Lactoferrin (Lf) nanoparticles have been developed as a carrier of drugs and gene. Two main methods, desolvation technique and emulsification method, for preparation of protein nanoparticles have been reported so far, but most of the previous reports of Lf nanoparticles preparation are limited to emulsification method. In this study, we investigated the optimal conditions by desolvation technique for the preparation of glutaraldehyde-crosslinked bovine Lf (bLf) nanoparticles within the size range of 100-200 nm, and evaluated their properties as a carrier for oral and intravenous drug delivery. The experimental results of dynamic light scattering and Transmission Electron Microscope suggested that glutaraldehyde-crosslinked bLf nanoparticles with 150 nm in size could be produced by addition of 2-propanol as the desolvating solvent into the bLf solution adjusted to pH 6, followed by crosslinking with glutaraldehyde. These cross-linked bLf nanoparticles were found to be compatible to blood components and resistant against rapid degradation by pepsin. Thus, cross-linked bLf nanoparticles prepared by desolvation technique can be applied as a drug carrier for intravenous administration and oral delivery.
Aripiprazole (ARP), a quinolinone derivative, is an atypical antipsychotic drug that is used in the treatment of schizophrenia. ARP has an extensive distribution and more than 99% of the ARP and dehydro-ARP, the main active metabolite, is bound to plasma proteins. However, information regarding the protein binding of ARP is limited. In this study, we report on a systematic study of the protein binding of ARP. The interaction of ARP and structurally related compounds with human serum albumin (HSA) was examined using equilibrium dialysis, circular dichroism (CD) spectroscopy, fluorescent probe displacement, and an X-ray crystallographic analysis. The binding affinities (nK) for ARP and its main metabolite, dehydro-ARP with HSA were found to be significantly higher than other structurally related compounds. The results of equilibrium dialysis experiments and CD spectral data indicated that the chloro-group linked to the phenylpiperazine ring in the ARP molecule plays a major role in the binding of these ligands to HSA. Furthermore, fluorescent probe displacement results indicated that ARP appears to bind at the site II pocket in subdomain III. A detailed CD spectral analysis suggests that the chloro-group linked to the phenylpiperazine ring may control the geometry of the ARP molecule when binding in the site II binding pocket. X-ray crystallographic analysis of the ARP-HSA complex revealed that the distance between the chlorine atom at the 3-positon of dichlorophenyl-piperazine on ARP and the sulfur atom of Cys392 in HSA was 3.4-3.6 Å. A similar halogen bond interaction has also been observed in the HSA structure complexed with diazepam, which also contains a chloro-group. Thus, the mechanism responsible for the binding of ARP to a protein elucidated here should be relevant for assessing the pharmacokinetics and pharmacodynamics of ARP in various clinical situations and for designing new drugs.
A search for new long-lived particles decaying to leptons is presented using proton-proton collisions produced by the LHC at √[s]=8 TeV. Data used for the analysis were collected by the CMS detector and correspond to an integrated luminosity of 19.7 fb(-1). Events are selected with an electron and muon with opposite charges that both have transverse impact parameter values between 0.02 and 2 cm. The search has been designed to be sensitive to a wide range of models with nonprompt e-μ final states. Limits are set on the "displaced supersymmetry" model, with pair production of top squarks decaying into an e-μ final state via R-parity-violating interactions. The results are the most restrictive to date on this model, with the most stringent limit being obtained for a top squark lifetime corresponding to cτ=2 cm, excluding masses below 790 GeV at 95% confidence level.
A study of vector boson scattering in pp collisions at a center-of-mass energy of 8 TeV is presented. The data sample corresponds to an integrated luminosity of 19.4 fb(-1) collected with the CMS detector. Candidate events are selected with exactly two leptons of the same charge, two jets with large rapidity separation and high dijet mass, and moderate missing transverse energy. The signal region is expected to be dominated by electroweak same-sign W-boson pair production. The observation agrees with the standard model prediction. The observed significance is 2.0 standard deviations, where a significance of 3.1 standard deviations is expected based on the standard model. Cross section measurements for W(±)W(±) and WZ processes in the fiducial region are reported. Bounds on the structure of quartic vector-boson interactions are given in the framework of dimension-eight effective field theory operators, as well as limits on the production of doubly charged Higgs bosons.
Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top quark (the top squark) and the Higgs boson (Higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 fb-1 of proton-proton collision data at s=8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the top squark mass below 360 to 410 GeV, depending on the Higgsino mass.
Searches for the direct electroweak production of supersymmetric charginos, neutralinos, and sleptons in a variety of signatures with leptons and [Formula: see text], [Formula: see text], and Higgs bosons are presented. Results are based on a sample of proton-proton collision data collected at center-of-mass energy [Formula: see text] with the CMS detector in 2012, corresponding to an integrated luminosity of 19.5 [Formula: see text]. The observed event rates are in agreement with expectations from the standard model. These results probe charginos and neutralinos with masses up to 720 [Formula: see text], and sleptons up to 260 [Formula: see text], depending on the model details.
Observation of the diphoton decay mode of the recently discovered Higgs boson and measurement of some of its properties are reported. The analysis uses the entire dataset collected by the CMS experiment in proton-proton collisions during the 2011 and 2012 LHC running periods. The data samples correspond to integrated luminosities of 5.1[Formula: see text]at [Formula: see text] and 19.7[Formula: see text]at 8[Formula: see text] . A clear signal is observed in the diphoton channel at a mass close to 125[Formula: see text] with a local significance of [Formula: see text], where a significance of [Formula: see text] is expected for the standard model Higgs boson. The mass is measured to be [Formula: see text] , and the best-fit signal strength relative to the standard model prediction is [Formula: see text][Formula: see text][Formula: see text]. Additional measurements include the signal strength modifiers associated with different production mechanisms, and hypothesis tests between spin-0 and spin-2 models.
Results are presented from a search for new decaying massive particles whose presence is inferred from an imbalance in transverse momentum and which are produced in association with a single top quark that decays into a bottom quark and two light quarks. The measurement is performed using 19.7 fb^{-1} of data from proton-proton collisions at a center-of-mass energy of 8 TeV, collected with the CMS detector at the CERN LHC. No deviations from the standard model predictions are observed and lower limits are set on the masses of new invisible bosons. In particular, scalar and vector particles, with masses below 330 and 650 GeV, respectively, are excluded at 95% confidence level, thereby substantially extending a previous limit published by the CDF Collaboration.
Using a data sample of proton-proton collisions at sqrt[s]=13 TeV, corresponding to an integrated luminosity of 140 fb^{-1} collected by the CMS experiment in 2016-2018, the B_{s}^{0}→X(3872)ϕ decay is observed. Decays into J/ψπ^{+}π^{-} and K^{+}K^{-} are used to reconstruct, respectively, the X(3872) and ϕ. The ratio of the product of branching fractions B[B_{s}^{0}→X(3872)ϕ]B[X(3872)→J/ψπ^{+}π^{-}] to the product B[B_{s}^{0}→ψ(2S)ϕ]B[ψ(2S)→J/ψπ^{+}π^{-}] is measured to be [2.21±0.29(stat)±0.17(syst)]%. The ratio B[B_{s}^{0}→X(3872)ϕ]/B[B^{0}→X(3872)K^{0}] is found to be consistent with one, while the ratio B[B_{s}^{0}→X(3872)ϕ]/B[B^{+}→X(3872)K^{+}] is two times smaller. This suggests a difference in the production dynamics of the X(3872) in B^{0} and B_{s}^{0} meson decays compared to B^{+}. The reported observation may shed new light on the nature of the X(3872) particle.
