Polyphenols have attained pronounced attention due to their ability to provide numerous health benefits and prevent several chronic diseases. In this study, we designed, synthesized and analyzed a water-soluble molecule presenting a good antioxidant activity, namely catechol hydrazinyl-thiazole (CHT). This molecule contains 3′,4′-dihydroxyphenyl and 2-hydrazinyl-4-methyl-thiazole moieties linked through a hydrazone group with very good antioxidant activity in the in vitro evaluations performed. A preliminary validation of the CHT developing hypothesis was performed evaluating in silico the bond dissociation enthalpy (BDE) of the phenol O-H bonds, compared to our previous findings in the compounds previously reported by our group. In this paper, we report the binding mechanism of CHT to human serum albumin (HSA) using biophysical methods in combination with computational studies. ITC experiments reveal that the dominant forces in the binding mechanism are involved in the hydrogen bond or van der Waals interactions and that the binding was an enthalpy-driven process. NMR relaxation measurements were applied to study the CHT–protein interaction by changing the drug concentration in the solution. A molecular docking study added an additional insight to the experimental ITC and NMR analysis regarding the binding conformation of CHT to HSA.

In this work the complexation between desferioxamine B (DFOB), and beta-Cyclodextrin (beta-CD) in solution was investigated using 1 H NMR spectroscopy. Inclusion compound formation was confirmed by the up field shifts of H3 and H5 protons, located inside the cavity of beta-CD, and downfield shifts of some of the methylene protons of DFOB, observed during NMR titration experiments. Using the continuous variation method, we determined a 1:1 stoichiometry and the association constant was calculated using a nonlinear least-square regression analysis implemented in CONSTEQ, a software developed in our group. A theoretical molecular docking study was additionally performed to ascertain possible conformations of the inclusion complex. (C) 2021 Elsevier B.V. All rights reserved.

We present the latest and the near-future design of the KOTO data-acquisition system. The KOTO experiment is searching for the rare kaon decay $K_L^0\to\pi^0\nu\overline{\nu}$, which is sensitive to New Physics beyond the Standard Model due to the small theoretical uncertainty. In order to efficiently collect the candidate events under the high-intensity $K_L^0$ beam, the two-level trigger system was hence developed. The pulses from nearly 4000 channels were continuously digitized and pipelined with the depth of 5.2 $\mu s$ at customized flush analog-to-digital converters (FADC) for trigger-processing. The level-1 trigger required the total energy in the calorimeter and the absence of hits in the veto counters. The level-2 trigger required two electromagnetic showers (clusters) in the calorimeter. The system dead time was measured to be 0.16 $\mu s$ and the live time ratio was 99%. In the near future, the customized module with multiple optical connectors will be used to collect all data from the FADCs and perform the event-building. The complete events are sent to the PC farms via 10 Gbps throughput for more sophisticated trigger decisions. This not only improves the data collection efficiency but broadens the coverage of physics topics for the KOTO experiment.

In this study we designed, synthesized and analyzed a water-soluble molecule presenting a good antioxidant and antiradical activity, namely Dihydroxy-Phenyl-Thiazol-Hydrazinium chloride (DPTH). This molecule contains 2',4'-dihydroxyphenyl and the 2-hydrazinyl-4-methyl-thiazole fragments linked through a hydrazone and having very good antiradical scavenging, antioxidant activity and a low chelation activity in the in vitro evaluations. Knowing that, in the organism, the drugs are transported to the tissues generally bound to a plasma protein we, additionally, investigated its interaction with human serum albumin (HSA)-the main soluble protein in plasma capable of making complexes with various molecules, which deliver then, to the tissues. This binding can influence the pharmacokinetic and pharmacodynamic profile of drugs. Consequently, the interaction between DPTH and human serum albumin (HSA) was carefully examined using isothermal titration calorimetry (ITC) and T-1 NMR selective relaxation time spectroscopy. According to ITC, DPTH: HSA interaction process was spontaneous and endothermic with an affinity constant K-a = 4.31 x 10(2) M-1 and the stoichiometry coefficient (n) was equal 1, which was subsequently confirmed by H-1 NMR. Relaxation experiments provide quantitative information about the relationship between the binding affinity and structure of DPTH. Thus, association constant was determined as K-a = 9.65 x 10(2)M(-1). The results obtained by ITC and NMR were complemented with a molecular docking study. (C) 2021 Elsevier B.V. All rights reserved.

