P. Petkov

Our objective is to reveal the molecular mechanism of the anti-inflammatory action of low-molecular-weight heparin (LMWH) based on its influence on the activity of two key cytokines, IFNγ and IL-6. The mechanism of heparin binding to IFNγ and IL-6 and the resulting inhibition of their activity were studied by means of extensive molecular-dynamics simulations. The effect of LMWH on IFNγ signalling inside stimulated WISH cells was investigated by measuring its antiproliferative activity and the translocation of phosphorylated STAT1 in the nucleus. We found that LMWH binds with high affinity to IFNγ and is able to fully inhibit the interaction with its cellular receptor. It also influences the biological activity of IL-6 by binding to either IL-6 or IL-6/IL-6Rα, thus preventing the formation of the IL-6/IL-6Rα/gp130 signalling complex. These findings shed light on the molecular mechanism of the anti-inflammatory action of LMWH and underpin its ability to influence favourably conditions characterised by overexpression of these two cytokines. Such conditions are not only associated with autoimmune diseases, but also with inflammatory processes, in particular with COVID-19. Our results put forward heparin as a promising means for the prevention and suppression of severe CRS and encourage further investigations on its applicability as an anti-inflammatory agent.

The CMS Barrel resistive plate chambers quality tests are performed at three different sites (Bari, Pavia and Sofia), where equivalent software and hardware tools are used. Data from the first 210 detectors are available for a comprehensive analysis. The paper describes the general experimental set-up, the test procedure and the cosmic muon test results. The muon trajectory reconstruction algorithm, used for precise studies, is presented. The criteria to accept or reject a detector are also given. The CMS final-design chambers show an average efficiency greater than 95%.

Antimicrobial peptides (AMPs) are a diverse group of membrane-active peptides which play a crucial role as mediators of the primary host defense against microbial invasion. Many AMPs are found to be fully or partially disordered in solution and to acquire secondary structure upon interaction with a lipid membrane. Here, we report molecular dynamics simulations studies on the solution behaviour of a specific AMP, bombinin H2. We show that in monomeric form in water solution the peptide is somewhat disordered and preferably adopts a helix-loop-helix conformation. However, when more than a single monomer is placed in the solution, the peptides self-associate in aggregates. Within the aggregate, the peptides provide each other with an amphipathic environment that mimics the water-membrane interface, which allows them to adopt a single-helix structure. We hypothesise that this is the mechanism by which bombinin H2 and, possibly, other small linear AMPs reach the target membrane in a functional folded state and are able to effectively exert their antimicrobial action on it.

The formation of highly reactive compounds in the gas mixture during Resistive Plate Chambers (RPCs) operation at the CERN Gamma Irradiation Facility (GIF) is studied. Results from two different types of chambers are discussed: 50 × 50 cm2 RPC prototypes and two final CMS-RB1 chambers. The RB1 detectors were also connected to a closed loop gas system. Gas composition, possible additional impurities as well as fluoride ions have been monitored in different gamma irradiation conditions both in open and closed loop mode. The chemical composition of the RPC electrode surface has also been analyzed using an electron microscope equipped with an EDS/X-ray.

ORF6 protein of the SARS-CoV-2 virus plays a crucial role in blocking the innate immune response of the infected cells by inhibiting interferon pathways. Additionally, it binds and immobilises the RAE1 protein onto the cytoplasmic membranes, thereby blocking the transport of mRNA from the nucleus to the cytoplasm. In all these cases the host cell proteins are tethered by the flexible C-terminus of ORF6. A possible strategy to inhibit the biological activity of ORF6 is to bind its C-terminus with suitable ligands. Our in silico experiments suggest that hIFNγ binds the ORF6 protein with high affinity, thus impairing its interactions with RAE1 and, consequently, its activity in viral invasion. The here reported in vitro studies reveal a shift of the localization of RAE1 in ORF6 overexpressing cells upon treatment with hIFNγ from predominantly cytoplasmic to mainly nuclear, resulting in restoration of the export of mRNA from the nucleus. We also explored the expression of GFP in transfected with ORF6 cells by means of fluorescence microscopy and qRT-PCR, finding that treatment with hIFNγ unblocks the mRNA trafficking and reinstates the GFP expression level. The ability of the cytokine to block ORF6 is also reflected in minimising its negative effects on DNA replication by reducing accumulated RNA-DNA hybrids. Our results, therefore, suggest hIFNγ as a promising inhibitor of the most toxic SARS-CoV-2 protein.

The ORF6 protein of the SARS-CoV-2 virus plays a crucial role in blocking the innate immune response of the infected cells by inhibiting interferon pathways. Additionally, it binds to and immobilises the RAE1 protein on the cytoplasmic membranes, thereby blocking mRNA transport from the nucleus to the cytoplasm. In all these cases, the host cell proteins are tethered by the flexible C-terminus of ORF6. A possible strategy to inhibit the biological activity of ORF6 is to bind its C-terminus with suitable ligands. Our in silico experiments suggest that hIFNγ binds the ORF6 protein with high affinity, thus impairing its interactions with RAE1 and, consequently, its activity in viral invasion. The in vitro studies reported here reveal a shift of the localisation of RAE1 in ORF6 overexpressing cells upon treatment with hIFNγ from predominantly cytoplasmic to mainly nuclear, resulting in the restoration of the export of mRNA from the nucleus. We also explored the expression of GFP in transfected-with-ORF6 cells by means of fluorescence microscopy and qRT-PCR, finding that treatment with hIFNγ unblocks the mRNA trafficking and reinstates the GFP expression level. The ability of the cytokine to block ORF6 is also reflected in minimising its negative effects on DNA replication by reducing accumulated RNA-DNA hybrids. Our results, therefore, suggest hIFNγ as a promising inhibitor of the most toxic SARS-CoV-2 protein.

Proteins are currently the fastest-growing class of new therapeutic compounds but smaller proteins and peptides are generally not suitable for use as drugs. Using cyclotides – special knotted proteins stabilized by three pairs of disulphide bonds – as a transport means by grafting onto them as a scaffolding the bioactive peptides can enhance their stability, cellular uptake, and overall efficacy. Experimental methods for creating peptide aptamers are highly time- and resources-consuming. In silico approaches may speed up this process by pre-selecting the drug candidates based on certain biodynamic criteria. In this study, we probe the hypothesis about a relation between the scaffolding conformational stability in conjunction with certain plasticity upon grafting of functionally important domains and the desired biological activity of the modified through the grafting process molecules.

In view of the High Luminosity upgrade of the CERN LHC, the forward CMS Muon spectrometer will be extended with two new stations of improved Resistive Plate Chambers (iRPC) covering the pseudorapidity range from 1.8 to 2.4. Compared to the present RPC system, the gap thickness is reduced to lower the avalanche charge, and an innovative 2D strip readout geometry is proposed. These improvements will allow iRPC detector to cope with higher background rates. A new Front-End-Board (FEB) is designed to readout iRPC signals with a threshold as low as 30 fC and an integrated Time Digital Converter with a resolution of 30 ps. In addition, the communication bandwidth is significantly increased by using optical fibers. The history, final design, certification, and calibration of this FEB are presented.

Several small single gap Resistive Plate Chambers and two RB1 CMS final stations have been exposed during the last year at the CERN Gamma Irradiation Facility to study possible long-term ageing effects. Up to now, an integrated charge of about 0.05C/(cm2gap) and 0.025 C/(cm2 gap) has been accumulated for the small RPCs and the large RB1 stations, respectively. Current, rate, fast charge and efficiency have been continuously monitored with muon beam or cosmics. Results concerning operation with a moisty mixture are also reported.

Major histocompatibility complex (MHC) II proteins bind peptide fragments derived from pathogen antigens and present them at the cell surface for recognition by T cells. MHC proteins are divided into Class I and Class II. Human MHC Class II alleles are grouped into three loci: HLA-DP, HLA-DQ, and HLA-DR. They are involved in many autoimmune diseases. In contrast to HLA-DR and HLA-DQ proteins, the X-ray structure of the HLA-DP2 protein has been solved quite recently. In this study, we have used structure-based molecular dynamics simulation to derive a tool for rapid and accurate virtual screening for the prediction of HLA-DP2-peptide binding. A combinatorial library of 247 peptides was built using the "single amino acid substitution" approach and docked into the HLA-DP2 binding site. The complexes were simulated for 1 ns and the short range interaction energies (Lennard-Jones and Coulumb) were used as binding scores after normalization. The normalized values were collected into quantitative matrices (QMs) and their predictive abilities were validated on a large external test set. The validation shows that the best performing QM consisted of Lennard-Jones energies normalized over all positions for anchor residues only plus cross terms between anchor-residues.

