PLGA Nanoparticles for Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: A Novel Approach towards Reduction of Renal Radiation Dose

BACKGROUND:Peptide receptor radionuclide therapy (PRRT), employed for treatment of neuroendocrine tumors (NETs) is based on over-expression of Somatostatin Receptors (SSTRs) on NETs. It is, however, limited by high uptake and retention of radiolabeled peptide in kidneys resulting in unnecessary radiation exposure thus causing nephrotoxicity. Employing a nanocarrier to deliver PRRT drugs specifically to the tumor can reduce the associated nephrotoxicity. Based on this, (177)Lu-DOTATATE loaded PLGA nanoparticles (NPs) were formulated in the present study, as a potential therapeutic model for NETs. METHODOLOGY AND FINDINGS:DOTATATE was labeled with Lutetium-177 ((177)Lu) (labeling efficiency 98%; R(f)∼0.8). Polyethylene Glycol (PEG) coated (177)Lu-DOTATATE-PLGA NPs (50:50 and 75:25) formulated, were spherical with mean size of 304.5±80.8 and 733.4±101.3 nm (uncoated) and 303.8±67.2 and 494.3±71.8 nm (coated) for PLGA(50:50) and PLGA(75:25) respectively. Encapsulation efficiency (EE) and In-vitro release kinetics for uncoated and coated NPs of PLGA (50:50 & 75:25) were assessed and compared. Mean EE was 77.375±4.98% & 67.885±5.12% (uncoated) and 65.385±5.67% & 58.495±5.35% (coated). NPs showed initial burst release between 16.64-21.65% with total 42.83-44.79% over 21 days. The release increased with coating to 20.4-23.95% initially and 60.97-69.12% over 21 days. In-vivo studies were done in rats injected with (177)Lu-DOTATATE and (177)Lu-DOTATATE-NP (uncoated and PEG-coated) by imaging and organ counting after sacrificing rats at different time points over 24 hr post-injection. With (177)Lu-DOTATATE, renal uptake of 37.89±10.2%ID/g was observed, which reduced to 4.6±1.97% and 5.27±1.66%ID/g with uncoated and coated (177)Lu-DOTATATE-NP. The high liver uptake with uncoated (177)Lu-DOTATATE-NP (13.68±3.08% ID/g), reduced to 7.20±2.04%ID/g (p = 0.02) with PEG coating. CONCLUSION:PLGA NPs were easily formulated and modified for desired release properties. PLGA 50:50 NPs were a more suitable delivery vehicle for (177)Lu-DOTATATE than PLGA 75:25 because of higher EE and slower release rate. Reduced renal retention of (177)Lu-DOTATATE and reduced opsonisation strongly advocate the potential of (177)Lu-DOTATATE-PLGA-PEG NPs to reduce radiation dose in PRRT

COVID-19 vaccines based on viral nanoparticles displaying a conserved B-cell epitope show potent immunogenicity and a long-lasting antibody response

The COVID-19 pandemic caused by SARS-CoV-2 sparked intensive research into the development of effective vaccines, 50 of which have been approved thus far, including the novel mRNA-based vaccines developed by Pfizer and Moderna. Although limiting the severity of the disease, the mRNA-based vaccines presented drawbacks, such as the cold chain requirement. Moreover, antibody levels generated by these vaccines decline significantly after 6 months. These vaccines deliver mRNA encoding the full-length spike (S) glycoprotein of SARS-CoV-2, but must be updated as new strains and variants of concern emerge, creating a demand for adjusted formulations and booster campaigns. To overcome these challenges, we have developed COVID-19 vaccine candidates based on the highly conserved SARS CoV-2, 809-826 B-cell peptide epitope (denoted 826) conjugated to cowpea mosaic virus (CPMV) nanoparticles and bacteriophage Qβ virus-like particles, both platforms have exceptional thermal stability and facilitate epitope delivery with inbuilt adjuvant activity. We evaluated two administration methods: subcutaneous injection and an implantable polymeric scaffold. Mice received a prime–boost regimen of 100 μg per dose (2 weeks apart) or a single dose of 200 μg administered as a liquid formulation, or a polymer implant. Antibody titers were evaluated longitudinally over 50 weeks. The vaccine candidates generally elicited an early Th2-biased immune response, which stimulates the production of SARS-CoV-2 neutralizing antibodies, followed by a switch to a Th1-biased response for most formulations. Exceptionally, vaccine candidate 826-CPMV (administered as prime-boost, soluble injection) elicited a balanced Th1/Th2 immune response, which is necessary to prevent pulmonary immunopathology associated with Th2 bias extremes. While the Qβ-based vaccine elicited overall higher antibody titers, the CPMV-induced antibodies had higher avidity. Regardless of the administration route and formulation, our vaccine candidates maintained high antibody titers for more than 50 weeks, confirming a potent and durable immune response against SARS-CoV-2 even after a single dose

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Search for supersymmetry in events with one lepton and multiple jets in proton-proton collisions at root s=13 TeV

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Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

Measurement of the top quark mass using charged particles in pp collisions at root s=8 TeV

Peer reviewe