High-resolution Time-of-flight Research Articles

NTIMP1—A Fast Pulse Readout Chip With 1.2 V Power Supply Applied to the Diamond Detector in HIAF

A very fast pulse readout ASIC, NTIMP1, with 1.2 V power supply is presented in this work. It is going to be used as front-end electronics (FEE) for reading out the diamond detector signals in the TOF (Time of Flight) wall of RIBLL2 experiment of the High Intensity Heavy Ion Accelerator Facility (HIAF), China. So that an 8-channel fast front-edge readout chip named as NTIMP1 is proposed in this work. Each channel of NTIMP1 has a high-bandwidth preamplifier (with adjustable thresholds) dealing with differential current input, a fast hysteresis discriminator, and a LVDS (Low-Voltage Differential Signaling) module ensuring long-distance signal transmission. Fabricated with 0.13 μm standard CMOS Technology, NTIMP1 can get an input ranging from 2 fC to 2000 fC and the input impedance of the preamplifier can be adjusted externally with an off-chip resistor, so as to match with the electrode impedance of diamond detector. The bandwidth of the preamplifier is 495.5 MHz, which allows a very short signal peaking time of no more than 1 ns. The jitter of the leading edge is lower than 15 ps with 100 fC input charge suggesting that NTIMP1 is suitable for high-resolution TOF measurement as well as time-slewing correction.

Clinical application of ultra-high resolution compressed sensing time-of-flight MR angiography at 7T to detect small vessel pathology.

3D time-of-flight (TOF) MR angiography (MRA) benefits from ultra-high-field MRI (≥7T) due to improved contrast and increased signal-to-noise ratio. However, high-resolution TOF MRA at 7T usually requires longer acquisition times. In addition, relatively higher specific absorption rate (SAR) at 7T limits the choice of optimal pulse sequence parameters, especially if venous saturation is employed. Here, we illustrate the clinical application of ultra-high resolution cerebral 7T TOF MRA using compressed sensing in cases of artery of Percheron and lacunar infarcts, which showed superior resolution and exquisite details pertinent to the clinical diagnosis. The technical challenges associated with high-resolution 7T imaging were alleviated by optimization of sequence parameters and utilization of compressed sensing acceleration.

Caulophyine A, a Rare Azapyrene Alkaloid from the Roots of Caulophyllum robustum.

A novel alkaloid caulophyine A (1) was isolated from the roots of Caulophyllum robustum Maxim., along with six known alkaloids 2-7. The structure of 1 was elucidated by extensive NMR and high resolution-time-of-flight (HR-TOF)-MS analyses, it is a rare nitrogen containing polycyclic aromatic hydrocarbon. The in vitro bioassays revealed that 2 presented remarkable cytotoxicity against A549 with an IC50 value of 3.83 µM in comparison with the positive control etoposide (IC50 = 11.63 µM). Compounds 1 and 2 also displayed weak Acetylcholinesterase (AChE) inhibitory activity with IC50 values of 123.03 and 80.74 µM respectively.

Excimer Formation of Perylene Bisimide Dyes within Stacking-Restrained Folda-Dimers: Insight into Anomalous Temperature Responsive Dual Fluorescence

Excimer Formation of Perylene Bisimide Dyes within Stacking-Restrained Folda-Dimers: Insight into Anomalous Temperature Responsive Dual Fluorescence

Multi-strategy Measurement of High-resolution Ultrasonic TOF

Jiao, Y.; Li, Z.; Zhu, J., and Zhang, B., 2020. Multi-strategy measurement of high-resolution ultrasonic TOF. In: Zheng, C.W.; Wang, Q.; Zhan, C., and Yang, S.B. (eds.), Air-Sea Interaction and Coastal Environments of the Maritime and Polar Silk Roads. Journal of Coastal Research, Special Issue No. 99, pp. 389–395. Coconut Creek (Florida), ISSN 0749-0208.Ultrasonic transducers are widely used in liquid sound velocity measurement. Acquisition of time-of-flight (TOF) is the key technology of high precision measurement of sound velocity.In this paper, to measure TOF with high precision, a Multi-strategy Measurement technique is proposed, which is able to locate the region of interest of the signals received echo waveform, and the wavelet denoising is carried out. To evaluate the proposed method, in an identified environment, the experiments were performed under defined the distance between transmitter and receiver in pure water at 30°C. The experiments were performed that, in the sound velocity measurement, the method has a high adaptability, which can achieve the goal of removing noise and improving detection accuracy. Although this paper focus on sound velocity in pure water, the method described may also find application in air.