The formation of reactive compounds in the gas mixture during Resistive Plate Chambers (RPCs) operation at the CERN Gamma Irradiation Facility (GIF) is studied. Results from two different types of chambers are discussed: 50×50cm2 RPC prototypes and two final CMS-RB1 chambers. The RB1 detectors were also connected to a closed loop gas system. Gas composition and possible additional impurities have been monitored in different gamma irradiation conditions both in open and closed loop modes using a gas chromatograph. Dedicated measurements for fluoride concentration in the exhausted gas line were performed at different irradiations and operation conditions using a specific electrode and a High-Performance Liquid Chromatograph. The efficiency of the purifiers system present in the closed loop in removing the F- and others impurities has also been investigated. Finally, the chemical composition of the RPC electrode surface has been analyzed using an electron microscope equipped with an EDS/X-ray.

Due to its large volume (18 m3)the Resistive Plate Chamber (RPC) detector of the Compact Muon Solenoid (CMS) experiment at the LHC proton collider (CERN, Switzerland) will employ a gas re-circulation system. Since the mixture composition and quality are crucial issues for the detector operation, CMS-RPC will use an online gas analysis and monitoring system. An overview of both the CMS-RPC gas system and gas monitoring system is given and the project parameters are described.

Transforming the resistive plate chambers from charged-particle into gamma-quanta detectors opens the way towards their application as a basic element of a hybrid imaging system, which combines positron emission tomography (PET) with magnetic resonance imaging (MRI) in a single device and provides non- and minimally- invasive quantitative methods for diagnostics. To this end, we performed detailed investigations encompassing the whole chain from the annihilation of the positron in the body, through the conversion of the created photons into electrons and to the optimization of the electron yield in the gas. GEANT4 based simulations of the efficiency of the RPC photon detectors with different converter materials and geometry were conducted for optimization of the detector design. The results justify the selection of a sandwich-type gas-insulator-converter design, with Bi or Pb as converter materials.

Resistive Plate Chambers have been chosen as dedicated trigger muon detector for the Compact Muon Solenoid experiment [1] at the Large Hadron Collider [2] at CERN. The system consists of about 3000 m2 of double gap RPC chambers placed in both the barrel and endcap muon regions.

The structure and scaling properties of inwardly curved polymer brushes, tethered under good solvent conditions to the inner surface of spherical shells such as membranes and vesicles, are studied by extensive molecular dynamics simulations and compared with earlier scaling and self-consistent field theory predictions for different molecular weights of the polymer chains N and grafting densities σg in the case of strong surface curvature, R-1. We examine the variation of the critical radius R*(σg), separating the regimes of weak concave brushes and compressed brushes, predicted earlier by Manghi et al. [Eur. Phys. J. E 5, 519-530 (2001)], as well as various structural properties such as the radial monomer- and chain-end density profiles, orientation of bonds, and brush thickness. The impact of chain stiffness, κ, on concave brush conformations is briefly considered as well. Eventually, we present the radial profiles of the local pressure normal, PN, and tangential, PT, to the grafting surface, and the surface tension γ(σg), for soft and rigid brushes, and find a new scaling relationship PN(R)∝σg4, independent of the degree of chain stiffness.

ORF6 is responsible for suppressing the immune response of cells infected by the SARS-CoV-2 virus. It is also the most toxic protein of SARS-CoV-2, and its actions are associated with the viral pathogenicity. Here we study in silico and in vitro the structure of the protein, its interaction with RAE1, and the mechanism of action behind its high toxicity. We show both computationally and experimentally that SARS-CoV-2 ORF6, embedded in the membranes of the endoplasmic reticulum, binds to RAE1 and sequesters it in the cytoplasm, thus depleting its availability in the nucleus and impairing nucleocytoplasmic mRNA transport. This negatively affects the cellular genome stability by compromising the cell cycle progression into the S-phase and by promoting the accumulation of RNA-DNA hybrids. Understanding the multiple ways in which ORF6 affects DNA replication may also have important implications for elucidating the pathogenesis of SARS-CoV-2 and developing therapeutic strategies to mitigate its deleterious effects on host cells.

ORF6 is responsible for suppressing the immune response of cells infected by the SARS-CoV-2 virus. It is also the most toxic protein of SARS-CoV-2, and its actions are associated with the viral pathogenicity. Here, we study in silico and in vitro the structure of the protein, its interaction with RAE1 and the mechanism of action behind its high toxicity. We show both computationally and experimentally that SARS-CoV-2 ORF6, embedded in the cytoplasmic membranes, binds to RAE1 and sequesters it in the cytoplasm, thus depleting its availability in the nucleus and impairing nucleocytoplasmic mRNA transport. This negatively affects the cellular genome stability by compromising the cell cycle progression into the S-phase and by promoting the accumulation of RNA–DNA hybrids. Understanding the multiple ways in which ORF6 affects DNA replication may also have important implications for elucidating the pathogenicity of SARS-CoV-2 and developing therapeutic strategies to mitigate its deleterious effects on host cells.

The Resistive Plate Chambers (RPCs) are employed in the CMS experiment at the LHC as dedicated trigger system both in the barrel and in the endcap. This note presents results of the RPC detector uniformity and stability during the 2011 data taking period, and preliminary results obtained with 2012 data. The detector uniformity has been ensured with a dedicated High Voltage scan with LHC collisions, in order to determine the optimal operating working voltage of each individual RPC chamber installed in CMS. Emphasis is given on the procedures and results of the High Voltage calibration. Moreover, an increased detector stability has been obtained by automatically taking into account temperature and atmospheric pressure variations in the CMS cavern.

During the summer 2006, a first integrated test of a part of the CMS experiment was performed at CERN collecting a data sample of several millions of cosmic rays events. A fraction of the Resistive Plate Chambers system was successfully operated. Results on the RPC performance are reported.

The CMS experiment, located at the Large Hadron Collider (LHC) in CERN, has a redundant muon system composed by three different gaseous detector technologies: Cathode Strip Chambers (in the forward regions), Drift Tubes (in the central region), and Resistive Plate Chambers (both its central and forward regions). All three are used for muon reconstruction and triggering. The CMS RPC system confers robustness and redundancy to the muon trigger. The RPC system operation in the challenging background and pileup conditions of the LHC environment is presented. The RPC system provides information to all muon track finders and thus contributing to both muon trigger and reconstruction. The summary of the detector performance results obtained with proton-proton collision at √s = 13 TeV during 2016 and 2017 data taking have been presented. The stability of the system is presented in terms of efficiency and cluster size vs time and increasing instantaneous luminosity. Data-driven predictions about the expected performance during High Luminosity LHC (HL-LHC) stage have been reported.

Abstract A new generation of resistive plate chambers, capable of withstanding high particle fluxes (up to 2000 Hz · cm -2 ) and instrumented with precise timing readout electronics is proposed to equip two of the four high pseudorapidity stations of the CMS muon system. Double-gap RPC detectors, with each gap made of two 1.4 mm High Pressure Laminate electrodes and separated by a gas gap of the same thickness, are proposed. The new layout reduces the amount of the avalanche charge produced by the passage of a charged particle through the detector. This improves the RPC rate capability by reducing the needed time to collect this charge. To keep the RPC efficiency high, a sensitive, low-noise and high time resolution front-end electronics is needed to cope with the lower charge signal of the new RPC. An ASIC called PETIROC that has all these characteristics has been selected to read out the strips of new chambers. Thin (0.6 mm) printed circuit board, 160 cm long, equipped with pickup strips of 0.75 cm average pitch, will be inserted between the two new RPC's gaps. The strips will be read out from both ends, and the arrival time difference of the two ends will be used to determine the hit position along the strip. Results from the improved RPC equipped with the new readout system and exposed to cosmic muons in the high irradiation environment at CERN GIF++ facility are presented in this work.

(2005). Genetic Modification of Alfalfa (Medicago Sativa L.) for Quality Improvement and Production of Novel Compounds. Biotechnology & Biotechnological Equipment: Vol. 19, 20th Anniversary AgroBioInstitute—R&D, pp. 56-62.

The Resistive Plate Chambers (RPCs) are employed in the CMS Experiment at the LHC as dedicated trigger system both in the barrel and in the endcap. This article presents results of the radiation background measurements performed with the 2011 and 2012 proton-proton collision data collected by CMS. Emphasis is given to the measurements of the background distribution inside the RPCs. The expected background rates during the future running of the LHC are estimated both from extrapolated measurements and from simulation.

