Mycobacterium tuberculosis has a remarkable ability of long-term persistence despite vigorous host immunity and prolonged therapy. The bacteria persist in secure niches such as the mesenchymal stem cells in the bone marrow and reactivate the disease, leading to therapeutic failure. Many bacterial cells can remain latent within a diseased tissue so that their genetic material can be incorporated into the genetic material of the host tissue. This incorporated genetic material reproduces in a manner similar to that of cellular DNA. After the cell division, the incorporated gene is reproduced normally and distributed proportionately between the two progeny. This inherent adoption of long-term persistence and incorporating the bacterial genetic material into that of the host tissue remains and is considered imperative for microbial advancement and chemotherapeutic resistance; moreover, new evidence indicates that the bacteria might pass on genetic material to the host DNA sequence. Several studies focused on the survival mechanism of M. tuberculosis in the host immune system with the aim of helping the efforts to discover new drugs and vaccines against tuberculosis. This review explored the mechanisms through which this bacterium affects the expression of human genes. The first part of the review summarizes the current knowledge about the interactions between microbes and host microenvironment, with special reference to the M. tuberculosis neglected persistence in immune cells and stem cells. Then, we focused on how bacteria can affect human genes and their expression. Furthermore, we analyzed the literature base on the process of cell death during tuberculosis infection, giving particular emphasis to gene methylation as an inherited process in the neutralization of possibly injurious gene components in the genome. The final section discusses recent advances related to the M. tuberculosis interaction with host epigenetic circuitry.
Current clinical trials that evaluate human pluripotent stem cell (hPSC)-based therapies predominantly target treating macular degeneration of the eyes because the eye is an isolated tissue that is naturally weakly immunogenic. Here, we discuss current bioengineering approaches and biomaterial usage in combination with stem cell therapy for macular degeneration disease treatment. Retinal pigment epithelium (RPE) differentiated from hPSCs is typically used in most clinical trials for treating patients, whereas bone marrow mononuclear cells (BMNCs) or mesenchymal stem cells (MSCs) are intravitreally transplanted, undifferentiated, into patient eyes. We also discuss reported negative effects of stem cell therapy, such as patients becoming blind following transplantation of adipose-derived stem cells, which are increasingly used by 'stem-cell clinics'.
In this research, we characterized the histopathological impact of dengue virus (serotype DENV-2) infection in livers of BALB/c mice. The mice were infected with different doses of DENV-2 via intraperitoneal injection and liver tissues were processed for histological analyses and variation was documented. In the BALB/c mouse model, typical liver tissues showed regular hepatocyte architecture, with normal endothelial cells surrounding sinusoid capillary. Based on histopathological observations, the liver sections of BALB/c mice infected by DENV-2 exhibited a loss of cell integrity, with a widening of the sinusoidal spaces. There were marked increases in the infiltration of mononuclear cells. The areas of hemorrhage and micro- and macrovesicular steatosis were noted. Necrosis and apoptosis were abundantly present. The hallmark of viral infection, i.e., cytopathic effects, included intracellular edema and vacuole formation, cumulatively led to sinusoidal and lobular collapse in the liver. The histopathological studies on autopsy specimens of fatal human DENV cases are important to shed light on tissue damage for preventive and treatment modalities, in order to manage future DENV infections. In this framework, the method present here on BALB/c mouse model may be used to study not only the effects of infections by other DENV serotypes, but also to investigate the effects of novel drugs, such as recently developed nano-formulations, and the relative recovery ability with intact immune functions of host.
Ticks serve as vectors of a wide range of infectious agents deleterious to humans and animals. Tick bite prevention is based to a large extent on the use of chemical repellents and acaricides. However, development of resistance in targeted ticks, environmental pollution, and contamination of livestock meat and milk are major concerns. Recently, metal, metal oxide and carbon nanoparticles, particularly those obtained through green fabrication routes, were found to be highly effective against a wide array of arthropod pests and vectors. We summarize current knowledge on the toxicity of nanoparticles against tick vectors of medical and veterinary importance. We also discuss the toxicity of products from botanical- and bacterial-based as well as classic chemical nanosynthesis routes, showing differences in bioactivity against ticks based on the products used for the fabrication of nanoparticles. Further research is needed, to validate the efficacy of nanoparticle-based acaricides in the field and clarify mechanisms of action of nanoparticles against ticks. From a technical point of view, the literature analyzed here showed little standardization of size and weight of tested ticks, a lack of uniform methods to assess toxicity and concerns related to data analysis. Finally, an important challenge for future research is the need for ecotoxicology studies to evaluate potential negative effects on non-target organisms and site contamination arising from nanoparticle-based treatments in close proximity of livestock and farmers.
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.