Characterization and analysis of estrogenic cyclic phenone metabolites produced in vitro by rainbow trout liver slices using GC-MS, LC-MS and LC-TOF-MS

Cyclic phenones are chemicals of interest to the USEPA and international organizations due to their potential for endocrine disruption to aquatic and terrestrial species. The metabolic conversion of cyclic phenones by liver hepatocytes and the structure of main metabolites yielded have not been assessed in fish species. As part of a larger project, in this study we investigated the structure of metabolites produced in vitro by rainbow trout (rt) liver slices after exposure to the model cyclic phenones benzophenone (DPK), cyclobutyl phenyl ketone (CBP) and cyclohexyl phenyl ketone (CPK). While only one distinct metabolite was detected for DPK and CBP (benzhydrol and CBPOH, respectively), CPK yielded nine positional isomers (M1-M9) as products. In absence of standards, improved inference of CPK metabolites tentative structures was achieved by combining GC–MS with and without derivatization, LC with tandem MS, LC with high resolution time of flight (TOF) MS and LC fractionation data with CPK phase II conjugative metabolism information. Data supported that CPK is metabolized by phase I oxidation of the cyclohexyl ring and not the phenyl group as predicted by metabolism simulators. CPK metabolites M1 and M2 (MW 186), were proposed to be cyclohexenyl-derivatives. Also, M6-M9 were proposed to be hydroxylated metabolites (MW 204), with the potential for undergoing phase II conjugative metabolism to glucuronides and sulfates. Finally, M3, M4 and M5 were proposed as cyclohexanone-derivatives of CPK (MW 202), resulting from the limited redox-interconversion of their hydroxylated pairs M8, M6 and M7, respectively. Assessment of metabolite role in biological responses associated with endocrine disruption will advance the development of methods for species extrapolation and the understanding of differential sensitivity of species to chemical exposure.

A Middle-Up Approach with Online Capillary Isoelectric Focusing/Mass Spectrometry for In-Depth Characterization of Cetuximab Charge Heterogeneity.

Previously, we reported a new online capillary isoelectric focusing/mass spectrometric (CIEF/MS) method for intact monoclonal antibody (mAb) charge variant analysis that uses an electrokinetically pumped sheath-flow nanospray ion source on a time-of-flight (TOF) MS with a pressure-assisted chemical mobilization. The direct online CIEF/MS method exhibited excellent resolution of charge variants conforming to those of imaged capillary isoelectric focusing with ultraviolet detection (iCIEF/UV). However, for complex mAbs, CIEF/MS spectra of the intact charge variant peaks may be too convoluted to be effectively interpreted. In the present study, we implemented a middle-up approach to enhance the capability of the CIEF/MS method for characterizing complex mAb charge variants by reducing sample complexity. To demonstrate such a strategy, we fragmented cetuximab through IdeS enzymatic cleavage and dithiothreitol (DTT) reduction. For the first time, online CIEF/MS resolved the complex charge variants of cetuximab at subunit level, corroborating the profiles obtained by iCIEF/UV. Furthermore, high-resolution TOF mass spectra with high mass accuracy were obtained for the eight charge variants separated by CIEF/MS after IdeS cleavage and for the 11 charge variants after IdeS digestion with subsequent DTT reduction. In-depth analyses revealed the identities of all charge variants and pinpointed the causes of charge heterogeneity, which are in accord with those reported in the literature. The main sources of charge heterogeneity of cetuximab were identified as terminal lysine on the Fc domain (up to one on each single-chain Fc), glycolylneuraminic acid residues on the Fd' domain (up to two on each Fd'), and likely several deamidation species on the Fd' domain. No charge heterogeneity contribution was found from light chain. The in-depth characterization of complex charge variants for cetuximab demonstrates the remarkable capability of this middle-up CIEF/MS approach. This novel workflow holds great potential for detecting and elucidating charge variants to help understand proteins with complex charge heterogeneity.

A digital, constant-frequency pulsed phase-locked-loop instrument for real-time, absolute ultrasonic phase measurements.

