditorineural response. This pattern suggests general and divergent biological pathways associated with psychosis, yet may reflect complications with conditioning solely on clinical phenomenology. Copyright © 2014 Society for Psychophysiological Research.
Measurement of ortho-positronium properties in liquid scintillators
NASA Astrophysics Data System (ADS)
Perasso, S.; Consolati, G.; Franco, D.; Hans, S.; Jollet, C.; Meregaglia, A.; Tonazzo, A.; Yeh, M.
2013-08-01
Pulse shape discrimination in liquid scintillator detectors is a well-established technique for the discrimination of heavy particles from light particles. Nonetheless, it is not efficient in the separation of electrons and positrons, as they give rise to indistinguishable scintillator responses. This inefficiency can be overtaken through the exploitation of the formation of ortho-Positronium (o-Ps), which alters the time profile of light pulses induced by positrons. We characterized the o-Ps properties in the most commonly used liquid scintillators, i.e. PC, PXE, LAB, OIL and PC + PPO. In addition, we studied the effects of scintillator doping on the o-Ps properties for dopants currently used in neutrino experiments, Gd and Nd. Further measurements for Li-loaded and Tl-loaded liquid scintillators are foreseen. We found that the o-Ps properties are suitable for enhancing the electron-positron discrimination.
Takayama, Kazuo; Morisaki, Yuta; Kuno, Shuichi; Nagamoto, Yasuhito; Harada, Kazuo; Furukawa, Norihisa; Ohtaka, Manami; Nishimura, Ken; Imagawa, Kazuo; Sakurai, Fuminori; Tachibana, Masashi; Sumazaki, Ryo; Noguchi, Emiko; Nakanishi, Mahito; Hirata, Kazumasa; Kawabata, Kenji; Mizuguchi, Hiroyuki
2014-11-25
Interindividual differences in hepatic metabolism, which are mainly due to genetic polymorphism in its gene, have a large influence on individual drug efficacy and adverse reaction. Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells have the potential to predict interindividual differences in drug metabolism capacity and drug response. However, it remains uncertain whether human iPSC-derived HLCs can reproduce the interindividual difference in hepatic metabolism and drug response. We found that cytochrome P450 (CYP) metabolism capacity and drug responsiveness of the primary human hepatocytes (PHH)-iPS-HLCs were highly correlated with those of PHHs, suggesting that the PHH-iPS-HLCs retained donor-specific CYP metabolism capacity and drug responsiveness. We also demonstrated that the interindividual differences, which are due to the diversity of individual SNPs in the CYP gene, could also be reproduced in PHH-iPS-HLCs. We succeeded in establishing, to our knowledge, the first PHH-iPS-HLC panel that reflects the interindividual differences of hepatic drug-metabolizing capacity and drug responsiveness.
NASA Astrophysics Data System (ADS)
Zaug, Joseph M.; Austin, Ryan A.; Armstrong, Michael R.; Crowhurst, Jonathan C.; Goldman, Nir; Ferranti, Louis; Saw, Cheng K.; Swan, Raymond A.; Gross, Richard; Fried, Laurence E.
2018-05-01
We report experimental and computational studies of shock wave dynamics in single-crystal β-HMX on an ultrafast time scale. Here, a laser-based compression drive (˜1 ns in duration; stresses of up to ˜40 GPa) is used to propagate shock waves normal to the (110) and (010) lattice planes. Ultrafast time-domain interferometry measurements reveal distinct, time-dependent relationships between the shock wave velocity and particle velocity for each crystal orientation, which suggest evolving physical processes on a sub-nanosecond time scale. To help interpret the experimental data, elastic shock wave response was simulated using a finite-strain model of crystal thermoelasticity. At early propagation times (<500 ps), the model is in agreement with the data, which indicates that the mechanical response is dominated by thermoelastic deformation. The model agreement depends on the inclusion of nonlinear elastic effects in both the spherical and deviatoric stress-strain responses. This is achieved by employing an equation-of-state and a pressure-dependent stiffness tensor, which was computed via atomistic simulation. At later times (>500 ps), the crystal samples exhibit signatures of inelastic deformation, structural phase transformation, or chemical reaction, depending on the direction of wave propagation.
Roig, Cristina; Fita, Ana; Ríos, Gabino; Hammond, John P; Nuez, Fernando; Picó, Belén
2012-11-08
Monosporascus cannonballus is the main causal agent of melon vine decline disease. Several studies have been carried out mainly focused on the study of the penetration of this pathogen into melon roots, the evaluation of symptoms severity on infected roots, and screening assays for breeding programs. However, a detailed molecular view on the early interaction between M. cannonballus and melon roots in either susceptible or resistant genotypes is lacking. In the present study, we used a melon oligo-based microarray to investigate the gene expression responses of two melon genotypes, Cucumis melo 'Piel de sapo' ('PS') and C. melo 'Pat 81', with contrasting resistance to the disease. This study was carried out at 1 and 3 days after infection (DPI) by M. cannonballus. Our results indicate a dissimilar behavior of the susceptible vs. the resistant genotypes from 1 to 3 DPI. 'PS' responded with a more rapid infection response than 'Pat 81' at 1 DPI. At 3 DPI the total number of differentially expressed genes identified in 'PS' declined from 451 to 359, while the total number of differentially expressed transcripts in 'Pat 81' increased from 187 to 849. Several deregulated transcripts coded for components of Ca2+ and jasmonic acid (JA) signalling pathways, as well as for other proteins related to defence mechanisms. Transcriptional differences in the activation of the JA-mediated response in 'Pat 81' compared to 'PS' suggested that JA response might be partially responsible for their observed differences in resistance. As a result of this study we have identified for the first time a set of candidate genes involved in the root response to the infection of the pathogen causing melon vine decline. This information is useful for understanding the disease progression and resistance mechanisms few days after inoculation.
NASA Astrophysics Data System (ADS)
Mermut, Ozzy; Bouchard, Jean-Pierre; Cormier, Jean-Francois; Diamond, Kevin R.; Noiseux, Isabelle; Vernon, Marcia L.; Patterson, Michael S.
2007-07-01
A broadband frequency domain fluorescence lifetime system (from ns to ms time scale) has been developed to study the photochemical and photodynamic behavior of model, well-controlled photosensitizer-encapsulating liposomes. Liposomes are known to be efficient and selective photosensitizer (PS) drug delivery vesicles, however, their chemical and physical effects on the photochemical properties of the photosensitizer have not been well characterized. The liposomes employed in this study (both blank and photosensitizer-complexed) were characterized to determine their: a) size distribution (dynamic light scattering), b) image (scanning electron microscope, confocal fluorescence microscopy), c) concentration of particles (flow cytometry), d) temperature-dependant phase transition behavior (differential scanning calorimetry, and e) spectrofluorescent spectrophotometric properties, e.g. aggregation, in the confined environment. The fluorescence decay behavior of two families of encapsulated photosensitizers, di-and tetrasulfonated metallophthalocyanines, and 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH), has been examined as a function of the liposome's physical properties (size-scale, distribution and concentration of scatterer) and the impact of the photosensitizer spatial confinement determined. It is found that the achievable size range and distribution of the PS-liposomes is controlled by the chemical nature of the PS for large liposomes (1000 nm), and is PS independent for small PS-liposomes (~140nm). The lifetime decay behavior was studied for all three photosensitizer-liposome systems and compared before and after confinement. We found the nature of the decay to be similar before and after encapsulation for the sulfonated phthalocyanines containing ionic moieties (primarily monoexponential) but not for HPPH. In the latter, the decay transitioned from multi- to monoexponential decay upon localizing lypophilic HPPH to the liposomal membrane. This behavior was confirmed by obtaining a similar change in lifetime response with an independent timedomain system. We also varied the environment in temperature and oxygen content to examine the effects on the fluorescent lifetimes of the liposomal complexes. The fluorescence decay of all three PS-containing liposomes showed that the local spatial confinement of PS (dictated by the PS chemistry) into different domains within the liposome directly controls the temperature-response. Membrane-bound photosensitizers were less sensitive to temperature effects as illustrated by the decay dynamics observed in solu, that is, they developed a unique decay behavior that correlated with the phase transition of the membrane. The fluorescent lifetime of PS-encapsulated liposomes in deoxygenated environments, relevant to oxygen independent type I phototoxicity, was also probed in the frequency-domain revealing that liposome-confined PS display very different trends than those observed in solu.
Time-resolved photon echoes from donor-bound excitons in ZnO epitaxial layers
NASA Astrophysics Data System (ADS)
Poltavtsev, S. V.; Kosarev, A. N.; Akimov, I. A.; Yakovlev, D. R.; Sadofev, S.; Puls, J.; Hoffmann, S. P.; Albert, M.; Meier, C.; Meier, T.; Bayer, M.
2017-07-01
The coherent optical response from 140 nm and 65 nm thick ZnO epitaxial layers is studied using four-wave-mixing spectroscopy with picosecond temporal resolution. Resonant excitation of neutral donor-bound excitons results in two-pulse and three-pulse photon echoes. For the donor-bound A exciton (D0XA ) at temperature of 1.8 K we evaluate optical coherence times T2=33 -50 ps corresponding to homogeneous line widths of 13 -19 μ eV , about two orders of magnitude smaller as compared with the inhomogeneous broadening of the optical transitions. The coherent dynamics is determined mainly by the population decay with time T1=30 -40 ps, while pure dephasing is negligible. Temperature increase leads to a significant shortening of T2 due to interaction with acoustic phonons. In contrast, the loss of coherence of the donor-bound B exciton (D0XB ) is significantly faster (T2=3.6 ps ) and governed by pure dephasing processes.
Therapeutic Responses to Different Antimalarial Drugs in Vivax Malaria
Pukrittayakamee, Sasithon; Chantra, Arun; Simpson, Julie A.; Vanijanonta, Sirivan; Clemens, Ralf; Looareesuwan, Sornchai; White, Nicholas J.
2000-01-01
The therapeutic responses to the eight most widely used antimalarial drugs were assessed in 207 adult patients with Plasmodium vivax malaria. This parasite does not cause marked sequestration, so parasite clearance can be used as a direct measure of antimalarial activity. The activities of these drugs in descending order were artesunate, artemether, chloroquine, mefloquine, quinine, halofantrine, primaquine, and pyrimethamine-sulfadoxine (PS). Therapeutic responses to PS were poor; parasitemias did not clear in 5 of the 12 PS-treated patients, whereas all the other patients made an initial recovery. Of 166 patients monitored for ≥28 days, 35% had reappearance of vivax malaria 11 to 65 days later and 7% developed falciparum malaria 5 to 21 days after the start of treatment. There were no significant differences in the times taken for vivax malaria reappearance among the different groups except for those given mefloquine and chloroquine, in which all vivax malaria reappearances developed >28 days after treatment, suggesting suppression of the first relapse by these slowly eliminated drugs. There was no evidence of chloroquine resistance. The antimalarial drugs vary considerably in their intrinsic activities and stage specificities of action. PMID:10817728
Nie, Hailiang; Jing, Jing; Tian, Yong; Yang, Wen; Zhang, Rubo; Zhang, Xiaoling
2016-04-13
Cellular self-regulation of reactive oxygen species (ROS) stress via glutathione (GSH) antioxidant repair plays a crucial role in maintaining redox balance, which affects various physiological and pathological pathways. In this work, we developed a simple yet effective strategy for reversible, dynamic, and real-time fluorescence imaging of ROS stress and GSH repair, based on novel Ge-pyronine dyes (GePs). Unlike the current O-pyronine (OP) dye, the fluorescence of GePs can be quenched in GSH reduction and then greatly restored by ROS (e.g., ClO(-), ONOO(-), and HO(•)) oxidation because of their unique affinity toward thiols. The "on-off" and "off-on" fluorescence switch can complete in 10 and 20 s, respectively, and exhibit excellent reversibility in vitro and in cells. GePs also show excitation in the long wavelength from the deep-red to near-infrared (NIR) (621-662 nm) region, high fluorescence quantum yield (Φ(fl) = 0.32-0.44) in aqueous media, and excellent cell permeability. Our results demonstrated that GePs can be used for real-time monitoring of the reversible and dynamic interconversion between ROS oxidation and GSH reduction in living cells. GePs might be a useful tool for investigating various redox-related physiological and pathological pathways.
NASA Technical Reports Server (NTRS)
Sugano, Mami; Nakagawa, Yuriko; Nyunoya, Hiroshi; Nakamura, Teruko
2004-01-01
Expressions of the gibberellin biosynthesis gene were investigated in a normal upright type and a gravi-response mutant, a weeping type of Japanese flowering cherry (Prunus spachiana), that is unable to support its own weight and elongates downward. A segment of the gibberellin 3 beta-hydroxylase cDNA of Prunus spachiana (Ps3ox), which is responsible for active gibberellin synthesis, was amplified by using real-time RT-PCR. The content of Ps3ox mRNA in the weeping type was much greater than that in the upright type, while the endogenous gibberellin level was much higher in the elongating zone of the weeping type. These results suggest that the amount and distribution of synthesized gibberellin regulate secondary xylem formation, and the unbalanced distribution of gibberellin affects the gravi-response of the Prunus tree.
Predictors of response to intra-articular steroid injection in psoriatic arthritis.
Eder, Lihi; Chandran, Vinod; Ueng, Joanna; Bhella, Sita; Lee, Ker-Ai; Rahman, Proton; Pope, Angela; Cook, Richard J; Gladman, Dafna D
2010-07-01
To assess the effectiveness of IA corticosteroid (IAS) injections in PsA and to determine the association between macrophage migration inhibition factor (MIF) gene polymorphism and response to IAS injections. A cohort analysis of PsA patients who were followed prospectively was performed. Clinical response was defined as no tenderness or effusion in the injected joint at 3 months. Relapse was defined as re-occurrence of joint pain or effusion. MIF 173C > G genotyping (rs755622) was performed. Two hundred and twenty patients with 245 IAS injections were included in the study. The probability of responding at 3 months was 41.6%. Within 12 months, 25.5% of the joints relapsed. Clinical factors that were associated with response included duration of psoriasis [Odds ratio (OR) 1.03] and the use of MTX or anti-TNF agents at the time of injection (OR 2.68). Factors that were associated with relapse included injection into large joints (OR 4.58) and elevated sedimentation rate (OR 15.0), whereas absence of clinical and/or radiographic damage (OR 0.23) and duration of PsA (OR 0.92) reduced risk of relapse. MIF polymorphism was not associated with clinical response, but was associated with relapse (OR 3.2). On multivariate analysis including clinical covariates, the association between MIF polymorphism and relapse was lost. IAS injections are effective in PsA. MIF gene polymorphism is associated with relapse. However, this effect is explained by clinical variables that reflect disease activity, suggesting that MIF gene polymorphism influences inflammatory activity.
Time-resolved terahertz dynamics in thin films of the topological insulator Bi 2Se 3
Valdés Aguilar, R.; Qi, J.; Brahlek, M.; ...
2015-01-07
We use optical pump–THz probe spectroscopy at low temperatures to study the hot carrier response in thin Bi 2Se 3 films of several thicknesses, allowing us to separate the bulk from the surface transient response. We find that for thinner films the photoexcitation changes the transport scattering rate and reduces the THz conductivity, which relaxes within 10 picoseconds (ps). For thicker films, the conductivity increases upon photoexcitation and scales with increasing both the film thickness and the optical fluence, with a decay time of approximately 5 ps as well as a much higher scattering rate. Furthermore, these different dynamics aremore » attributed to the surface and bulk electrons, respectively, and demonstrate that long-lived mobile surface photo-carriers can be accessed independently below certain film thicknesses for possible optoelectronic applications.« less
NASA Astrophysics Data System (ADS)
Régis, J.-M.; Saed-Samii, N.; Rudigier, M.; Ansari, S.; Dannhoff, M.; Esmaylzadeh, A.; Fransen, C.; Gerst, R.-B.; Jolie, J.; Karayonchev, V.; Müller-Gatermann, C.; Stegemann, S.
2016-07-01
The electronic γ-γ fast-timing technique using arrays consisting of many LaBr3(Ce) detectors is a powerful method to determine lifetimes of nuclear excited states with a lower limit of about 5 ps. This method requires the determination of the energy-dependent time walk of the zero time which is represented by the centroid of a prompt γ-γ time distribution. The full-energy peak versus full-energy peak prompt response difference which represents the linearly combined mean γ-γ time walk of a fast-timing array consisting of 8 LaBr3(Ce) detectors was measured using a standard 152Eu γ-ray source for the energy region of 40-1408 keV. The data were acquired using a "multiplexed-start and multiplexed-stop" analogue electronics circuitry and analysed by employing the generalized centroid difference method. Concerning the cylindrical 1.5 in.×1.5 in. LaBr3(Ce) crystals which are coupled to the Hamamatsu R9779 photomultiplier tubes, the best fast-timing array time resolution of 202(3) ps is obtained for the two prompt γ lines of 60Co by using the leading-edge timing principle. When using the zero-crossover timing principle the time resolution is degraded by up to 30%, dependent on the energy and the shaping delay time of the constant fraction discriminator model Ortec 935. The smallest γ-γ time walk to below 50 ps is obtained by using a shaping delay time of about 17 ns and an optimum "time-walk adjustment" needed for detector output pulses with amplitudes smaller than 400 mV.
NASA Astrophysics Data System (ADS)
Isabelle, Martin; O'Hara, Julia A.; Samkoe, Kimberley S.; Hoopes, P. Jack; Mosse, Sandy; Pereira, Stephen; Hasan, Tayyaba; Pogue, Brian W.
2010-02-01
Photodynamic therapy (PDT) mediated with Verteporfin is being investigated as a pancreatic cancer treatment in the cases for non-surgical candidates. Tissue response to PDT is based on a number of parameters including photosensitizer (PS) dose, light dose and time interval between light application and PS injection. In this study, PS uptake and distribution in animal leg muscle, oral cavity tissues, pancreas and tumor was measured in vivo using light-induced fluorescence spectroscopy (LIFS) via an Aurora Optics Inc. PDT fluorescence dosimeter. An orthotopic pancreatic cancer model (AsPC-1) was implanted in SCID mice and treated with the PS. Probe measurements were made using a surface probe and an interstitial needle probe before and up to one hour after intravenous tail vein injection of the PS. The study demonstrated that it is possible to correlate in-vivo LIFS measurements of the PS uptake in the pancreas with measurements taken from the oral cavity indicating that light dosimetry of PDT of the pancreas can be ascertained from the LIFS measurements in the oral cavity. These results emphasize the importance of light dosimetry in improving the therapeutic outcome of PDT through light dose adaptation to the relative in situ tissue PS concentration.
Morgan, Janet; Jackson, Jennifer D.; Zheng, Xiang; Pandey, Suresh K.; Pandey, Ravindra K.
2010-01-01
Photosensitizers (PS) synthesized with the aim of optimizing photodynamic therapy (PDT) of tumors do not always fulfill their potential when tested in vitro and in vivo in different tumor models. The ATP-dependent transporter ABCG2 a multi-drug resistant pump expressed at variable levels in cancerous cells, can bind and efflux a wide range of structurally different classes of compounds including several PS used pre-clinically and clinically such as porphyrins and chlorins. ABCG2 may lower intracellular levels of substrate PS below the threshold for cell death in tumors treated by PDT, leaving resistant cells to re-populate the tumor. To determine some of the structural factors that affect substrate affinity of PS for ABCG2, we used an ABCG2 expressing cell line (HEK 293 482R) and its non-expressing counterpart, and tyrosine kinase ABCG2 inhibitors in a simple flow cytometric assay to identify PS effluxed by the ABCG2 pump. We tested a series of conjugates of substrate PS with different groups attached at different positions on the tetrapyrrole macrocycle to examine whether a change in affinity for the pump occurred and whether such changes depended on the position or the structure/type of the attached group. PS without substitutions including pyropheophorbides and purpurinimides were generally substrates for ABCG2, but carbohydrate groups conjugated at positions 8, 12, 13 and 17 but not at position 3 abrogated ABCG2 affinity regardless of structure or linking moiety. At position 3, affinity was retained with the addition of iodobenzene, alkyl chains and monosaccharides, but not with disaccharides. This suggests that structural characteristics at position 3 may offer important contributions to requirements for binding to ABCG2. We examined several tumor cell lines for ABCG2 activity, and found that although some cell lines had negligible ABCG2 activity in bulk, they contained a small ABCG2-expressing side population (SP) thought to contain cells which are responsible for initiating tumor regrowth. We examined the relevance of the SP to PDT resistance with ABCG2 substrates in vitro and in vivo in the murine mammary tumor 4T1. We show for the first time in vivo that the substrate PS HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a) but not the non-substrate PS HPPH-Gal (a galactose conjugate of HPPH) selectively preserved the SP which was primarily responsible for regrowth in vitro. The SP could be targeted by addition of imatinib mesylate, a tyrosine kinase inhibitor which inhibits the ATPase activity of ABCG2, and prevents efflux of substrates. A PDT resistant SP may be responsible for recurrences observed both pre-clinically and clinically. To prevent ABCG2 mediated resistance, choosing non-substrate PS or administering an ABCG2 inhibitor alongside a substrate PS might be advantageous when treating ABCG2 expressing tumors with PDT. PMID:20684544
Laird, Barry J A; Fallon, Marie; Hjermstad, Marianne J; Tuck, Sharon; Kaasa, Stein; Klepstad, Pål; McMillan, Donald C
2016-08-10
Quality of life is a key component of cancer care; however, the factors that determine quality of life are not well understood. The aim of this study was to examine the relationship between quality of life parameters, performance status (PS), and the systemic inflammatory response in patients with advanced cancer. An international biobank of patients with advanced cancer was analyzed. Quality of life was assessed at a single time point by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ-C30). PS was assessed by using the Eastern Cooperative Oncology Group (ECOG) classification. Systemic inflammation was assessed by using the modified Glasgow Prognostic Score (mGPS), which combines C-reactive protein and albumin. The relationship between quality of life parameters, ECOG PS, and the mGPS was examined. Data were available for 2,520 patients, and the most common cancers were GI (585 patients [22.2%]) and pulmonary (443 patients [17.6%]). The median survival was 4.25 months (interquartile range, 1.36 to 12.9 months). Increasing mGPS (systemic inflammation) and deteriorating PS were associated with deterioration in quality-of-life parameters (P < .001). Increasing systemic inflammation was associated with deterioration in quality-of-life parameters independent of PS. Systemic inflammation was associated with quality-of-life parameters independent of PS in patients with advanced cancer. Further investigation of these relationships in longitudinal studies and investigations of possible effects of attenuating systemic inflammation are now warranted. © 2016 by American Society of Clinical Oncology.
Excited-state dynamics of the medicinal pigment curcumin in a hydrogel.
Harada, Takaaki; Lincoln, Stephen F; Kee, Tak W
2016-10-12
Curcumin is a yellow polyphenol with multiple medicinal effects. These effects, however, are limited due to its poor aqueous stability and solubility. A hydrogel of 3% octadecyl randomly substituted polyacrylate (PAAC18) has been shown to provide high aqueous stability for curcumin under physiological conditions, offering a route for photodynamic therapy. In this study, the excited-state photophysics of curcumin in the PAAC18 hydrogel is investigated using a combination of femtosecond transient absorption and fluorescence upconversion spectroscopy. The transient absorption results reveal a multiexponential decay in the excited-state kinetics with fast (1 ps & 15 ps) and slow (110 ps & ≈5 ns) components. The fast decay component exhibits a deuterium isotope effect with D 2 O in the hydrogel, indicating that the 15 ps decay component is attributable to excited-state intramolecular hydrogen atom transfer of curcumin in the PAAC18 hydrogel. In addition, solvent reorganisation of excited-state curcumin is investigated using multiwavelength femtosecond fluorescence upconversion spectroscopy. The results show that the dominant solvation response (τ = 0.08 ps) is a fast inertial motion owing to the presence of bulk-like water in the vicinity of the hydrophobic octadecyl substituents of the PAAC18 hydrogel. The results also show an additional response with longer time constants of 1 and 6 ps, which is attributable to translational diffusion of confined water molecules in the three-dimensional, cross-linking network of the octadecyl substituents of PAAC18. Overall, we show that excited-state intramolecular hydrogen atom transfer and solvent reorganisation are major photophysical events for curcumin in the PAAC18 hydrogel.
Wang, Bin; Shen, Fei; Zhu, Shijiang
2018-01-01
Harvested fruits are still living organs and respond to environmental stimuli. Low temperature storage is effective in extending life of harvested fruit, but it may also cause chilling injury. Cold acclimation has been shown to induce chilling tolerance in plants, but what proteomic changes caused by cold acclimation are related to defense against chilling stress remains largely unclear. Here, 3 d of pre-storage cold acclimation (PsCA) at 10°C reduced chilling injury and secondary disease severity in cucumber stored at 5°C by 51 and 94%, respectively, compared with the control which was directly stored at 5°C. Proteomic analysis of cucumber peel identified 21 significant differentially-accumulated proteins (SDAPs) right after PsCA treatment and 23 after the following cold storage (PsCA+CS). These proteins are mainly related to stress response and defense (SRD), energy metabolism, protein metabolism, signal transduction, primary metabolism, and transcription. The SRD proteins, which made up 37% of the 21 and 47% of the 23, respectively, represented the largest class of SDAPs, and all but one protein were up-regulated, suggesting accumulation of proteins involved in defense response is central feature of proteomic profile changes brought about by PsCA. In fruit just after PsCA treatment, the identified SDAPs are related to responses to various stresses, including chilling, salt stress, dehydration, fungi, bacteria, insects, and DNA damage. However, after prolonged cold storage, the targeted proteins in acclimated fruit were narrowed down in scope to those involved in defense against chilling and pathogens. The change patterns at the transcription level of the majority of the up-regulated differentially-accumulated proteins were highly consistent with those at protein level. Taken all, the results suggest that the short-time cold acclimation initiated comprehensive defense responses in cucumber fruit at first, while the long term storage thereafter altered the responses more specifically to chilling. These findings add to the understanding of plants' molecular responses to cold acclimation. PMID:29403505
Wang, Bin; Shen, Fei; Zhu, Shijiang
2017-01-01
Harvested fruits are still living organs and respond to environmental stimuli. Low temperature storage is effective in extending life of harvested fruit, but it may also cause chilling injury. Cold acclimation has been shown to induce chilling tolerance in plants, but what proteomic changes caused by cold acclimation are related to defense against chilling stress remains largely unclear. Here, 3 d of pre-storage cold acclimation (PsCA) at 10°C reduced chilling injury and secondary disease severity in cucumber stored at 5°C by 51 and 94%, respectively, compared with the control which was directly stored at 5°C. Proteomic analysis of cucumber peel identified 21 significant differentially-accumulated proteins (SDAPs) right after PsCA treatment and 23 after the following cold storage (PsCA+CS). These proteins are mainly related to stress response and defense (SRD), energy metabolism, protein metabolism, signal transduction, primary metabolism, and transcription. The SRD proteins, which made up 37% of the 21 and 47% of the 23, respectively, represented the largest class of SDAPs, and all but one protein were up-regulated, suggesting accumulation of proteins involved in defense response is central feature of proteomic profile changes brought about by PsCA. In fruit just after PsCA treatment, the identified SDAPs are related to responses to various stresses, including chilling, salt stress, dehydration, fungi, bacteria, insects, and DNA damage. However, after prolonged cold storage, the targeted proteins in acclimated fruit were narrowed down in scope to those involved in defense against chilling and pathogens. The change patterns at the transcription level of the majority of the up-regulated differentially-accumulated proteins were highly consistent with those at protein level. Taken all, the results suggest that the short-time cold acclimation initiated comprehensive defense responses in cucumber fruit at first, while the long term storage thereafter altered the responses more specifically to chilling. These findings add to the understanding of plants' molecular responses to cold acclimation.
NASA Astrophysics Data System (ADS)
Miller, Joseph Daniel
Hybrid femtosecond/picosecond coherent anti-Stokes Raman scattering (fs/ps CARS) is employed for quantitative gas-phase temperature measurements in combustion processes and heated flows. In this approach, ultrafast 100-fs laser pulses are used to induce vibrational and rotational transitions in N2 and O2, while a third spectrally narrowed picosecond pulse is used to probe the molecular response. Temporal suppression of the nonresonant contribution and elimination of collisional effects are achieved by delay of the probe pulse, while sufficient spectral resolution is maintained for frequency-domain detection and thermometry. A theoretical framework is developed to model experimental spectra by phenomenologically describing the temporal evolution of the vibrational and rotational wavepackets as a function of temperature and pressure. Interference-free, single-shot vibrational fs/ps CARS thermometry is demonstrated at 1-kHz from 1400-2400 K in a H2-air flame, with accuracy better than 3%. A time-asymmetric exponential pulse shape is introduced to optimize nonresonant suppression with a 103 reduction at a probe delay of 0.31 ps. Low-temperature single-shot thermometry (300-700 K) with better than 1.5% accuracy is demonstrated using a fully degenerate rotational fs/ps CARS scheme, and the influence of collision energy transfer on thermometry error is quantified at atmospheric pressure. Interference-free thermometry, without nonresonant contributions and collision-induced error, is demonstrated for the first time using rotational fs/ps CARS at room temperature and pressures from 1-15 atm. Finally, the temporal and spectral resolution of fs/ps CARS is exploited for transition-resolved time-domain measurements of N2 and O2 self-broadened
Currie, Marc; Dianat, Pouya; Persano, Anna; Martucci, Maria Concetta; Quaranta, Fabio; Cola, Adriano; Nabet, Bahram
2013-01-01
Low temperature growth of GaAs (LT-GaAs) near 200 °C results in a recombination lifetime of nearly 1 ps, compared with approximately 1 ns for regular temperature ∼600 °C grown GaAs (RT-GaAs), making it suitable for ultra high speed detection applications. However, LT-GaAs detectors usually suffer from low responsivity due to low carrier mobility. Here we report electro-optic sampling time response measurements of a detector that employs an AlGaAs heterojunction, a thin layer of LT-GaAs, a channel of RT-GaAs, and a vertical electric field that together facilitate collection of optically generated electrons while suppressing collection of lower mobility holes. Consequently, these devices have detection efficiency near that of RT-GaAs yet provide pulse widths nearly an order of magnitude faster—∼6 ps for a cathode-anode separation of 1.3 μm and ∼12 ps for distances more than 3 μm. PMID:23429510
Pseudomonas aeruginosa Type III Secretory Toxin ExoU and Its Predicted Homologs.
Sawa, Teiji; Hamaoka, Saeko; Kinoshita, Mao; Kainuma, Atsushi; Naito, Yoshifumi; Akiyama, Koichi; Kato, Hideya
2016-10-26
Pseudomonas aeruginosa ExoU, a type III secretory toxin and major virulence factor with patatin-like phospholipase activity, is responsible for acute lung injury and sepsis in immunocompromised patients. Through use of a recently updated bacterial genome database, protein sequences predicted to be homologous to Ps. aeruginosa ExoU were identified in 17 other Pseudomonas species ( Ps. fluorescens , Ps. lundensis , Ps. weihenstephanensis , Ps. marginalis, Ps. rhodesiae, Ps. synxantha , Ps. libanensis , Ps. extremaustralis , Ps. veronii , Ps. simiae , Ps. trivialis , Ps. tolaasii , Ps. orientalis , Ps. taetrolens , Ps. syringae , Ps. viridiflava , and Ps. cannabina ) and 8 Gram-negative bacteria from three other genera ( Photorhabdus , Aeromonas , and Paludibacterium ). In the alignment of the predicted primary amino acid sequences used for the phylogenetic analyses, both highly conserved and nonconserved parts of the toxin were discovered among the various species. Further comparative studies of the predicted ExoU homologs should provide us with more detailed information about the unique characteristics of the Ps. aeruginosa ExoU toxin.
Correlates of protection for enteric vaccines.
Holmgren, Jan; Parashar, Umesh D; Plotkin, Stanley; Louis, Jacques; Ng, Su-Peing; Desauziers, Eric; Picot, Valentina; Saadatian-Elahi, Mitra
2017-06-08
An immunological Correlate of Protection (CoP) is an immune response that is statistically interrelated with protection. Identification of CoPs for enteric vaccines would help design studies to improve vaccine performance of licensed vaccines in low income settings, and would facilitate the testing of future vaccines in development that might be more affordable. CoPs are lacking today for most existing and investigational enteric vaccines. In order to share the latest information on CoPs for enteric vaccines and to discuss novel approaches to correlate mucosal immune responses in humans with protection, the Foundation Mérieux organized an international conference of experts where potential CoPs for vaccines were examined using case-studies for both bacterial and viral enteric pathogens. Experts on the panel concluded that to date, all established enteric vaccine CoPs, such as those for hepatitis A, Vi typhoid and poliovirus vaccines, are based on serological immune responses even though these may poorly reflect the relevant gut immune responses or predict protective efficacy. Known CoPs for cholera, norovirus and rotavirus could be considered as acceptable for comparisons of similarly composed vaccines while more work is still needed to establish CoPs for the remaining enteric pathogens and their candidate vaccines. Novel approaches to correlate human mucosal immune responses with protection include the investigation of gut-originating antibody-secreting cells (ASCs), B memory cells and follicular helper T cells from samples of peripheral blood during their recirculation. Copyright © 2017.
Zorek, Joseph A; MacLaughlin, Eric J; Fike, David S; MacLaughlin, Anitra A; Samiuddin, Mohammed; Young, Rodney B
2014-05-20
The Student Perceptions of Physician-Pharmacist Interprofessional Clinical Education (SPICE) instrument contains 10 items, 3 factors (interprofessional teamwork and team-based practice, roles/responsibilities for collaborative practice, and patient outcomes from collaborative practice), and utilizes a five-point response scale (1 = strongly disagree, 5 = strongly agree). Given the SPICE instrument's demonstrated validity and reliability, the objective of this study was to evaluate whether it was capable of measuring changes in medical (MS) and pharmacy students' (PS) perceptions following an interprofessional education (IPE) experience. In this prospective cohort study, MS and PS completed the SPICE instrument before and after participation in a predefined IPE experience. Descriptive statistics were used to characterize students and pre-post responses. Independent samples t tests and Fisher's Exact tests were used to assess group difference in demographic variables. Mann Whitney U tests were used to assess between-group differences in item scores. Wilcoxon Signed-Rank tests were used to evaluate post-participation changes in item scores. Spearman correlations were calculated to assess associations between ordinal demographic variables and item scores, and whether the number of clinic visits completed was associated with post-test responses. Paired samples t tests were used to calculate mean score changes for each of the factors. Thirty-four MS and 15 PS were enroled. Baseline differences included age (25.3. ± 1.3 MS vs. 28.7 ± 4.4 PS; p = 0.013), years full-time employment (0.71 ± 0.97 MS vs. 4.60 ± 4.55 PS; p < 0.001), and number of prior IPE rotations (1.41 ± 1.74 MS vs. 3.13 ± 2.1 PS; p < 0.001). Two items generated baseline differences; 1 persisted post-participation: whether MS/PS should be involved in teamwork (3.91 MS vs. 4.60 PS; p < 0.001). For all students, significant mean score increases were observed for role clarity ("my role" [3.72 vs. 4.11; p = 0.001] and "others' roles" [3.87 vs. 4.17; p = 0.001]), impact of teamwork on patient satisfaction (3.72 vs. 4.34; p < 0.001), and ideal curricular location for IPE (4.06 vs. 4.34; p = 0.002). Significant increases were observed for all three factors (teamwork, p = 0.003; roles/responsibilities and patient outcomes, p < 0.001). This study demonstrated the SPICE instrument's ability to measure changes in perception for medical and pharmacy students exposed to an IPE experience, both at the individual item level and at the factor level.
Seydoux, Emilie; Rothen-Rutishauser, Barbara; Nita, Izabela M; Balog, Sandor; Gazdhar, Amiq; Stumbles, Philip A; Petri-Fink, Alke; Blank, Fabian; von Garnier, Christophe
2014-01-01
Introduction Nanosized particles may enable therapeutic modulation of immune responses by targeting dendritic cell (DC) networks in accessible organs such as the lung. To date, however, the effects of nanoparticles on DC function and downstream immune responses remain poorly understood. Methods Bone marrow–derived DCs (BMDCs) were exposed in vitro to 20 or 1,000 nm polystyrene (PS) particles. Particle uptake kinetics, cell surface marker expression, soluble protein antigen uptake and degradation, as well as in vitro CD4+ T-cell proliferation and cytokine production were analyzed by flow cytometry. In addition, co-localization of particles within the lysosomal compartment, lysosomal permeability, and endoplasmic reticulum stress were analyzed. Results The frequency of PS particle–positive CD11c+/CD11b+ BMDCs reached an early plateau after 20 minutes and was significantly higher for 20 nm than for 1,000 nm PS particles at all time-points analyzed. PS particles did not alter cell viability or modify expression of the surface markers CD11b, CD11c, MHC class II, CD40, and CD86. Although particle exposure did not modulate antigen uptake, 20 nm PS particles decreased the capacity of BMDCs to degrade soluble antigen, without affecting their ability to induce antigen-specific CD4+ T-cell proliferation. Co-localization studies between PS particles and lysosomes using laser scanning confocal microscopy detected a significantly higher frequency of co-localized 20 nm particles as compared with their 1,000 nm counterparts. Neither size of PS particle caused lysosomal leakage, expression of endoplasmic reticulum stress gene markers, or changes in cytokines profiles. Conclusion These data indicate that although supposedly inert PS nanoparticles did not induce DC activation or alteration in CD4+ T-cell stimulating capacity, 20 nm (but not 1,000 nm) PS particles may reduce antigen degradation through interference in the lysosomal compartment. These findings emphasize the importance of performing in-depth analysis of DC function when developing novel approaches for immune modulation with nanoparticles. PMID:25152619
Gilio, Karen; van Kruchten, Roger; Braun, Attila; Berna-Erro, Alejandro; Feijge, Marion A H; Stegner, David; van der Meijden, Paola E J; Kuijpers, Marijke J E; Varga-Szabo, David; Heemskerk, Johan W M; Nieswandt, Bernhard
2010-07-30
In platelets, STIM1 has been recognized as the key regulatory protein in store-operated Ca(2+) entry (SOCE) with Orai1 as principal Ca(2+) entry channel. Both proteins contribute to collagen-dependent arterial thrombosis in mice in vivo. It is unclear whether STIM2 is involved. A key platelet response relying on Ca(2+) entry is the surface exposure of phosphatidylserine (PS), which accomplishes platelet procoagulant activity. We studied this response in mouse platelets deficient in STIM1, STIM2, or Orai1. Upon high shear flow of blood over collagen, Stim1(-/-) and Orai1(-/-) platelets had greatly impaired glycoprotein (GP) VI-dependent Ca(2+) signals, and they were deficient in PS exposure and thrombus formation. In contrast, Stim2(-/-) platelets reacted normally. Upon blood flow in the presence of thrombin generation and coagulation, Ca(2+) signals of Stim1(-/-) and Orai1(-/-) platelets were partly reduced, whereas the PS exposure and formation of fibrin-rich thrombi were normalized. Washed Stim1(-/-) and Orai1(-/-) platelets were deficient in GPVI-induced PS exposure and prothrombinase activity, but not when thrombin was present as co-agonist. Markedly, SKF96365, a blocker of (receptor-operated) Ca(2+) entry, inhibited Ca(2+) and procoagulant responses even in Stim1(-/-) and Orai1(-/-) platelets. These data show for the first time that: (i) STIM1 and Orai1 jointly contribute to GPVI-induced SOCE, procoagulant activity, and thrombus formation; (ii) a compensating Ca(2+) entry pathway is effective in the additional presence of thrombin; (iii) platelets contain two mechanisms of Ca(2+) entry and PS exposure, only one relying on STIM1-Orai1 interaction.
Lynn, Freyja; Mocca, Brian; Borrow, Ray; Findlow, Helen; Hassan-King, Musa; Preziosi, Marie-Pierre; Idoko, Olubukola; Sow, Samba; Kulkarni, Prasad; LaForce, F. Marc
2014-01-01
A meningococcal group A polysaccharide (PS) conjugate vaccine (PsA-TT) has been developed for African countries affected by epidemic meningitis caused by Neisseria meningitidis. Complement-mediated serum bactericidal antibody (SBA) assays are used to assess protective immune responses to meningococcal vaccination. Human complement (hC′) was used in early studies demonstrating antibody-mediated protection against disease, but it is difficult to obtain and standardize. We developed and evaluated a method for sourcing hC′ and then used the SBA assay with hC′ (hSBA) to measure bactericidal responses to PsA-TT vaccination in 12- to 23-month-old African children. Sera with active complement from 100 unvaccinated blood donors were tested for intrinsic bactericidal activity, SBA titer using rabbit complement (rSBA), and anti-group A PS antibody concentration. Performance criteria and pooling strategies were examined and then verified by comparisons of three independently prepared hC′ lots in two laboratories. hSBA titers of clinical trial sera were then determined using this complement sourcing method. Two different functional antibody tests were necessary for screening hC′. hSBA titers determined using three independent lots of pooled hC′ were within expected assay variation among lots and between laboratories. In African toddlers, PsA-TT elicited higher hSBA titers than meningococcal polysaccharide or Hib vaccines. PsA-TT immunization or PS challenge of PsA-TT-primed subjects resulted in vigorous hSBA memory responses, and titers persisted in boosted groups for over a year. Quantifying SBA using pooled hC′ is feasible and showed that PsA-TT was highly immunogenic in African toddlers. PMID:24671551
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Tong; Meng, Zhiyun; Zhu, Xiaoxia
Protamine sulfate (PS), the only clinically approved antidote to unfractionated heparin (UFH), is widely used for cardiopulmonary surgery or other extracorporeal circulation situations. However, the applications of PS have accompanied various severe side-effects. In this study, we presented a novel synthesized peptide compound (RRRRR-RRRRR-RRRRR-sulfate, R15S) served as a safer UFH antidote. Comparison studies were conducted between PS and R15S on efficacy and safety, aided by heparin neutralization studies, drug toxicity studies and anaphylactic analysis. Our research demonstrated that R15S contained comparable UFH neutralization activity in vitro and in rats in vivo as to active partial thromboplastin time (APTT) and anti-FXa assays. Theremore » was no cytotoxicity for R15S at 60 μg mg{sup −1} or below and the median lethal dose (LD{sub 50}) of R15S in mice was 35.4 mg kg{sup −1}, both of which were similar to that of PS. Furthermore, R15S exhibited no immunogenicity while it was obvious in guinea pigs immunized with PS. The level of cross-reactivity to anti-PS antibodies of R15S was about 30%. Both of which indicated much safer properties of R15S than PS. In conclusion, we presented a promising candidate R15S for UFH reversal, which is effective in neutralizing UFH and potentially safer in use. - Highlights: • R15 sulfate has a comparable unfractionated heparin neutralization activity to PS. • R15 sulfate avoided severe anaphylactic responses which happened to PS in clinical use. • R15 sulfate could provide a stricter quality control compared to PS which may vary with different batches.« less
NASA Astrophysics Data System (ADS)
Régis, J.-M.; Dannhoff, M.; Jolie, J.; Müller-Gatermann, C.; Saed-Samii, N.
2016-03-01
Employing the γ-γ fast-timing technique with LaBr3(Ce) scintillator detectors allows the direct determination of lifetimes of nuclear excited states with a lower limit of about 5 ps. This limit is increased as soon as background is present in the coincidence spectra underneath the full-energy peaks of the γ-γ cascade. Our aim was to identify the components of the γ-ray background by systematic γ-γ fast-timing measurements using different types of γ shielding within a large γ-ray spectrometer. The energy dependent physical zero-time response was measured using background-free full-energy peak events from the 152Eu γ-ray source. This is compared with the time response of the (Compton-) background distribution as obtained using the prompt 60Co γ-ray source. The time response of the typical Compton background is about 15 ps faster than the time response of background-free full-energy peak events. Below about 500 keV, a second type of background contributes by the detection of Compton-scattered γ rays generated in the materials of the spectrometer around the detector. Due to the additional time-of-flight of the Compton-scattered γ rays, this low-energy background is largely delayed. Compared with a bare cylindrical 1.5 in . × 1.5 in . LaBr3(Ce) detector, the BGO-shielded detector in the Compton-suppression mode improves the peak-to-total ratio by a factor of 1.66(5), while the Pb-shielded detector only slightly reduces the low-energy background.
The preparatory set: a novel approach to understanding stress, trauma, and the bodymind therapies
Payne, Peter; Crane-Godreau, Mardi A.
2015-01-01
Basic to all motile life is a differential approach/avoid response to perceived features of environment. The stages of response are initial reflexive noticing and orienting to the stimulus, preparation, and execution of response. Preparation involves a coordination of many aspects of the organism: muscle tone, posture, breathing, autonomic functions, motivational/emotional state, attentional orientation, and expectations. The organism organizes itself in relation to the challenge. We propose to call this the “preparatory set” (PS). We suggest that the concept of the PS can offer a more nuanced and flexible perspective on the stress response than do current theories. We also hypothesize that the mechanisms of body-mind therapeutic and educational systems (BTES) can be understood through the PS framework. We suggest that the BTES, including meditative movement, meditation, somatic education, and the body-oriented psychotherapies, are approaches that use interventions on the PS to remedy stress and trauma. We discuss how the PS can be adaptive or maladaptive, how BTES interventions may restore adaptive PS, and how these concepts offer a broader and more flexible view of the phenomena of stress and trauma. We offer supportive evidence for our hypotheses, and suggest directions for future research. We believe that the PS framework will point to ways of improving the management of stress and trauma, and that it will suggest directions of research into the mechanisms of action of BTES. PMID:25883565
Flow induced streamer formation in particle laden complex flows
NASA Astrophysics Data System (ADS)
Debnath, Nandini; Hassanpourfard, Mahtab; Ghosh, Ranajay; Trivedi, Japan; Thundat, Thomas; Kumar, Aloke
2016-11-01
We study the combined flow of a polyacrylamide (PAM)solution with polystyrene (PS) nanoparticles, through a microfluidic device containing an array of micropillars. The flow is characterized by a very low Reynolds number (Re<<1). We find that for exceeding a critical Weissenberg number (Wi >= 20), PS nanoparticles localize near pillar walls to form thin slender string-like structures, which we call 'streamers' due to their morphology. Post-formation, these streamers show significant viscous behavior for short observational time-scales, and at longer observational time scales elastic response dominates. Our abiotic streamers could provide a framework for understanding similar structures that often form in biological systems. PhD student, Department of Mechanical Engineering.
Poupin, María Josefina; Timmermann, Tania; Vega, Andrea; Zuñiga, Ana; González, Bernardo
2013-01-01
Plant growth-promoting rhizobacteria (PGPR) induce positive effects in plants, such as increased growth or reduced stress susceptibility. The mechanisms behind PGPR/plant interaction are poorly understood, as most studies have described short-term responses on plants and only a few studies have analyzed plant molecular responses under PGPR colonization. Here, we studied the effects of the PGPR bacterial model Burkholderiaphytofirmans PsJN on the whole life cycle of Arabidopsis thaliana plants. We reported that at different plant developmental points, strain PsJN can be found in the rhizosphere and also colonizing their internal tissues. In early ontogeny, strain PsJN increased several growth parameters and accelerated growth rate of the plants. Also, an Arabidopsis transcriptome analysis revealed that 408 genes showed differential expression in PsJN-inoculated plants; some of these genes are involved in stress response and hormone pathways. Specifically, genes implicated in auxin and gibberellin pathways were induced. Quantitative transcriptional analyses of selected genes in different developmental stages revealed that the beginning of these changes could be evidenced early in development, especially among the down-regulated genes. The inoculation with heat-killed bacteria provoked a more severe transcriptional response in plants, but was not able to induce plant growth-promotion. Later in ontogeny, the growth rates of inoculated plants decreased with respect to the non-inoculated group and, interestingly, the inoculation accelerated the flowering time and the appearance of senescence signs in plants; these modifications correlate with the early up-regulation of flowering control genes. Then, we show that a single inoculation with a PGPR could affect the whole life cycle of a plant, accelerating its growth rate and shortening its vegetative period, both effects relevant for most crops. Thus, these findings provide novel and interesting aspects of these relevant biological interactions.
Towards a Narrowband Photonic Sigma-Delta Digital Antenna
2012-02-01
High Speed Photodiode/ Amplifier 26 G no amplifier 50 k transimpedance amplifier N/A 12 ps rise time 50 Ω output impedance HP 8447A Amplifier ......Response for the optical amplifier as a function of input drive current
Ultrafast Primary Reactions in the Photosystems of Oxygen-Evolving Organisms
NASA Astrophysics Data System (ADS)
Holzwarth, A. R.
In oxygen-evolving photosynthetic organisms (plants, green algae, cyanobacteria), the primary steps of photosynthesis occur in two membrane-bound protein supercomplexes, Photosystem I (PS I) and Photosystem II (PS II), located in the thylakoid membrane (c.f. Fig. 7.1) along with two other important protein complexes, the cytochrome b6/f complex and the ATP-synthase [1]. Each of the photosystems consists of a reaction center (RC) where the photoinduced early electron transfer processes occur, of a so-called core antenna consisting of chlorophyll (Chl) protein complexes responsible for light absorption and ultrafast energy transfer to the RC pigments, and additional peripheral antenna complexes of various kinds that increase the absorption cross-section. The peripheral complexes are Chl a/b-protein complexes in higher plants and green algae (LHC I or LHC II for PS I or PS II, respectively) and so-called phycobilisomes in cyanobacteria and red algae [2-4]. The structures and light-harvesting functions of these antenna systems have been extensively reviewed [2, 5-9]. Recently, X-ray structures of both PS I and PS II antenna/RC complexes have been determined, some to atomic resolution. Although many details of the pigment content and organization of the RCs and antenna systems of PS I and PS II have been known before, the high resolution structures of the integral complexes allow us for the first time to try to understand structure/function relationships in detail. This article covers our present understanding of the ultrafast energy transfer and early electron transfer processes occurring in the photosystems of oxygen-evolving organisms. The main emphasis will be on the electron transfer processes. However, in both photosystems the kinetics of the energy transfer processes in the core antennae is intimately interwoven with the kinetics of the electron transfer steps. Since both types of processes occur on a similar time scale, their kinetics cannot be considered separately in any experiment and consequently they have to be discussed together.
Ability to Maintain Internal Arousal and Motivation Modulates Brain Responses to Emotions
Sterpenich, Virginie; Schwartz, Sophie; Maquet, Pierre; Desseilles, Martin
2014-01-01
Persistence (PS) is defined as the ability to generate and maintain arousal and motivation internally in the absence of immediate external reward. Low PS individuals tend to become discouraged when expectations are not rapidly fulfilled. The goal of this study was to investigate whether individual differences in PS influence the recruitment of brain regions involved in emotional processing and regulation. In a functional MRI study, 35 subjects judged the emotional intensity of displayed pictures. When processing negative pictures, low PS (vs. high PS) subjects showed higher amygdala and right orbito-frontal cortex (OFC) activity but lower left OFC activity. This dissociation in OFC activity suggests greater prefrontal cortical asymmetry for approach/avoidance motivation, suggesting an avoidance response to aversive stimuli in low PS. For positive or neutral stimuli, low PS subjects showed lower activity in the amygdala, striatum, and hippocampus. These results suggest that low PS may involve an imbalance in processing distinct emotional inputs, with greater reactivity to aversive information in regions involved in avoidance behaviour (amygdala, OFC) and dampened response to positive and neutral stimuli across circuits subserving motivated behaviour (striatum, hippocampus, amygdala). Low PS affective style was associated with depression vulnerability. These findings in non-depressed subjects point to a neural mechanism whereby some individuals are more likely to show systematic negative emotional biases, as frequently observed in depression. The assessment of these individual differences, including those that may cause vulnerability to depressive disorders, would therefore constitute a promising approach to risk assessment for depression. PMID:25438046
Ability to maintain internal arousal and motivation modulates brain responses to emotions.
Sterpenich, Virginie; Schwartz, Sophie; Maquet, Pierre; Desseilles, Martin
2014-01-01
Persistence (PS) is defined as the ability to generate and maintain arousal and motivation internally in the absence of immediate external reward. Low PS individuals tend to become discouraged when expectations are not rapidly fulfilled. The goal of this study was to investigate whether individual differences in PS influence the recruitment of brain regions involved in emotional processing and regulation. In a functional MRI study, 35 subjects judged the emotional intensity of displayed pictures. When processing negative pictures, low PS (vs. high PS) subjects showed higher amygdala and right orbito-frontal cortex (OFC) activity but lower left OFC activity. This dissociation in OFC activity suggests greater prefrontal cortical asymmetry for approach/avoidance motivation, suggesting an avoidance response to aversive stimuli in low PS. For positive or neutral stimuli, low PS subjects showed lower activity in the amygdala, striatum, and hippocampus. These results suggest that low PS may involve an imbalance in processing distinct emotional inputs, with greater reactivity to aversive information in regions involved in avoidance behaviour (amygdala, OFC) and dampened response to positive and neutral stimuli across circuits subserving motivated behaviour (striatum, hippocampus, amygdala). Low PS affective style was associated with depression vulnerability. These findings in non-depressed subjects point to a neural mechanism whereby some individuals are more likely to show systematic negative emotional biases, as frequently observed in depression. The assessment of these individual differences, including those that may cause vulnerability to depressive disorders, would therefore constitute a promising approach to risk assessment for depression.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shcheslavskiy, V., E-mail: vis@becker-hickl.de; Becker, W.; Morozov, P.
Time resolution is one of the main characteristics of the single photon detectors besides quantum efficiency and dark count rate. We demonstrate here an ultrafast time-correlated single photon counting (TCSPC) setup consisting of a newly developed single photon counting board SPC-150NX and a superconducting NbN single photon detector with a sensitive area of 7 × 7 μm. The combination delivers a record instrument response function with a full width at half maximum of 17.8 ps and system quantum efficiency ∼15% at wavelength of 1560 nm. A calculation of the root mean square value of the timing jitter for channels withmore » counts more than 1% of the peak value yielded about 7.6 ps. The setup has also good timing stability of the detector–TCSPC board.« less
The influence of light on temperature preference in Drosophila
Head, Lauren M.; Tang, Xin; Hayley, Sean E.; Goda, Tadahiro; Umezaki, Yujiro; Chang, Elaine C.; Leslie, Jennifer R.; Fujiwara, Mana; Garrity, Paul A.; Hamada, Fumika N.
2015-01-01
Ambient light affects multiple physiological functions and behaviors, such as circadian rhythms, sleep-wake activities, and development from flies to mammals [1–6]. Mammals exhibit a higher body temperature when exposed to acute light compared to when they are exposed to dark, but the underlying mechanisms are largely unknown [7–10]. The body temperature of small ecotherms, such as Drosophila, rely on the temperature of their surrounding environment and these animals exhibit a robust temperature preference behavior [11–13]. Here, we demonstrate that Drosophila prefer a one-degree higher temperature when exposed to acute light rather than dark. This acute light response, light dependent temperature preference (LDTP), was observed regardless of the time of day, suggesting that LDTP is regulated separately from the circadian clock. However, screening of eye and circadian clock mutants suggests that the circadian clock neurons, posterior dorsal neurons 1 (DN1ps) and pigment-dispersing factor receptor (pdfr) play a role in LDTP. To further investigate the role of DN1ps in LDTP, pdfr in DN1ps was knocked down, resulting in an abnormal LDTP. The phenotype of the pdfr mutant was sufficiently rescued by expressing pdfr in DN1ps, indicating that pdfr expression in DN1ps is responsible for LDTP. These results suggest that light positively influences temperature preference via the circadian clock neurons, DN1ps, which may result from the integration of light and temperature information. Given that both Drosophila and mammals respond to acute light by increasing their body temperature, the effect of acute light on temperature regulation may be conserved evolutionarily between flies and humans. PMID:25866391
Cawson, Matthew Richard; Mitchell, Stephen Andrew; Knight, Chris; Wildey, Henry; Spurden, Dean; Bird, Alex; Orme, Michelle Elaine
2014-01-20
An updated economic evaluation was conducted to compare the cost-effectiveness of the four tumour necrosis factor (TNF)-α inhibitors adalimumab, etanercept, golimumab and infliximab in active, progressive psoriatic arthritis (PsA) where response to standard treatment has been inadequate. A systematic review was conducted to identify relevant, recently published studies and the new trial data were synthesised, via a Bayesian network meta-analysis (NMA), to estimate the relative efficacy of the TNF-α inhibitors in terms of Psoriatic Arthritis Response Criteria (PsARC) response, Health Assessment Questionnaire (HAQ) scores and Psoriasis Area and Severity Index (PASI). A previously developed economic model was updated with the new meta-analysis results and current cost data. The model was adapted to delineate patients by PASI 50%, 75% and 90% response rates to differentiate between psoriasis outcomes. All four licensed TNF-α inhibitors were significantly more effective than placebo in achieving PsARC response in patients with active PsA. Adalimumab, etanercept and infliximab were significantly more effective than placebo in improving HAQ scores in patients who had achieved a PsARC response and in improving HAQ scores in PsARC non-responders. In an analysis using 1,000 model simulations, on average etanercept was the most cost-effective treatment and, at the National Institute for Health and Care Excellence willingness-to-pay threshold of between £20,000 to £30,000, etanercept is the preferred option. The economic analysis agrees with the conclusions from the previous models, in that biologics are shown to be cost-effective for treating patients with active PsA compared with the conventional management strategy. In particular, etanercept is cost-effective compared with the other biologic treatments.
Kopljar, Ivan; Hermans, An N; Teisman, Ard; Gallacher, David J; Lu, Hua Rong
Calcium-based screening of hiPS-CMs is a useful preclinical safety evaluation platform with the ability to generate robust signals that facilitates high-throughput screening and data analysis. However, due to the potential inherent toxicities, it is important to understand potential effects of different calcium-sensitive dyes on the hiPS-CMs model. We compared three calcium-sensitive fluorescence dyes (Cal520, ACTOne and Calcium 5) for their impact on the variability, the beating properties and the pharmacological responses of hiPS-CMs using the Hamamatsu FDSS/μCell imaging platform. Direct effects of three dyes on the electrophysiological properties of hiPS-CMs were evaluated with the multi-electrode array (MEA) Axion Maestro platform. We propose a specific experimental protocol for each dye which gives the most optimal assay conditions to minimize variability and possible adverse effects. We showed that Cal520 had the smallest effect on hiPS-CMs together with the longest-lasting stable amplitude signal (up to 4 h). Although all dyes had a (minor) acute effect on hiPS-CMs, in the form of reduced beat rate and prolonged field potential duration, the selection of the dye did not influence the pharmacological response of four cardioactive drugs (dofetilide, moxifloxacin, nimodipine and isoprenaline). In conclusion, we have documented that different calcium sensitive dyes have only minor direct (acute) effects on hiPS-CMs with Cal520 showing the least effects and the longest lasting signal amplitude. Importantly, drug-induced pharmacological responses in hiPS-CMs were comparable between the three dyes. These findings should help further improve the robustness of the hiPS-CMs-based calcium transient assay as a predictive, preclinical cardiac safety evaluation tool. Copyright © 2018 Elsevier Inc. All rights reserved.
Super-diffusion of excited carriers in semiconductors
Najafi, Ebrahim; Ivanov, Vsevolod; Zewail, Ahmed; Bernardi, Marco
2017-01-01
The ultrafast spatial and temporal dynamics of excited carriers are important to understanding the response of materials to laser pulses. Here we use scanning ultrafast electron microscopy to image the dynamics of electrons and holes in silicon after excitation with a short laser pulse. We find that the carriers exhibit a diffusive dynamics at times shorter than 200 ps, with a transient diffusivity up to 1,000 times higher than the room temperature value, D0≈30 cm2s−1. The diffusivity then decreases rapidly, reaching a value of D0 roughly 500 ps after the excitation pulse. We attribute the transient super-diffusive behaviour to the rapid expansion of the excited carrier gas, which equilibrates with the environment in 100−150 ps. Numerical solution of the diffusion equation, as well as ab initio calculations, support our interpretation. Our findings provide new insight into the ultrafast spatial dynamics of excited carriers in materials. PMID:28492283
7 CFR 1753.37 - Plans and specifications (P&S).
Code of Federal Regulations, 2010 CFR
2010-01-01
... the preparation of P&S, the borrower shall review with the GFR the current and future requirements for..., and others responsible for the installation of the equipment. (b) Preparation of P&S. (1) The P&S... required equipment for each exchange, provision for spare parts, and all other pertinent data needed by the...
Jin, Qi; Pehrson, Steen; Jacobsen, Peter Karl; Chen, Xu
2015-11-01
The objectives of this study were to assess the procedural outcomes of persistent and long-standing persistent atrial fibrillation (PsAF and L-PsAF) ablation guided by remote magnetic navigation (RMN), and to detect factors predicting acute restoration of sinus rhythm (SR) by ablation with RMN. A total of 313 patients (275 male, age 59 ± 9.5 years) with PsAF (187/313) or L-PsAF (126/313) undergoing ablation using RMN were included. Patients' disease history, pulmonary venous anatomy, left atrial (LA) volume, procedure time, mapping plus ablation time, radiofrequency (RF) ablation time, fluoroscopy time, radiation dose, and complications were assessed. Stepwise regression was used to predict which variable could best predict acute restoration from AF to SR by ablation. Compared to PsAF, procedure time and RF ablation time were significantly increased in patients with L-PsAF (P = 0.01 and P < 0.001, respectively). No major complications occurred during the procedures in either PsAF or L-PsAF patients. Fifty five of 313 patients converted directly to SR by ablation. Compared to L-PsAF, the rate of SR restoration was significantly higher in PsAF (21 vs 12%, P = 0.03). Stepwise regression analysis showed LA volume was the primary parameter affecting SR restoration (P = 0.01). The LA volume of patients without direct SR restoration by ablation was 24% greater than that of patients with SR restoration (P < 0.001). Catheter ablation using RMN is a safe and effective method for PsAF and L-PsAF. LA volume could be a predictor of direct restoration of SR from sustaining AF by ablation using RMN.
Zhang, Meixiang; Li, Qi; Liu, Tingli; Liu, Li; Shen, Danyu; Zhu, Ye; Liu, Peihan; Zhou, Jian-Min; Dou, Daolong
2015-01-01
Plant pathogenic oomycetes, such as Phytophthora sojae, secrete an arsenal of host cytoplasmic effectors to promote infection. We have shown previously that P. sojae PsCRN63 (for crinkling- and necrosis-inducing proteins) induces programmed cell death (PCD) while PsCRN115 blocks PCD in planta; however, they are jointly required for full pathogenesis. Here, we find that PsCRN63 alone or PsCRN63 and PsCRN115 together might suppress the immune responses of Nicotiana benthamiana and demonstrate that these two cytoplasmic effectors interact with catalases from N. benthamiana and soybean (Glycine max). Transient expression of PsCRN63 increases hydrogen peroxide (H2O2) accumulation, whereas PsCRN115 suppresses this process. Transient overexpression of NbCAT1 (for N. benthamiana CATALASE1) or GmCAT1 specifically alleviates PsCRN63-induced PCD. Suppression of the PsCRN63-induced PCD by PsCRN115 is compromised when catalases are silenced in N. benthamiana. Interestingly, the NbCAT1 is recruited into the plant nucleus in the presence of PsCRN63 or PsCRN115; NbCAT1 and GmCAT1 are destabilized when PsCRN63 is coexpressed, and PsCRN115 inhibits the processes. Thus, PsCRN63/115 manipulates plant PCD through interfering with catalases and perturbing H2O2 homeostasis. Furthermore, silencing of catalase genes enhances susceptibility to Phytophthora capsici, indicating that catalases are essential for plant resistance. Taken together, we suggest that P. sojae secretes these two effectors to regulate plant PCD and H2O2 homeostasis through direct interaction with catalases and, therefore, overcome host immune responses. PMID:25424308
Zhang, Meixiang; Li, Qi; Liu, Tingli; Liu, Li; Shen, Danyu; Zhu, Ye; Liu, Peihan; Zhou, Jian-Min; Dou, Daolong
2015-01-01
Plant pathogenic oomycetes, such as Phytophthora sojae, secrete an arsenal of host cytoplasmic effectors to promote infection. We have shown previously that P. sojae PsCRN63 (for crinkling- and necrosis-inducing proteins) induces programmed cell death (PCD) while PsCRN115 blocks PCD in planta; however, they are jointly required for full pathogenesis. Here, we find that PsCRN63 alone or PsCRN63 and PsCRN115 together might suppress the immune responses of Nicotiana benthamiana and demonstrate that these two cytoplasmic effectors interact with catalases from N. benthamiana and soybean (Glycine max). Transient expression of PsCRN63 increases hydrogen peroxide (H(2)O(2)) accumulation, whereas PsCRN115 suppresses this process. Transient overexpression of NbCAT1 (for N. benthamiana CATALASE1) or GmCAT1 specifically alleviates PsCRN63-induced PCD. Suppression of the PsCRN63-induced PCD by PsCRN115 is compromised when catalases are silenced in N. benthamiana. Interestingly, the NbCAT1 is recruited into the plant nucleus in the presence of PsCRN63 or PsCRN115; NbCAT1 and GmCAT1 are destabilized when PsCRN63 is coexpressed, and PsCRN115 inhibits the processes. Thus, PsCRN63/115 manipulates plant PCD through interfering with catalases and perturbing H(2)O(2) homeostasis. Furthermore, silencing of catalase genes enhances susceptibility to Phytophthora capsici, indicating that catalases are essential for plant resistance. Taken together, we suggest that P. sojae secretes these two effectors to regulate plant PCD and H(2)O(2) homeostasis through direct interaction with catalases and, therefore, overcome host immune responses. © 2015 American Society of Plant Biologists. All Rights Reserved.
Casas-Agustench, Patricia; Serra, Mercè; Pérez-Heras, Ana; Cofán, Montserrat; Pintó, Xavier; Trautwein, Elke A; Ros, Emilio
2012-06-01
Plant sterol (PS)-supplemented foods are recommended to help in lowering serum LDL-cholesterol (LDL-C). Few studies have examined the efficacy of PS-enriched skimmed milk (SM) or semi-SM enriched with vegetable fat (PS-VFM). There is also insufficient information on factors predictive of LDL-C responses to PS. We examined the effects of PS-SM (0·1 % dairy fat) and PS-VFM (0·1 % dairy fat plus 1·5 % vegetable fat) on serum lipids and non-cholesterol sterols in hypercholesterolaemic individuals. In a placebo-controlled, crossover study, forty-three subjects with LDL-C>1300 mg/l were randomly assigned to three 4-week treatment periods: control SM, PS-SM and PS-VFM, with 500 ml milk with or without 3·4 g PS esters (2 g free PS). Serum concentrations of lipids and non-cholesterol sterols were measured. Compared to control, LDL-C decreased by 8·0 and 7·4 % (P < 0·015, both) in the PS-SM and PS-VFM periods, respectively. Serum lathosterol:cholesterol (C) ratios increased by 11-25 %, while sitosterol:C and campesterol:C ratios increased by 70-120 % with both the PS-fortified milk. Adjusted LDL-C reductions were variably enhanced in participants with basal low serum lathosterol/C or conversely high sitosterol/C and campesterol/C. Subjects with post-treatment serum PS:C ratios above the median showed mean LDL-C changes of - 5·9 to - 10·4 %, compared with 1·7 to - 2·9 % below the median. In conclusion, consumption of 2 g/d of PS as PS-SM and PS-VFM lowered LDL-C in hypercholesterolaemic subjects to a similar extent. Basal and post-treatment changes in markers of cholesterol metabolism indicating low cholesterol synthesis and high cholesterol absorption predicted improved LDL-C responses to PS.
Presenilin 1 mutation decreases both calcium and contractile responses in cerebral arteries.
Toussay, Xavier; Morel, Jean-Luc; Biendon, Nathalie; Rotureau, Lolita; Legeron, François-Pierre; Boutonnet, Marie-Charlotte; Cho, Yoon H; Macrez, Nathalie
2017-10-01
Mutations or upregulation in presenilin 1 (PS1) gene are found in familial early-onset Alzheimer's disease or sporadic late-onset Alzheimer's disease, respectively. PS1 has been essentially studied in neurons and its mutation was shown to alter intracellular calcium (Ca 2+ ) signals. Here, we showed that PS1 is expressed in smooth muscle cells (SMCs) of mouse cerebral arteries, and we assessed the effects of the deletion of exon 9 of PS1 (PS1dE9) on Ca 2+ signals and contractile responses of vascular SMC. Agonist-induced contraction of cerebral vessels was significantly decreased in PS1dE9 both in vivo and ex vivo. Spontaneous activity of Ca 2+ sparks through ryanodine-sensitive channels (RyR) was unchanged, whereas the RyR-mediated Ca 2+ -release activated by caffeine was shorter in PS1dE9 SMC when compared with control. Moreover, PS1dE9 mutation decreased the caffeine-activated capacitive Ca 2+ entry, and inhibitors of SERCA pumps reversed the effects of PS1dE9 on Ca 2+ signals. PS1dE9 mutation also leads to the increased expression of SERCA3, phospholamban, and RyR3. These results show that PS1 plays a crucial role in the cerebrovascular system and the vascular reactivity is decreased through altered Ca 2+ signals in PS1dE9 mutant mice. Copyright © 2017 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dang, Liem X.; Schenter, Gregory K.
To enhance our understanding of the solvent exchange mechanism in liquid methanol, we report a systematic study of this process using molecular dynamics simulations. We use transition state theory, the Impey-Madden-McDonald method, the reactive flux method, and Grote-Hynes theory to compute the rate constants for this process. Solvent coupling was found to dominate, resulting in a significantly small transmission coefficient. We predict a positive activation volume for the methanol exchange process. The essential features of the dynamics of the system as well as the pressure dependence are recovered from a Generalized Langevin Equation description of the dynamics. We find thatmore » the dynamics and response to anharmonicity can be decomposed into two time regimes, one corresponding to short time response (< 0.1 ps) and long time response (> 5 ps). An effective characterization of the process results from launching dynamics from the planar hypersurface corresponding to Grote-Hynes theory. This results in improved numerical convergence of correlation functions. This work was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences. The calculations were carried out using computer resources provided by the Office of Basic Energy Sciences.« less
Kines, Rhonda C.; Zarnitsyn, Vladimir; Johnson, Teresa R.; Pang, Yuk-Ying S.; Corbett, Kizzmekia S.; Nicewonger, John D.; Gangopadhyay, Anu; Chen, Man; Liu, Jie; Prausnitz, Mark R.; Schiller, John T.; Graham, Barney S.
2015-01-01
Human papilloma virus-like particles (HPV VLP) serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV) in HPV pseudovirions (PsV) is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1) whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2) whether HPV16 PsV-encapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene. Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge. Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV) were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively. HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge. In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids. Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust. Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation. PMID:25785935
Kines, Rhonda C; Zarnitsyn, Vladimir; Johnson, Teresa R; Pang, Yuk-Ying S; Corbett, Kizzmekia S; Nicewonger, John D; Gangopadhyay, Anu; Chen, Man; Liu, Jie; Prausnitz, Mark R; Schiller, John T; Graham, Barney S
2015-01-01
Human papilloma virus-like particles (HPV VLP) serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV) in HPV pseudovirions (PsV) is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1) whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2) whether HPV16 PsV-encapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene. Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge. Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV) were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively. HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge. In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids. Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust. Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation.
Timing of PMMA cement application for pedicle screw augmentation affects screw anchorage.
Schmoelz, Werner; Heinrichs, Christian Heinz; Schmidt, Sven; Piñera, Angel R; Tome-Bermejo, Felix; Duart, Javier M; Bauer, Marlies; Galovich, Luis Álvarez
2017-11-01
Cement augmentation is an established method to increase the pedicle screw (PS) anchorage in osteoporotic vertebral bodies. The ideal timing for augmentation when a reposition maneuver is necessary is controversial. While augmentation of the PS before reposition maneuver may increase the force applied it on the vertebrae, it bears the risk to impair PS anchorage, whereas augmenting the PS after the maneuver may restore this anchorage and prevent early screw loosening. The purpose of the present study was to evaluate the effect of cement application timing on PS anchorage in the osteoporotic vertebral body. Ten lumbar vertebrae (L1-L5) were used for testing. The left and right pedicles of each vertebra were instrumented with the same PS size and used for pairwise comparison of the two timing points for augmentation. For the reposition maneuver, the left PS was loaded axially under displacement control (2 × ±2 mm, 3 × ±6 mm, 3 × ±10 mm) to simulate a reposition maneuver. Subsequently, both PS were augmented with 2 ml PMMA cement. The same force as measured during the left PS maneuver was applied to the previously augmented right hand side PS [2 × F (±2 mm), 3 × F (±6 mm), 3 × F (±10 mm)]. Both PS were cyclically loaded with initial forces of +50 and -50 N, while the lower force was increased by 5 N every 100 cycles until total failure of the PS. The PS motion was measured with a 3D motion analysis system. After cyclic loading stress, X-rays were taken to identify the PS loosening mechanism. In comparison with PS augmented prior to the reposition maneuver, PS augmented after the reposition maneuver showed a significant higher number of load cycles until failure (5930 ± 1899 vs 3830 ± 1706, p = 0.015). The predominant loosening mechanism for PS augmented after the reposition maneuver was PS toggling with the attached cement cloud within the trabecular bone. While PS augmented prior to the reposition, maneuver showed a motion of the screw within the cement cloud. The time of cement application has an effect on PS anchorage in the osteoporotic vertebral body if a reposition maneuver of the instrumented vertebrae is carried out. PS augmented after the reposition maneuver showed a significant higher number of load cycles until screw loosening.
Pandya, Kalgi D; Palomo-Caturla, Isabel; Walker, Justin A; K Sandilya, Vijay; Zhong, Zhijiu; Alugupalli, Kishore R
2018-06-15
T cell-dependent B cell responses typically develop in germinal centers. Abs generated during such responses are isotype switched and have a high affinity to the Ag because of somatic hypermutation of Ab genes. B cell responses to purified polysaccharides are T cell independent and do not result in the formation of bona fide germinal centers, and the dominant Ab isotype produced during such responses is IgM with very few or no somatic mutations. Activation-induced cytidine deaminase (AID) is required for both somatic hypermutation and Ig isotype switching in humans and mice. To test the extent to which unmutated polysaccharide-specific IgM confers protective immunity, we immunized wildtype and AID -/- mice with either heat-killed Salmonella enterica serovar Typhi ( S. Typhi) or purified Vi polysaccharide (ViPS). We found that wildtype and AID -/- mice immunized with heat-killed S. Typhi generated similar anti-ViPS IgM responses. As expected, wildtype, but not AID -/- mice generated ViPS-specific IgG. However, the differences in the Ab-dependent killing of S. Typhi mediated by the classical pathway of complement activation were not statistically significant. In ViPS-immunized wildtype and AID -/- mice, the ViPS-specific IgM levels and S. Typhi bactericidal Ab titers at 7 but not at 28 d postimmunization were also comparable. To test the protective immunity conferred by these immunizations, mice were challenged with a chimeric S. Typhimurium strain expressing ViPS. Compared with their naive counterparts, immunized wildtype and AID -/- mice exhibited significantly reduced bacterial burden regardless of the route of infection. These data indicate that an unmutated IgM response to ViPS contributes to protective immunity to S. Typhi. Copyright © 2018 by The American Association of Immunologists, Inc.
Protein S Protects against Podocyte Injury in Diabetic Nephropathy.
Zhong, Fang; Chen, Haibing; Xie, Yifan; Azeloglu, Evren U; Wei, Chengguo; Zhang, Weijia; Li, Zhengzhe; Chuang, Peter Y; Jim, Belinda; Li, Hong; Elmastour, Firas; Riyad, Jalish M; Weber, Thomas; Chen, Hongyu; Wang, Yongjun; Zhang, Aihua; Jia, Weiping; Lee, Kyung; He, John C
2018-05-01
Background Diabetic nephropathy (DN) is a leading cause of ESRD in the United States, but the molecular mechanisms mediating the early stages of DN are unclear. Methods To assess global changes that occur in early diabetic kidneys and to identify proteins potentially involved in pathogenic pathways in DN progression, we performed proteomic analysis of diabetic and nondiabetic rat glomeruli. Protein S (PS) among the highly upregulated proteins in the diabetic glomeruli. PS exerts multiple biologic effects through the Tyro3, Axl, and Mer (TAM) receptors. Because increased activation of Axl by the PS homolog Gas6 has been implicated in DN progression, we further examined the role of PS in DN. Results In human kidneys, glomerular PS expression was elevated in early DN but suppressed in advanced DN. However, plasma PS concentrations did not differ between patients with DN and healthy controls. A prominent increase of PS expression also colocalized with the expression of podocyte markers in early diabetic kidneys. In cultured podocytes, high-glucose treatment elevated PS expression, and PS knockdown further enhanced the high-glucose-induced apoptosis. Conversely, PS overexpression in cultured podocytes dampened the high-glucose- and TNF- α -induced expression of proinflammatory mediators. Tyro3 receptor was upregulated in response to high glucose and mediated the anti-inflammatory response of PS. Podocyte-specific PS loss resulted in accelerated DN in streptozotocin-induced diabetic mice, whereas the transient induction of PS expression in glomerular cells in vivo attenuated albuminuria and podocyte loss in diabetic OVE26 mice. Conclusions Our results support a protective role of PS against glomerular injury in DN progression. Copyright © 2018 by the American Society of Nephrology.