We report on a systematic study of double-gap and four-gap phenolic resistive plate chambers (RPCs) for the Phase-2 upgrade of the CMS muon system at high η. In the present study, we constructed real-sized double-gap and four-gap RPCs with gap thicknesses of 1.6 and 0.8 mm, respectively, with 2-mm-thick phenolic high-pressure-laminated (HPL) plates. We examined the prototype RPCs with cosmic rays and with 100-GeV muons provided by the SPS H4 beam line at CERN. To examine the rate capability of the prototype RPCs both at Korea University and at the CERN GIF++ facility, the chambers were irradiated with 137Cs sources providing maximum gamma rates of about 1.5 kHz cm−2. For the 1.6-mm-thick double-gap RPCs, we found the relatively high threshold on the produced detector charge was conducive to effectively suppressing the rapid increase of strip cluster sizes of muon hits with high voltage, especially when measuring the narrow-pitch strips. The gamma-induced currents drawn in the four-gap RPC were about one-fourth of those drawn in the double-gap RPC. The rate capabilities of both RPC types, proven through the present testing using gamma-ray sources, far exceeded the maximum rate expected in the new high-η endcap RPCs planned for future phase-II runs of the Large Hadron Collider (LHC).

Human interferon-gamma (hIFN-γ) is an important antiviral and immunomodulating signaling molecule. The upregulation of its production, however, is related to the etiology of certain autoimmune diseases. In the search for a mechanism for suppressing the hIFN-γ biological activity, we investigated the possibility to obtain mutant derivatives of the protein, capable to bind to hIFN-γ cellular receptors, but lacking the ability to trigger the biological response inside the cell. In order to preserve the affinity to the receptor, the introduced mutations should not induce conformational changes in the secondary structure of the mutants. Molecular dynamics simulations were performed to study the secondary structure of 100 randomly chosen hIFN-γ derivatives with substitutions in amino acids 86–88. The stability of the local structure of all hIFN-γ forms was investigated by means of metadynamics. It was found that some of the mutated forms preserve the local secondary structure and show similar or higher stability of the mutated helix, compared to the native form. The 12 most promising mutants were suggested for experimental investigation.

Human interferon gamma (hIFN- $$\gamma $$ ) is an important signalling molecule, which plays a key role in the formation and modulation of immune response. The controversial conclusions concerning the function of hIFN- $$\gamma $$ C-termini as well as the lack of structural information about this domain motivated us to perform molecular dynamics simulations in order to model the structure of the hIFN- $$\gamma $$ C-terminal part. The simulations were carried out with the CHARMM22 force field, starting from a fully extended conformation of the C-termini. They showed unambiguously that the C-termini tend to approach the globular part of the protein, so that the whole hIFN- $$\gamma $$ molecule adopts a more compact conformation. The energetic favourability of the more compact conformations of the whole cytokine was also confirmed by means of free energy perturbation simulations.

Antimicrobial peptides (AMPs) play crucial role as mediators of the primary host defense against microbial invasion. They are considered a promising alternative to antibiotics for multidrug resistant bacterial strains. For complete understanding of the antimicrobial defense mechanism, a detailed knowledge of the dynamics of peptide-membrane interactions, including atomistic studies on AMPs geometry and both peptide and membrane structural changes during the whole process is a prerequisite. We aim at clarifying the conformation dynamics of small linear AMPs in solution as a first step of in silico protocol for establishing a correspondence between certain amino-acid sequence motifs, secondary-structure elements, conformational dynamics in solution and the intensity and mode of interaction with the bacterial membrane. To this end, we use molecular dynamics simulations augmented by well-tempered metadynamics to study the free-energy landscape of two AMPs with close primary structure and different antibacterial activity - the native magainin 2 (MG2) and an analog (MG2m, with substitutions F5Y and F16W) in aqueous solution. We observe that upon solvation, the initial α-helical structures change differently. The native form remains structured, with three shorter α-helical motifs, connected by random coils, while the synthetic analog tends predominantly to a disordered conformation. Our results indicate the importance of the side-chains at positions 5 and 16 for maintaining the solvated peptide conformation. They also provide a modeling background for recent experimental observations, relating the higher α-helical content in solution (peptide pre-folding) in the case of small linear AMPs to a lower antibacterial activity.

Resistive Plate Chambers, working in avalanche mode, have been choosen as dedicated muon detector both in barrel and endcap region of the CMS experiment for their fast response and for their capability to be produced as tracking devices on large areas. The production of the barrel RPC chambers will be reported here with special enphasis on the quality control and on the acceptation criteria carried out during the production. Results of the tests with cosmic rays both in production and testing sites will be summerized putting in evidence the problems and the critical issues characterizing the different phases of the construction.

In order to obtain glycosylated human interferon-gamma (hIFNγ) and its highly prone to aggregation mutant K88Q, a secretory expression in insect cells was employed. To facilitate recombinant proteins purification, detection, and stability the baculovirus expression vectors were constructed to bear N-terminal His6-FLAG tag. Although the obtained proteins were glycosylated, we found that their biological activity was 100 times lower than expected. Our attempts to recover the biological properties of both proteins by tag removal failed due to enterokinase resistance of the tag. Surprisingly, the tag was easily cleaved when the proteins were expressed in E. coli cells and the tag-free proteins showed fully restored activity. To shed light on this phenomenon we performed molecular dynamics simulations. The latter showed that the tags interact with the receptor binding domains and the flexible C-termini of the fusion proteins thus suppressing their complex formation with the hIFNγ receptor. We hypothesize that in the case of glycosylated proteins the tag/C-terminal interaction positions the FLAG peptide in close proximity to the glycans thus sterically impeding the enterokinase access to its recognition site.

Four double-gap CMS resistive plate chambers are being tested at the CERN Gamma Irradiation Facility to determine the performance and aging effects at the expected conditions of the High Luminosity-Large Hadron Collider. Results up to an integrated charge of 290 millicoulomb/cm2 are reported.

Understanding the mechanism of action of antimicrobial peptides (AMPs) on bacterial cells requires detailed knowledge of how AMPs interact with bacterial membranes. Our hypothesis is that the peptides do not interact with the membrane as monomers, but rather form clusters, that collectively approach the cell and attack the membrane. In this paper we investigate the behavior of the antimicrobial peptide indolicidin in solution, prior to their interaction with the bacterial membrane, by means of coarse grain molecular dynamics simulations (CG-MD). We show that indolicidin in particular and, probably, charged linear AMPs in general tend to aggregate in solution, forming globular amphipathic clusters with a central hydrophobic core. The dependence of the clusters size on the peptide concentration and on the temperature is studied, as well as the influence of the finite size of the simulation box. Our results manifest the investigation of the AMPs behavior in solution prior to membrane impact as an indispensable element in revealing the mechanism of their antimicrobial activity.

The high pseudo-rapidity region of the CMS muon system is covered by Cathode Strip Chambers (CSC) only and lacks redundant coverage despite the fact that it is a challenging region for muons in terms of backgrounds and momentum resolution. In order to maintain good efficiency for the muon trigger in this region additional RPCs are planned to be installed in the two outermost stations at low angle named RE3/1 and RE4/1. These stations will use RPCs with finer granularity and good timing resolution to mitigate background effects and to increase the redundancy of the system.

Abstract During the upcoming High Luminosity phase of the Large Hadron Collider (HL-LHC), the integrated luminosity of the accelerator will increase to 3000 fb −1 . The expected experimental conditions in that period in terms of background rates, event pileup, and the probable aging of the current detectors present a challenge for all the existing experiments at the LHC, including the Compact Muon Solenoid (CMS) experiment. To ensure a highly performing muon system for this period, several upgrades of the Resistive Plate Chamber (RPC) system of the CMS are currently being implemented. These include the replacement of the readout system for the present system, and the installation of two new RPC stations with improved chamber and front-end electronics designs. The current overall status of this CMS RPC upgrade project is presented.

CMS experiment will use resistive plate chambers (RPCs) as dedicated muon trigger detectors. This requires good chamber global and local performance. To verify the chamber performance intensive tests are going on using a telescope installed at Bari Physics Department. The chamber efficiency is obtained by track reconstruction, which offers also the possibility to perform local efficiency studies. A brief description of the test set-up, reconstruction algorithm and test results are presented in this paper.