A digitally controlled instrument for conducting single-frequency and swept-frequency ultrasonic phase measurements has been developed based on a constant-frequency pulsed phase-locked-loop (CFPPLL) design. This instrument uses a pair of direct digital synthesizers to generate an ultrasonically transceived tone-burst and an internal reference wave for phase comparison. Real-time, constant-frequency phase tracking in an interrogated specimen is possible with a resolution of 0.000 38 rad (0.022°), and swept-frequency phase measurements can be obtained. Using phase measurements, an absolute thickness in borosilicate glass is presented to show the instrument's efficacy, and these results are compared to conventional ultrasonic pulse-echo time-of-flight (ToF) measurements. The newly developed instrument predicted the thickness with a mean error of -0.04 μm and a standard deviation of error of 1.35 μm. Additionally, the CFPPLL instrument shows a lower measured phase error in the absence of changing temperature and couplant thickness than high-resolution cross-correlation ToF measurements at a similar signal-to-noise ratio. By showing higher accuracy and precision than conventional pulse-echo ToF measurements and lower phase errors than cross-correlation ToF measurements, the new digitally controlled CFPPLL instrument provides high-resolution absolute ultrasonic velocity or path-length measurements in solids or liquids, as well as tracking of material property changes with high sensitivity. The ability to obtain absolute phase measurements allows for many new applications than possible with previous ultrasonic pulsed phase-locked loop instruments. In addition to improved resolution, swept-frequency phase measurements add useful capability in measuring properties of layered structures, such as bonded joints, or materials which exhibit non-linear frequency-dependent behavior, such as dispersive media.

Elucidating Environmental Fingerprinting Mechanisms of Unconventional Gas Development through Hydrocarbon Analysis.

Hydraulic fracturing is an increasingly common technique for the extraction of natural gas entrapped in shale formations. This technique has been highly criticized due to the possibility of environmental contamination, underscoring the need for method development to identify chemical factors that could be utilized in point-source identification of environmental contamination events. Here, we utilize comprehensive two-dimensional gas chromatography (GC × GC) coupled to high-resolution time-of-flight (HRT) mass spectrometry, which offers a unique instrumental combination allowing for petroleomics hydrocarbon fingerprinting. Four flowback fluids from Marcellus shale gas wells in geographic proximity were analyzed for differentiating factors that could be exploited in environmental forensics investigations of shale gas impacts. Kendrick mass defect (KMD) plots of these flowback fluids illustrated well-to-well differences in heteroatomic substituted hydrocarbons, while GC × GC separations showed variance in cyclic hydrocarbons and polyaromatic hydrocarbons among the four wells. Additionally, generating plots that combine GC × GC separation with KMD established a novel data-rich visualization technique that further differentiated the samples.

Prospective motion correction enables highest resolution time-of-flight angiography at 7T.

Higher magnetic field strengths enable time-of-flight (TOF) angiography with higher resolution to depict small-vessel pathologies. However, this potential is limited by the subject's ability to remain motionless. Even small-scale, involuntary motion can degrade vessel depiction, thus limiting the effective resolution. The aim of this study was to overcome this resolution limit by deploying prospectively motion-corrected (PMC) TOF. An optical, marker-based, in-bore tracking system was used to update the imaging volume prospectively according to the subject's head motion. PMC TOF was evaluated in 12 healthy, cooperative subjects at isotropic resolution of up to 150 μm. Image quality was assessed qualitatively through reader rating and quantitatively with the average edge-strength metric. PMC significantly increased the average edge strength and qualitatively improved the vessel depiction in nine out of 11 cases. Image quality was never degraded by motion correction. PMC also enabled acquisition of the highest resolution human brain in vivo TOF angiography to date. With PMC enabled, high-resolution TOF is able to visualize brain vasculature beyond the effective resolution limit. Magn Reson Med 80:248-258, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

CS-ToF: High-resolution compressive time-of-flight imaging.