The first observation is reported of the combined production of three massive gauge bosons (VVV with V=W, Z) in proton-proton collisions at a center-of-mass energy of 13 TeV. The analysis is based on a data sample recorded by the CMS experiment at the CERN LHC corresponding to an integrated luminosity of 137 fb^{-1}. The searches for individual WWW, WWZ, WZZ, and ZZZ production are performed in final states with three, four, five, and six leptons (electrons or muons), or with two same-sign leptons plus one or two jets. The observed (expected) significance of the combined VVV production signal is 5.7 (5.9) standard deviations and the corresponding measured cross section relative to the standard model prediction is 1.02_{-0.23}^{+0.26}. The significances of the individual WWW and WWZ production are 3.3 and 3.4 standard deviations, respectively. Measured production cross sections for the individual triboson processes are also reported.
Ultrarelativistic heavy ion collisions recreate in the laboratory the thermodynamical conditions prevailing in the early universe up to 10^{-6} sec, thereby allowing the study of the quark-gluon plasma (QGP), a state of quantum chromodynamics (QCD) matter with deconfined partons. The top quark, the heaviest elementary particle known, is accessible in nucleus-nucleus collisions at the CERN LHC, and constitutes a novel probe of the QGP. Here, we report the first evidence for the production of top quarks in nucleus-nucleus collisions, using lead-lead collision data at a nucleon-nucleon center-of-mass energy of 5.02 TeV recorded by the CMS experiment. Two methods are used to measure the cross section for top quark pair production (σ_{tt[over ¯]}) via the selection of charged leptons (electrons or muons) and bottom quarks. One method relies on the leptonic information alone, and the second one exploits, in addition, the presence of bottom quarks. The measured cross sections, σ_{tt[over ¯]}=2.54_{-0.74}^{+0.84} and 2.03_{-0.64}^{+0.71} μb, respectively, are compatible with expectations from scaled proton-proton data and QCD predictions.
The first observation of the tt[over ¯]H process in a single Higgs boson decay channel with the full reconstruction of the final state (H→γγ) is presented, with a significance of 6.6 standard deviations (σ). The CP structure of Higgs boson couplings to fermions is measured, resulting in an exclusion of the pure CP-odd structure of the top Yukawa coupling at 3.2σ. The measurements are based on a sample of proton-proton collisions at a center-of-mass energy sqrt[s]=13 TeV collected by the CMS detector at the LHC, corresponding to an integrated luminosity of 137 fb^{-1}. The cross section times branching fraction of the tt[over ¯]H process is measured to be σ_{tt[over ¯]H}B_{γγ}=1.56_{-0.32}^{+0.34} fb, which is compatible with the standard model prediction of 1.13_{-0.11}^{+0.08} fb. The fractional contribution of the CP-odd component is measured to be f_{CP}^{Htt}=0.00±0.33.
The Ξ_{b}^{-}π^{+}π^{-} invariant mass spectrum is investigated with an event sample of proton-proton collisions at sqrt[s]=13 TeV, collected by the CMS experiment at the LHC in 2016-2018 and corresponding to an integrated luminosity of 140 fb^{-1}. The ground state Ξ_{b}^{-} is reconstructed via its decays to J/ψΞ^{-} and J/ψΛK^{-}. A narrow resonance, labeled Ξ_{b}(6100)^{-}, is observed at a Ξ_{b}^{-}π^{+}π^{-} invariant mass of 6100.3±0.2(stat)±0.1(syst)±0.6(Ξ_{b}^{-}) MeV, where the last uncertainty reflects the precision of the Ξ_{b}^{-} baryon mass. The upper limit on the Ξ_{b}(6100)^{-} natural width is determined to be 1.9 MeV at 95% confidence level. The low Ξ_{b}(6100)^{-} signal yield observed in data does not allow a measurement of the quantum numbers of the new state. However, following analogies with the established excited Ξ_{c} baryon states, the new Ξ_{b}(6100)^{-} resonance and its decay sequence are consistent with the orbitally excited Ξ_{b}^{-} baryon, with spin and parity quantum numbers J^{P}=3/2^{-}.