Imatinib is a selective tyrosine kinase inhibitor, successfully used for the treatment of chronic myelogenous leukaemia and gastrointestinal stromal tumors. Binding of drugs to proteins influence their pharmacokinetic and pharmacodynamics action. In the blood, the drug is distributed in the body in the free form or bound to plasma protein. Albumin and alpha-1 glycoprotein (AGP) are plasma proteins with the highest affinity for drug substances. Drugs which are weak acids mainly bind to plasma albumin, while drugs that are bases have affinity for alpha-1 glycoprotein. The main goal of this study is to quantitatively evaluate the interaction between imatinib mesylate (IMT) and alpha-1 glycoprotein to characterize the nature and forces underlying the formation of a molecular complex. Relaxation experiments provide quantitative information about the relationship between the binding affinity and structure of IMT. Thus, association constant was determined as K-a = 873.36 M-1. The ITC data revealed that the binding was an entropy driven process and the association constant K-a - 3.22 x 10(3) M-1, with a 1:1 stoichiometry. The results obtained by NMR and ITC were complemented with a molecular docking study. (C) 2020 Elsevier B.V. All rights reserved.

Spectroscopic investigation supported by molecular modeling methods has been used to describe the inclusion complex of β-cyclodextrin (β-CD) with 1-Methyl-1-({2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-4-yl}methyl) piperidinium chloride (1MPTMPC) in solution and in solid state. The formation of inclusion complex between the β-CD and the 1MPTMPC has been investigated both in solution and in the solid state. Solution-state complexation between the 1MPTMPC and β-CD was established using 1H NMR spectroscopy and isothermal titration calorimetry (ITC). From the 1H NMR spectroscopic studies, 1:1 complex stoichiometry was deduced with an association constant (K) of 925 M−1. Using an independent binding model, the ITC technique provides a K value of the same order with the one determined by NMR and the thermodynamic parameters ΔH, ΔS and ΔG which reveals driving forces involved during complex formation. The formation of the solid inclusion compound was confirmed by X-ray powder diffraction and differential scanning calorimetry. The most probable conformation of the inclusion complex obtained through a molecular docking investigation corroborates well to ROESY experiment.

We are developing a ground-based radio interferometric phased array for radio detection of high energy neutrinos, in an effort to lower the energy threshold of radio detection experiments while increasing the effective volume at high energies. The radio detection technique looks for Askaryan emission from neutrinos interacting in large volumes of glacial ice. The principle behind the phased array technique is coherent summing of the broadband, impulsive Askaryan signal from multiple antenna channels, increasing the signal-to-noise ratio for triggering on weak signals. We first discuss simulations and validation measurements related to the phased array technique, including results from a preliminary Monte Carlo simulation, a demonstration of beamforming and measurements of thermal noise correlation in an anechoic chamber, and results from a trigger simulation. We then discuss the design and development of the first ground-based interferometric phased array trigger system, a 16-channel system that has been built and will be deployed as part of one Askaryan Radio Array (ARA) station in December 2017 at the South Pole.

A quantitative analysis of the interaction between zidovudine (AZT) and human serum albumin (HSA) was achieved using Isothermal titration calorimetry (ITC) in combination with fluorescence and 1H NMR spectroscopy. ITC directly measure the heat during a biomolecular binding event and gave us thermodynamic parameters and the characteristic association constant. By fluorescence quenching, the binding parameters of AZT-HSA interaction was determined and location to binding site I of HSA was confirmed. Via T1 NMR selective relaxation time measurements the drug-protein binding extent was evaluated as dissociation constants Kd and the involvement of azido moiety of zidovudine in molecular complex formation was put in evidence. All three methods indicated a very weak binding interaction. The association constant determined by ITC (3.58×102M-1) is supported by fluorescence quenching data (2.74×102M-1). The thermodynamic signature indicates that at least hydrophobic and electrostatic type interactions played a main role in the binding process.