Three-dimensional imaging using Time-of-flight (ToF) sensors is rapidly gaining widespread adoption in many applications due to their cost effectiveness, simplicity, and compact size. However, the current generation of ToF cameras suffers from low spatial resolution due to physical fabrication limitations. In this paper, we propose CS-ToF, an imaging architecture to achieve high spatial resolution ToF imaging via optical multiplexing and compressive sensing. Our approach is based on the observation that, while depth is non-linearly related to ToF pixel measurements, a phasor representation of captured images results in a linear image formation model. We utilize this property to develop a CS-based technique that is used to recover high resolution 3D images. Based on the proposed architecture, we developed a prototype 1-megapixel compressive ToF camera that achieves as much as 4× improvement in spatial resolution and 3× improvement for natural scenes. We believe that our proposed CS-ToF architecture provides a simple and low-cost solution to improve the spatial resolution of ToF and related sensors.

Bisphenol A alternatives in thermal paper from the Netherlands, Spain, Sweden and Norway. Screening and potential toxicity

Thermal paper contains potentially toxic additives, such as bisphenol A (BPA), as a common color developer. Because of its known endocrine disrupting effects, structural analogues to BPA, such as bisphenol S (BPS), D-8 and Pergafast 201, have been used as alternatives, but little is known about the presence and toxicological effects of alternatives other than BPS. In this study, thermal paper is screened by direct probe ambient mass spectrometry (rapid pre-screening method not requiring sample preparation) and by liquid chromatography (LC) with high resolution time-of flight (TOF-MS) mass spectrometry. Cash receipts and other thermal paper products (cinema tickets, boarding passes and luggage tags) were analyzed. Besides BPA and BPS, other developers only recently reported (Pergafast 201, D-8) or to the best of our knowledge not reported before (D-90, TGSA, BPS-MAE) were frequently found as well as some related unreported impurities (2,4-BPS that is a BPS related impurity and a TGSA related impurity). To gain some insight into the potential estrogenicity of the detected developers, a selection of extracts was further analyzed using a LC-nanofractionation platform in combination with cell-based bioassay testing. These preliminary results seems to indicate very low or absence of estrogenic activity for Pergafast 201, D-8, D-90, TGSA and BPS-MAE in comparison to BPA and BPS, although further dose-response tests with authentic standards are required to confirm these results. Compounds for which standards were available were also tested for developmental toxicity and neurotoxicity using zebrafish (Danio rerio) embryos. TGSA and D-8 induced similar teratogenic effects as BPA in zebrafish embryos. BPS and 2,4-BPS did not induce any developmental effects but 2,4-BPS did alter the locomotor activity at the tested concentration. Our findings suggest that the alternatives used as alternatives to BPA (except BPS) might not be estrogenic. However, TGSA and D-8 showed abnormal developmental effects similar to BPA.

Identification of non-regulated polycyclic aromatic compounds and other markers of urban pollution in road tunnel particulate matter

A combination of silicone rubber extraction and non-target and suspect screening by gas chromatography coupled to high-resolution time-of flight mass spectrometry was used for the identification of compounds in particulate matter (PM). Tunnel PM is a proxy for local road pollution that constitutes a hazard to the urban environment and human health. The use of silicone rubber for the extraction of PM allowed the pre-concentration of a wide range of compounds for non-target analysis while minimising the effects of the sample matrix. As expected, polycyclic aromatic compounds (PACs) constituted the major group of compounds identified, but only 5 of 50 PACs identified were amongst those regularly monitored and many of them were alkylated or contained a heteroatom. Urban markers of contamination such as organophosphate flame-retardants, phthalates, benzothiazoles, musk compounds and a plasticiser were also identified. The level of confidence for the identifications was high based on accurate mass, the pattern of fragmentation and retention. The unequivocal identification of 16 compounds, from all groups, was confirmed by co-chromatography with standards and the compounds semi-quantified. Most of the PACs identified are not regularly monitored, and the hazards they pose are therefore unknown. Some of these PACs are known to be more persistent and mobile in the environment than the EPA PAH16.

Rapid Screening of Acetylcholinesterase Inhibitors by Effect-Directed Analysis Using LC × LC Fractionation, a High Throughput in Vitro Assay, and Parallel Identification by Time of Flight Mass Spectrometry.