A search for supersymmetry is presented based on events with at least one photon, jets, and large missing transverse momentum produced in proton-proton collisions at a center-of-mass energy of 13
Te
. The data correspond to an integrated luminosity of 35.9
fb
- 1
and were recorded at the LHC with the CMS detector in 2016. The analysis characterizes signal-like events by categorizing the data into various signal regions based on the number of jets, the number of b -tagged jets, and the missing transverse momentum. No significant excess of events is observed with respect to the expectations from standard model processes. Limits are placed on the gluino and top squark pair production cross sections using several simplified models of supersymmetric particle production with gauge-mediated supersymmetry breaking. Depending on the model and the mass of the next-to-lightest supersymmetric particle, the production of gluinos with masses as large as 2120
Ge
and the production of top squarks with masses as large as 1230
A search is presented for the single production of vector-like quarks in proton-proton collisions at
s
= 13
TeV
. The data, corresponding to an integrated luminosity of 35.9
fb
- 1
, were recorded with the CMS experiment at the LHC. The analysis focuses on the vector-like quark decay into a top quark and a W boson, with one muon or electron in the final state. The mass of the vector-like quark candidate is reconstructed from hadronic jets, the lepton, and the missing transverse momentum. Methods for the identification of b quarks and of highly Lorentz boosted hadronically decaying top quarks and W bosons are exploited in this search. No significant deviation from the standard model background expectation is observed. Exclusion limits at 95% confidence level are set on the product of the production cross section and branching fraction as a function of the vector-like quark mass, which range from 0.3 to 0.03
pb
for vector-like quark masses of 700 to 2000
GeV
. Mass exclusion limits up to 1660
GeV
are obtained, depending on the vector-like quark type, coupling, and decay width. These represent the most stringent exclusion limits for the single production of vector-like quarks in this channel.
Measurements are presented of the triple-differential cross section for inclusive isolated-photon+jet events in
p p
collisions at
s
= 8
TeV as a function of photon transverse momentum (
p
T
γ
), photon pseudorapidity (
η
γ
), and jet pseudorapidity (
η jet
). The data correspond to an integrated luminosity of
19.7
fb
- 1
that probe a broad range of the available phase space, for
|
η
γ
| < 1.44
and
1.57 < |
η
γ
| < 2.50
,
|
η jet
| < 2.5
,
40 <
p
T
γ
< 1000
GeV
, and jet transverse momentum,
p
T
jet
, > 25
GeV
. The measurements are compared to next-to-leading order perturbative quantum chromodynamics calculations, which reproduce the data within uncertainties.
A search is presented for an excess of events with heavy-flavor quark pairs (
t
t ¯
and
b
b ¯
) and a large imbalance in transverse momentum in data from proton-proton collisions at a center-of-mass energy of 13
TeV
. The data correspond to an integrated luminosity of 2.2
fb
- 1
collected with the CMS detector at the CERN LHC. No deviations are observed with respect to standard model predictions. The results are used in the first interpretation of dark matter production in
t
t ¯
and
b
b ¯
final states in a simplified model. This analysis is also the first to perform a statistical combination of searches for dark matter produced with different heavy-flavor final states. The combination provides exclusions that are stronger than those achieved with individual heavy-flavor final states.
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 .
The measurement of the luminosity recorded by the CMS detector installed at LHC interaction point 5, using proton-proton collisions at s = 13 TeV in 2015 and 2016, is reported. The absolute luminosity scale is measured for individual bunch crossings using beam-separation scans (the van der Meer method), with a relative precision of 1.3 and 1.0% in 2015 and 2016, respectively. The dominant sources of uncertainty are related to residual differences between the measured beam positions and the ones provided by the operational settings of the LHC magnets, the factorizability of the proton bunch spatial density functions in the coordinates transverse to the beam direction, and the modeling of the effect of electromagnetic interactions among protons in the colliding bunches. When applying the van der Meer calibration to the entire run periods, the integrated luminosities when CMS was fully operational are 2.27 and 36.3 fb - 1 in 2015 and 2016, with a relative precision of 1.6 and 1.2%, respectively. These are among the most precise luminosity measurements at bunched-beam hadron colliders.
Collinear (small-angle) and large-angle, as well as soft and hard radiations are investigated in three-jet and Z + two-jet events collected in proton-proton collisions at the LHC. The normalized production cross sections are measured as a function of the ratio of transverse momenta of two jets and their angular separation. The measurements in the three-jet and Z + two-jet events are based on data collected at a center-of-mass energy of 8 TeV , corresponding to an integrated luminosity of 19.8 fb - 1 . The Z + two-jet events are reconstructed in the dimuon decay channel of the Z boson. The three-jet measurement is extended to include s = 13 TeV data corresponding to an integrated luminosity of 2.3 fb - 1 . The results are compared to predictions from event generators that include parton showers, multiple parton interactions, and hadronization. The collinear and soft regions are in general well described by parton showers, whereas the regions of large angular separation are often best described by calculations using higher-order matrix elements.
