Half-life Values Research Articles

Development of an in vitro model to estimate mass transfer from the anterior cavity

Knowledge of drug mass transfer from the anterior chamber via the iris-lens barrier has important implications for the development of front of the eye medicines that can also deliver drugs to the vitreous cavity. Here, the design and evaluation of a novel in vitro model that estimates anterior clearance (CL) kinetics is described. To mimic some aspects of the human eye to aid with pharmaceutical modelling, the model incorporated a simulation of aqueous inflow from the ciliary inlet at the physiological flow rate, two CL elimination pathways [anterior hyaloid pathway and retina choroid sclera (RCS) pathway], human cavity dimensions and use of simulated vitreous fluid (SVF). An eye movement platform that incorporated 3 different eye movements (smooth pursuit, microsaccadic and saccadic) was tested against the control (no movement) to observe any difference in anterior kinetics profile and drug convection to the posterior cavity. Both timolol and brimonidine injected in the intracameral space were evaluated in the new in vitro prototype. An initial release study with one selected eye movement (smooth pursuit) with timolol (6.8 ± 0.4 µg, 30 μL) and brimonidine (15.3 ± 1.5 µg, 30 μL) showed half-life values of 105.3 and 97.8 min respectively in the anterior cavity (AC) space. Another study evaluated the effect of all eye movements against control with both drugs with higher doses of timolol (146.0 ± 39.1 μg, 25 μL) and brimonidine (134.5 ± 39.5 μg, 25 μL). The amounts of timolol in the back of the eye (RCS membrane and outflow) were 0.07 ± 0.05%, 1.36 ± 0.88%, 1.55 ± 1.03% and 0.98 ± 0.06% by 8 h with smooth pursuit, microsaccadic, saccadic and no movement respectively; whereas brimonidine amounts were 0.70 ± 0.21%, 0.94 ± 0.40%, 1.48 ± 1.02%, and 0.76 ± 0.33% respectively. A small amount of both drugs was seen in other compartments in the model (lens part, iris part, hyaloid membrane part and silicone cornea). These results indicate that this model can be used to determine transfer of small molecules via the iris-lens barrier to help optimise front of the eye formulations to treat tissues further back in the eye.

Identification and Dissipation of Chlorpyrifos and Its Main Metabolite 3,5,6-TCP during Wheat Growth with UPLC-QTOF/MS.

Ultrahigh-performance liquid chromatography system coupled to a hybrid quadrupole time-of-flight mass spectrometer (UPLC-QTOF/MS) technology was used to investigate the degradation and metabolism of chlorpyrifos during wheat growth by spraying plants with different doses of chlorpyrifos 7 days after the flowering and filling stage. We analyzed and identified chlorpyrifos metabolites in different parts of wheat in full-scan MSE mode, and established a chlorpyrifos metabolite screening library using UNIFI software. The results show that the residues of chlorpyrifos in wheat ears, leaves, and stems exhibited a decreasing trend with the prolongation of application time, and the degradation kinetics could be fitted with the first-order kinetic equation Ct = C0 e−kt. The initial residues of chlorpyrifos in different parts of the wheat were different, in the order of leaves > wheat ears > stems. The degradation rate of chlorpyrifos under field conditions is relatively fast, and the half-life value is 2.33−5.05 days. Chlorpyrifos can undergo a nucleophilic addition substitution reaction under the action of hydrolase to generate secondary metabolite 3,5,6-trichloro-2-pyridinol (3,5,6-TCP). The residual amount of 3,5,6-TCP in each part of wheat first showed an increasing trend and then decreased over time. It reached the maximum on the 3rd, 7th, or 11th day after application, and then gradually degraded. Considering that 3,5,6-TCP is a biomarker with potential threats to humans and animals, it is recommended that 3,5,6-TCP be included in the relevant regulations for dietary exposure risk assessment.

