Parkinson's disease is the second most common neurodegenerative condition with its prevalence projected to 8.9 million individuals globally in the year 2019. Parkinson's disease affects both motor and certain non-motor functions of an individual. Numerous research has focused on the neuroprotective effect of the glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease. Discovered in 1993, GDNF is a neurotrophic factor identified from the glial cells which was found to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. Given this property, recent studies have focused on the exogenous administration of GDNF for relieving Parkinson's disease-related symptoms both at a pre-clinical and a clinical level. This review will focus on enumerating the molecular connection between Parkinson's disease and GDNF and shed light on all the available drug delivery approaches to facilitate the selective delivery of GDNF into the brain paving the way as a potential therapeutic candidate for Parkinson's disease in the future.
The observation of WWγ production in proton-proton collisions at a center-of-mass energy of 13 TeV with an integrated luminosity of 138 fb^{-1} is presented. The observed (expected) significance is 5.6 (5.1) standard deviations. Events are selected by requiring exactly two leptons (one electron and one muon) of opposite charge, moderate missing transverse momentum, and a photon. The measured fiducial cross section for WWγ is 5.9±0.8(stat)±0.8(syst)±0.7(modeling) fb, in agreement with the next-to-leading order quantum chromodynamics prediction. The analysis is extended with a search for the associated production of the Higgs boson and a photon, which is generated by a coupling of the Higgs boson to light quarks. The result is used to constrain the Higgs boson couplings to light quarks.
A search is reported for near-threshold structures in the J/ψJ/ψ invariant mass spectrum produced in proton-proton collisions at sqrt[s]=13 TeV from data collected by the CMS experiment, corresponding to an integrated luminosity of 135 fb^{-1}. Three structures are found, and a model with quantum interference among these structures provides a good description of the data. A new structure is observed with a local significance above 5 standard deviations at a mass of 6638_{-38}^{+43}(stat)_{-31}^{+16}(syst) MeV. Another structure with even higher significance is found at a mass of 6847_{-28}^{+44}(stat)_{-20}^{+48}(syst) MeV, which is consistent with the X(6900) resonance reported by the LHCb experiment and confirmed by the ATLAS experiment. Evidence for another new structure, with a local significance of 4.7 standard deviations, is found at a mass of 7134_{-25}^{+48}(stat)_{-15}^{+41}(syst) MeV. Results are also reported for a model without interference, which does not fit the data as well and shows mass shifts up to 150 MeV relative to the model with interference.
The first search for scalar leptoquarks produced in τ-lepton-quark collisions is presented. It is based on a set of proton-proton collision data recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of 138 fb^{-1}. The reconstructed final state consists of a jet, significant missing transverse momentum, and a τ lepton reconstructed through its hadronic or leptonic decays. Limits are set on the product of the leptoquark production cross section and branching fraction and interpreted as exclusions in the plane of the leptoquark mass and the leptoquark-τ-quark coupling strength.
A search for dark matter in events with a displaced nonresonant muon pair and missing transverse momentum is presented. The analysis is performed using an integrated luminosity of 138 fb^{-1} of proton-proton (pp) collision data at a center-of-mass energy of 13 TeV produced by the LHC in 2016-2018. No significant excess over the predicted backgrounds is observed. Upper limits are set on the product of the inelastic dark matter production cross section σ(pp→A^{'}→χ_{1}χ_{2}) and the decay branching fraction B(χ_{2}→χ_{1}μ^{+}μ^{-}), where A^{'} is a dark photon and χ_{1} and χ_{2} are states in the dark sector with near mass degeneracy. This is the first dedicated collider search for inelastic dark matter.