Datte, P S; Eckart, M; Moore, A S; Thompson, W; Vergel de Dios, G
2016-11-01
Neutron-induced visible scintillation in neutron time of flight (NToF) diagnostics at the National Ignition Facility (NIF) is measured with 40 mm single stage micro-channel plate photomultipliers and a 40 mm vacuum photodiode, outside the neutron line of sight. In NIF experiments with 14 MeV neutron yields above Y > 10 × 10 15 these tubes are configured to deliver of order 1 nC of charge in the nominally 5 ns NToF into a 50 Ω load. We have examined a number of 40 mm tubes manufactured by Photek Ltd. of St. Leonards on Sea, UK, to determine possible changes in the instrument impulse response as a function of signal charge delivered in 1 ns. Precision NToF measurements at approximately 20 m require that we characterize changes in the impulse response moments to <40 ps for the first central moment and ∼2% rms for the square root of the second central moment with ∼500 ps value. Detailed results are presented for three different diode configurations.
National Trends in Pediatricians' Practices and Attitudes About Breastfeeding: 1995 to 2014.
Feldman-Winter, Lori; Szucs, Kinga; Milano, Aubri; Gottschlich, Elizabeth; Sisk, Blake; Schanler, Richard J
2017-10-01
The American Academy of Pediatrics (AAP) has affirmed breastfeeding as the preferred method of infant feeding; however, there has been little systematic examination of how pediatricians' recommendations, affiliated hospitals' policies, counseling practices, and attitudes toward breastfeeding have shifted over the past 2 decades. These trends were examined from 1995 to 2014. Data are from the Periodic Survey (PS) of Fellows, a nationally representative survey of AAP members. PS #30 (1995; response rate = 72%; N = 832), PS #57 (2004; response rate = 55%; N = 675), and PS #89 (2014; response rate = 51%; N = 620) collected demographics, patient and practice characteristics, and detailed responses on pediatricians' recommendations, affiliated hospitals' policies, counseling practices, and attitudes toward breastfeeding. By using bivariate statistics and logistic regression models, the analysis investigated changes over time with predicted values (PVs). From 1995 to 2014, more pediatricians reported their affiliated hospitals applied for "baby-friendly" designation (PV = 12% in 1995, PV = 56% in 2014; P < .05), and more reported that they recommend exclusive breastfeeding (65% to 76% [ P < .05]). However, fewer respondents indicated that mothers can be successful breastfeeding (PV = 70% in 1995, PV = 57% in 2014; P < .05) and that the benefits outweigh the difficulties (PV = 70% in 1995, PV = 50% in 2014; P < .05). Younger pediatricians were less confident than older pediatricians in managing breastfeeding problems ( P < .01). Pediatricians' recommendations and practices became more closely aligned with AAP policy from 1995 to 2014; however, their attitudes about the likelihood of breastfeeding success have worsened. These 2 divergent trends indicate that even as breastfeeding rates continue to rise, continued efforts to enhance pediatricians' training and attitudes about breastfeeding are necessary. Copyright © 2017 by the American Academy of Pediatrics.
Zhao, Xin; Zhao, Jie; Xie, Youzhuan; Mi, Jie
2016-01-01
This study assessed the utility of three-dimensional preoperative image reconstruction as digital virtual templating for junior surgeons in placing a pedicle screw (PS) in the lumbar spine. Twenty-three patients of lumbar disease were operated on with bilateral PS fixation in our hospital. The two sides of lumbar pedicles were randomly divided into "hand-free group" (HFG) and "digital virtual template group" (DVTG) in each patient. Two junior surgeons preoperatively randomly divided into these two groups finished the placement of PSs. The accuracy of PS and the procedure time of PS insertion were recorded. The accuracy of PS in DVTG was 91.8% and that in HFG was 87.7%. The PS insertion procedure time of DVTG was 74.5 ± 8.1 s and that of HFG was 90.9 ± 9.9 s. Although no significant difference was reported in the accurate rate of PS between the two groups, the PS insertion procedure time was significantly shorter in DVTG than in HFG (P < 0.05). Digital virtual template is simple and can reduce the procedure time of PS placement.
Hamilton, John P.; Vaillancourt, Brieanne; Buell, C. Robin; Day, Brad
2012-01-01
Pseudoperonospora cubensis, an oomycete, is the causal agent of cucurbit downy mildew, and is responsible for significant losses on cucurbit crops worldwide. While other oomycete plant pathogens have been extensively studied at the molecular level, Ps. cubensis and the molecular basis of its interaction with cucurbit hosts has not been well examined. Here, we present the first large-scale global gene expression analysis of Ps. cubensis infection of a susceptible Cucumis sativus cultivar, ‘Vlaspik’, and identification of genes with putative roles in infection, growth, and pathogenicity. Using high throughput whole transcriptome sequencing, we captured differential expression of 2383 Ps. cubensis genes in sporangia and at 1, 2, 3, 4, 6, and 8 days post-inoculation (dpi). Additionally, comparison of Ps. cubensis expression profiles with expression profiles from an infection time course of the oomycete pathogen Phytophthora infestans on Solanum tuberosum revealed similarities in expression patterns of 1,576–6,806 orthologous genes suggesting a substantial degree of overlap in molecular events in virulence between the biotrophic Ps. cubensis and the hemi-biotrophic P. infestans. Co-expression analyses identified distinct modules of Ps. cubensis genes that were representative of early, intermediate, and late infection stages. Collectively, these expression data have advanced our understanding of key molecular and genetic events in the virulence of Ps. cubensis and thus, provides a foundation for identifying mechanism(s) by which to engineer or effect resistance in the host. PMID:22545137
An ultrafast X-ray scintillating detector made of ZnO(Ga)
NASA Astrophysics Data System (ADS)
Zhang, Qingmin; Yan, Jun; Deng, Bangjie; Zhang, Jingwen; Lv, Jinge; Wen, Xin; Gao, Keqing
2017-12-01
Owing to its ultrafast scintillation, quite high light yield, strong radiation resistance, and non-deliquescence, ZnO(Ga) is a highly promising choice for an ultrafast X-ray detector. Because of its high deposition rate, good production repeatability and strong adhesive force, reactive magnetron sputtering was used to produce a ZnO(Ga) crystal on a quartz glass substrate, after the production conditions were optimized. The fluorescence lifetime of the sample was 173 ps. An ultrafast X-ray scintillating detector, equipped with a fast microchannel plate (MCP) photomultiplier tube (PMT), was developed and the X-ray tests show a signal full width at half maximum (FWHM) of only 385.5 ps. Moreover, derivation from the previous measurement shows the ZnO(Ga) has an ultrafast time response (FWHM = 355.1 ps) and a high light yield (14740 photons/MeV).
Ning, Na; Wen, Yinyuan; Dong, Shuqi; Yin, Meiqiang; Guo, Meijun; Wang, Binqiang; Feng, Lei; Guo, Pingyi
2014-01-01
Radix Isatidis (Isatis indigotica Fort.) is one of the most important traditional Chinese medicine plants. However, there is no suitable herbicide used for weed control in Radix Isatidis field during postemergence stage. To explore the safety of sulfonylurea herbicide nicosulfuron on Radix Isatidis (Isatis indigotica Fort.) seedlings and the photosynthetic physiological response of the plant to the herbicide, biological mass, leaf area, photosynthetic pigment content, photosynthetic rate, chlorophyll fluorescence characteristics, and P700 parameters of Radix Isatidis seedlings were analyzed 10 d after nicosulfuron treatment at 5th leaf stage in this greenhouse research. The results showed that biological mass, total chlorophyll, chlorophyll a, and carotenoids content, photosynthetic rate, stomatal conductance, PS II maximum quantum yield, PS II effective quantum yield, PS II electron transport rate, photochemical quenching, maximal P700 change, photochemical quantum yield of PS I, and PS I electron transport rate decreased with increasing herbicide concentrations, whereas initial fluorescence, quantum yield of non-regulated energy dissipation in PS II and quantum yield of non-photochemical energy dissipation due to acceptor side limitation in PS I increased. It suggests that nicosulfuron ≥1 mg L−1 causes the damage of chloroplast, PS II and PS I structure. Electron transport limitations in PS I receptor side, and blocked dark reaction process may be the main cause of the significantly inhibited growth and decreased photosynthetic rate of Radix Isatidis seedlings. PMID:25165819
Investigation of a Multi-Anode Microchannel Plate PMT for Time-of-Flight PET
NASA Astrophysics Data System (ADS)
Choong, Woon-Seng
2010-10-01
We report on an investigation of a mulit-anode microchannel plate PMT for time-of-flight PET detector modules. The primary advantages of an MCP lie in its excellent timing properties (fast rise time and low transit time spread), compact size, and reasonably large active area, thus making it a good candidate for TOF applications. In addition, the anode can be segmented into an array of collection electrodes with fine pitch to attain good position sensitivity. In this paper, we investigate using the Photonis Planacon MCP-PMT with a pore size of 10 μm to construct a PET detector module, specifically for time-of-flight applications. We measure the single electron response by exciting the Planacon with pulsed laser diode. We also measure the performance of the Planacon as a PET detector by coupling a 4 mm×4 mm×10 mm LSO crystal to individual pixel to study its gain uniformity, energy resolution, and timing resolution. The rise time of the Planacon is 440 ps with pulse duration of about 1 ns. A transit time spread of 120 ps FWHM is achieved. The gain is fairly uniform across the central region of the Planacon, but drops off by as much as a factor of 2.5 around the edges. The energy resolution is fairly uniform across the Planacon with an average value of 18.6 ± 0.7% FWHM. While the average timing resolution of 252 ± 7 ps FWHM is achieved in the central region of the Planacon, it degrades to 280 ± 9 ps FWHM for edge pixels and 316 ± 15 ps FWHM for corner pixels. We compare the results with measurements performed with a fast timing conventional PMT (Hamamatsu R-9800). We find that the R9800, which has significantly higher PDE, has a better timing resolution than the Planacon. Furthermore, we perform detector simulations to calculate the improvement that can be achieved with a higher PDE Planacon. The calculation shows that the Planacon can achieve significantly better timing resolution if it can attain the same PDE as the R-9800, while only a 30% improvement is needed to yield a similar timing resolution as the R-9800.
Rico, Mario C.; Dela Cadena, Raul A.; Kunapuli, Satya P.
2011-01-01
The P2Y12 receptor plays a crucial role in the regulation of platelet activation by several agonists, which is irreversibly antagonized by the active metabolite of clopidogrel, a widely used anti-thrombotic drug. In this study, we investigated whether reduction of platelet reactivity leads to reduced inflammatory responses using a rat model of erosive arthritis. We evaluated the effect of clopidogrel on inflammation in Lewis rats in a peptidoglycan polysaccharide (PG-PS)-induced arthritis model with four groups of rats: 1) untreated, 2) clopidogrel-treated, 3) PG-PS-induced, and 4) PG-PS-induced and clopidogrel-treated. There were significant differences between the PG-PS+clopidogrel group when compared to the PG-PS group including: increased joint diameter and clinical manifestations of inflammation, elevated plasma levels of pro-inflammatory cytokines (IL-1 beta, interferon (IFN) gamma, and IL-6), an elevated neutrophil blood count and an increased circulating platelet count. Plasma levels of IL-10 were significantly lower in the PG-PS+clopidogrel group compared to the PG-PS group. Plasma levels of platelet factor 4 (PF4) were elevated in both the PG-PS and the PG-PS+clopidogrel groups, however PF4 levels showed no difference upon clopidogrel treatment, suggesting that the pro- inflammatory effect of clopidogrel may be due to its action on cells other than platelets. Histology indicated an increase in leukocyte infiltration at the inflammatory area of the joint, increased pannus formation, blood vessel proliferation, subsynovial fibrosis and cartilage erosion upon treatment with clopidogrel in PG-PS-induced arthritis animals. In summary, animals treated with clopidogrel showed a pro-inflammatory effect in the PG-PS-induced arthritis animal model, which might not be mediated by platelets. Elucidation of the mechanism of clopidogrel-induced cell responses is important to understand the role of the P2Y12 receptor in inflammation. PMID:22028806
Chen, Quanyi; Cannons, Jennifer L.; Paton, James C.; Akiba, Hisaya; Schwartzberg, Pamela L.; Snapper, Clifford M.
2010-01-01
Polysaccharide (PS)- and protein-specific murine IgG responses to intact Streptococcus pneumoniae (Pn) are both dependent upon CD4+ T cell help, B7-dependent costimulation, and CD40/CD40-ligand interactions. However, the primary PS-, relative to protein-specific, IgG response terminates more rapidly, requires a shorter period of T cell help and B7-dependent costimulation, and fails to generate memory. In light of the critical role for ICOS/ICOS-ligand interactions in sustaining T cell-dependent Ig responses and promoting germinal center reactions, we hypothesized that this interaction was non-essential for PS-specific IgG responses to Pn. We now demonstrate that ICOS-/-, relative to WT, mice elicit a normal PS-specific IgG isotype response to Pn, despite marked inhibition of both the primary and secondary IgG anti-protein (i.e. PspA, PspC, and PsaA) response. A blocking anti-ICOS-ligand mAb injected during primary Pn immunization inhibits both the primary anti-protein response and the generation of protein-specific memory, but has no effect when injected during secondary immunization. In contrast to Pn, both PS- and protein-specific IgG responses to a pneumococcal conjugate vaccine are inhibited in ICOS-/- mice. ICOS-/- mice immunized with intact Pn or conjugate exhibit nearly complete abrogation in germinal center formation. Finally, although mice that lack the adaptor molecule SAP resemble ICOS-/- mice (and can exhibit decreased ICOS expression), we observe that the PS-, as well as protein-specific IgG responses to both Pn and conjugate are markedly defective in SAP-/- mice. These data define a novel T cell-, SAP-, and B7-dependent, but ICOS-independent, extrafollicular pathway of Ig induction. PMID:19050242
Zhang, Luoying; Chung, Brian Y; Lear, Bridget C; Kilman, Valerie L; Liu, Yixiao; Mahesh, Guruswamy; Meissner, Rose-Anne; Hardin, Paul E; Allada, Ravi
2010-04-13
Daily behaviors in animals are determined by the interplay between internal timing signals from circadian clocks and environmental stimuli such as light. How these signals are integrated to produce timely and adaptive behavior is unclear. The fruit fly Drosophila exhibits clock-driven activity increases that anticipate dawn and dusk and free-running rhythms under constant conditions. Flies also respond to the onset of light and dark with acute increases in activity. Mutants of a novel ion channel, narrow abdomen (na), lack a robust increase in activity in response to light and show reduced anticipatory behavior and free-running rhythms, providing a genetic link between photic responses and circadian clock function. We used tissue-specific rescue of na to demonstrate a role for approximately 16-20 circadian pacemaker neurons, a subset of the posterior dorsal neurons 1 (DN1(p)s), in mediating the acute response to the onset of light as well as morning anticipatory behavior. Circadian pacemaker neurons expressing the neuropeptide PIGMENT-DISPERSING FACTOR (PDF) are especially important for morning anticipation and free-running rhythms and send projections to the DN1(p)s. We also demonstrate that DN1(p)Pdfr expression is sufficient to rescue, at least partially, Pdfr morning anticipation defects as well as defects in free-running rhythms, including those in DN1 molecular clocks. Additionally, these DN1 clocks in wild-type flies are more strongly reset to timing changes in PDF clocks than other pacemaker neurons, suggesting that they are direct targets. Taking these results together, we demonstrate that the DN1(p)s lie at the nexus of PDF and photic signaling to produce appropriate daily behavior.
The effect of spinal manipulation impulse duration on spine neuromechanical responses
Pagé, Isabelle; Nougarou, François; Dugas, Claude; Descarreaux, Martin
2014-01-01
Introduction: Spinal manipulation therapy (SMT) is characterized by specific kinetic and kinematic parameters that can be modulated. The purpose of this study is to investigate fundamental aspects of SMT dose-physiological response relation in humans by varying SMT impulse duration. Methods: Twenty healthy adults were subjected to four different SMT force-time profiles delivered by a servo-controlled linear actuator motor and differing in their impulse duration. EMG responses of the left and right thoracic paraspinal muscles (T6 and T8 levels) and vertebral displacements of T7 and T8 were evaluated for all SMT phases. Results: Significant differences in paraspinal EMG were observed during the “Thrust phase” and immediately after (“Post-SMT1”) (all T8 ps < 0.01 and T6 during the thrust ps < 0.05). Sagittal vertebral displacements were similar across all conditions (p > 0.05). Conclusion: Decreasing SMT impulse duration leads to a linear increase in EMG response of thoracic paraspinal during and following the SMT thrust. PMID:24932018
Amaral, Larissa S; Azevedo, Eduardo B; Perussi, Janice R
2018-06-01
Antimicrobial Photodynamic Inactivation (a-PDI) is based on the oxidative destruction of biological molecules by reactive oxygen species generated by the photo-excitation of a photosensitive molecule. When a-PDT is performed with the use of mathematical models, the optimal conditions for maximum inactivation are found. Experimental designs allow a multivariate analysis of the experimental parameters. This is usually made using a univariate approach, which demands a large number of experiments, being time and money consuming. This paper presents the use of the response surface methodology for improving the search for the best conditions to reduce E. coli survival levels by a-PDT using methylene blue (MB) and toluidine blue (TB) as photosensitizers and white light. The goal was achieved by analyzing the effects and interactions of the three main parameters involved in the process: incubation time (IT), photosensitizer concentration (C PS ), and light dose (LD). The optimization procedure began with a full 2 3 factorial design, followed by a central composite one, in which the optimal conditions were estimated. For MB, C PS was the most important parameter followed by LD and IT whereas, for TB, the main parameter was LD followed by C PS and IT. Using the estimated optimal conditions for inactivation, MB was able to inactivate 99.999999% CFU mL -1 of E. coli with IT of 28 min, LD of 31 J cm -2 , and C PS of 32 μmol L -1 , while TB required 18 min, 39 J cm -2 , and 37 μmol L -1 . The feasibility of using the response surface methodology with a-PDT was demonstrated, enabling enhanced photoinactivation efficiency and fast results with a minimal number of experiments. Copyright © 2018 Elsevier B.V. All rights reserved.
The development of the Asian Forum for Polar Sciences (AFoPS)
NASA Astrophysics Data System (ADS)
Kim, Yeadong; Jeong, Jihoon
2015-12-01
The Asian Forum for Polar Sciences (AFoPS), an international forum of Asian polar research institutes, was established for the advancement of polar sciences among its members in 2004. The Forum has served as an important medium of Asian collective endeavors for polar affairs in human and information exchange, research collaboration, and logistics cooperation for the last decade. The historical development of the AFoPS in retrospect can be divided into four phases: inception and establishment (2003-2004), growth and expansion (2005-2007), review and restructuring (2008-2011), and achievements and further measures (2012-2014). The progress of the AFoPS has not been linear and this trend will continue into the next decades. The Forum, however, clearly made achievements in this period of time, realizing multilateral research and logistics cooperation that would have been previously unimaginable; by doing so, it has laid the foundation for the future. Responsible for a great portion of the world's polar activities, the AFoPS will rise to meet the expectations of the world by producing notable research output, initiating international cooperative programs, and supporting non-polar Asian countries with education and research collaboration. These are the tasks of the AFoPS for the next decade and they require strategy that promotes and facilitates collaboration in a practical way and draws attention of non-polar Asian countries to the polar sciences.
2007-01-01
primary IgG anti-PS, vs antiprotein, re- sponse and a greater dependence on B cell membrane Ig (mIg) signaling, mediated by Bruton’s tyrosine kinase ( Btk ...WT, wild type; TI, T cell independent; TD, T cell dependent; Pn, Streptococcus pneumoniae; mIg, membrane Ig; Btk , Bruton’s tyrosine kinase; GC...were more dependent than antiprotein responses, on Btk -dependent mIg FIGURE 2. Anti-PS responses to PPS14-PspA C-PS-PspA conjugate vaccine or to
Ueda, Norihiro; Uemura, Yasushi; Zhang, Rong; Kitayama, Shuichi; Iriguchi, Shoichi; Kawai, Yohei; Yasui, Yutaka; Tatsumi, Minako; Ueda, Tatsuki; Liu, Tian-Yi; Mizoro, Yasutaka; Okada, Chihiro; Watanabe, Akira; Nakanishi, Mahito; Senju, Satoru; Nishimura, Yasuharu; Kuzushima, Kiyotaka; Kiyoi, Hitoshi; Naoe, Tomoki; Kaneko, Shin
2018-06-05
CD4 + T helper (Th) cell activation is essential for inducing cytotoxic T lymphocyte (CTL) responses against malignancy. We reprogrammed a Th clone specific for chronic myelogenous leukemia (CML)-derived b3a2 peptide to pluripotency and re-differentiated the cells into original TCR-expressing T-lineage cells (iPS-T cells) with gene expression patterns resembling those of group 1 innate lymphoid cells. CD4 gene transduction into iPS-T cells enhanced b3a2 peptide-specific responses via b3a2 peptide-specific TCR. iPS-T cells upregulated CD40 ligand (CD40L) expression in response to interleukin-2 and interleukin-15. In the presence of Wilms tumor 1 (WT1) peptide, antigen-specific dendritic cells (DCs) conditioned by CD4-modified CD40L high iPS-T cells stimulated WT1-specific CTL priming, which eliminated WT1 peptide-expressing CML cells in vitro and in vivo. Thus, CD4 modification of CD40L high iPS-T cells generates innate lymphoid helper-like cells inducing bcr-abl-specific TCR signaling that mediates effectiveanti-leukemic CTL responses via DC maturation, showing potential for adjuvant immunotherapy against leukemia. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Nicotinic acetylcholine receptors in porcine hypophyseal intermediate lobe cells.
Zhang, Z W; Feltz, P
1990-01-01
1. Acetylcholine (ACh) was found to depolarize isolated porcine intermediate lobe cells maintained in primary cells culture. We investigated the ACh-induced responses in both whole-cell and cell-attached configurations of the patch-clamp technique. 2. From noise analysis of ACh-evoked whole-cell currents, we estimated an elementary conductance of 20 pS and a channel open duration of about 1.7 ms at -60 mV. From single-channel recordings, we obtained a slope conductance of 26 pS and a mean open time of 1.8 ms at membrane potentials between -60 and -80 mV. 3. ACh-evoked responses were blocked by d-tubocurarine (d-TC), hexamethonium and mecamylamine, but were insensitive to alpha-bungarotoxin. These characteristics define a neuronal type of nicotinic receptors. 4. The whole-cell current induced by ACh showed a strong inward rectification with no outward current being obtained. This phenomenon was observed when the intracellular ion is either sodium or caesium, and even when Ca2+ and Mg2+ were totally removed from the intracellular medium. 5. ACh-gated channels in intermediate lobe cells were cation selective and were permeable to Na+ and Cs+. In Ca2(+)-free extracellular solution, single-channel conductances were much larger (46 pS) than in the presence of 2 mM-Ca2+ (26 pS). 6. The possibility of an excitatory cholinergic control of intermediate lobe cells is discussed. PMID:1693685
Diffusion of liquid polystyrene into glassy poly(phenylene oxide) characterized by DSC
NASA Astrophysics Data System (ADS)
Li, Linling; Wang, Xiaoliang; Zhou, Dongshan; Xue, Gi
2013-03-01
We report a diffusion study on the polystyrene/poly(phenylene oxide) (PS/PPO) mixture consisted by the PS and PPO nanoparticles. Diffusion of liquid PS into glassy PPO (l-PS/g-PPO) is promoted by annealing the PS/PPO mixture at several temperatures below Tg of the PPO. By tracing the Tgs of the PS-rich domain behind the diffusion front using DSC, we get the relationships of PS weight fractions and diffusion front advances with the elapsed diffusion times at different diffusion temperatures using the Gordon-Taylor equation and core-shell model. We find that the plots of weight fraction of PS vs. elapsed diffusion times at different temperatures can be converted to a master curve by Time-Temperature superposition, and the shift factors obey the Arrhenius equation. Besides, the diffusion front advances of l-PS into g-PPO show an excellent agreement with the t1/2 scaling law at the beginning of the diffusion process, and the diffusion coefficients of different diffusion temperatures also obey the Arrhenius equation. We believe the diffusion mechanism for l-PS/g-PPO should be the Fickean law rather than the Case II, though there are departures of original linearity at longer diffusion times due to the limited liquid supply system. Diffusion of liquid polystyrene into glassy poly(phenylene oxide) characterized by DSC
Livraghi, Tito; Ceriani, R; Palmisano, A; Pedicini, V; Pich, M G; Tommasini, M A; Torzilli, G
2011-02-01
Hepatocellular carcinoma (HCC) represents the third cause of cancer-related death. Because HCC is multi-centric with time, excluding the few transplanted patients, sooner or later it becomes untreatable with loco-regional therapies and, until some years ago, it was not responsive to systemic therapies. In 2005 a randomized trial indicated the efficacy of a product containing stem cell differentiation stage factors (SCDSF) taken from zebra fish embryos during the stage in which the totipotent stem cells are differentiating into the pluripotent adult stem cells. In such a trial the patients, with "intermediate" and "advanced" HCC according to BCLC/AASLD guidelines, presented benefit in terms of performance status (PS) and objective tumoral response, with some cases (2.4%) of complete response (CR). The aim of this cohort study is to report the experience of a tertiary referral center on the evidence of cases of CR in patients with "advanced" stage HCC treated with SCDSF as supportive care. CR was regarded as sustained disappearance of the neoplastic areas or blood supply therein, accompanied by normalization of AFP levels. Out of 49 patients consecutively recruited and retrospectively evaluated, 38 had "advanced" stage and 11 "terminal" stage. In 5 patients with "advanced" stage a sustained CR was reported (13.1%). Improvement on PS was obtained in 17 patients (34.6%). No side effects occurred. SCDSF treatment confirmed its efficacy in patients with "advanced" HCC, in terms of PS and tumoral response.
Nuclear resonant scattering experiment with fast time response: Photonuclear excitation of 201Hg
NASA Astrophysics Data System (ADS)
Yoshimi, A.; Hara, H.; Hiraki, T.; Kasamatsu, Y.; Kitao, S.; Kobayashi, Y.; Konashi, K.; Masuda, R.; Masuda, T.; Miyamoto, Y.; Okai, K.; Okubo, S.; Ozaki, R.; Sasao, N.; Sato, O.; Seto, M.; Schumm, T.; Shigekawa, Y.; Stellmer, S.; Suzuki, K.; Uetake, S.; Watanabe, M.; Yamaguchi, A.; Yasuda, Y.; Yoda, Y.; Yoshimura, K.; Yoshimura, M.
2018-02-01
Nuclear resonant excitation and detection of its decay signal for the 26.27-keV level of 201Hg is demonstrated with high-brilliance synchrotron radiation (SR) and a fast x-ray detector system. This SR-based photonuclear excitation scheme, known as nuclear resonant scattering (NRS) in the field of materials science, is also useful for investigating nuclear properties, such as the half-lives and radiative widths of excited nuclear levels. To date, because of the limited time response of the x-ray detector, the nuclear levels to which this method could be applied have been limited to the one whose half-lives are longer than ˜1 ns. The faster time response of the NRS measurement makes possible NRS experiments on nuclear levels with much shorter half-lives. We have fabricated an x-ray detector system that has a time resolution of 56 ps and a shorter tail function than that reported previously. With the implemented detector system, the NRS signal of the 26.27-keV state of 201Hg could be clearly discriminated from the electronic scattering signal at an elapsed time of 1 ns after the SR pulse. The half-life of the state was determined as 629 ± 18 ps, which has better precision by a factor of three compared with that reported to date obtained from nuclear decay spectroscopy.
Reduced minimum model for the photosynthetic induction processes in photosystem I.
Matsuoka, Takeshi; Tanaka, Shigenori; Ebina, Kuniyoshi
2016-07-01
Photosystem I (PS I) is one of the most important protein complexes for photosynthesis, which is present in plants, algae and cyanobacteria. A variety of mechanisms for environmental response in and around PS I have been elucidated experimentally and theoretically. During the photosynthetic induction time, the congestion of electron occurs in PS I and then the over-reduced PS I states are realized. This means that the degree of freedom of the redox states of PS I becomes large and thus the understanding of phenomena based on the model describing PS I in the state space becomes difficult. To understand the phenomena intuitively, we have reduced the complicated PS I model which has the multi-timescale property for electron and excitation-energy transfer processes into a simple one which has only the mono-timescale property through the use of hierarchical coarse-graining (HCG) method. The coarse-grained model describes the state of PS I by seven variable states, while the original model describes the PS I by 3×2(7)(=384) states. Based on the derived model, the I820 (820nm transmittance signal) curve in photosynthetic induction term, which indicates the accumulations of P700(+) and Pc(+), is simulated and analyzed in comparison with experiment. With respect to this signal curve, it is revealed that the initial increase up to the shoulder at 10(-3) s, the increase from that point to the peak at 2 ×10(-2) s, and the decay after that peak reflect the accumulations of P700(+), Pc(+) and P700FA(-)FB(-) (PS I state in which P700,FA(-) and FB(-) are observed.), respectively. Besides, the important role of the charge recombination processes from P700(+)A0A(-) and P700(+)A1A(-) states for the dissipation of the extra absorbed energy in photosynthetic induction period is confirmed. Copyright © 2016 Elsevier B.V. All rights reserved.
Charge displacement in bacteriorhodopsin during the forward and reverse bR-K phototransition.
Groma, G I; Hebling, J; Ludwig, C; Kuhl, J
1995-01-01
Dried oriented purple membrane samples of Halobacterium salinarium were excited by 150 fs laser pulses of 620 nm with a 7 kHz repetition rate. An unusual complex picosecond electric response signal consisting of a positive and a negative peak was detected by a sampling oscilloscope. The ratio of the two peaks was changed by 1) reducing the repetition rate, 2) varying the intensity of the excitation beam, and 3) applying background illumination by light of 647 nm or 511 nm. All of these features can be explained by the simultaneous excitation of the bacteriorhodopsin ground form and the K intermediate. The latter was populated by the (quasi)continuous excitation attributable to its prolonged lifetime in a dehydrated state. Least-square analysis resulted in a 5 ps upper and 2.5 ps lower limit for the time constant of the charge displacement process, corresponding to the forward reaction. That is in good agreement with the formation time of K. The charge separation driven by the reverse phototransition was faster, having a time constant of a 3.5 ps upper limit. The difference in the rates indicates the existence of different routes for the forward and the reverse photoreactions. PMID:8580349
DOE Office of Scientific and Technical Information (OSTI.GOV)
Suyanto, Hery; Pardede, Marincan; Hedwig, Rinda
2016-08-15
A time-resolved spectroscopic study is performed on the enhancement signals of He gas plasma emission using nanosecond (ns) and picosecond (ps) lasers in an orthogonal configuration. The ns laser is used for the He gas plasma generation and the ps laser is employed for the ejection of fast electrons from a metal target, which serves to excite subsequently the He atoms in the plasma. The study is focused on the most dominant He I 587.6 nm and He I 667.8 nm emission lines suggested to be responsible for the He-assisted excitation (HAE) mechanism. The time-dependent intensity enhancements induced by themore » fast electrons generated with a series of delayed ps laser ablations are deduced from the intensity time profiles of both He emission lines. The results clearly lead to the conclusion that the metastable excited triplet He atoms are actually the species overwhelmingly produced during the recombination process in the ns laser-induced He gas plasma. These metastable He atoms are believed to serve as the major energy source for the delayed excitation of analyte atoms in ns laser-induced breakdown spectroscopy (LIBS) using He ambient gas.« less
Ren, Jun; Li, Qun; Wu, Shan; Li, Shi-Yan; Babcock, Sara A.
2007-01-01
Catalase, an enzyme which detoxifies H2O2, may interfere with cardiac aging. To test this hypothesis, contractile and intracellular Ca2+ properties were evaluated in cardiomyocytes from young (3–4 mo) and old (26–28 mo) FVB and transgenic mice with cardiac overexpression of catalase. Contractile indices analyzed included peak shortening (PS), time-to-90% PS (TPS90), time-to-90% relengthening (TR90), half-width duration (HWD), maximal velocity of shortening/relengthening (± dL/dt) and intracellular Ca2+ levels or decay rate. Levels of advanced glycation endproduct (AGE), Na+/Ca2+ exchanger (NCX), sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a), phospholamban (PLB), myosin heavy chain (MHC), membrane Ca2+ and K+ channels were measured by western blot. Catalase transgene prolonged survival while did not alter myocyte function by itself. Aging depressed ± dL/dt, prolonged HWD, TR90 and intracellular Ca2+ decay without affecting other indices in FVB myocytes. Aged FVB myocytes exhibited a stepper decline in PS in response to elevated stimulus or a dampened rise in PS in response to elevated extracellular Ca2+ levels. Interestingly, aging-induced defects were nullified or significantly attenuated by catalase. AGE level was elevated by 5-fold in aged FVB compared with young FVB mice, which was reduced by catalase. Expression of SERCA2a, NCX and Kv1.2 K+ channel was significantly reduced although levels of PLB, L-type Ca2+ channel dihydropyridine receptor and β-MHC isozyme remained unchanged in aged FVB hearts. Catalase restored NCX and Kv1.2 K+ channel but not SERCA2a level in aged mice. In summary, our data suggested that catalase protects cardiomyocytes from aging-induced contractile defect possibly via improved intracellular Ca2+ handling. PMID:17250874
Cao, Yan Jun; Wang, Qiong; Zheng, Xing Xing; Cheng, Ying; Zhang, Yan
2018-08-01
Prenatal stress (PS) exposure can cause depression-like behavior in offspring, and maladaptive responses including physiological and neurobiological changes. Glutamate neurotransmission is implicated in effects of PS and in antidepressant mechanisms; however, the mechanisms underlying its involvement remain unclear. In the synapse, the formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is essential for vesicular docking and neurotransmitter release. To explore effects of PS on the SNARE complex, pregnant rats were assigned to a control or PS group. Both male and female offspring in each group were used in this study. PS rats were exposed to restraint stress three times daily for 45 min on days 14-20 of pregnancy. In the PS offspring, the expression of the SNARE protein SNAP-25, vesicle-associated membrane protein (VAMP)-2, and Syntaxin 1a was significantly increased in the hippocampus and prefrontal cortex. These observations were associated with increased levels of proteins that chaperone SNARE complex formation, including Munc-18, α-synuclein, CSPα, complexin1, and complexin2. Immunoblotting of hippocampal and prefrontal cortex homogenates revealed significantly increased SNARE complex formation. vGluT1 protein expression was also significantly increased in the offspring. Additionally, PS was associated with increased mRNA expression of VAMP1, VAMP2, SNAP25, Syntaxin1a, and Syntaxin1b in the hippocampus and prefrontal cortex. Increased monomeric SNARE proteins, SNARE complex formation, vesicle-associated proteins, and vGluT1 may explain the increase in glutamate and its downstream excitotoxicity. These results support the hypothesis that glutamate release and vesicular glutamate transporters play a role in PS-induced depression-like behavior of rat offspring. Copyright © 2018. Published by Elsevier B.V.
Gilio, Karen; van Kruchten, Roger; Braun, Attila; Berna-Erro, Alejandro; Feijge, Marion A. H.; Stegner, David; van der Meijden, Paola E. J.; Kuijpers, Marijke J. E.; Varga-Szabo, David; Heemskerk, Johan W. M.; Nieswandt, Bernhard
2010-01-01
In platelets, STIM1 has been recognized as the key regulatory protein in store-operated Ca2+ entry (SOCE) with Orai1 as principal Ca2+ entry channel. Both proteins contribute to collagen-dependent arterial thrombosis in mice in vivo. It is unclear whether STIM2 is involved. A key platelet response relying on Ca2+ entry is the surface exposure of phosphatidylserine (PS), which accomplishes platelet procoagulant activity. We studied this response in mouse platelets deficient in STIM1, STIM2, or Orai1. Upon high shear flow of blood over collagen, Stim1−/− and Orai1−/− platelets had greatly impaired glycoprotein (GP) VI-dependent Ca2+ signals, and they were deficient in PS exposure and thrombus formation. In contrast, Stim2−/− platelets reacted normally. Upon blood flow in the presence of thrombin generation and coagulation, Ca2+ signals of Stim1−/− and Orai1−/− platelets were partly reduced, whereas the PS exposure and formation of fibrin-rich thrombi were normalized. Washed Stim1−/− and Orai1−/− platelets were deficient in GPVI-induced PS exposure and prothrombinase activity, but not when thrombin was present as co-agonist. Markedly, SKF96365, a blocker of (receptor-operated) Ca2+ entry, inhibited Ca2+ and procoagulant responses even in Stim1−/− and Orai1−/− platelets. These data show for the first time that: (i) STIM1 and Orai1 jointly contribute to GPVI-induced SOCE, procoagulant activity, and thrombus formation; (ii) a compensating Ca2+ entry pathway is effective in the additional presence of thrombin; (iii) platelets contain two mechanisms of Ca2+ entry and PS exposure, only one relying on STIM1-Orai1 interaction. PMID:20519511
2017-01-01
Myeloid cells play a central role in the context of viral eradication, yet precisely how these cells differentiate throughout the course of acute infections is poorly understood. In this study, we have developed a novel quantitative temporal in vivo proteomics (QTiPs) platform to capture proteomic signatures of temporally transitioning virus-driven myeloid cells directly in situ, thus taking into consideration host–virus interactions throughout the course of an infection. QTiPs, in combination with phenotypic, functional, and metabolic analyses, elucidated a pivotal role for inflammatory CD11b+, Ly6G–, Ly6Chigh-low cells in antiviral immune response and viral clearance. Most importantly, the time-resolved QTiPs data set showed the transition of CD11b+, Ly6G–, Ly6Chigh-low cells into M2-like macrophages, which displayed increased antigen-presentation capacities and bioenergetic demands late in infection. We elucidated the pivotal role of myeloid cells in virus clearance and show how these cells phenotypically, functionally, and metabolically undergo a timely transition from inflammatory to M2-like macrophages in vivo. With respect to the growing appreciation for in vivo examination of viral–host interactions and for the role of myeloid cells, this study elucidates the use of quantitative proteomics to reveal the role and response of distinct immune cell populations throughout the course of virus infection. PMID:28768414
Zheng, Xiao; Liu, Guan; Wang, Shengye; Zhang, Yunli; Bao, Wenlong; Deng, Dehou; Mao, Weiming; Fang, Meiyu
2014-10-01
Epidermal growth factor receptor (EGFR) is an important therapeutic target in lung cancer. Gefitinib and erlotinib, two reversible EGFR receptor tyrosine kinases inhibitors (TKIs), have been approved for the treatment of patients with metastatic non small-cell lung cancer. Icotinib, which is a selective EGFR-TKI, provides a similar efficacy to gefitinib. The present study aimed to investigate the survival and safety of icotinib in patients with lung adenocarcinoma with a poor performance status (PS). A total of 42 cases of lung adenocarcinoma, including 35 females and 7 males, were enrolled. Icotinib was used as the first-line of treatment due to poor PS of the patient or a more advanced age. Icotinib (125 mg) was orally administered three times per day. The overall response rate and disease control rates were 33.3 and 85.7%, respectively. The median survival time was 13.0 months (95% CI, 5.6-20.4), The median progression-free survival time was 7.0 months, and the 1-year survival rate was 71.4%. A total of 79% of patients had an improved PS following icotinib treatment. Grade 1 to 2 rashes and diarrhea were the most frequent side effects. One patient succumbed during the study due to interstitial pneumonia. In conclusion, this is the first study indicating that patients with lung adenocarcinoma and poor PS may benefit from first-line icotinib therapy, but should be cautious of the occurrence of interstitial lung disease.
NASA Astrophysics Data System (ADS)
Yu, Liuhua; Hao, Gazi; Gu, Junjun; Zhou, Shuai; Zhang, Ning; Jiang, Wei
2015-11-01
In this work, Fe3O4/PS composites with a rough surface and different coating rates were successfully designed and synthesized by emulsion polymerization. We carried out some comparative experiments to compare magnetic properties and oil absorption properties of the nano-magnetic materials. It had been found that several prepared groups of magnetic nanocomposites have a core-shell structure and good coating rates. These nanoparticles combined with unsinked, highly hydrophobic and superoleophilic properties. The absorption capacity of Fe3O4/PS composites for organic solvents and the composites could absorb diesel oil up to 2.492 times of its own weight. It is more important that the oil could be readily removed from the surfaces of nanoparticles by a simple ultrasonic treatment whereas the nanocomposites particles still kept highly hydrophobic and superoleophilic characteristics. With a combination of simple synthesis process, low density, magnetic responsibility and excellent hydrophobicity, Fe3O4/PS nanocomposites as a promising absorbent have great potential in the application of spilled oil recovery and environmental protection.
Ramakrishnan, Radha; Davidowitz, Andrew; Balu-Iyer, Sathy V
2015-08-01
A major complication of replacement therapy with Factor VIII (FVIII) for hemophilia A (HA) is the development of unwanted immune responses. Previous studies showed that administration of FVIII in the presence of phosphatidyl serine (PS) reduced the development of anti-FVIII antibodies in HA mice. However, the impact of PS-mediated effects on immunological memory, such as generation of memory B-cells, is not clear. The effect of PS on memory B-cells was therefore investigated using adoptive transfer approach in FVIII(-/-) HA mice. Adoptive transfer of memory B-cells from a PS-FVIII-treated group to naïve mice followed by challenge of the recipient mice with FVIII showed a significantly reduced anti-FVIII antibody response in the recipient mice, compared with animals that received memory B-cells from free FVIII and FVIII-charge matched phosphatidyl glycerol (PG) group. The decrease in memory B-cell response is accompanied by an increase in FoxP3 expressing regulatory T-cells (Tregs). Flow cytometry studies showed that the generation of Tregs is higher in PS-treated animals as compared with FVIII and FVIII-PG treated animals. The PS-mediated hyporesponsiveness was found to be antigen-specific. The PS-FVIII immunization showed hyporesponsiveness toward FVIII rechallenge but not against ovalbumin (OVA) rechallenge, an unrelated antigen. This demonstrates that PS reduces immunologic memory of FVIII and induces antigen-specific peripheral tolerance in HA mice. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.
Iannone, F; Lopriore, S; Bucci, R; Scioscia, C; Anelli, M G; Notarnicola, A; Lapadula, G
2015-05-01
To evaluate the 2-year drug survival rates of the tumour necrosis factor (TNF)-α blockers adalimumab, etanercept, and infliximab in psoriatic arthritis (PsA) patients with either oligoarticular (oligo-PsA) or polyarticular PsA (poly-PsA). We studied a prospective cohort of 328 PsA patients with peripheral arthritis (213 with poly-PsA and 115 with oligo-PsA), beginning their first ever anti-TNF-α treatment with adalimumab, etanercept, or infliximab. The aim of the study was to evaluate the drug survival rates and possible baseline predictors at 2 years. After 24 months, persistence in therapy with the first anti-TNF-α blocker was not statistically different in the oligo-PsA (70.4%) and poly-PsA (65.7%) subsets. Predictors of drug discontinuation were female sex [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.00-2.68, p = 0.04] and starting the therapy in years 2003-8 (HR 0.51, 95% CI 0.33-0.80, p = 0.003). In poly-PsA, the persistence of etanercept (68.3%) was significantly higher than that of adalimumab (51.9%, p = 0.01), whereas in oligo-PsA no significant difference was detected. In poly-PsA, the period 2003-8 was a negative predictor (HR 0.36, 95% CI 0.21-0.62, p = 0.0001) whereas in oligo-PsA female gender was a positive predictor of drug discontinuation (HR 2.08, 95% CI 1.02-4.24, p = 0.04). With regard to clinical outcomes, the best responses in terms of European League Against Rheumatism (EULAR) 'good' response or Disease Activity Score (DAS28) remission, crude or adjusted according to the LUND Efficacy indeX (LUNDEX), were seen in patients on etanercept or infliximab. Our study provides some evidence that anti-TNF-α drugs may perform differently in PsA, and that the analysis of clinical disease subsets may improve our knowledge and promote better management of PsA.
A theoretical model for the collective motion of proteins by means of principal component analysis
NASA Astrophysics Data System (ADS)
Kamberaj, Hiqmet
2011-02-01
A coarse grained model in the frame work of principal component analysis is presented. We used a bath of harmonic oscillators approach, based on classical mechanics, to derive the generalized Langevin equations of motion for the collective coordinates. The dynamics of the protein collective coordinates derived from molecular dynamics simulations have been studied for the Bovine Pancreatic Trypsin Inhibitor. We analyzed the stability of the method by studying structural fluctuations of the C a atoms obtained from a 20 ns molecular dynamics simulation. Subsequently, the dynamics of the collective coordinates of protein were characterized by calculating the dynamical friction coefficient and diffusion coefficients along with time-dependent correlation functions of collective coordinates. A dual diffusion behavior was observed with a fast relaxation time of short diffusion regime 0.2-0.4 ps and slow relaxation time of long diffusion about 1-2 ps. In addition, we observed a power law decay of dynamical friction coefficient with exponent for the first five collective coordinates varying from -0.746 to -0.938 for the real part and from -0.528 to -0.665 for its magnitude. It was found that only the first ten collective coordinates are responsible for configuration transitions occurring on time scale longer than 50 ps.
VECC array for Nuclear fast Timing and angUlar corRElation studies (VENTURE)
NASA Astrophysics Data System (ADS)
Alam, S. S.; Bhattacharjee, T.; Banerjee, D.; Saha, A.; Pandit, Deepak; Mondal, D.; Mukhopadhyay, S.; Pal, Surajit; Bhaskar, P.; Das, S. K.; Banerjee, S. R.
2017-12-01
The VECC array for Nuclear fast Timing and angUlar corRElation studies (VENTURE) has been developed using several fast Cerium-Bromide (CeBr3) scintillators coupled to Hamamatsu R9779 Photomultiplier tubes. The CeBr3 detector has been characterised for the spectroscopic properties like energy response, energy resolution, timing resolution and detection efficiency. The response and efficiency of the detector have been compared with the results obtained from a Monte Carlo simulation with GEANT3 package. A time resolution of 144(1) ps and 109(1) ps was obtained for a single detector using 622-512 keV and 1173-1332 keV cascades respectively. The Generalised Centroid Difference (GCD) method has been employed with CeBr3 detectors by measuring the level lifetimes for the 511.9 keV level of 106Pd and the 160.6 and 383.8 keV levels of 133Cs. The angular correlation measurement was performed for the 1173-1332 keV cascade in 60Ni and the 228-49 keV cascade of 132I nucleus, populated from the decay of 132Te produced via 238U(α, f) reaction.
Liu, Tingli; Ye, Wenwu; Ru, Yanyan; Yang, Xinyu; Gu, Biao; Tao, Kai; Lu, Shan; Dong, Suomeng; Zheng, Xiaobo; Shan, Weixing; Wang, Yuanchao; Dou, Daolong
2011-01-01
Phytophthora sojae encodes hundreds of putative host cytoplasmic effectors with conserved FLAK motifs following signal peptides, termed crinkling- and necrosis-inducing proteins (CRN) or Crinkler. Their functions and mechanisms in pathogenesis are mostly unknown. Here, we identify a group of five P. sojae-specific CRN-like genes with high levels of sequence similarity, of which three are putative pseudogenes. Functional analysis shows that the two functional genes encode proteins with predicted nuclear localization signals that induce contrasting responses when expressed in Nicotiana benthamiana and soybean (Glycine max). PsCRN63 induces cell death, while PsCRN115 suppresses cell death elicited by the P. sojae necrosis-inducing protein (PsojNIP) or PsCRN63. Expression of CRN fragments with deleted signal peptides and FLAK motifs demonstrates that the carboxyl-terminal portions of PsCRN63 or PsCRN115 are sufficient for their activities. However, the predicted nuclear localization signal is required for PsCRN63 to induce cell death but not for PsCRN115 to suppress cell death. Furthermore, silencing of the PsCRN63 and PsCRN115 genes in P. sojae stable transformants leads to a reduction of virulence on soybean. Intriguingly, the silenced transformants lose the ability to suppress host cell death and callose deposition on inoculated plants. These results suggest a role for CRN effectors in the suppression of host defense responses.
Rozas-Serri, M; Ildefonso, R; Peña, A; Enríquez, R; Barrientos, S; Maldonado, L
2017-10-01
Piscirickettsiosis (SRS) is the most prevalent bacterial disease in Chilean salmon aquaculture and is responsible for high economic losses. The aim of this study was to comparatively characterize the pathogenesis of SRS in post-smolt Atlantic salmon during the early and late stages of infection with Piscirickettsia salmonis LF-89-like (PS-LF-89) and EM-90-like (PS-EM-90) using a cohabitation challenge. The pathogenesis of cohabitant fish infected with the two isolates was relatively different due to cohabitant fish infected with PS-EM-90 showing higher cumulative mortality and shorter time until death compared with PS-LF-89 fish. PS-LF-89 caused an SRS infection characterized by kidney and liver lesions, whereas PS-EM-90 caused systemic and haemorrhagic disease characterized by kidney, liver, heart, brain, skeletal muscle and intestine lesions. Decreased serum concentration of total proteins and albumin as well as increased serum ALT, AST and creatinine levels in fish infected with both isolates confirmed that changes in liver and kidney function occurred during infection. Tissue damage, expressed as an SRS histoscore, showed a strong positive correlation with the bacterial load expressed as abundance of P. salmonis 16S rRNA transcripts in the livers and kidneys of fish affected with either isolate, but the correlation was significantly higher in fish infected with PS-EM-90. The results contribute to improving the understanding of the bacteria-host interaction. © 2017 John Wiley & Sons Ltd.
Khalil Zadeh, Neda; Robertson, Kirsten; Green, James A
2017-12-06
The factors determining individuals' self-reported behavioural responses to direct to consumer advertising of prescription drugs were explored with an emphasis on 'at-risk' individuals' responses. Nationally representative cross-sectional survey. Community living adults in New Zealand. 2057 adults (51% women). Self-reported behavioural responses to drug advertising (asking a physician for a prescription, asking a physician for more information about an illness, searching the internet for more information regarding an illness and asking a pharmacist for more information about a drug). Multivariate logistic regressions determined whether participants' self-reported behavioural responses to drug advertising were predicted by attitudes towards advertising and drug advertising, judgements about safety and effectiveness of advertised drugs, self-reported health status, materialism, online search behaviour as well as demographic variables. Identifying as Indian and to a less extent Chinese, Māori and 'other' ethnicities were the strongest predictors of one or more self-reported responses (ORs 1.76-5.00, Ps < 0.05). Poorer self-reported health status (ORs 0.90-0.94, all Ps<0.05), favourable attitude towards drug advertising (ORs 1.34-1.61, all Ps<0.001) and searching for medical information online (ORs 1.32-2.35, all Ps<0.01) predicted all self-reported behavioural outcomes. Older age (ORs 1.01-1.02, Ps<0.01), less education (OR 0.89, P<0.01), lower income (ORs 0.89-0.91, Ps<0.05) and higher materialism (ORs 1.02-1.03, Ps<0.01) also predicted one or more self-reported responses. Taken together, the findings suggest individuals, especially those who are 'at-risk' (ie, with poorer self-reported health status, older, less educated, lower income and ethnic minorities), may be more vulnerable to drug advertising and may make uninformed decisions accordingly. The outcomes raise significant concerns relating to the ethicality of drug advertising and suggest a need for stricter guidelines to ensure that drug advertisements provided by pharmaceutical companies are ethical. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
2017-01-01
Objectives The factors determining individuals’ self-reported behavioural responses to direct to consumer advertising of prescription drugs were explored with an emphasis on ‘at-risk’ individuals’ responses. Design Nationally representative cross-sectional survey. Setting Community living adults in New Zealand. Participants 2057 adults (51% women). Primary outcome measures Self-reported behavioural responses to drug advertising (asking a physician for a prescription, asking a physician for more information about an illness, searching the internet for more information regarding an illness and asking a pharmacist for more information about a drug). Methods Multivariate logistic regressions determined whether participants’ self-reported behavioural responses to drug advertising were predicted by attitudes towards advertising and drug advertising, judgements about safety and effectiveness of advertised drugs, self-reported health status, materialism, online search behaviour as well as demographic variables. Results Identifying as Indian and to a less extent Chinese, Māori and ‘other’ ethnicities were the strongest predictors of one or more self-reported responses (ORs 1.76–5.00, Ps<0.05). Poorer self-reported health status (ORs 0.90–0.94, all Ps<0.05), favourable attitude towards drug advertising (ORs 1.34–1.61, all Ps<0.001) and searching for medical information online (ORs 1.32–2.35, all Ps<0.01) predicted all self-reported behavioural outcomes. Older age (ORs 1.01–1.02, Ps<0.01), less education (OR 0.89, P<0.01), lower income (ORs 0.89–0.91, Ps<0.05) and higher materialism (ORs 1.02–1.03, Ps<0.01) also predicted one or more self-reported responses. Conclusions Taken together, the findings suggest individuals, especially those who are ‘at-risk’ (ie, with poorer self-reported health status, older, less educated, lower income and ethnic minorities), may be more vulnerable to drug advertising and may make uninformed decisions accordingly. The outcomes raise significant concerns relating to the ethicality of drug advertising and suggest a need for stricter guidelines to ensure that drug advertisements provided by pharmaceutical companies are ethical. PMID:29217723
Du, Hui; Wu, Jie; Ji, Kui-Xian; Zeng, Qing-Yin; Bhuiya, Mohammad-Wadud; Su, Shang; Shu, Qing-Yan; Ren, Hong-Xu; Liu, Zheng-An; Wang, Liang-Sheng
2015-01-01
Anthocyanins are major pigments in plants. Methylation plays a role in the diversity and stability of anthocyanins. However, the contribution of anthocyanin methylation to flower coloration is still unclear. We identified two homologous anthocyanin O-methyltransferase (AOMT) genes from purple-flowered (PsAOMT) and red-flowered (PtAOMT) Paeonia plants, and we performed functional analyses of the two genes in vitro and in vivo. The critical amino acids for AOMT catalytic activity were studied by site-directed mutagenesis. We showed that the recombinant proteins, PsAOMT and PtAOMT, had identical substrate preferences towards anthocyanins. The methylation activity of PsAOMT was 60 times higher than that of PtAOMT in vitro. Interestingly, this vast difference in catalytic activity appeared to result from a single amino acid residue substitution at position 87 (arginine to leucine). There were significant differences between the 35S::PsAOMT transgenic tobacco and control flowers in relation to their chromatic parameters, which further confirmed the function of PsAOMT in vivo. The expression levels of the two homologous AOMT genes were consistent with anthocyanin accumulation in petals. We conclude that AOMTs are responsible for the methylation of cyanidin glycosides in Paeonia plants and play an important role in purple coloration in Paeonia spp. PMID:26208646
Towards programming immune tolerance through geometric manipulation of phosphatidylserine.
Roberts, Reid A; Eitas, Timothy K; Byrne, James D; Johnson, Brandon M; Short, Patrick J; McKinnon, Karen P; Reisdorf, Shannon; Luft, J Christopher; DeSimone, Joseph M; Ting, Jenny P
2015-12-01
The possibility of engineering the immune system in a targeted fashion using biomaterials such as nanoparticles has made considerable headway in recent years. However, little is known as to how modulating the spatial presentation of a ligand augments downstream immune responses. In this report we show that geometric manipulation of phosphatidylserine (PS) through fabrication on rod-shaped PLGA nanoparticles robustly dampens inflammatory responses from innate immune cells while promoting T regulatory cell abundance by impeding effector T cell expansion. This response depends on the geometry of PS presentation as both PS liposomes and 1 micron cylindrical PS-PLGA particles are less potent signal inducers than 80 × 320 nm rod-shaped PS-PLGA particles for an equivalent dose of PS. We show that this immune tolerizing effect can be co-opted for therapeutic benefit in a mouse model of multiple sclerosis and an assay of organ rejection using a mixed lymphocyte reaction with primary human immune cells. These data provide evidence that geometric manipulation of a ligand via biomaterials may enable more efficient and tunable programming of cellular signaling networks for therapeutic benefit in a variety of disease states, including autoimmunity and organ rejection, and thus should be an active area of further research. Copyright © 2015. Published by Elsevier Ltd.
Al-Batran, S.-E.; Van Cutsem, E.; Oh, S. C.; Bodoky, G.; Shimada, Y.; Hironaka, S.; Sugimoto, N.; Lipatov, O. N.; Kim, T.-Y.; Cunningham, D.; Rougier, P.; Muro, K.; Liepa, A. M.; Chandrawansa, K.; Emig, M.; Ohtsu, A.; Wilke, H.
2016-01-01
Background The phase III RAINBOW trial demonstrated that the addition of ramucirumab to paclitaxel improved overall survival, progression-free survival, and tumor response rate in fluoropyrimidine–platinum previously treated patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Here, we present results from quality-of-life (QoL) and performance status (PS) analyses. Patients and methods Patients with Eastern Cooperative Oncology Group PS of 0/1 were randomized to receive ramucirumab (8 mg/kg i.v.) or placebo on days 1 and 15 of a 4-week cycle, with both arms receiving paclitaxel (80 mg/m2) on days 1, 8, and 15. Patient-reported outcomes were assessed with the QoL/health status questionnaires EORTC QLQ-C30 and EQ-5D at baseline and 6-week intervals. PS was assessed at baseline and day 1 of every cycle. Time to deterioration (TtD) in each QLQ-C30 scale was defined as randomization to first worsening of ≥10 points (on 100-point scale) and TtD in PS was defined as first worsening to ≥2. Hazard ratios (HRs) for treatment effect were estimated using stratified Cox proportional hazards models. Results Of the 665 patients randomized, 650 (98%) provided baseline QLQ-C30 and EQ-5D data, and 560 (84%) also provided data from ≥1 postbaseline time point. Baseline scores for both instruments were similar between arms. Of the 15 QLQ-C30 scales, 14 had HR < 1, indicating similar or longer TtD in QoL for ramucirumab + paclitaxel. Treatment with ramucirumab + paclitaxel was also associated with a delay in TtD in PS to ≥2 (HR = 0.798, P = 0.0941). Alternate definitions of PS deterioration yielded similar results: PS ≥ 3 (HR = 0.656, P = 0.0508), deterioration by ≥1 PS level (HR = 0.802, P = 0.0444), and deterioration by ≥2 PS levels (HR = 0.608, P = 0.0063). EQ-5D scores were comparable between treatment arms, stable during treatment, and worsened at discontinuation. Conclusion In patients with previously treated advanced gastric/GEJ adenocarcinoma, addition of ramucirumab to paclitaxel prolonged overall survival while maintaining patient QoL with delayed symptom worsening and functional status deterioration. ClinicalTrials.gov NCT01170663. PMID:26747859
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mei, Chuansheng; Nowak, Jerzy; Seiler, John
Switchgrass represents a promising feedstock crop for US energy sustainability. However, its broad utilization for bioenergy requires improvements of biomass yields and stress tolerance. In this DOE funded project, we have been working on harnessing beneficial bacterial endophytes to enhance switchgrass performance and to develop a low input feedstock production system for marginal lands that do not compete with the production of food crops. We have demonstrated that one of most promising plant growth-promoting bacterial endophytes, Burkholderia phytofirmans strain PsJN, is able to colonize roots and significantly promote growth of switchgrass cv. Alamo under in vitro, growth chamber, greenhouse, asmore » well as field conditions. Furthermore, PsJN bacterization improved growth and development of switchgrass seedlings, significantly stimulated plant root and shoot growth, and tiller number in the field, and enhanced biomass accumulation on both poor (p<0.001) and rich (p<0.05) soils, with more effective stimulation of plant growth in low fertility soil. Plant physiology measurements showed that PsJN inoculated Alamo had consistently lower transpiration, lower stomatal conductance, and higher water use efficiency in greenhouse conditions. These physiological changes may significantly contribute to the recorded growth enhancement. PsJN inoculation rapidly results in an increase in photosynthetic rates which contributes to the advanced growth and development. Some evidence suggests that this initial growth advantage decreases with time when resources are not limited such as in greenhouse studies. Additionally, better drought resistance and drought hardening were observed in PsJN inoculated switchgrass. Using the DOE-funded switchgrass EST microarray, in a collaboration with the Genomics Core Facility at the Noble Foundation, we have determined gene expression profile changes in both responsive switchgrass cv. Alamo and non-responsive cv. Cave-in-Rock (CR) following PsJN bacterization. With the MapMan software to analyze microarray data, the number of up- and down-regulated probes was calculated. The number of up-regulated probes in Alamo was 26, 14, 14, and 12% at 0.5, 2, 4 and 8 days after inoculation (DAI) with PsJN, respectively while the corresponding number in CR was 24, 22, 21, and 19%, respectively. In both cultivars, the largest number of up-regulated probes occurred at 0.5 DAI. Noticeable differences throughout the timeframe between Alamo and CR were that the number was dramatically decreased to half (12%) in Alamo but remained high in CR (approximately 20%). The number of down regulated genes demonstrated different trends in Alamo and CR. Alamo had an increasing trend from 9% at 0.5 DAI to 11, 17, and 28% at 2, 4, and 8 DAI, respectively. However, CR had 13% at 0.5 and 2 DAI, and declined to 10% at 4 and 8 DAI. With the aid of MapMan and PageMan, we mapped the response of the ID probes to the observed major gene regulatory network and major biosynthetic pathway changes associated with the beneficial bacterial endophyte infection, colonization, and early growth promotion process. We found significant differences in gene expression patterns between responsive and non-responsive cultivars in many pathways, including redox state regulation, signaling, proteolysis, transcription factors, as well as hormone (SA and JA in particular)-associated pathways. Form microarray data, a total of 50 key genes have been verified using qPCR. Ten of these genes were chosen for further functional study via either overexpression and/or RNAi knockout technologies. These genes were calmodulin-related calcium sensor protein (CAM), glutathione S-transferase (GST), histidine-containing phosphotransfer protein (H-221), 3 different zinc finger proteins (ZF-371, ZF131 and ZF242), EF hand transcription factor (EF-622), peroxidase, cellulose synthase catalytic submit A2 (CESA2), and Aux/IAA family. A total of 8 overexpression and 5 RNAi transgenic plants have been regenerated, and their gene expression levels determined using qPCR. Consequently high, medium and low expression lines were propagated in vitro for gene function study. When adequate numbers of individual transgenic lines were obtained, they were challenged with PsJN to see if PsJN promotes or inhibits growth of transgenic plants. Our results demonstrated that EF-622 overexpression, ZF-371, GST, H-221 and CAM RNAi transgenic lines lost responses to PsJN, i.e. PsJN had no growth promotive effects on these transgenic plants. Further study needs to be done to characterize this loss of responsiveness to PsJN. During this funding period, we have done more work related to this funded project and established collaborations with other institutions and obtained some interesting results, building a foundation for further research projects. For example, we isolated a naturally-occurring bacterium from surface-sterilized switchgrass seeds, identified as a unique Panteoa agglomerans species, and named strain PaKM. PaKM has been proved to be an efficient growth promoter of switchgrass over a broad spectrum of genotypes and has potential in applications with low input and sustainable production systems on marginal lands. In collaboration with Dr. Shuijin Hu (North Carolina State University), we conducted experiments on how endophyte-inoculated switchgrass affects soil N and P availability and the number of AMF in roots. Our preliminary results showed that PsJN increased AMF infection of switchgrass roots, and enhanced soil N availability and soil N mineralization on a low nutrient field. Further study of this phenomenon on different soils, over longer time periods, is needed to assess its potential impact on the productivity and longevity of switchgrass stands.« less
Raines, Alexander; Garwe, Tabitha; Adeseye, Ademola; Ruiz-Elizalde, Alejandro; Churchill, Warren; Tuggle, David; Mantor, Cameron; Lees, Jason
2015-06-01
Adding fellows to surgical departments with residency programs can affect resident education. Our specific aim was to evaluate the effect of adding a pediatric surgery (PS) fellow on the number of index PS cases logged by the general surgery (GS) residents. At a single institution with both PS and GS programs, we examined the number of logged cases for the fellows and residents over 10 years [5 years before (Time 1) and 5 years after (Time 2) the addition of a PS fellow]. Additionally, the procedure related relative value units (RVUs) recorded by the faculty were evaluated. The fellows averaged 752 and 703 cases during Times 1 and 2, respectively, decreasing by 49 (P = 0.2303). The residents averaged 172 and 161 cases annually during Time 1 and Time 2, respectively, decreasing by 11 (P = 0.7340). The total number of procedure related RVUs was 4627 and 6000 during Times 1 and 2, respectively. The number of cases logged by the PS fellows and GS residents decreased after the addition of a PS fellow; however, the decrease was not significant. Programs can reasonably add an additional PS fellow, but care should be taken especially in programs that are otherwise static in size.
Roy Chowdhury, Panchali; Meier, Christian; Laraway, Hewad; Tang, Yuxiao; Hodgson, Abraham; Sow, Samba O.; Enwere, Godwin C.; Plikaytis, Brian D.; Kulkarni, Prasad S.; Preziosi, Marie-Pierre; Niedrig, Matthias
2015-01-01
Background. Yellow fever (YF) is still a major public health problem in endemic regions of Africa and South America. In Africa, one of the main control strategies is routine vaccination within the Expanded Programme on Immunization (EPI). A new meningococcal A conjugate vaccine (PsA-TT) is about to be introduced in the EPI of countries in the African meningitis belt, and this study reports on the immunogenicity of the YF-17D vaccines in infants when administered concomitantly with measles vaccine and PsA-TT. Methods. Two clinical studies were conducted in Ghana and in Mali among infants who received PsA-TT concomitantly with measles and YF vaccines at 9 months of age. YF neutralizing antibody titers were measured using a microneutralization assay. Results. In both studies, the PsA-TT did not adversely affect the immune response to the concomitantly administered YF vaccine at the age of 9 months. The magnitude of the immune response was different between the 2 studies, with higher seroconversion and seroprotection rates found in Mali vs Ghana. Conclusions. Immunogenicity to YF vaccine is unaffected when coadministered with PsA-TT at 9 months of age. Further studies are warranted to better understand the determinants of the immune response to YF vaccine in infancy. Clinical Trials Registration. ISRCTN82484612 (PsA-TT-004); PACTR201110000328305 (PsA-TT-007). PMID:26553692
Roy Chowdhury, Panchali; Meier, Christian; Laraway, Hewad; Tang, Yuxiao; Hodgson, Abraham; Sow, Samba O; Enwere, Godwin C; Plikaytis, Brian D; Kulkarni, Prasad S; Preziosi, Marie-Pierre; Niedrig, Matthias
2015-11-15
Yellow fever (YF) is still a major public health problem in endemic regions of Africa and South America. In Africa, one of the main control strategies is routine vaccination within the Expanded Programme on Immunization (EPI). A new meningococcal A conjugate vaccine (PsA-TT) is about to be introduced in the EPI of countries in the African meningitis belt, and this study reports on the immunogenicity of the YF-17D vaccines in infants when administered concomitantly with measles vaccine and PsA-TT. Two clinical studies were conducted in Ghana and in Mali among infants who received PsA-TT concomitantly with measles and YF vaccines at 9 months of age. YF neutralizing antibody titers were measured using a microneutralization assay. In both studies, the PsA-TT did not adversely affect the immune response to the concomitantly administered YF vaccine at the age of 9 months. The magnitude of the immune response was different between the 2 studies, with higher seroconversion and seroprotection rates found in Mali vs Ghana. Immunogenicity to YF vaccine is unaffected when coadministered with PsA-TT at 9 months of age. Further studies are warranted to better understand the determinants of the immune response to YF vaccine in infancy. ISRCTN82484612 (PsA-TT-004); PACTR201110000328305 (PsA-TT-007). © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
Thangaraj, J; Andonian, G; Thurman-Keup, R; Ruan, J; Johnson, A S; Lumpkin, A; Santucci, J; Maxwell, T; Murokh, A; Ruelas, M; Ovodenko, A
2012-04-01
A real-time interferometer (RTI) has been developed to monitor the bunch length of an electron beam in an accelerator. The RTI employs spatial autocorrelation, reflective optics, and a fast response pyro-detector array to obtain a real-time autocorrelation trace of the coherent radiation from an electron beam thus providing the possibility of online bunch-length diagnostics. A complete RTI system has been commissioned at the A0 photoinjector facility to measure sub-mm bunches at 13 MeV. Bunch length variation (FWHM) between 0.8 ps (~0.24 mm) and 1.5 ps (~0.45 mm) has been measured and compared with a Martin-Puplett interferometer and a streak camera. The comparisons show that RTI is a viable, complementary bunch length diagnostic for sub-mm electron bunches. © 2012 American Institute of Physics
DOE Office of Scientific and Technical Information (OSTI.GOV)
Thangaraj, J.; Thurman-Keup, R.; Ruan, J.
2012-03-01
A real-time interferometer (RTI) has been developed to monitor the bunch length of an electron beam in an accelerator. The RTI employs spatial autocorrelation, reflective optics, and a fast response pyro-detector array to obtain a real-time autocorrelation trace of the coherent radiation from an electron beam thus providing the possibility of online bunch-length diagnostics. A complete RTI system has been commissioned at the A0 photoinjector facility to measure sub-mm bunches at 13 MeV. Bunch length variation (FWHM) between 0.8 ps (-0.24 mm) and 1.5 ps (-0.45 mm) has been measured and compared with a Martin-Puplett interferometer and a streak camera.more » The comparisons show that RTI is a viable, complementary bunch length diagnostic for sub-mm electron bunches.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Thangaraj, J.; Thurman-Keup, R.; Ruan, J.
2012-04-15
A real-time interferometer (RTI) has been developed to monitor the bunch length of an electron beam in an accelerator. The RTI employs spatial autocorrelation, reflective optics, and a fast response pyro-detector array to obtain a real-time autocorrelation trace of the coherent radiation from an electron beam thus providing the possibility of online bunch-length diagnostics. A complete RTI system has been commissioned at the A0 photoinjector facility to measure sub-mm bunches at 13 MeV. Bunch length variation (FWHM) between 0.8 ps ({approx}0.24 mm) and 1.5 ps ({approx}0.45 mm) has been measured and compared with a Martin-Puplett interferometer and a streak camera.more » The comparisons show that RTI is a viable, complementary bunch length diagnostic for sub-mm electron bunches.« less
TOFPET 2: A high-performance circuit for PET time-of-flight
NASA Astrophysics Data System (ADS)
Di Francesco, Agostino; Bugalho, Ricardo; Oliveira, Luis; Rivetti, Angelo; Rolo, Manuel; Silva, Jose C.; Varela, Joao
2016-07-01
We present a readout and digitization ASIC featuring low-noise and low-power for time-of flight (TOF) applications using SiPMs. The circuit is designed in standard CMOS 110 nm technology, has 64 independent channels and is optimized for time-of-flight measurement in Positron Emission Tomography (TOF-PET). The input amplifier is a low impedance current conveyor based on a regulated common-gate topology. Each channel has quad-buffered analogue interpolation TDCs (time binning 20 ps) and charge integration ADCs with linear response at full scale (1500 pC). The signal amplitude can also be derived from the measurement of time-over-threshold (ToT). Simulation results show that for a single photo-electron signal with charge 200 (550) fC generated by a SiPM with (320 pF) capacitance the circuit has 24 (30) dB SNR, 75 (39) ps r.m.s. resolution, and 4 (8) mW power consumption. The event rate is 600 kHz per channel, with up to 2 MHz dark counts rejection.
Ultrafast dynamic response of single crystal β-HMX
NASA Astrophysics Data System (ADS)
Zaug, Joseph M.; Armstrong, Michael R.; Crowhurst, Jonathan C.; Radousky, Harry B.; Ferranti, Louis; Swan, Raymond; Gross, Rick; Teslich, Nick E.; Wall, Mark A.; Austin, Ryan A.; Fried, Laurence E.
2017-01-01
We report results from ultrafast compression experiments conducted on β-HMX single crystals. Results consist of nominally 12 picosecond time-resolved wave profile data, (ultrafast time domain interferometry -TDI measurements), that were analyzed to determine high-velocity wave speeds as a function of piston velocity. TDI results are used to validate calculations of anisotropic stress-strain behavior of shocked loaded energetic materials. Our previous results derived using a 350 ps duration compression drive revealed anisotropic elastic wave response in single crystal β-HMX from (110) and (010) impact planes. Here we present results using a 1.05 ns duration compression drive with a 950 ps interferometry window to extend knowledge of the anisotropic dynamic response of β-HMX within eight microns of the initial impact plane. We observe two distinct wave profiles from (010) and three wave profiles from (010) impact planes. The (110) impact plane wave speeds typically exceed (010) impact plane wave speeds at the same piston velocities. The development of multiple hydrodynamic wave profiles begins at 20 GPa for the (110) impact plane and 28 GPa for the (10) impact plane. We compare our ultrafast TDI results with previous gun and plate impact results on β-HMX and PBX9501.
Kwon, Chang-Il; Kim, Gwangil; Jeong, Seok; Lee, Don Haeng; Kim, Kyoung Ah; Ko, Kwang Hyun; Cho, Joo Young; Hong, Sung Pyo
2017-05-01
In research and development of biliary plastic stents (PS), continuous efforts have been made to overcome short patency time and high rate of migration. The aim of this study was to evaluate the patency and migration rate of different PS shapes for a given period of time. Using an in vitro bile phantom model, we compared the patency among different shapes of PS (three straight PS, four double-pigtail PS, and a new screw-shaped PS). We performed an analysis of the degree of luminal narrowing by light microscopic examination. Using an in vivo swine model, we compared the patency and migration rate among the three different types of PS. Eight weeks after the bile exposure in the bile flow phantom model, 80 PS were retrieved and analyzed. The straight PS showed less biofilm formation and luminal narrowing than other types of PS (p < 0.05). Forty-nine PS were inserted into the dilated bile ducts of 10 swine models, and 39 PS were successfully retrieved 8 weeks later. The stent migration occurred less frequently in the double-pigtail PS and the screw-shaped PS than it did in the straight PS (11.1, 10, and 27.3%, respectively). However, there was no statistical difference in stent patency among the different shapes. Stent patency may not be significantly different depending on the shape of PS for 8 weeks. The screw-shaped PS showed similar patency and migration rate to the double-pigtail PS. These results may help guiding future PS development and clinical decisions.
Medini, Paolo
2011-11-23
Connectivity and dendritic properties are determinants of plasticity that are layer and cell-type specific in the neocortex. However, the impact of experience-dependent plasticity at the level of synaptic inputs and spike outputs remains unclear along vertical cortical microcircuits. Here I compared subthreshold and suprathreshold sensitivity to prolonged monocular deprivation (MD) in rat binocular visual cortex in layer 4 and layer 2/3 pyramids (4Ps and 2/3Ps) and in thick-tufted and nontufted layer 5 pyramids (5TPs and 5NPs), which innervate different extracortical targets. In normal rats, 5TPs and 2/3Ps are the most binocular in terms of synaptic inputs, and 5NPs are the least. Spike responses of all 5TPs were highly binocular, whereas those of 2/3Ps were dominated by either the contralateral or ipsilateral eye. MD dramatically shifted the ocular preference of 2/3Ps and 4Ps, mostly by depressing deprived-eye inputs. Plasticity was profoundly different in layer 5. The subthreshold ocular preference shift was sevenfold smaller in 5TPs because of smaller depression of deprived inputs combined with a generalized loss of responsiveness, and was undetectable in 5NPs. Despite their modest ocular dominance change, spike responses of 5TPs consistently lost their typically high binocularity during MD. The comparison of MD effects on 2/3Ps and 5TPs, the main affected output cells of vertical microcircuits, indicated that subthreshold plasticity is not uniquely determined by the initial degree of input binocularity. The data raise the question of whether 5TPs are driven solely by 2/3Ps during MD. The different suprathreshold plasticity of the two cell populations could underlie distinct functional deficits in amblyopia.