Pharmacokinetics and Pharmacodynamics of Nipocalimab Administered at Different Rates of Intravenous Infusion in Healthy Participants: Results of a Phase 1 Placebo-Controlled Single-Dose Study

Background: Warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune condition driven by autoantibodies that can significantly impact a patient's quality of life. wAIHA is characterized by the premature destruction of red blood cells (RBCs) in the presence of autoantibodies which preferentially bind to RBCs at 37°C. There is currently no approved treatment for wAIHA. Patients with severely symptomatic anemia are typically managed with corticosteroids and rituximab, both of which are associated with potential relapse and adverse events. Nipocalimab, which is in clinical development for the treatment of wAIHA (NCT04119050), is a fully human, aglycosylated, effectorless IgG1 monoclonal antibody that targets the IgG binding site on the neonatal Fc receptor (FcRn) with high affinity to lower circulating IgG levels. This study assessed the pharmacokinetics (PK) and pharmacodynamics (PD) of single doses of nipocalimab administered at different IV infusion rates in healthy adults to support the potential use of shortened infusions in future studies. Nipocalimab was generally safe and well-tolerated at all doses and infusion rates; detailed safety results have been presented separately [Leu JH, et al. EHA 2022. Presentation P1534]. Methods: The trial was a single dose, sequential, randomized, double-blind, placebo-controlled, escalating dose and infusion rate study. Eligible participants were males or females aged 18-55 years with no clinically significant medical or physical conditions. Participants were randomized to 1 of 5 cohorts (n=8 per cohort [6 nipocalimab, 2 placebo]) to receive nipocalimab 30 mg/kg IV infused over 60, 30, 15 or 7.5 min (0.5, 1, 2, or 4 mg/kg/min), nipocalimab 60 mg/kg IV infused over 15 min (4 mg/kg/min) or matching placebo. Escalation to the next dose level was permitted following review by a safety monitoring committee. Pharmacokinetic sampling of nipocalimab was conducted predose, midpoint of infusion (MOI), end of infusion (EOI), EOI + 0.083h, EOI + 0.25h, EOI + 1h, start of infusion + 24h, Day 8, and Day 15 postdose; MOI and EOI varied for each dose. In terms of PD, total serum IgG was assessed. Results: A total of 40 participants (70% female, 93% white) received study drug, of which 30 were included in the PK analysis; 39 completed the study. Mean serum nipocalimab concentration-time profiles were similar following all 30 mg/kg doses regardless of infusion rate; mean serum concentrations were ~2 times higher following a 60 mg/kg infusion. Nipocalimab remained detectable up to ~169 hours postdose for 30 mg/kg groups and ~337 hours postdose for the 60 mg/kg group. Geometric mean peak (Cmax) and overall exposure (AUC) to nipocalimab were unaffected by infusion rate when administered at 30 mg/kg. Following a 60 mg/kg infusion, AUCs were 2.4-2.8 times higher and Cmax was 2.0-2.2 times higher than with 30 mg/kg infusions. Median Tmax was approximately at EOI following the 60 mg/kg infusion. Mean half-life (t½) values were similar in all treatment groups. In terms of total serum IgG, changes from baseline were decreased among all nipocalimab cohorts at all postdose time points. The maximum decrease in mean serum IgG levels was 79% at day 15 with nipocalimab 60 mg/kg. Conclusion: Nipocalimab Cmax and AUC were not affected by infusion rates when given at a dose of 30 mg/kg, but Tmax was delayed at the fastest infusion rates. Following the 60 mg/kg infusion, peak and overall nipocalimab exposures were 2-2.8 times higher than following 30 mg/kg infusions.