Effect-directed analysis (EDA) is a useful tool to identify bioactive compounds in complex samples. However, identification in EDA is usually challenging, mainly due to limited separation power of the liquid chromatography based fractionation. In this study, comprehensive two-dimensional liquid chromatography (LC × LC) based microfractionation combined with parallel high resolution time of flight (HR-ToF) mass spectrometric detection and a high throughput acetylcholinesterase (AChE) assay was developed. The LC × LC fractionation method was validated using analytical standards and a C18 and pentafluorophenyl (PFP) stationary phase combination was selected for the two-dimensional separation and fractionation in four 96-well plates. The method was successfully applied to identify AChE inhibitors in a wastewater treatment plant (WWTP) effluent. Good orthogonality (>0.9) separation was achieved and three AChE inhibitors (tiapride, amisulpride, and lamotrigine), used as antipsychotic medicines, were identified and confirmed by two-dimensional retention alignment as well as their AChE inhibition activity.

PTRwid: A new widget tool for processing PTR-TOF-MS data

Abstract. PTRwid is a fast and user friendly tool that has been developed to process data from proton-transfer-reaction time-of-flight mass spectrometers (PTR-TOF-MS) that use HTOF (high-resolution time-of-flight) mass spectrometers from Tofwerk AG (Switzerland). PTRwid is designed for a comprehensive evaluation of whole laboratory or field-based studies. All processing runs autonomously, and entire laboratory or field campaigns can, in principle, be processed with a few mouse clicks. Unique features of PTRwid include (i) an autonomous and accurate mass scale calibration, (ii) the computation of a "unified mass list" that – in addition to a uniform data structure – provides a robust method to determine the precision of attributed peak masses, and (iii) fast data analysis due to well considered choices in data processing.

An Accurate Timing Alignment Method with Time-to-Digital Converter Linearity Calibration for High-Resolution TOF PET.

Accurate PET system timing alignment minimizes the coincidence time window and therefore reduces random events and improves image quality. It is also critical for time-of-flight (TOF) image reconstruction. Here, we use a thin annular cylinder (shell) phantom filled with a radioactive source and located axially and centrally in a PET camera for the timing alignment of a TOF PET system. This timing alignment method involves measuring the time differences between the selected coincidence detector pairs, calibrating the differential and integral nonlinearity of the time-to-digital converter (TDC) with the same raw data and deriving the intrinsic time biases for each detector using an iterative algorithm. The raw time bias for each detector is downloaded to the front-end electronics and the residual fine time bias can be applied during the TOF list-mode reconstruction. Our results showed that a timing alignment accuracy of better than ±25 ps can be achieved, and a preliminary timing resolution of 473 ps (full width at half maximum) was measured in our prototype TOF PET/CT system.

Preliminary measurements on the new TOF system installed at the AMS beamline of INFN-LABEC

A high resolution time of flight (TOF) system has been developed at LABEC, the 3MV Tandem accelerator laboratory in Florence, in order to improve the sensitivity of AMS measurements on carbon samples with ultra-low concentration and also to measure other isotopes, such as 129I. The system can be employed to detect and identify residual interfering particles originated from the break-up of molecular isobars. The set-up has been specifically designed for low energy heavy ions: it consists of two identical time pick-off stations, each made up of a thin conductive foil and a Micro-Channel Plate (MCP) multiplier. The beamline is also equipped with a silicon detector, installed downstream the stop TOF station.In this paper the design of the new system and the implemented readout electronics are presented. The tests performed on the single time pick-off station are reported: they show that the maximum contribution to the timing resolution given by both the intrinsic MCP resolution and the electronics is ⩽500ps (FWHM). For these tests, single particle pulsed beams of 2–5MeV protons and 10MeV 12C3+ ions, to simulate typical AMS conditions, were used.The preliminary TOF and TOF-E (TOF-energy) measurements performed with carbon beams after the installation of the new system on the AMS beam line are also discussed. These measurements were performed using the foil–MCP as the start stage and a silicon detector as the stop stage. The spectra acquired with carbon ions suggest the presence of a small residual background from neighboring masses reaching the end of the beamline with the same energy as the rare isotope.

The potential of selected Australian medicinal plants with anti-Proteus activity for the treatment and prevention of rheumatoid arthritis.