The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140 fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
Taurine is a sulfur-containing, semi-essential amino acid that occurs naturally in the body. It alternates between inflammation and oxidative stress-mediated injury in various disease models. As part of its limiting functions, taurine also modulates endoplasmic reticulum stress, Ca2+ homeostasis, and neuronal activity at the molecular level. Taurine effectively protects against a number of neurological disorders, including stroke, epilepsy, cerebral ischemia, memory dysfunction, and spinal cord injury. Although various therapies are available, effective management of these disorders remains a global challenge. Approximately 30 million people are affected worldwide. The design of taurine formation could lead to potential drugs/supplements for the health maintenance and treatment of central nervous system disorders. The general neuroprotective effects of taurine and the various possible underlying mechanisms are discussed in this review. This article is a good resource for understanding the general effects of taurine on various diseases. Given the strong evidence for the neuropharmacological efficacy of taurine in various experimental paradigms, it is concluded that this molecule should be considered and further investigated as a potential candidate for neurotherapeutics, with emphasis on mechanism and clinical studies to determine efficacy.
Piceatannol is a naturally occurring hydroxylated resveratrol analogue that can be found in a variety of fruits and vegetables. It has been documented to have a wide range of beneficial effects, including anti-inflammatory, antioxidant, anti-aging, anti-allergic, antidiabetic, neuroprotective, cardioprotective, and chemopreventive properties. Piceatannol has significantly higher antioxidant activity than resveratrol. Piceatannol has been shown in preclinical studies to have the ability to inhibit or reduce the growth of cancers in various organs such as the brain, breast, lung, colon, cervical, liver, prostate, and skin. However, the bioavailability of Piceatannol is comparatively lower than resveratrol and other stilbenes. Several approaches have been reported in recent years to enhance its bioavailability and biological activity, and clinical trials are required to validate these findings. This review focuses on several aspects of natural stilbene Piceatannol, its chemistry, and its mechanism of action, and its promising therapeutic potential for the prevention and treatment of a wide variety of complex human diseases.
Polysaccharides originating from marine sources have been studied as potential material for use in wound dressings because of their desirable characteristics of biocompatibility, biodegradability, and low toxicity. Marine-derived polysaccharides used as wound dressing, provide several benefits such as promoting wound healing by providing a moist environment that facilitates cell migration and proliferation. They can also act as a barrier against external contaminants and provide a protective layer to prevent further damage to the wound. Research studies have shown that marine-derived polysaccharides can be used to develop different types of wound dressings such as hydrogels, films, and fibres. These dressings can be personalised to meet specific requirements based on the type and severity of the wound. For instance, hydrogels can be used for deep wounds to provide a moist environment, while films can be used for superficial wounds to provide a protective barrier. Additionally, these polysaccharides can be modified to improve their properties, such as enhancing their mechanical strength or increasing their ability to release bioactive molecules that can promote wound healing. Overall, marine-derived polysaccharides show great promise for developing effective and safe wound dressings for various wound types.
Quasireal photons exchanged in relativistic heavy ion interactions are powerful probes of the gluonic structure of nuclei. The coherent J/ψ photoproduction cross section in ultraperipheral lead-lead collisions is measured as a function of photon-nucleus center-of-mass energies per nucleon (W_{γN}^{Pb}) over a wide range of 40
The present study focused on preparing and characterizing magnetite-polyvinyl alcohol (PVA) hybrid nanoparticles using Acanthophora spicifera marine algae extract as a reducing agent. Various analytical techniques, including UV-Visible spectrometry, Fourier-transform infrared (FTIR) analysis, energy-dispersive X-ray (EDX), scanning electron microscopy (SEM), and X-ray diffraction (XRD) analysis, were used to characterize the nanoparticles. The results showed the successful synthesis of nanoparticles with a characteristic color change and absorption peak at 400 nm in UV-Visible spectrometry. FTIR analysis indicated an interaction between the carboxyl group and magnetite-polyvinyl alcohol hybrid ions. SEM analysis revealed spherical nanoparticles with sizes ranging from 20 to 100 nm. EDX analysis confirmed the presence of strong magnetite peaks in Acanthophora spicifera, validating successful preparation. XRD analysis indicated the crystalline nature of the nanoparticles. Furthermore, the antimicrobial potential of As-PVA-MNPs was evaluated, demonstrating a significant zone of inhibition against tested bacterial and fungal samples at a concentration of 100 µg. These findings suggest the promising antimicrobial activity of the synthesized nanoparticles for potential applications in combating pathogenic microorganisms.