The CMS muon system is conceived for trigger and muon track reconstruction. The redundancy and robustness of the system are guaranteed by three complementary subsystems: drift tube in the barrel, cathode strip chamber in the end-cap and resistive plate chamber in barrel and end-cap. The installation of muon stations and read-out trigger electronic has been completed in middle 2007. Since than, a remarkable effort has been addressed to the detector commissioning in order to ensure the readiness of the hardware/software chain for the LHC start up operation. At the end of 2007, a test of an entire CMS slice has been performed, involving about 5% of muon stations. Several thousand cosmic muons events have been collected. Performance of the barrel chambers are reported.

In the CERN CMS experiment at LHC Collider special trigger signals called Technical Triggers will be used for the purpose of test and calibration. The Resistive Plate Chambers (RPC) based Technical Trigger system is a part of the CMS muon trigger system and is designed to detect cosmic muon tracks. It is based on two boards, namely RBC (RPC Balcony Collector) and TTU (Technical Trigger Unit). The proposed tracking algorithm (TA) written in VHDL and implemented in the TTU board detects single or multiple cosmic muon tracks at every bunch crossing along with their track lengths and corresponding chamber coordinates. The TA implementation in VHDL and its preliminary simulation results are presented.

In the CMS experiment, sub-detectors may send special trigger signals, called “Technical Triggers”, for purposes like test and calibration. The Resistive Plate Chambers are part of the Muon Trigger System of the experiment, but might also produce a cosmic muon trigger to be used during the commissioning of the detectors, the CMS Magnet Test-Cosmic Challenge and the later running of CMS. The proposed implementation is based on the development of a new board, the RPC Balcony Collector (RBC); the test results on prototypes and their performance during the recent CMS Cosmic Challenge are presented.

Resistive Plate Chambers (RPC) have been chosen as dedicated trigger muon detectors for the Compact Muon Solenoid [CMS collaboration, Technical Design Report, CERN/LHCC 94-38, 1994. [1]] experiment at the Large Hadron Collider [The LHC project at CERN, LHC-project-report-36, 1996. [2]] at CERN. Four Italian groups from Bari, Frascati, Napoli and Pavia and two Bulgarian groups from Sofia have participated in designing and constructing the RPC barrel system. A sophisticated and complex production line has been organized by the collaboration to build the 480 RPC chambers, with a quality assurance (QA) test, made by 3 consecutive steps, in order to assure full functionality of the chambers. A final certification of the chambers has been made at ISR (CERN) with a month-long test. After that the RPCs have been coupled to the Drift Tube chamber and installed in the iron return yoke of the CMS solenoid. The first chamber was produced in 2002 and last was installed in October 2007. The system is now completely installed and commissioning has been going on since the second half of 2005 to complete the Large Hadron Collider (LHC) startup in the summer of 2008. The chamber construction, the test made, the main results achieved and a short description of all the services needed to run the RPC barrel system will be described in this paper.

With the increase of the LHC luminosity foreseen in the coming years, many detectors currently used in the different LHC experiments will be dramatically impacted and some need to be replaced or upgraded. The new ones should be capable to provide time information to reduce the data ambiguity due to the expected high pileup. We propose to equip CMS high |η| muon chambers with pairs of single gap RPC detectors read out by long pickup strips PCB. The precise time measurement (0<15 ps) of the signal induced by particles crossing the detector on both ends of each strip will give an accurate measurement of the position of the incoming particle along the strip. The absolute time measurement, determined by RPC signal (around 1.5 ns) will also reduce the data ambiguity due to the highly expected pileup and help to identify Heavy Stable Charged Particles (HSCP). The development of a specific electronic chain (analog front-end ASIC, time-to-digital converter stage and printed circuit board design) and the corresponding first results on prototype chambers are presented.

The high luminosity expected from the HL-LHC will be a challenge for the CMS detector. The increased rate of particles coming from the collisions and the radioactivity induced in the detector material could cause significant damage and result in a progressive degradation of its performance. Simulation studies are very useful in these scenarios as they allow one to study the radiation environment and the impact on detector performance. Results are presented for CMS RPC stations considering the operating conditions expected at the HL-LHC.

The CMS experiment recorded 177.75 /fb of proton-proton collision data during the RUN-1 and RUN-2 data taking period. Successful data taking at increasing instantaneous luminosities with the evolving detector configuration was a big achievement of the collaboration. The CMS RPC system provided redundant information for the robust muon triggering, reconstruction, and identification. To ensure stable data taking, the CMS RPC collaboration has performed detector operation, calibration, and performance studies. Various software and related tools are developed and maintained accordingly. In this paper, the overall performance of the CMS RPC system and experiences of the data taking during the RUN-2 period are summarised.

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation N. Ilieva, J. Liu, R. Marinova, P. Petkov, L. Litov, J. He, A. J. Niemi; Are there folding pathways in the functional stages of intrinsically disordered proteins?. AIP Conf. Proc. 13 October 2016; 1773 (1): 110008. https://doi.org/10.1063/1.4965012 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAIP Publishing PortfolioAIP Conference Proceedings Search Advanced Search |Citation Search

The muon spectrometer of the CMS (Compact Muon Solenoid) experiment at the Large Hadron Collider (LHC) is equipped with a redundant system made of Resistive Plate Chambers and Drift Tube in barrel and RPC and Cathode Strip Chamber in endcap region. In this paper, the operations and performance of the RPC system during the first three years of LHC activity will be reported. The stability of RPC performance, such as efficiency, cluster size and noise, will be reported. Finally, the radiation background levels on the RPC system have been measured as a function of the LHC luminosity. Extrapolations to the LHC and High Luminosity LHC conditions are also discussed.

During Run-3, the LHC is preparing to deliver instantaneous luminosity in the range from 5 × 1034 cm−2 s−1 to 7.5 × 1034 cm−2 s−1. To ensure stable data taking, providing redundant information for robust muon triggering, reconstruction and identification, the CMS RPC collaboration has used the opportunity given by the LHC long shutdown 2 (LS2), to perform a series of maintenance and preparation activities for the new data taking period. The overall performance of the RPC system after the LS2 commissioning period and the activities in preparation for future data taking will be presented.

During Run2 the high instantaneous luminosity, up to 2.21034cm−2s−1, lead to a substantial hit rate in the Compact Muon Solenoid experiment’s muon chambers due to multiple background sources to physics processes sought for at LHC. In this article we will describe the analysis method devised to measure and identify the contributions to such background in the Resistive Plate Chambers. Thorough understanding of the background rates provides the base for the upgrade of the muon detectors for the High-Luminosity LHC.

The article focuses on some of the comparisons between China and the West on the pages of John Bell’s travel account. Regardless of how neutral or non-judgmental John Bell strives to be, his travel account contains a number of such comparisons. The majority of these are implicit and deserving of examination as well, but in this article I discuss some of those that are direct because they are the most striking and indicative of the British author’s attitude towards the East.

The Resistive Plate Chambers [M. Abbrescia, et al., Nucl. Instr. and Meth. A 550 (2005) 116] are used in the CMS experiment [CMS Collaboration, The CMS experiment at the CERN LHC 2008, J. Inst. 3 (2008) S08004] as a dedicated muon trigger both in barrel and endcap system. About 4000m2 of double gap RPCs have been produced and have been installed in the experiment since more than one and half Years. The full barrel system and a fraction of the endcaps have been monitored to study dark current behaviour and system stability, and have been extensively commissioned with Cosmic Rays collected by the full CMS experiment.

The Resistive Plate Chambers (RPC) are charged‐particle detectors with excellent spatial and time resolution. Transforming them into gamma‐quanta detectors opens the way towards their application as a basic element of a hybrid imaging system, which combines Positron Emission Tomography (PET) with Magnetic Resonance Imaging (MRI). We present results from the optimization of the RPC construction by means of GEANT4 simulations. Several different detector designs and converter materials are investigated to meet the objectives for a prospective RPCPET detector: maximal electron yield for 511 KeV photons and reduced efficiency for registration of lower‐energy scattered photons. The efficiency of a multi‐gap RPC detector is studied.

An RPC based system will be employed for the CMS muon first level trigger. Severe quality controls and certification have been established all along the entire production chain. Procedures are briefly described and results for the acceptance percentage are given for the second part of the single gaps and double gaps production. Summary results are also reported for the full sets of tested chambers.

Based on previous experience and attempt, a real-size mosaic Multi-gap Resistive Plate Chamber (MRPC) has been developed within the framework of the CMS muon upgrade efforts. The chamber is a 5-gap with plates made each of 6 pieces of low resistive glass. Cosmic ray test at CERN 904 shows that its efficiency can reach above 95% with a gas mixture of 90% C2H2F4, 5% i-C4H10 and 5% SF6. The chamber was also tested with CMS dry gas(95.2% C2H2F4, 4.5% i-C4H10, 0.3% SF6) at the CERN Gamma Irradiation Facility (GIF++). Efficiency results calculated by a simple tracking method show that the good performance is maintained at rates up to 10 kHz/cm2.