Response Surface Methodology for Design of Porous Hollow Sphere Thermal Insulator
NASA Astrophysics Data System (ADS)
Shohani, Nazanin; Pourmahdian, Saeed; Shirkavand Hadavand, Behzad
2017-11-01
In this study, response surface method is used for synthesizing polystyrene (PS) as sacrificial templates and optimizing the particle size. Three factors of initiator, stabilizer concentration and also stirring rate were selected as variable factors. Then, three different concentration of tetraethyl orthosilicate (TEOS) added to reaction media and core-shell structure with PS core and silica shell was developed. Finally, core-shell structure was changed to hollow silica sphere for using as thermal insulator. We observed that increased initiator concentration caused to larger PS particles, increase the stirring rate caused the smaller PS and also with increased the stabilizer concentration obtained that particle size decrease then after 2.5% began to increase. Also the optimum amount of TEOS was found.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Huang, Jun-ben; Xinjiang Key Laboratory of Electronic Information Material and Devices, Xinjiang Technical Institute of Physics & Chemistry, Chinese Academy of Sciences, 40-1 South Beijing Road, Urumqi 830011; Mamat, Mamatrishat, E-mail: mmtrxt@xju.edu.cn
In this research work, Ag-containing quaternary-chalcogenide compounds KAg{sub 2}TS{sub 4} (T=P, Sb) (I-II) and RbAg{sub 2}SbS{sub 4} (III) have been studied by means of Density Functional Theory as potential IR nonlinear optical materials. The origin of wide band gap, different optical anisotropy and large SHG response is explained via a combination of density of states, electronic density difference and bond population analysis. It is indicated that the different covalent interaction behavior of P-S and Sb-S bonds dominates the band gap and birefringence. Specifically, the Ag-containing chalcogenide compound KAg{sub 2}PS{sub 4} possesses wide band gap and SHG response comparable with thatmore » of AgGaS{sub 2}. By exploring the origin of the band gap and NLO response for compounds KAg{sub 2}TS{sub 4} (T=P, Sb), we found the determination factor to the properties is different, especially the roles of Ag-d orbitals and bonding behavior of P-S or Sb-S. Thus, the compounds KAg{sub 2}TS{sub 4} (T=P, Sb) and RbAg{sub 2}SbS{sub 4} can be used in infrared (IR) region. - Graphical abstract: Metal thiophosphates RbPbPS{sub 4} and KSbP{sub 2}S{sub 6} have a similar band gap with KAg{sub 2}PS{sub 4}. However, based on first principles calculated results it shown that KAg{sub 2}PS{sub 4} possesses wide band gap (3.02 eV) and relatively large SHG response. Display Omitted.« less
Miller, Joseph D; Roy, Sukesh; Slipchenko, Mikhail N; Gord, James R; Meyer, Terrence R
2011-08-01
High-repetition-rate, single-laser-shot measurements are important for the investigation of unsteady flows where temperature and species concentrations can vary significantly. Here, we demonstrate single-shot, pure-rotational, hybrid femtosecond/picosecond coherent anti-Stokes Raman scattering (fs/ps RCARS) thermometry based on a kHz-rate fs laser source. Interferences that can affect nanosecond (ns) and ps CARS, such as nonresonant background and collisional dephasing, are eliminated by selecting an appropriate time delay between the 100-fs pump/Stokes pulses and the pulse-shaped 8.4-ps probe. A time- and frequency-domain theoretical model is introduced to account for rotational-level dependent collisional dephasing and indicates that the optimal probe-pulse time delay is 13.5 ps to 30 ps. This time delay allows for uncorrected best-fit N2-RCARS temperature measurements with ~1% accuracy. Hence, the hybrid fs/ps RCARS approach can be performed with kHz-rate laser sources while avoiding corrections that can be difficult to predict in unsteady flows.
NASA Astrophysics Data System (ADS)
Miller, Joseph D.; Roy, Sukesh; Slipchenko, Mikhail N.; Gord, James R.; Meyer, Terrence R.
2011-08-01
High-repetition-rate, single-laser-shot measurements are important for the investigation of unsteady flows where temperature and species concentrations can vary significantly. Here, we demonstrate single-shot, pure-rotational, hybrid femtosecond/picosecond coherent anti-Stokes Raman scattering (fs/ps RCARS) thermometry based on a kHz-rate fs laser source. Interferences that can affect nanosecond (ns) and ps CARS, such as nonresonant background and collisional dephasing, are eliminated by selecting an appropriate time delay between the 100-fs pump/Stokes pulses and the pulse-shaped 8.4-ps probe. A time- and frequency-domain theoretical model is introduced to account for rotational-level dependent collisional dephasing and indicates that the optimal probe-pulse time delay is 13.5 ps to 30 ps. This time delay allows for uncorrected best-fit N2-RCARS temperature measurements with ~1% accuracy. Hence, the hybrid fs/ps RCARS approach can be performed with kHz-rate laser sources while avoiding corrections that can be difficult to predict in unsteady flows.
Berruga, M I; Yamaki, M; Althaus, R L; Molina, M P; Molina, A
2003-11-01
Milk collected at 12-h intervals throughout 6 days from three groups of Manchega ewes (n = 12 per group), treated intramuscularly with beta-lactams (benzyl penicillin procaine, ampicillin, and amoxicillin, respectively), was evaluated for antibiotic residue persistence with four microbial inhibitor tests (BRT MRL, CH ATK P&S, Delvotest SP, and Eclipse 100ov) and one enzymatic test (Penzym 100). Antibiotic depletion time was established using a logistic regression model. A clear effect (P < 0.0001) of milking order on the response of all tests was observed with the three antibiotics, but no significant effects were found for milk yield. Except with Eclipse 100ov, positive tests were observed after the recommended withdrawal period of benzyl penicillin procaine (five milkings) from 2% (Delvotest SP) to 11% (CH ATK P&S). There were almost no positive responses beyond the withdrawal period (six milkings) of ampicillin, except for the Penzym 100 test (7%). Residues of amoxicillin were found to persist beyond the six milkings established as the withdrawal period, from 2.8% (Eclipse 100ov) to 72.4% (CH ATK P&S) of positive cases. Higher frequencies of doubtful cases were found with BRT MRL and Delvotest SP assays with the three beta-lactams. Positive and doubtful results could be obtained when milk samples from individual ewes were analyzed using BRT MRL, CH ATK P&S, Delvotest SP, and Penzym 100 tests, even if farmers follow the antibiotic withdrawal periods.
Lai, Zengzu; Schreiber, John R
2011-05-01
Bacterial polysaccharides (PS) are T cell-independent antigens that do not induce immunologic memory and are poor immunogens in infants. Conjugate vaccines in which the PS is covalently linked to a carrier protein have enhanced immunogenicity that resembles that of T cell-dependent antigens. The Haemophilus influenzae type b (Hib) conjugate vaccine, which uses the outer membrane protein complex (OMPC) from meningococcus as a carrier protein, elicits protective levels of anti-capsular PS antibody (Ab) after a single dose, in contrast to other conjugate vaccines, which require multiple doses. We have previously shown that OMPC robustly engages Toll-like receptor 2 (TLR2) and enhances the early anti-Hib PS Ab titer associated with an increase in TLR2-mediated induction of cytokines. We now show that the addition of OMPC to the 7-valent pneumococcal PS-CRM₁₉₇ conjugate vaccine during immunization significantly increases the anti-PS IgG and IgM responses to most serotypes of pneumococcus contained in the vaccine. The addition of OMPC also increased the likelihood of anti-PS IgG3 production against serotypes 4, 6B, 9V, 18C, 19F, and 23F. Splenocytes from mice who had received OMPC with the pneumococcal conjugate vaccine produced significantly more interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) than splenocytes from mice who received phosphate-buffered saline (PBS) plus the conjugate vaccine. We conclude that OMPC enhances the anti-PS Ab response to pneumococcal PS-CRM₁₉₇ conjugate vaccine, an effect associated with a distinct change in cytokine profile. It may be possible to reduce the number of conjugate vaccine doses required to achieve protective Ab levels by priming with adjuvants that are TLR2 ligands.
Caplins, Benjamin W; Lomont, Justin P; Nguyen, Son C; Harris, Charles B
2014-12-11
Picosecond time-resolved infrared spectroscopy (TRIR) was performed for the first time on a dithiolate bridged binuclear iron(I) hexacarbonyl complex ([Fe₂(μ-bdt)(CO)₆], bdt = benzene-1,2-dithiolate) which is a structural mimic of the active site of the [FeFe]-hydrogenase enzyme. As these model active sites are increasingly being studied for their potential in photocatalytic systems for hydrogen production, understanding their excited and ground state dynamics is critical. In n-heptane, absorption of 400 nm light causes carbonyl loss with low quantum yield (<10%), while the majority (ca. 90%) of the parent complex is regenerated with biexponential kinetics (τ₁ = 21 ps and τ₂ = 134 ps). In order to understand the mechanism of picosecond bleach recovery, a series of UV-pump TRIR experiments were performed in different solvents. The long time decay (τ₂) of the transient spectra is seen to change substantially as a function of solvent, from 95 ps in THF to 262 ps in CCl₄. Broadband IR-pump TRIR experiments were performed for comparison. The measured vibrational lifetimes (T₁(avg)) of the carbonyl stretches were found to be in excellent correspondence to the observed τ₂ decays in the UV-pump experiments, signifying that vibrationally excited carbonyl stretches are responsible for the observed longtime decays. The fast spectral evolution (τ₁) was determined to be due to vibrational cooling of low frequency modes anharmonically coupled to the carbonyl stretches that were excited after electronic internal conversion. The results show that cooling of both low and high frequency vibrational modes on the electronic ground state give rise to the observed picosecond TRIR transient spectra of this compound, without the need to invoke electronically excited states.
NASA Astrophysics Data System (ADS)
Makhlouf, Houssin; Karam, Chantal; Lamouchi, Amina; Tingry, Sophie; Miele, Philippe; Habchi, Roland; Chtourou, Radhouane; Bechelany, Mikhael
2018-06-01
In this work, ZnO nanowires (ZnO NWs) and urchin-like ZnO nanowires (U-ZnO NWs) based on self-assembled ordered polystyrene sphere (PS) were successfully prepared by combining atomic layer deposition (ALD) and electrochemical deposition (ECD) processes to build UV photosensors. The photo-response of the prepared samples was investigated and compared. The growth of the nanowires on self-assembled, ordered PS introduces a significant modification on the morphology, crystal orientation and grain size of U-ZnO NWs compared to randomly, vertically aligned ZnO NWs, and therefore improves the photo-response of U-ZnO NWs. The photocurrent may be produced by either a surface or bulk-related process. For ZnO NW-based photosensors, the photocurrent was monitored by a surface related process, whereas, it was mainly governed by a bulk related process for U-ZnO NWs, resulting in a higher and faster photo-response. The study of the rise and decay time constants for both materials showed that these parameters were strikingly sensitive to the optical properties.
Murdaca, Giuseppe; Gulli, Rossella; Spanò, Francesca; Lantieri, Francesca; Burlando, Martina; Parodi, Aurora; Mandich, Paola; Puppo, Francesco
2014-10-01
The tumor necrosis factor-α (TNF-α) gene has been proposed as a major candidate gene in psoriatic arthritis (PsA). TNF-α is a therapeutic target for patients responding poorly to conventional treatments. We investigated the role of single-nucleotide polymorphisms (SNPs) at positions -238, -308, and +489 of the TNF-α gene in the genetic susceptibility to PsA, in the severity of the disease, and, finally, in the response to TNF-α inhibitors (adalimumab, etanercept, or infliximab). Fifty-seven Caucasian PsA patients and 155 healthy matched controls were studied. The SNP +489 variant allele A was significantly associated with PsA susceptibility (P=0.0136) and severity of clinical (Psoriasis Area and Severity Index score, American College of Rheumatology criteria, Disease Activity Score 28, and Disability Index Health Assessment Questionnaire) and laboratory (C-reactive protein and erythrocyte sedimentation rate) parameters (P-values ranging from 0.016 to 2.908 × 10(-12)). The difference in severity was accounted for by the differences between the AA and GA genotypes with respect to the GG genotype. The SNP +489A allele shows a trend of association with the response to PsA treatment with etanercept. These findings suggest a role of the SNP +489A allele in the susceptibility and severity of PsA.
Glerean, Enrico; Salmi, Juha; Lahnakoski, Juha M; Jääskeläinen, Iiro P; Sams, Mikko
2012-01-01
Functional brain activity and connectivity have been studied by calculating intersubject and seed-based correlations of hemodynamic data acquired with functional magnetic resonance imaging (fMRI). To inspect temporal dynamics, these correlation measures have been calculated over sliding time windows with necessary restrictions on the length of the temporal window that compromises the temporal resolution. Here, we show that it is possible to increase temporal resolution by using instantaneous phase synchronization (PS) as a measure of dynamic (time-varying) functional connectivity. We applied PS on an fMRI dataset obtained while 12 healthy volunteers watched a feature film. Narrow frequency band (0.04-0.07 Hz) was used in the PS analysis to avoid artifactual results. We defined three metrics for computing time-varying functional connectivity and time-varying intersubject reliability based on estimation of instantaneous PS across the subjects: (1) seed-based PS, (2) intersubject PS, and (3) intersubject seed-based PS. Our findings show that these PS-based metrics yield results consistent with both seed-based correlation and intersubject correlation methods when inspected over the whole time series, but provide an important advantage of maximal single-TR temporal resolution. These metrics can be applied both in studies with complex naturalistic stimuli (e.g., watching a movie or listening to music in the MRI scanner) and more controlled (e.g., event-related or blocked design) paradigms. A MATLAB toolbox FUNPSY ( http://becs.aalto.fi/bml/software.html ) is openly available for using these metrics in fMRI data analysis.
Okumura, Taiga; Yamaguchi, Noriko; Dohi, Terumi; Iijima, Kazuki; Kogure, Toshihiro
2018-06-26
Radiocesium-bearing microparticles (CsPs) substantially made of silicate glass are a novel form of radiocesium emitted from the broken containment vessel of Fukushima Dai-ichi nuclear power plant. CsPs have a potential risk of internal radiation exposure caused by inhalation. Radiation-contaminated waste including CsPs is being burned in incinerators; therefore, this study has investigated the responses of CsPs to heating in air. The radioactivity of CsPs gradually decreased from 600 °C and was almost lost when the temperature reached 1000 °C. The size and spherical morphology of CsPs were almost unchanged after heating, but cesium including radiocesium, potassium and chlorine were lost, probably diffused away from the CsPs. Iron, zinc and tin originally dissolved in the glass matrix were crystallized to oxide nanoparticles inside the CsPs. When the CsPs were heated together with weathered granitic soil that is common in Fukushima, the radiocesium released from CsPs was sorbed by the surrounding soil. From these results, it is expected that the radioactivity of CsPs will be lost when radiation-contaminated waste including CsPs is burned in incinerators.
Pinot, F; Bachelet, M; François, D; Polla, B S; Walti, H
1999-01-01
Tobacco smoke (TS) is a potent source of oxidants and oxidative stress is an important mechanism by which TS exerts its toxicity in the lung. We have shown that TS induces heat shock (HS)/stress protein (HSP) synthesis in human monocytes. Pulmonary surfactant (PS) whose major physiological function is to confer mechanical stability to alveoli, also modulates oxidative metabolism and other pro-inflammatory functions of monocytes-macrophages. In order to determine whether PS alters the stress response induced by TS, we incubated human peripheral blood monocytes overnight with modified natural porcine surfactant (Curosurf) (1 mg/ml) before exposure to TS. Curosurf decreased TS-induced, but not HS-induced, expression of the major cytosolic, inducible 72 kD HSP (Hsp70). Furthermore, TS-generated superoxide anions production was significantly decreased by Curosurf in an acellular system, suggesting a direct scavenging effect of PS. We also examined the effects of TS and PS on monocytes ultrastructure. Monocytes incubated with Curosurf presented smoother cell membranes than control monocytes, while TS-induced monocyte vacuolization was, at least in part, prevented by Curosurf. Taken together, our data suggest that PS plays a protective role against oxygen radical-mediated, TS-induced cellular stress responses.
Impact of Blood Flow Restriction Exercise on Muscle Fatigue Development and Recovery.
Husmann, Florian; Mittlmeier, Thomas; Bruhn, Sven; Zschorlich, Volker; Behrens, Martin
2018-03-01
The present study was designed to provide mechanistic insight into the time course and etiology of muscle fatigue development and recovery during and after low-intensity exercise when it is combined with blood flow restriction (BFR). Seventeen resistance-trained males completed four sets of low-intensity isotonic resistance exercise under two experimental conditions: knee extension exercise (i) with BFR and (ii) without BFR (CON). Neuromuscular tests were performed before, during (immediately after each set of knee extension exercise), and 1, 2, 4, and 8 min after each experimental condition. Maximal voluntary torque, quadriceps twitch torque in response to paired electrical stimuli at 10 Hz (PS10) and 100 Hz (PS100), PS10·PS100 ratio as an index of low-frequency fatigue, and voluntary activation were measured under isometric conditions. Perceptual and EMG data were recorded during each exercise condition. After the first set of exercise, BFR induced significantly greater reductions in maximal voluntary torque, PS100, and PS10·PS100 ratio compared with CON. These parameters progressively declined throughout the BFR protocol but recovered substantially within 2 min postexercise when blood flow was restored. Neither a progressive decline in the course of the exercise protocol nor a substantial recovery of these parameters occurred during and after CON. Only at exercise termination, voluntary activation differed significantly between BFR and CON with greater reductions during BFR. At the early stage of exercise, BFR exacerbated the development of muscle fatigue mainly due to a pronounced impairment in contractile function. Despite the high level of muscle fatigue during BFR exercise, the effect of BFR on muscle fatigue was diminished after 2 min of reperfusion, suggesting that BFR has a strong but short-lasting effect on neuromuscular function.
Glinatsi, Daniel; Bird, Paul; Gandjbakhch, Frederique; Mease, Philip J; Bøyesen, Pernille; Peterfy, Charles G; Conaghan, Philip G; Østergaard, Mikkel
2015-12-01
To assess changes following treatment and the reliability and responsiveness to change of the Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS) in a randomized controlled trial. Forty patients with PsA randomized to either placebo or abatacept (ABA) had MRI of either 1 hand (n = 20) or 1 foot (n = 20) at baseline and after 6 months. Images were scored blindly twice by 3 independent readers according to the PsAMRIS (for synovitis, tenosynovitis, periarticular inflammation, bone edema, bone erosion, and bone proliferation). Inflammatory features improved numerically but statistically nonsignificantly in the ABA group but not the placebo group. Baseline intrareader intraclass correlation coefficients (ICC) were good (≥ 0.50) to very good (≥ 0.80) for all features in both hand and foot. Baseline interreader ICC were good (ICC 0.72-0.96) for all features, except periarticular inflammation and bone proliferation in the hand and tenosynovitis in the foot (ICC 0.25-0.44). Intrareader and interreader ICC for change scores varied. Guyatt's responsiveness index (GRI) was high for inflammatory features in the hand and metatarsophalangeal joints (GRI -0.67 to -3.13; bone edema not calculable). Minimal change and low prevalence resulted in low ICC and GRI for bone damage. PsAMRIS showed overall good intrareader agreement in the hand and foot, and inflammatory feature scores were responsive to change, suggesting that PsAMRIS may be a valid tool for MRI assessment of hands and feet in PsA clinical trials.
Hirve, Siddhivinayak; Bavdekar, Ashish; Pandit, Anand; Juvekar, Sanjay; Patil, Malini; Preziosi, Marie-Pierre; Tang, Yuxiao; Marchetti, Elisa; Martellet, Lionel; Findlow, Helen; Elie, Cheryl; Parulekar, Varsha; Plikaytis, Brian; Borrow, Ray; Carlone, George; Kulkarni, Prasad S; Goel, Akshay; Suresh, Karupothula; Beri, Suresh; Kapre, Subhash; Jadhav, Suresh; Preaud, Jean-Marie; Viviani, Simonetta; LaForce, F Marc
2012-10-05
This study compares the immunogenicity and safety of a single dose of a new meningococcal A conjugate vaccine (PsA-TT, MenAfriVac™, Serum Institute of India Ltd., Pune) against the meningococcal group A component of a licensed quadrivalent meningococcal polysaccharide vaccine (PsACWY, Mencevax ACWY(®), GSK, Belgium) 28 days after vaccination in Indian children. This double-blind, randomized, controlled study included 340 Indian children aged 2-10 years enrolled from August to October 2007; 169 children received a dose of PsA-TT while 171 children received a dose of PsACWY. Intention-to-treat analysis showed that 95.2% of children in PsA-TT group had a ≥4-fold response in serum bactericidal titers (rSBA) 28 days post vaccination as compared to 78.2% in the PsACWY group. A significantly higher rSBA GMT (11,209, 95%CI 9708-12,942) was noted in the PsA-TT group when compared to PsACWY group (2838, 95%CI 2368-3401). Almost all children in both vaccine groups had a ≥4-fold response in group A-specific IgG concentration but the IgG GMC was significantly greater in the PsA-TT group (89.1 μg/ml, 95%CI 75.5-105.0) when compared to the PsACWY group (15.3 μg/ml, 95%CI 12.3-19.2). Local and systemic reactions during the 4 days after immunization were similar for both vaccine groups except for tenderness (30.2% in PsA-TT group vs 12.3% in PsACWY group). None of the adverse events or serious adverse events was related to the study vaccines. We conclude that MenAfriVac™ is well tolerated and significantly more immunogenic when compared to a licensed polysaccharide vaccine, in 2-to-10-year-old Indian children. Copyright © 2012 Elsevier Ltd. All rights reserved.
Compact first and second order polarization mode dispersion emulator
NASA Astrophysics Data System (ADS)
Zhang, Yang; Li, Shiguang; Yang, Changxi
2005-08-01
We propose a 1st and 2nd order polarization mode dispersion emulator (PMDE) with one variable differential group delay (DGD) element using birefringence crystals and four polarization controllers (PCs). Monte Carlo simulations demonstrate that the output 1st and 2nd order polarization mode dispersion (PMD) generated by the PMDE consists with statistic theory. Compared with former PMDEs, this design is tunable, lower-cost, and more integrated for fabrication, which shows response time of 150 ?s, response frequency of 3.8 kHz, working wavelength of 1550 nm, total power consumption of less than 3 W, working range of 0---84 ps and 0---3600 ps2 for 1st and 2nd order PMD emulation, respectively. Also, it is programmable and can be controlled by either singlechip or computer. It can be applied to study the outage probability of optical communication systems due to PMD effect and the effectiveness of PMD compensation.
Södergren, A L; Tynngård, N; Berlin, G; Ramström, S
2016-02-01
Storage lesions may prevent transfused platelets to respond to agonists and arrest bleeding. The aim of this study was to evaluate and quantify the capacity of platelet activation during storage using flow cytometry and new markers of platelet activation. Activation responses of platelets prepared by apheresis were measured on days 1, 5, 7 and 12. In addition, comparisons were made for platelet concentrates stored until swirling was affected. Lysosome-associated membrane protein-1 (LAMP-1), P-selectin and phosphatidylserine (PS) exposure were assessed by flow cytometry on platelets in different subpopulations in resting state or following stimulation with platelet agonists (cross-linked collagen-related peptide (CRP-XL), PAR1- and PAR4-activating peptides). The ability to form subpopulations upon activation was significantly decreased already at day 5 for some agonist combinations. The agonist-induced exposure of PS and LAMP-1 also gradually decreased with time. Spontaneous exposure of P-selectin and PS increased with time, while spontaneous LAMP-1 exposure was unchanged. In addition, agonist-induced LAMP-1 expression clearly discriminated platelet concentrates with reduced swirling from those with retained swirling. This suggests that LAMP-1 could be a good marker to capture changes in activation capacity in stored platelets. The platelet activation potential seen as LAMP-1 exposure and fragmentation into platelet subpopulations is potential sensitive markers for the platelet storage lesion. © 2015 International Society of Blood Transfusion.
Ahmadi, Mehdi; Ghanbari, Farshid
2016-10-01
Greywater (GW) is a potential source for water reuse in various applications. However, GW treatment is still a vital issue in water reuse in cases of environmental standards and risk to public health. This study investigates optimization and modeling of a hybrid process for COD removal from GW. Persulfate (PS) was simultaneously activated by electrogenerated ferrous ion (EC) and UV to generate sulfate radical. Photoelectro-persulfate (PEPS) was optimized by Box-Behnken design and the effects of four variables (pH, PS dosage, current density, and electrolysis time) were evaluated on COD removal. The results and several coefficients showed that the obtained model was acceptable for predicting the COD removal. Moreover, under optimum conditions (pH = 6.9, PS = 8.8 mM, current density = 2.0 mA/cm(2), and 49.3 min electrolysis time), BOD5, turbidity, TSS, phosphate, and UV254 were effectively removed and COD and BOD5 values reached to discharge standards. Different configurations of the processes were assessed for COD removal. The order of COD removal efficiency followed: PS < Fe(II) < UV/PS ≤ Fe(II)/PS < Fe(II)/PS/UV < electrocoagulation ≤ electrocoagulation/UV < electro-PS < PEPS. The monitoring PS concentration during 60 min reaction time in the aforesaid processes indicated that PEPS could remarkably activate PS. The solution pH was also monitored and related results revealed that the presence of PS during the 10 min first time decreased pH value while production of hydroxide ion at cathode increased pH significantly. Finally, the contribution of electrochemical process in the electrical energy consumption was far less than that of photolysis process in hybrid PEPS process.
Attenuating a sickle cell crisis with annexin V.
Kennedy, James Randall
2015-05-01
A sickle cell crisis is a painful and dangerous condition that defies effective treatment but fortunately it usually terminates spontaneously and patients spend far more time crisis free than in its painful throes. This suggests that an unstable physiologic balance exists between steady state sickle cell disease (SCD) and the crisis state and if this is so a therapeutic nudge during a crisis may help to terminate it. Annexin V may be able to provide this push. The phosphatidylserine (PS) molecules normally appear on the surface of senescent erythrocytes where they are recognized by macrophages and rapidly removed so that normally only about 1% are present in the circulation but in SCD 30-40% are prematurely senescent and their removal is delayed. The PS+ sickle erythrocytes remaining in the circulation adhere to the endothelium and their exposed PS acts as a platform for the initiation of the coagulation cascade that is responsible for clot propagation. Annexin V's great affinity for PS allows it to bond to it forming a shield that blocks both of these actions suggesting that its therapeutic administration during a sickle crisis may be able to hasten its termination. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.
Screening and identification of novel B cell epitopes of Toxoplasma gondii SAG1.
Wang, Yanhua; Wang, Guangxiang; Zhang, Delin; Yin, Hong; Wang, Meng
2013-04-30
The identification of protein epitopes is useful for diagnostic purposes and for the development of peptide vaccines. In this study, the epitopes of Toxoplasma gondii SAG1 were identified using synthetic peptide techniques with the aid of bioinformatics. Eleven peptides derived from T. gondii SAG1 were assessed by ELISA using pig sera from different time points after infection. Four (PS4, PS6, PS10 and PS11), out of the eleven peptides tested were recognized by all sera. Then, shorter peptides that were derived from PS4, PS6, PS10 and PS11 were predicted using bioinformatics and tested by experimentation. Four out of nine shorter peptides were identified successfully (amino acids 106-120, 166-180, 289-300 and 313-332). We have precisely located the epitopes of T. gondii SAG1 using pig sera collected at different time points after infection. The identified epitopes may be useful for the further study of epitope-based vaccines and diagnostic reagents.
Heyes, Logan C; Reichau, Sebastian; Cross, Penelope J; Jameson, Geoffrey B; Parker, Emily J
2014-12-01
3-Deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyses the first committed step of the shikimate pathway, which produces the aromatic amino acids as well as many other aromatic metabolites. DAH7PS catalyses an aldol-like reaction between phosphoenolpyruvate and erythrose 4-phosphate. Three phosphoenolpyruvate mimics, (R)-phospholactate, (S)-phospholactate and vinyl phosphonate [(E)-2-methyl-3-phosphonoacrylate], were found to competitively inhibit DAH7PS from Neisseria meningitidis, which is the pathogen responsible for bacterial meningitis. The most potent inhibitor was the vinyl phosphonate with a Ki value of 3.9±0.4μM. We report for the first time crystal structures of these compounds bound in the active site of a DAH7PS enzyme which reveals that the inhibitors bind to the active site of the enzyme in binding modes that mimic those of the predicted oxocarbenium and tetrahedral intermediates of the enzyme-catalysed reaction. Furthermore, the inhibitors accommodate the binding of a key active site water molecule. Together, these observations provide strong evidence that this active site water participates directly in the DAH7PS reaction, enabling the facial selectivity of the enzyme-catalysed reaction sequence to be delineated. Copyright © 2014 Elsevier Inc. All rights reserved.
English, L K; Fearnbach, S N; Lasschuijt, M; Schlegel, A; Anderson, K; Harris, S; Wilson, S J; Fisher, J O; Savage, J S; Rolls, B J; Keller, K L
2016-10-01
Large portions of energy-dense foods drive energy intake but the brain mechanisms underlying this effect are not clear. Our main objective was to investigate brain function in response to food images varied by portion size (PS) and energy density (ED) in children using functional magnetic resonance imaging (fMRI). Blood-oxygen-level-dependent (BOLD) fMRI was completed in 36 children (ages 7-10 years) after a 2-h fast while viewing food images at two levels of PS (Large PS, Small PS) and two levels of ED (High ED, Low ED). Children rated perceived fullness pre- and post-fMRI, as well as liking of images on visual analog scales post-fMRI. Anthropometrics were completed 4 weeks before the fMRI. Large PS vs Small PS and High ED vs Low ED were compared with region-of-interest analyses using Brain Voyager v 2.8. Region-of-interest analyses revealed that activation in the right inferior frontal gyrus (P=0.03) was greater for Large PS vs Small PS. Activation was reduced for High ED vs Low ED in the left hypothalamus (P=0.03). Main effects were no longer significant after adjustment for pre-fMRI fullness and liking ratings (PS, P=0.92; ED, P=0.58). This is the first fMRI study to report increased activation to large portions in a brain region that is involved in inhibitory control. These findings may contribute to understanding why some children overeat when presented with large portions of palatable food.
Intermolecular Structural Change for Thermoswitchable Polymeric Photosensitizer
DOE Office of Scientific and Technical Information (OSTI.GOV)
Park, Wooram; Park, Sin-Jung; Cho, Soojeong
2016-08-17
A switchable photosensitizer (PS), which can be activated at a spe-cific condition beside light, has tremendous advantages for photo-dynamic therapy (PDT). Herein, we developed a thermo-switchable polymeric photosensitizer (T-PPS) by conjugating PS (Pheophor-bide-a, PPb-a) to a temperature-responsive polymer backbone of biocompatible hydroxypropyl cellulose (HPC). Self-quenched PS molecules linked in close proximity by pi-pi stacking in T-PPS were easily transited to an active monomeric state by the tempera-ture induced phase transition of polymer backbones. The tempera-ture responsive inter-molecular interaction changes of PS molecules in T-PPS were demonstrated in synchrotron small-angle X-ray scattering (SAXS) and UV-Vis spectrophotometer analysis. The T-PPS allowed switchablemore » activation and synergistically enhanced cancer cell killing effect at the hyperthermia temperature (45 °C). Our developed T-PPS has the considerable potential not only as a new class of photomedicine in clinics but also as a biosensor based on temperature responsiveness.« less
Quantification of Tumor Vascular Permeability and Blood Volume by Positron Emission Tomography
Chen, Haojun; Tong, Xiao; Lang, Lixin; Jacobson, Orit; Yung, Bryant C.; Yang, Xiangyu; Bai, Ruiliang; Kiesewetter, Dale O.; Ma, Ying; Wu, Hua; Niu, Gang; Chen, Xiaoyuan
2017-01-01
Purpose: Evans Blue (EB) is an azo dye that binds quantitatively with serum albumin. With an albumin binding, NOTA conjugated truncated Evan's blue (NEB) dye derived PET tracer, we aimed to establish a strategy for evaluating vascular permeability in malignant tumors via non-invasive PET. Experimental design: Sixty-minute dynamic PET using [18F]FAl-NEB was performed in three xenograft tumor models including INS-1 rat insulinoma, UM-SCC-22B human head and neck carcinoma and U-87 MG human glioblastoma. Tumor vascular permeability was quantified by the difference of the slopes between tumor and blood time-activity curve (TACs, expressed as Ps). The method was further substantiated by EB extraction and colorimetric assay and correlates with that calculated from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). The changes in tumor vasculature at different time points were assessed with NEB PET in U-87 MG and UM-SCC-22B tumor models after treatment with bevacizumab or doxorubicin. Result: The Ps values calculated from tumor and blood TACs from multiple time-point static images are consistent with those from dynamic images. Moreover, the Ps showed a positive and significant correlation with extracted EB concentration and KPS-MRI generated from DCE-MRI, which further confirmed the soundness of this methodology. The antiangiogenic effect of bevacizumab could be revealed by NEB PET in U-87 MG tumors as early as 8 hrs after therapy, demonstrated by a substantial decrease of Ps. On the contrary, there was no significant change of Ps in bevacizumab treated UM-SCC-22B tumors, compared with control group. However, the significant changes of Pswere overestimated in doxorubicin treated UM-SCC-22B tumors. Conclusions: We successfully developed a relatively convenient and novel strategy to evaluate vascular permeability and blood volume using NEB PET. This method will be advantageous in evaluating vascular permeability, promoting drug delivery, and monitoring tumor response to therapeutics that affect tumor angiogenesis. PMID:28744320
NASA Astrophysics Data System (ADS)
Di Francesco, A.; Bugalho, R.; Oliveira, L.; Pacher, L.; Rivetti, A.; Rolo, M.; Silva, J. C.; Silva, R.; Varela, J.
2016-03-01
We present a readout and digitization ASIC featuring low-noise and low-power for time-of flight (TOF) applications using SiPMs. The circuit is designed in standard CMOS 110 nm technology, has 64 independent channels and is optimized for time-of-flight measurement in Positron Emission Tomography (TOF-PET). The input amplifier is a low impedance current conveyor based on a regulated common-gate topology. Each channel has quad-buffered analogue interpolation TDCs (time binning 20 ps) and charge integration ADCs with linear response at full scale (1500 pC). The signal amplitude can also be derived from the measurement of time-over-threshold (ToT). Simulation results show that for a single photo-electron signal with charge 200 (550) fC generated by a SiPM with 320 pF capacitance the circuit has 24 (30) dB SNR, 75(39) ps r.m.s. resolution, and 4(8) mW power consumption. The event rate is 600 kHz per channel, with up to 2 MHz dark counts rejection.
NASA Astrophysics Data System (ADS)
Straton, Alexandru; Gidu, Diana Victoria; Micu, Alexandru
2015-02-01
Poor lateral flexor muscle strength can be an important source of lumbar/thoracic back pain in women. The purpose of this study was to evaluate pelvic stabilization (PS) and no pelvic stabilization (NoPS) lateral flexion strength exercise training on the development of isolated right and left lateral flexion strength. Isometric torque of the isolated right and left lateral flexion muscles was measured at two positions (0° and 30° opposed angle range of motion) on 42 healthy women before and after 8 weeks of PS and NoPS lateral flexion strength exercise training. Subjects were assigned in three groups, the first (n=14) trained 3 times/week with PS lateral flexion strength exercise, the second (n=14) trained 3 times/week with NoPS lateral flexion strength exercise and the third (control, n=14) did not train. Post training isometric strength values describing PS and NoPS lateral flexion strength improved in greater extent for the PS lateral flexion strength exercise group and in lesser extent for the NoPS lateral flexion strength exercise group, in both angles (p<0.05) relative to controls. These data indicate that the most effective way of training the spine lateral flexion muscles is PS lateral flexion strength exercises; NoPS lateral flexion strength exercises can be an effective way of training for the spine lateral flexion muscles, if there is no access to PS lateral flexion strength training machines.
Valentijn, K; Tranchand Bunel, D; Vaudry, H
1992-07-01
The rat thyrotropin-releasing hormone (TRH) precursor (prepro-TRH) contains five copies of the TRH progenitor sequence linked together by intervening sequences. Recently, we have shown that the connecting peptides prepro-TRH-(160-169) (Ps4) and prepro-TRH-(178-199) (Ps5) are released from rat hypothalamic neurones in response to elevated potassium concentrations, in a calcium-dependent manner. In the present study, the role of voltage-operated calcium channels in potassium-induced release of Ps4 and Ps5 was investigated, using a perifusion system for rat hypothalamic slices. The release of Ps4 and Ps5 stimulated by potassium (70 mM) was blocked by the inorganic ions Co2+ (2.6 mM) and Ni2+ (5 mM). In contrast, the stimulatory effect of KCl was insensitive to Cd2+ (100 microM). The dihydropyridine antagonist nifedipine (10 microM) had no effect on K(+)-evoked release of Ps4 and Ps5. Furthermore, the response to KCl was not affected by nifedipine (10 microM) in combination with diltiazem (1 microM), a benzothiazepine which increases the affinity of dihydropyridine antagonists for their receptor. The dihydropyridine agonist BAY K 8644, at concentrations as high as 1 mM, did not stimulate the basal secretion of Ps4 and Ps5. In addition, BAY K 8644 had no potentiating effect on K(+)-induced release of Ps4 and Ps5. The marine cone snail toxin omega-conotoxin, a blocker of both L- and N-type calcium channels had no effect on the release of Ps4 and Ps5 stimulated by potassium. Similarly, the omega-conopeptide SNX-111, a selective blocker of N-type calcium channels, did not inhibit the stimulatory effect of potassium. The release of Ps4 and Ps5 evoked by high K+ was insensitive to the non-selective calcium channel blocker verapamil (20 microM). Amiloride (1 microM), a putative blocker of T-type calcium channels, did not affect KCl-induced secretion of the two connecting peptides. Taken together, these results indicate that two connecting peptides derived from the pro-TRH, Ps4 and Ps5, are released by K(+)-induced depolarization through activation of voltage-sensitive calcium channels. The calcium channels appear to have a pharmacological profile different from that of L- and N-type channels. Although, their insensitivity to low Cd2+ concentrations and sensitivity to Ni2+ ions would support the involvement of T-type calcium channels, the lack of effect of amiloride suggests that they belong to a yet undefined class of calcium channels.
USDA-ARS?s Scientific Manuscript database
Benefits of plant sterols (PS) for cholesterol lowering are compromised by large variability in efficacy across individuals. High fractional cholesterol synthesis measured by deuterium incorporation has been associated with non-response to PS consumption; however, prospective studies showing this as...
Katagiri, Kiyofumi; Shishijima, Yoshinori; Koumoto, Kunihito; Inumaru, Kei
2018-01-01
pH-Responsive smart capsules were developed by the layer-by-layer assembly with a colloidtemplating technique. Polystyrene (PS) particles were employed as core templates. Acid-soluble inorganic nanosheets were prepared from Mg-Al layered double hydroxide (LDH) by an exfoliation technique. LDH nanosheets and anionic polyelectrolytes were alternatively deposited on PS core particles by the layer-by-layer assembly using electrostatic interaction. Hollow capsules were obtained by the removal of the PS core particles. The hollow capsules obtained thus were collapsed at acidic conditions by dissolution of LDH nanosheets in the hollow shells. The dissolution rate, i.e., the responsiveness of capsule, is tunable according to the strength of acids.
NASA Astrophysics Data System (ADS)
Luchowski, R.; Kapusta, P.; Szabelski, M.; Sarkar, P.; Borejdo, J.; Gryczynski, Z.; Gryczynski, I.
2009-09-01
Förster resonance energy transfer (FRET) can be utilized to achieve ultrashort fluorescence responses in time-domain fluorometry. In a poly(vinyl) alcohol matrix, the presence of 60 mM Rhodamine 800 acceptor shortens the fluorescence lifetime of a pyridine 1 donor to about 20 ps. Such a fast fluorescence response is very similar to the instrument response function (IRF) obtained using scattered excitation light. A solid fluorescent sample (e.g a film) with picosecond lifetime is ideal for IRF measurements and particularly useful for time-resolved microscopy. Avalanche photodiode detectors, commonly used in this field, feature color- dependent-timing responses. We demonstrate that recording the fluorescence decay of the proposed FRET-based reference sample yields a better IRF approximation than the conventional light-scattering method and therefore avoids systematic errors in decay curve analysis.
Pi, Chia-Chen; Chu, Ching-Liang; Lu, Chu-Ying; Zhuang, Yu-Jing; Wang, Cheng-Li; Yu, Yao-Hsuan; Wang, Hui-Yi; Lin, Chih-Chung; Chen, Chun-Jen
2014-01-09
The fungus of Ganoderma is a basidiomycete that possesses a variety of pharmacological effects and has been used in traditional Asian medicine for centuries. Ganoderma formosanum is a native Ganoderma species isolated in Taiwan, and we have previously demonstrated that PS-F2, a polysaccharide fraction purified from the submerged culture broth of G. formosanum, exhibits immunostimulatory properties in macrophages. In this study, we further characterized the adjuvant functions of PS-F2. In vitro, PS-F2 stimulated dendritic cells (DCs) to produce proinflammatory cytokines, including TNF-α, interleukin (IL)-6, and IL-12/IL-23 p40. PS-F2 also stimulated DCs to express the maturation markers CD40, CD80, CD86, and MHC class II. In a murine splenocyte culture, PS-F2 treatment resulted in elevated expression of T-bet and interferon (IFN)-γ in T lymphocytes. When used as an adjuvant in vivo with the ovalbumin (OVA) antigen, PS-F2 stimulated OVA-specific antibody production and primed IFN-γ production in OVA-specific T lymphocytes. PS-F2-adjuvated immunization also induced OVA-specific CTLs, which protected mice from a challenge with tumor cells expressing OVA. Collectively, our data show that PS-F2 functions as an adjuvant capable of inducing a Th1-polarized adaptive immune response, which would be useful in vaccines against viruses and tumors. Copyright © 2013 Elsevier Ltd. All rights reserved.
[Opinion of healthcare professionals on patient safety in a primary level hospital].
Skodová, M; Velasco Rodríguez, M J; Fernández Sierra, M A
2011-01-01
To identify the patient safety (PS) culture perceived by health professionals of the Hospital Universitario Virgen de las Nieves (HUVN) in Granada. A descriptive cross-sectional study of professionals working in HUVN using the Spanish version of the questionnaire Hospital Survey On Patient Safety Culture (AHRQ), in July-August 2008. The sample size was estimated as 476 surveys (included 60% losses). The response rate was 62.8% (299 questionnaires). In the previous 12 months, 90.2% of professionals had not notified any adverse event (AE). The average perception of PS was 6.57 ± 1.82 (scale 0-10). Teamwork in the unit for PS was the best rated dimension (66.9%). There was a positive correlation (c. Pearson) between the perception of PS and the years that professionals had worked in specialisation (0.21), hospital (0.197) and unit (0.138), respectively (all, p < 0.05). According to category, the physicians have reported an AE with a likelihood 32.26 times greater than the assistants and technicians (p < 0.05). The PS perception dimension was viewed favourably by 34.1%. The management support (3.7%) and staffing (9%) were the main areas for improvement. The perception of PS at HUVN is good, even if the communication of errors is poor. The main area for improvement is a non-punitive communication of errors. It is advisable to promote a campaign to raise public awareness of the problem, to perform training programs for professionals and to implement systems for recording adverse events. Copyright © 2010 SECA. Published by Elsevier Espana. All rights reserved.
Zhao, Liyan; Odaka, Hideho; Ono, Hiroshi; Kajimoto, Shinji; Hatanaka, Koji; Hobley, Jonathan; Fukumura, Hiroshi
2005-01-01
The dynamics of Re(2,2'-bipyridine)(CO)3Cl MLCT state formation and decay were determined after femtosecond UV laser excitation and picosecond pulsed X-ray excitation, in an N,N-dimethylformamide (DMF) solution as well as in its solid form. At room temperature, after UV excitation, this MLCT excited state emits both in DMF solution and in the solid form. Transient absorption spectra were measured in solution at various delay times following excitation by a 160 fs, 390 nm laser pulse. There was a prompt absorption increase at around 460 nm occurring within the pump probe convolution (<1 ps), which was assigned to the formation of the 3MLCT state. This transient absorbance was constant over 100 ps. In contrast to the solution state, in the solid state, the emission maximum slightly red-shifts with increasing time after laser excitation. In both solid and solution the emission rises within the system response time. The solid sample exhibited a 1.4 ns emission decay that was not observed for the solution sample. The emission rise from a solid sample after 20 ps pulsed X-ray excitation was significantly slower than the system's time resolution. It is proposed that kinetically energetic electrons are ejected following X-ray induced ionisation, creating ionised tracks in which energetic cations and electrons take time to recombine yielding delayed 3MLCT states that emit.
NASA Astrophysics Data System (ADS)
Winter, Jan; Rapp, Stephan; Schmidt, Michael; Huber, Heinz P.
2017-09-01
In this paper, we present ultrafast measurements of the complex refractive index for copper up to a time delay of 20 ps with an accuracy <1% at laser fluences in the vicinity of the ablation threshold. The measured refractive index n and extinction coefficient k are supported by a simulation including the two-temperature model with an accurate description of thermal and optical properties and a thermomechanical model. Comparison of the measured time resolved optical properties with results of the simulation reveals underlying physical mechanisms in three distinct time delay regimes. It is found that in the early stage (-5 ps to 0 ps) the thermally excited d-band electrons make a major contribution to the laser pulse absorption and create a steep increase in transient optical properties n and k. In the second time regime (0-10 ps) the material expansion influences the plasma frequency, which is also reflected in the transient extinction coefficient. In contrast, the refractive index n follows the total collision frequency. Additionally, the electron-ion thermalization time can be attributed to a minimum of the extinction coefficient at ∼10 ps. In the third time regime (10-20 ps) the transient extinction coefficient k indicates the surface cooling-down process.
Food portion size and energy density evoke different patterns of brain activation in children12
Fearnbach, S Nicole; Wilson, Stephen J; Fisher, Jennifer O; Savage, Jennifer S; Rolls, Barbara J; Keller, Kathleen L
2017-01-01
Background: Large portions of food promote intake, but the mechanisms that drive this effect are unclear. Previous neuroimaging studies have identified the brain-reward and decision-making systems that are involved in the response to the energy density (ED) (kilocalories per gram) of foods, but few studies have examined the brain response to the food portion size (PS). Objective: We used functional MRI (fMRI) to determine the brain response to food images that differed in PSs (large and small) and ED (high and low). Design: Block-design fMRI was used to assess the blood oxygen level–dependent (BOLD) response to images in 36 children (7–10 y old; girls: 50%), which was tested after a 2-h fast. Pre-fMRI fullness and liking were rated on visual analog scales. A whole-brain cluster-corrected analysis was used to compare BOLD activation for main effects of the PS, ED, and their interaction. Secondary analyses were used to associate BOLD contrast values with appetitive traits and laboratory intake from meals for which the portions of all foods were increased. Results: Compared with small-PS cues, large-PS cues were associated with decreased activation in the inferior frontal gyrus (P < 0.01). Compared with low-ED cues, high-ED cues were associated with increased activation in multiple regions (e.g., in the caudate, cingulate, and precentral gyrus) and decreased activation in the insula and superior temporal gyrus (P < 0.01 for all). A PS × ED interaction was shown in the superior temporal gyrus (P < 0.01). BOLD contrast values for high-ED cues compared with low-ED cues in the insula, declive, and precentral gyrus were negatively related to appetitive traits (P < 0.05). There were no associations between the brain response to the PS and either appetitive traits or intake. Conclusions: Cues regarding food PS may be processed in the lateral prefrontal cortex, which is a region that is implicated in cognitive control, whereas ED activates multiple areas involved in sensory and reward processing. Possible implications include the development of interventions that target decision-making and reward systems differently to moderate overeating. PMID:27881393
Deodhar, A.; Fleischmann, R.; Mease, P. J.; Rudwaleit, M.; Nurminen, T.; Davies, O.
2017-01-01
Objective Early identification of patients unlikely to achieve good long‐term disease control with anti–tumor necrosis factor therapy in axial spondyloarthritis (SpA) and psoriatic arthritis (PsA) is important for physicians following treat‐to‐target recommendations. Here we assess associations between disease activity or clinical response during the first 12 weeks of treatment and attainment of treatment targets at week 48 in axial SpA and PsA patients receiving certolizumab pegol. Methods The relationship between disease activity or clinical response during the first 12 weeks of treatment and achievement of week‐48 targets (for axial SpA: inactive disease based on Ankylosing Spondylitis Disease Activity Score [ASDAS] using the C‐reactive protein [CRP] level, or Bath Ankylosing Spondylitis Disease Activity Index <2 with normal CRP level; and for PsA: minimal disease activity) was assessed post hoc using RAPID‐axSpA and RAPID‐PsA trial data. Results A clear relationship between disease activity from week 2 to 12 and achievement of week‐48 treatment targets was observed in both axial SpA and PsA populations. In axial SpA, week‐48 ASDAS inactive disease was achieved by 0% of patients (0 of 21) with ASDAS very high disease activity at week 12, compared to 68% of patients (34 of 50) with week‐12 ASDAS inactive disease. For PsA, week‐48 minimal disease activity was achieved by 0% of patients (0 of 26) with Disease Activity Score in 28 joints (DAS28) using the CRP level >5.1 at week 12, compared to 73% of patients (57 of 78) with DAS28‐CRP <2.6. Similar results were observed regardless of the disease activity measure used. Clinical response at week 12 also predicted week‐48 outcomes, though to a lesser extent than disease activity. Conclusion Using disease activity and the clinical response state during the first 12 weeks of certolizumab pegol treatment, it was possible to identify a subset of axial SpA and PsA patients unlikely to achieve long‐term treatment goals. PMID:27696727
Mor, Ahmet; Kayacan, Yildirim; Ipekoglu, Gokhan; Arslanoglu, Erkal
2018-04-21
This study aimed to examine the effect of CHO-E consumption after high-intensity exercise on insulin, cortisol hormones and blood glucose responses, which is important for performance and recovery in athletes. Sixteen volunteers, male athletes, participated into this study. Athletes were divided into two groups as experiment (CHO-E) and placebo (PLA). Blood was taken from the athletes three times as basal, post-exercise (PE) and 2 h after ingestion of supplement (PS). When inter-group comparisons, insulin was significantly higher in the CHO-E group than the PLA group at the PS phase (p < .05). Cortisol significantly decreased in the CHO-E group at the PS compared to the PE (p < .05). Carbohydrate-electrolyte consumption after high-intensity exercise, accelerates the recovery process by providing optimal recovery, and enable the metabolism to remain in the anabolic state by preventing it from entering in the catabolic process as well as provides hormonal balance in metabolism.
Al-Batran, S-E; Van Cutsem, E; Oh, S C; Bodoky, G; Shimada, Y; Hironaka, S; Sugimoto, N; Lipatov, O N; Kim, T-Y; Cunningham, D; Rougier, P; Muro, K; Liepa, A M; Chandrawansa, K; Emig, M; Ohtsu, A; Wilke, H
2016-04-01
The phase III RAINBOW trial demonstrated that the addition of ramucirumab to paclitaxel improved overall survival, progression-free survival, and tumor response rate in fluoropyrimidine-platinum previously treated patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Here, we present results from quality-of-life (QoL) and performance status (PS) analyses. Patients with Eastern Cooperative Oncology Group PS of 0/1 were randomized to receive ramucirumab (8 mg/kg i.v.) or placebo on days 1 and 15 of a 4-week cycle, with both arms receiving paclitaxel (80 mg/m(2)) on days 1, 8, and 15. Patient-reported outcomes were assessed with the QoL/health status questionnaires EORTC QLQ-C30 and EQ-5D at baseline and 6-week intervals. PS was assessed at baseline and day 1 of every cycle. Time to deterioration (TtD) in each QLQ-C30 scale was defined as randomization to first worsening of ≥10 points (on 100-point scale) and TtD in PS was defined as first worsening to ≥2. Hazard ratios (HRs) for treatment effect were estimated using stratified Cox proportional hazards models. Of the 665 patients randomized, 650 (98%) provided baseline QLQ-C30 and EQ-5D data, and 560 (84%) also provided data from ≥1 postbaseline time point. Baseline scores for both instruments were similar between arms. Of the 15 QLQ-C30 scales, 14 had HR < 1, indicating similar or longer TtD in QoL for ramucirumab + paclitaxel. Treatment with ramucirumab + paclitaxel was also associated with a delay in TtD in PS to ≥2 (HR = 0.798, P = 0.0941). Alternate definitions of PS deterioration yielded similar results: PS ≥ 3 (HR = 0.656, P = 0.0508), deterioration by ≥1 PS level (HR = 0.802, P = 0.0444), and deterioration by ≥2 PS levels (HR = 0.608, P = 0.0063). EQ-5D scores were comparable between treatment arms, stable during treatment, and worsened at discontinuation. In patients with previously treated advanced gastric/GEJ adenocarcinoma, addition of ramucirumab to paclitaxel prolonged overall survival while maintaining patient QoL with delayed symptom worsening and functional status deterioration. NCT01170663. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
Berg, Eric; Roncali, Emilie; Hutchcroft, Will; Qi, Jinyi; Cherry, Simon R.
2016-01-01
In a scintillation detector, the light generated in the scintillator by a gamma interaction is converted to photoelectrons by a photodetector and produces a time-dependent waveform, the shape of which depends on the scintillator properties and the photodetector response. Several depth-of-interaction (DOI) encoding strategies have been developed that manipulate the scintillator’s temporal response along the crystal length and therefore require pulse shape discrimination techniques to differentiate waveform shapes. In this work, we demonstrate how maximum likelihood (ML) estimation methods can be applied to pulse shape discrimination to better estimate deposited energy, DOI and interaction time (for time-of-flight (TOF) PET) of a gamma ray in a scintillation detector. We developed likelihood models based on either the estimated detection times of individual photoelectrons or the number of photoelectrons in discrete time bins, and applied to two phosphor-coated crystals (LFS and LYSO) used in a previously developed TOF-DOI detector concept. Compared with conventional analytical methods, ML pulse shape discrimination improved DOI encoding by 27% for both crystals. Using the ML DOI estimate, we were able to counter depth-dependent changes in light collection inherent to long scintillator crystals and recover the energy resolution measured with fixed depth irradiation (~11.5% for both crystals). Lastly, we demonstrated how the Richardson-Lucy algorithm, an iterative, ML-based deconvolution technique, can be applied to the digitized waveforms to deconvolve the photodetector’s single photoelectron response and produce waveforms with a faster rising edge. After deconvolution and applying DOI and time-walk corrections, we demonstrated a 13% improvement in coincidence timing resolution (from 290 to 254 ps) with the LFS crystal and an 8% improvement (323 to 297 ps) with the LYSO crystal. PMID:27295658
Berg, Eric; Roncali, Emilie; Hutchcroft, Will; Qi, Jinyi; Cherry, Simon R
2016-11-01
In a scintillation detector, the light generated in the scintillator by a gamma interaction is converted to photoelectrons by a photodetector and produces a time-dependent waveform, the shape of which depends on the scintillator properties and the photodetector response. Several depth-of-interaction (DOI) encoding strategies have been developed that manipulate the scintillator's temporal response along the crystal length and therefore require pulse shape discrimination techniques to differentiate waveform shapes. In this work, we demonstrate how maximum likelihood (ML) estimation methods can be applied to pulse shape discrimination to better estimate deposited energy, DOI and interaction time (for time-of-flight (TOF) PET) of a gamma ray in a scintillation detector. We developed likelihood models based on either the estimated detection times of individual photoelectrons or the number of photoelectrons in discrete time bins, and applied to two phosphor-coated crystals (LFS and LYSO) used in a previously developed TOF-DOI detector concept. Compared with conventional analytical methods, ML pulse shape discrimination improved DOI encoding by 27% for both crystals. Using the ML DOI estimate, we were able to counter depth-dependent changes in light collection inherent to long scintillator crystals and recover the energy resolution measured with fixed depth irradiation (~11.5% for both crystals). Lastly, we demonstrated how the Richardson-Lucy algorithm, an iterative, ML-based deconvolution technique, can be applied to the digitized waveforms to deconvolve the photodetector's single photoelectron response and produce waveforms with a faster rising edge. After deconvolution and applying DOI and time-walk corrections, we demonstrated a 13% improvement in coincidence timing resolution (from 290 to 254 ps) with the LFS crystal and an 8% improvement (323 to 297 ps) with the LYSO crystal.
Gilbert, Peter B; Gabriel, Erin E; Miao, Xiaopeng; Li, Xiaoming; Su, Shu-Chih; Parrino, Janie; Chan, Ivan S F
2014-11-15
The phase III Zostavax Efficacy and Safety Trial of 1 dose of licensed zoster vaccine (ZV; Zostavax; Merck) in 50-59-year-olds showed approximately 70% vaccine efficacy (VE) to reduce the incidence of herpes zoster (HZ). An objective of the trial was to assess immune response biomarkers measuring antibodies to varicella zoster virus (VZV) by glycoprotein-based enzyme-linked immunosorbent assay as correlates of protection (CoPs) against HZ. The principal stratification vaccine efficacy curve framework for statistically evaluating immune response biomarkers as CoPs was applied. The VE curve describes how VE against the clinical end point (HZ) varies across participant subgroups defined by biomarker readout measuring vaccine-induced immune response. The VE curve was estimated using several subgroup definitions. The fold rise in VZV antibody titers from the time before immunization to 6 weeks after immunization was an excellent CoP, with VE increasing sharply with fold rise: VE was estimated at 0% for the subgroup with no rise and at 90% for the subgroup with 5.26-fold rise. In contrast, VZV antibody titers measured 6 weeks after immunization did not predict VE, with similar estimated VEs across titer subgroups. The analysis illustrates the value of the VE curve framework for assessing immune response biomarkers as CoPs in vaccine efficacy trials. NCT00534248. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Li, Siyang; Feng, Jinxi; Tian, Shuanghong; Lan, Shenyu; Fan, Chao; Liu, Xiaosheng; Xiong, Ya
2018-02-15
For the first time, paint sludge waste (PS) was used as a pore forming agent in the preparation of sewage sludge derived carbon (SC). The tuning role and mechanism of PS for characteristics of SC were explored. It was found that a sludge carbon (SC PS-Zn ) with rich macro-, meso- and micro- porous could be produced by one-step pyrolytic process of sludge in the presence of PS and ZnCl 2. Its surface area could reach as high as 680.5m 2 g -1 as 88.4 times and 4.8 times of sludge carbon without addition of PS and ZnCl 2 (SC) and only addition of ZnCl 2 (SC Zn ) , respectively. The macro- pores fabricated by PS provided much inner-space for ZnCl 2 to generate meso- and micro- porous, leading to a hierarchical porous structure. SC PS-Zn showed a high adsorption capacity of 685.4mgg -1 for Chrysophenine, which is 1.3 and 1.7 times that of SC PS and SC Zn respectively. The adsorption difference could be simply attributed to the fact that the great molecules were difficult to enter micro- pores of SC Zn . It was also found that the difference was also dependent on orientation of Chrysophenine, which was related to pH value of solution. Copyright © 2017. Published by Elsevier B.V.
Hong, Danping; Ding, Jiongyan; Li, Ouyang; He, Quan; Ke, Minxia; Zhu, Mengyi; Liu, Lili; Ou, Wen-Bin; He, Yulong; Wu, Yuehong
2018-02-26
Induced pluripotent stem cells (iPS) represent an innovative source for the standardized in vitro generation of macrophages (Mφ). Mφ show great promise in disease pathogenesis, particularly tuberculosis. However, there is no information about human iPS-derived (hiPS) macrophages (hiPS-Mφ) in response to tuberculosis infection. In the present study, macrophages derived from hiPS were established via embryoid body (EB) formation by using feeder-free culture conditions, and the human monocyte cell line THP-1 (THP-1-Mφ) was used as control. iPS-Mφ were characterized by using morphology, Giemsa staining, nonspecific esterase staining (α-NAE), phagocytosis, and surface phenotype. Additionally, after treatment with Bacillus Calmette-Guérin (BCG) for 24 h, cell apoptosis was detected by using an Annexin V-FITC Apoptosis Detection assay. The production of nitric oxide (NO), expression of tumor necrosis factor alpha (TNF-α), activity of apoptosis-related protein cysteine-3 (Caspase-3) and expression of B-cell lymphoma-2 (Bcl-2) were analyzed. With respect to morphology, surface phenotype, and function, the iPS-Mφ closely resembled their counterparts generated in vitro from a human monocyte cell line. iPS-Mφ exhibited the typically morphological characteristics of macrophages, such as round, oval, fusiform and irregular characteristics. The cells were Giemsa-stained-positive, α-NAE-positive, and possessed phagocytic ability. iPS-Mφ express high levels of CD14, CD11b, CD40, CD68, and major histocompatibility complex II (MHC-II). Moreover, with regard to the apoptotic rate, the production of NO, expression of TNF-α, and activity of Caspase-3 and Bcl-2, iPS-Mφ closely resemble that of their counterparts generated in vitro from human monocyte cell line in response to BCG infection. The rate of apoptosis of BCG-treated iPS-Mφ was 37.77 ± 7.94% compared to that of the untreated group at 4.97 ± 1.60% (P < 0.01) by using Annexin V-FITC Apoptosis Detection. Additionally, the rate of apoptosis of BCG-treated THP-1-Mφ was 37.1 ± 2.84% compared to that of the untreated group at 6.19 ± 1.68% (P < 0.001). The expression of TNF-α and the production of NO were significantly increased (P < 0.001), and the activity of Caspase-3 was increased. However, the expression of Bcl-2 was inhibited (P < 0.001). Our results demonstrate that Mφ derived from hiPS perform the immunological function in response to Bacillus Calmette-Guérin infection by undergoing apoptosis, increasing the production of NO and expression of TNF-α. Thus, our study may help to overcome the limitations of research into certain rare diseases due to the lack of adequate supply of disease-specific primary cells.
Interfacial activity of polymeric surfactants at the polystyrene-carbon dioxide interface
DOE Office of Scientific and Technical Information (OSTI.GOV)
Harrison, K.L.; Rocha, S.R.P. da; Yates, M.Z.
1998-11-24
The reduction of the interfacial tension at the polystyrene (PS, M{sub n} = 1850)-supercritical CO{sub 2} interface is reported for poly(1,1-dihydroperfluorooctyl acrylate)(PFOA) and the block copolymers PS-b-PFOA(3.7K/27K) and PS-b-poly(dimethylsiloxane) (PDMS) (2K/16K, 500/10K) at 45 C. PS-b-PDMS (2K/16K) lowers the interfacial tension to 0.5 dyn/cm at 45 C and 238 bar, more than that of any of the other copolymers. On the basis of the dynamics of the lowering of the interfacial tension, the apparent diffusion coefficient of PS-b-PDMS (2K/16K) is 8 {times} 10{sup {minus}6} cm{sup 2}/s. The critical micelle concentration of PS-b-PFOA (3.7K/27K) is 9 {times} 10{sup {minus}4} wt %.more » Whereas both the PDMS- and PFOA-based copolymers studied adsorb on the PS surface, PS-b-PFOA is much more effective in stabilizing the PS emulsions. The difference in stabilization is discussed in terms of the surfactant adsorption and the interactions of the anchor and buoy blocks with CO{sub 2} and the PS surface.« less
van Dam, Herman T; Borghi, Giacomo; Seifert, Stefan; Schaart, Dennis R
2013-05-21
Digital silicon photomultiplier (dSiPM) arrays have favorable characteristics for application in monolithic scintillator detectors for time-of-flight positron emission tomography (PET). To fully exploit these benefits, a maximum likelihood interaction time estimation (MLITE) method was developed to derive the time of interaction from the multiple time stamps obtained per scintillation event. MLITE was compared to several deterministic methods. Timing measurements were performed with monolithic scintillator detectors based on novel dSiPM arrays and LSO:Ce,0.2%Ca crystals of 16 × 16 × 10 mm(3), 16 × 16 × 20 mm(3), 24 × 24 × 10 mm(3), and 24 × 24 × 20 mm(3). The best coincidence resolving times (CRTs) for pairs of identical detectors were obtained with MLITE and measured 157 ps, 185 ps, 161 ps, and 184 ps full-width-at-half-maximum (FWHM), respectively. For comparison, a small reference detector, consisting of a 3 × 3 × 5 mm(3) LSO:Ce,0.2%Ca crystal coupled to a single pixel of a dSiPM array, was measured to have a CRT as low as 120 ps FWHM. The results of this work indicate that the influence of the optical transport of the scintillation photons on the timing performance of monolithic scintillator detectors can at least partially be corrected for by utilizing the information contained in the spatio-temporal distribution of the collection of time stamps registered per scintillation event.
NASA Astrophysics Data System (ADS)
van Dam, Herman T.; Borghi, Giacomo; Seifert, Stefan; Schaart, Dennis R.
2013-05-01
Digital silicon photomultiplier (dSiPM) arrays have favorable characteristics for application in monolithic scintillator detectors for time-of-flight positron emission tomography (PET). To fully exploit these benefits, a maximum likelihood interaction time estimation (MLITE) method was developed to derive the time of interaction from the multiple time stamps obtained per scintillation event. MLITE was compared to several deterministic methods. Timing measurements were performed with monolithic scintillator detectors based on novel dSiPM arrays and LSO:Ce,0.2%Ca crystals of 16 × 16 × 10 mm3, 16 × 16 × 20 mm3, 24 × 24 × 10 mm3, and 24 × 24 × 20 mm3. The best coincidence resolving times (CRTs) for pairs of identical detectors were obtained with MLITE and measured 157 ps, 185 ps, 161 ps, and 184 ps full-width-at-half-maximum (FWHM), respectively. For comparison, a small reference detector, consisting of a 3 × 3 × 5 mm3 LSO:Ce,0.2%Ca crystal coupled to a single pixel of a dSiPM array, was measured to have a CRT as low as 120 ps FWHM. The results of this work indicate that the influence of the optical transport of the scintillation photons on the timing performance of monolithic scintillator detectors can at least partially be corrected for by utilizing the information contained in the spatio-temporal distribution of the collection of time stamps registered per scintillation event.
Structure and photoluminescence properties of ZnS films grown on porous Si substrates
NASA Astrophysics Data System (ADS)
Wang, Cai-feng; Hu, Bo; Yi, Hou-hui; Li, Wei-bing
2011-11-01
ZnS films were deposited on porous silicon (PS) substrates with different porosities. With the increase of PS substrate porosity, the XRD diffraction peak intensity decreases and the surface morphology of the ZnS films becomes rougher. Voids appear in the films, due to the increased roughness of PS structure. The photoluminescence (PL) spectra of the samples before and after deposition of ZnS were measured to study the effect of substrate porosity on the luminescence properties of ZnS/PS composites. As-prepared PS substrates emit strong red light. The red PL peak of PS after deposition of ZnS shows an obvious blueshift. As PS substrate porosity increases, the trend of blueshift increases. A green emission at about 550 nm was also observed when the porosity of PS increased, which is ascribed to the defect-center luminescence of ZnS. The effect of annealing time on the structural and luminescence properties of ZnS/PS composites were also studied. With the increase of annealing time, the XRD diffraction peak intensity and the self-activated luminescence intensity of ZnS increase, and, the surface morphology of the ZnS films becomes smooth and compact. However, the red emission intensity of PS decreases, which was associated with a redshift. White light emission was obtained by combining the luminescence of ZnS with the luminescence of PS.
Maiser, Samuel; Estrada-Stephen, Karen; Sahr, Natasha; Gully, Jonathan; Marks, Sean
2017-09-01
A variety of terms and attitudes surround palliative sedation (PS) with little research devoted to hospice and palliative care (HPC) clinicians' perceptions and experiences with PS. These factors may contribute to the wide variability in the reported prevalence of PS. This study was designed to better identify hospice and palliative care (HPC) clinician attitudes toward, and clinical experiences with palliative sedation (PS). A 32-question survey was distributed to members of the American Academy of Hospice and Palliative Medicine (n = 4678). The questions explored the language clinicians use for PS, and their experiences with PS. Nine hundred thirty-six (20% response rate) responded to the survey. About 83.21% preferred the terminology of PS compared with other terms. A majority felt that PS is a bioethically appropriate treatment for refractory physical and nonphysical symptoms in dying patients. Most felt PS was not an appropriate term in clinical scenarios when sedation occurred as an unintended side effect from standard treatments. Hospice clinicians use PS more consistently and with less distress than nonhospice clinician respondents. Benzodiazepines (63.1%) and barbiturates (18.9%) are most commonly prescribed for PS. PS is the preferred term among HPC clinicians for the proportionate use of pharmacotherapies to intentionally lower awareness for refractory symptoms in dying patients. PS is a bioethically appropriate treatment for refractory symptoms in dying patients. However, there is a lack of clear agreement about what is included in PS and how the practice of PS should be best delivered in different clinical scenarios. Future efforts to investigate PS should focus on describing the clinical scenarios in which PS is utilized and on the level of intended sedation necessary, in an effort to better unify the practice of PS.
USDA-ARS?s Scientific Manuscript database
The objective of this experiment was to assess physiological responses to an endotoxin challenge in crossbred male progeny whose Brahman sires experienced prenatal transportation stress (PS) in utero. Sixteen steers (PNS group) sired by 3 PS bulls (gestating dams were transported for 2 h at 60, 80, ...
Rideout, Todd C.; Carrier, Bradley; Wen, Shin; Raslawsky, Amy; Browne, Richard W.; Harding, Scott V.
2015-01-01
To investigate the cholesterol-lowering effectiveness of a phytosterol/α-lipoic acid (PS/αLA) therapy, thirty-two male Zucker rats were randomly assigned to 1 of 4 diets for 30 days: (i) high fat diet (HF, 40% energy from fat); (ii) HF diet supplemented with 3% phytosterols; (iii) HF diet supplemented with 0.25% αLA; or (iv) HF diet supplemented with PS (3%) and αLA (0.25%, PS/αLA). Compared with the HF diet, combination PS/αLA proved more effective in reducing non-HDL cholesterol (−55%) than either the PS (−24%) or the αLA (−25%) therapies alone. PS supplementation did not affect LDL particle number, however, αLA supplementation reduced LDL particle number when supplemented alone (−47%) or in combination with PS (−54%). Compared with the HF-fed animals, evidence of increased HDL-particle number was evident in all treatment groups to a similar extent (21–22%). PS-mediated interruption of intestinal cholesterol absorption was evident by increased fecal cholesterol loss (52%) and compensatory increase in HMG-CoA reductase mRNA (1.6 fold of HF), however, αLA supplementation did not affect fecal cholesterol loss. Hepatic mRNA and protein expression patterns suggested that αLA modulated multiple aspects of cholesterol homeostasis including reduced synthesis (HMG-CoA reductase mRNA, 0.7 fold of HF), reduced bile acid synthesis (CYP7a1 expression, 0.17 of HF), and increased cholesterol clearance (reduced PCSK9 mRNA, 0.5 fold of HF; increased LDLr protein, 2 fold of HF). Taken together, this data suggests that PS and αLA work through unique and complementary mechanisms to provide a superior and more comprehensive cholesterol lowering response than either therapy alone. PMID:25664679
Screening and identification of novel B cell epitopes of Toxoplasma gondii SAG1
2013-01-01
Background The identification of protein epitopes is useful for diagnostic purposes and for the development of peptide vaccines. In this study, the epitopes of Toxoplasma gondii SAG1 were identified using synthetic peptide techniques with the aid of bioinformatics. Findings Eleven peptides derived from T. gondii SAG1 were assessed by ELISA using pig sera from different time points after infection. Four (PS4, PS6, PS10 and PS11), out of the eleven peptides tested were recognized by all sera. Then, shorter peptides that were derived from PS4, PS6, PS10 and PS11 were predicted using bioinformatics and tested by experimentation. Four out of nine shorter peptides were identified successfully (amino acids 106–120, 166–180, 289–300 and 313–332). Conclusions We have precisely located the epitopes of T. gondii SAG1 using pig sera collected at different time points after infection. The identified epitopes may be useful for the further study of epitope-based vaccines and diagnostic reagents. PMID:23631709
Phase-locked-loop-based delay-line-free picosecond electro-optic sampling system
NASA Astrophysics Data System (ADS)
Lin, Gong-Ru; Chang, Yung-Cheng
2003-04-01
A delay-line-free, high-speed electro-optic sampling (EOS) system is proposed by employing a delay-time-controlled ultrafast laser diode as the optical probe. Versatile optoelectronic delay-time controllers (ODTCs) based on modified voltage-controlled phase-locked-loop phase-shifting technologies are designed for the laser. The integration of the ODTC circuit and the pulsed laser diode has replaced the traditional optomechanical delay-line module used in the conventional EOS system. This design essentially prevents sampling distortion from misalignment of the probe beam, and overcomes the difficulty in sampling free-running high-speed transients. The maximum tuning range, error, scanning speed, tuning responsivity, and resolution of the ODTC are 3.9π (700°), <5% deviation, 25-2405 ns/s, 0.557 ps/mV, and ˜1 ps, respectively. Free-running wave forms from the analog, digital, and pulsed microwave signals are sampled and compared with those measured by the commercial apparatus.
Borisov, A Y
2008-02-01
Discrepancy is revealed between the values of excitation transfer times measured experimentally, and those calculated, for the atomic structures of B800 --> B850 bacteriochlorophylls within the LH2 light-harvesting pigment-protein complex of the purple bacterium Rhodopseudomonas acidophila. The value 2.9-3.2 ps for the B800 --> B850 excitation transfer, calculated on the basis of atomic structure of LH2, is about 4-times longer than that measured for this bacterium (0.7 ps). This discrepancy appears common in at least two purple bacteria. Possible sources responsible for this discrepancy are discussed. It may either signify some drawback/s/ in our notions about the precise in vivo structure of LH2 complexes, for example, possible changes of LH2 structure during crystallization, or it may reflect our ignorance of some mechanisms involved in excitation migration.
Liao, Chun-De; Tsauo, Jau-Yih; Wu, Yen-Tzu; Cheng, Chin-Pao; Chen, Hui-Chuen; Huang, Yi-Ching; Chen, Hung-Chou; Liou, Tsan-Hon
2017-10-01
Background: Overweight and obese older people face a high risk of muscle loss and impaired physical function, which may contribute to sarcopenic obesity. Resistance exercise training (RET) has a beneficial effect on muscle protein synthesis and can be augmented by protein supplementation (PS). However, whether body weight affects the augmentation of muscular and functional performance in response to PS in older people undergoing RET remains unclear. Objective: This study was conducted to identify the effects of PS on the body composition and physical function of older people undergoing RET. Design: We performed a comprehensive search of online databases to identify randomized controlled trials (RCTs) reporting the efficacy of PS for lean mass gain, strength gain, and physical mobility improvements in older people undergoing RET. Results: We included 17 RCTs; the overall mean ± SD age and body mass index (BMI; in kg/m 2 ) in these RCTs were 73.4 ± 8.1 y and 29.7 ± 5.5, respectively. The participants had substantially greater lean mass and leg strength gains when PS and RET were used than with RET alone, with the standard mean differences (SMDs) being 0.58 (95% CI: 0.32, 0.84) and 0.69 (95% CI: 0.39, 0.98), respectively. The subgroup of studies with a mean BMI ≥30 exhibited substantially greater lean mass (SMD: 0.53; 95% CI: 0.19, 0.87) and leg strength (SMD: 0.88; 95% CI: 0.42, 1.34) gains in response to PS. The subgroup of studies with a mean BMI <30 also exhibited relevant gains in response to PS. Conclusions: Compared with RET alone, PS combined with RET may have a stronger effect in preventing aging-related muscle mass attenuation and leg strength loss in older people, which was found in studies with a mean BMI ≥30 and in studies with a mean BMI <30. Clinicians could use nutrition supplement and exercise strategies, especially PS plus RET, to effectively improve the physical activity and health status of all older patients. © 2017 American Society for Nutrition.
Krasnov, Boris R; Shenbrot, Georgy I; van der Mescht, Luther; Warburton, Elizabeth M; Khokhlova, Irina S
2018-04-12
To understand existence, patterns and mechanisms behind phylogenetic heritability in the geographic range size (GRS) of parasites, we measured phylogenetic signal (PS) in the sizes of both regional (within a region) and continental (within a continent) geographic ranges of fleas in five regions. We asked whether (a) GRS is phylogenetically heritable and (b) the manifestation of PS varies between regions. We also asked whether geographic variation in PS reflects the effects of the environment's spatiotemporal stability (e.g. glaciation disrupting geographic ranges) or is associated with time since divergence (accumulation differences among species over time). Support for the former hypothesis would be indicated by stronger PS in southern than in northern regions, whereas support for the latter hypothesis would be shown by stronger PS in regions with a large proportion of species belonging to the derived lineages than in regions with a large proportion of species belonging to the basal lineages. We detected significant PS in both regional and continental GRSs of fleas from Canada and in continental GRS of fleas from Mongolia. No PS was found in the GRS of fleas from Australia and Southern Africa. Venezuelan fleas demonstrated significant PS in regional GRS only. Local Indicators of Phylogenetic Association detected significant local positive autocorrelations of GRS in some clades even in regions in which PS has not been detected across the entire phylogeny. This was mainly characteristic of younger taxa.
Nagle Zera, Jacquelyn; Nagle, Elizabeth F; Nagai, Takashi; Lovalekar, Mita; Abt, John P; Lephart, Scott M
2018-02-14
The purpose of this study was three-fold: (a) to examine the test-retest reliability of a 30 second maximal tethered freestyle swimming test (TST), (b) to assess the validity of the TST by examining the association to sprint swimming performance and, (c) to examine the associations between a swim-specific and land-based measure of anaerobic performance. A total of twenty-nine male and female swimmers were recruited to participate in the study. Each participant completed a Wingate Anaerobic cycling test (WAnT), two or four TST, and a 22.9 meter (25 yard), 45.7 meter (50 yard), and 91.4 meter (100 yard) maximal freestyle performance swims (PS). Mean and peak force (Fmean, Fpeak) were recorded for both the WAnT and TST, and average swimming velocity and time were recorded for the PS. Additionally, physiological and perceptual measures were recorded immediate post exercise for all tests. The results of the present investigation showed strong intersession and intrasession reliability (R= 0.821-0.975; p<0.001) for force parameters of the TST. Moderate correlations were found between Fmean and PS time and velocity of all distances, with slightly weaker correlations between Fpeak and the 22.9 meter (time and velocity) and 45.7 meter (velocity) PS. Finally, moderate correlations were found for Fmean and Fpeak of the TST and WAnT. This study demonstrated that the TST is a reliable measure, with moderate association to swimming performance, producing similar physiological responses compared to free swimming. Therefore, future research shoulSd focus on investigating the potential benefits of utilizing the TST as a regular assessment tool as a part of a competitive swimming training program to track adaptations and inform training decisions.
Fast capacitive probe for electromagnetic pulse diagnostic.