A fiducial cross section for Wγ production in proton-proton collisions is measured at a center-of-mass energy of 13 TeV in 137 fb^{-1} of data collected using the CMS detector at the LHC. The W→eν and μν decay modes are used in a maximum-likelihood fit to the lepton-photon invariant mass distribution to extract the combined cross section. The measured cross section is compared with theoretical expectations at next-to-leading order in quantum chromodynamics. In addition, 95% confidence level intervals are reported for anomalous triple-gauge couplings within the framework of effective field theory.
The CMS experiment at the LHC has measured the differential cross sections of Z bosons decaying to pairs of leptons, as functions of transverse momentum and rapidity, in lead-lead collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV. The measured Z boson elliptic azimuthal anisotropy coefficient is compatible with zero, showing that Z bosons do not experience significant final-state interactions in the medium produced in the collision. Yields of Z bosons are compared to Glauber model predictions and are found to deviate from these expectations in peripheral collisions, indicating the presence of initial collision geometry and centrality selection effects. The precision of the measurement allows, for the first time, for a data-driven determination of the nucleon-nucleon integrated luminosity as a function of lead-lead centrality, thereby eliminating the need for its estimation based on a Glauber model.
The first measurement of the dependence of γγ→μ^{+}μ^{-} production on the multiplicity of neutrons emitted very close to the beam direction in ultraperipheral heavy ion collisions is reported. Data for lead-lead interactions at sqrt[s_{NN}]=5.02 TeV, with an integrated luminosity of approximately 1.5 nb^{-1}, are collected using the CMS detector at the LHC. The azimuthal correlations between the two muons in the invariant mass region 88.3. The back-to-back correlation structure from leading-order photon-photon scattering is found to be significantly broader for events with a larger number of emitted neutrons from each nucleus, corresponding to interactions with a smaller impact parameter. This observation provides a data-driven demonstration that the average transverse momentum of photons emitted from relativistic heavy ions has an impact parameter dependence. These results provide new constraints on models of photon-induced interactions in ultraperipheral collisions. They also provide a baseline to search for possible final-state effects on lepton pairs caused by traversing a quark-gluon plasma produced in hadronic heavy ion collisions.
This paper presents new sets of parameters ("tunes") for the underlying-event model of the H E R W I G 7 event generator. These parameters control the description of multiple-parton interactions (MPI) and colour reconnection in H E R W I G 7 , and are obtained from a fit to minimum-bias data collected by the CMS experiment at s = 0.9 , 7, and 13 Te . The tunes are based on the NNPDF 3.1 next-to-next-to-leading-order parton distribution function (PDF) set for the parton shower, and either a leading-order or next-to-next-to-leading-order PDF set for the simulation of MPI and the beam remnants. Predictions utilizing the tunes are produced for event shape observables in electron-positron collisions, and for minimum-bias, inclusive jet, top quark pair, and Z and W boson events in proton-proton collisions, and are compared with data. Each of the new tunes describes the data at a reasonable level, and the tunes using a leading-order PDF for the simulation of MPI provide the best description of the data.
Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV , corresponding to an integrated luminosity of 35.9 fb - 1 , are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.
A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 Te at the CERN LHC, corresponding to an integrated luminosity of 137 fb - 1 collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on the model, the combined result excludes a top squark mass up to 1325 Ge for a massless neutralino, and a neutralino mass up to 700 Ge for a top squark mass of 1150 Ge . Top squarks with masses from 145 to 295 Ge , for neutralino masses from 0 to 100 Ge , with a mass difference between the top squark and the neutralino in a window of 30 Ge around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 Ge .
A search for charged Higgs bosons produced in vector boson fusion processes and decaying into vector bosons, using proton-proton collisions at s = 13 TeV at the LHC, is reported. The data sample corresponds to an integrated luminosity of 137 fb - 1 collected with the CMS detector. Events are selected by requiring two or three electrons or muons, moderate missing transverse momentum, and two jets with a large rapidity separation and a large dijet mass. No excess of events with respect to the standard model background predictions is observed. Model independent upper limits at 95% confidence level are reported on the product of the cross section and branching fraction for vector boson fusion production of charged Higgs bosons as a function of mass, from 200 to 3000 GeV . The results are interpreted in the context of the Georgi-Machacek model.