We present an observation of photon-photon production of τ lepton pairs in ultraperipheral lead-lead collisions. The measurement is based on a data sample with an integrated luminosity of 404 μb^{-1} collected by the CMS experiment at a center-of-mass energy per nucleon pair of sqrt[s_{NN}]=5.02 TeV. The γγ→τ^{+}τ^{-} process is observed for τ^{+}τ^{-} events with a muon and three charged hadrons in the final state. The measured fiducial cross section is σ(γγ→τ^{+}τ^{-})=4.8±0.6(stat)±0.5(syst) μb, where the second (third) term corresponds to the statistical (systematic) uncertainty in σ(γγ→τ^{+}τ^{-}) in agreement with leading-order QED predictions. Using σ(γγ→τ^{+}τ^{-}), we estimate a model-dependent value of the anomalous magnetic moment of the τ lepton of a_{τ}=0.001_{-0.089}^{+0.055}.
Leukemia is a cancer of white blood cells characterized by immature lymphocytes. Due to blood cancer, many people die every year. Hence, the early detection of these blast cells is necessary for avoiding blood cancer. A novel deep convolutional neural network (CNN) 3SNet that has depth-wise convolution blocks to reduce the computation costs has been developed to aid the diagnosis of leukemia cells. The proposed method includes three inputs to the deep CNN model. These inputs are grayscale and their corresponding histogram of gradient (HOG) and local binary pattern (LBP) images. The HOG image finds the local shape, and the LBP image describes the leukaemia cell's texture pattern. The suggested model was trained and tested with images from the AML-Cytomorphology_LMU dataset. The mean average precision (MAP) for the cell with less than 100 images in the dataset was 84%, whereas for cells with more than 100 images in the dataset was 93.83%. In addition, the ROC curve area for these cells is more than 98%. This confirmed proposed model could be an adjunct tool to provide a second opinion to a doctor.
The dependence of the ratio between the B_{s}^{0} and B^{+} hadron production fractions, f_{s}/f_{u}, on the transverse momentum (p_{T}) and rapidity of the B mesons is studied using the decay channels B_{s}^{0}→J/ψϕ and B^{+}→J/ψK^{+}. The analysis uses a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the CMS experiment in 2018 and corresponding to an integrated luminosity of 61.6 fb^{-1}. The f_{s}/f_{u} ratio is observed to depend on the B p_{T} and to be consistent with becoming asymptotically constant at large p_{T}. No rapidity dependence is observed. The ratio of the B^{0} to B^{+} meson production fractions, f_{d}/f_{u}, is also measured, for the first time in proton-proton collisions, using the B^{0}→J/ψK^{*0} decay channel. The result is found to be within 1 standard deviation of unity and independent of p_{T} and rapidity, as expected from isospin invariance.
We present the first direct search for exotic Higgs boson decays H→AA, A→γγ in events with two photonlike objects. The hypothetical particle A is a low-mass spin-0 particle decaying promptly to a merged diphoton reconstructed as a single photonlike object. We analyze the data collected by the CMS experiment at sqrt[s]=13 TeV corresponding to an integrated luminosity of 136 fb^{-1}. No excess above the estimated background is found. We set upper limits on the branching fraction B(H→AA→4γ) of (0.9-3.3)×10^{-3} at 95% confidence level for masses of A in the range 0.1-1.2 GeV.