Abstract The expected radiation background in the CMS RPC system has been studied using the MC prediction with the CMS FLUKA simulation of the detector and the cavern. The MC geometry used in the analysis describes very accurately the present RPC system but still does not include the complete description of the RPC upgrade region with pseudorapidity 1.9 &lt; |η| &lt; 2.4. Present results will be updated with the final geometry description, once it is available. The radiation background has been studied in terms of expected particle rates, absorbed dose and fluence. Two High Luminosity LHC (HL-LHC) scenarios have been investigated — after collecting 3000 and 4000 fb -1 . Estimations with safety factor of 3 have been considered, as well.

ABSTRACT Timely control of the cytokine release syndrome (CRS) at the severe stage of COVID-19 is key to improving the treatment success and reducing the mortality rate. The inhibition of the activity of the two key cytokines, IFNγ and IL-6, can significantly reduce or even reverse the development of the cytokine storm. The objective of our investigations is to reveal the anti-inflammatory potential of heparin for prevention and suppression of the development of CRS in acute COVID-19 patients. The effect of low-molecular-weight heparin (LMWH) on IFNγ signalling inside the stimulated WISH cells was investigated by measuring its antiproliferative activity and the translocation of phosphorylated STAT1 in the nucleus. The mechanism of heparin binding to IFNγ and IL-6 and therefore inhibition of their activity was studied by means of extensive molecular-dynamics simulations. We find that LMWH binds with high affinity to IFNγ and is able to inhibit fully the interaction with its cellular receptor. It also influences the biological activity of IL-6 by binding to either IL-6 or IL-6/IL-6Rα thus preventing the formation of the IL-6/IL-6Rα/gp130 signaling complex. Our conclusion is that heparin is a potent anti-inflammatory agent that can be used in acute inflammatory conditions, due to its potential to inhibit both IFN γ and IL-6 signalling pathways. Based on our results and available clinical observations, we suggest the administration of LMWH to COVID-19 patients in the initial stages of the acute phase. The beginning of the treatment and the dosage should be based on a careful follow-up of the platelet count and the D-dimer, IL-6, IFN, T-cells, and B-cells levels.

The CMS experiment implements a two-level triggering system composed of Level-1, instrumented by custom-design hardware boards, and a software High Level Trigger. To cope with the more challenging luminosity conditions, a new Level-1 architecture has been deployed during run II. This new architecture exploits in a better way the redundancy and complementarity of the three muon subsystems: Cathode Strip Chambers (CSC), Drift Tubes (DT) and Resistive Plate Chambers (RPC). The role of each subsystem in the Level-1 Muon Trigger is described here, highlighting the contribution from the RPC system. Challenges brought by the HL-LHC environment and new possibilities coming from detector and trigger upgrades are also discussed.

The high pseudorapidity ($\eta$) region of the Compact Muon Solenoid (CMS) muon system is covered by Cathode Strip Chambers only and lacks redundant coverage despite the fact that it is a challenging region for muons in terms of backgrounds and momentum resolution. During the annual Year-End Technical Stops 2022 & 2023, two new layers of improved Resistive Plate Chambers (iRPC) will be added, RE3/1 & RE4/1, which will completely cover the region of $1.8 < |\eta| < 2.4$ in the endcap. Thus, the additional new chambers will lead to increase efficiency for both trigger and offline reconstruction in the difficult region where the background is the highest and the magnetic field is the lowest within the muon system. The extended RPC system will improve the performance and the robustness of the muon trigger. The final design of iRPC chambers and the concept to integrate and install them in the CMS muon system have been finalized. In this report, the main results demonstrating the implementation and installation of the new iRPC detectors in the CMS muon system at high $|\eta|$ region will be presented.

Abstract The present RPC Link System has been servicing as one of the CMS subsystems since installation in 2008. Although the current Link System has been functioning well for the past 13 years, the aging of its electronic components and lack of radiation hard ASICs could present problems for future operations. Additionally, the needs to have a more robust control interface against electromagnetic interference, to improve the trigger performance with finer time granularity and to incorporate a higher bandwidth transmission lines led the idea of upgrading the Link System for the HL-LHC. This paper reviews the features of the recently developed prototype of the new Link System.

The extremely controversial conclusions about the function of human interferon-gamma (hIFNγ) C-terminus as well as the lack of a consistent model explaining its role in the receptor binding prompted us to scrutinize the interaction of hIFNγ with its extracellular receptor hIFNGR1 in different scenarios by means of molecular dynamics simulations. We find that the two molecules alone fail to form a stable complex but the presence of heparan-sulfate-like oligosaccharides largely facilitates the process by both demobilizing the highly flexible C-termini of the cytokine and assisting in the proper positioning of its globule between the receptor subunits. An antiproliferative-activity essay on cells depleted from surface sulfation confirms qualitatively the simulation-based multistage complex-formation model. Our results reveal the key role of HS and its proteoglycans in all processes involving hIFNγ signalling.

The Large Hadron Collider (LHC) at European Organization for Nuclear Research is planned to be upgraded to the high luminosity LHC. Increasing the luminosity makes muon triggering reliable and offline reconstruction very challenging. To enhance the redundancy of the Compact Muon Solenoid (CMS) Muon system and resolve the ambiguity of track reconstruction in the forward region, an improved Resistive Plate Chamber (iRPC) with excellent time resolution will be installed in the Phase-2 CMS upgrade. The iRPC will be equipped with Front-End Electronics (FEE), which can perform high-precision time measurements of signals from both ends of the strip. New Back-End Electronics (BEE) need to be researched and developed to provide sophisticated functionalities such as interacting with FEE with shared links for fast, slow control (SC) and data, in addition to trigger primitives (TPs) generation and data acquisition (DAQ). The BEE prototype uses a homemade hardware board compatible with the MTCA standard, the back-end board (BEB). BEE interacts with FEE via a bidirectional 4.8 Gbps optical paired-link that integrates clock, data, and control information. The clock and fast/slow control commands are distributed from BEB to the FEE via the downlink. The uplink is used for BEB to receive the time information of the iRPC’s fired strips and the responses to the fast/slow control commands. To have a pipelined detector data for cluster finding operation, recover (DeMux) the time relationship of which is changed due to the transmission protocol for the continuous incoming MUXed data from FEE. Then at each bunch crossing (BX), clustering fired strips that satisfy time and spatial constraints to generate TPs. Both incoming raw MUXed detector data and TPs in a time window and latency based on the trigger signal are read out to the DAQ system. Gigabit Ethernet (GbE) of SiTCP and commercial 10-GbE are used as link standards for SC and DAQ, respectively, for the BEB to interact with the server. The joint test results of the BEB with iRPC and Front-End Board (FEB) show a Bit Error Rate of the transmission links less than $$1\times {10^{-16}}$$ , a time resolution of the FEB Time-to-Digital Converter of 16 ps, and the resolution of the time difference between both ends of 160 ps which corresponding a spatial resolution of the iRPC of approximately 1.5 cm. Test results showed the correctness and stable running of the BEB prototype, of which the functionalities fulfill the iRPC requirements.

A new muon reconstruction algorithm is introduced at the CMS experiment. This algorithm reconstructs muons using only the central tracker and the Resistive Plate Chamber (RPC). The aim of this work is to study how a muon reconstructed only with tracker and RPC information would perform compared to the standard muon reconstruction of the CMS detector. The efficiencies to reconstruct and identify a RPC muon with a transverse momentum greater than 20 GeV/c are measured. The probabilities to misidentify hadrons as muons at low transverse momentum are also reported. These probabilities are compared to the standard muon identification used at CMS.

Human interferon gamma (hIFN-γ) is an important signalling molecule, which plays a key role in the formation and modulation of immune response. The role of the cytokine C-termini in the formation of a complex with the extracellular receptor is still controversial due to the lack of structural information about this domain. Moreover, the C-termini are also responsible for the high affinity interaction of hIFN-γ with the glycosaminoglicans heparan sulfate and heparin. This interaction can drastically change the properties and behaviour of the protein.We performed molecular dynamics simulations in order to model the structure of the hIFN-γ C-terminal part and the interaction of the cytokine with heparin-derived oligosaccharides. For this purpose we reconstructed the missing C-terminal amino acid residues and performed folding simulations to determine their conformation. In order to simulate the interaction with heparin-like fragments, we developed CHARMM 36 compatible force field for the sulfamate anion group that is present in the glucosamine sugar to complete the heparin and heparan sulfate force field. The new topology and parameters reproduce the available experimental structural properties of heparin-like fragments. The simulations show that the oligosaccharides quickly bind the IFN-γ C-termini and reduce their solvent accessible surface area.