Lorusso, A; Nassisi, V; Siciliano, M V
2008-06-01
In this work, we report the study and the development of a capacitive probe which is suitable for getting fast and high voltage/current measurements. Due to the fact that fast pulses propagate generally in coaxial structures, the probe realized in this work was a capacitive divider with the divider electrode properly designed to assure the same characteristic impedance of the coaxial structure and the recombination time of the split signals during the propagation. It was a folded cylindrical ring of 1.4 cm long and 0.8 cm thick, which introduce a theoretical delay time of about 100 ps. Analyzing the behavior of the probe closed on 520 Omega, the voltage amplification resulted to be of (3.6+/-0.1) x 10(-4) and, as a consequence, the current attenuation factor of 56+/-1 AV. The response rise time was less than 320 ps, which was limited by oscilloscope bandwave. The capacitor probe can operate voltage measurements of the order of 100 kV.
Stimuli-Responsive, Shape-Transforming Nanostructured Particles.
Lee, Junhyuk; Ku, Kang Hee; Kim, Mingoo; Shin, Jae Man; Han, Junghun; Park, Chan Ho; Yi, Gi-Ra; Jang, Se Gyu; Kim, Bumjoon J
2017-08-01
Development of particles that change shape in response to external stimuli has been a long-thought goal for producing bioinspired, smart materials. Herein, the temperature-driven transformation of the shape and morphology of polymer particles composed of polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) block copolymers (BCPs) and temperature-responsive poly(N-isopropylacrylamide) (PNIPAM) surfactants is reported. PNIPAM acts as a temperature-responsive surfactant with two important roles. First, PNIPAM stabilizes oil-in-water droplets as a P4VP-selective surfactant, creating a nearly neutral interface between the PS and P4VP domains together with cetyltrimethylammonium bromide, a PS-selective surfactant, to form anisotropic PS-b-P4VP particles (i.e., convex lenses and ellipsoids). More importantly, the temperature-directed positioning of PNIPAM depending on its solubility determines the overall particle shape. Ellipsoidal particles are produced above the critical temperature, whereas convex lens-shaped particles are obtained below the critical temperature. Interestingly, given that the temperature at which particle shape change occurs depends solely on the lower critical solution temperature (LCST) of the polymer surfactants, facile tuning of the transition temperature is realized by employing other PNIPAM derivatives with different LCSTs. Furthermore, reversible transformations between different shapes of PS-b-P4VP particles are successfully demonstrated using a solvent-adsorption annealing with chloroform, suggesting great promise of these particles for sensing, smart coating, and drug delivery applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
NASA Astrophysics Data System (ADS)
Zhang, Hong-yan
2016-03-01
CdS nanocrystals have been successfully grown on porous silicon (PS) by sol-gel method. The plan-view field emission scanning electron microscopy (FESEM) shows that the pore size of PS is smaller than 5 μm in diameter and the agglomerates of CdS are broadly distributed on the surface of PS substrate. With the increase of annealing time, the CdS nanoparticles grow in both length and diameter along the preferred orientation. The cross-sectional FESEM images of ZnO/PS show that CdS nanocrystals are uniformly penetrated into all PS layers and adhere to them very well. photoluminescence (PL) spectra demonstrate that the intensity of PL peak located at about 425 nm has almost no change after the annealing time increases. The range of emission wavelength of CdS/PS is from 425 nm to 455 nm and the PL intensity is decreasing with the annealing temperature increasing from 100 °C to 200 °C.
Lin, Gong-Ru; Chiu, I-Hsiang; Wu, Ming-Chung
2005-02-07
Optically harmonic mode-locking of a semiconductor optical amplifier fiber laser (SOAFL) induced by backward injecting a dark-optical comb is demonstrated for the first time. The dark-optical comb with 60-ps pulsewidth is generated from a Mach-Zehnder modulator, which is driven by an electrical comb at a DC offset of 0.3Vn. Theoretical simulation indicates that the backward injection of dark-optical comb results in a narrow gain window of 60 ps within one modulating period, providing a cross-gainmodulation induced mode-locking in the SOAFL with a shortest pulsewidth of 15 ps at repetition frequency of 1 GHz. The mode-locked SOAFL pulsewidth can be slightly shortened to 10.8 ps with a 200m-long dispersion compensating fiber. After nonlinearly soliton compression in a 5km-long single mode fiber, the pulsewidth, linewidth and time-bandwidth product become 1.2 ps, 2.06 nm and 0.31, respectively.
Imaizumi, Mitsuyoshi; Li-Jessen, Nicole Y K; Sato, Yuka; Yang, David T; Thibeault, Susan L
2017-04-01
One prospective treatment option for vocal fold scarring is regeneration with an engineered scaffold containing induced pluripotent stem cells (iPS). In the present study, we investigated the feasibility of utilizing an injectable hyaluronic acid (HA) scaffold encapsulated with human-iPS cell (hiPS) for regeneration of vocal folds. Thirty athymic nude rats underwent unilateral vocal fold injury. Contralateral vocal folds served as uninjured controls. Hyaluronic acid hydrogel scaffold, HA hydrogel scaffold containing hiPS, and HA hydrogel scaffold containing hiPS with epidermal growth factor (EGF) were injected in both vocal folds immediately after surgery. One and 2 weeks after injection, larynges were excised for histology, immunohistochemistry, and fluorescence in situ hybridization (FISH). Presence of HA hydrogel was confirmed in vocal folds 1 and 2 weeks post injection. The FISH analysis confirmed the presence and viability of hiPS in the injected vocal folds. Histological results demonstrated that vocal folds injected with HA hydrogel scaffold containing EGF demonstrated less fibrosis than those with HA hydrogel only. Human-iPS survived in injured rat vocal folds. The HA hydrogel with hiPS and EGF ameliorated the fibrotic response. Additional work is necessary to optimize hiPS differentiation and further confirm the safety of hiPS for clinical applications.
Tillett, William; Charlton, Rachel; Nightingale, Alison; Snowball, Julia; Green, Amelia; Smith, Catherine; Shaddick, Gavin; McHugh, Neil
2017-12-01
To describe the time interval between the onset of psoriasis and PsA in the UK primary care setting and compare with a large, well-classified secondary care cohort. Patients with PsA and/or psoriasis were identified in the UK Clinical Practice Research Datalink (CPRD). The secondary care cohort comprised patients from the Bath PsA longitudinal observational cohort study. For incident PsA patients in the CPRD who also had a record of psoriasis, the time interval between PsA diagnosis and first psoriasis record was calculated. Comparisons were made with the time interval between diagnoses in the Bath cohort. There were 5272 eligible PsA patients in the CPRD and 815 in the Bath cohort. In both cohorts, the majority of patients (82.3 and 61.3%, respectively) had psoriasis before their PsA diagnosis or within the same calendar year (10.5 and 23.8%), with only a minority receiving their PsA diagnosis first (7.1 and 14.8%). Excluding those who presented with arthritis before psoriasis, the median time between diagnoses was 8 years [interquartile range (IQR) 2-15] in the CPRD and 7 years (IQR 0-20) in the Bath cohort. In the CPRD, 60.1 and 75.1% received their PsA diagnosis within 10 and 15 years of their psoriasis diagnosis, respectively; this was comparable with 57.2 and 67.7% in the Bath cohort. A similar distribution for the time interval between psoriasis and arthritis was observed in the CPRD and secondary care cohort. These data can inform screening strategies and support the validity of data from each cohort. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ishii, Yoshiyuki, E-mail: yishii@nih.go.jp
2013-04-19
Highlights: •HPV16 pseudovirions (16PsVs) infection induces an autophagy response. •The autophagy was analyzed by transmission electron microscope (TEM). •TEM showed the double-membrane vesicles in HeLa cells inoculated with 16PsVs. •These vesicles incorporated 16PsVs particles in the lumen. •These results imply that autophagosomes are generated from the plasma membrane. -- Abstract: Autophagy is a bulk degradation process for subcellular proteins and organelles to manage cell starvation. Autophagy is associated with the formation of autophagosomes and further functions as a defense mechanism against infection by various pathogens. Human papillomavirus (HPV) infection induces an autophagy response, such as up-regulation of marker proteins formore » autophagy, in host keratinocytes. However, direct microscopic evidence for autophagy induction by HPV infection is still lacking. Here, I report an electron microscopic analysis of autophagosomes elicited by the entry of HPV pseudovirions (PsVs). HeLa cells showed enhanced infectivity for PsVs of HPV type 16 (16PsVs) when treated with an autophagy inhibitor, suggesting the involvement of autophagy in HPV infection. In HeLa cells inoculated with 16PsVs, transmission electron microscopy showed the presence of cup-shaped, double-membrane vesicles (phagophores) and double-membrane-bound vesicles, which are typical structures of autophagosomes. These double-membrane vesicles displayed a large lumen volume and incorporated 10–50 16PsVs particles in the lumen. These results demonstrate that autophagy is indeed induced during the HPV16 entry process and imply that autophagosomes are generated from the plasma membrane by HPV infection.« less
Optimally shaped narrowband picosecond pulses for femtosecond stimulated Raman spectroscopy.
Hoffman, David P; Valley, David; Ellis, Scott R; Creelman, Mark; Mathies, Richard A
2013-09-09
A comparison between a Fabry-Pérot etalon filter and a conventional grating filter for producing the picosecond (ps) Raman pump pulses for femtosecond stimulated Raman spectroscopy (FSRS) is presented. It is shown that for pulses of equal energy the etalon filter produces Raman signals twice as large as that of the grating filter while suppressing the electronically resonant background signal. The time asymmetric profile of the etalon-generated pulse is shown to be responsible for both of these observations. A theoretical discussion is presented which quantitatively supports this hypothesis. It is concluded that etalons are the ideal method for the generation of narrowband ps pulses for FSRS because of the optical simplicity, efficiency, improved FSRS intensity and reduced backgrounds.
Characterization of PsMPK2, the first C1 subgroup MAP kinase from pea (Pisum sativum L.).
Ortiz-Masia, Dolores; Perez-Amador, Miguel A; Carbonell, Pablo; Aniento, Fernando; Carbonell, Juan; Marcote, Maria J
2008-05-01
Mitogen-activated protein kinase (MAPK) cascades play a key role in plant growth and development as well as in biotic and abiotic stress responses. They are classified according to their sequence homology into four major groups (A-D). A large amount of information about MAPKs in groups A and B is available but few data of the C group have been reported. In this study, a C1 subgroup MAP kinase cDNA, PsMPK2, was isolated from Pisum sativum. PsMPK2 is expressed in vegetative (root and leaf) and reproductive (stamen, pistil and fruit) organs. Expression of PsMPK2 in Arabidopsis thaliana shows that mechanical injury and other stress signals as abscisic acid, jasmonic acid and hydrogen peroxide increase its kinase activity, extending previous results indicating that C1 subgroup MAPKs may be involved in the response to stress.
On the timing performance of thin planar silicon sensors
NASA Astrophysics Data System (ADS)
Akchurin, N.; Ciriolo, V.; Currás, E.; Damgov, J.; Fernández, M.; Gallrapp, C.; Gray, L.; Junkes, A.; Mannelli, M.; Martin Kwok, K. H.; Meridiani, P.; Moll, M.; Nourbakhsh, S.; Pigazzini, S.; Scharf, C.; Silva, P.; Steinbrueck, G.; de Fatis, T. Tabarelli; Vila, I.
2017-07-01
We report on the signal timing capabilities of thin silicon sensors when traversed by multiple simultaneous minimum ionizing particles (MIP). Three different planar sensors, with depletion thicknesses 133, 211, and 285 μm, have been exposed to high energy muons and electrons at CERN. We describe signal shape and timing resolution measurements as well as the response of these devices as a function of the multiplicity of MIPs. We compare these measurements to simulations where possible. We achieve better than 20 ps timing resolution for signals larger than a few tens of MIPs.
Ash, Anthony; Burnett, Gary R; Parker, Roger; Ridout, Mike J; Rigby, Neil M; Wilde, Peter J
2014-04-01
In this study we investigated the differences in the properties of pellicles formed from stimulated parotid saliva (PS), which contains little or no mucin; and stimulated whole mouth saliva (WMS), which contains mainly two types of mucin: MUC5B and MUC7. By contacting WMS and PS with quartz-crystal microbalance with dissipation monitoring (QCM-D) and dual polarisation interferometer (DPI) hydroxyapatite (the main component of enamel) coated sensors, we observed the formation and structure of the respective salivary pellicles. As this was the first time that DPI hydroxyapatite sensors have been used to measure salivary pellicle adsorption; the techniques combined allowed us to measure the hydrated mass, dry mass, thickness and viscoelastic properties of the pellicle; but also to record the density of the PS and WMS formed pellicles. Subsequently, the PS pellicle was shown to form a denser layer than WMS pellicle; which would suggest that the proteins present in PS are also responsible for forming the dense basal layer of the acquired enamel pellicle. Whereas proteins present in the WMS are more likely to help form the softer outer layer of the pellicle. The data presented help to further define the mechanisms leading to the multi-layered structure of the salivary pellicle and demonstrate that salivary composition has an important effect on the structural properties of the adsorbed pellicle. Copyright © 2013 Elsevier B.V. All rights reserved.
Role of Activin A in Immune Responses to Breast Cancer
2013-12-01
Demaria. APPENDIX 2 ( PS4 -57) Radiation-induced activin-a fosters tumor-mediated immunosuppression in breast cancer. Claire Vanpouille-Box, Julie...with immunotherapy in the clinic. APPENDIX 2 ( PS4 -57) Radiation-induced activin-a fosters tumor-mediated immunosuppression in breast cancer...Claire Vanpouille-Box, Julie Diamond, Silvia Formenti and Sandra Demaria. POSTER PRESENTATION – 59th RRS annual Meeting. ( PS4 -57) Radiation-induced
An Oomycete CRN Effector Reprograms Expression of Plant HSP Genes by Targeting their Promoters
Song, Tianqiao; Ma, Zhenchuan; Shen, Danyu; Li, Qi; Li, Wanlin; Su, Liming; Ye, Tingyue; Zhang, Meixiang; Wang, Yuanchao; Dou, Daolong
2015-01-01
Oomycete pathogens produce a large number of CRN effectors to manipulate plant immune responses and promote infection. However, their functional mechanisms are largely unknown. Here, we identified a Phytophthora sojae CRN effector PsCRN108 which contains a putative DNA-binding helix-hairpin-helix (HhH) motif and acts in the plant cell nucleus. Silencing of the PsCRN108 gene reduced P. sojae virulence to soybean, while expression of the gene in Nicotiana benthamiana and Arabidopsis thaliana enhanced plant susceptibility to P. capsici. Moreover, PsCRN108 could inhibit expression of HSP genes in A. thaliana, N. benthamiana and soybean. Both the HhH motif and nuclear localization signal of this effector were required for its contribution to virulence and its suppression of HSP gene expression. Furthermore, we found that PsCRN108 targeted HSP promoters in an HSE- and HhH motif-dependent manner. PsCRN108 could inhibit the association of the HSE with the plant heat shock transcription factor AtHsfA1a, which initializes HSP gene expression in response to stress. Therefore, our data support a role for PsCRN108 as a nucleomodulin in down-regulating the expression of plant defense-related genes by directly targeting specific plant promoters. PMID:26714171
An Oomycete CRN Effector Reprograms Expression of Plant HSP Genes by Targeting their Promoters.
Song, Tianqiao; Ma, Zhenchuan; Shen, Danyu; Li, Qi; Li, Wanlin; Su, Liming; Ye, Tingyue; Zhang, Meixiang; Wang, Yuanchao; Dou, Daolong
2015-12-01
Oomycete pathogens produce a large number of CRN effectors to manipulate plant immune responses and promote infection. However, their functional mechanisms are largely unknown. Here, we identified a Phytophthora sojae CRN effector PsCRN108 which contains a putative DNA-binding helix-hairpin-helix (HhH) motif and acts in the plant cell nucleus. Silencing of the PsCRN108 gene reduced P. sojae virulence to soybean, while expression of the gene in Nicotiana benthamiana and Arabidopsis thaliana enhanced plant susceptibility to P. capsici. Moreover, PsCRN108 could inhibit expression of HSP genes in A. thaliana, N. benthamiana and soybean. Both the HhH motif and nuclear localization signal of this effector were required for its contribution to virulence and its suppression of HSP gene expression. Furthermore, we found that PsCRN108 targeted HSP promoters in an HSE- and HhH motif-dependent manner. PsCRN108 could inhibit the association of the HSE with the plant heat shock transcription factor AtHsfA1a, which initializes HSP gene expression in response to stress. Therefore, our data support a role for PsCRN108 as a nucleomodulin in down-regulating the expression of plant defense-related genes by directly targeting specific plant promoters.
Wang, Lixiu; Bi, Yayan; Cao, Muhua; Ma, Ruishuang; Wu, Xiaoming; Zhang, Yan; Ding, Wenbo; Liu, Yan; Yu, Qian; Zhang, Yingqian; Jiang, Hua; Sun, Yingchun; Tong, Dongxia; Guo, Li; Dong, Zengxiang; Tian, Ye; Kou, Junjie; Shi, Jialan
2016-11-15
Relatively little is known about the role of phosphatidylserine (PS) in procoagulant activity (PCA) in patients with non-ST-elevated myocardial infarction (NSTEMI) after stent implantation. This study was designed to evaluate whether exposed PS on microparticles (MPs) and blood cells were involved in the hypercoagulable state in NSTEMI patients with stent implantation. NSTEMI patients (n=90) and healthy controls (n=20) were included in our study. PS exposure on MPs and blood cells was analyzed with flow cytometer and confocal microscope. PCA was evaluated by clotting time, purified coagulation complex assays and fibrin production assays. Baseline levels of MPs and PS + blood cells were significantly higher (P<0.001) in the patients than in controls. After stent implantation, a remarkable increase was observed in both MPs and PS + blood cells. Specifically, PS + MPs, PS + platelets and erythrocytes peaked at 18h following stent implantation, while PS + leukocytes peaked on day 2. In addition, circulating MPs (mostly derived from platelets, leukocytes, erythrocytes and endothelial cells) cooperating with PS + blood cells, contributed to markedly shortened coagulation time and markedly increased FXa/thrombin/fibrin (all P<0.01) generation in patient group. Moreover, blockade of exposed PS on MPs and cells with lactadherin inhibited PCA by approximately 70%. Our results suggest that PS + MPs and blood cells play a procoagulant role in NSTEMI patients following stent implantation. Blockade of PS could become a novel therapeutic modality for the prevention of thrombosis in these patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Scher, Jose U.; Ubeda, Carles; Artacho, Alejandro; Attur, Mukundan; Isaac, Sandrine; Reddy, Soumya M.; Marmon, Shoshana; Neimann, Andrea; Brusca, Samuel; Patel, Tejas; Manasson, Julia; Pamer, Eric G.; Littman, Dan R.; Abramson, Steven B.
2014-01-01
Objective To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA). Methods High-throughput 16S rRNA pyrosequencing was utilized to compare community composition of gut microbiota in PsA patients (n=16), subjects with psoriasis of the skin (Ps) (n=15) and healthy, matched-controls (n=17). Samples were further assessed for the presence and levels of fecal and serum secretory immunoglobulin A (sIgA), pro-inflammatory proteins and fatty-acids. Results The gut microbiota observed in PsA and Ps patients was less diverse when compared to healthy controls. These could be attributed to the reduced presence of several taxa. While both groups showed a relative decrease in Coprococcus spp., PsA samples were characterized by a significant reduction in Akkermansia, Ruminococcus, and Pseudobutyrivibrio. Supernatants of fecal samples from PsA patients revealed an increase in sIgA and a decrease in receptor activator of nuclear factor kappa-B ligand (RANKL) levels. Fatty acid analysis revealed low levels of hexanoate and heptanoate in PsA and Ps patients. Conclusion PsA and Ps patients had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that published for patients with IBD and was associated with changes in specific inflammatory proteins unique to this group, and distinct from Ps and controls. Thus, the role of gut microbiota in the continuum of Ps-PsA pathogenesis and the associated immune response merits further study. PMID:25319745
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dang, Liem X.; Chang, Tsun-Mei
In this paper, we describe our efforts to apply rate theories in studies of solvent exchange around Li +(aq) and the kinetics of ion pairings in lithium-ion batteries (LIB). We report one of the first computer simulations of the exchange dynamics around hydrated Li + in acetonitrile (ACN), which is common solvent used in LIBs. We also provide details of the ion-pairing kinetics of Li +-[BF 4] and Li +-[PF 6] in ACN. Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine the ACN exchange process between the first and second solvation shells aroundmore » Li +(aq). We calculate exchange rates using transition state theory and weighted them with transmission coefficients determined by the reactive flux and Impey, Madden, and McDonald approaches and Grote-Hynes theory. We found the relaxation times changed from 180 ps to 4600 ps and from 30 ps to 280 ps for Li +-[BF 4] and Li +-[PF 6] ion pairs, respectively. These results confirm that the solvent response to the kinetics of ion pairing is significant. Our results also show that, in addition to affecting the free energy of solvation into ACN, the anion type also should significantly influence the kinetics of ion pairing. These results will increase our understanding of the thermodynamic and kinetic properties of LIB systems.« less
NASA Astrophysics Data System (ADS)
Jeeju, Pullarkat P.; Jayalekshmi, S.; Chandrasekharan, K.; Sudheesh, P.
2012-11-01
Using simple wet chemical method at room temperature, zinc oxide (ZnO) nanoparticles embedded in polystyrene (PS) matrix were synthesized. The size of the ZnO nanoparticles could be varied by varying the precursor concentration, reaction time and stirring speed. Transparent films of ZnO/PS nanocomposites of thickness around 1 μm were coated on ultrasonically cleaned glass substrates by spin coating. The optical absorptive nonlinearity in ZnO/PS nanocomposite films was investigated using open aperture Z-scan technique with nanosecond laser pulses at 532 nm. The results indicate optical limiting type nonlinearity in the films due to two-photon absorption in ZnO. These films also show a self-defocusing type negative nonlinear refraction in closed aperture Z-scan experiment. The observed nonlinear absorption is strongly dependent on particle size and the normalized transmittance could be reduced to as low as 0.43 by the suitable choice of the ZnO nanoparticle size. These composite films can hence be used as efficient optical limiters for sensor protection. The much-pronounced nonlinear response of these composite films, compared to pure ZnO, combined with the improved stability of ZnO nanoparticles in the PS matrix offer prospects of application of these composite films in the fabrication of stable non-linear optical devices.
Zhang, Yanzhao; Cheng, Yanwei; Ya, Huiyuan; Xu, Shuzhen; Han, Jianming
2015-01-01
The pigmented cells in defined region of a petal constitute the petal spots. Petal spots attract pollinators and are found in many angiosperm families. Several cultivars of tree peony contain a single red or purple spot at the base of petal that makes the flower more attractive for the ornamental market. So far, the understanding of the molecular mechanism of spot formation is inadequate. In this study, we sequenced the transcriptome of the purple spot and the white non-spot of tree peony flower. We assembled and annotated 67,892 unigenes. Comparative analyses of the two transcriptomes showed 1,573 differentially expressed genes, among which 933 were up-regulated, and 640 were down-regulated in the purple spot. Subsequently, we examined four anthocyanin structural genes, including PsCHS, PsF3'H, PsDFR, and PsANS, which expressed at a significantly higher level in the purple spot than in the white non-spot. We further validated the digital expression data using quantitative real-time PCR. Our result uncovered transcriptome variance between the spot and non-spot of tree peony flower, and revealed that the co-expression of four anthocyanin structural genes was responsible for spot pigment in tree peony. The data will further help to unravel the genetic mechanism of peony flower spot formation.
The bovine TRPV3 as a pathway for the uptake of Na+, Ca2+, and NH4+
Liebe, Franziska; Liebe, Hendrik
2018-01-01
Absorption of ammonia from the gastrointestinal tract results in problems that range from hepatic encephalopathy in humans to poor nitrogen efficiency of cattle with consequences for the global climate. Previous studies on epithelia and cells from the native ruminal epithelium suggest functional involvement of the bovine homologue of TRPV3 (bTRPV3) in ruminal NH4+ transport. Since the conductance of TRP channels to NH4+ has never been studied, bTRPV3 was overexpressed in HEK-293 cells and investigated using the patch-clamp technique and intracellular calcium imaging. Control cells contained the empty construct. Divalent cations blocked the conductance for monovalent cations in both cell types, with effects higher in cells expressing bTRPV3. In bTRPV3 cells, but not in controls, menthol, thymol, carvacrol, or 2-APB stimulated whole cell currents mediated by Na+, Cs+, NH4+, and K+, with a rise in intracellular Ca2+ observed in response to menthol. While only 25% of control patches showed single-channel events (with a conductance of 40.8 ± 11.9 pS for NH4+ and 25.0 ± 5.8 pS for Na+), 90% of bTRPV3 patches showed much larger conductances of 127.8 ± 4.2 pS for Na+, 240.1 ± 3.6 pS for NH4+, 34.0 ± 1.7 pS for Ca2+, and ~ 36 pS for NMDG+. Open probability, but not conductance, rose with time after patch excision. In conjunction with previous research, we suggest that bTRPV3 channels may play a role in the transport of Na+, K+, Ca2+ and NH4+ across the rumen with possible repercussions for understanding the function of TRPV3 in other epithelia. PMID:29494673
The bovine TRPV3 as a pathway for the uptake of Na+, Ca2+, and NH4.
Schrapers, Katharina T; Sponder, Gerhard; Liebe, Franziska; Liebe, Hendrik; Stumpff, Friederike
2018-01-01
Absorption of ammonia from the gastrointestinal tract results in problems that range from hepatic encephalopathy in humans to poor nitrogen efficiency of cattle with consequences for the global climate. Previous studies on epithelia and cells from the native ruminal epithelium suggest functional involvement of the bovine homologue of TRPV3 (bTRPV3) in ruminal NH4+ transport. Since the conductance of TRP channels to NH4+ has never been studied, bTRPV3 was overexpressed in HEK-293 cells and investigated using the patch-clamp technique and intracellular calcium imaging. Control cells contained the empty construct. Divalent cations blocked the conductance for monovalent cations in both cell types, with effects higher in cells expressing bTRPV3. In bTRPV3 cells, but not in controls, menthol, thymol, carvacrol, or 2-APB stimulated whole cell currents mediated by Na+, Cs+, NH4+, and K+, with a rise in intracellular Ca2+ observed in response to menthol. While only 25% of control patches showed single-channel events (with a conductance of 40.8 ± 11.9 pS for NH4+ and 25.0 ± 5.8 pS for Na+), 90% of bTRPV3 patches showed much larger conductances of 127.8 ± 4.2 pS for Na+, 240.1 ± 3.6 pS for NH4+, 34.0 ± 1.7 pS for Ca2+, and ~ 36 pS for NMDG+. Open probability, but not conductance, rose with time after patch excision. In conjunction with previous research, we suggest that bTRPV3 channels may play a role in the transport of Na+, K+, Ca2+ and NH4+ across the rumen with possible repercussions for understanding the function of TRPV3 in other epithelia.
Rochman, Chelsea M.; Manzano, Carlos; Hentschel, Brian T.; Massey Simonich, Staci L.; Hoh, Eunha
2014-01-01
Polycyclic aromatic hydrocarbons (PAHs) on virgin polystyrene (PS) and PS marine debris led us to examine PS as a source and sink for PAHs in the marine environment. At two locations in San Diego Bay, we measured sorption of PAHs to PS pellets, sampling at 0, 1, 3, 6, 9 and 12 months. We detected 25 PAHs using a new analytical method with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry. Several congeners were detected on samples before deployment. After deployment, some concentrations decreased (1,3-dimethylnaphthalene and 2,6-methylnaphthalene) while most increased (2-methylanthracene and all parent PAHs (PPAHs) except fluorene and fluoranthene), suggesting PS debris is a source and sink for PAHs. When comparing sorbed concentrations of PPAHs on PS to the five most common polymers (polyethylene terephthalate (PET), high-density polyethylene (HDPE), polyvinyl chloride (PVC), low-density polyethylene (LDPE), and polypropylene (PP)), PS sorbed greater concentrations than PP, PET and PVC, similar to HDPE and LDPE. Most strikingly, at 0 months, PPAHs on PS ranged from 8-200 times greater than on PET, HDPE, PVC, LDPE, and PP. The combination of greater PAHs in virgin pellets and large sorption suggests that PS may pose a greater risk of exposure to PAHs upon ingestion. PMID:24341360
Rochman, Chelsea M; Manzano, Carlos; Hentschel, Brian T; Simonich, Staci L Massey; Hoh, Eunha
2013-12-17
Polycyclic aromatic hydrocarbons (PAHs) on virgin polystyrene (PS) and PS marine debris led us to examine PS as a source and sink for PAHs in the marine environment. At two locations in San Diego Bay, we measured sorption of PAHs to PS pellets, sampling at 0, 1, 3, 6, 9, and 12 months. We detected 25 PAHs using a new analytical method with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry. Several congeners were detected on samples before deployment. After deployment, some concentrations decreased (1,3-dimethylnaphthalene and 2,6-methylnaphthalene), while most increased [2-methylanthracene and all parent PAHs (PPAHs), except fluorene and fluoranthene], suggesting that PS debris is a source and sink for PAHs. When sorbed concentrations of PPAHs on PS are compared to the five most common polymers [polyethylene terephthalate (PET), high-density polyethylene (HDPE), polyvinyl chloride (PVC), low-density polyethylene (LDPE), and polypropylene (PP)], PS sorbed greater concentrations than PP, PET, and PVC, similar to HDPE and LDPE. Most strikingly, at 0 months, PPAHs on PS ranged from 8 to 200 times greater than on PET, HDPE, PVC, LDPE, and PP. The combination of greater PAHs in virgin pellets and large sorption suggests that PS may pose a greater risk of exposure to PAHs upon ingestion.
Frick, Chris; Dietz, Andrew C; Merritt, Katharine; Umbreit, Thomas H; Tomazic-Jezic, Vesna J
2006-01-01
The main causes for the long-term prosthetic implants' failure are the body's reaction to the implanted material or mechanical stress on the device resulting in the formation of wear particles. Particulate wear debris attracts macrophages, and depending on the chemical composition of the material and particle size, various levels of inflammatory response may occur. While transient inflammation is common, development of chronic inflammation may have serious consequences, leading to implant failure. Such a process may also cause systemic changes to immune functions and long-term effects on the host immune responses. In this study, we evaluated the effects of polystyrene (PS), polyethylene (PE), and polymethylmethacrylate (PMMA) particles on macrophage function and the generation of T-cell responses. Particles of various diameters were injected intraperitoneally into Balb/c mice, and immune functions were examined at 3, 10, and 21 days after the injection. The intensity of phagocytosis by peritoneal exudate cells (PECs) and the proliferative response of spleen cells from treated mice were evaluated. Enumeration of PECs revealed an increase in the total number of cells. Mice injected with PS or PE particles had a higher percentage of cells containing particles than PMMA-injected mice. Macrophages with PS or PE particles tended to adhere to and/or infiltrate peritoneal fibro-fatty tissues surrounding the spleen and pancreas, while the PMMA-carrying macrophages infiltrated the spleen, resulting in an increase of spleen size and "weight. The spleen cell proliferation assay revealed only mild and transient effects on the mitogen response in both PE and PS particle-injected mice. However, in the PMMA-injected mice we observed a lasting increase of the Con A response and a decrease of the LPS response. In vitro exposure of PECs from untreated mice showed a dose-response pattern in nitric oxide (NO) and TNFalpha production. While exposure to either PMMA or PE induced comparable levels of NO, exposure to PMMA induced a markedly higher production of TNFalpha than exposure to PE. The results indicate that particulate biomaterials may, in addition to the initial activation of phagocytes, significantly affect immune functions and compromise the host response to other antigenic stimuli.
Evans, John R.; Jensen, E. Gray; Sell, Russell; Stephens, Christopher D.; Nyman, Douglas J.; Hamilton, Robert C.; Hager, William C.
2006-01-01
In September, 2003, the Alyeska Pipeline Service Company (APSC) and the U.S. Geological Survey (USGS) embarked on a joint effort to extract, test, and calibrate the accelerometers, amplifiers, and bandpass filters from the earthquake monitoring systems (EMS) at Pump Stations 09, 10, and 11 of the Trans-Alaska Pipeline System (TAPS). These were the three closest strong-motion seismographs to the Denali fault when it ruptured in the MW 7.9 earthquake of 03 November 2002 (22:12:41 UTC). The surface rupture is only 3.0 km from PS10 and 55.5 km from PS09 but PS11 is 124.2 km away from a small rupture splay and 126.9 km from the main trace. Here we briefly describe precision calibration results for all three instruments. Included with this report is a link to the seismograms reprocessed using these new calibrations: http://nsmp.wr.usgs.gov/data_sets/20021103_2212_taps.html Calibration information in this paper applies at the time of the Denali fault earthquake (03 November 2002), but not necessarily at other times because equipment at these stations is changed by APSC personnel at irregular intervals. In particular, the equipment at PS09, PS10, and PS11 was changed by our joint crew in September, 2003, so that we could perform these calibrations. The equipment stayed the same from at least the time of the earthquake until that retrieval, and these calibrations apply for that interval.
Coral reef fish predator maintains olfactory acuity in degraded coral habitats.
Natt, Michael; Lönnstedt, Oona M; McCormick, Mark I
2017-01-01
Coral reefs around the world are rapidly degrading due to a range of environmental stressors. Habitat degradation modifies the sensory landscape within which predator-prey interactions occur, with implications for olfactory-mediated behaviours. Predator naïve settlement-stage damselfish rely on conspecific damage-released odours (i.e., alarm odours) to inform risk assessments. Yet, species such as the Ambon damselfish, Pomacentrus amboinensis, become unable to respond appropriately to these cues when living in dead-degraded coral habitats, leading to increased mortality through loss of vigilance. Reef fish predators also rely on odours from damaged prey to locate, assess prey quality and engage in prey-stealing, but it is unknown whether their responses are also modified by the change to dead-degraded coral habitats. Implications for prey clearly depend on how their predatory counterparts are affected, therefore the present study tested whether olfactory-mediated foraging responses in the dusky dottyback, Pseudochromis fuscus, a common predator of P. amboinensis, were similarly affected by coral degradation. A y-maze was used to measure the ability of Ps. fuscus to detect and move towards odours, against different background water sources. Ps. fuscus were exposed to damage-released odours from juvenile P. amboinensis, or a control cue of seawater, against a background of seawater treated with either healthy or dead-degraded hard coral. Predators exhibited an increased time allocation to the chambers of y-mazes injected with damage-released odours, with comparable levels of response in both healthy and dead-degraded coral treated waters. In control treatments, where damage-released odours were replaced with a control seawater cue, fish showed no increased preference for either chamber of the y-maze. Our results suggest that olfactory-mediated foraging behaviours may persist in Ps. fuscus within dead-degraded coral habitats. Ps. fuscus may consequently gain a sensory advantage over P. amboinensis, potentially altering the outcome of predator-prey interactions.
NASA Astrophysics Data System (ADS)
Jia, Man; Lou, Sen Yue
2018-05-01
In natural and social science, many events happened at different space-times may be closely correlated. Two events, A (Alice) and B (Bob) are defined as correlated if one event is determined by another, say, B = f ˆ A for suitable f ˆ operators. A nonlocal AB-KdV system with shifted-parity (Ps, parity with a shift), delayed time reversal (Td, time reversal with a delay) symmetry where B =Ps ˆ Td ˆ A is constructed directly from the normal KdV equation to describe two-area physical event. The exact solutions of the AB-KdV system, including PsTd invariant and PsTd symmetric breaking solutions are shown by different methods. The PsTd invariant solution show that the event happened at A will happen also at B. These solutions, such as single soliton solutions, infinitely many singular soliton solutions, soliton-cnoidal wave interaction solutions, and symmetry reduction solutions etc., show the AB-KdV system possesses rich structures. Also, a special Bäcklund transformation related to residual symmetry is presented via the localization of the residual symmetry to find interaction solutions between the solitons and other types of the AB-KdV system.
Light activated compounds as antimicrobial agents - patently obvious?
Phoenix, D A; Harris, F
2006-06-01
Microbial pathogens with resistance to conventional drugs are a problem of global proportions and may be viral such as HIV, bacterial as in the case of MRSA or eukaryotic as seen with the malarial parasite Plasmodium falciparum. In response, photodynamic antimicrobial chemotherapy (PACT) has been developed, which is the delivery of a non-toxic photosensitiser (PS) to the site of a microbial infection. When taken up by the pathogen, illumination of the PS by light at an appropriate wavelength can lead to inactivation of the pathogen through the production of highly reactive free radical species, which induce oxidative damage to lipid, proteins and DNA / RNA, and / or adduct formation between the PS and these microbial biomolecules. Here the photochemical and photophysical steps underlying PS antimicrobial action along with the desirable electronic and physiochemical properties of PS are briefly reviewed. The therapeutic uses of PS are then illustrated with reference to a number that have featured in recent patents, including: The induction of endogenous PS by aminolevulinic acid; phenothiazinium based PS, which are the most studied of PACT agents, psoralens and organorhodium complexes.
O electrolyte for bio-application
NASA Astrophysics Data System (ADS)
Naddaf, M.; Almariri, A.
2014-09-01
Porous silicon (PS) has been prepared in the dark by anodic etching of n+-type (111) silicon substrate in a HF:HCl:C2H5OH:H2O2:H2O electrolyte. The processed PS layer is characterized by means of photoluminescence (PL) spectroscopy, scanning electron microscope (SEM), water contact angle (CA) measurements, Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and micro-Raman scattering. The CA of fresh PS layer is found to be ~142°. On aging at ambient conditions, the CA decreases gently to reach ~133° after 3 month, and then it is stabilized for a prolonged time of aging. The visible PL emission from the PS layer also exhibits a good stability against aging time. The FTIR and XPS measurements and analysis show that the stable aged PS layer has rather SiO2-rich surface. The micro/nanostructure nature of the PS layer is revealed from SEM and micro-Raman results and correlated to CA results. Stable hydrophobic surface of oxidized PS layer is attractive for bio-applications. The efficiency of the produced PS layers as an entrapping template for specific immobilization of IgG2a antibody via physical absorption process is demonstrated.
Neutron temporal diagnostic for high-yield deuterium-tritium cryogenic implosions on OMEGA
Stoeckl, C.; Boni, R.; Ehrne, F.; ...
2016-05-10
A next-generation neutron temporal diagnostic (NTD) capable of recording high-quality data for the highest anticipated yield cryogenic DT implosion experiments was recently installed at the Omega Laser Facility. A high-quality measurement of the neutron production width is required to determine the hot-spot pressure achieved in inertial confinement fusion experiments—a key metric in assessing the quality of these implosions. The design of this NTD is based on a fast-rise-time plastic scintillator, which converts the neutron kinetic energy to 350- to 450-nm-wavelength light. The light from the scintillator inside the nose-cone assembly is relayed ~16 m to a streak camera in amore » well-shielded location. An ~200× reduction in neutron background was observed during the first high-yield DT cryogenic implosions compared to the current NTD installation on OMEGA. An impulse response of ~40±10 ps was measured in a dedicated experiment using hard x rays from a planar target irradiated with a 10-ps short pulse from the OMEGA EP laser. Furthermore, the measured instrument response includes contributions from the scintillator rise time, optical relay, and streak camera.« less
Neutron temporal diagnostic for high-yield deuterium–tritium cryogenic implosions on OMEGA
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stoeckl, C.; Boni, R.; Ehrne, F.
A next-generation neutron temporal diagnostic (NTD) capable of recording high-quality data for the highest anticipated yield cryogenic deuterium–tritium (DT) implosion experiments was recently installed at the Omega Laser Facility. A high-quality measurement of the neutron production width is required to determine the hot-spot pressure achieved in inertial confinement fusion experiments—a key metric in assessing the quality of these implosions. The design of this NTD is based on a fast-rise-time plastic scintillator, which converts the neutron kinetic energy to 350- to 450-nm-wavelength light. The light from the scintillator inside the nose-cone assembly is relayed ∼16 m to a streak camera inmore » a well-shielded location. An ∼200× reduction in neutron background was observed during the first high-yield DT cryogenic implosions compared to the current NTD installation on OMEGA. An impulse response of ∼40 ± 10 ps was measured in a dedicated experiment using hard x-rays from a planar target irradiated with a 10-ps short pulse from the OMEGA EP laser. The measured instrument response includes contributions from the scintillator rise time, optical relay, and streak camera.« less
Neutron temporal diagnostic for high-yield deuterium-tritium cryogenic implosions on OMEGA
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stoeckl, C.; Boni, R.; Ehrne, F.
A next-generation neutron temporal diagnostic (NTD) capable of recording high-quality data for the highest anticipated yield cryogenic DT implosion experiments was recently installed at the Omega Laser Facility. A high-quality measurement of the neutron production width is required to determine the hot-spot pressure achieved in inertial confinement fusion experiments—a key metric in assessing the quality of these implosions. The design of this NTD is based on a fast-rise-time plastic scintillator, which converts the neutron kinetic energy to 350- to 450-nm-wavelength light. The light from the scintillator inside the nose-cone assembly is relayed ~16 m to a streak camera in amore » well-shielded location. An ~200× reduction in neutron background was observed during the first high-yield DT cryogenic implosions compared to the current NTD installation on OMEGA. An impulse response of ~40±10 ps was measured in a dedicated experiment using hard x rays from a planar target irradiated with a 10-ps short pulse from the OMEGA EP laser. Furthermore, the measured instrument response includes contributions from the scintillator rise time, optical relay, and streak camera.« less
NASA Astrophysics Data System (ADS)
Li, J.; Song, X.; Wang, P.; Zhu, L.
2017-12-01
The H-κ method (Zhu and Kanamori, 2000) has been widely used to estimate the crustal thickness and Vp/Vs ratio with receiver functions. However, in regions where the crustal structure is complicated, the method may produce uncertain or even unrealistic results, arising particularly from dipping Moho and/or crustal anisotropy. Here, we propose an improved H-κ method, which corrects for these effects first before stacking. The effect of dipping Moho and crustal anisotropy on Ps receiver function has been well studied, but not as much on crustal multiples (PpPs and PpSs+PsPs). Synthetic tests show that the effect of crustal anisotropy on the multiples are similar to Ps, while the effect of dipping Moho on the multiples is 5 times that on Ps (same cosine trend but 5 times in time shift). A Harmonic Analysis (HA) method for dipping/anisotropy was developed by Wang et al. (2017) for crustal Ps receiver functions to extract parameters of dipping Moho and crustal azimuthal anisotropy. In real data, the crustal multiples are much more complicated than the Ps. Therefore, we use the HA method (Wang et al., 2017), but apply separately to Ps and the multiples. It shows that although complicated, the trend of multiples can still be reasonably well represented by the HA. We then perform separate azimuthal corrections for Ps and the multiples and stack to obtain a combined receiver function. Lastly, the traditional H-κ procedure is applied to the stacked receiver function. We apply the improved H-κ method on 40 CNDSN (Chinese National Digital Seismic Network) stations distributed in a variety of geological setting across the Chinese continent. The results show apparent improvement compared to the traditional H-κ method, with clearer traces of multiples and stronger stacking energy in the grid search, as well as more reliable H-κ values.
NASA Astrophysics Data System (ADS)
Furuki, Makoto; Tian, Minquan; Sato, Yasuhiro; Pu, Lyong Sun; Tatsuura, Satoshi; Wada, Osamu
2000-07-01
We applied time-to-space conversion using femtosecond nonlinear-optical response of squarylium-dye (SQ) J-aggregates film. A pump pulse and a train of four probe pulses were illuminated on the same area (10 mm φ) of the film in direction of oblique and normal to the film plane, respectively. Due to the oblique illumination, the pump pulse met probe pulses (interval time: 1 ps) at separate places. The film picked out part of each probe pulse by its transmittance change, which was observed for a transmitted image of spatially separated four lines. Response time of the SQ J aggregates is enough for the single-shot 1 THz demultiplexing.
NASA Astrophysics Data System (ADS)
Stauffer, Hans U.; Miller, Joseph D.; Slipchenko, Mikhail N.; Meyer, Terrence R.; Prince, Benjamin D.; Roy, Sukesh; Gord, James R.
2014-01-01
The hybrid femtosecond/picosecond coherent anti-Stokes Raman scattering (fs/ps CARS) technique presents a promising alternative to either fs time-resolved or ps frequency-resolved CARS in both gas-phase thermometry and condensed-phase excited-state dynamics applications. A theoretical description of time-dependent CARS is used to examine this recently developed probe technique, and quantitative comparisons of the full time-frequency evolution show excellent accuracy in predicting the experimental vibrational CARS spectra obtained for two model systems. The interrelated time- and frequency-domain spectral signatures of gas-phase species produced by hybrid fs/ps CARS are explored with a focus on gas-phase N2 vibrational CARS, which is commonly used as a thermometric diagnostic of combusting flows. In particular, we discuss the merits of the simple top-hat spectral filter typically used to generate the ps-duration hybrid fs/ps CARS probe pulse, including strong discrimination against non-resonant background that often contaminates CARS signal. It is further demonstrated, via comparison with vibrational CARS results on a time-evolving solvated organic chromophore, that this top-hat probe-pulse configuration can provide improved spectral resolution, although the degree of improvement depends on the dephasing timescales of the observed molecular modes and the duration and timing of the narrowband final pulse. Additionally, we discuss the virtues of a frequency-domain Lorentzian probe-pulse lineshape and its potential for improving the hybrid fs/ps CARS technique as a diagnostic in high-pressure gas-phase thermometry applications.
Stauffer, Hans U; Miller, Joseph D; Slipchenko, Mikhail N; Meyer, Terrence R; Prince, Benjamin D; Roy, Sukesh; Gord, James R
2014-01-14
The hybrid femtosecond∕picosecond coherent anti-Stokes Raman scattering (fs∕ps CARS) technique presents a promising alternative to either fs time-resolved or ps frequency-resolved CARS in both gas-phase thermometry and condensed-phase excited-state dynamics applications. A theoretical description of time-dependent CARS is used to examine this recently developed probe technique, and quantitative comparisons of the full time-frequency evolution show excellent accuracy in predicting the experimental vibrational CARS spectra obtained for two model systems. The interrelated time- and frequency-domain spectral signatures of gas-phase species produced by hybrid fs∕ps CARS are explored with a focus on gas-phase N2 vibrational CARS, which is commonly used as a thermometric diagnostic of combusting flows. In particular, we discuss the merits of the simple top-hat spectral filter typically used to generate the ps-duration hybrid fs∕ps CARS probe pulse, including strong discrimination against non-resonant background that often contaminates CARS signal. It is further demonstrated, via comparison with vibrational CARS results on a time-evolving solvated organic chromophore, that this top-hat probe-pulse configuration can provide improved spectral resolution, although the degree of improvement depends on the dephasing timescales of the observed molecular modes and the duration and timing of the narrowband final pulse. Additionally, we discuss the virtues of a frequency-domain Lorentzian probe-pulse lineshape and its potential for improving the hybrid fs∕ps CARS technique as a diagnostic in high-pressure gas-phase thermometry applications.
Denadai, Rafael; Samartine Junior, Hugo; Denadai, Rodrigo; Raposo-Amaral, Cassio Eduardo
2015-11-01
The aim of this study is to assess the public perception of plastic surgeons (PS) as craniofacial surgery specialists. Members of the public (N = 1514) were asked to choose 1 or 2 specialists that they perceived to be an expert for 13 craniofacial surgery-related scenarios. Response patterns were distributed as "plastic surgeon alone" (PS alone), "PS combined with other specialists", or "no plastic surgeon" (No PS). Sociodemographic data, previous plastic surgery contact, and source of reported information were also collected. "Plastic surgeon alone" was significantly (all P < 0.05) more recognized as experts than all other response patterns particularly in congenital anomalies-related scenarios (83.33%). There was a significantly (all P < 0.05) poor understanding of the role of PSs in head/neck infection management, chronic facial palsy management, dental disease management, head and neck cancer surgery, vascular malformation surgery, and facial fracture surgery. Sex, age, education level, health care professional, prior plastic surgery contact, and source of reported information were not significant (all P < 0.05) determinants of "PS" as the response in bivariate and multivariate analyses. Public recognized PSs as experts primarily in treatment of congenital cleft and craniofacial anomalies, but as the overall scope of craniofacial surgery practice was poorly understood and known, improved public education is needed.
Quantification of Triacylglycerol Positional Isomers in Rat Milk.
Watanabe, Natsuko; Nagai, Toshiharu; Mizobe, Hoyo; Yoshinaga, Kazuaki; Yoshida, Akihiko; Kitamura, Yohei; Shimizu, Takashi; Beppu, Fumiaki; Gotoh, Naohiro
2016-12-01
The absolute amount of triacylglycerol (TAG) positional isomers was analyzed in rat milk fat, a representative of non-ruminant milk fat, using a HPLC-UV-atmospheric pressure chemical ionization-MS/MS system equipped with an octacosyl silylation column or polymeric ODS column. TAGs consisting of two oleic acids (O) and one palmitic acid (P) were the most abundant. In particular, β-OPO, a TAG binding P at the β-position (sn-2) and two Os at the α-positions (sn-1/3), was prominent. The β-OPO content decreased over time, while a TAG consisting of two Ps and one capric acid, a medium-chain fatty acid, increased. TAGs consisting of two Ps and one docosahexaenoic acid were present in small amounts and decreased with time. These results indicated that the recombination of fatty acids in TAGs in milk fat occurs in the mother, and is thought to depend on the infant's stage of growth, in response to their nutritional needs. It was also demonstrated that medium-chain fatty acids were mainly located at the α-position (sn-3), while Ps were mainly located at the β-position (sn-2). Therefore, the combination and binding positions of fatty acids of TAG are considered very important in infant nutrition.
2014-01-01
Background The challenge of priority setting (PS) in health care within contexts of severe resource limitations has continued to receive attention. Accountability for Reasonableness (AFR) has emerged as a useful framework to guide the implementation of PS processes. In 2006, the AFR approach to enhance legitimate and fair PS was introduced by researchers and decision makers within the health sector in the EU funded research project entitled ‘Response to Accountable priority setting for Trust in health systems’ (REACT). The project aimed to strengthen fairness and accountability in the PS processes of health systems at district level in Zambia, Tanzania and Kenya. This paper focuses on local perceptions and practices of fair PS (baseline study) as well as at the evolution of such perceptions and practices in PS following an AFR based intervention (evaluation study), carried out at district level in Kapiri-Mposhi District in Zambia. Methods Data was collected using in depth interviews (IDIs), focus group discussions (FGDs) and review of documents from national to district level. The study population for this paper consisted of health related stakeholders employed in the district administration, in non-governmental organizations (NGO) and in health facilities. Results During the baseline study, concepts of legitimacy and fairness in PS processes were found to be grounded in local values of equity and impartiality. Government and other organizational strategies strongly supported devolution of PS and decision making procedures. However, important gaps were identified in terms of experiences of stakeholder involvement and fairness in PS processes in practice. The evaluation study revealed that a transformation of the views and methods regarding fairness in PS processes was ongoing in the study district, which was partly attributed to the AFR based intervention. Conclusions The study findings suggest that increased attention was given to fairness in PS processes at district level. The changes were linked to a number of simultaneous factors among them the concepts introduced by the present project with its emphasis on fairness and enhanced participation. A responsive leadership that was increasingly accountable to its operational staff and communities emerged as one of the key elements in driving the processes forward. PMID:24548767
Zulu, Joseph M; Michelo, Charles; Msoni, Carol; Hurtig, Anna-Karin; Byskov, Jens; Blystad, Astrid
2014-02-18
The challenge of priority setting (PS) in health care within contexts of severe resource limitations has continued to receive attention. Accountability for Reasonableness (AFR) has emerged as a useful framework to guide the implementation of PS processes. In 2006, the AFR approach to enhance legitimate and fair PS was introduced by researchers and decision makers within the health sector in the EU funded research project entitled 'Response to Accountable priority setting for Trust in health systems' (REACT). The project aimed to strengthen fairness and accountability in the PS processes of health systems at district level in Zambia, Tanzania and Kenya. This paper focuses on local perceptions and practices of fair PS (baseline study) as well as at the evolution of such perceptions and practices in PS following an AFR based intervention (evaluation study), carried out at district level in Kapiri-Mposhi District in Zambia. Data was collected using in depth interviews (IDIs), focus group discussions (FGDs) and review of documents from national to district level. The study population for this paper consisted of health related stakeholders employed in the district administration, in non-governmental organizations (NGO) and in health facilities. During the baseline study, concepts of legitimacy and fairness in PS processes were found to be grounded in local values of equity and impartiality. Government and other organizational strategies strongly supported devolution of PS and decision making procedures. However, important gaps were identified in terms of experiences of stakeholder involvement and fairness in PS processes in practice. The evaluation study revealed that a transformation of the views and methods regarding fairness in PS processes was ongoing in the study district, which was partly attributed to the AFR based intervention. The study findings suggest that increased attention was given to fairness in PS processes at district level. The changes were linked to a number of simultaneous factors among them the concepts introduced by the present project with its emphasis on fairness and enhanced participation. A responsive leadership that was increasingly accountable to its operational staff and communities emerged as one of the key elements in driving the processes forward.
NASA Astrophysics Data System (ADS)
Kubota, Jun; Wada, Akihide; Domen, Kazunari; Kano, Satoru S.
2002-08-01
The behavior of D 2O ice on CO/Pt(1 1 1) and Pt(1 1 1) under the irradiation of near-IR pulses (NIR) was studied by sum-frequency generation (SFG) spectroscopy. The peaks assigned to the O-D stretching modes of ice were obtained for the first 30 molecular layers on Pt(1 1 1). When the D2O/ CO/ Pt(1 1 1) was irradiated, the signal of D 2O was weakened after 500 ps, but that of CO was weakened immediately after the pumping. A similar time response was observed for the D 2O peak in D2O/ Pt(1 1 1) . The weakening of SFG is attributed to the broadening of bands due to thermal excitation. This indicates that the energy of the pump pulse is deposited on the Pt(1 1 1) surface and diffused into the layers of D 2O ice in the 500 ps timescale.
NASA Astrophysics Data System (ADS)
Yücel, H.; Çubukçu, Ş.; Uyar, E.; Engin, Y.
2014-11-01
The energy dependence of the response of BC-408 plastic scintillator (PS), an approximately water-equivalent material, has been investigated by employing standardized x-ray beams. IEC RQA and ISO N series x-ray beam qualities, in the range of 40-100 kVp, were calibrated using a PTW-type ionization chamber. The energy response of a thick BC-408 PS detector was measured using the multichannel pulse height analysis method. The response of BC-408 PS increased gradually with increasing energy in the energy range of 40-80 kVp and then showed a flat behavior at about 80 to 120 kVp. This might be due to the self-attenuation of scintillation light by the scintillator itself and may also be partly due to the ionization quenching, leading to a reduction in the intensity of the light output from the scintillator. The results indicated that the sensitivity drop in BC-408 PS material at lower photon energies may be overcome by adding some high-Z elements to its polyvinyltoluene (PVT) base. The material modification may compensate for the drop in the response at lower photon energies. Thus plastic scintillation dosimetry is potentially suitable for applications in diagnostic radiology.
Yücel, H; Çubukçu, Ş; Uyar, E; Engin, Y
2014-11-21
The energy dependence of the response of BC-408 plastic scintillator (PS), an approximately water-equivalent material, has been investigated by employing standardized x-ray beams. IEC RQA and ISO N series x-ray beam qualities, in the range of 40-100 kVp, were calibrated using a PTW-type ionization chamber. The energy response of a thick BC-408 PS detector was measured using the multichannel pulse height analysis method. The response of BC-408 PS increased gradually with increasing energy in the energy range of 40-80 kVp and then showed a flat behavior at about 80 to 120 kVp. This might be due to the self-attenuation of scintillation light by the scintillator itself and may also be partly due to the ionization quenching, leading to a reduction in the intensity of the light output from the scintillator. The results indicated that the sensitivity drop in BC-408 PS material at lower photon energies may be overcome by adding some high-Z elements to its polyvinyltoluene (PVT) base. The material modification may compensate for the drop in the response at lower photon energies. Thus plastic scintillation dosimetry is potentially suitable for applications in diagnostic radiology.
Skin Resistivity Value of Upper Trapezius Latent Trigger Points
Skorupska, Elżbieta; Zawadziński, Jarosław
2015-01-01
Introduction. The skin resistivity (SkR) measurement is commonly recommended for acupoints measurement, but for trigger points (TrPs) only one study is available. The purpose of the study was to evaluate SkR for latent TrPs compared to non-TrPs and the surrounding tissue. Material and Methods. Forty-two healthy volunteers with unilateral latent upper trapezius TrPs (12 men, 30 women) aged 21–23 (mean age: 22.1 ± 0.6 y) participated in the study. Keithley electrometer 610B was used for measuring SkR (Ag/AgCl self-adhesive, disposable ground electrode: 30 mm diameter). SkR was measured for latent TrPs and compared to opposite non-TrPs sites and the surrounding tissue. Results. The SkR decrease of TrPs-positive sites as compared to TrPs-negative sites and the surrounding tissue was confirmed. However, no statistically significant difference in the SkR value occurred when all data were analyzed. The same was confirmed after gender division and for TrPs-positive subjects examined for referred pain and twitch response presence. Conclusion. SkR reactive changes at latent TrPs are possible but the results were not consistent with the previous study. Thus, caution in applying SkR to latent TrPs isolation is recommended and its clinical use should not be encouraged yet. Further studies, especially on active TrPs, are yet required. PMID:26180796
Iron allocation in leaves of Fe-deficient cucumber plants fed with natural Fe complexes.
Zanin, Laura; Tomasi, Nicola; Rizzardo, Cecilia; Gottardi, Stefano; Terzano, Roberto; Alfeld, Matthias; Janssens, Koen; De Nobili, Maria; Mimmo, Tanja; Cesco, Stefano
2015-05-01
Iron (Fe) sources available for plants in the rhizospheric solution are mainly a mixture of complexes between Fe and organic ligands, including phytosiderophores (PS) and water-extractable humic substances (WEHS). In comparison with the other Fe sources, Fe-WEHS are more efficiently used by plants, and experimental evidences show that Fe translocation contributes to this better response. On the other hand, very little is known on the mechanisms involved in Fe allocation in leaves. In this work, physiological and molecular processes involved in Fe distribution in leaves of Fe-deficient Cucumis sativus supplied with Fe-PS or Fe-WEHS up to 5 days were studied combining different techniques, such as radiochemical experiments, synchrotron micro X-ray fluorescence, real-time reverse transcription polymerase chain reaction and in situ hybridization. In Fe-WEHS-fed plants, Fe was rapidly (1 day) allocated into the leaf veins, and after 5 days, Fe was completely transferred into interveinal cells; moreover, the amount of accumulated Fe was much higher than with Fe-PS. This redistribution in Fe-WEHS plants was associated with an upregulation of genes encoding a ferric(III) -chelate reductase (FRO), a Fe(2+) transporter (IRT1) and a natural resistance-associated macrophage protein (NRAMP). The localization of FRO and IRT1 transcripts next to the midveins, beside that of NRAMP in the interveinal area, may suggest a rapid and efficient response induced by the presence of Fe-WEHS in the extra-radical solution for the allocation in leaves of high amounts of Fe. In conclusion, Fe is more efficiently used when chelated to WEHS than PS and seems to involve Fe distribution and gene regulation of Fe acquisition mechanisms operating in leaves. © 2014 Scandinavian Plant Physiology Society.
Mui, B; Raney, S G; Semple, S C; Hope, M J
2001-09-01
The therapeutic benefit from phosphorothioate oligodeoxynucleotides (PS ODN) containing immune stimulatory sequences (ISS) has been demonstrated in animal models of cancer and infection. In particular, when CpG-containing PS ODN are administered to mice, activation of macrophages and dendritic, NK, T, and B cells occurs, resulting in the release of an array of cytokines, including interleukin-12 (IL-12), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). We have previously described stabilized antisense-lipid particles (SALP) for the i.v. administration of antisense ODN [Biochim Biophys Acta (2001) 1510:152--166]. Given the propensity for SALP to target macrophages in vivo it was of interest to determine whether they could enhance the potency of CpG ODN to induce an immune response. In this report we show that when CpG-containing SALP are administered intravenously to ICR mice the plasma concentrations of IL-12, IFN-gamma, IL-6, monocyte chemoattractant protein-1, and TNF-alpha are greatly increased compared with the same dose of free ODN. The pattern of cytokine induction indicates that the immune response is T helper cell type 1-biased, similar to that observed for PS CpG ODN ISS in general. Furthermore, when phosphodiester (PO) ODN is substituted for PS ODN in the SALP formulation cytokine induction is even greater at the early time points, in marked contrast to free PO ODN, which is inactive. These results demonstrate that the immunogenicity of ISS is not only enhanced by encapsulation in lipid particles, which more closely mimic the way ISS DNA would normally be presented to antigen presenting cells by pathogens in vivo, but also SALP enable unmodified PO CpG ODN to be used as immune stimulants.
NASA Astrophysics Data System (ADS)
Régis, J.-M.; Mach, H.; Simpson, G. S.; Jolie, J.; Pascovici, G.; Saed-Samii, N.; Warr, N.; Bruce, A.; Degenkolb, J.; Fraile, L. M.; Fransen, C.; Ghita, D. G.; Kisyov, S.; Koester, U.; Korgul, A.; Lalkovski, S.; Mărginean, N.; Mutti, P.; Olaizola, B.; Podolyak, Z.; Regan, P. H.; Roberts, O. J.; Rudigier, M.; Stroe, L.; Urban, W.; Wilmsen, D.
2013-10-01
A novel method for direct electronic “fast-timing” lifetime measurements of nuclear excited states via γ-γ coincidences using an array equipped with N∈N equally shaped very fast high-resolution LaBr3(Ce) scintillator detectors is presented. Analogous to the mirror symmetric centroid difference method, the generalized centroid difference method provides two independent “start” and “stop” time spectra obtained by a superposition of the N(N-1)γ-γ time difference spectra of the N detector fast-timing system. The two fast-timing array time spectra correspond to a forward and reverse gating of a specific γ-γ cascade. Provided that the energy response and the electronic time pick-off of the detectors are almost equal, a mean prompt response difference between start and stop events is calibrated and used as a single correction for lifetime determination. These combined fast-timing arrays mean γ-γ time-walk characteristics can be determined for 40 keV
Terranova, Lisa; Dragusin, Diana Maria; Mallet, Romain; Vasile, Eugeniu; Stancu, Izabela-Cristina; Behets, Catherine; Chappard, Daniel
2017-02-01
Non-biodegradable porous polystyrene (PS) scaffolds, composed of microfibers, have been prepared by electrospinning for the reconstruction of large bone defects. PS microfibers were prepared by incorporating β-TCP grains inside the polymer or grafting gold nanoparticles surface functionalized with mercaptosuccinic acid. Cytocompatibility of the three types of scaffolds (PS, β-TCP-PS and Au-PS) was studied by seeding human mesenchymal stem cells. Biocompatibility was evaluated by implanting β-TCP-PS and Au-PS scaffolds into a critical size (4mm) calvarial defect in mice. Calvaria were taken 6, 9, and 12 weeks after implantation; newly formed bone and cellular response was analyzed by microcomputed tomography (microCT) and histology. β-TCP-PS scaffolds showed a significantly higher cell proliferation in vitro than on PS or Au-PS alone; clearly, the presence of β-TCP grains improved cytocompatibility. Biocompatibility study in the mouse calvaria model showed that β-TCP-PS scaffolds were significantly associated with more newly-formed bone than Au-PS. Bone developed by osteoconduction from the defect margins to the center. A dense fibrous connective tissue containing blood vessels was identified histologically in both types of scaffolds. There was no inflammatory foci nor giant cell in these areas. AuNPs aggregates were identified histologically in the fibrosis and also incorporated in the newly-formed bone matrix. Although the different types of PS microfibers appeared cytocompatible during the in vitro experiment, they appeared biotolerated in vivo since they induced a fibrotic reaction associated with newly formed bone. Copyright © 2016 Elsevier Ltd. All rights reserved.
Du, Ping; Brendle, Sarah; Milici, Janice; Camacho, Fabian; Zurlo, John; Christensen, Neil; Meyers, Craig
2015-01-01
Objective Human papillomavirus (HPV)-associated cancers are important public health problems in HIV-infected people. Assays based on HPV virus-like particles (VLP) and pseudoviruses (PsV) are commonly used to examine HPV antibody responses in HIV-infected people, but neutralization assays with native HPV have not been utilized and a comparison of these three assays is lacking. We evaluated the agreement of assays using VLP, native HPV and PsV in detecting HPV16 and 18 antibodies in HIV-infected women. Methods The VLP-based ELISA (VLP-ELISA) was used to detect antibody responses to HPV16 and 18 and cottontail rabbit papillomavirus (CRPV) VLP antigens. Neutralization assays with native HPV (NA-HPV) and with PsV (NA-PsV) were conducted to examine HPV16 or 18 neutralizing antibodies. Intra class correlation coefficients (ICC) and kappa coefficients were used to assess the agreements of seropositivity between the assays. Results The seroprevalence detected by the VLP-ELISA, NA-HPV and NA-PsV in 94 HIV-infected women was 35%, 51% and 27% for HPV16 and 14%, 44% and 21% for HPV18. Cross-reactivity between HPV16 and HPV18 was 0.35, 0.04 and 0.33 (kappa coefficients) for the VLP-ELISA, NA-HPV and NA-PsV. The agreements of seropositivity between the three assays were low. Six women who were HPV16 DNA positive were seropositive by the NA-HPV but only two were HPV16 seropositive by the VLP-ELISA or NA-PsV. One HPV18 DNA positive woman was seropositive by all three assays. Repeated tests indicated excellent reproducibility of the NA-HPV. Conclusion HPV serology results vary across different assays. The NA-HPV appears to be a sensitive and reliable approach in detecting natural HPV antibodies in HIV-infected women. The NA-HPV can be applied in both HPV natural history studies and vaccine studies in HIV-infected people. PMID:26085957
Niu, Jun; Bi, Quanxin; Deng, Shuya; Chen, Huiping; Yu, Haiyan; Wang, Libing; Lin, Shanzhi
2018-01-24
Auxin response factors (ARFs) in auxin signaling pathway are an important component that can regulate the transcription of auxin-responsive genes involved in almost all aspects of plant growth and development. To our knowledge, the comprehensive and systematic characterization of ARF genes has never been reported in Prunus sibirica, a novel woody biodiesel feedstock in China. In this study, we identified 14 PsARF genes with a perfect open reading frame (ORF) in P. sibirica by using its previous transcriptomic data. Conserved motif analysis showed that all identified PsARF proteins had typical DNA-binding and ARF domain, but 5 members (PsARF3, 8 10, 16 and 17) lacked the dimerization domain. Phylogenetic analysis of the ARF proteins generated from various plant species indicated that ARFs could be categorized into 4 major groups (Class I, II, III and IV), in which all identified ARFs from P. sibirica showed a closest relationship with those from P. mume. Comparison of the expression profiles of 14 PsARF genes in different developmental stages of Siberian apricot mesocarp (SAM) and kernel (SAK) reflected distinct temporal or spatial expression patterns for PsARF genes. Additionally, based on the expressed data from fruit and seed development of multiple plant species, we identified 1514 ARF-correlated genes using weighted gene co-expression network analysis (WGCNA). And the major portion of ARF-correlated gene was characterized to be involved in protein, nucleic acid and carbohydrate metabolic, transport and regulatory processes. In summary, we systematically and comprehensively analyzed the structure, expression pattern and co-expression network of ARF gene family in P. sibirica. All our findings provide theoretical foundation for the PsARF gene family and will pave the way for elucidating the precise role of PsARF genes in SAM and SAK development.
Savada, Raghavendra P; Ozga, Jocelyn A; Jayasinghege, Charitha P A; Waduthanthri, Kosala D; Reinecke, Dennis M
2017-10-01
Ethylene biosynthesis is regulated in reproductive tissues in response to heat stress in a manner to optimize resource allocation to pollinated fruits with developing seeds. High temperatures during reproductive development are particularly detrimental to crop fruit/seed production. Ethylene plays vital roles in plant development and abiotic stress responses; however, little is known about ethylene's role in reproductive tissues during development under heat stress. We assessed ethylene biosynthesis and signaling regulation within the reproductive and associated tissues of pea during the developmental phase that sets the stage for fruit-set and seed development under normal and heat-stress conditions. The transcript abundance profiles of PsACS [encode enzymes that convert S-adenosyl-L-methionine to 1-aminocyclopropane-1-carboxylic acid (ACC)] and PsACO (encode enzymes that convert ACC to ethylene), and ethylene evolution were developmentally, environmentally, and tissue-specifically regulated in the floral/fruit/pedicel tissues of pea. Higher transcript abundance of PsACS and PsACO in the ovaries, and PsACO in the pedicels was correlated with higher ethylene evolution and ovary senescence and pedicel abscission in fruits that were not pollinated under control temperature conditions. Under heat-stress conditions, up-regulation of ethylene biosynthesis gene expression in pre-pollinated ovaries was also associated with higher ethylene evolution and lower retention of these fruits. Following successful pollination and ovule fertilization, heat-stress modified PsACS and PsACO transcript profiles in a manner that suppressed ovary ethylene evolution. The normal ethylene burst in the stigma/style and petals following pollination was also suppressed by heat-stress. Transcript abundance profiles of ethylene receptor and signaling-related genes acted as qualitative markers of tissue ethylene signaling events. These data support the hypothesis that ethylene biosynthesis is regulated in reproductive tissues in response to heat stress to modulate resource allocation dynamics.
Zhao, Lu; Wu, Xiaoming; Si, Yu; Yao, Zhipeng; Dong, Zengxiang; Novakovic, Valerie A; Guo, Li; Tong, Dongxia; Chen, He; Bi, Yayan; Kou, Junjie; Shi, Huaizhang; Tian, Ye; Hu, Shaoshan; Zhou, Jin; Shi, Jialan
2017-11-01
OBJECTIVE Phosphatidylserine (PS) is a major component of the inner leaflet of membrane bilayers. During cell activation or apoptosis, PS is externalized to the outer membrane, providing an important physiological signal necessary for the release of the microparticles (MPs) that are generated through the budding of cellular membranes. MPs express PS and membrane antigens that reflect their cellular origin. PS exposure on the cell surface and the release of MPs provide binding sites for factor Xa and prothrombinase complexes that promote thrombin formation. Relatively little is known about the role of PS exposure on blood cells and MPs in patients with internal carotid artery (ICA) stenosis who have undergone carotid artery stenting (CAS). The authors aimed to investigate the extent of PS exposure on blood cells and MPs and to define its role in procoagulant activity (PCA) in the 7 days following CAS. METHODS The study included patients with ICA stenosis who had undergone CAS (n = 70), matched patients who had undergone catheter angiography only (n = 30), and healthy controls (n = 30). Blood samples were collected from all patients just before the procedure after an overnight fast and at 2, 6, 24, 48, and 72 hours and 7 days after the CAS procedure. Blood was collected from healthy controls after an overnight fast. Phosphatidylserine-positive (PS+) MPs and blood cells were analyzed by flow cytometry, while PCA was assessed with clotting time analysis, purified coagulation complex assays, and fibrin formation assays. RESULTS The authors found that levels of PS+ blood cells and PS+ blood cell-derived MPs (platelets and platelet-derived MPs [PMPs], neutrophils and neutrophil-derived MPs [NMPs], monocytes and monocyte-derived MPs [MMPs], erythrocytes and erythrocyte-derived MPs [RMPs], and endothelial cells and endothelial cell-derived MPs [EMPs]) were increased in the 7 days following the CAS procedure. Specifically, elevation of PS exposure on platelets/PMPs, neutrophils/NMPs, and monocytes/MMPs was detected within 2 hours of CAS, whereas PS exposure was delayed on erythrocytes/RMPs and EMPs, with an increase detected 24 hours after CAS. In addition, PS+ platelets/PMPs peaked at 2 hours, while PS+ neutrophils/NMPs, monocytes/MMPs, and erythrocytes/RMPs peaked at 48 hours. After their peak, all persisted at levels above baseline for 7 days post-CAS. Moreover, the level of PS+ blood cells/MPs was correlated with shortened coagulation time and significantly increased intrinsic and extrinsic Xase, thrombin generation, and fibrin formation. Pretreatment of blood cells with lactadherin at their peak time point after CAS blocked PS, resulting in prolonged coagulation times, decreased procoagulant enzyme activation, and fibrin production. CONCLUSIONS The results of this study suggest that increased exposure of PS on blood cells and MPs may contribute to enhanced PCA in patients with ICA stenosis who have undergone CAS, explaining the risk of perioperative thromboembolic complications in these patients. PS on blood cells and MPs may serve as an important biomarker for predicting, and as a pivotal target for monitoring and treating, acute postoperative complications after CAS. ■ CLASSIFICATION OF EVIDENCE Type of question: association; study design: prospective cohort trial; evidence: Class I.
NASA Astrophysics Data System (ADS)
Hogiu, S.; Werncke, W.; Pfeiffer, M.; Dreyer, J.; Elsaesser, T.
2000-07-01
Vibrational relaxation in the electronic ground state initiated by intramolecular back-electron transfer (b-ET) of betaine-30 (B-30) is studied by picosecond time-resolved anti-Stokes Raman spectroscopy. Measurements were carried out with B-30 dissolved in slowly as well as in rapidly relaxing solvents. We observed a risetime of the Raman band with the highest frequency near 1600 cm-1 which is close to the b-ET time τb-ET of B-30. For B-30 dissolved in propylene carbonate (τb-ET˜1 ps), the population of this mode exhibits a rise time of 1 ps whereas vibrational populations between 400 and 1400 cm-1 increase substantially slower. In contrast, in glycerol triacetin (τb-ET˜3.5 ps) and in ethanol (τb-ET˜6 ps) rise times of all modes are close to the respective b-ET times. Within the first few picoseconds, direct vibrational excitation through b-ET is favored for modes with the highest frequencies and high Franck-Condon factors. Later on, indirect channels of population due to vibrational energy redistribution (IVR) become effective. Thermal equilibrium populations of the Raman active modes are established within 10 to 15 ps after optical excitation.
Habib, Basant A; Sayed, Sinar; Elsayed, Ghada M
2018-03-30
This study aimed to formulate suitable nanovesicles (NVs) for transdermal delivery of Ondansetron. It also illustrated a practical example for the importance of Box-Cox transformation. A 2 3 full factorial design was used to enable testing transfersomes, ethosomes, and transethosomes of Ondansetron simultaneously. The independent variables (IVs) studied were sodium taurocholate amount, ethanol volume in hydration medium and sonication time. The studied dependent variables (DVs) were: particle size (PS), zeta potential (ZP) and entrapment efficiency (EE). Polynomial equations were used to study the influence of IVs on each DV. Numerical multiple response optimization was applied to select an optimized formula (OF) with the goals of minimizing PS and maximizing ZP absolute value and EE. Box-Cox transformation was adopted to enable modeling PS raised to the power of 1.2 with an excellent prediction R 2 of 1.000. ZP and EE were adequately represented directly with prediction R 2 of 0.9549 and 0.9892 respectively. Response surface plots helped in explaining the influence of IVs on each DV. Two-sided 95% prediction interval test and percent deviation of actual values from predicted ones proved the validity of the elucidated models. The OF was a transfersomal formula with desirability of 0.866 and showed promising results in ex-vivo permeation study. Copyright © 2018 Elsevier B.V. All rights reserved.
Viers, Boyd R; Viers, Lyndsay D; Hull, Nathan C; Hanson, Theodore J; Mehta, Ramila A; Bergstralh, Eric J; Vrtiska, Terri J; Krambeck, Amy E
2015-11-01
To evaluate the association between clinicoradiographic features and need for prestenting (PS) because of inability of the ureter to accommodate the ureteroscope, or ureteral access sheath, at the time of stone treatment. From 2009 to 2013, 120 consecutive nonstented patients underwent ureteroscopic stone treatment with preoperative computerized tomography urogram. Acute stone events with obstruction or infection were excluded. Preoperative radiographic imaging underwent radiologist review. Clinicoradiographic features were characterized, and multivariable logistic regression models were used to identify covariates independently associated with need for PS. Of the 154 renal units treated, 25 (16%) required PS for failed primary access. PS ureters were less likely to have a history of prior ipsilateral ureteral stent (4% vs 31%) or surgery (8% vs 36%; P <.05). Radiographically, PS ureters had a narrower ureteropelvic junction (4 mm vs 5 mm) and were more likely to have <50% ureteral opacification on computerized tomography urogram (32% vs 9%; P <.05). On multivariable analysis, prior ipsilateral ureteral stent (odds ratio [OR] = 0.11) and stone surgery (OR = 0.15) reduced the need for PS; meanwhile, <50% ureteral opacification (OR = 4.41) was independently associated with an increased risk of access failure. We report a 16% incidence of access failure requiring PS at time of ureteroscopy. Clinically, there was an 89% and 85% risk reduction in the need for PS with prior history of ipsilateral ureteral stent or surgery. Radiographically, there was a 4.4-fold increased risk of PS with <50% ureteral opacification. Accordingly, our findings may assist in counseling and operative management of the difficult ureter. Copyright © 2015 Elsevier Inc. All rights reserved.