Leading pathological markers of Alzheimer's disease (AD) include Acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), Amyloid beta (Aβ) and reactive oxygen species (ROS). Indole derivatives were identified and optimized to improve the potency against AChE, BuChE, Aβ and ROS. The lead molecule IND-30 was found to be selective for AChE (selectivity ratio: 22.92) in comparison to BuChE and showed maximum inhibition potential for human AChE (IC50: 4.16 ± 0.063 μM). IND-30 was found to be safe on the SH-SY5Y cell line until the dose of 30 mM. Further, molecule IND-30 was evaluated for its ability to inhibit AChE-induced Aβ aggregation at 0.5, 10 and 20 μM doses. Approximately, 50% of AChE-induced Aβ aggregation was inhibited by IND-30. Thus, IND-30 was found to be multitargeting for AD.
The first observation of the production of W^{±}W^{±} bosons from double parton scattering processes using same-sign electron-muon and dimuon events in proton-proton collisions is reported. The data sample corresponds to an integrated luminosity of 138 fb^{-1} recorded at a center-of-mass energy of 13 TeV using the CMS detector at the CERN LHC. Multivariate discriminants are used to distinguish the signal process from the main backgrounds. A binned maximum likelihood fit is performed to extract the signal cross section. The measured cross section for production of same-sign W bosons decaying leptonically is 80.7±11.2(stat) _{-8.6}^{+9.5}(syst)±12.1(model) fb, whereas the measured fiducial cross section is 6.28±0.81(stat)±0.69(syst)±0.37(model) fb. The observed significance of the signal is 6.2 standard deviations above the background-only hypothesis.
A search for the rare η→μ^{+}μ^{-}μ^{+}μ^{-} double-Dalitz decay is performed using a sample of proton-proton collisions, collected by the CMS experiment at the CERN LHC with high-rate muon triggers during 2017 and 2018 and corresponding to an integrated luminosity of 101 fb^{-1}. A signal having a statistical significance well in excess of 5 standard deviations is observed. Using the η→μ^{+}μ^{-} decay as normalization, the branching fraction B(η→μ^{+}μ^{-}μ^{+}μ^{-})=[5.0±0.8(stat)±0.7(syst)±0.7(B_{2μ})]×10^{-9} is measured, where the last term is the uncertainty in the normalization channel branching fraction. This work achieves an improved precision of over 5 orders of magnitude compared to previous results, leading to the first measurement of this branching fraction, which is found to agree with theoretical predictions.
A search for the standard model Higgs boson decaying to a charm quark-antiquark pair, H→cc[over ¯], produced in association with a leptonically decaying V (W or Z) boson is presented. The search is performed with proton-proton collisions at sqrt[s]=13 TeV collected by the CMS experiment, corresponding to an integrated luminosity of 138 fb^{-1}. Novel charm jet identification and analysis methods using machine learning techniques are employed. The analysis is validated by searching for Z→cc[over ¯] in VZ events, leading to its first observation at a hadron collider with a significance of 5.7 standard deviations. The observed (expected) upper limit on σ(VH)B(H→cc[over ¯]) is 0.94 (0.50_{-0.15}^{+0.22})pb at 95% confidence level (C.L.), corresponding to 14 (7.6_{-2.3}^{+3.4}) times the standard model prediction. For the Higgs-charm Yukawa coupling modifier, κ_{c}, the observed (expected) 95% C.L. interval is 1.1
The structure of nucleons is multidimensional and depends on the transverse momenta, spatial geometry, and polarization of the constituent partons. Such a structure can be studied using high-energy photons produced in ultraperipheral heavy-ion collisions. The first measurement of the azimuthal angular correlations of exclusively produced events with two jets in photon-lead interactions at large momentum transfer is presented, a process that is considered to be sensitive to the underlying nuclear gluon polarization. This study uses a data sample of ultraperipheral lead-lead collisions at sqrt[s_{NN}]=5.02 TeV, corresponding to an integrated luminosity of 0.38 nb^{-1}, collected with the CMS experiment at the LHC. The measured second harmonic of the correlation between the sum and difference of the two jet transverse momentum vectors is found to be positive, and rising, as the dijet transverse momentum increases. A well-tuned model that has been successful at describing a wide range of proton scattering data from the HERA experiments fails to describe the observed correlations, suggesting the presence of gluon polarization effects.