The KOTO data acquisition system (DAQ) collects detector PMT waveform signals and saves digitized events to permanent storage using frontend ADC modules, two levels of hardware triggers, and a computing farm. The KOTO DAQ system ran stably in 2013 with 24 kW beam power. To maintain high DAQ livetime with increasing beam power, we implemented lossless data compression inside the ADC modules and developed a new L3 computing farm. The upgraded KOTO DAQ system was able to maintain livetime above 80% with 42 kW beam power during the 2015 and 2016 runs. To sustain high DAQ livetime for data taking with beam power of 50 kW and above, an upgrade of our hardware trigger is proposed.

Complexation in solution between meclofenamate sodium (MCF) and β-cyclodextrin was studied using one- and two-dimensional 1H NMR spectroscopy and molecular docking coupled with ab initio calculations. The large variation of chemical shifts from protons located inside the hydrophobic cavity of β-cyclodextrin, provided clear evidence of inclusion complexation. The stoichiometry of the inclusion complex was determined to be 1:1, using the method of continuous variation. To ascertain the solution geometry of the host–guest complex a ROESY experiment was carried out. The results suggested a preferential binding of the dichlorophenyl moiety of the guest molecule within the β-cyclodextrin cavity, conformation which also sustained by the theoretical computational investigations. The association constant of the inclusion complex was determined using 1H NMR titration method in solution followed by a non-linear least-square regression implemented in CONSTEQ, a software developed in our group. After a preliminary molecular docking investigation, the most probable conformation was subjected to ab initio calculations using SIESTA software package, to characterize more precisely the stabilization energy of the 1:1 inclusion complex.

We describe a modular multi-channel data acquisition system based on the 5-15 Gigasample-per-second waveform-recording PSEC4 chip. The system architecture incorporates two levels of hardware with FPGA-embedded system control and inline data processing. The front-end unit is a 30-channel circuit board that holds five PSEC4 ASICs, a clock jitter cleaner, and a control FPGA. The analog bandwidth of the front-end signal path is 1.5 GHz. Each channel has an on-chip threshold-level discriminator that is monitored in the FPGA, from which a flexible on-board trigger decision can be formed. To instrument larger channel counts, a `back-end' 6U VME32 control card has been designed. Called the `Central Card', it incorporates an Altera Arria-V FPGA that manages up to 8 front-end cards using one or two CAT5 network cables per board, which transmits the clock and communicates data packets over a custom serial protocol. Data can be read from the Central Card via USB, Ethernet, or dual SFP links, in addition to the VME interface. The Central Card can be configured as either Master or Slave, allowing one Master to receive data from up to 8 Slaves, with each Slave managing 8 30-channel front-end cards, allowing a single VME crate to control up to 1920 channels of the PSEC4 chip.

The KOTO experiment at J-PARC in Tokai, Ibaraki, Japan, aims to observe rare neutral kaon decay mode K L → π 0 νν. Followed by the first KOTO physics run in May 2013 with 24 kW beam power, we upgraded the KOTO data acquisition system in 2015 to accommodate efficient and reliable data collection with higher beam intensities. Lossless data compression inside the ADC modules was implemented to reduced the size of data packets. The lossless data compression enhanced the data collection rate by a factor of three. We designed a new software trigger, which consists of 47 computer nodes. It uses Infiniband hardware with MPI protocol to establish mesh network within the computer cluster and parallel data processing. The upgrades of the KOTO data acquisition system were commissioned in 2015 and used to successfully collect data with beam intensity up to 42 kW. In preparation for increasing beam intensities in 2016 runs, we are developing the hardware trigger upgrades using the RCE Platform Technology (RPT).