Peters, Sanne A E; Dogan, Soner; Meijer, Rudy; Palmer, Mike K; Grobbee, Diederick E; Crouse, John R; O'Leary, Daniel H; Evans, Gregory W; Raichlen, Joel S; Bots, Michiel L
2011-01-01
To evaluate whether plaque scoring measurements are able to track changes in atherosclerotic plaque burden over time and to study whether this is affected by lipid-lowering therapy. Data used were from METEOR (Measuring Effects on Intima-Media Thickness: an Evaluation Of Rosuvastatin), a randomized controlled trial of rosuvastatin 40 mg among 984 low-risk patients with modest carotid intima-media thickening (CIMT). In this analysis, duplicate ultrasound images from 12 carotid sites were collected at the baseline and end of the study from 495 European patients and were evaluated for plaque presence and severity. Plaques were scored from near and far walls of the 12 sites (0= none; 1= minimal; 2= moderate; 3= severe) and plaque scores (PS) were combined into two summary measures for each examination. The MeanMaxPS is the mean over the 12 carotid sites of the maximum score at each site and the MaxMaxPS reflects the most severe lesion at any site. Baseline MeanMaxPS and MaxMaxPS were 0.31 (SD: 0.20) and 1.15 (SD: 0.51), respectively. Changes in MeanMaxPS and MaxMaxPS significantly differed between rosuvastatin and placebo (mean difference: -0.03 [SE: 0.01; p =0.016] and -0.09 [SE: 0.04; p =0.027], respectively). In contrast to rosuvastatin, which demonstrated no change from the baseline, placebo showed significant progression in MeanMaxPS and MaxMaxPS (p =0.002; both). The plaque-scoring method proved capable of assessing the change in atherosclerotic plaque burden over time and proved useful to evaluate lipid-lowering in asymptomatic individuals with a low risk of cardiovascular disease and subclinical atherosclerosis.
Medubi, O O; Iranloye, B O; Adegoke, O A
2017-06-30
Stress has been acknowledged as one of the aetiologies of female reproductive dysfunction, yet the mechanismsinvolved are not totally elucidated. Based on the paucity of information on how predator-induced stress (PS) affects oestrouscycle in rats, this study was designed to investigate the effect of PS on the oestrous cycle in rats. Forty-eight (48) SpragueDawley rats were used for this study. They were randomly divided into Control and PS group. Each group was divided intofour subgroups (n=6/group) according to the phases of oestrous cycle. Stress was induced by exposing rats to cat (predator)for 60 minutes/day for 14 consecutive days. PS caused significant disruption of the oestrous cycle. In animals subjected toPS at proestrus (PS-proestrus) and oestrus (PS-oestrus), percentage occurrence of proestrus, oestrus and metestrus phaseswere significantly reduced compared with control. In animals subjected to PS at metestrus (PS-metestrus) and diestrus (PSdiestrus), percentage occurrence of oestrus phase was not significantly affected. In all animals exposed to PS, percentageoccurrence of diestrus was significantly increased regardless of the phase of first exposure compared with control.Corticosterone and prolactin levels were significantly elevated in PS groups compared with control. Progesterone wassignificantly increased in animals at diestrus phase compared with oestrus phase and respective phases in control. Oestradiolwas significantly reduced in PS group compared with control at oestrus phase but not significantly different at diestrus phase.Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were significantly lower in PS groups at oestrusphase compared with diestrus phase. This study shows that PS disrupts the oestrous cycle secondary to perturbation ofhormonal control of female reproduction and is influenced by the phase at first exposure to stress.
A comparative study of the time performance between NINO and FlexToT ASICs
NASA Astrophysics Data System (ADS)
Sarasola, I.; Nemallapudi, M. V.; Gundacker, S.; Sánchez, D.; Gascón, D.; Rato, P.; Marín, J.; Auffray, E.
2017-04-01
Universitat de Barcelona (UB) and CIEMAT have designed the FlexToT ASIC for the front-end readout of SiPM-based scintillator detectors. This ASIC is aimed at time of flight (ToF) positron emission tomography (PET) applications. In this work we have evaluated the time performance of the FlexToT v2 ASIC compared to the NINO ASIC, a fast ASIC developped at CERN. NINO electronics give 64 ps sigma for single-photon time resolution (SPTR) and 93 ps FWHM for coincidence time resolution (CTR) with 2 × 2 × 5 mm3 LSO:Ce,Ca crystals and S13360-3050CS SiPMs. Using the same SiPMs and crystals, the FlexToT v2 ASIC yields 91 ps sigma for SPTR and 123 ps FWHM for CTR. Despite worse time performace than NINO, FlexToT v2 features lower power consumption (11 vs. 27 mW/ch) and linear ToT energy measurement.
Interfacial fields in organic field-effect transistors and sensors
NASA Astrophysics Data System (ADS)
Dawidczyk, Thomas J.
Organic electronics are currently being commercialized and present a viable alternative to conventional electronics. These organic materials offer the ability to chemically manipulate the molecule, allowing for more facile mass processing techniques, which in turn reduces the cost. One application where organic semiconductors (OSCs) are being investigated is sensors. This work evaluates an assortment of n- and p-channel semiconductors as organic field-effect transistor (OFET) sensors. The sensor responses to dinitrotoluene (DNT) vapor and solid along with trinitrotoluene (TNT) solid were studied. Different semiconductor materials give different magnitude and direction of electrical current response upon exposure to DNT. Additional OFET parameters---mobility and threshold voltage---further refine the response to the DNT with each OFET sensor requiring a certain gate voltage for an optimized response to the vapor. The pattern of responses has sufficient diversity to distinguish DNT from other vapors. To effectively use these OFET sensors in a circuit, the threshold voltage needs to be tuned for each transistor to increase the efficiency of the circuit and maximize the sensor response. The threshold voltage can be altered by embedding charges into the dielectric layer of the OFET. To study the quantity and energy of charges needed to alter the threshold voltage, charge carriers were injected into polystyrene (PS) and investigated with scanning Kelvin probe microscopy (SKPM) and thermally stimulated discharge current (TSDC). Lateral heterojunctions of pentacene/PS were scanned using SKPM, effectively observing polarization along a side view of a lateral nonvolatile organic field-effect transistor dielectric interface. TSDC was used to observe charge migration out of PS films and to estimate the trap energy level inside the PS, using the initial rise method. The process was further refined to create lateral heterojunctions that were actual working OFETs, consisting of a PS or poly (3-trifluoro)styrene (F-PS) gate dielectric and a pentacene OSC. The charge storage inside the dielectric was visualized with SKPM, correlated to a threshold voltage shift in the transistor operation, and related to bias stress as well. The SKPM method allows the dielectric/OSC interface of the OFET to be visualized without any alteration of the OFET. Furthermore, this technique allows for the observation of charge distribution between the two dielectric interfaces, PS and F-PS. The SKPM is used to visualize the charge from conventional gate biasing and also as a result of embedding charges deliberately into the dielectric to shift the threshold voltage. Conventional gate biasing shows considerable residual charge in the PS dielectric, which results in gate bias stress. Gate bias stress is one of the major hurdles left in the commercialization of OFETs. To prevent this bias stress, additives of different energy levels were inserted into the dielectric to limit the gate bias stress. Additionally, the dielectrics were pre-charged to try and prevent further bias stress. Neither pre-charging the dielectric or the addition of additive has been used in gate bias prevention, but both methods offer improved resistance to gate bias stress, and help to further refine the dielectric design.
Liu, Bin; Frost, Jeffrey L; Sun, Jing; Fu, Hongjun; Grimes, Stephen; Blackburn, Peter; Lemere, Cynthia A
2013-04-17
Active amyloid-β (Aβ) immunotherapy is under investigation to prevent or treat early Alzheimer's disease (AD). In 2002, a Phase II clinical trial (AN1792) was halted due to meningoencephalitis in ∼6% of the AD patients, possibly caused by a T-cell-mediated immunological response. Thus, generating a vaccine that safely generates high anti-Aβ antibody levels in the elderly is required. In this study, MER5101, a novel conjugate of Aβ1-15 peptide (a B-cell epitope fragment) conjugated to an immunogenic carrier protein, diphtheria toxoid (DT), and formulated in a nanoparticular emulsion-based adjuvant, was administered to 10-month-old APPswe/PS1ΔE9 transgenic (Tg) and wild-type (Wt) mice. High anti-Aβ antibody levels were observed in both vaccinated APPswe/PS1ΔE9 Tg and Wt mice. Antibody isotypes were mainly IgG1 and IgG2b, suggesting a Th2-biased response. Restimulation of splenocytes with the Aβ1-15:DT conjugate resulted in a strong proliferative response, whereas proliferation was absent after restimulation with Aβ1-15 or Aβ1-40/42 peptides, indicating a cellular immune response against DT while avoiding an Aβ-specific T-cell response. Moreover, significant reductions in cerebral Aβ plaque burden, accompanied by attenuated microglial activation and increased synaptic density, were observed in MER5101-vaccinated APPswe/PS1ΔE9 Tg mice compared with Tg adjuvant controls. Last, MER5101-immunized APPswe/PS1ΔE9 Tg mice showed improvement of cognitive deficits in both contextual fear conditioning and the Morris water maze. Our novel, highly immunogenic Aβ conjugate vaccine, MER5101, shows promise for improving Aβ vaccine safety and efficacy and therefore, may be useful for preventing and/or treating early AD.
Martínez-Martin, Pablo; Carod-Artal, Francisco Javier; da Silveira Ribeiro, Luciola; Ziomkowski, Sofia; Vargas, Antonio Pedro; Kummer, Wladimir; Mesquita, Hudson Mourão
2008-08-15
The objective of this study was to illustrate the analysis of longitudinal validity, responsiveness, and importance of change, using the SCOPA-Psychosocial Questionnaire (SCOPA-PS) as a source of empirical data. Sixty-seven patients with PD in Hoehn and Yahr (HY) stage 2 were followed up for 1 year and assessed by means of the Schwab and England Scale, Unified PD Rating Scale (UPDRS), Hospital Anxiety and Depression Scale (HADS), PDQ-39, and SCOPA-PS. A range of methods was applied to enable each of the target attributes to be analyzed from different conceptual stances. The SCOPA-PS displayed satisfactory acceptability (no floor or ceiling effect), internal consistency (alpha = 0.80-0.84), convergent validity (r(S) = 0.70-0.82 with PDQ-39), and precision (SEM = 8.80), both at baseline and at the end of follow-up. The threshold value for significant change ranged from 17.25 (1.96 SEM) to 24.39 (Smallest real difference and Reliable change index). Threshold values for a clinically meaningful change were 0.73-1.26 (effect size, standardized response mean, responsiveness statistic). Change in SCOPA-PS scores correlated strongly with change in total UPDRS, HADS, and PDQ-39 scores, and reliably detected 70% of cases that worsened according to the PDQ-39. The minimally important change (MIC) for "minimally impaired" patients as per the PDQ39 was 8.30-9.10 points. Indices such as 1.96 SEM, effect size, and correlation with the change in other measures provide useful information about different concepts of responsiveness. The MIC should be determined for each specific setting, using distribution- and anchor-based methods. The SCOPA-PS showed satisfactory longitudinal attributes and responsiveness in stage-2 Brazilian patients with PD across 1 year of follow-up. (c) 2008 Movement Disorder Society.
Patel, Ilabahen; Kracher, Daniel; Ma, Su; Garajova, Sona; Haon, Mireille; Faulds, Craig B; Berrin, Jean-Guy; Ludwig, Roland; Record, Eric
2016-01-01
Lytic polysaccharide monooxygenases (LPMOs) belong to the "auxiliary activities (AA)" enzyme class of the CAZy database. They are known to strongly improve the saccharification process and boost soluble sugar yields from lignocellulosic biomass, which is a key step in the efficient production of sustainable economic biofuels. To date, most LPMOs have been characterized from terrestrial fungi, but novel fungal LPMOs isolated from more extreme environments such as an estuary mangrove ecosystem could offer enzymes with unique properties in terms of salt tolerance and higher stability under harsh condition. Two LPMOs secreted by the mangrove-associated fungus Pestalotiopsis sp. NCi6 (PsLPMOA and PsLPMOB) were expressed in the yeast Pichia pastoris and produced in a bioreactor with >85 mg L(-1) for PsLPMOA and >260 mg L(-1) for PsLPMOB. Structure-guided homology modeling of the PsLPMOs showed a high abundance of negative surface charges, enabling enhanced protein stability and activity in the presence of sea salt. Both PsLPMOs were activated by a cellobiose dehydrogenase (CDH) from Neurospora crassa, with an apparent optimum of interaction at pH 5.5. Investigation into their regioselective mode of action revealed that PsLPMOA released C1- and C4-oxidized cello-oligosaccharide products, while PsLPMOB released only C4-oxidized products. PsLPMOA was found to cleave polymeric cellulose in the presence of up to 6 % sea salt, which emphasizes the use of sea water in the industrial saccharification process with improved ecological footprints. Two new LPMOs from the mangrove fungus Pestalotiopsis sp. NCi6 were found to be fully reactive against cellulose. The combined hydrolytic activities of these salt-responsive LPMOs could therefore facilitate the saccharification process using sea water as a reaction medium for large-scale biorefineries.
Root exudation of phytosiderophores from soil-grown wheat
Oburger, Eva; Gruber, Barbara; Schindlegger, Yvonne; Schenkeveld, Walter D C; Hann, Stephan; Kraemer, Stephan M; Wenzel, Walter W; Puschenreiter, Markus
2014-01-01
For the first time, phytosiderophore (PS) release of wheat (Triticum aestivum cv Tamaro) grown on a calcareous soil was repeatedly and nondestructively sampled using rhizoboxes combined with a recently developed root exudate collecting tool. As in nutrient solution culture, we observed a distinct diurnal release rhythm; however, the measured PS efflux was c. 50 times lower than PS exudation from the same cultivar grown in zero iron (Fe)-hydroponic culture. Phytosiderophore rhizosphere soil solution concentrations and PS release of the Tamaro cultivar were soil-dependent, suggesting complex interactions of soil characteristics (salinity, trace metal availability) and the physiological status of the plant and the related regulation (amount and timing) of PS release. Our results demonstrate that carbon and energy investment into Fe acquisition under natural growth conditions is significantly smaller than previously derived from zero Fe-hydroponic studies. Based on experimental data, we calculated that during the investigated period (21–47 d after germination), PS release initially exceeded Fe plant uptake 10-fold, but significantly declined after c. 5 wk after germination. Phytosiderophore exudation observed under natural growth conditions is a prerequisite for a more accurate and realistic assessment of Fe mobilization processes in the rhizosphere using both experimental and modeling approaches. PMID:24890330
Kinetic energy of Ps formed by Ore mechanism in Ar gas
NASA Astrophysics Data System (ADS)
Sano, Yosuke; Kino, Yasushi; Oka, Toshitaka; Sekine, Tsutomu
2015-06-01
In order to investigate kinetic energy of positronium(Ps) formed by Ore mechanism, we performed positron annihilation age-momentum correlation (AMOC) measurements in Argas for 5.0 MPa and 7.5 MPa at room temperature. From the time dependence of Doppler broadening of para-Ps (p-Ps) self-annihilation gramma-ray component, we observed Ps slowing down process. Using a simple slowing down model, we obtained the initial kinetic energy of Ps formed by Ore mechanism and Ps-Armomentum transfer cross section. The initial kinetic energy was 3.9 eV which was higher than the kinetic energy of Ps formed at the upper limit of Ore gap. The momentum transfer cross section was 0.019 ± 0.010 nm2 in between 1 eV and 3.9 eV, and was close to the theoretical calculation.
In-situ observation of switchable nanoscale topography for y-shaped binary brushes in fluids.
Lin, Yen-Hsi; Teng, Jing; Zubarev, Eugene R; Shulha, Hennady; Tsukruk, Vladimir V
2005-03-01
Direct, in-fluid observation of the surface morphology and nanomechanical properties of the mixed brushes composed of Y-shaped binary molecules PS-PAA revealed nanoscale network-like surface topography formed by coexisting stretched soluble PAA arms and collapsed insoluble PS chains in water. Placement of Y-shaped brushes in different fluids resulted in dramatic reorganization ranging from soft repellent layer covered by swollen PS arms in toluene to an adhesive, mixed layer composed of coexisting swollen PAA and collapsed PS arms in water. These binary layers with the overall nanoscale thickness can serve as adaptive nanocoatings with stimuli-responsive properties.
Electron spin relaxation in carbon nanotubes: Dyakonov-Perel mechanism
NASA Astrophysics Data System (ADS)
Semenov, Yuriy; Zavada, John; Kim, Ki Wook
2010-03-01
The long standing problem of unaccountable short spin relaxation in carbon nanotubes (CNT) meets a disclosure in terms of curvature-mediated spin-orbital interaction that leads to spin fluctuating precession analogous to Dyakonov-Perel mechanism. Strong anisotropy imposed by arbitrary directed magnetic field has been taken into account in terms of extended Bloch equations. Especially, stationary spin current through CNT can be controlled by spin-flip processes with relaxation time as less as 150 ps, the rate of transversal polarization (i.e. decoherence) runs up to 1/(70 ps) at room temperature while spin interference of the electrons related to different valleys can be responsible for shorter spin dephasing. Dependencies of spin-relaxation parameters on magnetic field strength and orientation, CNT curvature and chirality have been analyzed.
Tidal Disruption Events in Pan-STARRS1
NASA Astrophysics Data System (ADS)
Gezari, Suvi
2018-01-01
The Pan-STARRS1 (PS1) Medium Deep Survey made an important contribution to the study of tidal disruption events (TDEs) by discovering TDEs on the rise to peak and enabling prompt spectroscopic follow-up observations. The two PS1 TDEs, PS1-10jh and PS1-11af, were the first TDEs to have detailed light curves and transient broad line features in their spectra, both of which could be used to constrain the physical parameters of the events. I will describe how cotemporal NUV observations from the GALEX Time Domain Survey were critical in the identification of these relatively rare events as bonifide TDEs among the PS1 transient alert stream. I will also show how we can use the PS1+GALEX data set as a training set to prepare for culling TDEs from the deluge of transients to be produced by the next generation of optical time domain surveys, in order that they may be used as effective probes of supermassive black hole demographics and accretion physics.
Collisional Processes Probed by using Resonant Four-Wave Mixing Spectroscopy
NASA Astrophysics Data System (ADS)
McCormack, E. F.; Stampanoni, A.; Hemmerling, B.
2000-06-01
Collisionally-induced decay processes in excited-state nitric oxide (NO) have been measured by using time-resolved two-color, resonant four-wave mixing (TC-RFWM) spectroscopy and polarization spectroscopy (PS). Markedly different time dependencies were observed in the data obtained by using TC-RFWM when compared to PS. Oscillations in the PS signal as a function of delay between the pump and probe laser pulses were observed and it was determined that their characteristics depend very sensitively on laser polarization. Analysis reveals that the oscillations in the decay curves are due to coherent excitation of unresolved hyperfine structure in the A state of NO. A comparison of beat frequencies obtained by taking Fourier transforms of the time data to the predicted hyperfine structure of the A state support this explanation. Further, based on a time-dependent model of PS as a FWM process, the signal’s dependence as a function of time on polarization configuration and excitation scheme can be predicted. By using the beat frequency values, fits of the model results to experimental decay curves for different pressures allows a study of the quenching rate in the A state due to collisional processes. A comparison of the PS data to laser-induced fluorescence decay measurements reveals different decay rates which suggests that the PS signal decay depends on the orientation and alignment of the excited molecules. The different behavior of the decay curves obtained by using TC-RFWM and PS can be understood in terms of the various contributions to the decay as described by the model and this has a direct bearing on which technique is preferable for a given set of experimental parameters.
Phase-sensitive dual-inversion recovery for accelerated carotid vessel wall imaging.
Bonanno, Gabriele; Brotman, David; Stuber, Matthias
2015-03-01
Dual-inversion recovery (DIR) is widely used for magnetic resonance vessel wall imaging. However, optimal contrast may be difficult to obtain and is subject to RR variability. Furthermore, DIR imaging is time-inefficient and multislice acquisitions may lead to prolonged scanning times. Therefore, an extension of phase-sensitive (PS) DIR is proposed for carotid vessel wall imaging. The statistical distribution of the phase signal after DIR is probed to segment carotid lumens and suppress their residual blood signal. The proposed PS-DIR technique was characterized over a broad range of inversion times. Multislice imaging was then implemented by interleaving the acquisition of 3 slices after DIR. Quantitative evaluation was then performed in healthy adult subjects and compared with conventional DIR imaging. Single-slice PS-DIR provided effective blood-signal suppression over a wide range of inversion times, enhancing wall-lumen contrast and vessel wall conspicuity for carotid arteries. Multislice PS-DIR imaging with effective blood-signal suppression is enabled. A variant of the PS-DIR method has successfully been implemented and tested for carotid vessel wall imaging. This technique removes timing constraints related to inversion recovery, enhances wall-lumen contrast, and enables a 3-fold increase in volumetric coverage at no extra cost in scanning time.
Pastor, Verónica; Pallarés, María Eugenia; Antonelli, Marta C
2018-02-26
Prenatal stress (PS) induces long-lasting molecular alterations in brain circuits of the offspring and increases the propensity to develop neuropsychiatric diseases during adulthood, including mood disorders and drug addiction. A major goal of this study was to assess the impact of PS on pubertal behaviour and adult vulnerability to cocaine-induced conditioning place preference (CPP). We therefore evaluated pubertal novelty response and anxiety-like behaviour in control (C) and PS rats, and then, we examined cocaine-induced CPP in those animals during adulthood. We found no differences between C and PS groups on pubertal behaviour, however, only PS rats showed a significant cocaine-induced CPP. To further analyze our results, we classified cocaine-treated rats regarding their CPP score in Low CPP or High CPP and we then analysed their pubertal behaviour. We found different relations of anxiety-like behaviour to cocaine reward as a function of PS exposure: for C group, High CPP and Low CPP had shown similar levels of anxiety-like behaviour at puberty; on the contrary, for PS group, High CPP had shown lower anxiety-like behaviour than Low CPP rats. This study underscores the importance of considering prenatal exposure to stress when analysing the relationship between anxiety and cocaine vulnerability. Moreover, the evaluation of behavioural traits at puberty opens the possibility of early intervention and will allow the development of specific prevention strategies to avoid the devastating consequences of drug addiction later in life. Copyright © 2017 Elsevier B.V. All rights reserved.
High-precision two-way optic-fiber time transfer using an improved time code.
Wu, Guiling; Hu, Liang; Zhang, Hao; Chen, Jianping
2014-11-01
We present a novel high-precision two-way optic-fiber time transfer scheme. The Inter-Range Instrumentation Group (IRIG-B) time code is modified by increasing bit rate and defining new fields. The modified time code can be transmitted directly using commercial optical transceivers and is able to efficiently suppress the effect of the Rayleigh backscattering in the optical fiber. A dedicated codec (encoder and decoder) with low delay fluctuation is developed. The synchronization issue is addressed by adopting a mask technique and combinational logic circuit. Its delay fluctuation is less than 27 ps in terms of the standard deviation. The two-way optic-fiber time transfer using the improved codec scheme is verified experimentally over 2 m to100 km fiber links. The results show that the stability over 100 km fiber link is always less than 35 ps with the minimum value of about 2 ps at the averaging time around 1000 s. The uncertainty of time difference induced by the chromatic dispersion over 100 km is less than 22 ps.
Ablation of silicon with bursts of femtosecond laser pulses
NASA Astrophysics Data System (ADS)
Gaudiuso, Caterina; Kämmer, Helena; Dreisow, Felix; Ancona, Antonio; Tünnermann, Andreas; Nolte, Stefan
2016-03-01
We report on an experimental investigation of ultrafast laser ablation of silicon with bursts of pulses. The pristine 1030nm-wavelength 200-fs pulses were split into bursts of up to 16 sub-pulses with time separation ranging from 0.5ps to 4080ps. The total ablation threshold fluence was measured depending on the burst features, finding that it strongly increases with the number of sub-pulses for longer sub-pulse delays, while a slowly increasing trend is observed for shorter separation time. The ablation depth per burst follows two different trends according to the time separation between the sub-pulses, as well as the total threshold fluence. For delays shorter than 4ps it decreases with the number of pulses, while for time separations longer than 510ps, deeper craters were achieved by increasing the number of subpulses in the burst, probably due to a change of the effective penetration depth.
Schwalb, Nina K; Michalak, Thomas; Temps, Friedrich
2009-12-24
The optically excited electronic states of hydrogen-bonded homo- and heterodimers of guanosine (G) and deoxycytidine (C) were investigated by femtosecond fluorescence up-conversion spectroscopy. The base pairs were prepared in CHCl(3) solution by employing tert-butyldimethylsilyl (TBDMS) groups at the OH positions of the ribose (G) or deoxyribose (C) moieties to enhance the solubilities of the nucleosides in organic solvents. The H-bonded complexes that were obtained were characterized by FTIR spectroscopy. Fluorescence lifetime measurements were performed following electronic excitation at a series of UV wavelengths from lambda(pump) = 294 nm, close to the electronic origins of the bases, to lambda(pump) = 262 nm, where significant excess vibronic energy is deposited in the molecules, at nucleoside concentrations of c(0) = 0.1 and 1.0 mM. The experimental results revealed the existence of an ultrafast deactivation pathway for the optically prepared electronically excited state(s) of the G.C Watson-Crick base pair, which was found to have a lifetime of tau(GC) = 0.30(3) ps (with 2sigma error limits) irrespective of the pump wavelength. A similar short decay time, tau(GG) = 0.32(2) ps, was observed for the respective excited G.G homodimer. In contrast, the excited G monomer displayed a significantly longer-lived and wavelength-dependent deactivation, requiring three time constants, between 0.43(6) ps < or = tau(G,1) < or = 1.2(1) ps, 4.2(8) ps < or = tau(G,2) < or = 8(1) ps, and tau(G,3) = 195(32) ps. Self-complexation of C, on the other hand, led to a longer-lived excited state with a lifetime estimated between 1 ps < or = tau(CC) < or = 10 ps, compared to the dominant initial subpicosecond decay time of the C monomer of tau(C,1) = 0.80(4) ps.
Abbaszadeh-Amirdehi, Maryam; Ansari, Noureddin Nakhostin; Naghdi, Soofia; Olyaei, Gholamreza; Nourbakhsh, Mohammad Reza
2013-01-01
Introduction Dry needling (DN) is an effective method for the treatment of myofascial trigger points (MTrPs). There is no report on the neurophysiological effects of DN in patients with MTrPs. The aim of the present study will be to assess the immediate neurophysiological efficacy of deep DN in patients with upper trapezius MTrPs. Methods and analysis A prospective, controlled clinical trial was designed to include patients with upper trapezius MTrPs and volunteered healthy participants to receive one session of DN. The primary outcome measures are neuromuscular junction response and sympathetic skin response. The secondary outcomes are pain intensity and pressure pain threshold. Data will be collected at baseline and immediately after intervention. Ethics and dissemination This study protocol has been approved by the Research Council, School of Rehabilitation and the Ethics Committee of Tehran University of Medical Sciences. The results of the study will be disseminated in a peer-reviewed journal and presented at international congresses. PMID:23793673
Endoscopic spectral-domain polarization-sensitive optical coherence tomography system
NASA Astrophysics Data System (ADS)
Wang, Yi; Chen, Xiaodong; Hu, Zhiqiang; Li, Qiao; Yu, Daoyin
2008-02-01
In this paper, we introduced a fiber-based endoscopic Spectral-domain Polarization-sensitive OCT (SD-PS-OCT) experimental scheme for detecting the internal organ disease, which is based on low-coherence interferometer and two spectrometers. The SD-PS-OCT has the advantages of both Spectral-domain OCT (SD-OCT) and Polarization-sensitive OCT (PS-OCT). It is able to get the real-time image of reflectivity and birefringence distribution of tissue at the same time. The usage of SD-PS-OCT in endoscopic diagnosing system provides it the possibility to detect the internal organ disease. Since SD-PS-OCT can image the pathological changes of biological tissue below surface (1-3mm) with high resolution (1-15μm), it is able to help diagnosing early diseases of internal organs, which makes it a biomedical technology with bright future.
Schuurmans, Jolanda A M J; van Dongen, Joost T; Rutjens, Bas P W; Boonman, Alex; Pieterse, Corné M J; Borstlap, Adrianus C
2003-11-01
Water and nutrients required by developing seeds are mainly supplied by the phloem and have to be released from a maternal parenchyma tissue before being utilized by the filial tissues of embryo and endosperm. To identify aquaporins that could be involved in this process four full-length cDNAs were cloned and sequenced from a cDNA library of developing seed coats of pea (Pisum sativum L.). The cDNA of PsPIP1-1 appeared to be identical to that of clone 7a/TRG-31, a turgor-responsive gene cloned previously from pea roots. PsPIP1-1, PsPIP2-1, and PsTIP1-1, or their possible close homologues, were also expressed in cotyledons of developing and germinating seeds, and in roots and shoots of seedlings, but transcripts of PsNIP-1 were only detected in the seed coat. In mature dry seeds, high hybridization signals were observed with the probe for PsPIP1-1, but transcripts of PsPIP2-1, PsTIP1-1, and PsNIP-1 were not detected. Functional characterization after heterologous expression in Xenopus oocytes showed that PsPIP2-1 and PsTIP1-1 are aquaporins whereas PsNIP-1 is an aquaglyceroporin. PsNIP-1, like several other NIPs, contains a tryptophan residue corresponding with Trp-48 in GlpF (the glycerol facilitator of Escherichia coli) that borders the selectivity filter in the permeation channel. It is suggested that PsPIP1-1 and/or its possible close homologues could play a role in water absorption during seed imbibition, and that PsPIP2-1, possibly together with PsPIP1-1, could be involved in the release of phloem water from the seed coat symplast, which is intimately connected with the release of nutrients for the embryo.
Monitoring apoptosis in real time.
Green, Allan M; Steinmetz, Neil D
2002-01-01
Many therapeutically active anticancer treatments exert their effect by the induction of apoptosis and necrosis. Serial biopsies in breast cancer patients have suggested that response to therapy correlates with early posttreatment increases in tumor apoptotic index. Radiolabeled technetium Tc 99m-recombinant human (rh) annexin V provides a noninvasive technique for imaging treatment-induced cell death. Annexin V is a naturally occurring human protein that binds avidly to membrane-associated phosphatidylserine (PS). PS is normally found only on the inner leaflet of the cell membrane double layer, but it is actively transported to the outer layer as an early event in apoptosis and becomes available for annexin binding. Annexin also gains access to PS as a result of the membrane fragmentation associated with necrosis. In vitro studies of apoptosis using fluorescein annexin have shown good correlation with assessments of apoptosis documented by nuclear DNA degradation and caspase activation. In vivo localization of intravenously administered Tc 99m-annexin V has been demonstrated in numerous preclinical models of apoptosis, including anti-Fas-mediated hepatic apoptosis, rejection of allogeneic heterotopic cardiac allografts, cyclophosphamide treatment of murine lymphoma, cyclophosphamide-induced apoptosis in bone marrow, and leukocyte apoptosis associated with abscess formation. Scintigraphic studies in humans using Tc 99m-rh annexin V have demonstrated the feasibility of imaging cell death in acute myocardial infarction, in tumors with a high apoptotic index, and in response to anti-tumor chemotherapy of non-small cell lung cancer, small-cell lung cancer, breast cancer, lymphoma, and sarcoma. Increased localization of Tc 99m-rh annexin V within 1 to 3 days of chemotherapy has been noted in some, but not all, subjects with these tumors. To date, most subjects showing increased Tc 99m-rh annexin V uptake after the first course of chemotherapy have shown objective clinical responses. A single site study in 15 subjects with 1-year follow-up has suggested that increased posttreatment Tc 99m-rh annexin uptake is associated with improved time to progression of disease and survival time. In vivo imaging of cell death may have the potential to improve the treatment of cancer patients by allowing rapid, objective, patient-by-patient assessment of the efficacy of tumor cell killing.
Badcock, Nicholas A.; Nye, Abigail; Bishop, Dorothy V. M.
2011-01-01
Language is lateralised to the left hemisphere in most people, but it is unclear whether the same degree and direction of lateralisation is found for all verbal tasks and whether laterality is affected by task difficulty. We used functional transcranial Doppler ultrasonography (fTCD) to assess the lateralisation of language processing in 27 young adults using three tasks: word generation (WG), auditory naming (AN), and picture story (PS). WG and AN are active tasks requiring behavioural responses whereas PS is a passive task that involves listening to an auditory story accompanied by pictures. We also examined the effect of task difficulty by a post hoc behavioural categorisation of trials in the WG task and a word frequency manipulation in the AN task. fTCD was used to measure task-dependent blood flow velocity changes in the left and right middle cerebral arteries. All of these tasks were significantly left lateralised: WG, 77% of individuals left, 5% right; AN, 72% left: 4% right; PS, 56% left: 0% right. There were significant positive relationships between WG and AN (r = 0.56) as well as AN and PS (r = .76) but not WG and PS (r = −0.22). The task difficulty manipulation affected accuracy in both WG and AN tasks, as well as reaction time in the AN task, but did not significantly influence laterality indices in either task. It is concluded that verbal tasks are not interchangeable when assessing cerebral lateralisation, but that differences between tasks are not a consequence of task difficulty. PMID:23098198
Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice.
Huang, Huang; Nie, Sipei; Cao, Min; Marshall, Charles; Gao, Junying; Xiao, Na; Hu, Gang; Xiao, Ming
2016-08-01
Transgenic APPSwe/PS1dE9 (APP/PS1) mice that overproduce amyloid beta (Aβ) are extensively used in the studies of pathogenesis and experimental therapeutics and new drug screening for Alzheimer's disease (AD). However, most of the current literature uses young or adult APP/PS1 mice. In order to provide a broader view of AD-like phenotype of this animal model, in this study, we systematically analyzed behavioral and pathological profiles of 24-month-old male APP/PS1 mice. Aged APP/PS1 mice had reference memory deficits as well as anxiety, hyperactivity, and social interaction impairment. Consistently, there was obvious deposition of amyloid plaques in the dorsal hippocampus with decreased expression of insulin-degrading enzyme, a proteolytic enzyme responsible for degradation of intracellular Aβ. Furthermore, decreases in hippocampal volume, neuronal number and synaptophysin expression, and astrocyte atrophy were also observed in aged APP/PS1 mice. This finding suggests that aged APP/PS1 mice can well replicate cognitive and noncognitive behavioral abnormalities, hippocampal atrophy, and neuronal and astrocyte degeneration in AD patients, to enable more objective and refined preclinical evaluation of therapeutic drugs and strategies for AD treatment.
Molotokaite, Egle; Remelli, William; Casazza, Anna Paola; Zucchelli, Giuseppe; Polli, Dario; Cerullo, Giulio; Santabarbara, Stefano
2017-10-26
The dynamics of excited state equilibration and primary photochemical trapping have been investigated in the photosystem I-light harvesting complex I isolated from spinach, by the complementary time-resolved fluorescence and transient absorption approaches. The combined analysis of the experimental data indicates that the excited state decay is described by lifetimes in the ranges of 12-16 ps, 32-36 ps, and 64-77 ps, for both detection methods, whereas faster components, having lifetimes of 550-780 fs and 4.2-5.2 ps, are resolved only by transient absorption. A unified model capable of describing both the fluorescence and the absorption dynamics has been developed. From this model it appears that the majority of excited state equilibration between the bulk of the antenna pigments and the reaction center occurs in less than 2 ps, that the primary charge separated state is populated in ∼4 ps, and that the charge stabilization by electron transfer is completed in ∼70 ps. Energy equilibration dynamics associated with the long wavelength absorbing/emitting forms harbored by the PSI external antenna are also characterized by a time mean lifetime of ∼75 ps, thus overlapping with radical pair charge stabilization reactions. Even in the presence of a kinetic bottleneck for energy equilibration, the excited state dynamics are shown to be principally trap-limited. However, direct excitation of the low energy chlorophyll forms is predicted to lengthen significantly (∼2-folds) the average trapping time.
Pharmacological evidences for DFK167-sensitive presenilin-independent gamma-secretase-like activity.
Sevalle, Jean; Ayral, Erwan; Hernandez, Jean-François; Martinez, Jean; Checler, Frédéric
2009-07-01
Amyloid-beta (Abeta) peptides production is thought to be a key event in the neurodegenerative process ultimately leading to Alzheimer's disease (AD) pathology. A bulk of studies concur to propose that the C-terminal moiety of Abeta is released from its precursor beta-amyloid precursor protein by a high molecular weight enzymatic complex referred to as gamma-secretase, that is composed of at least, nicastrin (NCT), Aph-1, Pen-2, and presenilins (PS) 1 or 2. They are thought to harbor the gamma-secretase catalytic activity. However, several lines of evidence suggest that additional gamma-secretase-like activities could potentially contribute to Abeta production. By means of a quenched fluorimetric substrate (JMV2660) mimicking the beta-amyloid precursor protein sequence targeted by gamma-secretase, we first show that as expected, this probe allows monitoring of an activity detectable in several cell systems including the neuronal cell line telencephalon specific murine neurons (TSM1). This activity is reduced by DFK167, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), and LY68458, three inhibitors known to functionally interact with PS. Interestingly, JMV2660 but not the unrelated peptide JMV2692, inhibits Abeta production in an in vitrogamma-secretase assay as expected from a putative substrate competitor. This activity is enhanced by PS1 and PS2 mutations known to be responsible for familial forms of AD and reduced by aspartyl mutations inactivating PS or in cells devoid of PS or NCT. However, we clearly establish that residual JMV2660-hydrolysing activity could be recovered in PS- and NCT-deficient fibroblasts and that this activity remained inhibited by DFK167. Overall, our study describes the presence of a proteolytic activity displaying gamma-secretase-like properties but independent of PS and still blocked by DFK167, suggesting that the PS-dependent complex could not be the unique gamma-secretase activity responsible for Abeta production and delineates PS-independent gamma-secretase activity as a potential additional therapeutic target to fight AD pathology.
Anticipatory phase correction in sensorimotor synchronization.
Repp, Bruno H; Moseley, Gordon P
2012-10-01
Studies of phase correction in sensorimotor synchronization often introduce timing perturbations that are unpredictable with regard to direction, magnitude, and position in the stimulus sequence. If participants knew any or all of these parameters in advance, would they be able to anticipate perturbations and thus regain synchrony more quickly? In Experiment 1, we asked musically trained participants to tap in synchrony with short isochronous tone sequences containing a phase shift (PS) of -100, -40, 40, or 100 ms and provided advance information about its direction, position, or both (but not about its magnitude). The first two conditions had little effect, but in the third condition participants shifted their tap in anticipation of the PS, though only by about ±40 ms on average. The phase correction response to the residual PS was also enhanced. In Experiment 2, we provided complete advance information about PSs of various magnitudes either at the time of the immediately preceding tone ("late") or at the time of the tone one position back ("early") while also varying sequence tempo. Anticipatory phase correction was generally conservative and was impeded by fast tempo in the "late" condition. At fast tempi in both conditions, advancing a tap was more difficult than delaying a tap. The results indicate that temporal constraints on anticipatory phase correction resemble those on reactive phase correction. While the latter is usually automatic, this study shows that phase correction can also be controlled consciously for anticipatory purposes. Copyright © 2011 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Akchurin, Nural; CMS Collaboration
2017-11-01
We report on the signal timing capabilities of thin silicon sensors when traversed by multiple simultaneous minimum ionizing particles (MIP). Three different planar sensors, 133, 211, and 285 μm thick in depletion thickness, have been exposed to high energy muons and electrons at CERN. We describe signal shape and timing resolution measurements as well as the response of these devices as a function of the multiplicity of MIPs. We compare these measurements to simulations where possible. We achieve better than 20 ps timing resolution for signals larger than a few tens of MIPs.
Gao, Shan; Zheng, Zhenbing; Gu, Wenhui; Xie, Xiujun; Huan, Li; Pan, Guanghua; Wang, Guangce
2014-10-01
The photosynthetic performance of the desiccation-tolerant, intertidal macro-algae Ulva prolifera was significantly affected by sorbitol-induced osmotic stress. Our results showed that photosynthetic activity decreased significantly with increases in sorbitol concentration. Although the partial activity of both photosystem I (PS I) and photosystem II (PS II) was able to recover after 30 min of rehydration, the activity of PS II decreased more rapidly than PS I. At 4 M sorbitol concentration, the activity of PS II was almost 0 while that of PS I was still at about one third of normal levels. Following prolonged treatment with 1 and 2 M sorbitol, the activity of PS I and PS II decreased slowly, suggesting that the effects of moderate concentrations of sorbitol on PS I and PS II were gradual. Interestingly, an increase in non-photochemical quenching occurred under these conditions in response to moderate osmotic stress, whereas it declined significantly under severe osmotic stress. These results suggest that photoprotection in U. prolifera could also be induced by moderate osmotic stress. In addition, the oxidation of PS I was significantly affected by osmotic stress. P700(+) in the thalli treated with high concentrations of sorbitol could still be reduced, as PS II was inhibited by 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), but it could not be fully oxidized. This observation may be caused by the higher quantum yield of non-photochemical energy dissipation in PS I due to acceptor-side limitation (Y(NA)) during rehydration in seawater containing DCMU. © 2014 Scandinavian Plant Physiology Society.
Photosystem I assembly on chemically tailored SAM/ Au substrates for bio-hybrid device fabrication
NASA Astrophysics Data System (ADS)
Mukherjee, Dibyendu; Khomami, Bamin
2011-03-01
Photosystem I (PS I), a supra-molecular protein complex and a biological photodiode responsible for driving natural photosynthesis mechanism, charge separates upon exposure to light. Effective use of the photo-electrochemical activities of PS I for future bio-hybrid electronic devices requires controlled attachment of these proteins onto organic/ inorganic substrates. Our results indicate that various experimental parameters alter the surface topography of PS I deposited from colloidal aqueous buffer suspensions onto OH-terminated alkanethiolate SAM /Au substrates, thereby resulting in complex columnar structures that affect the electron capture pathway of PS I. Specifically, solution phase characterizations indicate that specific detergents used for PS I stabilization in buffer solutions drive the unique colloidal chemistry to tune protein-protein interactions and prevent aggregation, thereby allowing us to tailor the morphology of surface immobilized PS I. We present surface topographical, adsorption, and electrochemical characterizations of PSI /SAM/Au substrates to elucidate protein-surface attachment dynamics and its effect on the photo-activated electronic activities of surface immobilized PS I. Sustainable Energy Education and Research Center (SEERC).
Evidence that the C-terminus of Human Presenilin 1 is Located in the Extra-cytoplasmic Space
James Turner, R.
2005-01-01
The polytopic membrane protein presenilin 1 (PS1) is a component of the γ-secretase complex that is responsible for the intramembranous cleavage of a number of type I transmembrane proteins including the β-amyloid precursor protein (APP). Mutations of PS1, apparently leading to aberrant processing of APP, have been genetically linked to early-onset familial Alzheimer's disease. PS1 contains ten hydrophobic regions (HRs) sufficiently long to be α-helical membrane spanning segments. Most topology models for PS1 place its C-terminal ∼40 amino acids, which include the 10th HR, in the cytosolic space. However, several recent observations suggest that HR 10 may be integrated into the membrane and involved in the interaction between PS1 and APP. We have applied three independent methodologies to investigate the location of HR 10 and the extreme C-terminus of PS1. The results from these methods indicate that HR 10 spans the membrane and that the C-terminal amino acids of PS1 lie in the extra-cytoplasmic space. PMID:15843437
Transient Cooperative Processes in Dewetting Polymer Melts.
Chandran, Sivasurender; Reiter, Günter
2016-02-26
We compare the high velocity dewetting behavior, at elevated temperatures, of atactic polystyrene (aPS) and isotactic polystyrene (iPS) films, with the zero shear bulk viscosity (η_{bulk}) of aPS being approximately ten times larger than iPS. As expected, for aPS the apparent viscosity of the films (η_{f}) derived from high-shear dewetting is less than η_{bulk}, displaying a shear thinning behavior. Surprisingly, for iPS films, η_{f} is always larger than η_{bulk}, even at about 50 °C above the melting point, with η_{f}/η_{bulk} following an Arrhenius behavior. The corresponding activation energy of ∼160±10 kJ/mol for iPS films suggests a cooperative motion of segments which are aligned and agglomerated by fast dewetting.
NASA Astrophysics Data System (ADS)
Jiang, Xiao-Pan; Zhang, Zi-Liang; Qin, Xiu-Bo; Yu, Run-Sheng; Wang, Bao-Yi
2010-12-01
Positronium time of flight spectroscopy (Ps-TOF) is an effective technique for porous material research. It has advantages over other techniques for analyzing the porosity and pore tortuosity of materials. This paper describes a design for Ps-TOF apparatus based on the Beijing intense slow positron beam, supplying a new material characterization technique. In order to improve the time resolution and increase the count rate of the apparatus, the detector system is optimized. For 3 eV o-Ps, the time broadening is 7.66 ns and the count rate is 3 cps after correction.
Longitudinal uniformity, time performances and irradiation test of pure CsI crystals
NASA Astrophysics Data System (ADS)
Angelucci, M.; Atanova, O.; Baccaro, S.; Cemmi, A.; Cordelli, M.; Donghia, R.; Giovannella, S.; Happacher, F.; Miscetti, S.; Sarra, I.; Soleti, S. R.
2016-07-01
To study an alternative to BaF2, as the crystal choice for the Mu2e calorimeter, 13 pure CsI crystals from Opto Materials and ISMA producers have been characterized by determining their light yield (LY) and longitudinal response uniformity (LRU), when read with a UV extended PMT. The crystals show a LY of 100 p.e./MeV ( 150 p.e./MeV) when wrapped with Tyvek and coupled to the PMT without (with) optical grease. The LRU is well represented by a linear slope that is on average δ -0.6%/cm. The timing performances of the Opto Materials crystal, read with a UV extended MPPC, have been evaluated with minimum ionizing particles. A timing resolution of 330 ps ( 440 ps) is achieved when connecting the photosensor to the MPPC with (without) optical grease. The crystal radiation hardness to a ionization dose has also been studied for one pure CsI crystal from SICCAS. After exposing it to a dose of 900 Gy, a decrease of 33% in the LY is observed while the LRU remains unchanged.
Condensation of collective charge ordering in chromium
DOE Office of Scientific and Technical Information (OSTI.GOV)
Singer, A.; Marsh, M. J.; Dietze, S. H.
2015-03-01
We report on the dynamics of the structural order parameter in a chromium film using synchrotron radiation in response to photoinduced ultrafast excitations. Following transient optical excitations the effective lattice temperature of the film rises close to the Neel temperature and the charge-density wave (CDW) amplitude is reduced but does not appear to ever be fully destroyed. The persistence of the CDW diffraction signal demonstrates that the CDW, if destroyed by the laser pulse, must be reestablished within the 100-ps time resolution of the synchrotron x-ray pulses. Furthermore, at all times after photoexcitation, the CDW retains its low-temperature periodicity, rathermore » than regenerating with its high-temperature period shortly after photoexcitation. The long-term evolution shows that the CDW reverts to its ground state on a time scale of 370 +/- 40 ps. We attribute the apparent persistence of the CDW to the long-lived periodic lattice displacement in chromium. This study highlights the fundamental role of the lattice distortion and its impact on the recondensation dynamics of the charge ordered state in strongly correlated materials.« less
Widefield TSCSPC-systems with large-area-detectors: application in simultaneous multi-channel-FLIM
NASA Astrophysics Data System (ADS)
Stepanov, Sergei; Bakhlanov, Sergei; Drobchenko, Evgeny; Eckert, Hann-Jörg; Kemnitz, Klaus
2010-11-01
Novel proximity-type Time- and Space-Correlated Single Photon Counting (TSCSPC) crossed-delay-line (DL)- and multi-anode (MA)-systems of outstanding performance and homogeneity were developed, using large-area detector heads of 25 and 40 mm diameter. Instrument response functions IRF(space) = (60 +/- 5) μm FWHM and IRF(time) = (28 +/- 3) ps FWHM were achieved over the full 12 cm2 area of the detector. Deadtime at throughput of 105 cps is 10% for "high-resolution" system and 5% in the "video"-system at 106 cps, at slightly reduced time- and space resolution. A fluorescence lifetime of (3.5 +/- 1) ps can be recovered from multi-exponential dynamics of a single living cyanobacterium (Acaryochloris marina). The present large-area detectors are particularly useful in simultaneous multichannel applications, such as 2-colour anisotropy or 4-colour lifetime imaging, utilizing dual- or quad-view image splitters. The long-term stability, low- excitation-intensity (< 100 mW/cm2) widefield systems enable minimal-invasive observation, without significant bleaching or photodynamic reactions, thus allowing long-period observation of up to several hours in living cells.
Polymer Thin Film Stabilization.
NASA Astrophysics Data System (ADS)
Costa, A. C.; Oslanec, R.; Composto, R. J.; Vlcek, P.
1998-03-01
We study the dewetting dynamics of thin polystyrene (PS) films deposited on silicon oxide surfaces using optical (OM) and atomic force (AFM) microscopes. Quantitative analysis of the hole diameter as a function of annealing time at 175^oC shows that blending poly(styrene-block-methyl-methacrylate) (PS-b-PMMA) with PS acts to dramatically slow down the dewetting rate and even stops holes growth before they impinge. AFM studies show that the hole floor is smooth for a pure PS film but contains residual polymer for the blend. At 5% vol., a PS-b-PMMA with high molar mass and low PMMA is a more effective stabilizing agent than a low molar mass/high PMMA additive. The optimum copolymer concentration is 3% vol. beyond which film stability doesn't improve. Although dewetting is slowed down relative to pure PS, PS/PS-b-PMMA bilayers dewet at a faster rate than blends having the same overall additive concentration.
Jachymek, Wojciech; Srutkova, Dagmar; Brzozowska, Ewa; Kozakova, Hana; Gamian, Andrzej
2014-01-01
The structures of polysaccharides (PS) isolated from Lactobacillus rhamnosus LOCK 0900 and results from stimulation of mouse bone marrow-derived dendritic cells (BM-DC) and human embryonal kidney (HEK293) cells stably transfected with Toll-like receptors (TLR) upon exposure to these antigens were studied. L. rhamnosus LOCK 0900 produces PS that differ greatly in their structure. The polymer L900/2, with a high average molecular mass of 830 kDa, is a branched heteropolysaccharide with a unique repeating unit consisting of seven sugar residues and pyruvic acid, whereas L900/3 has a low average molecular mass of 18 kDa and contains a pentasaccharide repeating unit and phosphorus. Furthermore, we found that both described PS neither induce cytokine production and maturation of mouse BM-DC nor induce signaling through TLR2/TLR4 receptors. However, they differ profoundly in their abilities to modulate the BM-DC immune response to the well-characterized human isolate Lactobacillus plantarum WCFS1. Exposure to L900/2 enhanced interleukin-10 (IL-10) production induced by L. plantarum WCFS1, while in contrast, L900/3 enhanced the production of IL-12p70. We conclude that PS, probably due to their chemical features, are able to modulate the immune responses to third-party antigens. The ability to induce regulatory IL-10 by L900/2 opens up the possibility to use this PS in therapy of inflammatory conditions, such as inflammatory bowel disease, whereas L900/3 might be useful in reverting the antigen-dependent Th2-skewed immune responses in allergies. PMID:25107979
A longitudinal study in youth of heart rate variability at rest and in response to stress
Li, Zhibin; Snieder, Harold; Su, Shaoyong; Ding, Xiuhua; Thayer, Julian F.; Treiber, Frank A.; Wang, Xiaoling
2009-01-01
Background Few longitudinal studies have examined ethnic and sex differences, predictors and tracking stabilities of heart rate variability (HRV) at rest and in response to stress in youths and young adults. Methods Two evaluations were performed approximately 1.5 years apart on 399 youths and young adults (189 European Americans [EAs] and 210 African Americans [AAs]; 190 males and 209 females). HRV was measured at rest and during a video game challenge. Results AAs showed significantly higher resting root mean square of successive differences (RMSSD) of normal R-R intervals and high-frequency (HF) power than EAs (Ps< 0.01). Females displayed larger decrease of RMSSD and HF during video game challenge than males (Ps< 0.05). These ethnic and sex differences were consistent across 1.5 years. No significant sex difference of resting HRV or ethnic difference of HRV response to stress was observed. In addition to age, ethnicity or sex, baseline resting HRV or HRV response to stress are predictors of the corresponding variables 1.5 years later (Ps< 0.01). Furthermore, weight gain indexed by either body mass index or waist circumference predicts declined resting HRV levels during follow up (Ps < 0.05). Tracking stabilities were high (>0.5) for resting HRV, but relatively low (<0.3) for HRV in response to stress. Conclusion AAs show higher resting HRV than EAs, and females display greater HRV response to stress than males; and these ethnic and sex differences are consistent across 1.5 years. Resting HRV declines with weight gain. PMID:19285108
Optical pump terahertz probe studies of semiconducting polymers
NASA Astrophysics Data System (ADS)
Cunningham, Paul D.
Optical-pump terahertz-probe spectroscopy (OPTP) has been applied to study charge generation, transport and the evolution of the photo-induced excited states in thin film organic semiconductors, with emphasis on their relevance to photovoltaic technology. In these experiments the response of the photoexcited material to the AC electric field of a terahertz (THz) pulse was measured. From this response, the evolution of the complex conductivity in the far-infrared was monitored. OPTP presents advantages over other techniques by being an all-optical probe of the complex conductivity over nanometer scale distances with sub-picosecond resolution and exhibits particular sensitivity to carrier scattering rates, which typically lay in the THz range. Conductivity models were applied to the extracted conductivity curves in order to determine technologically relevant quantities like the charge carrier mobility and external quantum yield of charge carrier generation. We observed charge carriers generated on a subpicosecond time scale in thin films of polyhexylthiophene (P3HT). Through application of the Drude-Smith model (DSM) over the 0-2 THz band, we determined a room temperature intrinsic mobility of about 30 cm2/Vs. The temperature dependence of the conductivity dynamics showed signs of thermally activated polaron hopping influenced by torsional disorder. Both above and below gap excitation resulted in similar dynamics, showing that the majority of carriers recombine within 1 ps. We were able to observe charge transfer occurring on a sub-ps timescale to the soluble fullerene, PCBM, for both excited states, demonstrating that narrow gap polymers can be blended with PCBM for photovoltaic applications. We observed charge carrier generated on a sub-ps time scale in thin amorphous films of metalated polymers. The time evolution of the conductivity showed that charge carriers recombine and only excitons persist after 100 ps. This characteristic appears to be common to amorphous systems. An intrinsic mobility of 20 cm2/Vs was found for the most promising material. Broadband (0-6 THz) studies of the photoconductivity in P3HT suggest that the hole mobility is lower than initially determined. They also bring into question whether the DSM can describe the conductivity effectively or whether delocalized polaron transitions at higher frequencies are the origin of the observed features.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Boyun; Wang, Tao, E-mail: wangtao@hust.edu.cn; Tang, Jian
2014-10-07
We theoretically propose a dynamic and ultrafast group delay tuning mechanism in two microcavities side-coupled to a waveguide system through external optical pump beams. The optical Kerr effect modulation method is applied to improve tuning rate with response time of subpicoseconds or even femtoseconds. The group delay of an all-optical analog to electromagnetically induced transparency effect can be controlled by tuning either the frequency of photonic crystal microcavities or the propagation phase of line waveguide. Group delay is controlled between 5.88 and 70.98 ps by dynamically tuning resonant frequencies of the microcavities. Alternatively, the group delay is controlled between 1.86more » and 12.08 ps by dynamically tuning the propagation phase of line waveguide. All observed schemes are analyzed rigorously through finite-difference time-domain simulations and coupled-mode formalism. Results show a new direction toward microstructure integration optical pulse trapping and all-optical dynamical storage of light devices in optical communication and quantum information processing.« less
NASA Astrophysics Data System (ADS)
Li, Zhongguo; Gao, Feng; Xiao, Zhengguo; Wu, Xingzhi; Zuo, Jinglin; Song, Yinglin
2018-07-01
The third-order nonlinear optical properties of two di-lanthanide (Ln = Tb and Dy) sandwich complexes with mixed phthalocyanine and Schiff-base ligands were studied using Z-scan technique at 532 nm with 20 ps and 4 ns pulses. Both complexes exhibit reverse saturable absorption and self-focusing effect in ps regime, while the second-order hyperpolarizability decreases from Dy to Tb. Interestingly, the Tb triple-decker complexes show larger nonlinear absorption than Dy complexes on ns timescale. The time-resolved pump-probe measurements demonstrate that the nonlinear optical response was caused by excited-state mechanism related to the five-level model, while the singlet state lifetime of Dy complexes is 3 times shorter than that of Tb complexes. Our results indicate the lanthanide ions play a critical role in the photo-physical properties of triple-decker phthalocyanine complexes for their application as optical limiting materials.
Paerl, H.W.; Peierls, B.L.; Hall, N. S.; Joyner, A. R.; Christian, R.R.; Bales, Jerad D.; Riggs, S.R.
2010-01-01
The Pamlico Sound (PS) with its sub-estuaries is the largest lagoonal ecosystem in the United States. It exhibits periodically strong salinity stratification and an average freshwater residence time of 1 year for the sound proper. This relatively long residence time promotes effective use and cycling of nutrients, allowing the system to support high rates of primary and secondary production, and serve as a vitally important fisheries nursery. This hydrologic characteristic also makes the system highly sensitive to nutrient over-enrichment and eutrophication. The PS is experiencing ecological change in response to increasing human activity and climatic perturbations. Human impacts include a rise in nutrient, sediment, and other pollutant loads that accompany urbanization and agricultural and industrial growth in its watersheds and airsheds. Since the mid-1990s, the PS has witnessed a sudden rise in tropical storm and hurricane impacts, with eight hurricanes and four tropical storms having made landfall in the PS watershed during the 1996 to 2007 period. Each of these storms had unique hydrologic, nutrient, and other pollutant loading effects. In addition, since the early 2000s, the region has experienced record droughts, which are continuing. Variable freshwater discharges from storms and droughts have caused large oscillations in nutrient enrichment, reflected ultimately in differential phytoplankton production, biomass, and community compositional responses. Floodwaters from the two wettest hurricanes, Fran (1996) and Floyd (1999), and from Tropical Storm Ernesto (2006) exerted long-term (months) effects on hydrology, nutrient loads, and algal production. Windy but relatively dry hurricanes, like Irene (1999) and Isabel (2003), caused strong vertical mixing, storm surges, but relatively minor changes in river flow, flushing, and nutrient loads. These contrasting effects are accompanied by biogeochemical (hypoxia, nutrient cycling) and habitat alterations, and associated food web disturbances. Each storm type influenced algal growth and compositional dynamics; however, their respective ecological impacts differed substantially. Changes in hydrologic and wind forcing resulting from changes in frequency and intensity of storms and droughts strongly influence water and habitat quality. These changes must be integrated with nutrient loading/dilution effects when assessing and predicting ecological responses to nutrient and hydrologic variability on this and other large lagoonal ecosystems.
Zhang, Yanzhao; Cheng, Yanwei; Ya, Huiyuan; Xu, Shuzhen; Han, Jianming
2015-01-01
The pigmented cells in defined region of a petal constitute the petal spots. Petal spots attract pollinators and are found in many angiosperm families. Several cultivars of tree peony contain a single red or purple spot at the base of petal that makes the flower more attractive for the ornamental market. So far, the understanding of the molecular mechanism of spot formation is inadequate. In this study, we sequenced the transcriptome of the purple spot and the white non-spot of tree peony flower. We assembled and annotated 67,892 unigenes. Comparative analyses of the two transcriptomes showed 1,573 differentially expressed genes, among which 933 were up-regulated, and 640 were down-regulated in the purple spot. Subsequently, we examined four anthocyanin structural genes, including PsCHS, PsF3′H, PsDFR, and PsANS, which expressed at a significantly higher level in the purple spot than in the white non-spot. We further validated the digital expression data using quantitative real-time PCR. Our result uncovered transcriptome variance between the spot and non-spot of tree peony flower, and revealed that the co-expression of four anthocyanin structural genes was responsible for spot pigment in tree peony. The data will further help to unravel the genetic mechanism of peony flower spot formation. PMID:26583029
Rate theory of solvent exchange and kinetics of Li(+) - BF4 (-)/PF6 (-) ion pairs in acetonitrile.
Dang, Liem X; Chang, Tsun-Mei
2016-09-07
In this paper, we describe our efforts to apply rate theories in studies of solvent exchange around Li(+) and the kinetics of ion pairings in lithium-ion batteries (LIBs). We report one of the first computer simulations of the exchange dynamics around solvated Li(+) in acetonitrile (ACN), which is a common solvent used in LIBs. We also provide details of the ion-pairing kinetics of Li(+)-[BF4] and Li(+)-[PF6] in ACN. Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine the ACN exchange process between the first and second solvation shells around Li(+). We calculate exchange rates using transition state theory and weighted them with the transmission coefficients determined by the reactive flux, Impey, Madden, and McDonald approaches, and Grote-Hynes theory. We found the relaxation times changed from 180 ps to 4600 ps and from 30 ps to 280 ps for Li(+)-[BF4] and Li(+)-[PF6] ion pairs, respectively. These results confirm that the solvent response to the kinetics of ion pairing is significant. Our results also show that, in addition to affecting the free energy of solvation into ACN, the anion type also should significantly influence the kinetics of ion pairing. These results will increase our understanding of the thermodynamic and kinetic properties of LIB systems.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dang, Liem X.; Chang, Tsun-Mei
In this paper, we describe our efforts to apply rate theories in studies of solvent exchange around Li{sup +} and the kinetics of ion pairings in lithium-ion batteries (LIBs). We report one of the first computer simulations of the exchange dynamics around solvated Li{sup +} in acetonitrile (ACN), which is a common solvent used in LIBs. We also provide details of the ion-pairing kinetics of Li{sup +}-[BF{sub 4}] and Li{sup +}-[PF{sub 6}] in ACN. Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine the ACN exchange process between the first and second solvation shellsmore » around Li{sup +}. We calculate exchange rates using transition state theory and weighted them with the transmission coefficients determined by the reactive flux, Impey, Madden, and McDonald approaches, and Grote-Hynes theory. We found the relaxation times changed from 180 ps to 4600 ps and from 30 ps to 280 ps for Li{sup +}-[BF{sub 4}] and Li{sup +}-[PF{sub 6}] ion pairs, respectively. These results confirm that the solvent response to the kinetics of ion pairing is significant. Our results also show that, in addition to affecting the free energy of solvation into ACN, the anion type also should significantly influence the kinetics of ion pairing. These results will increase our understanding of the thermodynamic and kinetic properties of LIB systems.« less
Rate theory of solvent exchange and kinetics of Li+ - BF4-/PF6- ion pairs in acetonitrile
NASA Astrophysics Data System (ADS)
Dang, Liem X.; Chang, Tsun-Mei
2016-09-01
In this paper, we describe our efforts to apply rate theories in studies of solvent exchange around Li+ and the kinetics of ion pairings in lithium-ion batteries (LIBs). We report one of the first computer simulations of the exchange dynamics around solvated Li+ in acetonitrile (ACN), which is a common solvent used in LIBs. We also provide details of the ion-pairing kinetics of Li+-[BF4] and Li+-[PF6] in ACN. Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine the ACN exchange process between the first and second solvation shells around Li+. We calculate exchange rates using transition state theory and weighted them with the transmission coefficients determined by the reactive flux, Impey, Madden, and McDonald approaches, and Grote-Hynes theory. We found the relaxation times changed from 180 ps to 4600 ps and from 30 ps to 280 ps for Li+-[BF4] and Li+-[PF6] ion pairs, respectively. These results confirm that the solvent response to the kinetics of ion pairing is significant. Our results also show that, in addition to affecting the free energy of solvation into ACN, the anion type also should significantly influence the kinetics of ion pairing. These results will increase our understanding of the thermodynamic and kinetic properties of LIB systems.
Hashad, Rania A; Ishak, Rania A H; Geneidi, Ahmed S; Mansour, Samar
2016-10-01
The aim of this study was to assess the feasibility of employing a novel but critical formulation pH (6.2) to encapsulate an anionic model drug (methotrexate, MTX) into chitosan(Cs)-tripolyphosphate nanoparticles(NPs). A response surface methodology using a three-level full factorial design was applied studying the effects of two independent variables namely; Cs concentration and MTX concentration. The responses investigated were the entrapment efficiency (EE%), mean hydrodynamic particle size (PS), polydispersity index (PDI) and zeta potential (ZP). In order to simultaneously optimize the series of models obtained, the desirability function approach was applied with a goal to produce high percent of MTX encapsulated into highly charged Cs-TPP NPs of homogenous optimum PS. MTX-loaded CsNPs were successfully prepared at the novel pH applied. The suggested significant models were found quadratic for EE, PS and ZP responses, while 2-factor interaction model for PDI. The optimization overlay graph showed that the maximum global desirability, D=0.856, was reached when the conditions were set at high Cs and MTX concentration. Thus, the use of such optimized conditions, at this novel pH, achieved a maximum drug EE% (73.38%) into NPs characterized by optimum PS (232.6nm), small PDI value (0.195) and highly surface charged (+18.4mV). Copyright © 2016 Elsevier B.V. All rights reserved.
Spinor Bose-Einstein Condensates of Positronium
NASA Astrophysics Data System (ADS)
Wang, Yi-Hsieh; Anderson, Brandon; Clark, Charles
2014-05-01
Bose-Einstein condensates (BECs) of positronium (Ps) have been of experimental and theoretical interest due to their potential application as the gain medium of a γ-ray laser. Ps BECs are intrinsically spinor due to the presence of ortho-positronium (o-Ps) and para-positronium (p-Ps), whose annihilation lifetimes differ by three orders of magnitude. In this paper, we study the spinor dynamics and annihilation processes in the p-Ps/o-Ps system using both solutions of the time-dependent Gross-Pitaevskii equations and a semiclassical rate-equation approach. The spinor interactions have an O (4) symmetry which is broken to SO (3) by an internal energy difference between o-Ps and p-Ps. For an initially unpolarized condensate, there is a threshold density of ~1019 cm-3 at which spin mixing between o-Ps and p-Ps occurs. Beyond this threshold, there are unstable spatial modes accompanied by spin mixing. To ensure a high production yield above the critical density, a careful choice of external field must be made to avoid the spin mixing instability. NSF Physics Frontiers Center, ARO Atomtronics MURI, DARPA OLE.
Early photosensitizer uptake kinetics predict optimum drug-light interval for photodynamic therapy
NASA Astrophysics Data System (ADS)
Sinha, Lagnojita; Elliott, Jonathan T.; Hasan, Tayyaba; Pogue, Brian W.; Samkoe, Kimberley S.; Tichauer, Kenneth M.
2015-03-01
Photodynamic therapy (PDT) has shown promising results in targeted treatment of cancerous cells by developing localized toxicity with the help of light induced generation of reactive molecular species. The efficiency of this therapy depends on the product of the intensity of light dose and the concentration of photosensitizer (PS) in the region of interest (ROI). On account of this, the dynamic and variable nature of PS delivery and retention depends on many physiological factors that are known to be heterogeneous within and amongst tumors (e.g., blood flow, blood volume, vascular permeability, and lymph drainage rate). This presents a major challenge with respect to how the optimal time and interval of light delivery is chosen, which ideally would be when the concentration of PS molecule is at its maximum in the ROI. In this paper, a predictive algorithm is developed that takes into consideration the variability and dynamic nature of PS distribution in the body on a region-by-region basis and provides an estimate of the optimum time when the PS concentration will be maximum in the ROI. The advantage of the algorithm lies in the fact that it predicts the time in advance as it takes only a sample of initial data points (~12 min) as input. The optimum time calculated using the algorithm estimated a maximum dose that was only 0.58 +/- 1.92% under the true maximum dose compared to a mean dose error of 39.85 +/- 6.45% if a 1 h optimal light deliver time was assumed for patients with different efflux rate constants of the PS, assuming they have the same plasma function. Therefore, if the uptake values of PS for the blood and the ROI is known for only first 12 minutes, the entire curve along with the optimum time of light radiation can be predicted with the help of this algorithm.
NASA Astrophysics Data System (ADS)
Ponseca, C. S., Jr.; Sundström, V.
2016-03-01
Ultrafast charge carrier dynamics in organo metal halide perovskite has been probed using time resolved terahertz (THz) spectroscopy (TRTS). Current literature on its early time characteristics is unanimous: sub-ps charge carrier generation, highly mobile charges and very slow recombination rationalizing the exceptionally high power conversion efficiency for a solution processed solar cell material. Electron injection from MAPbI3 to nanoparticles (NP) of TiO2 is found to be sub-ps while Al2O3 NPs do not alter charge dynamics. Charge transfer to organic electrodes, Spiro-OMeTAD and PCBM, is sub-ps and few hundreds of ps respectively, which is influenced by the alignment of energy bands. It is surmised that minimizing defects/trap states is key in optimizing charge carrier extraction from these materials.
NASA Astrophysics Data System (ADS)
Xu, He-Lin; Mao, Kai-Li; Huang, Yin-Ping; Yang, Jing-Jing; Xu, Jie; Chen, Pian-Pian; Fan, Zi-Liang; Zou, Shuang; Gao, Zheng-Zheng; Yin, Jia-Yu; Xiao, Jian; Lu, Cui-Tao; Zhang, Bao-Lin; Zhao, Ying-Zheng
2016-07-01
Multifunctional nanoparticles capable of the specific delivery of therapeutics to diseased cells and the real-time imaging of these sites have the potential to improve cancer treatment through personalized therapy. In this study, we have proposed a multifunctional nanoparticle that integrate magnetic targeting, drug-carrier functionality and real-time MRI imaging capabilities in one platform for the theranostic treatment of tumors. The multifunctional nanoparticle was designed with a superparamagnetic iron oxide core and a multifunctional shell composed of PEG/PEI/polysorbate 80 (Ps 80) and was used to encapsulate DOX. DOX-loaded multifunctional nanoparticles (DOX@Ps 80-SPIONs) with a Dh of 58.0 nm, a zeta potential of 28.0 mV, and a drug loading content of 29.3% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 24.1 emu g-1. The cellular uptake of DOX@Ps 80-SPIONs by C6 cells under a magnetic field was significantly enhanced over that of free DOX in solution, resulting in stronger in vitro cytotoxicity. The real-time therapeutic outcome of DOX@Ps 80-SPIONs was easily monitored by MRI. Furthermore, the negative contrast enhancement effect of the nanoparticles was confirmed in glioma-bearing rats. Prussian blue staining and ex vivo DOX fluorescence assays showed that the magnetic Ps 80-SPIONs and encapsulated DOX were delivered to gliomas by imposing external magnetic fields, indicating effective magnetic targeting. Due to magnetic targeting and Ps 80-mediated endocytosis, DOX@Ps 80-SPIONs in the presence of a magnetic field led to the complete suppression of glioma growth in vivo at 28 days after treatment. The therapeutic mechanism of DOX@Ps 80-SPIONs acted by inducing apoptosis through the caspase-3 pathway. Finally, DOX@Ps 80-SPIONs' safety at therapeutic dosage was verified using pathological HE assays of the heart, liver, spleen, lung and kidney. Multifunctional SPIONs could be used as potential carriers for the theranostic treatment of CNS diseases.Multifunctional nanoparticles capable of the specific delivery of therapeutics to diseased cells and the real-time imaging of these sites have the potential to improve cancer treatment through personalized therapy. In this study, we have proposed a multifunctional nanoparticle that integrate magnetic targeting, drug-carrier functionality and real-time MRI imaging capabilities in one platform for the theranostic treatment of tumors. The multifunctional nanoparticle was designed with a superparamagnetic iron oxide core and a multifunctional shell composed of PEG/PEI/polysorbate 80 (Ps 80) and was used to encapsulate DOX. DOX-loaded multifunctional nanoparticles (DOX@Ps 80-SPIONs) with a Dh of 58.0 nm, a zeta potential of 28.0 mV, and a drug loading content of 29.3% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 24.1 emu g-1. The cellular uptake of DOX@Ps 80-SPIONs by C6 cells under a magnetic field was significantly enhanced over that of free DOX in solution, resulting in stronger in vitro cytotoxicity. The real-time therapeutic outcome of DOX@Ps 80-SPIONs was easily monitored by MRI. Furthermore, the negative contrast enhancement effect of the nanoparticles was confirmed in glioma-bearing rats. Prussian blue staining and ex vivo DOX fluorescence assays showed that the magnetic Ps 80-SPIONs and encapsulated DOX were delivered to gliomas by imposing external magnetic fields, indicating effective magnetic targeting. Due to magnetic targeting and Ps 80-mediated endocytosis, DOX@Ps 80-SPIONs in the presence of a magnetic field led to the complete suppression of glioma growth in vivo at 28 days after treatment. The therapeutic mechanism of DOX@Ps 80-SPIONs acted by inducing apoptosis through the caspase-3 pathway. Finally, DOX@Ps 80-SPIONs' safety at therapeutic dosage was verified using pathological HE assays of the heart, liver, spleen, lung and kidney. Multifunctional SPIONs could be used as potential carriers for the theranostic treatment of CNS diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr02448c
Study of SiRNA-loaded PS-mPEG/CaP nanospheres on lung cancer
NASA Astrophysics Data System (ADS)
Wang, Qi; Qin, Liubin; Sun, Ying; Shen, Ming; Duan, Yourong
2014-05-01
An ultrasound-adsorption method was used to prepare Bcl-2-SiRNA-loaded PS-mPEG/CaP nanospheres. The size and zeta potential were 18.41 ± 4.31 nm ( n = 5) and -23.5 ± 0.6 mV, respectively. The entrapment efficiency of SiRNA was 92.86 %. MTT assay results confirmed that the blank nanospheres demonstrated a negligible cytotoxicity response in H1299 cells. Flow cytometer analysis results demonstrated that PS-mPEG/CaP NSs could carry SiRNA into the cells effectively. RT-PCR experiments and apoptosis assay results approved that, compared with free SiRNA, SiRNA-loaded PS-mPEG/CaP NSs could silence Bcl-2 gene and induce cell apoptosis effectively. In vivo distribution results confirmed PS-mPEG/CaP NSs could carry SiRNA enter the tumor tissue effectively. Taken together, these results suggest that the Bcl-2-SiRNA-loaded PS-mPEG/CaP nanospheres have great potential to be used to cure lung cancer.
Caspase Activity Is Required for Engulfment of Apoptotic Cells
Shklyar, Boris; Levy-Adam, Flonia; Mishnaevski, Ketty
2013-01-01
Clearance of apoptotic cells by phagocytic neighbors is crucial for normal development of multicellular organisms. However, how phagocytes discriminate between healthy and dying cells remains poorly understood. We focus on glial phagocytosis of apoptotic neurons during development of the Drosophila central nervous system. We identified phosphatidylserine (PS) as a ligand on apoptotic cells for the phagocytic receptor Six Microns Under (SIMU) and report that PS alone is not sufficient for engulfment. Our data reveal that, additionally to PS exposure, caspase activity is required for clearance of apoptotic cells by phagocytes. Here we demonstrate that SIMU recognizes and binds PS on apoptotic cells through its N-terminal EMILIN (EMI), Nimrod 1 (NIM1), and NIM2 repeats, whereas the C-terminal NIM3 and NIM4 repeats control SIMU affinity to PS. Based on the structure-function analysis of SIMU, we discovered a novel mechanism of internal inhibition responsible for differential affinities of SIMU to its ligand which might prevent elimination of living cells exposing PS on their surfaces. PMID:23754750
Phosphatidylserine transport by Ups2-Mdm35 in respiration-active mitochondria.
Miyata, Non; Watanabe, Yasunori; Tamura, Yasushi; Endo, Toshiya; Kuge, Osamu
2016-07-04
Phosphatidylethanolamine (PE) is an essential phospholipid for mitochondrial functions and is synthesized mainly by phosphatidylserine (PS) decarboxylase at the mitochondrial inner membrane. In Saccharomyces cerevisiae, PS is synthesized in the endoplasmic reticulum (ER), such that mitochondrial PE synthesis requires PS transport from the ER to the mitochondrial inner membrane. Here, we provide evidence that Ups2-Mdm35, a protein complex localized at the mitochondrial intermembrane space, mediates PS transport for PE synthesis in respiration-active mitochondria. UPS2- and MDM35-null mutations greatly attenuated conversion of PS to PE in yeast cells growing logarithmically under nonfermentable conditions, but not fermentable conditions. A recombinant Ups2-Mdm35 fusion protein exhibited phospholipid-transfer activity between liposomes in vitro. Furthermore, UPS2 expression was elevated under nonfermentable conditions and at the diauxic shift, the metabolic transition from glycolysis to oxidative phosphorylation. These results demonstrate that Ups2-Mdm35 functions as a PS transfer protein and enhances mitochondrial PE synthesis in response to the cellular metabolic state. © 2016 Miyata et al.
Beam test results of a 16 ps timing system based on ultra-fast silicon detectors
Cartiglia, N.; Staiano, A.; Sola, V.; ...