A measurement for inclusive 2- and 3-jet events of the azimuthal correlation between the two jets with the largest transverse momenta, Δ ϕ 12 , is presented. The measurement considers events where the two leading jets are nearly collinear ("back-to-back") in the transverse plane and is performed for several ranges of the leading jet transverse momentum. Proton-proton collision data collected with the CMS experiment at a center-of-mass energy of 13 Te and corresponding to an integrated luminosity of 35.9 fb - 1 are used. Predictions based on calculations using matrix elements at leading-order and next-to-leading-order accuracy in perturbative quantum chromodynamics supplemented with leading-log parton showers and hadronization are generally in agreement with the measurements. Discrepancies between the measurement and theoretical predictions are as large as 15%, mainly in the region 177 ∘ < Δ ϕ 12 < 180 ∘ . The 2- and 3-jet measurements are not simultaneously described by any of models.
A search is presented for a heavy pseudoscalar boson A decaying to a Z boson and a Higgs boson with mass of 125 GeV . In the final state considered, the Higgs boson decays to a bottom quark and antiquark, and the Z boson decays either into a pair of electrons, muons, or neutrinos. The analysis is performed using a data sample corresponding to an integrated luminosity of 35.9 fb - 1 collected in 2016 by the CMS experiment at the LHC from proton-proton collisions at a center-of-mass energy of 13 Te . The data are found to be consistent with the background expectations. Exclusion limits are set in the context of two-Higgs-doublet models in the A boson mass range between 225 and 1000 GeV .
A search for the pair production of heavy vector-like partners T and B of the top and bottom quarks has been performed by the CMS experiment at the CERN LHC using proton-proton collisions at s = 13 Te . The data sample was collected in 2016 and corresponds to an integrated luminosity of 35.9 fb - 1 . Final states studied for T T ¯ production include those where one of the T quarks decays via T → t Z and the other via T → b W , t Z , or t H , where H is a Higgs boson. For the B B ¯ case, final states include those where one of the B quarks decays via B → b Z and the other B → t W , b Z , or b H . Events with two oppositely charged electrons or muons, consistent with coming from the decay of a Z boson, and jets are investigated. The number of observed events is consistent with standard model background estimations. Lower limits at 95% confidence level are placed on the masses of the T and B quarks for a range of branching fractions. Assuming 100% branching fractions for T → t Z , and B → b Z , T and B quark mass values below 1280 and 1130 Ge , respectively, are excluded.
A top quark mass measurement is performed using 35.9 fb - 1 of LHC proton-proton collision data collected with the CMS detector at s = 13 TeV . The measurement uses the t t ¯ all-jets final state. A kinematic fit is performed to reconstruct the decay of the t t ¯ system and suppress the multijet background. Using the ideogram method, the top quark mass ( m t ) is determined, simultaneously constraining an additional jet energy scale factor ( JSF ). The resulting value of m t = 172.34 ± 0.20 (stat+JSF) ± 0.70 (syst) GeV is in good agreement with previous measurements. In addition, a combined measurement that uses the t t ¯ lepton+jets and all-jets final states is presented, using the same mass extraction method, and provides an m t measurement of 172.26 ± 0.07 (stat+JSF) ± 0.61 (syst) GeV . This is the first combined m t extraction from the lepton+jets and all-jets channels through a single likelihood function.
A search for standard model production of four top quarks ( t t ¯ t t ¯ ) is reported using events containing at least three leptons ( e , μ ) or a same-sign lepton pair. The events are produced in proton-proton collisions at a center-of-mass energy of 13 TeV at the LHC, and the data sample, recorded in 2016, corresponds to an integrated luminosity of 35.9 fb - 1 . Jet multiplicity and flavor are used to enhance signal sensitivity, and dedicated control regions are used to constrain the dominant backgrounds. The observed and expected signal significances are, respectively, 1.6 and 1.0 standard deviations, and the t t ¯ t t ¯ cross section is measured to be 16 . 9 - 11.4 + 13.8 fb , in agreement with next-to-leading-order standard model predictions. These results are also used to constrain the Yukawa coupling between the top quark and the Higgs boson to be less than 2.1 times its expected standard model value at 95% confidence level.
A search for new physics in events with a Z boson produced in association with large missing transverse momentum at the LHC is presented. The search is based on the 2016 data sample of proton-proton collisions recorded with the CMS experiment at s = 13 TeV , corresponding to an integrated luminosity of 35.9 fb - 1 . The results of this search are interpreted in terms of a simplified model of dark matter production via spin-0 or spin-1 mediators, a scenario with a standard-model-like Higgs boson produced in association with the Z boson and decaying invisibly, a model of unparticle production, and a model with large extra spatial dimensions. No significant deviations from the background expectations are found, and limits are set on relevant model parameters, significantly extending the results previously achieved in this channel.