Resistive Plate Chambers have been chosen as dedicated trigger muon detectors for the Compact Muon Solenoid experiment at the Large Hadron Collider at CERN. The barrel RPC detector consists of 480 chambers of different forms and sizes, equipped with 75,000 strips and covering an area of about 2400 m2. About one-third of RPC barrel chambers have been produced up to the end of 2003 and these 150 chambers, produced and assembled in Italy, have been extensively tested at the two Italian test stands of Bari and Pavia by the RPC barrel collaboration. Preliminary results of the production and test of the chambers will be described here.

In the general framework of the computer‐aided drug design, the method of molecular‐dynamics simulations is applied for investigation of the human interferon‐gamma (hIFN‐γ) binding to its two known ligands (its extracellular receptor and the heparin‐derived oligosaccharides). A study of 100 mutated hIFN‐γ forms is presented, the mutations encompassing residues 86–88. The structural changes are investigated by comparing the lengths of the α‐helices, in which these residues are included, in the native hIFN‐γ molecule and in the mutated forms. The most intriguing cases are examined in detail.

The Muon System of the CMS experiment at CERN employees three different detector technologies—Drift Tube Chambers (DT) in the barrel part, Cathode Strip Chambers (CSC) in the endcaps and Resistive Plate Chambers (RPC) both in the barrel and the endcaps. TDs and CSCs serve as precise muon trajectory measurement devices. The RPCs are responsible for the bunch crossing identification and for a fast muon transverse momentum measurement. The total number of RPCs is 480 in the barrel and 756 in the endcaps, covering an area of about 3500 square meters. A brief overview of the system will be presented as well as some recent results about the system stability and performance.

Human interferon-gamma (hIFNγ) is a key cytokine in the realisation of cellular immunity. It accomplishes its biological activity upon binding to a specific cell receptor thus inducing the JAK/STAT1 signal transduction pathway. Two putative NLS sequences were pointed out to assist in the translocation of STAT1 into the nucleus. In order to employ mutational analysis for study the biological significance of the polybasic sequence Lys86-Lys87-Lys88 belonging to the upstream putative NLS, hIFNγ mutants with preserved structure and intact binding affinity to cell receptor need to be selected. To this end in silico studies of molecular stability of hIFNγ mutants was performed. The potential conformational changes in the structure of the mutant proteins were investigated employing molecular dynamics simulations. The free energy surface of Lys86 backbone torsion angles space in hIFNγ wild type and mutants was analyzed using metadynamic model. The obtained in silico results were verified by construction of selected mutant recombinant hIFNy proteins, which were analysed for biological activity. To judge for the secondary structure of the mutants the affinity to the cell receptor was investigated. High correlation between results of the molecular dynamics simulations and biological data was obtained.

In the next decades, the Large Hadron Collider (LHC) will run at very high luminosity (HL-LHC) 5×1034 cm−2s−1, factor five more than the nominal LHC luminosity. During this period the CMS RPC system will be subjected to high background rates which could affect the performance by inducing aging effects. A dedicated longevity program to qualify the present RPC system for the HL-LHC running period is ongoing. At the CERN Gamma Irradiation Facility (GIF++) four RPC detectors, from the spare production, are exposed to an intense gamma radiation for a dose equivalent to the one expected at the HL-LHC . The main detector parameters are under monitoring as a function of the integrated charge and the performance is studied with a muon beam. Preliminary results of the study after having collected ≈ 34% of the expected integrated charge will be presented.

The Resistive Plate Chambers (RPC) are used for muon triggers in the CMS experiment. To calibrate the high voltage working-points (WP) and identify degraded detectors due to radiation or chemical damage, a high voltage scan has been performed using 2017 data from pp collisions at a center-of-mass energy of 13 TeV. In this paper, we present the calibration method and the latest results obtained for the 2017 data. A comparison with all scans taken since 2011 is considered to investigate the stability of the detector performance in time.

Antimicrobial peptides (AMPs) are an abundant and diverse group of molecules produced by many tissues and cell types in a variety of invertebrate, plant and animal species in contact with infectious microorganisms. They play a crucial role as mediators of the primary host defense against microbial invasion. The characteristics, the broad spectrum and largely nonspecific activity of the antimicrobial peptides qualify them as possible candidates for therapeutic alternatives against multi-resistant bacterial strains. AMPs come in nature in the form of multicomponent secretory fluids that exhibit certain biological activity. For development of biologicals with some predesignated properties separation of the individual components, their purification and activity analysis are needed. In silico experiments are designed to speedup the identification of the active components in these substances, understanding of their structural specifics and biodynamics. Here we present the first results of a pilot in silico study on the primary structure formation of newly identified in the mucus of molluscs representatives peptides, as a prerequisite for understanding the possible role of complexation for their biological activity.

The second LHC long shutdown period (LS2) is an important opportunity for the CMS Resistive Plate Chambers (RPC) to complete their consolidation and upgrade projects. The consolidation includes detector maintenance for gas tightness, HV (high voltage), LV (low voltage) and slow control operation. All services for the RPC Phase-2 upgrade: improved RPC in stations RE3/1 and RE4/1, were anticipated for installation to LS2. This paper summarises the RPC system maintenance and upgrade activities.

Modular Supercomputer Architecture is an innovative idea to bring advantages of different HPC architectures currently available together and make it possible for the users to benefit from it by running different parts of their applications on the most appropriate hardware to reach the best performance with high energy efficiency. DEEP-EST project aims not just at building MSA prototype, but rather co-design it by a collaboration of hardware and application software experts. The HPC applications encompass scientific fields like neuroscience, molecular dynamics, radio astronomy, space weather, data analytics in earth science and high energy physics. Here, we present our research on running large-scale molecular dynamics simulations with one the worlds’ fastest MD software - Gromacs on two modules (Booster - KNL based HPC system and Cluster - Haswell based HPC system) of JURECA supercomputing system at Juelich Supercomputer Centre. We tested the performance scalability of the simulation of 20 million atoms biomolecular system running Gromacs in Cluster-Booster configuration. The long-range electrostatics calculations were conducted on the JURECA Cluster nodes, while all of the rest calculations - on JURECA Booster. Through source code profiling and Gromacs internal performance counters analysis, we investigated the influence of the performance scalability the different application’s parts on the overall application performance scalability. We optimized the job parameters like Cluster to Booster number of cores ration and the corresponding number of module-interconnecting gateways. Our results prove the applicability of the MSA concept in the field of Molecular Dynamics.

The CMS experiment has 1054 RPCs in its muon system. Monitoring their currents is the first essential step towards maintaining the stability of the CMS RPC detector performance. The current depends on several parameters such as applied voltage, luminosity, environmental conditions, etc. Knowing the influence of these parameters on the RPC current is essential for the correct interpretation of its instabilities as they can be caused either by changes in external conditions or by malfunctioning of the detector in the ideal case. We propose a Machine Learning(ML) based approach to be used for monitoring the CMS RPC currents. The approach is crucial for the development of an automated monitoring system capable of warning for possible hardware problems at a very early stage, which will contribute further to the stable operation of the CMS RPC detector.

The Muon Upgrade Phase II of the Compact Muon Solenoid (CMS) aims to guarantee the optimal conditions of the present system and extend the η coverage to ensure a reliable system for the High Luminosity Large Hadron Collider (HL-LHC) period. The Resistive Plate Chambers (RPCs) system will upgrade the off-detector electronics (called link system) of the chambers currently installed chambers and place improved RPCs (iRPCs) to cover the high pseudo−rapidity region, a challenging region for muon reconstruction in terms of background and momentum resolution. In order to find the best option for the iRPCs, an R&D program for new detectors was performed and real size prototypes have been tested in the Gamma Irradiation Facility (GIF++) at CERN. The results indicated that the technology suitable for the high background conditions is based on High Pressure Laminate (HPL) double-gap RPC. The RPC Upgrade Phase II program is planned to be ready after the Long Shutdown 3 (LS3).

Abstract As part of the Compact Muon Solenoid experiment Phase-II upgrade program, new resistive plate chambers will be installed in the region at low angle with respect to the beam collision axis, in order to improve the detection of muons with a low transverse momentum. High background conditions are expected in this region during the high-luminosity phase of the Large Hadron Collider, therefore an improved-RPC design has been proposed with a new front-end electronics to sustain a higher particle rate capability and better time resolution. A new technology is used in the front-end electronics resulting in low achievable signal detection of 1–20 fC. Crucial in the design of the improved-RPC is the capability of a two-dimensional readout in order to improve the spatial resolution, mainly motivated by trigger requirements. In this work, the first performance results towards this two-dimensional readout are presented, based on data taken on a real-size prototype chamber with two embedded readout planes with orthogonal strips.