Background:A wide variety of herbal medicines are used in indigenous Australian traditional medicinal systems to treat rheumatoid arthritis (RA) and inflammation. The current study was undertaken to test the ability of a panel of Australian plants with a history of the ethnobotanical usage in the treatment of inflammation for the ability to block the microbial trigger of RA.Materials and Methods:One hundred and six extracts from 40 plant species were investigated for the ability to inhibit the growth of the bacterial trigger of RA (Proteus mirabilis). The extracts were tested for toxicity in the Artemia nauplii bioassay. The most potent inhibitor of P. mirabilis growth was further analyzed by reversed-phase high performance liquid chromatography (RP-HPLC) coupled to high accuracy time-of-flight (TOF) mass spectroscopy.Results:Sixty-five of the 106 extracts tested (61.3%) inhibited the growth of P. The Aleurites moluccanus, Datura leichardtii, Eucalyptus major, Leptospermum bracteata, L. juniperium, Macadamia integriflora nut, Melaleuca alternifolia, Melaleuca quinquenervia, Petalostigma pubescens, P. triloculorae, P. augustifolium, Scaevola spinescens, Syzygiumaustrale, and Tasmannia lanceolata extracts were determined to be the most effective inhibitors of P. mirabilis growth, with minimum inhibitory concentration (MIC) values generally significantly below 1000 μg/ml. T. lanceolata fruit extracts were the most effective P. mirabilis growth inhibitors, with a MIC values of 11 and 126 μg/ml for the methanolic and aqueous extracts, respectively. Subsequent analysis of the T. lanceolata fruit extracts by RP-HPLC coupled to high-resolution TOF mass spectroscopy failed to detect resveratrol in either T. lanceolata fruit extract. However, the resveratrol glycoside piceid and 2 combretastatin stilbenes (A-1 and A-4) were detected in both T. lanceolata fruit extracts. With the exception of the Eucalyptus and Syzygium extracts, all extracts exhibiting Proteus inhibitory activity were also shown to be nontoxic, or of low toxicity in the Artemia nauplii bioassay.Conclusions:The low toxicity of these extracts and their inhibitory bioactivity against Proteus spp. indicate their potential in blocking the onset of rheumatoid arthritis.

Optimized light sharing for high-resolution TOF PET detector based on digital silicon photomultipliers

The majority of current whole-body PET scanners are based on pixelated scintillator arrays with a transverse pixel size of 4 mm. However, recent studies have shown that decreasing the pixel size to 2 mm can significantly improve image spatial resolution. In this study, the performance of Digital Photon Counter (DPC) from Philips Digital Photon Counting (PDPC) was evaluated to determine their potential for high-resolution whole-body time of flight (TOF) PET scanners. Two detector configurations were evaluated. First, the DPC3200-44-22 DPC array was coupled to a LYSO block of 15 × 15 2 × 2 × 22 mm3 pixels through a 1 mm thick light guide. Due to light sharing among the dies neighbour logic of the DPC was used. In a second setup the same DPC was coupled directly to a scalable 4 × 4 LYSO matrix of 1.9 × 1.9 × 22 mm3 crystals with a dedicated reflector arrangement allowing for controlled light sharing patterns inside the matrix. With the first approach an average energy resolution of 14.5% and an average CRT of 376 ps were achieved. For the second configuration an average energy resolution of 11% and an average CRT of 295 ps were achieved. Our studies show that the DPC is a suitable photosensor for a high-resolution TOF-PET detector. The dedicated reflector arrangement allows one to achieve better performances than the light guide approach. The count loss, caused by dark counts, is overcome by fitting the matrix size to the size of DPC single die.

Toward a better understanding of the magnetocaloric effect: An experimental and theoretical study of MnFe4Si3

The intermetallic compound MnFe4Si3 has been studied by high-resolution Time of Flight (TOF) neutron powder diffraction. MnFe4Si3 crystallizes in the hexagonal space group P63/mcm with lattice constants of a=b=6.8043(4)Å and c=4.7254(2)Å at 310K. Magnetic susceptibility measurements show clearly the magnetic transition from paramagnetism to ferromagnetism at about 302(2)K. Magnetic structure refinements based on neutron powder diffraction data with and without external magnetic field reveal strong evidence on the origin of the large magnetocaloric effect (MCE) in this material as a partial reordering of the spins between ~270K and 300K. In addition, electronic structure calculations using the self-consistent, spin-polarized Tight Binding-Linear MuffinTin Orbital (TB-LMTO) method were also accomplished to address the “coloring problem” (Mn/Fe site preference) as well as the unique ferromagnetic behavior of this intermetallic compound.