The Large Area Picosecond PhotoDetector (LAPPD) Collaboration was formed in 2009 to develop large-area photodetectors capable of time resolutions measured in pico-seconds, with accompanying sub-millimeter spatial resolution. During the next three and one-half years the Collaboration developed the LAPPD design of 20 x 20 cm modules with gains greater than $10^7$ and non-uniformity less than $15\%$, time resolution less than 50 psec for single photons and spatial resolution of 700~microns in both lateral dimensions. We describe the R\&D performed to develop large-area micro-channel plate glass substrates, resistive and secondary-emitting coatings, large-area bialkali photocathodes, and RF-capable hermetic packaging. In addition, the Collaboration developed the necessary electronics for large systems capable of precise timing, built up from a custom low-power 15-GigaSample/sec waveform sampling 6-channel integrated circuit and supported by a two-level modular data acquisition system based on Field-Programmable Gate Arrays for local control, data-sparcification, and triggering. We discuss the formation, organization, and technical successes and short-comings of the Collaboration. The Collaboration ended in December 2012 with a transition from R\&D to commercialization.

We developed and built a new system of readout and trigger electronics, based on the waveform digitization and pipeline readout, for the KOTO experiment at J-PARC, Japan. KOTO aims at observing the rare kaon decay K L → π 0 νν̅. A total of 4000 readout channels from various detector subsystems are digitized by 14-bit 125-MHz ADC modules equipped with a 10-pole Bessel filter in order to reduce the pile-up effects. The trigger decision is made every 8-ns using the digitized waveform information. To avoid dead time, the ADC and trigger modules have pipelines in their FPGA chips to store data while waiting for the trigger decision. The KOTO experiment performed the first physics run in May 2013. The data acquisition system worked stably during the run.

This paper presents a 16-Channel, 12-Bit, 500 MHz ADC/Data Processing Module, designed for the KOTO Experiment at the Japan Proton Accelerator Research Complex (J-PARC). Few hundreds of this 6U VME board will receive signals from various detectors of the apparatus, and will be the digitizing modules in the Experiment's Data Acquisition System (DAQ). In KOTO, the main ADC/DAQ system runs at a 125 MHz simultaneous sampling rate, provided by one low jitter system clock. The 500 MHz ADC Module receives this system clock and multiplies its frequency by four with an internal PLL. The 16 analog input pulses are passed to 8 dual channel ADC chips (ADS5407). After sampling, data are processed locally with two Field Programmable Gate Arrays (FPGA). The module is equipped with a pipeline up to 40us (20,480 samples) long, where digitized values are stored, awaiting the system Level 1 trigger. After the trigger, data are packed and buffered for readout. The readout can be performed via the VME32/64 backplane, or via the two front panel QSFPs at rates of up to 48Gbps. Designed specifically for the KOTO Experiment, this module can also be used in many other Physics applications. The design and preliminary test results will be described.

Assessment of interaction between β-cyclodextrin and 3-carboxy-1-[(2-phenyl-1,3-thiazol-4-yl) methyl]pyridin-1-ium iodide (3CPTMPI) in aqueous solution were investigated by isothermal titration calorimetry (ITC) and 1D and 2D 1H NMR spectroscopy at 298 K. Thermodynamic analysis using ITC revealed that the association constant of β-cyclodextrin and 3CPTMPI is 441.6 M−1 with favorable enthalpy and entropy changes. These thermodynamic parameters indicate that the binding is dominated by hydrophobic interactions, which is in agreement with inclusion complex formation. The details of β-CD/3CPTMPI molecular interaction was analyzed by 1H 2D NMR allowing the proposition of an inclusion model for 3CPTMPI into β-CD. Rotating frame NOE spectroscopy (ROESY) was used to certain the solution geometry host–guest complex. The results reveal that the 3CPTMPI molecule penetrates into β-CD cavity with both aromatic and thiazol rings. For this type of inclusion complex, the association constant K obtained by 1H NMR and ITC are in good agreement and both methods sustain a 1:1 stoichiometry.