Oxytocin (OT) is a neurohypophysial hormone, which acts both on the peripheral tissues (hormonal), and as a neurotransmitter in the brain. It plays an important role in the control of uterine contractions during labor, secretion of milk and many social and behavioral functions.  OT accomplishes its functions via interaction with specific oxytocin receptors, which belong to the rhodopsin-type (class I) group of G-protein coupled receptors (GPCR). High levels of oxytocin during pregnancy are the main cause for preterm birth. Oxytocin receptor antagonists are widely employed for prevention in such cases [1]. Design of these antagonists requires a proper model of the hormone – receptor interaction. However, the 3D structure of the OT receptor is not known. The aim of this investigation is to construct a three-dimensional model of the oxytocin receptor. Protein structure homology modelling is an efficient technique for generating 3D models of proteins in the absence of experimental data. We employed the software package Modeller to generate a family of oxytocin GPCR structures. The assessment of the structures was based on test MD simulations of their interactions with the natural ligand oxytocin.

The antimicrobial peptides AMPs represent abundant and diverse group of molecules, which are evolved from many tissues and cells in the plant and animal kingdoms as protective reaction against infection organisms. They build a very strong first line of innate immunity. Despite their enormous variety, most AMPs work directly against microbes, through a mechanism involving membrane disintegration or/and formation of pores, which allows easier passage of the ions and the basic nutrients. Molecular mechanisms, and the way of penetration through the membrane can be varied to various peptides, depending on the sequence of amino acids, the lipid composition of the membrane and the concentration of peptides, but for the beginning of their action, they must first be attracted to the bacterial surface. The objective of the present examination is namely the so called S-state, or an inactive state in which an AMP is oriented parallel before binding to the membrane. To this end  we have conducted molecular dynamics studies. The conformational changes in the quaternary structure of one of the most popular antimicrobial peptides -  magainin 2 (alpha-helical positively charged amphiphilic peptide) near to a charged lipid bilayer were examined. We have analyzed the behavior of peptides at their connection to the bilayers and their impact on the lateral organization of charged lipids. The system for MD simulation consists of a charged, equilibrated membrane (five uncharged POPE lipid molecules to three charged POPG lipid molecules) and eight copies of AMPs magainin 2 (located four on each side of bilayers), submerged in water.

Human interferon gamma is an important antiviral and im-munomodulating signaling molecule, which is also related to several au-toimmune deceases. The cytokine expresses its activity through a specicextracellular receptor, the Interferon gamma receptor. Understanding the process of ....

Antimicrobial peptides (AMPs) are a component of the innate immune system. They are  small proteins with broad spectrum antimicrobial activity against bacteria, viruses and fungi. As such, they must interact with pathogenic membranes, either through translocation or by disrupting their structural integrity [1]. To understand how this peptides permeabilize bacterial membrane, we performed coarse-grained simulation, using MARTINI force field. We studied the interaction between the 13-residue cationic peptide indolicidin, isolated from cytoplasmic granules of bovine neutrophils with different types of membranes. Indolicidin is an intensively studied antimicrobial peptide. This very efficient antimicrobial agent is the shortest natural AMPs and has a large proportion of tryptophan residues (39%) of any known protein. Furthermore, it exhibits activity against Gram-positive and Gram-negative bacteria, but it does not lyse the bacterial cells [2].  We investigated indolicidin interactions with both symmetric and asymmetric bilayers consisting of POPE and POPG lipids. In the former case, the peptide penetrate the membrane, but in the latter this process is faster and it induces reorganization of the bilayer, after forming a pore and crossing the membrane. We also examined the effect of  indolicidin concentration on the morphology of the membrane.

The Resistive Plate Chambers (RPC) are used in the CMS experiment at the trigger level and also in the standard offline muon reconstruction. In order to guarantee the quality of the data collected and to monitor online the detector performance, a set of tools has been developed in CMS which is heavily used in the RPC system. The Web-based monitoring (WBM) is a set of java servlets that allows users to check the performance of the hardware during data taking, providing distributions and history plots of all the parameters. The functionalities of the RPC WBM monitoring tools are presented along with studies of the detector performance as a function of growing luminosity and environmental conditions that are tracked over time.

February 1 th 2013 marked the end of the first period of running of the Large Hadron Collider (LHC) and the start of a two-year break from operation (LS1) aimed at consolidating both the accelerator as well as the detectors. By the end of LS1, the LHC is expected to provide collisions at 13 Tev. While, by 2020, the ultimate instantaneous luminosity is expected to be 1034/cm2/s. To prepare for this scenario, the Resistive Plate Chamber system at the CMS experiment is planning several detector maintainance and consolidation interventions. These include High Voltage and Low Voltage system reparations, gas leak identification and reparation, signal channel connectivity and functionality. Commissioning and upgrade plans for the existing CMS RPC system are presented here.

The key actors in the cell-cell interactions of the adaptive immune response are the major histocompatibility complex (MHC) molecule and the T cell antigen receptor (TCR). The former (in humans also known as human leukocyte antigen - HLA) is found on antigen presenting cells and serves as extraction tool to bring antigens in the intercellular space for recognition by the T cells through the TCR. T cells are selected for recognition of certain pMHC complexes, but often alloreact with foreign HLA, presenting different allopeptides, sometimes subject to extensive polymorphism and with disparate peptide sequences. Understanding mechanisms behind this phenomenon is of great theoretical and practical importance. We study two MHC molecules with a single-aminioacid polymorphism to the original (alloreactive) complex (LC13 TCR in complex with HLA B*4405 bound to EEYLQAFTY - a self peptide from the ABCD3 protein)  and significantly different binding affinities, resp. immunogenicity, in the context of molecular mimicry hypothesis. We use molecular dynamics (MD) to get insights into the TCRpMHC interaction and investigate these complexes from a structural point of view, augmenting the crisp-clustering analysis of their semi-rigid domains.

The antimicrobial peptides (AMPs) are small water-soluble peptides, evolving from organisms of all types. Because of cytolytic abilities they are in position to kill a variety of bacteria and other cells. The AMPs mode of action includes a stage of association with the cell border structures bacterial envelope (wall and membranes) and penetration through them. Many peptides are prone to conformational changes depending on the environmental conditions and characteristics of protein folding and denaturation, in general and specifically concerning AMPs, are intriguing in no lesser extent. Undoubtedly, any perturbation in AMPs 3D structure will be reflected in their interaction with the membrane. Magainins are good example in this regard, because it is still not absolutely clear what is the exact secondary structure of magainins before accessing the membrane surface and how this structure is responsible for their action. For this reason, we investigated the secondary structure stability of two magainin monomers in solution by atomistic level molecular dynamics simulations. We chose the regular form of magainin 2, MG2 (GIGKFLHSAKKFGKAFVGEIMNS) to compare its behavior with an analogue MG2m (F5Y, F16W-MG2) with a sequence GIGKYLHSAKKFGKAWVGEIMNS. We found that the initial alpha-helical structures changed in different ways for the two monomers after their exposure to the solution. The native form exhibited rich structural behavior, with a set of helical and random turn motifs, while the synthetic analogue turned out to be predominantly disordered, which indicates the importance of side chain groups around 5PHE and 16PHE for maintenance of the solvated-protein conformation. As these amino acid residues are responsible for dimmerization of MG2m, the knowledge about the dynamics of this region is of crucial interest for the prediction of free magainin structures prior to membrane binding. Here we present the free-energy landscape of the chosen monomers obtained by a well-tempered metadynamics study, and discuss their behavior with an emphasis on the conformations of three particular regions in their structure.