2017-04-01
In this paper we report on the timing resolution obtained in a beam test with pions of 180 GeV/c momentum at CERN for the first production of 45 μm thick Ultra-Fast Silicon Detectors (UFSD). UFSD are based on the Low- Gain Avalanche Detector (LGAD) design, employing n-on-p silicon sensors with internal charge multiplication due to the presence of a thin, low-resistivity diffusion layer below the junction. The UFSD used in this test had a pad area of 1.7 mm 2. The gain was measured to vary between 5 and 70 depending on the sensor bias voltage. The experimental setup includedmore » three UFSD and a fast trigger consisting of a quartz bar readout by a SiPM. The timing resolution was determined by doing Gaussian fits to the time-of-flight of the particles between one or more UFSD and the trigger counter. For a single UFSD the resolution was measured to be 34 ps for a bias voltage of 200 V, and 27 ps for a bias voltage of 230 V. For the combination of 3 UFSD the timing resolution was 20 ps for a bias voltage of 200 V, and 16 ps for a bias voltage of 230 V.« less
Beam test results of a 16 ps timing system based on ultra-fast silicon detectors
NASA Astrophysics Data System (ADS)
Cartiglia, N.; Staiano, A.; Sola, V.; Arcidiacono, R.; Cirio, R.; Cenna, F.; Ferrero, M.; Monaco, V.; Mulargia, R.; Obertino, M.; Ravera, F.; Sacchi, R.; Bellora, A.; Durando, S.; Mandurrino, M.; Minafra, N.; Fadeyev, V.; Freeman, P.; Galloway, Z.; Gkougkousis, E.; Grabas, H.; Gruey, B.; Labitan, C. A.; Losakul, R.; Luce, Z.; McKinney-Martinez, F.; Sadrozinski, H. F.-W.; Seiden, A.; Spencer, E.; Wilder, M.; Woods, N.; Zatserklyaniy, A.; Pellegrini, G.; Hidalgo, S.; Carulla, M.; Flores, D.; Merlos, A.; Quirion, D.; Cindro, V.; Kramberger, G.; Mandić, I.; Mikuž, M.; Zavrtanik, M.
2017-04-01
In this paper we report on the timing resolution obtained in a beam test with pions of 180 GeV/c momentum at CERN for the first production of 45 μm thick Ultra-Fast Silicon Detectors (UFSD). UFSD are based on the Low-Gain Avalanche Detector (LGAD) design, employing n-on-p silicon sensors with internal charge multiplication due to the presence of a thin, low-resistivity diffusion layer below the junction. The UFSD used in this test had a pad area of 1.7 mm2. The gain was measured to vary between 5 and 70 depending on the sensor bias voltage. The experimental setup included three UFSD and a fast trigger consisting of a quartz bar readout by a SiPM. The timing resolution was determined by doing Gaussian fits to the time-of-flight of the particles between one or more UFSD and the trigger counter. For a single UFSD the resolution was measured to be 34 ps for a bias voltage of 200 V, and 27 ps for a bias voltage of 230 V. For the combination of 3 UFSD the timing resolution was 20 ps for a bias voltage of 200 V, and 16 ps for a bias voltage of 230 V.
Waki, Fusako; Ando, Masashi; Takashima, Atsuo; Yonemori, Kan; Nokihara, Hiroshi; Miyake, Mototaka; Tateishi, Ukihide; Tsuta, Koji; Shimada, Yasuhiro; Fujiwara, Yasuhiro; Tamura, Tomohide
2009-06-01
Leptomeningeal metastasis (LM) occurs in 4-15% of patients with solid tumors. Although the clinical outcomes in cancer patients have been improving recently, no standard treatment for LM has been established as yet. The purpose of this study was to identify the prognostic factors in patients with solid tumors with cytologically proven LM. We retrospectively analyzed a series of 85 consecutive patients with cytologically proven LM who were treated between 1997 and 2005. The primary diseases were as follows; lung cancer (n = 36), breast cancer (n = 33), gastric cancer (n = 8), and others (n = 8). Forty-nine patients had brain metastasis at the time of diagnosis of the LM, and in 51 patients, MRI revealed meningeal dissemination in the brain or spine. The performance status (PS) was 0-1 in 26 patients and 2-4 in 59 patients. Thirty-one patients, including 19 with breast cancer, four with lung cancer, five with gastric cancer and three with other cancers, were treated by intrathecal (IT) chemotherapy. The response rate to the IT was 52% (95% confidence interval (CI): 41.4-62.6%). The median survival was 51 days (range, 3-759 days). A univariate analysis identified breast cancer, good PS (0-1), time to development of the LM (>1 year), and treatment by IT chemotherapy as being associated with a good prognosis, and multivariate analysis identified poor PS (HR: 1.72 (95% CI, 1.04-2.86) P = 0.04) and MRI-proven LM (HR: 1.82 (95% CI, 1.11-2.98) P = 0.02) as being associated with a poor prognosis. In patients with poor prognostic factors, such as poor PS or MRI-proven LM, palliative therapy might be the most suitable treatment strategy.
Immobility reaction at birth in newborn infant.
Rousseau, Pierre Victor; Francotte, Jacques; Fabbricatore, Maria; Frischen, Caroline; Duchateau, Delphine; Perin, Marie; Gauthier, Jean-Marie; Lahaye, Willy
2014-08-01
To describe an immobility reaction (IR) that was not previously reported at or immediately after birth in human newborns. We analyzed 31 videos of normal term vaginal deliveries recorded from Time 0 of birth defined as the as the moment that lies between the birth of the thorax and the pelvis of the infant. We searched for perinatal factors associated with newborn's IR. IR at birth was observed in 8 of the 31 newborns. The main features of their behavior were immobilization, frozen face, shallow breathing and bradycardia. One of the 8 newborns had sudden collapse 2h after birth. We found significant relationships between maternal prenatal stress (PS) and IR (p=.037), and a close to significant one between infants' lividness at Time 0 and IR (p=.053). The first breath of the 31 newborns occurred before and was not associated with the first cry (p<.001). The main features of IR at birth are similar to those of the universal most severe response to severe stress or danger. The relationship with PS suggests that children who had IR at birth might be at risk for similar disorders as those associated with PS. Sudden neonatal collapse of one of the IR newborns needs further research to determine if they are at risk for sudden infant death syndrome. This first report of an IR reaction at birth in human infants could open up new paths for improving early neonatal care. Further research is needed for maternal PS, stress hormones, umbilical cord blood pH measurements in IR newborns. The challenge of education and support for parents of IR newborns is outlined. Copyright © 2014 Elsevier Inc. All rights reserved.
An 18-ps TDC using timing adjustment and bin realignment methods in a Cyclone-IV FPGA
NASA Astrophysics Data System (ADS)
Cao, Guiping; Xia, Haojie; Dong, Ning
2018-05-01
The method commonly used to produce a field-programmable gate array (FPGA)-based time-to-digital converter (TDC) creates a tapped delay line (TDL) for time interpolation to yield high time precision. We conduct timing adjustment and bin realignment to implement a TDC in the Altera Cyclone-IV FPGA. The former tunes the carry look-up table (LUT) cell delay by changing the LUT's function through low-level primitives according to timing analysis results, while the latter realigns bins according to the timing result obtained by timing adjustment so as to create a uniform TDL with bins of equivalent width. The differential nonlinearity and time resolution can be improved by realigning the bins. After calibration, the TDC has a 18 ps root-mean-square timing resolution and a 45 ps least-significant bit resolution.
Bulfone, Giampiera; Fida, Roberta; Ghezzi, Valerio; Macale, Loreana; Sili, Alessandro; Alvaro, Rosaria; Palese, Alvisa
Student perceptions of self-efficacy (SE) prevent stress and burnout and improve engagement in nursing education, thus increasing learning outcomes. The study aims were to (1) validate a scale measuring nursing SE in psychomotor skills (NSE-PS), (2) describe changes in NSE-PS over time, and (3) explore NSE-PS correlations with burnout and engagement. A total of 1117 nursing students participated. A significant increase in the NSE-PS scores over the years has emerged; in addition, all NSE-PS dimensions were correlated negatively with burnout and positively with engagement.
JOB, MARTIN O.; KUHAR, MICHAEL J.
2017-01-01
In this study, we reexamined the effect of CART peptide on psychostimulant (PS)-induced locomotor activity (LMA) in individual rats. The Methods utilized were as previously published. The PS-induced LMA was defined as the distance traveled after PS administration (intraperitoneal), and the CART peptide effect was defined as the change in the PS-induced activity after bilateral intra-NAc administration of CART peptide. The experiments included both male and female Sprague-Dawley rats, and varying the CART peptide dose and the PS dose. While the average effect of CART peptide was to inhibit PS-induced LMA, the effect of CART peptide on individual PS treated animals was not always inhibitory and sometimes even produced an increase or no change in PS-induced LMA. Upon further analysis, we observed a linear correlation, reported for the first time, between the magnitude of PS-induced LMA and the CART peptide effect. Because CART peptide inhibits PS-induced LMA when it is large, and increases PS-induced LMA when it is small, the peptide can be considered a homeostatic regulator of dopamine (DA)-induced LMA, which supports our earlier homeostatic hypothesis. PMID:28215744
2015-11-04
Kirtland AFB, NM 87117-5776 10. SPONSOR/MONITOR’S ACRONYM(S) AFRL /RVBYE 11. SPONSOR/MONITOR’S REPORT NUMBER(S) AFRL -RV-PS-TR-2016-0012 12. DISTRIBUTION...DISTRIBUTION LIST DTIC/OCP 8725 John J. Kingman Rd, Suite 0944 Ft Belvoir, VA 22060-6218 1 cy AFRL /RVIL Kirtland AFB, NM 87117-5776 2 cys Official... AFRL -RV-PS- TR-2016-0012 AFRL -RV-PS- TR-2016-0012 TOWARD UNIFIED CORRECTION OF REGIONAL PHASES FOR AMPLITUDE AND TRAVEL TIME EFFECTS
2015-11-04
Kirtland AFB, NM 87117-5776 10. SPONSOR/MONITOR’S ACRONYM(S) AFRL /RVBYE 11. SPONSOR/MONITOR’S REPORT NUMBER(S) AFRL -RV-PS-TR-2016-0012 12. DISTRIBUTION...DISTRIBUTION LIST DTIC/OCP 8725 John J. Kingman Rd, Suite 0944 Ft Belvoir, VA 22060-6218 1 cy AFRL /RVIL Kirtland AFB, NM 87117-5776 2 cys Official... AFRL -RV-PS- TR-2016-0012 AFRL -RV-PS- TR-2016-0012 TOWARD UNIFIED CORRECTION OF REGIONAL PHASES FOR AMPLITUDE AND TRAVEL TIME EFFECTS
The 4 Ps as a Guiding Perspective
ERIC Educational Resources Information Center
Kalsbeek, David H.
2013-01-01
A 4 Ps perspective addresses immediate needs: to help institutions gain traction in their retention strategies by framing and reframing the challenges and the possible responses, by challenging some of the traditional mental models about retention that can distract or dilute those strategies, and by offering focus and coherence to institutional…
Ammonia modification for flotation separation of polycarbonate and polystyrene waste plastics.
Wang, Chong-Qing; Wang, Hui; Gu, Guo-Hua; Lin, Qing-Quan; Zhang, Ling-Ling; Huang, Luo-Luo; Zhao, Jun-Yao
2016-05-01
A promising method, ammonia modification, was developed for flotation separation of polycarbonate (PC) and polystyrene (PS) waste plastics. Ammonia modification has little effect on flotation behavior of PS, while it changes significantly that of PC. The PC recovery in the floated product drops from 100% to 3.17% when modification time is 13min and then rises to 100% after longer modification. The mechanism of ammonia modification was studied by contact angle, and Fourier transform infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS) measurements. Contact angle of PC indicates the decline of PC recovery in the floated product is ascribed to an increase in surface wettability. FT-IR and XPS spectra suggest that ammonia modification causes chemical reactions occurred on PC surface. Flotation behavior of ammonia-modified PC and PS was investigated with respect to flotation time, frother concentration and particle sizes. Flotation separation of PC and PS waste plastics was conducted based on the flotation behavior of single plastic. PC and PS mixtures with different particle sizes are separated efficiently, implying that the technology possesses superior applicability to particle sizes of plastics. The purity of PS and PC is up to 99.53% and 98.21%, respectively, and the recovery of PS and PC is larger than 92.06%. A reliable, cheap and effective process is proposed for separation of PC and PS waste plastics. Copyright © 2016 Elsevier Ltd. All rights reserved.
Ou, Sai-Hong Ignatius; Klempner, Samuel J; Azada, Michele C; Rausei-Mills, Veronica; Duma, Christopher
2015-06-01
Radiation necrosis presenting as pseudoprogression (PsP) is relatively common after radiation and temozolomide (TMZ) treatment in glioblastoma multiforme (GBM), especially among patients with GBM that harbors intrinsic increased responsiveness to TMZ (methylated O6-methylguanine-DNA methyltransferase [MGMT] promoter). Alectinib is a second generation ALK inhibitor that has significant CNS activity against brain metastases in anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) patients. We report 2 ALK+ NSCLC patients who met RECIST criteria for progressive disease by central radiologic review due to increased in size from increased contrast enhancement in previously stereotactically radiated brain metastases with ongoing extra-cranial response to alectinib. In both patients alectinib was started within 4 months of completing stereotactic radiosurgery (SRS). The enlarging lesions in both patients were resected and found to have undergone extensive necrosis with no residual tumor pathologically. PsP was incorrectly classified as progressive disease even by central independent imaging review. Treatment-related necrosis of previously SRS-treated brain metastasis during alectinib treatment can present as PsP. It may be impossible to distinguish PsP from true disease progression without a pathologic examination from resected sample. High degree of clinical suspicion, close monitoring and more sensitive imaging modalities may be needed to distinguish PsP versus progression in radiated brain lesions during alectinib treatment especially if there is no progression extra-cranially. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Gong, Lu; Pan, Xiao; Chen, Haide; Rao, Lingjun; Zeng, Yelin; Hang, Honghui; Peng, Jinrong; Xiao, Lei; Chen, Jun
2016-11-22
Human induced pluripotent stem (iPS) cells have great potential in regenerative medicine, but this depends on the integrity of their genomes. iPS cells have been found to contain a large number of de novo genetic alterations due to DNA damage response during reprogramming. Thus, to maintain the genetic stability of iPS cells is an important goal in iPS cell technology. DNA damage response can trigger tumor suppressor p53 activation, which ensures genome integrity of reprogramming cells by inducing apoptosis and senescence. p53 isoform Δ133p53 is a p53 target gene and functions to not only antagonize p53 mediated apoptosis, but also promote DNA double-strand break (DSB) repair. Here we report that Δ133p53 is induced in reprogramming. Knockdown of Δ133p53 results 2-fold decrease in reprogramming efficiency, 4-fold increase in chromosomal aberrations, whereas overexpression of Δ133p53 with 4 Yamanaka factors showes 4-fold increase in reprogamming efficiency and 2-fold decrease in chromosomal aberrations, compared to those in iPS cells induced only with 4 Yamanaka factors. Overexpression of Δ133p53 can inhibit cell apoptosis and promote DNA DSB repair foci formation during reprogramming. Our finding demonstrates that the overexpression of Δ133p53 not only enhances reprogramming efficiency, but also results better genetic quality in iPS cells.
STIC3 - Silicon Photomultiplier Timing Chip with picosecond resolution
NASA Astrophysics Data System (ADS)
Stankova, Vera; Shen, Wei; Briggl, Konrad; Chen, Huangshan; Fischer, Peter; Gil, Alejandro; Harion, Tobias; Kiworra, Volker; Munwes, Yonathan; Ritzert, Michael; Schultz-Coulon, Hans-Christian
2015-07-01
The diagnostic of pancreas and prostate cancer is a challenging task due to the background noise coming from the closer organs. The EndoToFPET-US project aims to combine the synergy between metabolic and anatomical (ultrasound) image in order to improve the precision in the tumor localization. The goal of the project is to develop a Positron Emission Tomography (PET) system that provides a time-of-flight resolution of 200 ps FWHM for improving the signal to noise ratio and further to improve the medical image quality. In order to achieve this purpose an ASIC has been designed for very high timing resolution in time-of-flight (ToF) applications. In this paper we present the ASIC performance and the first characterization measurements with the 64-channels prototype version (STiC3). Measurements are performed with LYSO scintillator crystal and a Multi Pixel Photon Counter (MPPC). Measurements with the chip show an analog-front-end stage jitter of 35 ps for the first photo-electron equivalent charge and reach 18 ps for the third photo-electron. Coincidence time resolution (CTR) of 240 ps FWHM is measured with 3.1×3.1×15 mm3 LYSO crystal and 50 μm pixel pitch MPPC. Further optimization including the Time-to-Digital Converter (TDC) non-linearity corrections and setup fine tuning are ongoing for achieving the desired CTR of 200 ps FWHM.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kinoshita, Taisuke; Nagamatsu, Go, E-mail: gonag@sc.itc.keio.ac.jp; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012
2011-04-08
Highlights: {yields} iPS cells were induced with a fluorescence monitoring system. {yields} ATM-deficient tail-tip fibroblasts exhibited quite a low reprogramming efficiency. {yields} iPS cells obtained from ATM-deficient cells had pluripotent cell characteristics. {yields} ATM-deficient iPS cells had abnormal chromosomes, which were accumulated in culture. -- Abstract: During cell division, one of the major features of somatic cell reprogramming by defined factors, cells are potentially exposed to DNA damage. Inactivation of the tumor suppressor gene p53 raised reprogramming efficiency but resulted in an increased number of abnormal chromosomes in established iPS cells. Ataxia-telangiectasia mutated (ATM), which is critical in the cellularmore » response to DNA double-strand breaks, may also play an important role during reprogramming. To clarify the function of ATM in somatic cell reprogramming, we investigated reprogramming in ATM-deficient (ATM-KO) tail-tip fibroblasts (TTFs). Although reprogramming efficiency was greatly reduced in ATM-KO TTFs, ATM-KO iPS cells were successfully generated and showed the same proliferation activity as WT iPS cells. ATM-KO iPS cells had a gene expression profile similar to ES cells and WT iPS cells, and had the capacity to differentiate into all three germ layers. On the other hand, ATM-KO iPS cells accumulated abnormal genome structures upon continuous passages. Even with the abnormal karyotype, ATM-KO iPS cells retained pluripotent cell characteristics for at least 20 passages. These data indicate that ATM does participate in the reprogramming process, although its role is not essential.« less
Coexistence of WiFi and WiMAX systems based on PS-request protocols.
Kim, Jongwoo; Park, Suwon; Rhee, Seung Hyong; Choi, Yong-Hoon; Chung, Young-uk; Hwang, Ho Young
2011-01-01
We introduce both the coexistence zone within the WiMAX frame structure and a PS-Request protocol for the coexistence of WiFi and WiMAX systems sharing a frequency band. Because we know that the PS-Request protocol has drawbacks, we propose a revised PS-Request protocol to improve the performance. Two PS-Request protocols are based on the time division operation (TDO) of WiFi system and WiMAX system to avoid the mutual interference, and use the vestigial power management (PwrMgt) bit within the Frame Control field of the frames transmitted by a WiFi AP. The performance of the revised PS-Request protocol is evaluated by computer simulation, and compared to those of the cases without a coexistence protocol and to the original PS-Request protocol.
Coexistence of WiFi and WiMAX Systems Based on PS-Request Protocols†
Kim, Jongwoo; Park, Suwon; Rhee, Seung Hyong; Choi, Yong-Hoon; Chung, Young-uk; Hwang, Ho Young
2011-01-01
We introduce both the coexistence zone within the WiMAX frame structure and a PS-Request protocol for the coexistence of WiFi and WiMAX systems sharing a frequency band. Because we know that the PS-Request protocol has drawbacks, we propose a revised PS-Request protocol to improve the performance. Two PS-Request protocols are based on the time division operation (TDO) of WiFi system and WiMAX system to avoid the mutual interference, and use the vestigial power management (PwrMgt) bit within the Frame Control field of the frames transmitted by a WiFi AP. The performance of the revised PS-Request protocol is evaluated by computer simulation, and compared to those of the cases without a coexistence protocol and to the original PS-Request protocol. PMID:22163721
Fertilization Induces a Transient Exposure of Phosphatidylserine in Mouse Eggs
Curia, Claudio A.; Ernesto, Juan I.; Stein, Paula; Busso, Dolores; Schultz, Richard M.; Cuasnicu, Patricia S.; Cohen, Débora J.
2013-01-01
Phosphatidylserine (PS) is normally localized to the inner leaflet of the plasma membrane and the requirement of PS translocation to the outer leaflet in cellular processes other than apoptosis has been demonstrated recently. In this work we investigated the occurrence of PS mobilization in mouse eggs, which express flippase Atp8a1 and scramblases Plscr1 and 3, as determined by RT-PCR; these enzyme are responsible for PS distribution in cell membranes. We find a dramatic increase in binding of flouresceinated-Annexin-V, which specifically binds to PS, following fertilization or parthenogenetic activation induced by SrCl2 treatment. This increase was not observed when eggs were first treated with BAPTA-AM, indicating that an increase in intracellular Ca2+ concentration was required for PS exposure. Fluorescence was observed over the entire egg surface with the exception of the regions overlying the meiotic spindle and sperm entry site. PS exposure was also observed in activated eggs obtained from CaMKIIγ null females, which are unable to exit metaphase II arrest despite displaying Ca2+ spikes. In contrast, PS exposure was not observed in TPEN-activated eggs, which exit metaphase II arrest in the absence of Ca2+ release. PS exposure was also observed when eggs were activated with ethanol but not with a Ca2+ ionophore, suggesting that the Ca2+ source and concentration are relevant for PS exposure. Last, treatment with cytochalasin D, which disrupts microfilaments, or jasplakinolide, which stabilizes microfilaments, prior to egg activation showed that PS externalization is an actin-dependent process. Thus, the Ca2+ rise during egg activation results in a transient exposure of PS in fertilized eggs that is not associated with apoptosis. PMID:23951277
Plastic scintillation detectors for precision Time-of-Flight measurements of relativistic heavy ions
NASA Astrophysics Data System (ADS)
Lin, Wen-Jian; Zhao, Jian-Wei; Sun, Bao-Hua; He, Liu-Chun; Lin, Wei-Ping; Liu, Chuan-Ye; Tanihata, Isao; Terashima, Satoru; Tian, Yi; Wang, Feng; Wang, Meng; Zhang, Guang-Xin; Zhang, Xue-Heng; Zhu, Li-Hua; Duan, Li-Min; Hu, Rong-Jiang; Liu, Zhong; Lu, Chen-Gui; Ren, Pei-Pei; Sheng, Li-Na; Sun, Zhi-Yu; Wang, Shi-Tao; Wang, Tao-Feng; Xu, Zhi-Guo; Zheng, Yong
2017-06-01
Plastic scintillation detectors for Time-of-Flight (TOF) measurements are almost essential for event-by-event identification of relativistic rare isotopes. In this work, a pair of plastic scintillation detectors of dimensions 50 × 50 × 3t mm3 and 80 × 100 × 3t mm3 have been set up at the External Target Facility (ETF), Institute of Modern Physics (IMP). Their time, energy and position responses are measured with the 18O primary beam at 400 MeV/nucleon. After off-line corrections for walk effect and position, the time resolutions of the two detectors are determined to be 27 ps (σ) and 36 ps (σ), respectively. Both detectors have nearly the same energy resolution of 3.1% (σ) and position resolution of about 3.4 mm (σ). The detectors have been used successfully in nuclear reaction cross section measurements, and will be be employed for upgrading the RIBLL2 beam line at IMP as well as for the high energy branch at HIAF. Supported by National Natural Science Foundation of China (11475014,11235002) and National Key Research and Development Program (2016YFA0400500)
Zhang, Ju; Shi, Ruona; Li, Haifeng; Xiang, Yanxia; Xiao, Lingyun; Hu, Minghua; Ma, Fangli; Ma, Chung Wah; Huang, Zebo
2016-11-04
Dictyophora indusiata is a medicinal mushroom traditionally used in China for a variety of conditions, including inflammatory and neural diseases. D. indusiata polysaccharides (DiPS) are shown to have in vitro antioxidant activity but in vivo evidence is lacking. This study aimes to explore the antioxidant capacity and related neuroptotective activities of DiPS using wild-type and neurodegenerative Caenorhabditis elegans models. The antioxidant capacities of DiPS were first determined using paraquat survival and Pgst-4::GFP expression assays in wild-type and transgenic C. elegans models, respectively, and then further investigated by determining reactive oxygen species (ROS) level, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity as well as functional parameters of mitochondria. The activation of stress response transcription factors and neuroptotective activities were examined using nuclear localization and chemosensory behavioral assays in transgenic nematodes, respectively. DiPS was shown not only to increase survival rate and reduce stress level under paraquat-induced oxidative conditions but also to decrease ROS and MDA levels and increase SOD activity in C. elegans models. Moreover, DiPS was also able to restore the functional parameters of mitochondria, including membrane potential and ATP content, in paraquat-stressed nematodes. In addition, nuclear translocation assays demonstrate that the stress response transcription factor DAF-16/FOXO was involved in the antioxidant activity of the polysaccharide. Further experiments reveal that DiPS was capable of reducing ROS levels and alleviating chemosensory behavior dysfunction in transgenic nematode models of neurodegenerative diseases mediated by polyglutamine and amyloid-β protein. These findings demonstrate the antioxidant and neuroprotective activities of the D. indusiata polysaccharide DiPS in wild-type and neurodegenerative C. elegans models, and thus provide an important pharmacological basis for the therapeutic potential of D. indusiata in neurodegeneration. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Ramakrishnan, Radha; Balu-Iyer, Sathy V
2016-10-01
A major complication in the replacement therapy of Factor VIII (FVIII) for Hemophilia A is the development of unwanted immune responses. Previous studies from our laboratory have shown that pretreatment of FVIII in the presence of phosphatidylserine (PS) resulted in hyporesponsiveness to subsequent administration of FVIII alone, due to the ability of PS to convert an immunogen to a tolerogen. We investigated the importance of biophysical properties of PS liposomes on its ability to convert an immunogen to a tolerogen. PS particles were prepared differing in size, protein-lipid topology, lamellarity, and % association to FVIII keeping the composition of the particle same. PS particles were prepared in 2 different sizes with differing biophysical properties: smaller particles in the nanometer range (200 nm) and larger size particles in the micron range (2 μm). Hemophilia A animals treated with both the nanometer and micron size PS particles showed a significant reduction in anti-FVIII antibody titers when compared to animals receiving free FVIII alone. Upon rechallenge with free FVIII animals that received FVIII along with the nanometer size particle continued to show reduced antibody responses. Animals receiving the micron size particle showed a slight increase in titers although they remained significantly lower than the free FVIII treated group. Upon culture with bone marrow derived dendritic cells, the nanometer size particle showed a reduction in CD40 expression and an increase in transforming growth factor-β cytokine production, which was not observed with the micron size particle. These results show that biophysical properties of PS play an important role in tolerance. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Paul, Rituparna; Karabiyik, Ufuk; Swift, Michael C; Hottle, John R; Esker, Alan R
2008-05-06
Morphological evolution in dewetting thin film bilayers of polystyrene (PS) and a polyhedral oligomeric silsesquioxane (POSS), trisilanolphenyl-POSS (TPP), was studied as a function of annealing temperature and annealing time. The results demonstrate unique dewetting morphologies in PS/TPP bilayers at elevated temperatures that are significantly different from those typically observed in dewetting polymer/polymer bilayers. During temperature ramp studies by optical microscopy (OM) in the reflection mode, PS/TPP bilayers form cracks with a weak optical contrast at approximately 130 degrees C. The crack formation is attributed to tensile stresses within the upper TPP layer. The weak optical contrast of the cracks observed in the bilayers for annealing temperatures below approximately 160 degrees C is consistent with the cracking and dewetting of only the upper TPP layer from the underlying PS layer. The optical contrast of the morphological features is significantly enhanced at annealing temperatures of >160 degrees C. This observation suggests dewetting of both the upper TPP and the lower PS layers that results in the exposure of the silicon substrate. Upon annealing the PS/TPP bilayers at 200 degrees C in a temperature jump experiment, the upper TPP layer undergoes instantaneous cracking as observed by OM. These cracks in the upper TPP layer serve as nucleation sites for rapid dewetting and aggregation of the TPP layer, as revealed by OM and atomic force microscopy (AFM). X-ray photoelectron spectroscopy (XPS) results indicated that dewetting of the lower PS layer ensued for annealing times >5 min and progressed up to 90 min. For annealing times >90 min, OM, AFM, and XPS results revealed complete dewetting of both the layers with the formation of TPP encapsulated PS droplets.
ARSRP Signal Processing Software
1993-02-01
Hardcopy of plot? Y or N : Y Enter name of postscript output file. : wave2 .ps Postscript file created. Another plot? Y or N :N 19 The two plots...created and stored in wavel.ps and wave2 .ps are shown in Figures 4 and 5 with the corresponding MSS real- time plots from the ARSRP Monitoring Support
Pijuan-Galitó, Sara; Tamm, Christoffer; Schuster, Jens; Sobol, Maria; Forsberg, Lars; Merry, Catherine L. R.; Annerén, Cecilia
2016-01-01
Reliable, scalable and time-efficient culture methods are required to fully realize the clinical and industrial applications of human pluripotent stem (hPS) cells. Here we present a completely defined, xeno-free medium that supports long-term propagation of hPS cells on uncoated tissue culture plastic. The medium consists of the Essential 8 (E8) formulation supplemented with inter-α-inhibitor (IαI), a human serum-derived protein, recently demonstrated to activate key pluripotency pathways in mouse PS cells. IαI efficiently induces attachment and long-term growth of both embryonic and induced hPS cell lines when added as a soluble protein to the medium at seeding. IαI supplementation efficiently supports adaptation of feeder-dependent hPS cells to xeno-free conditions, clonal growth as well as single-cell survival in the absence of Rho-associated kinase inhibitor (ROCKi). This time-efficient and simplified culture method paves the way for large-scale, high-throughput hPS cell culture, and will be valuable for both basic research and commercial applications. PMID:27405751
Clough, S; Shehabi, Z; Morgan, C
2016-02-12
Medical risk assessment is essential to safe patient management and the delivery of appropriate dental care. The American Society of Anesthesiologists Physical Status (ASA PS) Classification is widely used within medicine and dentistry, but has received significant criticism. This is the first UK survey to assess the consistency of medical risk assessment in dentistry. (i) To determine the use and consistency of the ASA PS among dentists and anaesthetists. (ii) To consider the appropriateness of the ASA PS in relation to dental treatment planning and delivery of care. A cross-sectional online questionnaire was distributed to anaesthetists and dental practitioners in general practice, community and hospital dental services. Questions focused on professional backgrounds, use of the ASA PS, alternative approaches to risk assessment in everyday practice and scoring of eight hypothetical patients using ASA PS. There were 101 responses, 82 were complete. Anaesthetists recorded ASA PS score more frequently than dental practitioners and found it more useful. Inconsistencies were evident in the assignment of ASA PS scores both between and within professional groups. Many dental practitioners did not use or find ASA PS helpful, with significant inconsistencies in its use. An awareness of alternative assessment scales may be useful across settings. Accepting its limitations, it would be helpful for all dentists to be educated in ASA PS and its use in medical risk assessment, particularly in relation to conscious sedation.
Song, Dong-Po; Wang, Xinyu; Lin, Ying; Watkins, James J
2014-11-06
We demonstrate the facile synthesis of gold nanoparticles (GNPs) functionalized by UV-responsive block copolymer ligands, poly(styrene)-b-poly(o-nitrobenzene acrylate)-SH (PS-b-PNBA-SH), followed by their targeted distribution within a lamellae-forming poly(styrene)-b-poly(2-vinylpyridine) (PS-b-P2VP) block copolymer. The multilayer, micelle-like structure of the GNPs consists of a gold core, an inner PNBA layer, and an outer PS layer. The UV-sensitive PNBA segment can be deprotected into a layer containing poly(acrylic acid) (PAA) when exposed to UV light at 365 nm, which enables the simple and precise tuning of GNP surface properties from hydrophobic to amphiphilic. The GNPs bearing ligands of different chemical compositions were successfully and selectively incorporated into the PS-b-P2VP block copolymer, and UV light showed a profound influence on the spatial distributions of GNPs. Prior to UV exposure, GNPs partition along the interfaces of PS and P2VP domains, while the UV-treated GNPs are incorporated into P2VP domains as a result of hydrogen bond interactions between PAA on the gold surface and P2VP domains. This provides an easy way of controlling the arrangement of nanoparticles in polymer matrices by tailoring the nanoparticle surface using UV light.
Wagner, Travis P
2013-03-01
Increasingly, Extended Producer Responsibility (EPR) and Product Stewardship (PS) frameworks are being adopted as a preferred policy approach to promote cost-effective diversion and recovery of post-consumer solid waste. Because the application of EPR/PS generally requires the creation of a separate and often parallel collection and/or management system, key to increasing the amount of waste recovered is to maximize the convenience of the collection system to maximize consumer participation. Convenient collection is often mandated in EPR/PS laws, however it is not defined. Convenience is a subjective construct rendering it extremely difficult to define. However, based on a dissection of post-consumer collection efforts under a generic EPR/PS system, this paper identifies and examines five categories of convenience - knowledge requirements, proximity to a collection site, opportunity to drop-off materials, the draw of the collection site, and the ease of the process-and the various factors of convenience within each of these categories. By using a simplified multiple criteria decision analysis, this paper proposes a performance matrix of criteria of convenience. Stakeholders can use this matrix to assist in the design, assessment, and/or implementation of a convenient post-consumer collection system under an EPR/PS framework. Copyright © 2012 Elsevier Ltd. All rights reserved.
Sanda, Satoko; Yoshida, Kazuo; Kuwano, Masayoshi; Kawamura, Tadayuki; Munekage, Yuri Nakajima; Akashi, Kinya; Yokota, Akiho
2011-07-01
In plants, drought stress coupled with high levels of illumination causes not only dehydration of tissues, but also oxidative damage resulting from excess absorbed light energy. In this study, we analyzed the regulation of electron transport under drought/high-light stress conditions in wild watermelon, a xerophyte that shows strong resistance to this type of stress. Under drought/high-light conditions that completely suppressed CO(2) fixation, the linear electron flow was diminished between photosystem (PS) II and PS I, there was no photoinhibitory damage to PS II and PS I and no decrease in the abundance of the two PSs. Proteome analyses revealed changes in the abundance of protein spots representing the Rieske-type iron-sulfur protein (ISP) and I and K subunits of NAD(P)H dehydrogenase in response to drought stress. Two-dimensional electrophoresis and immunoblot analyses revealed new ISP protein spots with more acidic isoelectric points in plants under drought stress. Our findings suggest that the modified ISPs depress the linear electron transport activity under stress conditions to protect PS I from photoinhibition. The qualitative changes in photosynthetic proteins may switch the photosynthetic electron transport from normal photosynthesis mode to stress-tolerance mode. Copyright © Physiologia Plantarum 2011.
High speed cross-amplitude modulation in concatenated SOA-EAM-SOA.
Cleary, Ciaran S; Manning, Robert J
2012-06-18
We observe a near-ideal high speed amplitude impulse response in an SOA-EAM-SOA configuration under optimum conditions. Full amplitude recovery times as low as 10 ps with modulation depths of 70% were observed in pump-probe measurements. System behavior could be controlled by the choice of signal wavelength, SOA current biases and EAM reverse bias voltages. Experimental data and impulse response modelling indicated that the slow tail in the gain response of first SOA was negated by a combination of cross-absorption modulation between pump and modulated CW probe, and self-gain modulation of the modulated CW probe in both the EAM and second SOA.
Wang, Lixiu; Bi, Yayan; Yu, Muxin; Li, Tao; Tong, Dongxia; Yang, Xiaoyan; Zhang, Cong; Guo, Li; Wang, Chunxu; Kou, Yan; Dong, Zengxiang; Novakovic, Valerie A; Tian, Ye; Kou, Junjie; Shammas, Masood A; Shi, Jialan
2018-05-01
The definitive role of phosphatidylserine (PS) in the prothrombotic state of non-valvular atrial fibrillation (NVAF) remains unclear. Our objectives were to study the PS exposure on blood cells and microparticles (MPs) in NVAF, and evaluate their procoagulant activity (PCA). NVAF patients without (n = 60) and with left atrial thrombi (n = 18) and controls (n = 36) were included in our study. Exposed PS was analyzed with flow cytometry and confocal microscopy. PCA was evaluated using clotting time, factor Xa (FXa), thrombin and fibrin formation. PS + blood cells and MPs were significantly higher in NVAF patients without and with left atrial thrombi (both P < 0.01) than in controls. Patients with left atrial thrombi showed increased PS + platelets, neutrophils, erythrocytes and MPs compared with patients without thrombi (all P < 0.05). Moreover, in patients with left atrial thrombi, MPs primarily originated from platelets (56.1%) followed by leukocytes (21.9%, including MPs from neutrophils, monocytes and lymphocytes), erythrocytes (12.2%) and endothelial cells (8.9%). Additionally, PS + blood cells and MPs contributed to markedly shortened coagulation time and dramatically increased FXa/thrombin/fibrin (all P < 0.001) generation in both NVAF groups. Furthermore, blockade of exposed PS on blood cells and MPs with lactadherin inhibited PCA by approximately 80%. Lastly, we found that the amount of PS + platelets and MPs was positively correlated with thrombus diameter (all p < 0.005). Our results suggest that exposed PS on blood cells and MPs play a procoagulant role in NVAF patients. Blockade of PS prior to thrombus formation might be a novel therapeutic approach in these patients. Copyright © 2018 Elsevier B.V. All rights reserved.
Sasahira, Naoki; Hamada, Tsuyoshi; Togawa, Osamu; Yamamoto, Ryuichi; Iwai, Tomohisa; Tamada, Kiichi; Kawaguchi, Yoshiaki; Shimura, Kenji; Koike, Takero; Yoshida, Yu; Sugimori, Kazuya; Ryozawa, Shomei; Kakimoto, Toshiharu; Nishikawa, Ko; Kitamura, Katsuya; Imamura, Tsunao; Mizuide, Masafumi; Toda, Nobuo; Maetani, Iruru; Sakai, Yuji; Itoi, Takao; Nagahama, Masatsugu; Nakai, Yousuke; Isayama, Hiroyuki
2016-01-01
AIM: To determine the optimal method of endoscopic preoperative biliary drainage for malignant distal biliary obstruction. METHODS: Multicenter retrospective study was conducted in patients who underwent plastic stent (PS) or nasobiliary catheter (NBC) placement for resectable malignant distal biliary obstruction followed by surgery between January 2010 and March 2012. Procedure-related adverse events, stent/catheter dysfunction (occlusion or migration of PS/NBC, development of cholangitis, or other conditions that required repeat endoscopic biliary intervention), and jaundice resolution (bilirubin level < 3.0 mg/dL) were evaluated. Cumulative incidence of jaundice resolution and dysfunction of PS/NBC were estimated using competing risk analysis. Patient characteristics and preoperative biliary drainage were also evaluated for association with the time to jaundice resolution and PS/NBC dysfunction using competing risk regression analysis. RESULTS: In total, 419 patients were included in the study (PS, 253 and NBC, 166). Primary cancers included pancreatic cancer in 194 patients (46%), bile duct cancer in 172 (41%), gallbladder cancer in three (1%), and ampullary cancer in 50 (12%). The median serum total bilirubin was 7.8 mg/dL and 324 patients (77%) had ≥ 3.0 mg/dL. During the median time to surgery of 29 d [interquartile range (IQR), 30-39 d]. PS/NBC dysfunction rate was 35% for PS and 18% for NBC [Subdistribution hazard ratio (SHR) = 4.76; 95%CI: 2.44-10.0, P < 0.001]; the pig-tailed tip was a risk factor for PS dysfunction. Jaundice resolution was achieved in 85% of patients and did not depend on the drainage method (PS or NBC). CONCLUSION: PS has insufficient patency for preoperative biliary drainage. Given the drawbacks of external drainage via NBC, an alternative method of internal drainage should be explored. PMID:27076764
USDA-ARS?s Scientific Manuscript database
S100 calcium-binding protein A8 (S100A8) and S100 calcium-binding protein A9 (S100A9) are pivotal mediators of inflammatory and protective anti-infection responses for the mammalian host. In this study, we present the molecular cloning of porcine S100A8 (pS100A8) and porcine S100A9 (pS100A9). Both ...
Time-resolved x-ray spectra from laser-generated high-density plasmas
NASA Astrophysics Data System (ADS)
Andiel, U.; Eidmann, Klaus; Witte, Klaus-Juergen
2001-04-01
We focused frequency doubled ultra short laser pulses on solid C, F, Na and Al targets, K-shell emission was systematically investigated by time resolved spectroscopy using a sub-ps streak camera. A large number of laser shots can be accumulated when triggering the camera with an Auston switch system at very high temporal precision. The system provides an outstanding time resolution of 1.7ps accumulating thousands of laser shots. The time duration of the He-(alpha) K-shell resonance lines was observed in the range of (2-4)ps and shows a decrease with the atomic number. The experimental results are well reproduced by hydro code simulations post processed with an atomic kinetics code.
Comparative genome analysis of non-toxigenic non-O1 versus toxigenic O1 Vibrio cholerae
Mukherjee, Munmun; Kakarla, Prathusha; Kumar, Sanath; Gonzalez, Esmeralda; Floyd, Jared T.; Inupakutika, Madhuri; Devireddy, Amith Reddy; Tirrell, Selena R.; Bruns, Merissa; He, Guixin; Lindquist, Ingrid E.; Sundararajan, Anitha; Schilkey, Faye D.; Mudge, Joann; Varela, Manuel F.
2015-01-01
Pathogenic strains of Vibrio cholerae are responsible for endemic and pandemic outbreaks of the disease cholera. The complete toxigenic mechanisms underlying virulence in Vibrio strains are poorly understood. The hypothesis of this work was that virulent versus non-virulent strains of V. cholerae harbor distinctive genomic elements that encode virulence. The purpose of this study was to elucidate genomic differences between the O1 serotypes and non-O1 V. cholerae PS15, a non-toxigenic strain, in order to identify novel genes potentially responsible for virulence. In this study, we compared the whole genome of the non-O1 PS15 strain to the whole genomes of toxigenic serotypes at the phylogenetic level, and found that the PS15 genome was distantly related to those of toxigenic V. cholerae. Thus we focused on a detailed gene comparison between PS15 and the distantly related O1 V. cholerae N16961. Based on sequence alignment we tentatively assigned chromosome numbers 1 and 2 to elements within the genome of non-O1 V. cholerae PS15. Further, we found that PS15 and O1 V. cholerae N16961 shared 98% identity and 766 genes, but of the genes present in N16961 that were missing in the non-O1 V. cholerae PS15 genome, 56 were predicted to encode not only for virulence–related genes (colonization, antimicrobial resistance, and regulation of persister cells) but also genes involved in the metabolic biosynthesis of lipids, nucleosides and sulfur compounds. Additionally, we found 113 genes unique to PS15 that were predicted to encode other properties related to virulence, disease, defense, membrane transport, and DNA metabolism. Here, we identified distinctive and novel genomic elements between O1 and non-O1 V. cholerae genomes as potential virulence factors and, thus, targets for future therapeutics. Modulation of such novel targets may eventually enhance eradication efforts of endemic and pandemic disease cholera in afflicted nations. PMID:25722857
Comparative genome analysis of non-toxigenic non-O1 versus toxigenic O1 Vibrio cholerae.
Mukherjee, Munmun; Kakarla, Prathusha; Kumar, Sanath; Gonzalez, Esmeralda; Floyd, Jared T; Inupakutika, Madhuri; Devireddy, Amith Reddy; Tirrell, Selena R; Bruns, Merissa; He, Guixin; Lindquist, Ingrid E; Sundararajan, Anitha; Schilkey, Faye D; Mudge, Joann; Varela, Manuel F
Pathogenic strains of Vibrio cholerae are responsible for endemic and pandemic outbreaks of the disease cholera. The complete toxigenic mechanisms underlying virulence in Vibrio strains are poorly understood. The hypothesis of this work was that virulent versus non-virulent strains of V. cholerae harbor distinctive genomic elements that encode virulence. The purpose of this study was to elucidate genomic differences between the O1 serotypes and non-O1 V. cholerae PS15, a non-toxigenic strain, in order to identify novel genes potentially responsible for virulence. In this study, we compared the whole genome of the non-O1 PS15 strain to the whole genomes of toxigenic serotypes at the phylogenetic level, and found that the PS15 genome was distantly related to those of toxigenic V. cholerae . Thus we focused on a detailed gene comparison between PS15 and the distantly related O1 V. cholerae N16961. Based on sequence alignment we tentatively assigned chromosome numbers 1 and 2 to elements within the genome of non-O1 V. cholerae PS15. Further, we found that PS15 and O1 V. cholerae N16961 shared 98% identity and 766 genes, but of the genes present in N16961 that were missing in the non-O1 V. cholerae PS15 genome, 56 were predicted to encode not only for virulence-related genes (colonization, antimicrobial resistance, and regulation of persister cells) but also genes involved in the metabolic biosynthesis of lipids, nucleosides and sulfur compounds. Additionally, we found 113 genes unique to PS15 that were predicted to encode other properties related to virulence, disease, defense, membrane transport, and DNA metabolism. Here, we identified distinctive and novel genomic elements between O1 and non-O1 V. cholerae genomes as potential virulence factors and, thus, targets for future therapeutics. Modulation of such novel targets may eventually enhance eradication efforts of endemic and pandemic disease cholera in afflicted nations.
Zero-valent aluminum-mediated degradation of Bisphenol A in the presence of common oxidants.
Arslan-Alaton, I; Olmez-Hanci, T; Dogan, M; Ozturk, T
2017-11-01
The use of a commercial, nano-scale zero-valent aluminum (ZVA) powder was explored for the treatment of aqueous Bisphenol A (BPA). The study focused on the (i) activation of hydrogen peroxide (HP) and persulfate (PS) oxidants with ZVA to accelerate BPA degradation, (ii) comparison of the treatment performance in pure and real surface water (SW) samples, (iii) effects on toxicity and (iv) reuse potential of ZVA nanoparticles after ZVA/HP and ZVA/PS treatments. In pure water, ZVA coupled with HP or PS provided an effective means of BPA treatment particularly when PS was employed as the oxidant. On the other hand, in BPA-spiked SW, the ZVA/HP treatment combination outperformed ZVA/PS oxidation in terms of BPA removal, whereas ZVA/PS oxidation was superior in terms of organic carbon removal. According to the bioassays conducted in pure and real SW samples with the marine photobacteria Vibrio fischeri and the freshwater microalgae Pseudokirchneriella subcapitata, the toxicity response of BPA and its oxidation products was sensitive to the test organism and water matrix. The inhibitory effect of the reaction solution increased at the early stages of ZVA/PS treatment. The reuse potential of the ZVA/HP treatment system was higher than that of the ZVA/PS treatment system.
Ke, Hua; Li, Zhan-Kui; Yu, Xi-Ping; Guo, Jin-Zhen
2016-05-01
To study the efficacy of different preparations of budesonide combined with pulmonary surfactant (PS) in improving blood gas levels and preventing bronchopulmonary dysplasia (BPD) in preterm infants with neonatal respiratory distress syndrome (NRDS). A total of 184 preterm infants who developed NRDS within 4 hours after birth were randomly administered with PS + continuous inhalation of budesonide aerosol (continuous aerosol group), PS+budesonide solution (solution group), PS + single inhalation of budesonide aerosol (single aerosol group), and PS alone, with 46 neonates in each group. The changes in arterial blood gas levels, rate of invasive mechanical ventilation after treatment, time of assisted ventilation, rate of repeated use of PS, and the incidence of BPD were compared between the four groups. On the 2nd to 4th day after treatment, pH, PCO2, and oxygenation index (FiO2/PaO2) showed significant differences among the four groups, and the continuous aerosol group showed the most improvements of all indicators, followed by the solution group, single aerosol group, and PS alone group. The continuous aerosol group had a significantly shorter time of assisted ventilation than the other three groups (P<0.05). The solution group had a significantly shorter time of assisted ventilation than the single aerosol and PS alone groups (P<0.05). The rate of invasive mechanical ventilation after treatment, rate of repeated use of PS, and incidence of BPD showed significant differences among the four groups (P<0.05), and the continuous aerosol group had the lowest rates, followed by the solution group. A combination of PS and continuous inhalation of budesonide aerosol has a better efficacy in the treatment of NRDS than a combination of PS and budesonide solution. The difference in reducing the incidence of BDP between the two administration methods awaits further investigation with a larger sample size.
Superior piezoelectric composite films: taking advantage of carbon nanomaterials.
Saber, Nasser; Araby, Sherif; Meng, Qingshi; Hsu, Hung-Yao; Yan, Cheng; Azari, Sara; Lee, Sang-Heon; Xu, Yanan; Ma, Jun; Yu, Sirong
2014-01-31
Piezoelectric composites comprising an active phase of ferroelectric ceramic and a polymer matrix have recently found numerous sensory applications. However, it remains a major challenge to further improve their electromechanical response for advanced applications such as precision control and monitoring systems. We here investigated the incorporation of graphene platelets (GnPs) and multi-walled carbon nanotubes (MWNTs), each with various weight fractions, into PZT (lead zirconate titanate)/epoxy composites to produce three-phase nanocomposites. The nanocomposite films show markedly improved piezoelectric coefficients and electromechanical responses (50%) besides an enhancement of ~200% in stiffness. The carbon nanomaterials strengthened the impact of electric field on the PZT particles by appropriately raising the electrical conductivity of the epoxy. GnPs have been proved to be far more promising in improving the poling behavior and dynamic response than MWNTs. The superior dynamic sensitivity of GnP-reinforced composite may be caused by the GnPs' high load transfer efficiency arising from their two-dimensional geometry and good compatibility with the matrix. The reduced acoustic impedance mismatch resulting from the improved thermal conductance may also contribute to the higher sensitivity of GnP-reinforced composite. This research pointed out the potential of employing GnPs to develop highly sensitive piezoelectric composites for sensing applications.
Likelihood-based methods for evaluating principal surrogacy in augmented vaccine trials.
Liu, Wei; Zhang, Bo; Zhang, Hui; Zhang, Zhiwei
2017-04-01
There is growing interest in assessing immune biomarkers, which are quick to measure and potentially predictive of long-term efficacy, as surrogate endpoints in randomized, placebo-controlled vaccine trials. This can be done under a principal stratification approach, with principal strata defined using a subject's potential immune responses to vaccine and placebo (the latter may be assumed to be zero). In this context, principal surrogacy refers to the extent to which vaccine efficacy varies across principal strata. Because a placebo recipient's potential immune response to vaccine is unobserved in a standard vaccine trial, augmented vaccine trials have been proposed to produce the information needed to evaluate principal surrogacy. This article reviews existing methods based on an estimated likelihood and a pseudo-score (PS) and proposes two new methods based on a semiparametric likelihood (SL) and a pseudo-likelihood (PL), for analyzing augmented vaccine trials. Unlike the PS method, the SL method does not require a model for missingness, which can be advantageous when immune response data are missing by happenstance. The SL method is shown to be asymptotically efficient, and it performs similarly to the PS and PL methods in simulation experiments. The PL method appears to have a computational advantage over the PS and SL methods.
NASA Astrophysics Data System (ADS)
Farag, O. F.
2018-06-01
Polystyrene-copper (PS-Cu) nanocomposite films were treated with DC N2 plasma and gamma rays irradiations. The plasma treatment of PS-Cu film surface was carried out at different treatment times, gas pressure 0.4 Torr and the applied power 3.5 W. On the other hand, the treatment with gamma rays irradiation were carried out at irradiation doses 10, 30 and 50 kGy. The induced changes in surface properties of PS-Cu films were investigated with UV-viss spectroscopy, scanning electron microscopy (SEM) and FTIR spectroscopy techniques. In addition, the wettability property, surface free energy, spreading coefficient and surface roughness of the treated samples were studied by measuring the contact angle. The UV-viss spectroscopy analysis revealed that the optical band gap decreases with increasing the treatment time and the irradiation dose for plasma and gamma treatments, respectively. SEM observations showed that the particle size of copper particles was increased with increasing the treatment time and the irradiation dose, but gamma treatment changes the copper particles size from nano scale to micro scale. The contact angle measurements showing that the wettability property, surface free energy, spreading coefficient and surface roughness of the treated PS-Cu samples were increased remarkably with increasing the treatment time and the irradiation dose for plasma and gamma treatments, respectively. The contact angle, surface free energy, spreading coefficient and surface roughness of the treated PS-Cu samples are more influenced by plasma treatment than gamma treatment.
NASA Astrophysics Data System (ADS)
Tamborini, D.; Portaluppi, D.; Villa, F.; Tisa, S.; Tosi, A.
2014-11-01
We present a Time-to-Digital Converter (TDC) card with a compact form factor, suitable for multichannel timing instruments or for integration into more complex systems. The TDC Card provides 10 ps timing resolution over the whole measurement range, which is selectable from 160 ns up to 10 μs, reaching 21 ps rms precision, 1.25% LSB rms differential nonlinearity, up to 3 Mconversion/s with 400 mW power consumption. The I/O edge card connector provides timing data readout through either a parallel bus or a 100 MHz serial interface and further measurement information like input signal rate and valid conversion rate (typically useful for time-correlated single-photon counting application) through an independent serial link.
Tamborini, D; Portaluppi, D; Villa, F; Tisa, S; Tosi, A
2014-11-01
We present a Time-to-Digital Converter (TDC) card with a compact form factor, suitable for multichannel timing instruments or for integration into more complex systems. The TDC Card provides 10 ps timing resolution over the whole measurement range, which is selectable from 160 ns up to 10 μs, reaching 21 ps rms precision, 1.25% LSB rms differential nonlinearity, up to 3 Mconversion/s with 400 mW power consumption. The I/O edge card connector provides timing data readout through either a parallel bus or a 100 MHz serial interface and further measurement information like input signal rate and valid conversion rate (typically useful for time-correlated single-photon counting application) through an independent serial link.
Investigation on the structural characterization of pulsed p-type porous silicon
NASA Astrophysics Data System (ADS)
Wahab, N. H. Abd; Rahim, A. F. Abd; Mahmood, A.; Yusof, Y.
2017-08-01
P-type Porous silicon (PS) was sucessfully formed by using an electrochemical pulse etching (PC) and conventional direct current (DC) etching techniques. The PS was etched in the Hydrofluoric (HF) based solution at a current density of J = 10 mA/cm2 for 30 minutes from a crystalline silicon wafer with (100) orientation. For the PC process, the current was supplied through a pulse generator with 14 ms cycle time (T) with 10 ms on time (Ton) and pause time (Toff) of 4 ms respectively. FESEM, EDX, AFM, and XRD have been used to characterize the morphological properties of the PS. FESEM images showed that pulse PS (PPC) sample produces more uniform circular structures with estimated average pore sizes of 42.14 nm compared to DC porous (PDC) sample with estimated average size of 16.37nm respectively. The EDX spectrum for both samples showed higher Si content with minimal presence of oxide.
Transactivation domain of p53 regulates DNA repair and integrity in human iPS cells.
Kannappan, Ramaswamy; Mattapally, Saidulu; Wagle, Pooja A; Zhang, Jianyi
2018-05-18
The role of p53 transactivation domain (p53-TAD), a multifunctional and dynamic domain, on DNA repair and retaining DNA integrity in human iPS cells has never been studied. p53-TAD was knocked out in iPS cells using CRISPR/Cas9 and was confirmed by DNA sequencing. p53-TAD KO cells were characterized by: accelerated proliferation, decreased population doubling time, and unaltered Bcl2, BBC3, IGF1R, Bax and altered Mdm2, p21, and PIDD transcripts expression. In p53-TAD KO cells p53 regulated DNA repair proteins XPA, DNA polH and DDB2 expression were found to be reduced compared to p53-WT cells. Exposure to low dose of doxorubicin (Doxo) induced similar DNA damage and DNA damage response (DDR) measured by RAD50 and MRE11 expression, Checkpoint kinase 2 activation and γH2A.X recruitment at DNA strand breaks in both the cell groups indicating silencing p53-TAD do not affect DDR mechanism upstream of p53. Following removal of Doxo p53-WT hiPS cells underwent DNA repair, corrected their damaged DNA and restored DNA integrity. Conversely, p53-TAD KO hiPS cells did not undergo complete DNA repair and failed to restore DNA integrity. More importantly continuous culture of p53-TAD KO hiPS cells underwent G2/M cell cycle arrest and expressed cellular senescent marker p16 INK4a . Our data clearly shows that silencing transactivation domain of p53 did not affect DDR but affected the DNA repair process implying the crucial role of p53 transactivation domain in maintaining DNA integrity. Therefore, activating p53-TAD domain using small molecules may promote DNA repair and integrity of cells and prevent senescence.
Alberts, David S.; Liu, P. Y.; Wilczynski, Sharon P.; Clouser, Mary C.; Lopez, Ana Maria; Michelin, David P.; Lanzotti, Victor J.; Markman, Maurie
2008-01-01
Objective Because debate continues over the role of combination, platinum-based chemotherapy for platinum sensitive (PS), recurrent ovarian cancer (OC), we compared overall survival (OS), progression-free survival (PFS), confirmed complete response rate and time to treatment failure in this population. Methods Patients with recurrent stage III or IV OC, a progression-free and platinum-free interval of 6- 24 months after first-line platinum-based chemotherapy and up to 12 courses of a non-platinum containing consolidation treatment were eligible. Patients were randomized to IV pegylated liposomal doxorubicin (PLD) (30 mg/m2) plus IV carboplatin (AUC=5 mg/mL × min) once every 4 weeks (PLD arm) or IV carboplatin alone (AUC=5mg/mL × min) once every 4 weeks. Results The PLD arm enrolled 31 patients and the carboplatin alone arm 30 for a total of 61 patients out of 900 planned. Response rates were 67% for the PLD arm and 32% for the carboplatin only arm (Fisher’s exact p=0.02). The estimated median PFS was 12 and 8 months for PLD versus carboplatin alone. The estimated median OS on the PLD arm was 26 months and 18 months on the carboplatin only arm (p=0.02). Twenty-six percent of the patients on the PLD arm reported grade 4 toxicities, all hematological in nature. Conclusion This study was closed early because of slow patient accrual. The response rate, median PFS and OS results are intriguing. These data suggest that there may be an advantage to the PLD plus carboplatin combination treatment in patients with PS, recurrent OC. The regimen should be further tested. PMID:17949799
Li, Mengjie; Thapa, Pritam; Rajaputra, Pallavi; Bio, Moses; Peer, Cody J; Figg, William D; You, Youngjae; Woo, Sukyung
2017-12-01
The combination of photodynamic therapy (PDT) with anti-tumor agents is a complimentary strategy to treat local cancers. We developed a unique photosensitizer (PS)-conjugated paclitaxel (PTX) prodrug in which a PS is excited by near-infrared wavelength light to site-specifically release PTX while generating singlet oxygen (SO) to effectively kill cancer cells with both PTX and SO. The aim of the present study was to identify the determinants influencing the combined efficacy of this light-activatable prodrug, especially the bystander killing effects from released PTX. Using PS-conjugated PTX as a model system, we developed a quantitative mathematical model describing the intracellular trafficking. Dynamics of the prodrug and the model predictions were verified with experimental data using human cancer cells in vitro. The sensitivity analysis suggested that parameters related to extracellular concentration of released PTX, prodrug uptake, target engagement, and target abundance are critical in determining the combined killing efficacy of the prodrug. We found that released PTX cytotoxicity was most sensitive to the retention time of the drug in extracellular space. Modulating drug internalization and conjugating the agents targeted to abundant receptors may provide a new strategy for maximizing the killing capacity of the far-red light-activatable prodrug system. These results provide guidance for the design of the PDT combination study in vivo and have implications for other stimuli-responsive drug delivery systems.
Mattheij, Nadine J A; Braun, Attila; van Kruchten, Roger; Castoldi, Elisabetta; Pircher, Joachim; Baaten, Constance C F M J; Wülling, Manuela; Kuijpers, Marijke J E; Köhler, Ralf; Poole, Alastair W; Schreiber, Rainer; Vortkamp, Andrea; Collins, Peter W; Nieswandt, Bernhard; Kunzelmann, Karl; Cosemans, Judith M E M; Heemskerk, Johan W M
2016-02-01
Scott syndrome is a rare bleeding disorder, characterized by altered Ca(2+)-dependent platelet signaling with defective phosphatidylserine (PS) exposure and microparticle formation, and is linked to mutations in the ANO6 gene, encoding anoctamin (Ano)6. We investigated how the complex platelet phenotype of this syndrome is linked to defective expression of Anos or other ion channels. Mice were generated with heterozygous of homozygous deficiency in Ano6, Ano1, or Ca(2+)-dependent KCa3.1 Gardos channel. Platelets from these mice were extensively analyzed on molecular functions and compared with platelets from a patient with Scott syndrome. Deficiency in Ano1 or Gardos channel did not reduce platelet responses compared with control mice (P > 0.1). In 2 mouse strains, deficiency in Ano6 resulted in reduced viability with increased bleeding time to 28.6 min (control 6.4 min, P < 0.05). Platelets from the surviving Ano6-deficient mice resembled platelets from patients with Scott syndrome in: 1) normal collagen-induced aggregate formation (P > 0.05) with reduced PS exposure (-65 to 90%); 2) lowered Ca(2+)-dependent swelling (-80%) and membrane blebbing (-90%); 3) reduced calpain-dependent protein cleavage (-60%); and 4) moderately affected apoptosis-dependent PS exposure. In conclusion, mouse deficiency of Ano6 but not of other channels affects viability and phenocopies the complex changes in platelets from hemostatically impaired patients with Scott syndrome. © FASEB.
Preparation and encapsulation of white/yellow dual colored suspensions for electrophoretic displays
NASA Astrophysics Data System (ADS)
Han, Jingjing; Li, Xiaoxu; Feng, Yaqing; Zhang, Bao
2014-11-01
C.I. Pigment Yellow 181 (PY181) composite particles encapsulated by polyethylene (PE) were prepared by dispersion polymerization method, and C.I. Pigment Yellow 110 (PY110) composite particles encapsulated by polystyrene (PS) with mini-emulsion polymerization method were achieved, respectively. The modified pigments were characterized by fourier transform infrared spectroscopy, scanning electron microscope and transmission electron microscope. Compared with the PE-coated PY 181 pigments, the PS-coated PY-110 particles had a narrow particle size distribution, regular spherical and average particle size of 450 nm. Suspension 1 and suspension 3 were prepared by the two composite particles dispersed in isopar M. A chromatic electrophoretic display cell consisting of yellow particles was successfully fabricated using dispersions of yellow ink particles in a mixed dielectric solvent with white particles as contrast. The response behavior and the contrast ratio to the electric voltage were also examined. The contrast ratio of pigments modified by polystyrene was 1.48, as well as the response time was 2 s, which were better than those of pigments modified by polyethylene.
Lonjon, Guillaume; Porcher, Raphael; Ergina, Patrick; Fouet, Mathilde; Boutron, Isabelle
2017-05-01
To describe the evolution of the use and reporting of propensity score (PS) analysis in observational studies assessing a surgical procedure. Assessing surgery in randomized controlled trials raises several challenges. Observational studies with PS analysis are a robust alternative for comparative effectiveness research. In this methodological systematic review, we identified all PubMed reports of observational studies with PS analysis that evaluated a surgical procedure and described the evolution of their use over time. Then, we selected a sample of articles published from August 2013 to July 2014 and systematically appraised the quality of reporting and potential bias of the PS analysis used. We selected 652 reports of observational studies with PS analysis. The publications increased over time, from 1 report in 1987 to 198 in 2013. Among the 129 reports assessed, 20% (n = 24) did not detail the covariates included in the PS and 77% (n = 100) did not report a justification for including these covariates in the PS. The rate of missing data for potential covariates was reported in 9% of articles. When a crossover by conversion was possible, only 14% of reports (n = 12) mentioned this issue. For matched analysis, 10% of articles reported all 4 key elements that allow for reproducibility of a PS-matched analysis (matching ratio, method to choose the nearest neighbors, replacement and method for statistical analysis). Observational studies with PS analysis in surgery are increasing in frequency, but specific methodological issues and weaknesses in reporting exist.
Müller, D; Hauer, J; Schöttner, K; Fritzsche, P; Weinert, D
2015-12-01
The genus Phodopus consists of three species--P. campbelli (Pc), P. sungorus (Ps), and P. roborovskii (Pr). They inhabit steppes, semi-deserts, and deserts in continental Asia with a climate changing from a moderate to a hard Continental one with extreme daily and seasonal variations. These different environmental challenges are likely to have consequences for hamsters' morphology, physiology, and behavior. Hamsters of all three species were investigated during the course of the year in the laboratory though using natural lighting and temperature conditions. Motor activity and body temperature were measured continuously, and body mass, testes size, and fur coloration every 1-2 weeks. With regard to the pattern of activity, nearly twice as many Pc as Ps hamsters (25 vs. 14%) failed to respond to changes of photoperiod, whereas all Pr hamsters did. Body mass and testes size were high in summer and low in winter, with the biggest relative change in Ps and the lowest in Pr hamsters. Changes of fur coloration were found in Ps hamsters only. All responding animals (that is excluding Pr), exhibited regular torpor bouts during the short winter days. In autumn, seasonal changes started considerably earlier in Ps hamsters. To investigate the putative causes of these different time courses, a further experiment was performed, to identify the critical photoperiod. Hamsters were kept for 10 weeks under different photoperiods, changing from 16 to 8 h light per day. Motor activity was recorded continuously, to identify responding and non-responding animals. Body mass was measured at the beginning and the end of the experiment, testes mass only at the end. The critical photoperiod was found to be similar in all three species. Though in a further experiment, Pc and Pr hamsters showed a delayed response, whereas the changes in Ps hamsters started immediately following transfer to short-day conditions. The results show that interspecific differences in seasonal adaptation exist, even between the closely related Ps and Pc hamsters, possibly due to different conditions in their natural habitat. Also, the impact of environmental factors like climatic conditions and food resources may differ between species.
Responsive Block Copolymer and Gold Nanoparticle Hybrid Nanotubes.
NASA Astrophysics Data System (ADS)
Chang, Sehoon; Singamaneni, Srikanth; Young, Seth; Tsukruk, Vladimir
2009-03-01
We demonstrate the facile fabrication of responsive polymer and metal nanoparticle composite nanotube structures. The nanotubes are comprised of responsive block copolymer, polystyrene-block-poly (2-vinylpyridine) (PS-b-P2VP), and gold nanoparticles. PS-b-P2VP nanotubes were fabricated using porous alumina template and in situ reduction of the gold nanoparticles in P2VP domains. Owing to the pH sensitive nature of P2VP (anionic polymer with a pKa of 3.8), the nanotubes exhibit a dramatic change in topology in response to the changes in the external pH. Furthermore, the gold nanoparticles in the responsive block exhibit a reversible aggregation, causing a reversible change in optical properties such as absorption.
Moots, Robert J; Curiale, Cinzia; Petersel, Danielle; Rolland, Catherine; Jones, Heather; Mysler, Eduardo
2018-05-22
Regulatory approval of biosimilar versions of originator biotherapeutics requires that new biological products be highly similar to originator products, with no clinically meaningful differences in safety, purity, and potency. In some trials of biosimilars of tumor necrosis factor inhibitors for the treatment of rheumatoid arthritis (RA) and plaque psoriasis (PsO), pre-specified margins for efficacy and safety have been met, but differences in treatment responses between pivotal originator trials and biosimilar trials have been noted. The objective of this systematic review was to examine these differences. Searches were conducted to identify comparative randomized clinical trials of approved or proposed biosimilars of adalimumab, etanercept, and infliximab. Of 83 publications identified, 16 publications were included for analysis (RA: originators, n = 5; biosimilars, n = 6; PsO: originators, n = 2; biosimilars, n = 3). American College of Rheumatology 20% response rates were higher among patients with RA receiving originator biologics and biosimilars in biosimilar trials than among patients receiving the originator biologics in pivotal trials. In etanercept studies in PsO, a difference was observed in Psoriasis Area and Severity Index 75% response rates between biosimilar and pivotal trials. Insufficient efficacy data were available from adalimumab and infliximab biosimilar studies in PsO to determine any differences in treatment responses between pivotal and biosimilar studies. Observed differences in treatment response rates between pivotal originator trials and trials of originator biologics and their respective biosimilars may be attributable to fundamental differences in study design and/or baseline patient characteristics, which require further analysis.
Bicarbonate-activated persulfate oxidation of acetaminophen.
Jiang, Mengdi; Lu, Junhe; Ji, Yuefei; Kong, Deyang
2017-06-01
Persulfate (PS) is widely used as an oxidant for in situ chemical remediation of contaminated groundwater. In this study we demonstrated for the first time that PS could be activated by bicarbonate. Acetaminophen was used as the probe compound to examine the reactivity of PS/bicarbonate system. It was found that acetaminophen could be effectively transformed and the reaction rate appeared pseudo-first-order to the concentrations of both acetaminophen and PS. Radical scavenger tests indicated that neither free radicals (SO 4 - and HO) nor superoxide (O 2 - ) was responsible for acetaminophen transformation. Generation of singlet oxygen ( 1 O 2 ) was verified using furfuryl alcohol (FFA) as a probe. Formation of 1 O 2 was further quantified in D 2 O fortified solution based on kinetic solvent isotopic effect (KSIE) but it was found that 1 O 2 contributed only 51.4% of the total FFA transformation. The other 48.6% was presumed to be ascribed to the reaction with peroxymonocarbonate (HCO 4 - ). However, the transformation of acetaminophen was mostly due to the reaction with HCO 4 - but not 1 O 2 . Instead of degradation, HCO 4 - oxidized acetaminophen via a one-electron abstraction mechanism resulting in the generation of acetaminophen radicals which coupled to each other to form dimers and trimers. HCO 4 - also hydrolyzed rapidly to form hydrogen peroxide (H 2 O 2 ) which led to the formation of 1 O 2 , during which O 2 - was a key intermediates. Because bicarbonate is ubiquitously presented in groundwater, the findings of this research provide important insights into the fundamental processes involved in PS oxidation in subsurface. Copyright © 2017 Elsevier Ltd. All rights reserved.
Moraska, Albert F.; Stenerson, Lea; Butryn, Nathan; Krutsch, Jason P.; Schmiege, Sarah J.; Mann, J. Douglas
2014-01-01
Objective Myofascial trigger points (MTrPs) are focal disruptions in skeletal muscle that can refer pain to the head and reproduce the pain patterns of tension-type headache (TTH). The present study applied massage focused on MTrPs of subjects with TTH in a placebo-controlled, clinical trial to assess efficacy on reducing headache pain. Methods Fifty-six subjects with TTH were randomized to receive 12 massage or placebo (detuned ultrasound) sessions over six weeks, or to wait-list. Trigger point release (TPR) massage focused on MTrPs in cervical musculature. Headache pain (frequency, intensity and duration) was recorded in a daily headache diary. Additional outcome measures included self-report of perceived clinical change in headache pain and pressure-pain threshold (PPT) at MTrPs in the upper trapezius and sub-occipital muscles. Results From diary recordings, group differences across time were detected in headache frequency (p=0.026), but not for intensity or duration. Post hoc analysis indicated headache frequency decreased from baseline for both massage (p<0.0003) and placebo (p=0.013), but no difference was detected between massage and placebo. Subject report of perceived clinical change was a greater reduction in headache pain for massage than placebo or wait-list groups (p=0.002). PPT improved in all muscles tested for massage only (all p's<0.002). Discussion Two findings from this study are apparent: 1) MTrPs are important components in the treatment of TTH, and 2) TTH, like other chronic conditions, is responsive to placebo. Clinical trials on headache that do not include a placebo group are at risk for overestimating the specific contribution from the active intervention. PMID:25329141
Moraska, Albert F; Stenerson, Lea; Butryn, Nathan; Krutsch, Jason P; Schmiege, Sarah J; Mann, John D
2015-02-01
Myofascial trigger points (MTrPs) are focal disruptions in the skeletal muscle that can refer pain to the head and reproduce the pain patterns of tension-type HA (TTH). The present study applied massage focused on MTrPs of patients with TTH in a placebo-controlled, clinical trial to assess efficacy on reducing headache (HA) pain. Fifty-six patients with TTH were randomized to receive 12 massage or placebo (detuned ultrasound) sessions over 6 weeks, or to wait-list. Trigger point release massage focused on MTrPs in cervical musculature. HA pain (frequency, intensity, and duration) was recorded in a daily HA diary. Additional outcome measures included self-report of perceived clinical change in HA pain and pressure-pain threshold at MTrPs in the upper trapezius and suboccipital muscles. From diary recordings, group differences across time were detected in HA frequency (P=0.026), but not for intensity or duration. Post hoc analysis indicated that HA frequency decreased from baseline for both massage (P<0.0003) and placebo (P=0.013), but no difference was detected between massage and placebo. Patient report of perceived clinical change was greater reduction in HA pain for massage than placebo or wait-list groups (P=0.002). Pressure-pain threshold improved in all muscles tested for massage only (all P's<0.002). Two findings from this study are apparent: (1) MTrPs are important components in the treatment of TTH, and (2) TTH, like other chronic conditions, is responsive to placebo. Clinical trials on HA that do not include a placebo group are at risk for overestimating the specific contribution from the active intervention.
USDA-ARS?s Scientific Manuscript database
Sepsis disrupts skeletal muscle proteostasis and mitigates the anabolic response to leucine (Leu) in muscle of mature animals. We have shown that Leu stimulates muscle protein synthesis (PS) in healthy neonatal piglets. To determine if supplemental Leu can stimulate PS and reduce protein degradation...
Tarasenko, V F; Rybka, D V; Burachenko, A G; Lomaev, M I; Balzovsky, E V
2012-08-01
This note reports the time-amplitude characteristic of the supershort avalanche electron beam with up to 20 ps time resolution. For the first time it is shown that the electron beam downstream of small-diameter diaphragms in atmospheric pressure air has a complex structure which depends on the interelectrode gap width and cathode design. With a spherical cathode and collimator the minimum duration at half maximum of the supershort avalanche electron beam current pulse was shown to be ~25 ps. The minimum duration at half maximum of one peak in the pulses with two peaks can reach ~25 ps too.
Oyler-Yaniv, Jennifer; Oyler-Yaniv, Alon; Shakiba, Mojdeh; Min, Nina K; Chen, Ying-Han; Cheng, Sheue-Yann; Krichevsky, Oleg; Altan-Bonnet, Nihal; Altan-Bonnet, Grégoire
2017-06-01
Immune cells constantly survey the host for pathogens or tumors and secrete cytokines to alert surrounding cells of these threats. In vivo, activated immune cells secrete cytokines for several hours, yet an acute immune reaction occurs over days. Given these divergent timescales, we addressed how cytokine-responsive cells translate brief cytokine exposure into phenotypic changes that persist over long timescales. We studied melanoma cell responses to transient exposure to the cytokine interferon γ (IFNγ) by combining a systems-scale analysis of gene expression dynamics with computational modeling and experiments. We discovered that IFNγ is captured by phosphatidylserine (PS) on the surface of viable cells both in vitro and in vivo then slowly released to drive long-term transcription of cytokine-response genes. This mechanism introduces an additional function for PS in dynamically regulating inflammation across diverse cancer and primary cell types and has potential to usher in new immunotherapies targeting PS and inflammatory pathways. Published by Elsevier Inc.
Emission of positronium in a nanometric PMMA film
NASA Astrophysics Data System (ADS)
Palacio, C. A.; De Baerdemaeker, J.; Van Thourhout, D.; Dauwe, C.
2008-10-01
Positron beam experiments have been performed for the first time on a self-supporting polymethyl metacrylate (PMMA) film of 310 nm-thick made by spin coating. The positronium (Ps) emission from the PMMA surface is studied as a function of the positron implantation energy by using Doppler profile spectroscopy and Compton-to-peak ratio analysis. When the sample and the Ge-detector are perpendicular to the positron beam, the emission of para-positronium ( p-Ps) is detected as a narrow central peak. By rotating the sample 45° with respect to the beam, the emission of p-Ps is detected as a blue-shifted fly-away peak. The bulk Ps fraction, the efficiency for the emission of Ps by picking up an electron from the surface, and the diffusion lengths of positrons (thermal and or epithermal), p-Ps and ortho-positronium ( o-Ps) are obtained.
Hardware solution for continuous time-resolved burst detection of single molecules in flow
NASA Astrophysics Data System (ADS)
Wahl, Michael; Erdmann, Rainer; Lauritsen, Kristian; Rahn, Hans-Juergen
1998-04-01
Time Correlated Single Photon Counting (TCSPC) is a valuable tool for Single Molecule Detection (SMD). However, existing TCSPC systems did not support continuous data collection and processing as is desirable for applications such as SMD for e.g. DNA-sequencing in a liquid flow. First attempts at using existing instrumentation in this kind of operation mode required additional routing hardware to switch between several memory banks and were not truly continuous. We have designed a hard- and software system to perform continuous real-time TCSPC based upon a modern solid state Time to Digital Converter (TDC). Short dead times of the fully digital TDC design combined with fast Field Programmable Gay Array logic permit a continuous data throughput as high as 3 Mcounts/sec. The histogramming time may be set as short as 100 microsecond(s) . Every histogram or every single fluorescence photon can be real-time tagged at 200 ns resolution in addition to recording its arrival time relative to the excitation pulse. Continuous switching between memory banks permits concurrent histogramming and data read-out. The instrument provides a time resolution of 60 ps and up to 4096 histogram channels. The overall instrument response function in combination with a low cost picosecond diode laser and an inexpensive photomultiplier tube was found to be 180 ps and well sufficient to measure sub-nanosecond fluorescence lifetimes.