The extended use of tracking information at the trigger level in the LHC is crucial for the trigger and data acquisition (TDAQ) system to fulfill its task.Precise and fast tracking is important to identify specific decay products of the Higgs boson or new phenomena, as well as to distinguish the contributions coming from the many collisions that occur at every bunch crossing.However, track reconstruction is among the most demanding tasks performed by the TDAQ computing farm; in fact, complete reconstruction at full Level-1 trigger accept rate (100 kHz) is not possible.In order to overcome this limitation, the ATLAS experiment is planning the installation of a dedicated processor, the Fast Tracker (FTK), which is aimed at achieving this goal.The FTK is a pipeline of high performance electronics, based on custom and commercial devices, which is expected to reconstruct, with high resolution, the trajectories of charged-particle tracks with a transverse momentum above 1 GeV, using the ATLAS inner tracker information.Pattern recognition and the track parameter extraction are expected to be performed in roughly 100 µs, allowing all the high level trigger selections to use the tracks provided by FTK in order to build high quality and robust triggering.

We present a design for increasing the buffer length from 25.6ns to 3.3us in a 2-channel prototype of PSEC5, a custom integrated circuit designed for analog-to-digital conversion of fast analog signals at a sampling rate between 5 and 15 Gigasamples/second. The prototype is being designed in the same 0.13um IBM-8RF CMOS process as the PSEC4 ASIC [1]. The major improvements are the increase of the storage buffer from 256 cells to 32,768 cells per channel, allowing a trigger latency of ~3.3us at 10GS/sec, and an increased readout rate. The input signal is continuously sampled into a Primary Array with 256 capacitors which, for a 100ns sampling rate, is rewritten every 25.6ns. The sampling pulses are generated by a Voltage-Controlled Delay Line in 256 stages, run as a Delay-Locked Loop (DLL). The deep Storage Array is organized as two arrays, each 128 capacitors wide by 128 deep. The contents of each half of the Primary Array are transferred into the Storage Array at fixed time intervals in an alternate fashion. The writing and reading of the Storage Array is done with full external control. The design allows uninterrupted writing of the Storage Array after a trigger by selecting a region-of-interest for read-out and temporarily removing it from the recording chain. Depending on the size of the region-of-interest window, the dead time can be greatly reduced or eliminated. The sampled signals are digitized on-chip, and read out serially. The design status and simulation results will be presented.

The inclusion of local anesthetic drug procaine hydrochloride by β-cyclodextrin was investigated by 1D and 2D proton NMR spectroscopy and isothermal titration calorimetry (ITC) at 298 K. The stoichiometry of the complex was determinate by the method of continuous variation, using the chemical induced shift of both host and guest protons. The association constant K, of the obtained complex was calculated and found to be 293.17 M−1. Rotating frame NOE spectroscopy, was used to ascertain the solution geometry of the host–guest complex. The result reveals that the procaine molecule penetrates into the β-cyclodextrin cavity with the aromatic ring. The energetics of complexation process is investigated by ITC technique. The analysis indicates that the complexation of procaine by β-CD is an exothermic process and show that both enthalpy and entropy contribute to the binding process. The obtained value for the association constant is in good agreement with that obtained from NMR.

The interaction between stavudine, a nucleoside reverse transcriptase inhibitor and human serum albumin (HSA), was investigated by fluorescence quenching technique and isothermal titration calorimetry (ITC). A good linearity of albumin fluorescence quenching in the presence of stavudine was determined. Analyzing these data we obtained for the dissociation constant the value Kd=(18.18±0.46)×10−5M. However, due to contradictory results obtained in ITC experiments, we checked the fluorescence quenching data for the inner-filter effect, the main confounding factor in the observed quenching. Based on the UV–vis absorption data we have corrected the observed fluorescence intensities and concluded, in accordance with ITC results, that stavudine binding to HSA is negligible and the observed quenching effect is entirely caused by a failure to correct for the inner-filter effect.