The antimicrobial peptides (AMPs) are small water-soluble peptides, evolving from organisms of all types. Because of cytolytic abilities they are in position to kill a variety of bacteria and other cells. The AMPs mode of action includes a stage of association with the cell border structures bacterial envelope (wall and membranes) and penetration through them. Many peptides are prone to conformational changes depending on the environmental conditions and characteristics of protein folding and denaturation, in general and specifically concerning AMPs, are intriguing in no lesser extent. Undoubtedly, any perturbation in AMPs 3D structure will be reflected in their interaction with the membrane. Magainins are good example in this regard, because it is still not absolutely clear what is the exact secondary structure of magainins before accessing the membrane surface and how this structure is responsible for their action. For this reason, we investigated the secondary structure stability of two magainin monomers in solution by atomistic level molecular dynamics simulations. We chose the regular form of magainin 2, MG2 (GIGKFLHSAKKFGKAFVGEIMNS) to compare its behavior with an analogue MG2m (F5Y, F16W-MG2). We found that the initial alpha-helical structures changed in different ways for the two monomers after their exposure to the solution. The native form exhibited rich structural behavior, with a set of helical and random turn motifs, while the synthetic analogue turned out to be predominantly disordered, which indicates the importance of side chain groups around 5PHE and 16PHE for maintenance of the solvated-protein conformation. As these amino acid residues are responsible for  dimmerization of MG2m, the knowledge about the dynamics of this region is of crucial interest for the prediction of free magainin structures prior to membrane binding. Here we present the free-energy landscape of the chosen monomers obtained by a well-tempered metadynamics study, and discuss their behavior with an emphasis on the conformations of three particular regions in their structure.

The CMS experiment, located at the CERN Large Hadron Collider, has a redundant muon system composed by three different detector technologies: Cathode Strip Chambers (in the forward regions), Drift Tubes (in the central region) and Resistive Plate Chambers (both its central and forward regions). All three are used for muon reconstruction and triggering. During the first long shutdown (LS1) of the LHC (2013-2014) the CMS muon system has been upgraded with 144 newly installed RPCs on the forth forward stations. The new chambers ensure and enhance the muon trigger efficiency in the high luminosity conditions of the LHC Run2. The chambers have been successfully installed and commissioned. The system has been run successfully and experimental data has been collected and analyzed. The performance results of the newly installed RPCs will be presented.

In silico investigations of biological molecules rely on the adequate sampling of the systems’ conformation space. In the case of large systems, this is a highly non trivial task, which requires the development and refinement of enhanced sampling techniques. Metadynamics — one of these techniques — is based on computation of the free energy of the system as a function of a small set of collective variables (CVs) that are assumed to be able to adequately describe the investigated process. No standard procedures or selection criteria exist for the selection of the optimal set of collective variables. The purpose of our work is to develop a CV selection protocol based on the conformational rigidity of the protein in the most sensitive for the investigated process domains. The structure identification is performed using the spatiotemporal multistage consensus clustering (SMCC), with an appropriate selection of the algorithm parameters.

Ru were populated in ( ,n ) reactions. Half-lives in the sub-nanosecond range were measured by using the ROSPHERE ray array. Re- sults for the first 3/2 + states in 99;101 Ru and the first 7/2 + states in 99;101;103 Ru were obtained and are discussed within the Rigid-Triaxial-Rotor-plus-Particle model. Calculated level energies are in good agreement with the experimental level scheme but the model fails in reproduction of some of the reduced tran- sition probabilities. This is, most probably, due to wave function admixtures which are outside the model space.

The CMS experiment, located at the CERN Large Hadron Collider, has a redundant muon system composed by three different detector technologies: Cathode Strip Chambers (in the forward regions), Drift Tubes (in the central region) and Resistive Plate Chambers (both its central and forward regions). All three are used for muon reconstruction and triggering. During the first long shutdown (LS1) of the LHC (2013-2014) the CMS muon system has been upgraded with 144 newly installed RPCs on the forth forward stations. The new chambers ensure and enhance the muon trigger efficiency in the high luminosity conditions of the LHC Run2. The chambers have been successfully installed and commissioned. The system has been run successfully and experimental data has been collected and analyzed. The performance results of the newly installed RPCs will be presented.

In the framework of the High Luminosity LHC upgrade program, the CMS muon group built several different RPC prototypes that are now under test at the new CERN Gamma Irradiation Facility (GIF++). A dedicated Detector Control System (DCS) has been developed using the WinCC-OA tool to control and monitor these prototype detectors and to store the measured parameters data. Preliminary efficiency studies that set the base performance measurements of CMS RPC for starting aging studies are also presented.

We report on a systematic study of double-gap and four-gap phenolic resistive plate chambers (RPCs) for future high-η RPC triggers in the CMS. In the present study, we constructed real-sized double-gap and four-gap RPCs with gap thicknesses of 1.6 and 0.8 mm, respectively, with 2-mm-thick phenolic high-pressure-laminated (HPL) plates. We examined the prototype RPCs for cosmic rays and 100 GeV muons provided by the SPS H4 beam line at CERN. We applied maximum gamma rates of 1.5 kHz cm-2 provided by 137Cs sources at Korea University and the GIF++ irradiation facility installed at the SPS H4 beam line to examine the rate capabilities of the prototype RPCs. In contrast to the case of the four-gap RPCs, we found the relatively high threshold was conducive to effectively suppressing the rapid increase of strip cluster sizes of muon hits with high voltage, especially when measuring the narrow-pitch strips. The gamma-induced currents drawn in the four-gap RPC were about one-fourth of those drawn in the double-gap RPC. The rate capabilities of both RPC types, proven through the present testing using gamma-ray sources, far exceeded the maximum rate expected in the new high-η endcap RPCs planned for future phase-II LHC runs.

The RPC muon detector of the CMS experiment at the LHC (CERN, Geneva, Switzerland) is equipped with a Gas Gain Monitoring (GGM) system. A report on the stability of the system during the 2011-2012 data taking run is given, as well as the observation of an effect which suggests a novel method for the monitoring of gas mixture composition.

The contents of IAA and ACC in different explants like globular structures, residual explants and cultural media were investigated, during induction of somatic embryogenesis in common bean (Phaseolus vulgaris L.): variety Dobrudjanski 7 and the mutant one, Plovdiv 11M. Somatic embryogenesis was induced in liquid media B5, containing 2,4-D in concentrations of I and 2 mg/l. The endogenous content of IAA varied in dependence of the genotype, explant's type and their age. The concentration of exogenous applied auxin 2,4-D and the endogenous content of IAA in the induced globular structures were inversely related. In spite of the exogenous auxin concentrations the embryos of Dobrudjanski 7 variety contained more IAA. With some exceptions, the residual explants were with low endogenous content of IAA. The concentration of 2,4-D and the content of IAA in the media, at the moment of somatic embryogenesis induction were positively related. The content of IAA was many times higher in embryos than in the residual explants and cultural media.

Prion proteins are found on the surface of nerve cells. Their function is not fully understood yet, but they are related to the etiology of certain rare deseases, like CJD, GSS, Kuru, FFI etc [1]. Prions exist in a native (PrP) and in a highly infective pathological form (PrPSc – scrapie form). PrPSc proteins can transform native prions into scrapie forms, aggregate and thus lead to cellular death. Experimental insights on the scrapie form suggest a higher fibrilar beta-structure content, in contrast to the mostly globular alpha-helical native form [2]. However, the 3D structure of PrPSc is still unknown. The present study aims at identification of scrapie form candidates, investigating the prion conformational space by means of replica exchange molecular dynamics. Thus, a conformation of a chicken prion protein is constructed with beta-structure content in agreement with the experimental data.

Transforming the resistive plate chambers from charged-particle into gamma-quanta detectors opens the way towards their application as a basic element of a hybrid imaging system, which combines positron emission tomography (PET) with magnetic resonance imaging (MRI) in a single device and provides non- and minimally- invasive quantitative methods for diagnostics. To this end, we performed detailed investigations encompassing the whole chain from the annihilation of the positron in the body, through the conversion of the created photons into electrons and to the optimization of the electron yield in the gas. GEANT4 based simulations of the efficiency of the RPC photon detectors with different converter materials and geometry were conducted for optimization of the detector design. The results justify the selection of a sandwich-type gas-insulator-converter design, with Bi or Pb as converter materials.

Cytokines play an important role in cellular communication and in modulation of the cellular immune responses. A computational protocol is presented that allows the prediction and analysis of the effect of particular mutations in the cytokine molecules on the interactions with their receptors. It is based on the theory developed by B. Jayaram and D. L. Beverige [1] and relies on collecting statistical data from molecular dynamics simulations.The protocol was first tested on a native cytokine – receptor complexes against experimental data such as association/dissociation constants or binding free energies on a particular cytokine – receptor system, namely the human interferon gamma (hIFNg) – human interferon gamma receptor (hIFNgR) complex.

We investigated the possible way for treatment of electrostatic interactions by solving numerically Poisson’s equation using Conjugate Gradient method and Stabilized BiConjugate Gradient method. The aim of the research was to test the execution time of prototype programs running on BLueGene/P and CPU/GPU system. The results show that the tested methods are applicable for electrostatics treatment in molecular-dynamics simulations.