NASA Astrophysics Data System (ADS)
Kim, Sehee; Char, Kookheon; Sohn, Byeong-Hyeok
2010-03-01
Diblock copolymers consisting of two immiscible polymer blocks covalently bonded together form various self-assembled nanostructures such as spheres, cylinders, and lamellae in bulk phase. In a selective solvent, however, they assemble into micelles with soluble corona brushes and immiscible cores. Both polystyrene-poly(4-vinylpyridine) (PS-b-P4VP) and polystyrene-poly(2-vinylpyridine) (PS-b-P2VP) diblock copolymers form micelles with PS coronas and P4VP or P2VP cores in a PS selective solvent (toluene). By varying the mixture ratio between PS-b-P4VP and PS-b-P2VP, composite films based on the micellar mixtures of PS-b-P4VP and PS-b-P2VP were obtained by spin-coating, followed by the solvent annealing with tetrahydrofuran (THF) vapor. Since THF is a solvent for both PS and P2VP blocks and, at the same time, a non-solvent for the P4VP block, PS-P2VP micelles transformed to lamellar multilayers while PS-P4VP micelles remained intact during the THF annealing. The spontaneous evolution of nanostructure in composite films consisting of lamellae layers with BCP micelles were investigated in detail by cross-sectional TEM and AFM.
Molecular cloning and potential function prediction of homologous SOC1 genes in tree peony.
Wang, Shunli; Beruto, Margherita; Xue, Jingqi; Zhu, Fuyong; Liu, Chuanjiao; Yan, Yueming; Zhang, Xiuxin
2015-08-01
The central flower integrator PsSOC1 was isolated and its expression profiles were analyzed; then the potential function of PsSOC1 in tree peony was postulated. The six flowering genes PrSOC1, PdSOC1, PsSOC1, PsSOC1-1, PsSOC1-2, and PsSOC1-3 were isolated from Paeonia rockii, Paeonia delavayi, and Paeonia suffruticosa, respectively. Sequence comparison analysis showed that the six genes were highly conserved and shared 99.41% nucleotide identity. Further investigation suggested PsSOC1 was highly homologous to the floral integrators, SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1), from Arabidopsis. Phylogenetic analysis showed that the SOC1 protein clustering has family specificity and PsSOC1 has a close relationship with homologous SOC1 from Asteraceae species. The studies of PsSOC1's expression patterns in different buds and flower buds, and vegetative organs indicated that PsSOC1 could express in both vegetative and reproductive organs. While the expression of PsSOC1 in different developmental stages of buds was different; high expression levels of PsSOC1 occurred in the bud at the bud sprouting stage and the type I aborted the flower bud. PsSOC1 expression was also shown to be affected by gibberellins (GA), low temperature, and photoperiod. One of the pathways that regulates tree peony flowering may be the GA-inductive pathway. Ectopic expression of PsSOC1 in tobacco demonstrated that greater PsSOC1 expression in the transgenic tobacco plants not only promoted plant growth, but also advanced the flowering time. Finally, the potential function of PsSOC1 in tree peony was postulated.
Optimisation of multiplet identifier processing on a PLAYSTATION® 3
NASA Astrophysics Data System (ADS)
Hattori, Masami; Mizuno, Takashi
2010-02-01
To enable high-performance computing (HPC) for applications with large datasets using a Sony® PLAYSTATION® 3 (PS3™) video game console, we configured a hybrid system consisting of a Windows® PC and a PS3™. To validate this system, we implemented the real-time multiplet identifier (RTMI) application, which identifies multiplets of microearthquakes in terms of the similarity of their waveforms. The cross-correlation computation, which is a core algorithm of the RTMI application, was optimised for the PS3™ platform, while the rest of the computation, including data input and output remained on the PC. With this configuration, the core part of the algorithm ran 69 times faster than the original program, accelerating total computation speed more than five times. As a result, the system processed up to 2100 total microseismic events, whereas the original implementation had a limit of 400 events. These results indicate that this system enables high-performance computing for large datasets using the PS3™, as long as data transfer time is negligible compared with computation time.
Nakamura, Ryosuke; Hamada, Norio
2015-05-14
Vibrational energy flow in the electronic ground state of photoactive yellow protein (PYP) is studied by ultrafast infrared (IR) pump-visible probe spectroscopy. Vibrational modes of the chromophore and the surrounding protein are excited with a femtosecond IR pump pulse, and the subsequent vibrational dynamics in the chromophore are selectively probed with a visible probe pulse through changes in the absorption spectrum of the chromophore. We thus obtain the vibrational energy flow with four characteristic time constants. The vibrational excitation with an IR pulse at 1340, 1420, 1500, or 1670 cm(-1) results in ultrafast intramolecular vibrational redistribution (IVR) with a time constant of 0.2 ps. The vibrational modes excited through the IVR process relax to the initial ground state with a time constant of 6-8 ps in parallel with vibrational cooling with a time constant of 14 ps. In addition, upon excitation with an IR pulse at 1670 cm(-1), we observe the energy flow from the protein backbone to the chromophore that occurs with a time constant of 4.2 ps.
Kim, George P; Mahoney, Michelle R; Szydlo, Daniel; Mok, Tony S K; Marshke, Robert; Holen, Kyle; Picus, Joel; Boyer, Michael; Pitot, Henry C; Rubin, Joseph; Philip, Philip A; Nowak, Anna; Wright, John J; Erlichman, Charles
2012-02-01
Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitin-proteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. The primary endpoint was confirmed tumor response rate (RR) with secondary endpoints including duration of response, time to disease progression, survival and toxicity. Treatment consisted of bortezomib, 1.3 mg/m2 IV bolus on days 1, 4, 8, and 11 of each 21-day treatment cycle. Eligibility included: no prior systemic chemotherapy, ECOG PS 0-2, Child-Pugh A or B, preserved hematologic, hepatic and neurologic function; prior liver-directed therapy was permitted. Thirty-five patients enrolled and received a median of 2 cycles of treatment (range 1-12). Overall, 24 and 4 patients had a maximum severity of grade 3 and 4 adverse events (AEs), respectively. No treatment related deaths occurred. Only thrombocytopenia (11%) was seen in greater than 10% of patients. One patient achieved a partial response, lasting 13 weeks during treatment and progressed 11.6 months later; two patients received treatment for greater than 6 months. Median time-to-progression was 1.6 months and median survival was 6.0 months. This international, multicenter trial evaluated bortezomib as monotherapy in unresectable HCC patients. And, despite the lack of significant activity, this report serves as a baseline clinical experience for the development of future dual biologic approaches including bortezomib.
An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma
Kim, George P.; Mahoney, Michelle R.; Szydlo, Daniel; Mok, Tony S. K.; Marshke, Robert; Holen, Kyle; Picus, Joel; Boyer, Michael; Pitot, Henry C.; Rubin, Joseph; Philip, Philip A.; Nowak, Anna; Wright, John J.; Erlichman, Charles
2013-01-01
Summary Background and Rationale Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitinproteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. Methods The primary endpoint was confirmed tumor response rate (RR) with secondary endpoints including duration of response, time to disease progression, survival and toxicity. Treatment consisted of bortezomib, 1.3 mg/m2 IV bolus on days 1, 4, 8, and 11 of each 21-day treatment cycle. Eligibility included: no prior systemic chemotherapy, ECOG PS 0-2, Child-Pugh A or B, preserved hematologic, hepatic and neurologic function; prior liver-directed therapy was permitted. Results Thirty-five patients enrolled and received a median of 2 cycles of treatment (range 1–12). Overall, 24 and 4 patients had a maximum severity of grade 3 and 4 adverse events (AEs), respectively. No treatment related deaths occurred. Only thrombocytopenia (11%) was seen in greater than 10% of patients. One patient achieved a partial response, lasting 13 weeks during treatment and progressed 11.6 months later; two patients received treatment for greater than 6 months. Median time-to-progression was 1.6 months and median survival was 6.0 months. Conclusions This international, multicenter trial evaluated bortezomib as monotherapy in unresectable HCC patients. And, despite the lack of significant activity, this report serves as a baseline clinical experience for the development of future dual biologic approaches including bortezomib. PMID:20839030
NASA Astrophysics Data System (ADS)
Weiying, Ou; Lei, Zhao; Hongwei, Diao; Jun, Zhang; Wenjing, Wang
2011-05-01
Porous silicon (PS) layers were formed on textured crystalline silicon by electrochemical etching in HF-based electrolyte. Optical and electrical properties of the TMAH textured surfaces with PS formation are studied. Moreover, the influences of the initial structures and the anodizing time on the optical and electrical properties of the surfaces after PS formation are investigated. The results show that the TMAH textured surfaces with PS formation present a dramatic decrease in reflectance. The longer the anodizing time is, the lower the reflectance. Moreover, an initial surface with bigger pyramids achieved lower reflectance in a short wavelength range. A minimum reflectance of 3.86% at 460 nm is achieved for a short anodizing time of 2 min. Furthermore, the reflectance spectrum of the sample, which was etched in 3 vol.% TMAH for 25 min and then anodized for 20 min, is extremely flat and lies between 3.67% and 6.15% in the wavelength range from 400 to 1040 nm. In addition, for a short anodizing time, a slight increase in the effective carrier lifetime is observed. Our results indicate that PS layers formed on a TMAH textured surface for a short anodization treatment can be used as both broadband antireflection coatings and passivation layers for the application in solar cells.
Sub-nanosecond clock synchronization and trigger management in the nuclear physics experiment AGATA
NASA Astrophysics Data System (ADS)
Bellato, M.; Bortolato, D.; Chavas, J.; Isocrate, R.; Rampazzo, G.; Triossi, A.; Bazzacco, D.; Mengoni, D.; Recchia, F.
2013-07-01
The new-generation spectrometer AGATA, the Advanced GAmma Tracking Array, requires sub-nanosecond clock synchronization among readout and front-end electronics modules that may lie hundred meters apart. We call GTS (Global Trigger and Synchronization System) the infrastructure responsible for precise clock synchronization and for the trigger management of AGATA. It is made of a central trigger processor and nodes, connected in a tree structure by means of optical fibers operated at 2Gb/s. The GTS tree handles the synchronization and the trigger data flow, whereas the trigger processor analyses and eventually validates the trigger primitives centrally. Sub-nanosecond synchronization is achieved by measuring two different types of round-trip times and by automatically correcting for phase-shift differences. For a tree of depth two, the peak-to-peak clock jitter at each leaf is 70 ps; the mean phase difference is 180 ps, while the standard deviation over such phase difference, namely the phase equalization repeatability, is 20 ps. The GTS system has run flawlessly for the two-year long AGATA campaign, held at the INFN Legnaro National Laboratories, Italy, where five triple clusters of the AGATA sub-array were coupled with a variety of ancillary detectors.
Yu, Muxin; Xie, Rujuan; Zhang, Yan; Liang, Hui; Hou, Li; Yu, Chengyuan; Zhang, Jinming; Dong, Zengxiang; Tian, Ye; Bi, Yayan; Kou, Junjie; Novakovic, Valerie A; Shi, Jialan
2018-02-26
Relatively little is known about the role of phosphatidylserine (PS) in procoagulant activity (PCA) in patients with diabetic kidney disease (DKD). This study was designed to evaluate whether exposed PS on microparticles (MPs) and MP-origin cells were involved in the hypercoagulability in DKD patients. DKD patients (n = 90) were divided into three groups based on urinary albumin excretion rate, defined as normoalbuminuria (No-A) (<30 mg/24 h), microalbuminuria (Mi-A) (30-299 mg/24 h) or macroalbuminuria (Ma-A) (>300 mg/24 h), and compared with healthy controls (n = 30). Lactadherin was used to quantify PS exposure on MPs and their original cells. Healthy blood cells (BCs) and human umbilical vein endothelial cells (HUVECs) were treated with 25, 5 or 2.5 mmol/L glucose as well as 3-12 mg/dL uric acid and cells were evaluated by clotting time and purified coagulation complex assays. Fibrin production was determined by turbidity. PS exposure and fibrin strands were observed using confocal microscopy. Using flow cytometry, we found that PS+ MPs (derived from platelets, erythrocytes, HUVECs, neutrophils, monocytes and lymphocytes) and BCs were significantly higher in patients than in controls. Furthermore, the number of PS+ MPs and BCs in patients with Ma-A was significantly higher than in patients with No-A. Similarly, we observed markedly elevated PS exposure on HUVECs cultured with serum from patients with Ma-A versus serum from patients with Mi-A or normoalbuminuria. In addition, circulating PS+ MPs cooperated with PS+ cells, contributing to markedly shortened coagulation time and dramatically increased FXa/thrombin generation and fibrin formation in each DKD group. Confocal microscopy images demonstrated colocalization of fibrin with PS on HUVECs. Moreover, blockade of exposed PS on MPs and cells with lactadherin inhibited PCA by ∼80%. In vitro, BCs and endothelial cells exposed more PS in hypoglycemia or hyperglycemia. Interestingly, reconstitution experiments showed that hypoglycemia-treated cells could be further activated or injured when recovery is obtained reaching hyperglycemia. Moreover, uric acid induced PS exposure on cells (excluding platelets) at concentrations >6 mg/dL. Linear regression analysis showed that levels of PS+ BCs and microparticles were positively correlated with uric acid and proteinuria, but negatively correlated with glomerular filtration rate. Our results suggest that PS+ MPs and MP-origin cells play procoagulant roles in patients with DKD. Blockade of PS could become a novel therapeutic modality for the prevention of thrombosis in these patients.
Qiu, Zhifang; Mishra, Anuja; Li, Miao; Farnsworth, Steven L; Guerra, Bernadette; Lanford, Robert E; Hornsby, Peter J
2015-07-01
The marmoset is an important nonhuman primate model for regenerative medicine. For experimental autologous cell therapy based on induced pluripotent (iPS) cells in the marmoset, cells must be able to undergo robust and reliable directed differentiation that will not require customization for each specific iPS cell clone. When marmoset iPS cells were aggregated in a hanging drop format for 3 days, followed by exposure to dual SMAD inhibitors and retinoic acid in monolayer culture for 3 days, we found substantial variability in the response of different iPS cell clones. However, when clones were pretreated with 0.05-2% dimethyl sulfoxide (DMSO) for 24 hours, all clones showed a very similar maximal response to the directed differentiation scheme. Peak responses were observed at 0.5% DMSO in two clones and at 1% DMSO in a third clone. When patterns of gene expression were examined by microarray analysis, hierarchical clustering showed very similar responses in all 3 clones when they were pretreated with optimal DMSO concentrations. The change in phenotype following exposure to DMSO and the 6 day hanging drop/monolayer treatment was confirmed by immunocytochemistry. Analysis of DNA content in DMSO-exposed cells indicated that it is unlikely that DMSO acts by causing cells to exit from the cell cycle. This approach should be generally valuable in the directed neural differentiation of pluripotent cells for experimental cell therapy. Copyright © 2015. Published by Elsevier B.V.
Feletar, Marie; Hall, Stephen; Bird, Paul
2016-01-01
To assess the responsiveness of high- and low-field extremity magnetic resonance imaging (MRI) variables at multiple timepoints in the first 12 weeks post-antitumor necrosis factor (anti-TNF) therapy initiation in patients with psoriatic arthritis (PsA) and active dactylitis. Twelve patients with active PsA and clinical evidence of dactylitis involving at least 1 digit were recruited. Patients underwent sequential high-field conventional (1.5 Tesla) and extremity low-field MRI (0.2 Tesla) of the affected hand or foot, pre- and postgadolinium at baseline (pre-TNF), 2 weeks (post-TNF), 6 weeks, and 12 weeks. A blinded observer scored all images on 2 occasions using the PsA MRI scoring system. Eleven patients completed the study, but only 6 patients completed all high-field and low-field MRI assessments. MRI scores demonstrated rapid response to TNF inhibition with score reduction in tenosynovitis, synovitis, and osteitis at 2 weeks. Intraobserver reliability was good to excellent for all variables. High-field MRI demonstrated greater sensitivity to tenosynovitis, synovitis, and osteitis and greater responsiveness to change posttreatment. Treatment responses were maintained to 12 weeks. This study demonstrates the use of MRI in detecting early response to biologic therapy. MRI variables of tenosynovitis, synovitis, and osteitis demonstrated responsiveness posttherapy with high-field scores more responsive to change than low-field scores.
Polinski, Jennifer M.; Schneeweiss, Sebastian; Glynn, Robert J.; Lii, Joyce; Rassen, Jeremy
2012-01-01
Purpose Under Medicare Part D, patient characteristics influence plan choice, which in turn influences Part D coverage gap entry. We compared pre-defined propensity score (PS) and high-dimensional propensity score (hdPS) approaches to address such ‘confounding by health system use’ in assessing whether coverage gap entry is associated with cardiovascular events or death. Methods We followed 243,079 Medicare patients aged 65+ with linked prescription, medical, and plan-specific data in 2005–2007. Patients reached the coverage gap and were followed until an event or year’s end. Exposed patients were responsible for drug costs in the gap; unexposed patients (patients with non-Part D drug insurance and Part D patients receiving a low-income subsidy (LIS)) received financial assistance. Exposed patients were 1:1 PS- or hdPS-matched to unexposed patients. The PS model included 52 predefined covariates; the hdPS model added 400 empirically identified covariates. Hazard ratios for death and any of five cardiovascular outcomes were compared. In sensitivity analyses, we explored residual confounding using only LIS patients in the unexposed group. Results In unadjusted analyses, exposed patients had no greater hazard of death (HR=1.00; 95% CI, 0.84–1.20) or other outcomes. PS- (HR=1.29;0.99–1.66) and hdPS- (HR=1.11;0.86–1.42) matched analyses showed elevated but non-significant hazards of death. In sensitivity analyses, the PS analysis showed a protective effect (HR=0.78;0.61–0.98), while the hdPS analysis (HR=1.06;0.82–1.37) confirmed the main hdPS findings. Conclusion Although the PS-matched analysis suggested elevated though non-significant hazards of death among patients with no financial assistance during the gap, the hdPS analysis produced lower estimates that were stable across sensitivity analyses. PMID:22552984
Roach, Christopher R; Hall, Dawn E; Zerbe, Philipp; Bohlmann, Jörg
2014-08-22
The monoterpene (+)-3-carene is associated with resistance of Sitka spruce against white pine weevil, a major North American forest insect pest of pine and spruce. High and low levels of (+)-3-carene in, respectively, resistant and susceptible Sitka spruce genotypes are due to variation of (+)-3-carene synthase gene copy number, transcript and protein expression levels, enzyme product profiles, and enzyme catalytic efficiency. A family of multiproduct (+)-3-carene synthase-like genes of Sitka spruce include the three (+)-3-carene synthases, PsTPS-3car1, PsTPS-3car2, PsTPS-3car3, and the (-)-sabinene synthase PsTPS-sab. Of these, PsTPS-3car2 is responsible for the relatively higher levels of (+)-3-carene in weevil-resistant trees. Here, we identified features of the PsTPS-3car1, PsTPS-3car2, PsTPS-3car3, and PsTPS-sab proteins that determine different product profiles. A series of domain swap and site-directed mutations, supported by structural comparisons, identified the amino acid in position 596 as critical for product profiles dominated by (+)-3-carene in PsTPS-3car1, PsTPS-3car2, and PsTPS-3car3, or (-)-sabinene in PsTPS-sab. A leucine in this position promotes formation of (+)-3-carene, whereas phenylalanine promotes (-)-sabinene. Homology modeling predicts that position 596 directs product profiles through differential stabilization of the reaction intermediate. Kinetic analysis revealed position 596 also plays a role in catalytic efficiency. Mutations of position 596 with different side chain properties resulted in a series of enzymes with different product profiles, further highlighting the inherent plasticity and potential for evolution of alternative product profiles of these monoterpene synthases of conifer defense against insects. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Knuf, Markus; Pankow-Culot, Heidemarie; Grunert, Detlef; Rapp, Michael; Panzer, Falko; Köllges, Ralph; Fanic, Aurélie; Habib, Ahsan; Borys, Dorota; Dieussaert, Ilse; Schuerman, Lode
2012-01-01
Induction of immunologic memory was assessed following primary vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Infants were randomized (1:1) to receive 3 doses of PHiD-CV or 7vCRM (7-valent CRM197-conjugated pneumococcal conjugate vaccine [PCV]) at 2, 3, and 4 months of age followed by 23-valent pneumococcal polysaccharide vaccine (23vPS) booster dose at 11 to 14 months of age. Pneumococcal geometric mean antibody concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers were measured. Postprimary immune responses were consistent with those in previous PHiD-CV and 7vCRM studies. Following 23vPS boosting, vaccine serotype-specific antibody GMCs increased 6.5- to 33.3-fold and 4.8- to 32.2-fold versus prebooster in the PHiD-CV and 7vCRM groups, respectively. Postbooster OPA titers increased 2.8- to 38.8-fold and 2.6- to 58.9-fold, respectively. Postbooster antibody GMCs exceeded postprimary levels but, for some serotypes, postbooster OPA geometric mean titers were lower than postprimary in both groups. An additional dose of the same PCV received for priming was administered to 52 children aged 46 to 50 months, resulting in higher responses versus postprimary vaccination for all serotypes, but not always higher than post-23vPS booster. Induction of immunologic memory following PHiD-CV priming was confirmed. Additional PCV boosting in 4-year-olds did not provide strong evidence of hyporesponsiveness induced by previous 23vPS boosting. However, our results did not rule out depletion of the memory B cell pool following 23vPS vaccination, resulting in subsequent attenuated immune responses, and therefore support the use of PCV rather than 23vPS for booster vaccination in the second year of life.
Lominchar, Miguel A; Rodríguez, Sergio; Lorenzo, David; Santos, Noelia; Romero, Arturo; Santos, Aurora
2018-01-01
Three persulfate (PS) activation methods (nanoparticles of zero-valent iron (nZVI), hydrogen peroxide and alkali) were compared using phenol as target pollutant. Firstly, four experiments were conducted at 25°C in a batch way using the same initial phenol and oxidant concentrations (10 mM and 420 mM, respectively), being the molar ratio activator/PS fixed to 0.005 with nZVI (mass ratio 0.0011 nZVI/PS), to 2 using hydrogen peroxide and to 2 and 4 with NaOH. Phenol and PS conversions and aromatic byproducts profiles during 168 h reaction time were measured and compared, as well as mineralization and ecotoxicity of the samples. It was found that both phenol and aromatic byproducts (catechol and hydroquinone) totally disappeared using PS activated by alkali before 24 h, while a significant amount of aromatic intermediates was obtained with nZVI and H 2 O 2 . Additional runs were carried out using shorter times (0-2 h) to discriminate the oxidation route and the kinetic model of phenol abatement by using PS activated by alkali. Different initial concentrations of phenol (5-15 mM), PS (210 and 420 mM) and molar ratio NaOH/PS (2 and 4) were employed. The kinetic model obtained predicts accurately the evolution of phenol, persulfate, hydroquinone and catechol.
Mohuczy, Dagmara; Qian, Keping; Phillips, M Ian
2002-12-31
Cardiac cells are subjected to hypoxia in many cardiovascular diseases. We studied a broad spectrum of genes using a macroarrays-based method to analyze RNA of rat cardiac fetal cell line H9c2 after 4 h of hypoxic conditions in the incubator-1% oxygen concentration, as compared to normoxic conditions (21% oxygen). The cDNAs were prepared from total RNAs using Atlas Rat 1.2 Array (Clontech Laboratories) and hybridized to the membrane containing 1176 rat cDNAs and 9 housekeeping control cDNAs. Genes expression was analyzed using AtlasImage 1.01 software. We found over 45 genes up-regulated in a range of 1.5-2.9 times and 9 genes down-regulated to a range of 0.4-0.7 times, under hypoxia versus normoxia. Presenilin-2 (PS2) was detected in the cultured heart cells. RT-PCR confirmed the presence of PS2 in the heart of adult rats. Using quantitative real-time RT-PCR, we further studied the expression of presenilin-2 mRNA under conditions of low oxygen supply and glucose starvation. Glucose deprivation itself caused significant up-regulation of the presenilin-2 (to 160%) and with low oxygen increased presenilin-2 level to over 200% of the control. Presenilin-2 has previously been associated with intercellular signaling in the central nervous system, in Alzheimer's disease. The finding of presenilin-2 in the heart and the responsiveness to low glucose and hypoxia suggests that PS2 may be regulated by conditions of ischemia, a condition which both the heart and brain may experience.
Nakajima, Mitsunari; Watanabe, Sono; Okuyama, Satoshi; Shen, Jie; Furukawa, Yoshiko
2012-01-01
Presenilin-1 (PS1) is a transmembrane protein that is in many cases responsible for the development of early-onset familial Alzheimer’s disease. PS1 is essential for neurogenesis, somitogenesis, angiogenesis, and cardiac morphogenesis. We report here that PS1 is also required for maturation and/or maintenance of the pituitary gland. We generated PS1-conditional knockout (PS1-cKO) mice by crossing floxed PS1 and Wnt1-cre mice, in which PS1 was lacking in the neural crest-derived cell lineage. Although the PS1-cKO mice exhibited no obvious phenotypic abnormalities for several days after birth, reduced body weight in the mutant was evident by the age of 3 to 5 weeks. Pituitary weight and serum insulin-like growth factor (IGF)-1 level were also reduced in the mutant. Histologic analysis revealed severe atrophy of the cytosol in the anterior and intermediate pituitary lobes of the mutant. Immunohistochemistry did not reveal clear differences in the expression levels of thyroid-stimulating hormone, adrenocorticotropic hormone, or prolactin in the mutant pituitary. In contrast, growth hormone expression levels were reduced in the anterior lobe of the mutant. PS1 was defective in the posterior lobe, but not the anterior or intermediate lobes, in the mutant pituitary. These findings suggest that PS1 indirectly mediates the development and/or maintenance of the anterior and intermediate lobes in the pituitary gland via actions in other regions, such as the posterior lobe. PMID:19665542
Kaneko, Kosuke; Oto, Kodai; Kawai, Toshiaki; Choi, Hyunseok; Kikuchi, Hirotsugu; Nakamura, Naotake
2013-08-26
The electrorheological (ER) effect and the electro-optical properties of a ''side-on'' liquid crystalline polysiloxane (PS) are investigated. A large ER effect is observed and the response to the shear stress of neat PS in the nematic phase is shown to be affected by the shear rate. PS is also mixed with a low-molar nematic liquid crystal (5CB) in order to improve the response behavior to the applied electric field. The rheological properties of such mixtures are highly dependent on the concentration of 5CB. The composites respond faster to the applied electric field and have improved electro-optical properties. This study offers a new perspective on the development of liquid crystal materials for the ER effect. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Biomarkers in psoriasis and psoriatic arthritis.
Villanova, Federica; Di Meglio, Paola; Nestle, Frank O
2013-04-01
Psoriasis is a common immune-mediated disease of the skin, which associates in 20-30% of patients with psoriatic arthritis (PsA). The immunopathogenesis of both conditions is not fully understood as it is the result of a complex interaction between genetic, environmental and immunological factors. At present there is no cure for psoriasis and there are no specific markers that can accurately predict disease progression and therapeutic response. Therefore, biomarkers for disease prognosis and response to treatment are urgently needed to help clinicians with objective indications to improve patient management and outcomes. Although many efforts have been made to identify psoriasis/PsA biomarkers none of them has yet been translated into routine clinical practice. In this review we summarise the different classes of possible biomarkers explored in psoriasis and PsA so far and discuss novel strategies for biomarker discovery.
Yamazaki, Masakazu; Oishi, Keiya; Nakazawa, Hiroyuki; Zhu, Chaoyuan; Takahashi, Masahiko
2015-03-13
We report a time-resolved (e, 2e) experiment on the deuterated acetone molecule in the S2 Rydberg state with a lifetime of 13.5 ps. The acetone S2 state was prepared by a 195 nm pump laser and probed with electron momentum spectroscopy using a 1.2 keV incident electron beam of 1 ps temporal width. In spite of the low data statistics as well as of the limited time resolution (±35 ps) due to velocity mismatch, the experimental results clearly demonstrate that electron momentum spectroscopy measurements of short-lived transient species are feasible, opening the door to time-resolved orbital imaging in momentum space.
Xu, Ting; Xie, Jiasong; Yang, Shoubao; Ye, Shigen; Luo, Ming; Wu, Xinzhong
2016-08-01
Cyclophilins (CyPs) are a family of proteins that bind the immunosuppressive agent cyclosporin A (CsA) with high-affinity and belong to one of the three superfamilies of peptidyl-prolyl cis-trans isomerases (PPIase). In this report, three cyclophilin genes (Ca-CyPs), including Ca-CyPA, Ca-CyPB and Ca-PPIL3, were identified from oyster, Crassostrea ariakensis Gould in which Ca-CyPA encodes a protein with 165 amino acid sequences, Ca-CyPB encodes a protein with 217 amino acid sequences and Ca-PPIL3 encodes a protein with 162 amino acid sequences. All of the three Ca-CyPs genes contain a typical CyP-PPIase domain with its signature sequences and Ca-CyPB contains an N-signal peptide sequences. Tissue distribution study revealed that Ca-CyPs were ubiquitously expressed in all examined tissues and the highest levels were observed in hemocytes. RLO incubation upregulated the mRNA expression levels of Ca-CyPs, indicating that three Ca-CyPs might be involved in oyster immune response against RLO infection. Copyright © 2016 Elsevier Ltd. All rights reserved.
Qu, Jian-Bo; Chen, Yan-Li; Huan, Guan-Sheng; Zhou, Wei-Qing; Liu, Jian-Guo; Zhu, Hu; Zhang, Xiao-Yun
2015-01-01
A high-speed thermoresponsive medium was developed by grafting poly(N-isopropylacrylamide-co-butyl methacrylate) (P(NIPAM-co-BMA)) brushes onto gigaporous polystyrene (PS) microspheres via surface-initiated atom transfer radical polymerization (ATRP) technique, which has strong mechanical strength, good chemical stability and high mass transfer rate for biomacromolecules. The gigaporous structure, surface chemical composition, static protein adsorption, and thermoresponsive chromatographic properties of prepared medium (PS-P(NIPAM-co-BMA)) were characterized in detail. Results showed that the PS microspheres were successfully grafted with P(NIPAM-co-BMA) brushes and that the gigaporous structure was robustly maintained. After grafting, the nonspecific adsorption of proteins on PS microspheres was greatly reduced. A column packed with PS-P(NIPAM-co-BMA) exhibited low backpressure and significant thermo-responsibility. By simply changing the column temperature, it was able to separate three model proteins at the mobile phase velocity up to 2167 cm h(-1). In conclusion, the thermoresponsive polymer brushes grafted gigaporous PS microspheres prepared by ATRP are very promising in 'green' high-speed preparative protein chromatography. Copyright © 2014 Elsevier B.V. All rights reserved.
Griffioen, A W; Rijkers, G T; Janssens-Korpela, P; Zegers, B J
1991-01-01
The immunoregulatory function of the complement system has been the focus of many investigations. In particular, fragments of complement factor C3 have been shown to play a role in B-lymphocyte activation and proliferation, lymphokine production, and the generation of in vitro antibody production. Purified pneumococcal polysaccharides (PS) can induce direct activation of C3 via the alternative pathway. Using sera of C1q-deficient patients and healthy subjects, we demonstrated that C3d, a split product of C3 that is generated after degradation of iC3b, can be bound to PS antigens. The binding of C3d to PS can occur in the absence of specific antibodies. Subsequently, we showed that PS complexed with C3d can be recognized by complement receptor type 2 that is expressed on B cells. Treatment of B cells with a monoclonal antibody recognizing the C3d-binding site of complement receptor type 2 reduces the binding of PS-C3d to the cells. In addition, we showed that PS4 complexed with C3d exerted an increased immunogenicity compared with free PS4. Our results show that the complement system plays a role in the activation of PS-specific B cells, carrying membrane receptors for C3d. Consequently, the complement system plays a regulatory role in the antibody response to T-cell-independent type 2 antigens such as PS. PMID:1826897
The directed differentiation of human iPS cells into kidney podocytes.
Song, Bi; Smink, Alexandra M; Jones, Christina V; Callaghan, Judy M; Firth, Stephen D; Bernard, Claude A; Laslett, Andrew L; Kerr, Peter G; Ricardo, Sharon D
2012-01-01
The loss of glomerular podocytes is a key event in the progression of chronic kidney disease resulting in proteinuria and declining function. Podocytes are slow cycling cells that are considered terminally differentiated. Here we provide the first report of the directed differentiation of induced pluripotent stem (iPS) cells to generate kidney cells with podocyte features. The iPS-derived podocytes share a morphological phenotype analogous with cultured human podocytes. Following 10 days of directed differentiation, iPS podocytes had an up-regulated expression of mRNA and protein localization for podocyte markers including synaptopodin, nephrin and Wilm's tumour protein (WT1), combined with a down-regulation of the stem cell marker OCT3/4. In contrast to human podocytes that become quiescent in culture, iPS-derived cells maintain a proliferative capacity suggestive of a more immature phenotype. The transduction of iPS podocytes with fluorescent labeled-talin that were immunostained with podocin showed a cytoplasmic contractile response to angiotensin II (AII). A permeability assay provided functional evidence of albumin uptake in the cytoplasm of iPS podocytes comparable to human podocytes. Moreover, labeled iPS-derived podocytes were found to integrate into reaggregated metanephric kidney explants where they incorporated into developing glomeruli and co-expressed WT1. This study establishes the differentiation of iPS cells to kidney podocytes that will be useful for screening new treatments, understanding podocyte pathogenesis, and offering possibilities for regenerative medicine.
1980-01-01
A method is presented for covalently bonding Haemophilus influenzae type b capsular polysaccharide (HIB Ps) to several proteins. The method is efficient and relies upon the use of adipic dihydrazide as a spacer between the capsular polysaccharide and the carrier protein. In contrast to the poor immunogenicity of the purified HIB Ps in mice and rabbits, the HIB Ps-protein conjugates induced serum anti-type b antibodies having bactericidal activity at levels shown to be protective in humans when low doses were injected subcutaneously in a saline solution. The antibody response in mice was related to the dose of the conjugates, increased with the number of injections, and could be primed by the previous injection of the carrier protein. The HIB Ps- protein conjugates were immunogenic in three different mouse strains. The importance of the carrier molecule for the enhanced immunogenicity of the HIB Ps-protein conjugates was shown by the failure of HIB Ps hybrids prepared with either the homologous polysaccharide or pneumococcus type 3 polysaccharide to induce antibodie in mice. Rabbits injected with the HIB Ps-protein conjugates emulsified in Freund's adjuvant produced high levels of serum anti-type b antibodies which induced a bactericidal effect upon H. influenzae type b organisms. It is proposed that the HIB Ps component of the polysaccharide protein conjugates has been converted to a thymic-dependent immunogen. This method may be used to prepare protein-polysaccharide conjugates with HIB Ps and other polysaccharides to be considered for human use. PMID:6967514
Do, Young S.; Schmidt, Thomas M.; Zahn, James A.; Boyd, Eric S.; de la Mora, Arlene; DiSpirito, Alan A.
2003-01-01
Temporal pigmentation changes resulting from the development of a purple color in anaerobic swine waste lagoons were investigated during a 4-year period. The major purple photosynthetic bacterium responsible for these color changes and the corresponding reductions in odor was isolated from nine photosynthetic lagoons. By using morphological, physiological, and phylogenetic characterization methods we identified the predominant photosynthetic bacterium as a new strain of Rhodobacter, designated Rhodobacter sp. strain PS9. Rhodobacter sp. strain PS9 is capable of photoorganotrophic growth on a variety of organic compounds, including all of the characteristic volatile organic compounds (VOC) responsible for the odor associated with swine production facilities (J. A. Zahn, A. A. DiSpirito, Y. S. Do, B. E. Brooks, E. E. Copper, and J. L. Hatfield, J. Environ. Qual. 30:624-634, 2001). The seasonal variations in airborne VOC emitted from waste lagoons showed that there was a 80 to 93% decrease in the concentration of VOC during a photosynthetic bloom. During the height of a bloom, the Rhodobacter sp. strain PS9 population accounted for 10% of the total community and up to 27% of the eubacterial community based on 16S ribosomal DNA signals. Additional observations based on seasonal variations in meteorological, biological, and chemical parameters suggested that the photosynthetic blooms of Rhodobacter sp. strain PS9 were correlated with lagoon water temperature and with the concentrations of sulfate and phosphate. In addition, the photosynthetic blooms of Rhodobacter sp. strain PS9 were inversely correlated with the concentrations of protein and fluoride. PMID:12620863
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tamborini, D., E-mail: davide.tamborini@polimi.it; Portaluppi, D.; Villa, F.
We present a Time-to-Digital Converter (TDC) card with a compact form factor, suitable for multichannel timing instruments or for integration into more complex systems. The TDC Card provides 10 ps timing resolution over the whole measurement range, which is selectable from 160 ns up to 10 μs, reaching 21 ps rms precision, 1.25% LSB rms differential nonlinearity, up to 3 Mconversion/s with 400 mW power consumption. The I/O edge card connector provides timing data readout through either a parallel bus or a 100 MHz serial interface and further measurement information like input signal rate and valid conversion rate (typically usefulmore » for time-correlated single-photon counting application) through an independent serial link.« less
2017-12-30
from the Defense Technical Information Center (DTIC) (http://www.dtic.mil). AFRL-RV-PS-TR-2018-0008 HAS BEEN REVIEWED AND IS APPROVED FOR...report is published in the interest of scientific and technical information exchange, and its publication does not constitute the Government’s approval... information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and
2006-07-01
precision of the determination of Rmax, we established a refined method based on the model of bubble formation described above in section 3.6.1 and the...development can be modeled by hydrodynamic codes based on tabulated equation-of-state data . This has previously demonstrated on ps optical breakdown...per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and
Performance of the Tachyon Time-of-Flight PET Camera
NASA Astrophysics Data System (ADS)
Peng, Q.; Choong, W.-S.; Vu, C.; Huber, J. S.; Janecek, M.; Wilson, D.; Huesman, R. H.; Qi, Jinyi; Zhou, Jian; Moses, W. W.
2015-02-01
We have constructed and characterized a time-of-flight Positron Emission Tomography (TOF PET) camera called the Tachyon. The Tachyon is a single-ring Lutetium Oxyorthosilicate (LSO) based camera designed to obtain significantly better timing resolution than the 550 ps found in present commercial TOF cameras, in order to quantify the benefit of improved TOF resolution for clinically relevant tasks. The Tachyon's detector module is optimized for timing by coupling the 6.15 ×25 mm2 side of 6.15 ×6.15 ×25 mm3 LSO scintillator crystals onto a 1-inch diameter Hamamatsu R-9800 PMT with a super-bialkali photocathode. We characterized the camera according to the NEMA NU 2-2012 standard, measuring the energy resolution, timing resolution, spatial resolution, noise equivalent count rates and sensitivity. The Tachyon achieved a coincidence timing resolution of 314 ps +/- 20 ps FWHM over all crystal-crystal combinations. Experiments were performed with the NEMA body phantom to assess the imaging performance improvement over non-TOF PET. The results show that at a matched contrast, incorporating 314 ps TOF reduces the standard deviation of the contrast by a factor of about 2.3.
Performance of the Tachyon Time-of-Flight PET Camera.
Peng, Q; Choong, W-S; Vu, C; Huber, J S; Janecek, M; Wilson, D; Huesman, R H; Qi, Jinyi; Zhou, Jian; Moses, W W
2015-02-01
We have constructed and characterized a time-of-flight Positron Emission Tomography (TOF PET) camera called the Tachyon. The Tachyon is a single-ring Lutetium Oxyorthosilicate (LSO) based camera designed to obtain significantly better timing resolution than the ~ 550 ps found in present commercial TOF cameras, in order to quantify the benefit of improved TOF resolution for clinically relevant tasks. The Tachyon's detector module is optimized for timing by coupling the 6.15 × 25 mm 2 side of 6.15 × 6.15 × 25 mm 3 LSO scintillator crystals onto a 1-inch diameter Hamamatsu R-9800 PMT with a super-bialkali photocathode. We characterized the camera according to the NEMA NU 2-2012 standard, measuring the energy resolution, timing resolution, spatial resolution, noise equivalent count rates and sensitivity. The Tachyon achieved a coincidence timing resolution of 314 ps +/- ps FWHM over all crystal-crystal combinations. Experiments were performed with the NEMA body phantom to assess the imaging performance improvement over non-TOF PET. The results show that at a matched contrast, incorporating 314 ps TOF reduces the standard deviation of the contrast by a factor of about 2.3.
Performance of the Tachyon Time-of-Flight PET Camera
Peng, Q.; Choong, W.-S.; Vu, C.; Huber, J. S.; Janecek, M.; Wilson, D.; Huesman, R. H.; Qi, Jinyi; Zhou, Jian; Moses, W. W.
2015-01-01
We have constructed and characterized a time-of-flight Positron Emission Tomography (TOF PET) camera called the Tachyon. The Tachyon is a single-ring Lutetium Oxyorthosilicate (LSO) based camera designed to obtain significantly better timing resolution than the ~ 550 ps found in present commercial TOF cameras, in order to quantify the benefit of improved TOF resolution for clinically relevant tasks. The Tachyon’s detector module is optimized for timing by coupling the 6.15 × 25 mm2 side of 6.15 × 6.15 × 25 mm3 LSO scintillator crystals onto a 1-inch diameter Hamamatsu R-9800 PMT with a super-bialkali photocathode. We characterized the camera according to the NEMA NU 2-2012 standard, measuring the energy resolution, timing resolution, spatial resolution, noise equivalent count rates and sensitivity. The Tachyon achieved a coincidence timing resolution of 314 ps +/− ps FWHM over all crystal-crystal combinations. Experiments were performed with the NEMA body phantom to assess the imaging performance improvement over non-TOF PET. The results show that at a matched contrast, incorporating 314 ps TOF reduces the standard deviation of the contrast by a factor of about 2.3. PMID:26594057
Performance of the Tachyon Time-of-Flight PET Camera
Peng, Q.; Choong, W. -S.; Vu, C.; ...
2015-01-23
We have constructed and characterized a time-of-flight Positron Emission Tomography (TOF PET) camera called the Tachyon. The Tachyon is a single-ring Lutetium Oxyorthosilicate (LSO) based camera designed to obtain significantly better timing resolution than the ~ 550 ps found in present commercial TOF cameras, in order to quantify the benefit of improved TOF resolution for clinically relevant tasks. The Tachyon's detector module is optimized for timing by coupling the 6.15 ×25 mm 2 side of 6.15 ×6.15 ×25 mm 3 LSO scintillator crystals onto a 1-inch diameter Hamamatsu R-9800 PMT with a super-bialkali photocathode. We characterized the camera according tomore » the NEMA NU 2-2012 standard, measuring the energy resolution, timing resolution, spatial resolution, noise equivalent count rates and sensitivity. The Tachyon achieved a coincidence timing resolution of 314 ps +/- 20 ps FWHM over all crystal-crystal combinations. Experiments were performed with the NEMA body phantom to assess the imaging performance improvement over non-TOF PET. We find that the results show that at a matched contrast, incorporating 314 ps TOF reduces the standard deviation of the contrast by a factor of about 2.3.« less
Evaluation of a clinical TOF-PET detector design that achieves ⩽100 ps coincidence time resolution
NASA Astrophysics Data System (ADS)
Cates, Joshua W.; Levin, Craig S.
2018-06-01
Commercially available clinical positron emission tomography (PET) detectors employ scintillation crystals that are long (20 mm length) and narrow (4–5 mm width) optically coupled on their narrow end to a photosensor. The aspect ratio of this traditional crystal rod configuration and 511 keV photon attenuation properties yield significant variances in scintillation light collection efficiency and transit time to the photodetector, due to variations in the 511 keV photon interaction depth in the crystal. These variances contribute significant to coincidence time resolution degradation. If instead, crystals are coupled to a photosensor on their long side, near-complete light collection efficiency can be achieved, and scintillation photon transit time jitter is reduced. In this work, we compare the achievable coincidence time resolution (CTR) of LGSO:Ce(0.025 mol%) crystals 3–20 mm in length when optically coupled to silicon photomultipliers (SiPMs) on either their short end or long side face. In this ‘side readout’ configuration, a CTR of 102 ± 2 ps FWHM was measured with mm3 crystals coupled to rows of mm2 SensL-J SiPMs using leading edge time pickoff and a single timing channel. This is in contrast to a CTR of 137 ± 3 ps FWHM when the same crystals were coupled to single mm2 SiPMs on their narrow ends. We further study the statistical limit on CTR using side readout via the Cramér–Rao lower bound (CRLB), with consideration given to ongoing work to further improve photosensor technologies and exploit fast phenomena to ultimately achieve 10 ps FWHM CTR. Potential design aspects of scalable front-end signal processing readout electronics using this side readout configuration are discussed. Altogether, we demonstrate that the side readout configuration offers an immediate solution for 100 ps CTR clinical PET detectors and mitigates factors prohibiting future efforts to achieve 10 ps FWHM CTR.
In vivo imaging of tumor vascular endothelial cells
NASA Astrophysics Data System (ADS)
Zhao, Dawen; Stafford, Jason H.; Zhou, Heling; Thorpe, Philip E.
2013-02-01
Phosphatidylserine (PS), normally restricted to the inner leaflet of the plasma membrane, becomes exposed on the outer surface of viable (non-apoptotic) endothelial cells in tumor blood vessels, probably in response to oxidative stresses present in the tumor microenvironment. In the present study, we optically imaged exposed PS on tumor vasculature in vivo using PGN635, a novel human monoclonal antibody that targets PS. PGN635 F(ab')2 was labeled with the near infrared (NIR) dye, IRDye 800CW. Human glioma U87 cells or breast cancer MDA-MB-231 cells were implanted subcutaneously or orthotopically into nude mice. When the tumors reached ~5 mm in diameter, 800CW- PGN635 was injected via a tail vein and in vivo dynamic NIR imaging was performed. For U87 gliomas, NIR imaging allowed clear detection of tumors as early as 4 h later, which improved over time to give a maximal tumor/normal ratio (TNR = 2.9 +/- 0.5) 24 h later. Similar results were observed for orthotopic MDA-MB-231 breast tumors. Localization of 800CW-PGN635 to tumors was antigen specific since 800CW-Aurexis, a control probe of irrelevant specificity, did not localize to the tumors, and pre-administration of unlabeled PGN635 blocked the uptake of 800CW-PGN635. Fluorescence microscopy confirmed that 800CW-PGN635 was binding to PS-positive tumor vascular endothelium. Our studies suggest that tumor vasculature can be successfully imaged in vivo to provide sensitive tumor detection.
Song, Peipei; Inagaki, Yoshinori; Sugawara, Yasuhiko; Kokudo, Norihiro
2013-06-01
A research project involving sheets of retinal pigment epithelium constructed from iPS cells derived from patients with age-related maculopathy is one step closer to being approved for clinical trials by the Japanese Government. Now is the time to make therapies using iPS cells clinically available.
Nearly penalty-free, less than 4 ps supercontinuum Gbit/s pulse generation over 1535-1560 nm
NASA Astrophysics Data System (ADS)
Morioka, T.; Kawanishi, S.; Mori, K.; Saruwatari, M.
1994-05-01
Nearly penalty-free less than 4ps supercontinuum WDM pulses are generated at 6.3 Gbit/s over 1535-1560 nm for the first time using a 200 nm superbroadened supercontinuum in an optical fibre pumped by 1.7 W, 3.3 ps, 1542 nm short pulses from an Er(3+)-doped fibre ring laser.
Karupaiah, Tilakavati; Sundram, Kalyana
2013-08-16
Postprandial lipemia (PL) contributes to coronary artery disease. The fatty acid composition of dietary fats is potentially a modifiable factor in modulating PL response. This human postprandial study evaluated 3 edible fat blends with differing polyunsaturated to saturated fatty acids (P/S) ratios (POL = 0.27, AHA = 1.00, PCAN = 1.32). A cross-over design included mildly hypercholestrolemic subjects (9 men and 6 women) preconditioned on test diets fats at 31% energy for 7 days prior to the postprandial challenge on the 8th day with 50 g test fat. Plasma lipids and lipoproteins were monitored at 0, 1.5, 3.5, 5.5 and 7 hr. Plasma triacylglycerol (TAG) concentrations in response to POL, AHA or PCAN meals were not significant for time x test meal interactions (P > 0.05) despite an observed trend (POL > AHA > PCAN). TAG area-under-the-curve (AUC) increased by 22.58% after POL and 7.63% after PCAN compared to AHA treatments (P > 0.05). Plasma total cholesterol (TC) response was not significant between meals (P > 0.05). Varying P/S ratios of test meals significantly altered prandial high density lipoprotein-cholesterol (HDL-C) concentrations (P < 0.001) which increased with decreasing P/S ratio (POL > AHA > PCAN). Paired comparisons was significant between POL vs PCAN (P = 0.009) but not with AHA or between AHA vs PCAN (P > 0.05). A significantly higher HDL-C AUC for POL vs AHA (P = 0.015) and PCAN (P = 0.001) was observed. HDL-C AUC increased for POL by 25.38% and 16.0% compared to PCAN and AHA respectively. Plasma low density lipoprotein-cholesterol (LDL-C) concentrations was significant (P = 0.005) between meals and significantly lowest after POL meal compared to PCAN (P = 0.004) and AHA (P > 0.05) but not between AHA vs PCAN (P > 0.05). AUC for LDL-C was not significant between diets (P > 0.05). Palmitic (C16:0), oleic (C18:1), linoleic (C18:2) and linolenic (C18:3) acids in TAGs and cholesteryl esters were significantly modulated by meal source (P < 0.05). P/S ratio of dietary fats significantly affected prandial HDL-C levels without affecting lipemia.
2013-01-01
Background Postprandial lipemia (PL) contributes to coronary artery disease. The fatty acid composition of dietary fats is potentially a modifiable factor in modulating PL response. Methods This human postprandial study evaluated 3 edible fat blends with differing polyunsaturated to saturated fatty acids (P/S) ratios (POL = 0.27, AHA = 1.00, PCAN = 1.32). A cross-over design included mildly hypercholestrolemic subjects (9 men and 6 women) preconditioned on test diets fats at 31% energy for 7 days prior to the postprandial challenge on the 8th day with 50 g test fat. Plasma lipids and lipoproteins were monitored at 0, 1.5, 3.5, 5.5 and 7 hr. Results Plasma triacylglycerol (TAG) concentrations in response to POL, AHA or PCAN meals were not significant for time x test meal interactions (P > 0.05) despite an observed trend (POL > AHA > PCAN). TAG area-under-the-curve (AUC) increased by 22.58% after POL and 7.63% after PCAN compared to AHA treatments (P > 0.05). Plasma total cholesterol (TC) response was not significant between meals (P > 0.05). Varying P/S ratios of test meals significantly altered prandial high density lipoprotein-cholesterol (HDL-C) concentrations (P < 0.001) which increased with decreasing P/S ratio (POL > AHA > PCAN). Paired comparisons was significant between POL vs PCAN (P = 0.009) but not with AHA or between AHA vs PCAN (P > 0.05). A significantly higher HDL-C AUC for POL vs AHA (P = 0.015) and PCAN (P = 0.001) was observed. HDL-C AUC increased for POL by 25.38% and 16.0% compared to PCAN and AHA respectively. Plasma low density lipoprotein-cholesterol (LDL-C) concentrations was significant (P = 0.005) between meals and significantly lowest after POL meal compared to PCAN (P = 0.004) and AHA (P > 0.05) but not between AHA vs PCAN (P > 0.05). AUC for LDL-C was not significant between diets (P > 0.05). Palmitic (C16:0), oleic (C18:1), linoleic (C18:2) and linolenic (C18:3) acids in TAGs and cholesteryl esters were significantly modulated by meal source (P < 0.05). Conclusions P/S ratio of dietary fats significantly affected prandial HDL-C levels without affecting lipemia. PMID:23953645
Haroon, Muhammad; Ahmad, Muddassar; Baig, Muhammad Nouman; Mason, Olivia; Rice, John; FitzGerald, Oliver
2018-04-17
The efficacy of corticosteroids in patients with psoriatic arthritis (PsA) and inflammatory back pain has not been studied to date. In this controlled trial, we aimed to investigate the comparative performance of corticosteroids in patients with active axial-PsA (AxPsA) versus those with active ankylosing spondylitis (AS). Patients with AxPsA and AS (naïve to biologic therapies), who not only had clinically active disease, but also had bone marrow oedema on magnetic resonance imaging of the sacroiliac joints, were recruited. Clinically active disease was defined as inflammatory back pain (fulfilling Assessment of Spondyloarthritis International Society (ASAS) expert criteria), with spinal pain score (numerical rating scale 0-10) ≥4 and Bath AS Disease Activity Index (BASDAI) score ≥4 despite taking nonsteroidal anti-inflammatory drugs. Moreover, we recruited a control group of patients with non-inflammatory lower back pain. All patients received a single, intra-muscular dose of depot corticosteroid injection (triamcinolone acetonide 80 mg) at baseline. The intra-muscular corticosteroid option was used to overcome any drug compliance issues. Clinical outcome assessments were made at the following time points: baseline, week 2, and week 4. The primary efficacy end point was mean change in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 2. Key secondary outcomes were mean change in the BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI) and Ankylosing Spondylitis Quality of Life (ASQoL) at weeks 2 and 4. In total, 40 patients were recruited (15 with AxPsA, 15 with AS, and 10 controls). At week 2 following corticosteroid treatment, patients with AxPsA had significantly greater improvement in the mean ASDAS compared to patients with AS (1.43 ± 0.39 vs. 1.03 ± 0.30, p = 0.004), and also when compared to controls (p < 0.001). At week-4, similar significant trend of ASDAS improvement was seen among AxPsA patients compared to AS patients (1.09 ± 0.32 vs. 0.77 ± 0.27, p = 0.007) and controls (p < 0.001). Similarly, the mean BASDAI, visual analogue scale spinal pain score, ASQoL and BASFI improved significantly among patients with AxPsA compared to patients with AS and controls at week 2 (p < 0.05), with this trend also largely maintained at week 4. Axial inflammation in patients with PsA responds significantly better to corticosteroids than in patients with AS. This furthers the argument and adds to the growing evidence that AxPsA and AS are distinct entities.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kumada, Takayuki, E-mail: kumada.takayuki@jaea.go.jp; Otobe, Tomohito; Nishikino, Masaharu
2016-01-04
The dynamics of photomechanical spallation during femtosecond laser ablation of fused silica was studied by time-resolved reflectivity with double pump pulses. Oscillation of reflectivity was caused by interference between the probe pulses reflected at the sample surface and the spallation layer, and was enhanced when the surface was irradiated with the second pump pulse within a time interval, Δτ, of several picoseconds after the first pump pulse. However, as Δτ was increased, the oscillation amplitude decreased with an exponential decay time of 10 ps. The oscillation disappeared when Δτ exceeded 20 ps. This result suggests that the formation time of the spallationmore » layer is approximately 10 ps. A second pump pulse with Δτ shorter than 10 ps excites the bulk sample. The spallation layer that is photo-excited by the first and second pump pulses is separated afterward. In contrast, a pulse with Δτ longer than the formation time excites and breaks up the spallation layer that has already been separated from the bulk. The formation time of the spallation layer, as determined in this experiment, is attributed to the characteristic time of the mechanical equilibration corresponding to the thickness divided by the sound velocity of the photo-excited layer.« less
Phuc, Le Thi Minh; Taniguchi, Akiyoshi
2017-01-01
The interaction between nanoparticles and cells has been studied extensively, but most research has focused on the effect of various nanoparticle characteristics, such as size, morphology, and surface charge, on the cellular uptake of nanoparticles. In contrast, there have been very few studies to assess the influence of cellular factors, such as growth factor responses, on the cellular uptake efficiency of nanoparticles. The aim of this study was to clarify the effects of epidermal growth factor (EGF) on the uptake efficiency of polystyrene nanoparticles (PS NPs) by A431 cells, a human carcinoma epithelial cell line. The results showed that EGF enhanced the uptake efficiency of A431 cells for PS NPs. In addition, inhibition and localization studies of PS NPs and EGF receptors (EGFRs) indicated that cellular uptake of PS NPs is related to the binding of EGF–EGFR complex and PS NPs. Different pathways are used to enter the cells depending on the presence or absence of EGF. In the presence of EGF, cellular uptake of PS NPs is via clathrin-mediated endocytosis, whereas, in the absence of EGF, uptake of PS NPs does not involve clathrin-mediated endocytosis. Our findings indicate that EGF enhances cellular uptake of PS NPs by clathrin-mediated endocytosis. This result could be important for developing safe nanoparticles and their safe use in medical applications. PMID:28629179
Shaw, Jonathan; Saunders, John Michael; Hughes, Gwenda
2018-05-01
Chlamydia trachomatis and Neisseria gonorrhoeae testing guidance recommends extragenital screening with locally validated nucleic acid amplification tests, with anatomical sites tested separately. Evidence supports multi-patient combined aliquot pooled sampling (PS) for population screening; evidence for within-patient PS is sparse. Within-patient PS could be more cost-effective for triple-site testing, but requires distinct clinical pathways and consideration over loss of information to guide risk assessments and treatment. We explored PS attitudes and practices amongst clinicians in England. A cross-sectional web-based survey was distributed to clinical leads of sexual health services throughout England in February 2016. Fifty-two (52/216, 23%) services responded. One service reported current within-patient PS and two were awaiting implementation. Of the 49 services not pooling, five were considering implementation. Concerns raised included the inability to distinguish infection site(s) (36/52, 69%), absence of national guidance (34/52, 65%) and reduced assay performance (18/52, 34%). Only 8/52 (15%) considered the current level of evidence sufficient to support PS, with 40/52 (77%) requesting further validation studies and 39/52 (77%) national guidance. PS was rarely used by respondents to this survey, although the response rate was low. The clinical challenges presented by PS need to be addressed through further development of the evidence base.
Kaneko, Shun; Kakinuma, Sei; Asahina, Yasuhiro; Kamiya, Akihide; Miyoshi, Masato; Tsunoda, Tomoyuki; Nitta, Sayuri; Asano, Yu; Nagata, Hiroko; Otani, Satoshi; Kawai-Kitahata, Fukiko; Murakawa, Miyako; Itsui, Yasuhiro; Nakagawa, Mina; Azuma, Seishin; Nakauchi, Hiromitsu; Nishitsuji, Hironori; Ujino, Saneyuki; Shimotohno, Kunitada; Iwamoto, Masashi; Watashi, Koichi; Wakita, Takaji; Watanabe, Mamoru
2016-01-01
Hepatitis B virus (HBV) is not eradicated by current antiviral therapies due to persistence of HBV covalently closed circular DNA (cccDNA) in host cells, and thus development of novel culture models for productive HBV infection is urgently needed, which will allow the study of HBV cccDNA eradication. To meet this need, we developed culture models of HBV infection using human induced pluripotent stem cell-derived hepatocyte lineages, including immature proliferating hepatic progenitor-like cell lines (iPS-HPCs) and differentiated hepatocyte-like cells (iPS-Heps). These cells were susceptible to HBV infection, produced HBV particles, and maintained innate immune responses. The infection efficiency of HBV in iPS-HPCs predominantly depended on the expression levels of sodium taurocholate cotransporting polypeptide (NTCP), and was low relative to iPS-Heps: however, long-term culture of iPS-Heps was difficult. To provide a model for HBV persistence, iPS-HPCs overexpressing NTCP were established. The long-term persistence of HBV cccDNA was detected in iPS-HPCs overexpressing NTCP, and depended on the inhibition of the Janus-kinase signaling pathway. In conclusion, this study provides evidence that iPS-derived hepatic cell lines can be utilized for novel HBV culture models with genetic variation to investigate the interactions between HBV and host cells and the development of anti-HBV strategies. PMID:27386799
Phuc, Le Thi Minh; Taniguchi, Akiyoshi
2017-06-19
The interaction between nanoparticles and cells has been studied extensively, but most research has focused on the effect of various nanoparticle characteristics, such as size, morphology, and surface charge, on the cellular uptake of nanoparticles. In contrast, there have been very few studies to assess the influence of cellular factors, such as growth factor responses, on the cellular uptake efficiency of nanoparticles. The aim of this study was to clarify the effects of epidermal growth factor (EGF) on the uptake efficiency of polystyrene nanoparticles (PS NPs) by A431 cells, a human carcinoma epithelial cell line. The results showed that EGF enhanced the uptake efficiency of A431 cells for PS NPs. In addition, inhibition and localization studies of PS NPs and EGF receptors (EGFRs) indicated that cellular uptake of PS NPs is related to the binding of EGF-EGFR complex and PS NPs. Different pathways are used to enter the cells depending on the presence or absence of EGF. In the presence of EGF, cellular uptake of PS NPs is via clathrin-mediated endocytosis, whereas, in the absence of EGF, uptake of PS NPs does not involve clathrin-mediated endocytosis. Our findings indicate that EGF enhances cellular uptake of PS NPs by clathrin-mediated endocytosis. This result could be important for developing safe nanoparticles and their safe use in medical applications.
USDA-ARS?s Scientific Manuscript database
The benefits of plant sterols (PS) for cholesterol lowering are hampered by large heterogeneity across individuals, potentially due to genetic polymorphisms. We investigated the impact of candidate genetic variations on cholesterol response to PS, in a trial which recruited individuals with high or ...
Time resolution deterioration with increasing crystal length in a TOF-PET system
NASA Astrophysics Data System (ADS)
Gundacker, S.; Knapitsch, A.; Auffray, E.; Jarron, P.; Meyer, T.; Lecoq, P.
2014-02-01
Highest time resolution in scintillator based detectors is becoming more and more important. In medical detector physics L(Y)SO scintillators are commonly used for time of flight positron emission tomography (TOF-PET). Coincidence time resolutions (CTRs) smaller than 100 ps FWHM are desirable in order to improve the image signal to noise ratio and thus give benefit to the patient by shorter scanning times. Also in high energy physics there is the demand to improve the timing capabilities of calorimeters down to 10 ps. To achieve these goals it is important to study the whole chain, i.e. the high energy particle interaction in the crystal, the scintillation process itself, the scintillation light transfer in the crystal, the photodetector and the electronics. Time resolution measurements for a PET like system are performed with the time-over-threshold method in a coincidence setup utilizing the ultra-fast amplifier-discriminator NINO. With 2×2×3 mm3 LSO:Ce codoped 0.4%Ca crystals coupled to commercially available SiPMs (Hamamatsu S10931-050P MPPC) we achieve a CTR of 108±5 ps FWHM at an energy of 511 keV. Under the same experimental conditions an increase in crystal length to 5 mm deteriorates the CTR to 123±7 ps FWHM, 10 mm to 143±7 ps FWHM and 20 mm to 176±7 ps FWHM. This degradation in CTR is caused by the light transfer efficiency (LTE) and light transfer time spread (LTTS) in the crystal. To quantitatively understand the measured values, we developed a Monte Carlo simulation tool in MATLAB incorporating the timing properties of the photodetector and electronics, the scintillation properties of the crystal and the light transfer within the crystal simulated by SLITRANI. In this work, we show that the predictions of the simulation are in good agreement with the experimental data. We conclude that for longer crystals the deterioration in CTR is mainly caused by the LTE, i.e. the ratio of photons reaching the photodetector to the total amount of photons generated by the scintillation whereas the LTTS influence is partly offset by the gamma absorption in the crystal.
Rosado, M Manuela; Gesualdo, Francesco; Marcellini, Valentina; Di Sabatino, Antonio; Corazza, Gino Roberto; Smacchia, Maria Paola; Nobili, Bruno; Baronci, Carlo; Russo, Lidia; Rossi, Francesca; Vito, Rita De; Nicolosi, Luciana; Inserra, Alessandro; Locatelli, Franco; Tozzi, Alberto E; Carsetti, Rita
2013-10-01
Splenectomized patients are exposed to an increased risk of septicemia caused by encapsulated bacteria. Defense against infection is ensured by preformed serum antibodies produced by long-lived plasma cells and by memory B cells that secrete immunoglobulin in response to specific antigenic stimuli. Studying a group of asplenic individuals (57 adults and 21 children) without additional immunologic defects, we found that spleen removal does not alter serum anti-pneumococcal polysaccharide (PnPS) IgG concentration, but reduces the number of PnPS-specific memory B cells, of both IgM and IgG isotypes. The number of specific memory B cells was low in splenectomized adults and children that had received the PnPS vaccine either before or after splenectomy. Seven children were given the 13-valent pneumococcal conjugated vaccine after splenectomy. In this group, the number of PnPS-specific IgG memory B cells was similar to that of eusplenic children, suggesting that pneumococcal conjugated vaccine administered after splenectomy is able to restore the pool of anti-PnPS IgG memory B cells. Our data further elucidate the crucial role of the spleen in the immunological response to infections caused by encapsulated bacteria and suggest that glycoconjugated vaccines may be the most suitable choice to generate IgG-mediated protection in these patients. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Interleukin 4 signals through two related pathways.
Pernis, A; Witthuhn, B; Keegan, A D; Nelms, K; Garfein, E; Ihle, J N; Paul, W E; Pierce, J H; Rothman, P
1995-08-15
The interleukin 4 (IL-4) signaling pathway involves activation, by tyrosine phosphorylation, of two distinct substrates, a signal-transducing factor (STF-IL4) and the IL-4-induced phosphotyrosine substrate (4PS). It is not known whether the IL-4-mediated activation of these substrates occurs via related or distinct signaling pathways. We report that 32D cells, an IL-3-dependent myeloid progenitor cell line in which no phosphorylated 4PS is found, activate high levels of STF-IL4 in response to IL-4. Consistent with the known requirement for 4PS or insulin receptor substrate 1 (IRS-1) in IL-4-mediated mitogenesis, activation of STF-IL4 in 32D cells is not sufficient for IL-4-inducible c-myc expression. In addition, we have examined the ability of 32D cells transfected with different truncation mutants of the human IL-4 receptor to activate Jak-3 kinase and STF-IL4 in response to human IL-4. As in the case of 4PS/IRS-1, we have found that activation of both Jak-3 and STF-IL4 requires the presence of the IL-4 receptor region comprising aa 437-557. The finding that the same region of the IL-4 receptor is required for the induction of both 4PS/IRS-1 and STF-IL4 suggests that the IL-4-stimulated activation of these two substrates might involve common factors.
NASA Astrophysics Data System (ADS)
Motwani, Tanuj
Starch-water interactions occurring during gelatinization are critical for developing a mechanistic understanding of the gelatinization process. The overall goal of this project was to investigate the state of water in starch-water systems in the gelatinization temperature range using dielectric relaxation spectroscopy. In the first part of the project, the dielectric response of native wheat starch-water slurries was measured at seven different starch concentrations between 5--60% starch (w/w) in the frequency range of 200 MHz--20 GHz at 25°C. The deconvolution of the dielectric spectra using the Debye model revealed presence of up to three relaxation processes. The relaxation time range of what were considered to be the high, intermediate and low frequency relaxations were 4--9 ps, 20--25 ps and 230--620 ps, respectively. The high frequency relaxation was observed at all starch concentrations, while the intermediate and low frequency relaxation were only observed at starch concentrations of 10% and above, and 30% and above, respectively. The high frequency relaxation was attributed to bulk water, while the intermediate and low frequency relaxations were attributed to rotationally restrained water molecules present in the starch-water system. To investigate the state of water in the gelatinization temperature range, the dielectric response, gelatinization enthalpy and water absorption by 10%, 30% or 50% starch slurries were measured after heating the slurries to different end temperatures between 40--90°C for 30 min. The high frequency relaxation time for 10% starch slurry dropped significantly (P<0.001) upon heating up to 60°C. For 30% and 50% starch slurries, high frequency relaxation times were not significantly influenced (P>0.159) by heating up to 80°C. The intermediate and low frequency relaxation times were not significantly influenced (P>0.712) by heating for all starch concentrations. Also, the amount of water associated with the three relaxations was not significantly influenced by heating (P >0.187). The water absorption results indicated that highest water uptake was achieved in the 10% starch slurry. The endothermic peak associated with gelatinization either vanished or was diminished after heating the slurries to 60°C and above, suggesting that native granular order was not necessary for the existence of the three separate states of water. In the second part of the project, the dielectric response of starch-water systems was investigated in the presence or absence of glucose or maltose. Dielectric response of 10% starch + 10% sugar, 10% starch + 20% sugar or 10% starch + 30% sugar slurries was measured in the frequency range of 200 MHz--20 GHz after heating the slurries to different end temperatures between 25--90°C for 30 min. The dielectric spectra of the slurries could be deconvoluted to obtain up to three Debye-type relaxations. The relaxation time range of high, intermediate and low frequency relaxations were 4--7 ps, 17--26 ps and 175--335 ps, respectively, at 25°C. The high frequency relaxation was the dominant relaxation in slurries containing 10% sugar, and the intermediate frequency relaxation was the dominant relaxation in slurries containing 30% sugar at 25°C. The high frequency relaxation time decreased upon heating up to 60°C but was not significantly influenced (P>0.102) by the concentration or the type of sugar. Intermediate and low frequency relaxation times were not significantly influenced (P>0.419) by heating or sugar type. The relative strengths of the intermediate frequency relaxation dropped while that of high frequency relaxation increased upon heating up to 50°C. The relative strength of low frequency relaxation (P>0.561) was not influenced by heating. The static dielectric constant decreased upon heating but was not influenced by the type of sugar or solids in the slurry. This indicated that the water molecules present in the system were the major contributors to the polarization observed. At the same concentration of solids, conductivity of the sugar containing slurries was lower than that of the non-sugar-containing starch slurries, which suggested that conductivity was mostly associated with starch. Glucose or maltose did not exert any differential effect on the swelling behavior or dielectric relaxation parameters of starch-water-sugar slurries. This project presents novel insights into the starch-water interactions occurring in the gelatinization temperature range. The results of this project can be used to develop a dielectric relaxation based technique to monitor water mobility during industrial processing of starch-based foods. Dielectric response was not unique to any of the solids used in the study suggesting that dielectric spectroscopy could be used for monitoring state of water in food systems containing different types of solids. Also, the dielectric relaxation parameters obtained in this study can be used to predict water mobility in simple food systems having water, sugar and starch as major components, and hence, can possibly be used to estimate shelf life of food products.
NASA Astrophysics Data System (ADS)
Choi, Seon-Jin; Chattopadhyay, Saptarshi; Kim, Jae Jin; Kim, Sang-Joon; Tuller, Harry L.; Rutledge, Gregory C.; Kim, Il-Doo
2016-04-01
Macroporous WO3 nanotubes (NTs) functionalized with nanoscale catalysts were fabricated using coaxial electrospinning combined with sacrificial templating and protein-encapsulated catalysts. The macroporous thin-walled nanotubular structures were obtained by introducing colloidal polystyrene (PS) particles to a shell solution of W precursor and poly(vinylpyrrolidone). After coaxial electrospinning with a core liquid of mineral oil and subsequent calcination, open pores with an average diameter of 173 nm were formed on the surface of WO3 NTs due to decomposition of the PS colloids. In addition, catalytic Pd nanoparticles (NPs) were synthesized using bio-inspired protein cages, i.e., apoferritin, and uniformly dispersed within the shell solution and subsequently on the WO3 NTs. The resulting Pd functionalized macroporous WO3 NTs were demonstrated to be high performance hydrogen (H2) sensors. In particular, Pd-functionalized macroporous WO3 NTs exhibited a very high H2 response (Rair/Rgas) of 17.6 at 500 ppm with a short response time. Furthermore, the NTs were shown to be highly selective for H2 compared to other gases such as carbon monoxide (CO), ammonia (NH3), and methane (CH4). The results demonstrate a new synthetic method to prepare highly porous nanotubular structures with well-dispersed nanoscale catalysts, which can provide improved microstructures for chemical sensing.Macroporous WO3 nanotubes (NTs) functionalized with nanoscale catalysts were fabricated using coaxial electrospinning combined with sacrificial templating and protein-encapsulated catalysts. The macroporous thin-walled nanotubular structures were obtained by introducing colloidal polystyrene (PS) particles to a shell solution of W precursor and poly(vinylpyrrolidone). After coaxial electrospinning with a core liquid of mineral oil and subsequent calcination, open pores with an average diameter of 173 nm were formed on the surface of WO3 NTs due to decomposition of the PS colloids. In addition, catalytic Pd nanoparticles (NPs) were synthesized using bio-inspired protein cages, i.e., apoferritin, and uniformly dispersed within the shell solution and subsequently on the WO3 NTs. The resulting Pd functionalized macroporous WO3 NTs were demonstrated to be high performance hydrogen (H2) sensors. In particular, Pd-functionalized macroporous WO3 NTs exhibited a very high H2 response (Rair/Rgas) of 17.6 at 500 ppm with a short response time. Furthermore, the NTs were shown to be highly selective for H2 compared to other gases such as carbon monoxide (CO), ammonia (NH3), and methane (CH4). The results demonstrate a new synthetic method to prepare highly porous nanotubular structures with well-dispersed nanoscale catalysts, which can provide improved microstructures for chemical sensing. Electronic supplementary information (ESI) available: Coaxial electrospinning with different feeding rates, additional TEM analysis for pore size analysis, XPS analysis of Pd-loaded macroporous WO3 NTs, and dynamic response transition properties of sensors. See DOI: 10.1039/c5nr06611e
Evidence for ACD5 ceramide kinase activity involvement in Arabidopsis response to cold stress.
Dutilleul, Christelle; Chavarria, Heidy; Rézé, Nathalie; Sotta, Bruno; Baudouin, Emmanuel; Guillas, Isabelle
2015-12-01
Although sphingolipids emerged as important signals for plant response to low temperature, investigations have been limited so far to the function of long-chain base intermediates. The formation and function of ceramide phosphates (Cer-Ps) in chilled Arabidopsis were explored. Cer-Ps were analysed by thin layer chromatography (TLC) following in vivo metabolic radiolabelling. Ceramide kinase activity, gene expression and growth phenotype were determined in unstressed and cold-stressed wild type (WT) and Arabidopsis ceramide kinase mutant acd5. A rapid and transient formation of Cer-P occurs in cold-stressed WT Arabidopsis plantlets and cultured cells, which is strongly impaired in acd5 mutant. Although concomitant, Cer-P formation is independent of long-chain base phosphate (LCB-P) formation. No variation of ceramide kinase activity was measured in vitro in WT plantlets upon cold stress but the activity in acd5 mutant was further reduced by cold stress. At the seedling stage, acd5 response to cold was similar to that of WT. Nevertheless, acd5 seed germination was hypersensitive to cold and abscisic acid (ABA), and ABA-dependent gene expression was modified in acd5 seeds when germinated at low temperature. Our data involve for the first time Cer-P and ACD5 in low temperature response and further underline the complexity of sphingolipid signalling operating during cold stress. © 2015 John Wiley & Sons Ltd.
Ultrafast compression of graphite observed with sub-ps time resolution diffraction on LCLS
NASA Astrophysics Data System (ADS)
Armstrong, Michael; Goncharov, A.; Crowhurst, J.; Zaug, J.; Radousky, H.; Grivickas, P.; Bastea, S.; Goldman, N.; Stavrou, E.; Belof, J.; Gleason, A.; Lee, H. J.; Nagler, R.; Holtgrewe, N.; Walter, P.; Pakaprenka, V.; Nam, I.; Granados, E.; Presher, C.; Koroglu, B.
2017-06-01
We will present ps time resolution pulsed x-ray diffraction measurements of rapidly compressed highly oriented pyrolytic graphite along its basal plane at the Materials under Extreme Conditions (MEC) sector of the Linac Coherent Light Source (LCLS). These experiments explore the possibility of rapid (<100 ps time scale) material transformations occurring under very highly anisotropic compression conditions. Under such conditions, non-equilibrium mechanisms may play a role in the transformation process. We will present experimental results and simulations which explore this possibility. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Security, LLC under Contract DE-AC52-07NA27344.
Progresses in Polystyrene Biodegradation and Prospects for Solutions to Plastic Waste Pollution
NASA Astrophysics Data System (ADS)
Yang, S. S.; Brandon, A. M.; Xing, D. F.; Yang, J.; Pang, J. W.; Criddle, C. S.; Ren, N. Q.; Wu, W. M.
2018-05-01
Petroleum-based plastic pollution has been a global environmental concern for decades. The obvious contrast between the remarkable durability of the plastics and their short service time leads to the increasing accumulation of plastic wastes in the environment. A cost-effective, sustainable strategy to solve the problem should focus on source control and clean up. Polystyrene (PS) wastes, a recalcitrant plastic polymer, are among the wide spread man-made plastic pollutants. Destruction of PS wastes can be achieved using various abiotic methods such as incineration but such methods release potential air pollution and generation of hazardous by-products. Biodegradation and bioremediation has been proposed for years. Since the 1970’s, the microbial biodegradation of plastics, including PS, has been evaluated with mixed and isolated cultures from different sources such as activated sludge, trash, soil, and manure. To date, PS biodegradation by these microbial cultures is still quite slow. Recently, the larvae of yellow mealworms (Tenebrio molitor Linnaeus) have demonstrated promising PS biodegradation performance. Mealworms have demonstrated the ability to chew and ingest PS foam as food and are capable of degrading and mineralizing PS into CO2 via microbe-dependent activities within the gut in less than the 12-15 hrs gut retention time. These research results have revealed a potential for microbial biodegradation and bioremediation of plastic pollutants.
Goodman, Y E; Wort, A J; Jackson, F L
1981-01-01
An enzyme-linked immunosorbent assay was developed for detection of immunoglobulin A (IgA) antibody to Bordetella pertussis (PsIgA) in nasopharyngeal secretions as an indicator of recent infection. Secretion specimens submitted for pertussis culture were examined for PsIgA by this technique. Of 348 specimens tested, B. pertussis was cultured from 57, and PsIgA was detected in 8 culture-positive and 40 culture-negative specimens. The average time between onset of symptoms and specimen collection for the culture-positive, PsIgA-negative specimens was 10 days; for the culture-positive, PsIgA-positive specimens, 15 days; and for the culture-negative, PsIgA-positive specimens, 36 days. Examination of paired samples available from several culture-proven cases demonstrated conversion from a negative PsIgA in the early sample to a positive PsIgA in the follow-up sample. Our results indicate that PsIgA is produced during natural human infection and does not arise as a result of parenteral vaccination. PsIgA usually appears in the nasopharyngeal secretions during the second or third week of illness and persists for at least 3 months. The detection of PsIgA in secretions may be a valuable diagnostic aid in culture-negative patients with pertussis. Images PMID:6259201
He, Yulu; Hua, Wei-Hsiang; Low, Meng-Chun; Tsai, Yu-Hsuan; Cai, Cheng-Jin; Chiang, Hsin-Chun; Yu, Jian-He; Hsiao, Jen-Hung; Tseng, Po-Hao; Kiang, Yean-Woei; Yang, C C; Zhang, Zhenxi
2018-06-08
We first illustrate the faster decrease of the photothermal (PT) effect with the delay time of laser treatment, in which the illumination of a 1064 nm laser effectively excites the localized surface plasmon (LSP) resonance of cell-up-taken gold nanoring (NRI) linked with a photosensitizer (PS), when compared with the photodynamic (PD) effect produced by the illumination of a 660 nm laser for effective PS excitation. The measurement results of the metal contents of Au NRI and PS based on inductively coupled plasma mass spectroscopy and the PS fluorescence intensity based on flow cytometry show that the linkage of NRI and PS is rapidly broken for releasing PS through the effect of glutathione in lysosome after cell uptake. Meanwhile, NRI escapes from a cell with a high rate such that the PT effect decays fast while the released PS can stay inside a cell longer for producing a prolonged PD effect. The effective delivery of PS through the linkage with Au NRI for cell uptake and the advantageous effect of LSP resonance at a PS absorption wavelength on the PD process are also demonstrated.
NASA Astrophysics Data System (ADS)
He, Yulu; Hua, Wei-Hsiang; Low, Meng-Chun; Tsai, Yu-Hsuan; Cai, Cheng-Jin; Chiang, Hsin-Chun; Yu, Jian-He; Hsiao, Jen-Hung; Tseng, Po-Hao; Kiang, Yean-Woei; Yang, C. C.; Zhang, Zhenxi
2018-06-01
We first illustrate the faster decrease of the photothermal (PT) effect with the delay time of laser treatment, in which the illumination of a 1064 nm laser effectively excites the localized surface plasmon (LSP) resonance of cell-up-taken gold nanoring (NRI) linked with a photosensitizer (PS), when compared with the photodynamic (PD) effect produced by the illumination of a 660 nm laser for effective PS excitation. The measurement results of the metal contents of Au NRI and PS based on inductively coupled plasma mass spectroscopy and the PS fluorescence intensity based on flow cytometry show that the linkage of NRI and PS is rapidly broken for releasing PS through the effect of glutathione in lysosome after cell uptake. Meanwhile, NRI escapes from a cell with a high rate such that the PT effect decays fast while the released PS can stay inside a cell longer for producing a prolonged PD effect. The effective delivery of PS through the linkage with Au NRI for cell uptake and the advantageous effect of LSP resonance at a PS absorption wavelength on the PD process are also demonstrated.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Muir, R.; Heebner, J.
In this study, we demonstrate a novel, single-shot recording technology for transient optical signals. A resolution of 0.4 ps over a record length of 54 ps was demonstrated. Here, a pump pulse crossing through a signal samples a diagonal “slice” of space–time, enabling a camera to record spatially the time content of the signal. Unlike related X (2)-based cross-correlation techniques, here the signal is sampled through optically pumped carriers that modify the refractive index of a silicon wafer. Surrounding the wafer with birefringent retarders enables two time-staggered, orthogonally polarized signal copies to probe the wafer. Recombining the copies at amore » final crossed polarizer destructively interferes with them, except during the brief stagger window, where a differential phase shift is incurred. This enables the integrating response of the rapidly excited but persistent carriers to be optically differentiated. Lastly, this sampling mechanism has several advantages that enable scaling to long record lengths, including making use of large, inexpensive semiconductor wafers, eliminating the need for phase matching, broad insensitivity to the spectral and angular properties of the pump, and overall hardware simplicity.« less
Ultrafast investigation of photoinduced charge transfer in aminoanthraquinone pharmaceutical product
NASA Astrophysics Data System (ADS)
Zhang, Song; Sun, Simei; Zhou, Miaomiao; Wang, Lian; Zhang, Bing
2017-02-01
We investigated the mechanism of intramolecular charge transfer and the following radiationless dynamics of the excited states of 1-aminoanthraquinone using steady state and time-resolved absorption spectroscopy combined with quantum chemical calculations. Following photoexcitation with 460 nm, conformational relaxation via twisting of the amino group, charge transfer and the intersystem crossing (ISC) processes have been established to be the major relaxation pathways responsible for the ultrafast nonradiative of the excited S1 state. Intramolecular proton transfer, which could be induced by intramolecular hydrogen bonding is inspected and excluded. Time-dependent density functional theory (TDDFT) calculations reveal the change of the dipole moments of the S0 and S1 states along the twisted coordinate of the amino group, indicating the mechanism of twisted intra-molecular charge transfer (TICT). The timescale of TICT is measured to be 5 ps due to the conformational relaxation and a barrier on the S1 potential surface. The ISC from the S1 state to the triplet manifold is a main deactivation pathway with the decay time of 28 ps. Our results observed here have yield a physically intuitive and complete picture of the photoinduced charge transfer and radiationless dynamics in anthraquinone pharmaceutial products.
Muir, R.; Heebner, J.
2017-10-24
In this study, we demonstrate a novel, single-shot recording technology for transient optical signals. A resolution of 0.4 ps over a record length of 54 ps was demonstrated. Here, a pump pulse crossing through a signal samples a diagonal “slice” of space–time, enabling a camera to record spatially the time content of the signal. Unlike related X (2)-based cross-correlation techniques, here the signal is sampled through optically pumped carriers that modify the refractive index of a silicon wafer. Surrounding the wafer with birefringent retarders enables two time-staggered, orthogonally polarized signal copies to probe the wafer. Recombining the copies at amore » final crossed polarizer destructively interferes with them, except during the brief stagger window, where a differential phase shift is incurred. This enables the integrating response of the rapidly excited but persistent carriers to be optically differentiated. Lastly, this sampling mechanism has several advantages that enable scaling to long record lengths, including making use of large, inexpensive semiconductor wafers, eliminating the need for phase matching, broad insensitivity to the spectral and angular properties of the pump, and overall hardware simplicity.« less
Time-to-digital converter card for multichannel time-resolved single-photon counting applications
NASA Astrophysics Data System (ADS)
Tamborini, Davide; Portaluppi, Davide; Tisa, Simone; Tosi, Alberto
2015-03-01
We present a high performance Time-to-Digital Converter (TDC) card that provides 10 ps timing resolution and 20 ps (rms) timing precision with a programmable full-scale-range from 160 ns to 10 μs. Differential Non-Linearity (DNL) is better than 1.3% LSB (rms) and Integral Non-Linearity (INL) is 5 ps rms. Thanks to the low power consumption (400 mW) and the compact size (78 mm x 28 mm x 10 mm), this card is the building block for developing compact multichannel time-resolved instrumentation for Time-Correlated Single-Photon Counting (TCSPC). The TDC-card outputs the time measurement results together with the rates of START and STOP signals and the number of valid TDC conversions. These additional information are needed by many TCSPC-based applications, such as: Fluorescence Lifetime Imaging (FLIM), Time-of-Flight (TOF) ranging measurements, time-resolved Positron Emission Tomography (PET), single-molecule spectroscopy, Fluorescence Correlation Spectroscopy (FCS), Diffuse Optical Tomography (DOT), Optical Time-Domain Reflectometry (OTDR), quantum optics, etc.
Dalldorf, F. G.; Anderle, S. K.; Brown, R. R.; Schwab, J. H.
1988-01-01
Acute edematous responses were induced in Sprague-Dawley rats by the intravenous injection of group-specific polysaccharide (PS) isolated from group A streptococci. Thirty minutes after the intravenous injection of PS there was marked degranulation of subcutaneous and periarticular mast cells in all 4 feet, carbon particle labeling of adjacent venules, and an 8-fold increase in Evans blue dye content of the extremities. This acute reaction to PS was completely blocked by pretreatment with compound 48/80, but the polyarticular relapsing arthritis following the systemic injection of an arthropathic dose of streptococcal cell wall fragments containing large, covalently bound peptidoglycan-polysaccharide (PG-PS) was not blocked. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:3041843
Origin of diverse time scales in the protein hydration layer solvation dynamics: A simulation study
NASA Astrophysics Data System (ADS)
Mondal, Sayantan; Mukherjee, Saumyak; Bagchi, Biman
2017-10-01
In order to inquire the microscopic origin of observed multiple time scales in solvation dynamics, we carry out several computer experiments. We perform atomistic molecular dynamics simulations on three protein-water systems, namely, lysozyme, myoglobin, and sweet protein monellin. In these experiments, we mutate the charges of the neighbouring amino acid side chains of certain natural probes (tryptophan) and also freeze the side chain motions. In order to distinguish between different contributions, we decompose the total solvation energy response in terms of various components present in the system. This allows us to capture the interplay among different self- and cross-energy correlation terms. Freezing the protein motions removes the slowest component that results from side chain fluctuations, but a part of slowness remains. This leads to the conclusion that the slow component approximately in the 20-80 ps range arises from slow water molecules present in the hydration layer. While the more than 100 ps component has multiple origins, namely, adjacent charges in amino acid side chains, hydrogen bonded water molecules and a dynamically coupled motion between side chain and water. In addition, the charges enforce a structural ordering of nearby water molecules and helps to form a local long-lived hydrogen bonded network. Further separation of the spatial and temporal responses in solvation dynamics reveals different roles of hydration and bulk water. We find that the hydration layer water molecules are largely responsible for the slow component, whereas the initial ultrafast decay arises predominantly (approximately 80%) due to the bulk. This agrees with earlier theoretical observations. We also attempt to rationalise our results with the help of a molecular hydrodynamic theory that was developed using classical time dependent density functional theory in a semi-quantitative manner.
Harju, Anni M; Venäläinen, Martti; Laakso, Tapio; Saranpää, Pekka
2009-01-01
In this greenhouse experiment, 3-year-old Scots pine (Pinus sylvestris L.) seedlings were wounded by drilling holes through the stem. In the xylem next to the wound, the concentration of resin acids (RAC) increased, and the production of extractives typical for heartwood (stilbenes) and knotwood (stilbenes and lignans) of mature trees was induced. The induced stilbenes were pinosylvin (PS) and pinosylvin monomethyl ether (PSM), and the lignans nortrachelogenin (NTG) and matairesinol (MR). There was positive phenotypic correlation between concentrations of the different extractives. Except for the RAC, the extractive concentrations showed no correlation with the size of the seedlings. The treated seedlings belonged to half-sib families, which enabled the estimation of the genetic parameters for the response variables. The proportion of heritable variation (heritability, h(2)) in the concentration of PS, NTG and MR varied between 0.71 and 1.03, whereas for PSM and RAC the heritability was lower (0.35 and 0.31). Genetic correlation was significant between PS and PSM (r = 0.55, P = 0.018), and between NTG and MR (r = 0.50, P = 0.033). Heritabilities were also estimated on the basis of the regression of the offspring on their mothers h(2)(0P). These estimates were assessed for the concentration of PS, PSM and RAC in the wound response area of the seedlings and correspondingly in the heartwood of their mothers. The heritability was highest for the concentration of PS h(2)(0P). The findings of this study support the suggestion that the wounding of Scots pine seedlings may facilitate the development of an early testing method for breeding heartwood durability.
VizieR Online Data Catalog: Superluminous supernovae in faint galaxies (McCrum+, 2015)
NASA Astrophysics Data System (ADS)
McCrum, M.; Smartt, S. J.; Rest, A.; Smith, K.; Kotak, R.; Rodney, S. A.; Young, D. R.; Chornock, R.; Berger, E.; Foley, R. J.; Fraser, M.; Wright, D.; Scolnic, D.; Tonry, J. L.; Urata, Y.; Huang, K.; Pastorello, A.; Botticella, M. T.; Valenti, S.; Mattila, S.; Kankare, E.; Farrow, D. J.; Huber, M. E.; Stubbs, C. W.; Kirshner, R. P.; Bresolin, F.; Burgett, W. S.; Chambers, K. C.; Draper, P. W.; Flewelling, H.; Jedicke, R.; Kaiser, N.; Magnier, E. A.; Metcalfe, N.; Morgan, J. S.; Price, P. A.; Sweeney, W.; Wainscoat, R. J.; Waters, C.
2015-09-01
From the period starting February 25th 2010 and ending July 9th 2011, 249 hostless transients or "orphans" were discovered in the PS1 Medium Deep fields. AN orphan is defined as an object that is >3.4" away from the centre of a catalogued galaxy or point source brighter than approximately 23.5m (in any of the gP1 rP1 iP1 filters that the transient was detected in). The PS1 observations are obtained through a set of five broadband filters, which we have designated as gP1, rP1, iP1, zP1, and yP1. Although the filter system for PS1 has much in common with that used in previous surveys, such as SDSS (Abazajian et al., 2009ApJS..182..543A), there are important differences. The gP1 filter extends 20nm redward of gSDSS, paying the price of 5577Å emission for greater sensitivity and lower systematics for photometric redshifts, and the zP1 filter is cut off at 930nm, giving it a different response than the detector response which defined zSDSS. SDSS has no corresponding yP1 filter. Further information on the passband shapes is described in Stubbs et al. (2010ApJS..191..376S). The PS1 photometric system and its response is covered in detailed in Tonry et al. (2012ApJ...750...99T, Cat. J/ApJ/750/99). Photometry is in the "natural" PS1 system, m=-2.5log(flux)+m', with a single zeropoint adjustment m' made in each band to conform to the AB magnitude scale. (8 data files).
Yang, Shan-Shan; Brandon, Anja Malawi; Andrew Flanagan, James Christopher; Yang, Jun; Ning, Daliang; Cai, Shen-Yang; Fan, Han-Qing; Wang, Zhi-Yue; Ren, Jie; Benbow, Eric; Ren, Nan-Qi; Waymouth, Robert M; Zhou, Jizhong; Criddle, Craig S; Wu, Wei-Min
2018-01-01
Commercial production of polystyrene (PS) -a persistent plastic that is not biodegradable at appreciable rates in most environments-has led to its accumulation as a major contaminant of land, rivers, lakes, and oceans. Recently, however, an environment was identified in which PS is susceptible to rapid biodegradation: the larval gut of Tenebrio molitor Linnaeus (yellow mealworms). In this study, we evaluate PS degradation capabilities of a previously untested strain of T. molitor and assess its survival and PS biodegradation rates for a range of conditions (two simulated food wastes, three temperatures, seven PS waste types). For larvae fed PS alone, the %PS removed in the short (12-15 h) residence time of the mealworm gut gradually increased for 2-3 weeks then stabilized at values up to 65%. Thirty two-day survival rates were >85% versus 54% for unfed larvae. For mealworms fed ∼10% w/w PS and ∼90% bran, an agricultural byproduct, rates of PS degradation at 25 °C nearly doubled compared to mealworms fed PS alone. Polymer residues in the frass showed evidence of partial depolymerization and oxidation. All of the tested PS wastes degraded, with the less dense foams degrading most rapidly. Mealworms fed bran and PS completed all life cycle stages (larvae, pupae, beetles, egg), and the second generation had favorable PS degradation, opening the door for selective breeding. Copyright © 2017 Elsevier Ltd. All rights reserved.
Fatigue-propagation du melange polymere polystyrene/polyethylene
NASA Astrophysics Data System (ADS)
Bureau, Martin N.
The interrelations between the morphology of PS/HDPE and PS/SEBS/HDPE immiscible polymer blends and their mechanical behavior, namely in monotonic loading and in cyclic loading, were studied. As predicted by theory, high shear rates encountered during extrusion blending led to efficient minor phase emulsification in PS/HDPE blends for which the viscosity ratio approaches unity. Consequently, the emulsifying effect of an SEBS triblock copolymer employed as a compatibilizer was found to be negligible. In subsequent molding process, disintegration, shape relaxation and coarsening of the minor phase domains were responsible for the morphological evolution of the blends. In the compression molding process, morphological observations showed that the rate of minor phase coarsening followed the predictions of the Ostwald ripening theory, in agreement with the rheological analysis. In the injection molding process, minor phase coarsening was attributed to shear coalescence. The fatigue crack propagation behavior of injection-molded specimens of pure PS as well as of 95/5, 85/15 and 70/30 PS/HDPE blends and of 95/(0.5/4.5), 85/(1.5/13.5) and 70/(3/27) PS/(SEBS/HDPE) blends was then studied. The fatigue fracture surface features of specimens of pure PS as well as of PS/HDPE and PS/SEBS/HDPE blends were analyzed in detail in order to interpret their fatigue crack propagation behavior. In pure PS specimens, discontinuous growth bands, associated with the fracture of crazes in the plastic zone, formed at low fatigue crack growth rates, large dimple-like features at intermediate fatigue crack growth rates and fatigue striations at high fatigue crack growth rates. The fracture toughness of injection-molded specimens of pure PS as well as of 95/5, 85/15 and 70/30 PS/HDPE blends and of 95/(0.5/4.5) PS/(SEBS/HDPE), 85/(1.5/13.5) and 70/(3/27) PS/(SEBS/HDPE) was finally studied. The results showed that the addition of HDPE to PS led to a reduction of the fracture toughness KQ following ASTM E-399 when compared to that of pure PS. This effect was attributed to the very fine minor phase morphology of the blends obtained after extrusion blending and injection molding. (Abstract shortened by UMI.)
Joshi, Amita; Dang, Hung Quang; Vaid, Neha; Tuteja, Narendra
2010-01-01
The plant lectin receptor-like kinases (LecRLKs) are involved in various signaling pathways but their role in salinity stress tolerance has not heretofore been well described. Salinity stress negatively affects plant growth/productivity and threatens food security worldwide. Based on functional gene-mining assay, we have isolated 34 salinity tolerant genes out of one million Escherichia coli (SOLR) transformants containing pea cDNAs grown in 0.8 M NaCl. Sequence analysis of one of these revealed homology to LecRLK, which possesses N-myristilation and N-glycosylation sites thus corroborating the protein to be a glycoconjugate. The homology based computational modeling of the kinase domain suggested high degree of conservation with the protein already known to be stress responsive in plants. The NaCl tolerance provided by PsLecRLK to the above bacteria was further confirmed in E. coli (DH5alpha). In planta studies showed that the expression of PsLecRLK cDNA was significantly upregulated in response to NaCl as compared to K(+) and Li(+) ions, suggesting the Na(+) ion specific response. Transcript of the PsLecRLK gene accumulates mainly in roots and shoots. The purified 47 kDa recombinant PsLecRLK-KD (kinase domain) protein has been shown to phosphorylate general substrates like MBP and casein. This study not only suggests the conservation of the cellular response to high salinity stress across prokaryotes and plant kingdom but also provides impetus to develop novel concepts for better understanding of mechanism of stress tolerance in bacteria and plants. It also opens up new avenues for studying practical aspects of plant salinity tolerance for enhanced agricultural productivity.
NASA Astrophysics Data System (ADS)
Plemmons, Dayne A.; Flannigan, David J.
2017-09-01
We determine the instrument response of an ultrafast electron microscope equipped with a conventional thermionic electron gun and absent modifications beyond the optical ports. Using flat, graphite-encircled LaB6 cathodes, we image space-charge effects as a function of photoelectron-packet population and find that an applied Wehnelt bias has a negligible effect on the threshold levels (>103 electrons per pulse) but does appear to suppress blurring at the upper limits (∼105 electrons). Using plasma lensing, we determine the instrument-response time for 700-fs laser pulses and find that single-electron packets are laser limited (1 ps), while broadening occurs well below the space-charge limit.
NASA Astrophysics Data System (ADS)
Burri, Samuel; Homulle, Harald; Bruschini, Claudio; Charbon, Edoardo
2016-04-01
LinoSPAD is a reconfigurable camera sensor with a 256×1 CMOS SPAD (single-photon avalanche diode) pixel array connected to a low cost Xilinx Spartan 6 FPGA. The LinoSPAD sensor's line of pixels has a pitch of 24 μm and 40% fill factor. The FPGA implements an array of 64 TDCs and histogram engines capable of processing up to 8.5 giga-photons per second. The LinoSPAD sensor measures 1.68 mm×6.8 mm and each pixel has a direct digital output to connect to the FPGA. The chip is bonded on a carrier PCB to connect to the FPGA motherboard. 64 carry chain based TDCs sampled at 400 MHz can generate a timestamp every 7.5 ns with a mean time resolution below 25 ps per code. The 64 histogram engines provide time-of-arrival histograms covering up to 50 ns. An alternative mode allows the readout of 28 bit timestamps which have a range of up to 4.5 ms. Since the FPGA TDCs have considerable non-linearity we implemented a correction module capable of increasing histogram linearity at real-time. The TDC array is interfaced to a computer using a super-speed USB3 link to transfer over 150k histograms per second for the 12.5 ns reference period used in our characterization. After characterization and subsequent programming of the post-processing we measure an instrument response histogram shorter than 100 ps FWHM using a strong laser pulse with 50 ps FWHM. A timing resolution that when combined with the high fill factor makes the sensor well suited for a wide variety of applications from fluorescence lifetime microscopy over Raman spectroscopy to 3D time-of-flight.
Inhibition of γ-Secretase Leads to an Increase in Presenilin-1.
Sogorb-Esteve, Aitana; García-Ayllón, María-Salud; Llansola, Marta; Felipo, Vicente; Blennow, Kaj; Sáez-Valero, Javier
2018-06-01
γ-Secretase inhibitors (GSIs) are potential therapeutic agents for Alzheimer's disease (AD); however, trials have proven disappointing. We addressed the possibility that γ-secretase inhibition can provoke a rebound effect, elevating the levels of the catalytic γ-secretase subunit, presenilin-1 (PS1). Acute treatment of SH-SY5Y cells with the GSI LY-374973 (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, DAPT) augments PS1, in parallel with increases in other γ-secretase subunits nicastrin, presenilin enhancer 2, and anterior pharynx-defective 1, yet with no increase in messenger RNA expression. Over-expression of the C-terminal fragment (CTF) of APP, C99, also triggered an increase in PS1. Similar increases in PS1 were evident in primary neurons treated repeatedly (4 days) with DAPT or with the GSI BMS-708163 (avagacestat). Likewise, rats examined after 21 days administered with avagacestat (40 mg/kg/day) had more brain PS1. Sustained γ-secretase inhibition did not exert a long-term effect on PS1 activity, evident through the decrease in CTFs of APP and ApoER2. Prolonged avagacestat treatment of rats produced a subtle impairment in anxiety-like behavior. The rebound increase in PS1 in response to GSIs must be taken into consideration for future drug development.
Integrated Optoelectronic Position Sensor for Scanning Micromirrors.
Cheng, Xiang; Sun, Xinglin; Liu, Yan; Zhu, Lijun; Zhang, Xiaoyang; Zhou, Liang; Xie, Huikai
2018-03-26
Scanning micromirrors have been used in a wide range of areas, but many of them do not have position sensing built in, which significantly limits their application space. This paper reports an integrated optoelectronic position sensor (iOE-PS) that can measure the linear displacement and tilting angle of electrothermal MEMS (Micro-electromechanical Systems) scanning mirrors. The iOE-PS integrates a laser diode and its driving circuits, a quadrant photo-detector (QPD) and its readout circuits, and a band-gap reference all on a single chip, and it has been fabricated in a standard 0.5 μm CMOS (Complementary Metal Oxide Semiconductor) process. The footprint of the iOE-PS chip is 5 mm × 5 mm. Each quadrant of the QPD has a photosensitive area of 500 µm × 500 µm and the spacing between adjacent quadrants is 500 μm. The iOE-PS chip is simply packaged underneath of an electrothermally-actuated MEMS mirror. Experimental results show that the iOE-PS has a linear response when the MEMS mirror plate moves vertically between 2.0 mm and 3.0 mm over the iOE-PS chip or scans from -5 to +5°. Such MEMS scanning mirrors integrated with the iOE-PS can greatly reduce the complexity and cost of the MEMS mirrors-enabled modules and systems.
Hilton, David J
2012-12-31
We develop a new characteristic matrix-based method to analyze cyclotron resonance experiments in high mobility two-dimensional electron gas samples where direct interference between primary and satellite reflections has previously limited the frequency resolution. This model is used to simulate experimental data taken using terahertz time-domain spectroscopy that show multiple pulses from the substrate with a separation of 15 ps that directly interfere in the time-domain. We determine a cyclotron dephasing lifetime of 15.1 ± 0.5 ps at 1.5 K and 5.0 ± 0.5 ps at 75 K.
Biosynthesis of glycerolipid molecular species in photoreceptor membranes of frog retina
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wiegand, R.D.; Louie, K.; Anderson, R.E.
1987-05-01
Phospholipid (PL) molecular species of vertebrate retinal photoreceptor cells are unique in that they contain two polyunsaturated fatty acids per molecule. Docosahexaenoic acid (22:6 {omega}3) is the major component of these dipolyunsaturate species (DPS), which also contain 20:4{omega}6, 22:4{omega}6, 22:5{omega}6, and 22:5{omega}3. We have studied the de novo synthesis and metabolism of the (DPS) and other PL molecular species in frog rod outer segments (ROS) following intravitreal injection of 2-({sup 3}H)-glycerol. At 1, 2, 4, and 8 days after injection, ROS were prepared, PL extracted, and phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) isolated. PC, PE, and PS were convertedmore » to diglycerides (DG's) with phospholipase C. DG's were derivatized, fractionated into molecular species by HPLC, quantitated, and counted for radioactivity. The following were observed: (1) Specific activities (SA) of the PC DPS were 3-5 times higher than the same species in either PE or PS. (2) SA of the PC monopolyunsaturate species (MPS) (species which contain 22:6{omega}3 and/or 16:0 or 18:0) were 3-5 times lower than the SA of the PC DPS. In contrast, SA of PE MPS were 2-5 times higher than the SA of the PE DPS. (3) The major PS MPS synthesized contained 18:0 and 22:6{omega}3. SA of that species were similar to SA of the PS DPS. The data support the suggestion that PC DPS are synthesized and/or incorporated in ROS at a greater rate than the same species in either PE or PS. Our study thus provides evidence for different rates of synthesis and/or incorporation of the various molecular species of PC, PE, and PS in ROS.« less
Bispectral Index monitoring in cancer patients undergoing palliative sedation: a preliminary report.
Monreal-Carrillo, Edith; Allende-Pérez, Silvia; Hui, David; García-Salamanca, Maria-Fernanda; Bruera, Eduardo; Verástegui, Emma
2017-10-01
Continuous palliative sedation (PS) is currently titrated based on clinical observation; however, it is often unclear if patients are still aware of their suffering. The aim of this prospective study is to characterize the level of consciousness in patients undergoing PS using Bispectral Index (BIS) monitoring. We enrolled consecutive patients with refractory symptoms requiring PS. We documented the level of sedation using Ramsay Sedation Scale (RSS) and BIS at 0, 2, 4, 6, 12, and 24 h during the first day of PS and examined their degree of association. Intravenous midazolam or propofol was titrated according to the sedation level. Twenty patients on PS were recruited and had BIS continuous monitoring. Delirium was the most frequent reason for PS (n = 15, 75%). The median time of sedation was 24.5 h (interquartile range 6-46). The average time to achieve the desired sedation level was 6 h, and dose titration was required in 80% of the cases. At baseline, 14 (70%) patients were considered to be awake according to RSS (i.e., 1-3) and 19 (95%) were awake according to BIS (i.e., >60%). This proportion decreased to 31 and 56% at 4 h, 27% and 53 at 6 h, and 22 and 33% at 24 h. RS and BIS had moderate correlation (rho = -0.58 to -0.65); however, a small proportion of patients were found to be awake by BIS (i.e., ≥60%) despite clinical observation (i.e., RSS 4-6) indicating otherwise. The BIS is a noninvasive, bedside, real-time continuous monitoring method that may facilitate the objective assessment of level of consciousness and dose titration in patients undergoing PS.
Alanazi, Abdullah; Al Enezi, Farhan; Alqahtani, Mohammd Mesfer; Alshammari, Turki Faleh; Ansari, Mumtaz Ahmed; Al-Oraibi, Saleh; Qureshi, Shoeb
2015-01-01
Background: Despite the recent campaigns to eliminate smoking, the rates are still increasing world-wide. Exposure to passive smoking (PS) is associated with morbidity and mortality from awful diseases. Although many college students smoke, little is known about their exposure to PS, common places and sources of exposures in Saudi Arabia. Aim: The aim of the following study is to identify prevalence and magnitude of PS among college students, exposure time, locations, sources of exposure, investigate the effects and make recommendations. Materials and Methods: A cross-sectional study was performed to identify factors associated with PS exposure among students of College of Applied Medical Sciences, Riyadh. Results: Out of 61 students included in the study, 91.8% were found exposed to PS. Exposure in Hospitality venues (Estirah) was the most common followed by other areas. Among the sources of exposure, the highest was among friends and the least were parents and guests. The frequency of highest exposure per month was >15 times and the lowest was 10-15 times. Levels of annoyance varied between 18% and 37.7%, respectively. Since the values obtained for different markers in the pulmonary function test are more than the predicted values, the observed spirometry is normal. The percent oxygen saturation in hemoglobin and blood pressure of PS were in normal range. Conclusion: Since the properties of mainstream smoke and environmental tobacco smoke are quite different, risk extrapolation from active to PS is uncertain, especially during a short period. Nevertheless, it can be deteriorating during a longer duration, hence; the administrators, policy makers and tobacco control advocates may endorse policies to restrict smoking in shared areas, particularly working environment. PMID:25810644
In vitro inhibition of human papillomavirus following use of a carrageenan-containing vaginal gel.
Novetsky, Akiva P; Keller, Marla J; Gradissimo, Ana; Chen, Zigui; Morgan, Stephanie L; Xue, Xiaonan; Strickler, Howard D; Fernández-Romero, José A; Burk, Robert; Einstein, Mark H
2016-11-01
To assess in vitro efficacy of Divine 9, a carrageenan-based vaginal lubricant that is being studied as a microbicide to inhibit HPV16 pseudovirus (PsV) infection. Sexually active US women between 19 and 35years without prior HPV vaccination or cervical intraepithelial neoplasia were instructed to use Divine 9 vaginally with an applicator either before sex only or before and after intercourse. Women who applied a single dose of gel returned for cervicovaginal lavage (CVL) collection 1, 4 or 8-12h after intercourse versus those who applied gel before and after intercourse returned 1, 4 or 8-12h after the second gel dose. Carrageenan concentrations were assessed using an ELISA assay and the inhibitory activity was assessed using a PsV-based neutralization assay against HPV16 infection. Carrageenan concentrations and the percentage of PsV16 inhibition were compared using the Wilcoxon rank sum test. Thirteen women were enrolled and thirty specimens from different time-points were assessed. 87% of CVL samples had detectable carrageenans with levels decreasing over time from intercourse. 93% of CVL samples had detectable PsV16 inhibition with median inhibition of 97.5%. PsV16 inhibition decreased over time, but remained high, with median inhibition of 98.1%, 97.4% and 83.4% at 1, 4 and 8-12h, respectively. Higher carrageenan concentrations were associated with higher levels of PsV16 inhibition (rho=0.69). This is the first report of a human study investigating in vitro HPV inhibition of a carrageenan-based vaginal lubricant with CVL collected after sexual intercourse. We demonstrate excellent efficacy in preventing PsV16 infection. Copyright © 2016 Elsevier Inc. All rights reserved.
In Vitro Inhibition of Human Papillomavirus Following Use of a Carrageenan-Containing Vaginal Gel
Novetsky, Akiva P.; Keller, Marla J.; Gradissimo, Ana; Chen, Zigui; Morgan, Stephanie L.; Xue, Xiaonan; Strickler, Howard D.; Fernández-Romero, José A.; Burk, Robert; Einstein, Mark H.
2016-01-01
Objective To assess in vitro efficacy of Divine 9, a carrageenan-based vaginal lubricant that is being studied as a microbicide to inhibit HPV16 pseudovirus (PsV) infection. Methods Sexually active US women between 19–35 years without prior HPV vaccination or cervical intraepithelial neoplasia were instructed to use Divine 9 vaginally with an applicator either before sex only or before and after intercourse. Women who applied a single dose of gel returned for cervicovaginal lavage (CVL) collection 1, 4 or 8–12 hours after intercourse versus those who applied gel before and after intercourse returned 1, 4 or 8–12 hours after the second gel dose. Carrageenan concentrations were assessed using an ELISA assay and the inhibitory activity was assessed using a PsV-based neutralization assay against HPV16 infection. Carrageenan concentrations and the percentage of PsV16 inhibition were compared using the Wilcoxon rank sum test. Results Thirteen women were enrolled and thirty specimens from different time-points were assessed. 87% of CVL samples had detectable carrageenans with levels decreasing over time from intercourse. 93% of CVL samples had detectable PsV16 inhibition with median inhibition of 97.5%. PsV16 inhibition decreased over time, but remained high, with median inhibition of 98.1%, 97.4% and 83.4% at 1, 4 and 8–12 hours, respectively. Higher carrageenan concentrations were associated with higher levels of PsV16 inhibition (rho=0.69). Conclusions This is the first report of a human study investigating in vitro HPV inhibition of a carrageenan-based vaginal lubricant with CVL collected after sexual intercourse. We demonstrate excellent efficacy in preventing PsV16 infection. PMID:27625046
Relling, David P; Esberg, Lucy B; Fang, Cindy X; Johnson, W Thomas; Murphy, Eric J; Carlson, Edward C; Saari, Jack T; Ren, Jun
2006-03-01
Obesity is associated with dyslipidemia, which leads to elevated triglyceride and ceramide levels, apoptosis and compromised cardiac function. To determine the role of high-fat diet-induced obesity on cardiomyocyte function, weanling male Sprague-Dawley rats were fed diets incorporating 10% of kcal or 45% of kcal from fat. Mechanical function of ventricular myocytes was evaluated including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocity of shortening and relengthening (+/- dl/dt). Intracellular Ca properties were assessed using fluorescent microscopy. High-fat diet induced hyperinsulinemic insulin-resistant obesity with depressed PS, +/- dl/dt, prolonged TPS/TR90 reduced intracellular Ca release and Ca clearing rate in the absence of hypertension, diabetes, lipotoxicity and apoptosis. Myocyte responsiveness to increased stimulus frequency and extracellular Ca was compromised. SERCA2a and phospholamban levels were increased, whereas phosphorylated phospholamban and potassium channel (Kv1,2) were reduced in high-fat diet group. High-fat diet upregulated the forkhead transcription factor Foxo3a, and suppressed mitochondrial aconitase activity without affecting expression of the caloric sensitive gene silent information regulator 2 (Sir2), protein nitrotyrosine formation, lipid peroxidation and apoptosis. Levels of endothelial nitric oxide synthase (NOS), inducible NOS, triglycerides and ceramide were similar between the two groups. Collectively, our data show that high-fat diet-induced obesity resulted in impaired cardiomyocyte function, upregulated Foxo3a transcription factor and mitochondrial damage without overt lipotoxicity or apoptosis.
USDA-ARS?s Scientific Manuscript database
Protein synthesis (PS) increases after a meal in neonates, but the time course of the changes in PS in different tissues after a meal is unknown. We aimed to evaluate the changes in tissue PS, mammalian target of rapamycin complex 1 (mTORC1) activation, and proportion of ribosomal protein (rp) mRNAs...
Foucher, Fabrice; Morin, Julie; Courtiade, Juliette; Cadioux, Sandrine; Ellis, Noel; Banfield, Mark J; Rameau, Catherine
2003-11-01
Genes in the TERMINAL FLOWER1 (TFL1)/CENTRORADIALIS family are important key regulatory genes involved in the control of flowering time and floral architecture in several different plant species. To understand the functions of TFL1 homologs in pea, we isolated three TFL1 homologs, which we have designated PsTFL1a, PsTFL1b, and PsTFL1c. By genetic mapping and sequencing of mutant alleles, we demonstrate that PsTFL1a corresponds to the DETERMINATE (DET) gene and PsTFL1c corresponds to the LATE FLOWERING (LF) gene. DET acts to maintain the indeterminacy of the apical meristem during flowering, and consistent with this role, DET expression is limited to the shoot apex after floral initiation. LF delays the induction of flowering by lengthening the vegetative phase, and allelic variation at the LF locus is an important component of natural variation for flowering time in pea. The most severe class of alleles flowers early and carries either a deletion of the entire PsTFL1c gene or an amino acid substitution. Other natural and induced alleles for LF, with an intermediate flowering time phenotype, present no changes in the PsTFL1c amino acid sequence but affect LF transcript level in the shoot apex: low LF transcript levels are correlated with early flowering, and high LF transcript levels are correlated with late flowering. Thus, different TFL1 homologs control two distinct aspects of plant development in pea, whereas a single gene, TFL1, performs both functions in Arabidopsis. These results show that different species have evolved different strategies to control key developmental transitions and also that the genetic basis for natural variation in flowering time may differ among plant species.
Miller, Joseph D; Slipchenko, Mikhail N; Meyer, Terrence R
2011-07-04
Hybrid femtosecond/picosecond coherent anti-Stokes Raman scattering (fs/ps CARS) offers accurate thermometry at kHz rates for combustion diagnostics. In high-temperature flames, selection of probe-pulse characteristics is key to simultaneously optimizing signal-to-nonresonant-background ratio, signal strength, and spectral resolution. We demonstrate a simple method for enhancing signal-to-nonresonant-background ratio by using a narrowband Lorentzian filter to generate a time-asymmetric probe pulse with full-width-half-maximum (FWHM) pulse width of only 240 fs. This allows detection within just 310 fs after the Raman excitation for eliminating nonresonant background while retaining 45% of the resonant signal at 2000 K. The narrow linewidth is comparable to that of a time-symmetric sinc2 probe pulse with a pulse width of ~2.4 ps generated with a conventional 4-f pulse shaper. This allows nonresonant-background-free, frequency-domain vibrational spectroscopy at high temperature, as verified using comparisons to a time-dependent theoretical fs/ps CARS model.
Kwiatkowski, Molly A.; Gabranski, Emily R.; Huber, Kristen E.; Chapline, M. Christine; Christie, Andrew E.; Dickinson, Patsy S.
2013-01-01
SUMMARY While many neurons are known to contain multiple neurotransmitters, the specific roles played by each co-transmitter within a neuron are often poorly understood. Here, we investigated the roles of the co-transmitters of the pyloric suppressor (PS) neurons, which are located in the stomatogastric nervous system (STNS) of the lobster Homarus americanus. The PS neurons are known to contain histamine; using RT-PCR, we identified a second co-transmitter as the FMRFamide-like peptide crustacean myosuppressin (Crust-MS). The modulatory effects of Crust-MS application on the gastric mill and pyloric patterns, generated in the stomatogastric ganglion (STG), closely resembled those recorded following extracellular PS neuron stimulation. To determine whether histamine plays a role in mediating the effects of the PS neurons in the STG, we bath-applied histamine receptor antagonists to the ganglion. In the presence of the antagonists, the histamine response was blocked, but Crust-MS application and PS stimulation continued to modulate the gastric and pyloric patterns, suggesting that PS effects in the STG are mediated largely by Crust-MS. PS neuron stimulation also excited the oesophageal rhythm, produced in the commissural ganglia (CoGs) of the STNS. Application of histamine, but not Crust-MS, to the CoGs mimicked this effect. Histamine receptor antagonists blocked the ability of both histamine and PS stimulation to excite the oesophageal rhythm, providing strong evidence that the PS neurons use histamine in the CoGs to exert their effects. Overall, our data suggest that the PS neurons differentially utilize their co-transmitters in spatially distinct locations to coordinate the activity of three independent networks. PMID:23393282
Kwiatkowski, Molly A; Gabranski, Emily R; Huber, Kristen E; Chapline, M Christine; Christie, Andrew E; Dickinson, Patsy S
2013-05-15
While many neurons are known to contain multiple neurotransmitters, the specific roles played by each co-transmitter within a neuron are often poorly understood. Here, we investigated the roles of the co-transmitters of the pyloric suppressor (PS) neurons, which are located in the stomatogastric nervous system (STNS) of the lobster Homarus americanus. The PS neurons are known to contain histamine; using RT-PCR, we identified a second co-transmitter as the FMRFamide-like peptide crustacean myosuppressin (Crust-MS). The modulatory effects of Crust-MS application on the gastric mill and pyloric patterns, generated in the stomatogastric ganglion (STG), closely resembled those recorded following extracellular PS neuron stimulation. To determine whether histamine plays a role in mediating the effects of the PS neurons in the STG, we bath-applied histamine receptor antagonists to the ganglion. In the presence of the antagonists, the histamine response was blocked, but Crust-MS application and PS stimulation continued to modulate the gastric and pyloric patterns, suggesting that PS effects in the STG are mediated largely by Crust-MS. PS neuron stimulation also excited the oesophageal rhythm, produced in the commissural ganglia (CoGs) of the STNS. Application of histamine, but not Crust-MS, to the CoGs mimicked this effect. Histamine receptor antagonists blocked the ability of both histamine and PS stimulation to excite the oesophageal rhythm, providing strong evidence that the PS neurons use histamine in the CoGs to exert their effects. Overall, our data suggest that the PS neurons differentially utilize their co-transmitters in spatially distinct locations to coordinate the activity of three independent networks.
Skyberg, Jerod A; Rollins, MaryClare F; Holderness, Jeff S; Marlenee, Nicole L; Schepetkin, Igor A; Goodyear, Andrew; Dow, Steven W; Jutila, Mark A; Pascual, David W
2012-01-01
Pulmonary Francisella tularensis and Burkholderia pseudomallei infections are highly lethal in untreated patients, and current antibiotic regimens are not always effective. Activating the innate immune system provides an alternative means of treating infection and can also complement antibiotic therapies. Several natural agonists were screened for their ability to enhance host resistance to infection, and polysaccharides derived from the Acai berry (Acai PS) were found to have potent abilities as an immunotherapeutic to treat F. tularensis and B. pseudomallei infections. In vitro, Acai PS impaired replication of Francisella in primary human macrophages co-cultured with autologous NK cells via augmentation of NK cell IFN-γ. Furthermore, Acai PS administered nasally before or after infection protected mice against type A F. tularensis aerosol challenge with survival rates up to 80%, and protection was still observed, albeit reduced, when mice were treated two days post-infection. Nasal Acai PS administration augmented intracellular expression of IFN-γ by NK cells in the lungs of F. tularensis-infected mice, and neutralization of IFN-γ ablated the protective effect of Acai PS. Likewise, nasal Acai PS treatment conferred protection against pulmonary infection with B. pseudomallei strain 1026b. Acai PS dramatically reduced the replication of B. pseudomallei in the lung and blocked bacterial dissemination to the spleen and liver. Nasal administration of Acai PS enhanced IFN-γ responses by NK and γδ T cells in the lungs, while neutralization of IFN-γ totally abrogated the protective effect of Acai PS against pulmonary B. pseudomallei infection. Collectively, these results demonstrate Acai PS is a potent innate immune agonist that can resolve F. tularensis and B. pseudomallei infections, suggesting this innate immune agonist has broad-spectrum activity against virulent intracellular pathogens.
Laurence, T. A.; Ly, S.; Shen, N.; ...
2017-06-22
Laser-induced damage with ps pulse widths straddles the transition from intrinsic, multi-photon ionization and avalanche ionization-based ablation with fs pulses to defect-dominated, thermal-based damage with ns pulses. We investigated the morphology of damage for fused silica and silica coatings between 1 ps and 60 ps at 1053 nm. Using calibrated laser-induced damage experiments, in situ imaging, and high-resolution optical microscopy, atomic force microscopy, and scanning electron microscopy, we show that defects play an important role in laser-induced damage down to 1 ps. Three types of damage are observed: ablation craters, ultra-high density pits, and smooth, circular depressions with central pits.more » For 10 ps and longer, the smooth, circular depressions limit the damage performance of fused silica and silica coatings. The observed high-density pits and material removal down to 3 ps indicate that variations in surface properties limit the laser-induced damage onset to a greater extent than expected below 60 ps. Below 3 ps, damage craters are smoother although there is still evidence as seen by AFM of inhomogeneous laser-induced damage response very near the damage onset. These results show that modeling the damage onset only as a function of pulse width does not capture the convoluted processes leading to laser induced damage with ps pulses. It is necessary to account for the effects of defects on the processes leading to laser-induced damage. In conclusion, the effects of isolated defects or inhomogeneities are most pronounced above 3 ps but are still discernible and possibly important down to the shortest pulse width investigated here.« less
Iwama, Eiji; Goto, Yasushi; Murakami, Haruyasu; Harada, Taishi; Tsumura, Shinsuke; Sakashita, Hiroyuki; Mori, Yoshiaki; Nakagaki, Noriaki; Fujita, Yuka; Seike, Masahiro; Bessho, Akihiro; Ono, Manabu; Okazaki, Akihito; Akamatsu, Hiroaki; Morinaga, Ryotaro; Ushijima, Shinichiro; Shimose, Takayuki; Tokunaga, Shoji; Hamada, Akinobu; Yamamoto, Nobuyuki; Nakanishi, Yoichi; Sugio, Kenji; Okamoto, Isamu
2017-07-01
Alectinib has shown marked efficacy and safety in patients with anaplastic lymphoma receptor tyrosine kinase gene (ALK) rearrangement-positive NSCLC and a good performance status (PS). It has remained unclear whether alectinib might also be beneficial for such patients with a poor PS. Eligible patients with advanced ALK rearrangement-positive NSCLC and a PS of 2 to 4 received alectinib orally at 300 mg twice daily. The primary end point of the study was objective response rate (ORR), and the most informative secondary end point was rate of PS improvement. Between September 2014 and December 2015, 18 patients were enrolled in this phase II study. Of those patients, 12, five, and one had a PS of 2, 3, or 4, respectively, whereas four patients had received prior crizotinib treatment. The ORR was 72.2% (90% confidence interval: 52.9-85.8%). The ORR did not differ significantly between patients with a PS of 2 and those with a PS of 3 or higher (58.3% and 100%, respectively [p = 0.114]). The PS improvement rate was 83.3% (90% confidence interval: 64.8-93.1%, p < 0.0001), with the frequency of improvement to a PS of 0 or 1 being 72.2%. The median progression-free survival was 10.1 months. Toxicity was mild, with the frequency of adverse events of grade 3 or higher being low. Neither dose reduction nor withdrawal of alectinib because of toxicity was necessary. Alectinib is a treatment option for patients with ALK rearrangement-positive NSCLC and a poor PS. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Laurence, T. A.; Ly, S.; Shen, N.
Laser-induced damage with ps pulse widths straddles the transition from intrinsic, multi-photon ionization and avalanche ionization-based ablation with fs pulses to defect-dominated, thermal-based damage with ns pulses. We investigated the morphology of damage for fused silica and silica coatings between 1 ps and 60 ps at 1053 nm. Using calibrated laser-induced damage experiments, in situ imaging, and high-resolution optical microscopy, atomic force microscopy, and scanning electron microscopy, we show that defects play an important role in laser-induced damage down to 1 ps. Three types of damage are observed: ablation craters, ultra-high density pits, and smooth, circular depressions with central pits.more » For 10 ps and longer, the smooth, circular depressions limit the damage performance of fused silica and silica coatings. The observed high-density pits and material removal down to 3 ps indicate that variations in surface properties limit the laser-induced damage onset to a greater extent than expected below 60 ps. Below 3 ps, damage craters are smoother although there is still evidence as seen by AFM of inhomogeneous laser-induced damage response very near the damage onset. These results show that modeling the damage onset only as a function of pulse width does not capture the convoluted processes leading to laser induced damage with ps pulses. It is necessary to account for the effects of defects on the processes leading to laser-induced damage. In conclusion, the effects of isolated defects or inhomogeneities are most pronounced above 3 ps but are still discernible and possibly important down to the shortest pulse width investigated here.« less
Laser-Interferometric Broadband Seismometer for Epicenter Location Estimation
Lee, Kyunghyun; Kwon, Hyungkwan; You, Kwanho
2017-01-01
In this paper, we suggest a seismic signal measurement system that uses a laser interferometer. The heterodyne laser interferometer is used as a seismometer due to its high accuracy and robustness. Seismic data measured by the laser interferometer is used to analyze crucial earthquake characteristics. To measure P-S time more precisely, the short time Fourier transform and instantaneous frequency estimation methods are applied to the intensity signal (Iy) of the laser interferometer. To estimate the epicenter location, the range difference of arrival algorithm is applied with the P-S time result. The linear matrix equation of the epicenter localization can be derived using P-S time data obtained from more than three observatories. We prove the performance of the proposed algorithm through simulation and experimental results. PMID:29065515
Excited state proton transfer in the lysosome of live lung cells: normal and cancer cells.
Chowdhury, Rajdeep; Saha, Abhijit; Mandal, Amit Kumar; Jana, Batakrishna; Ghosh, Surajit; Bhattacharyya, Kankan
2015-02-12
Dynamics of excited state proton transfer (ESPT) in the lysosome region of live lung cells (normal and cancer) is studied by picosecond time-resolved confocal microscopy. For this, we used a fluorescent probe, pyranine (8-hydroxy-pyrene-1,3,6-trisulfonate, HPTS). From the colocalization of HPTS with a lysotracker dye (lysotracker yellow), we confirmed that HPTS resides in the lysosome for both of the cells. The diffusion coefficient (Dt) in the lysosome region was obtained from fluorescence correlation spectroscopy (FCS). From Dt, the viscosity of lysosome is estimated to be ∼40 and ∼30 cP in the cancer and normal cells, respectively. The rate constants of the elementary steps of ESPT in a normal lung cell (WI38) are compared with those in a lung cancer cell (A549). It is observed that the time constant of the initial proton transfer process in a normal cell (τ(PT) = 40 ps) is similar to that in a cancer cell. The recombination of the geminate ion pair is slightly faster (τ(rec) = 25 ps) in the normal cell than that (τ(rec) = 30 ps) in a cancer cell. The time constant of the dissociation (τ(diss)) of the geminate ion pair for the cancer cell (τ(diss) = 80 ps) is 1.5 times faster compared to that (τ(diss) = 120 ps) in a normal cell.
Mease, P; Deodhar, A; Fleischmann, R; Wollenhaupt, J; Gladman, D; Leszczyński, P; Vitek, P; Turkiewicz, A; Khraishi, M; FitzGerald, O; Landewé, R; de Longueville, M; Hoepken, B; Peterson, L; van der Heijde, D
2015-01-01
Objective Previous reports of RAPID-PsA (NCT01087788) demonstrated efficacy and safety of certolizumab pegol (CZP) over 24 weeks in patients with psoriatic arthritis (PsA), including patients with prior antitumour necrosis factor (TNF) therapy. We report efficacy and safety data from a 96-week data cut of RAPID-PsA. Methods RAPID-PsA was placebo-controlled to week 24, dose-blind to week 48 and open-label to week 216. We present efficacy data including American College of Rheumatology (ACR)/Psoriasis Area and Severity Index (PASI) responses, HAQ-DI, pain, minimal disease activity (MDA), modified total Sharp score (mTSS) and ACR responses in patients with/without prior anti-TNF exposure, in addition to safety data. Results Of 409 patients randomised, 273 received CZP from week 0. 54 (19.8%) CZP patients had prior anti-TNF exposure. Of patients randomised to CZP, 91% completed week 24, 87% week 48 and 80% week 96. ACR responses were maintained to week 96: 60% of patients achieved ACR20 at week 24, and 64% at week 96. Improvements were observed with both CZP dose regimens. ACR20 responses were similar in patients with (week 24: 59%; week 96: 63%) and without (week 24: 60%; week 96: 64%) prior anti-TNF exposure. Placebo patients switching to CZP displayed rapid clinical improvements, maintained to week 96. In patients with ≥3% baseline skin involvement (60.8% week 0 CZP patients), PASI responses were maintained to week 96. No progression of structural damage was observed over the 96-week period. In the Safety Set (n=393), adverse events occurred in 345 patients (87.8%) and serious adverse events in 67 (17.0%), including 6 fatal events. Conclusions CZP efficacy was maintained to week 96 with both dose regimens and in patients with/without prior anti-TNF exposure. The safety profile was in line with that previously reported from RAPID-PsA, with no new safety signals observed with increased exposure. Trial registration number NCT01087788. PMID:26509074
D'Sa, Raechelle A; Raj, Jog; Dickinson, Peter J; McCabe, Fiona; Meenan, Brian J
2016-06-22
Recent advances in materials sciences have allowed for the development and fabrication of biomaterials that are capable of providing requisite cues to instigate cells to respond in a predictable fashion. We have developed a series of poly(methyl methacrylate)/polystyrene (PMMA/PS) polymer demixed thin films with nanotopographies ranging from nanoislands to nanopits to study the response of human fetal osteoblast cells (hFOBs). When PMMA was in excess in the blend composition, a nanoisland topography dominated, whereas a nanopit topography dominated when PS was in excess. PMMA was found to segregate to the top of the nanoisland morphology with PS preferring the substrate interface. To further ascertain the effects of surface chemistry vs topography, we plasma treated the polymer demixed films using an atmospheric pressure dielectric barrier discharge reactor to alter the surface chemistry. Our results have shown that hFOBs did not have an increased short-term cellular response on pristine polymer demixed surfaces. However, increasing the hydrophilicty/wettability of the surfaces by oxygen functionalization causes an increase in the cellular response. These results indicate that topography alone is not sufficient to induce a positive cellular response, but the underlying surface chemistry is also important in regulating cell function.
Yuan, Shuai; Ge, Fengyan; Yang, Xue; Guang, Shanyi
2016-11-01
A strategy for significantly enhancing fluorescence is developed based on the coupling of optical properties of colloidal photonic crystals (CPCs) with responsive microgel. In this paper, thermoresponsive microgel PNIPAM was employed for the fabrication of core-shell structure. The core-shell PS@PNIPAM nanoparticles (NPs) are then assembled to CPCs by a vertical deposition method. Subsequently, the novel functional material (RhB/CPCs) can be prepared by depositing fluorescent dye molecules (RhB) on the top of PS@PNIPAM CPCs. We obtained an increase in the fluorescent intensity up to 15-fold and 22-fold compared with RhB on the glass slid and the uneven film. Due to the unique responsive shrinking properties of PNIPAM shell, the amplifying fluorescence behavior of CPCs can be well tuned by varying the temperature. In contrast to RhB on the glass slid, a 15-fold and 12-fold fluorescence enhancement can be observed when the temperature of RhB/CPCs was 20 °C and 50 °C, respectively. The mechanism on enhancement fluorescence of tunable CPCs can be achieved by measurements of thermoresponsive properties. The results indicate that the responsive fluorescence-amplifying method based on CPCs made with responsive core-shell NPs has a potential application for the development of efficient fluorescence sensors.
Hansen, Katrina J; Favreau, John T; Gershlak, Joshua R; Laflamme, Michael A; Albrecht, Dirk R; Gaudette, Glenn R
2017-08-01
Differentiation of human pluripotent stem cells into cardiomyocytes (hPS-CMs) holds promise for myocardial regeneration therapies, drug discovery, and models of cardiac disease. Potential cardiotoxicities may affect hPS-CM mechanical contraction independent of calcium signaling. Herein, a method using an image capture system is described to measure hPS-CM contractility and intracellular calcium concurrently, with high spatial and temporal resolution. The image capture system rapidly alternates between brightfield and epifluorescent illumination of contracting cells. Mechanical contraction is quantified by a speckle tracking algorithm applied to brightfield image pairs, whereas calcium transients are measured by a fluorescent calcium reporter. This technique captured changes in contractile strain, calcium transients, and beat frequency of hPS-CMs over 21 days in culture, as well as acute responses to isoproterenol and Cytochalasin D. The technique described above can be applied without the need to alter the culture platform, allowing for determination of hPS-CM behavior over weeks in culture for drug discovery and myocardial regeneration applications.
Nizzari, Mario; Thellung, Stefano; Corsaro, Alessandro; Villa, Valentina; Pagano, Aldo; Porcile, Carola; Russo, Claudio; Florio, Tullio
2012-01-01
Alzheimer disease (AD) is a heterogeneous neurodegenerative disorder characterized by (1) progressive loss of synapses and neurons, (2) intracellular neurofibrillary tangles, composed of hyperphosphorylated Tau protein, and (3) amyloid plaques. Genetically, AD is linked to mutations in few proteins amyloid precursor protein (APP) and presenilin 1 and 2 (PS1 and PS2). The molecular mechanisms underlying neurodegeneration in AD as well as the physiological function of APP are not yet known. A recent theory has proposed that APP and PS1 modulate intracellular signals to induce cell-cycle abnormalities responsible for neuronal death and possibly amyloid deposition. This hypothesis is supported by the presence of a complex network of proteins, clearly involved in the regulation of signal transduction mechanisms that interact with both APP and PS1. In this review we discuss the significance of novel finding related to cell-signaling events modulated by APP and PS1 in the development of neurodegeneration.
A 7.4 ps FPGA-Based TDC with a 1024-Unit Measurement Matrix
Zhang, Min; Wang, Hai; Liu, Yan
2017-01-01
In this paper, a high-resolution time-to-digital converter (TDC) based on a field programmable gate array (FPGA) device is proposed and tested. During the implementation, a new architecture of TDC is proposed which consists of a measurement matrix with 1024 units. The utilization of routing resources as the delay elements distinguishes the proposed design from other existing designs, which contributes most to the device insensitivity to variations of temperature and voltage. Experimental results suggest that the measurement resolution is 7.4 ps, and the INL (integral nonlinearity) and DNL (differential nonlinearity) are 11.6 ps and 5.5 ps, which indicates that the proposed TDC offers high performance among the available TDCs. Benefitting from the FPGA platform, the proposed TDC has superiorities in easy implementation, low cost, and short development time. PMID:28420121
A 7.4 ps FPGA-Based TDC with a 1024-Unit Measurement Matrix.
Zhang, Min; Wang, Hai; Liu, Yan
2017-04-14
In this paper, a high-resolution time-to-digital converter (TDC) based on a field programmable gate array (FPGA) device is proposed and tested. During the implementation, a new architecture of TDC is proposed which consists of a measurement matrix with 1024 units. The utilization of routing resources as the delay elements distinguishes the proposed design from other existing designs, which contributes most to the device insensitivity to variations of temperature and voltage. Experimental results suggest that the measurement resolution is 7.4 ps, and the INL (integral nonlinearity) and DNL (differential nonlinearity) are 11.6 ps and 5.5 ps, which indicates that the proposed TDC offers high performance among the available TDCs. Benefitting from the FPGA platform, the proposed TDC has superiorities in easy implementation, low cost, and short development time.
NASA Astrophysics Data System (ADS)
Solovev, I. A.; Poltavtsev, S. V.; Kapitonov, Yu. V.; Akimov, I. A.; Sadofev, S.; Puls, J.; Yakovlev, D. R.; Bayer, M.
2018-06-01
We study optically the coherent evolution of trions and excitons in a δ -doped 3.5-nm-thick ZnO/Zn0.91Mg0.09O multiple quantum well by means of time-resolved four-wave mixing at a temperature of 1.5 K. Employing spectrally narrow picosecond laser pulses in the χ(3 ) regime allows us to address differently localized trion and exciton states, thereby avoiding many-body interactions and excitation-induced dephasing. The signal in the form of photon echoes from the negatively charged A excitons (TA, trions) decays with coherence times varying from 8 up to 60 ps, depending on the trion energy: more strongly localized trions reveal longer coherence dynamics. The localized neutral excitons decay on the picosecond time scale with coherence times up to T2=4.5 ps. The coherent dynamics of the XB exciton and TB trion are very short (T2<1 ps), which is attributed to the fast energy relaxation from the trion and exciton B states to the respective A states. The trion population dynamics is characterized by the decay time T1, rising from 30 to 100 ps with decreasing trion energy.
Mu, Ying; Valim, Niksa; Niedre, Mark
2013-06-15
We tested the performance of a fast single-photon avalanche photodiode (SPAD) in measurement of early transmitted photons through diffusive media. In combination with a femtosecond titanium:sapphire laser, the overall instrument temporal response time was 59 ps. Using two experimental models, we showed that the SPAD allowed measurement of photon-density sensitivity functions that were approximately 65% narrower than the ungated continuous wave case at very early times. This exceeds the performance that we have previously achieved with photomultiplier-tube-based systems and approaches the theoretical maximum predicted by time-resolved Monte Carlo simulations.
Morphological Analysis of Live Undifferentiated Cells Derived from Induced Pluripotent Stem Cells.
Osawa, Yukihiko; Miyamoto, Tomoyuki; Ohno, Setsuyo; Ohno, Eiji
2018-01-01
Induced pluripotent stem (iPS) cells possess pluripotency and self-renewal ability. Therefore, iPS cells are expected to be useful in regenerative medicine. However, iPS cells form malignant immature teratomas after transplantation into animals, even after differentiation induction. It has been suggested that undifferentiated cells expressing Nanog that remain after differentiation induction are responsible for teratoma formation. Various methods of removing these undifferentiated cells have therefore been investigated, but few methods involve morphological approaches, which may induce less cell damage. In addition, for cells derived from iPS cells to be applied in regenerative medicine, they must be alive. However, detailed morphological analysis of live undifferentiated cells has not been performed. For the above reasons, we assessed the morphological features of live undifferentiated cells remaining after differentiation induction as a basic investigation into the clinical application of iPS cells. As a result, live undifferentiated cells remaining after differentiation induction exhibited a round or oval cytoplasm about 12 μm in diameter and a nucleus. They exhibited nucleo-cytoplasmic (N/C) ratio of about 60% and eccentric nuclei, and they possessed partially granule-like structures in the cytoplasm and prominent nucleoli. Although they were similar to iPS cells, they were smaller than live iPS cells. Furthermore, very small cells were present among undifferentiated cells after differentiation induction. These results suggest that the removal of undifferentiated cells may be possible using the morphological features of live iPS cells and undifferentiated cells after differentiation induction. In addition, this study supports safe regenerative medicine using iPS cells.
NASA Astrophysics Data System (ADS)
Salehiyan, Reza; Song, Hyeong Yong; Hyun, Kyu
2015-05-01
Dynamic oscillatory measurement, i.e., small amplitude oscillatory shear (SAOS) and large amplitude oscillatory shear (LAOS) test was used to investigate linear and non-linear viscoelastic properties of Polypropylene (PP)/Polystyrene (PS) blends with and without 5 wt.% clay (C20A). Fourier transform (FT-Rheology), Lissajous curves and stress decomposition methods were used to analyze non-linear responses under LAOS flow. Composition effects of blends were investigated prior to compatibilization effects. Elevated concentrations of dispersed phase (PS) increased the moduli G'(ω) from SAOS test and G*( γ 0) from LAOS test of the blends as well as strain thinning behavior. Interestingly, addition of 5 wt.% clay (C20A) boosted moduli of the blends as well as led to similar strain thinning behaviors among the PP/PS/C20A blends, except for the (90/10) PP/PS blend. The latter did not show improved rheological properties despite morphological improvements, as shown by SEM. Results from SEM and improved rheological properties of PP/PS/C20A blends revealed the compatibilization effects of clay (C20A) particles regardless of size reduction mechanisms. Third relative intensities ( I 3/1) from FT-rheology were found to be sensitive to clay (C20A) additions for the (70/30) and (30/70) PP/PS blends. Similarly, Lissajous curves could detect changes upon clay (C20A) addition, specifically at lower strain amplitudes whereupon addition of 5 wt.% clay resulted in the closed loops of Lissajous curves showing a more ellipsoidal shape due to increased elasticity in the blends. However, detection of these changes at larger strain amplitudes was more challenging. Therefore, stress decomposition (SD) method was applied for more precise characterization as it decomposes the total stress (σ) into elastic stress (σ') and viscous stress (σ″). Using SD method, elastic stress was more distorted, especially, strain hardening, while the total stress response remained almost unchanged at larger strain amplitudes.
Shargh, Vahid Heravi; Jaafari, Mahmoud Reza; Khamesipour, Ali; Jaafari, Iman; Jalali, Seyed Amir; Abbasi, Azam; Badiee, Ali
2012-06-06
First generation Leishmania vaccines consisting of whole killed parasites with or without adjuvants have reached phase 3 trial and failed to show enough efficacy mainly due to the lack of an appropriate adjuvant. In this study, the nuclease-resistant phosphorothioate CpG oligodeoxynucleotides (PS CpG) or nuclease-sensitive phosphodiester CpG ODNs (PO CpG) were used as adjuvants to enhance immunogenicity and rate of protection against leishmaniasis. Due to the susceptibility of PO CpG to nuclease degradation, an efficient liposomal delivery system was developed to protect them from degradation. 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) as a cationic lipid was used because of its unique adjuvanticity and electrostatic interaction with negatively charged CpG ODNs. To evaluate the role of liposomal formulation in protection rate and enhanced immune response, BALB/c mice were immunized subcutaneously with liposomal soluble Leishmania antigens (SLA) co-incorporated with PO CpG (Lip-SLA-PO CpG), Lip-SLA-PS CpG, SLA+PO CpG, SLA+PS CpG, SLA or buffer. As criteria for protection, footpad swelling at the site of challenge, parasite loads, the levels of IFN-γ and IL-4, and the IgG subtypes were evaluated. The groups of mice receiving Lip-SLA-PO CpG or Lip-SLA-PS CpG showed a high protection rate compared with the control groups. In addition, there was no significant difference in immune response generation between mice immunized with PS CpG and the group receiving PO CpG when incorporated into the liposomes. The results suggested that liposomal form of PO CpG might be used instead of PS CpG in future vaccine formulations as an efficient adjuvant. Copyright © 2012 Elsevier Ltd. All rights reserved.
[Quenched fluorescein: a reference dye for instrument response function of TCSPC].
Pan, Hai-feng; Ding, Jing-xin; Liang, Rong-rong; Tao, Zhan-dong; Liu, Meng-wei; Zhang, San-jun; Xu, Jian-hua
2014-08-01
Measuring the instrument response function (IRF) and fitting by reconvolution algorithms are routines to improve time resolution in fluorescence lifetime measurements. Iodide ions were successfully used to quench the fluorescence of fluorescein in this study. By systematically adding saturated NaI water solution in basic fluorescein solution, the lifetimes of fluorescein were reduced from 4 ns to 24 ps. The quenched lifetime of fluorescein obtained from the analysis of Time-Correlated Single Photon Counting (TCSPC) measurement agrees well with that from femtosecond frequency up-conversion measurement. In time resolved excitation spectra measurements, the IRF should be measured at various detection wavelengths providing scattring materials are used. This study could not only reduce the complexity of IRF measurement, but also avoid the existing color effect in system. This study should have wide applications in time resolved fluorescence spectroscopy and fluorescence lifetime imaging.
Optoelectronic frequency discriminated phase tuning technology and its applications
NASA Astrophysics Data System (ADS)
Lin, Gong-Ru; Chang, Yung-Cheng
2000-07-01
By using a phase-tunable optoelectronic phase-locked loop, we are able to continuously change the phase as well as the delay-time of optically distributed microwave clock signals or optical pulse train. The advantages of the proposed technique include such as wide-band operation up to 20GHz, wide-range tuning up to 640 degrees, high tuning resolution of <6x10-2 degree/mV, ultra-low short-term phase fluctuation and drive of 4.7x10-2 degree and 3.4x10- 3 degree/min, good linearity with acceptable deviations, and frequency-independent transferred function with slope of nearly 90 degrees/volt, etc. The novel optoelectronic phase shifter is performed by using a DC-voltage controlled, optoelectronic-mixer-based, frequency-down-converted digital phase-locked-loop. The maximum delay-time is continuously tunable up to 3.9 ns for optical pulses repeated at 500 MHz from a gain-switched laser diode. This corresponds to a delay responsivity of about 0.54 ps/mV. The using of the OEPS as being an optoelectronic delay-time controller for optical pulses is demonstrated with temporal resolution of <0.2 ps. Electro-optic sampling of high-frequency microwave signals by using the in-situ delay-time-tunable pulsed laser as a novel optical probe is primarily reported.
Van Kuiken, Benjamin E.; Ross, Matthew R.; Strader, Matthew L.; ...
2017-05-08
Picosecond X-ray absorption (XA) spectroscopy at the S K-edge (~2.4 keV) is demonstrated and used to monitor excited state dynamics in a small organosulfur molecule (2-Thiopyridone, 2TP) following optical excitation. Multiple studies have reported that the thione (2TP) is converted into the thiol (2-Mercaptopyridine, 2MP) following photoexcitation. However, the timescale and photochemical pathway of this reaction remain uncertain. In this work, time-resolved XA spectroscopy at the S K-edge is used to monitor the formation and decay of two transient species following 400nm excitation of 2TP dissolved in acetonitrile. The first transient species forms within the instrument response time (70 ps)more » and decays within 6 ns. The second transient species forms on a timescale of ~400 ps and decays on a 15 ns timescale. Time-dependent density functional theory is used to identify the first and second transient species as the lowestlying triplet states of 2TP and 2MP, respectively. This study demonstrates transient S K-edge XA spectroscopy as a sensitive and viable probe of time-evolving charge dynamics near sulfur sites in small molecules with future applications towards studying complex biological and material systems.« less
Potentials and Limits of Sar Permanent Scatterers In Ground Deformation Monitoring
NASA Astrophysics Data System (ADS)
Rocca, F.; Colesanti, C.; Ferretti, A.; Prati, C.
The Permanent Scatterers (PS) technique allows the identification of individual radar targets particularly suitable for SAR interferometric measurements. In fact, despite its remarkable potential, spaceborne SAR Differential Interferometry (DInSAR) has not been fully exploited as a reference tool for ground deformation mapping, due to the presence of atmospheric artefacts as well as geometrical and temporal phase decorrelation. Both drawbacks are overcome in a multi-image framework of interfer- ometric data (>25-30 images) jointly used in order to properly identify and exploit the subset of image pixels corresponding to privileged reflectors, the so-called Per- manent Scatterers. Provided that at least 3-4 PS/sqkm are available, accurate phase measurements carried out on the sparse PS grid allow one to compensate data for the atmospheric phase contributions. Average ground deformation rate as well as full dis- placement time series (both along the satellite Line of Sight, LOS) are estimated with millimetric accuracy on individual PS locations. The PS subset of image pixels can be thought of as a high density (100-400 PS/sqkm, in urban areas) "natural" geode- tic network. This study aims at discussing in detail potentials and limits of the PS approach in monitoring ground deformation phenomena characterised by a complex time non-uniform evolution (Non-Linear Motion, NLM). PS results highlighting sea- sonal displacement effects beneath San Jose (Santa Clara Valley, California) are going to be discussed. The deformation occurring there is related to the seasonal variation of the ground water level in the area delimited by the Silver Creek and the San Jose fault. The San Jose PS analysis is exploited as a significant case study to assess the main requirements for a successful detection of NLM phenomena (by means of PS), and to analyse their impact on the quality of results. Particular attention will be de- voted to the effect of irregularly sampled data and missing acquisitions. The strategies used in order to isolate the phase contribution relative to time non-uniform displace- ment phenomena from other phase terms (mainly atmospheric artefacts and residual topography) are going to be illustrated. Moreover, the main aspects to be considered envisaging a synergistic use of PS results and both GPS and optical levelling data are going to be outlined. Finally, attention will be paid to key issues to be taken into account for designing future SAR missions dedicated to detection and monitoring of ground deformation phenomena.
Bautista-Herrera, L A; De la Cruz-Mosso, U; Morales-Zambrano, R; Villanueva-Quintero, G D; Hernández-Bello, J; Ramírez-Dueñas, M G; Martínez-López, E; Brennan-Bourdon, L M; Baños-Hernández, C J; Muñoz-Valle, J F
2018-05-01
Psoriatic arthritis (PsA) is an autoimmune inflammatory disease associated with psoriasis. The cause of this pathology is still unknown, but research suggests the diseases are caused by a deregulated cytokine production. MIF is a cytokine associated with immunomodulation of Th1, Th2, and Th17 cytokine profiles in inflammatory diseases. Based on this knowledge, the aim of this study was to determine the association of MIF and TNFA expression with Th1, Th2, and Th17 cytokine profiles in serum levels of PsA patients. A cross-sectional study was performed in 50 PsA patients and 30 control subjects (CS). The cytokine profiles were quantified by BioPlex MagPix system and the mRNA expression levels by real-time PCR. TNFA mRNA expression was 138.81-folds higher in PsA patients than CS (p < 0.001). Regarding MIF mRNA expression, no significant differences were observed; however, a positive correlation was identified between MIF mRNA expression and PsA time of evolution (r = - 0.53, p = 0.009). An increase of Th1 (IFNγ: PsA = 37.1 pg/mL vs. CS = 17 pg/mL, p < 0.05; TNFα: PsA = 24.6 pg/mL vs. CS = 9.8 pg/mL, p < 0.0001) and Th17 cytokine profiles (IL-17: PsA = 6.4 pg/mL vs. CS = 2.7 pg/mL, p < 0.05; IL-22: PsA = 8.4 pg/mL vs. CS = 1.8 pg/mL, p < 0.001), were found in PsA patients. Th2 cytokines were not significantly different in both groups. In conclusion, a high expression of TNFA mRNA, as well as an increase of Th1 and Th17 cytokine profiles evaluated by IFNγ, TNFα, IL-17, and IL-22 cytokines, was observed in PsA patients.
Liu, Rui; Xiao, Teng; Cui, Weipan; Shinar, Joseph; Shinar, Ruth
2013-05-17
Key issues in using organic light emitting diodes (OLEDs) as excitation sources in structurally integrated photoluminescence (PL)-based sensors are the low forward light outcoupling, the OLEDs' broad electroluminescence (EL) bands, and the long-lived remnant EL that follows an EL pulse. The outcoupling issue limits the detection sensitivity (S) as only ~20% of the light generated within standard OLEDs can be forward outcoupled and used for sensor probe excitation. The EL broad band interferes with the analyte-sensitive PL, leading to a background that reduces S and dynamic range. In particular, these issues hinder designing compact sensors, potentially miniaturizable, that are devoid of optical filters and couplers. We address these shortcomings by introducing easy-to-employ multiple approaches for outcoupling improvement, PL enhancement, and background EL reduction leading to novel, compact all-organic device architectures demonstrated for simultaneous monitoring of oxygen and pH. The sensor comprises simply-fabricated, directionally-emitting, narrower-band, multicolor microcavity OLED excitation and small molecule- and polymer-based organic photodetectors (OPDs) with a more selective spectral response. Additionally, S and PL intensity for oxygen are enhanced by using polystyrene (PS):polyethylene glycol (PEG) blends as the sensing film matrix. By utilizing higher molecular weight PS, the ratio τ0/τ100 (PL decay time τ at 0% O2/τ at 100% O2) that is often used to express S increases ×1.9 to 20.7 relative to the lower molecular weight PS, where this ratio is 11.0. This increase reduces to ×1.7 when the PEG is added (τ0/τ100=18.2), but the latter results in an increase ×2.7 in the PL intensity. The sensor's response time is <10s in all cases. The microporous structure of these blended films, with PEG decorating PS pores, serves a dual purpose. It results in light scattering that reduces the EL that is waveguided in the substrate of the OLEDs and consequently enhances light outcoupling from the OLEDs by ~60%, and it increases the PL directed toward the OPD. The multiple functional structures of multicolor microcavity OLED pixels/microporous scattering films/OPDs enable generation of enhanced individually addressable sensor arrays, devoid of interfering issues, for O2 and pH as well as for other analytes and biochemical parameters. Copyright © 2013 Elsevier B.V. All rights reserved.
Improvements in diagnostic tools for early detection of psoriatic arthritis.
D'Angelo, Salvatore; Palazzi, Carlo; Gilio, Michele; Leccese, Pietro; Padula, Angela; Olivieri, Ignazio
2016-11-01
Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease characterized by a wide clinical spectrum. The early diagnosis of PsA is currently a challenging topic. Areas covered: The literature was extensively reviewed for studies addressing the topic area "diagnosis of psoriatic arthritis". This review will summarize improvements in diagnostic tools, especially referral to the rheumatologist, the role of patient history and clinical examination, laboratory tests, and imaging techniques in getting an early and correct diagnosis of PsA. Expert commentary: Due to the heterogeneity of its expression, PsA may be easily either overdiagnosed or underdiagnosed. A diagnosis of PsA should be taken into account every time a patient with psoriasis or a family history of psoriasis shows peripheral arthritis, especially if oligoarticular or involving the distal interphalangeal joints, enthesitis or dactylitis. Magnetic resonance imaging and ultrasonography are useful for diagnosing PsA early, particularly when isolated enthesitis or inflammatory spinal pain occur.