Two-proton radioactivity within a Coulomb and proximity potential model for deformed nuclei

The half-lives of two-proton $(2p)$ emitters $^{6}\mathrm{Be}$, $^{12}\mathrm{O}$, $^{16}\mathrm{Ne}$, $^{19}\mathrm{Mg}$, $^{45}\mathrm{Fe}$, $^{48}\mathrm{Ni}$, $^{54}\mathrm{Zn}$, and $^{67}\mathrm{Kr}$ have been predicted using the Coulomb and proximity potential model for deformed nuclei (CPPMDN) incorporating ground-state deformation (${\ensuremath{\beta}}_{2}$) and orientation effect, and the predicted values are compared with experimental data. As predicted values are in agreement with experimental data I extended my studies to 51 nuclei, whose decay are energetically possible with released energy ${Q}_{2p}>0$ for which $2p$ radioactivity is not yet experimentally detected, and the predicted half-life values are compared with other theoretical models/formulas. I hope the future experimental investigations will be guided by these predictions. The new Geiger Nuttall plot connecting ${log}_{10}[{T}_{1/2}(s)]$ computed using the CPPMDN versus $[{Z}_{d}^{0.8}+{\ensuremath{\ell}}^{\ensuremath{\beta}}]{Q}_{2p}^{\ensuremath{-}1/2}$ is found to be linear which shows the reliability of my calculations. It is found for the first time that $2p$ radioactivity also obeys the linear nature of a universal curve connecting ${log}_{10}[{T}_{1/2}(s)]$ versus $\ensuremath{-}lnP$ as that of the proton, $\ensuremath{\alpha}$, and cluster radioactivity.

Estimation of the double alpha-decay half-life

The model for the description of the simultaneous emission of two α-particles from the opposite sides of the nucleus (the double α-decay) is discussed in detail. The 32 smallest values of the half-lives of the double α-decay of nuclei are calculated. The daughter nuclei formed after the double α-decay are even-even and spherical in the ground state in the model. It is shown that the half-lives of the double α-decay are much smaller than the emission of 8Be cluster with sequential decay of 8Be into two α-particles. The calculated values of the double α-decay half-lives show that measuring this decay is possible in the accelerator experiments by forming the proton-rich nuclei. A detailed comparison of the characteristics of the single and double α-decays as well as the emission of 8Be cluster is presented.

Bioavailability and Pharmacokinetics of Endoxifen in Female Rats and Dogs: Evidence to Support the Use of Endoxifen to Overcome the Limitations of CYP2D6-Mediated Tamoxifen Metabolism.

Endoxifen (ENDX) is an active metabolite of tamoxifen (TAM), a drug commonly used for the treatment of estrogen receptor-positive breast cancer and metabolized by CYP2D6. Genetic or drug-induced reductions in CYP2D6 activity decrease plasma ENDX concentrations and TAM efficacy. It was proposed that direct oral administration of ENDX would circumvent the issues related to metabolic activation of TAM by CYP2D6 and increase patient response. Here, we characterized the pharmacokinetics and oral bioavailability of ENDX in female rats and dogs. Additionally, ENDX exposure was compared following equivalent doses of ENDX and TAM. ENDX exposure was 100-fold and 10-fold greater in rats and dogs, respectively, with ENDX administration compared with an equivalent dose of TAM. In single-dose administration studies, the terminal elimination half-life and plasma clearance values were 6.3 hours and 2.4 L/h per kg in rats given 2 mg/kg i.v. ENDX and 9.2 hours and 0.4 L/h/kg in dogs given 0.5 mg/kg i.v. ENDX, respectively. Plasma concentrations above 0.1 µM and 1 µM ENDX were achieved with 20-mg/kg and 200-mg/kg doses in rats, and concentrations above 1 µM and 10 µM were achieved with 15-mg/kg and 100-mg/kg doses in dogs. Oral absorption of ENDX was linear in rats and dogs, with bioavailability greater than 67% in rats and greater than 50% in dogs. In repeated-dose administration studies, ENDX peak plasma concentrations reached 9 µM in rats and 20 µM in dogs following four daily doses of 200 mg/kg or 30 mg/kg ENDX, respectively. The results indicate that ENDX has high oral bioavailability, and therapeutic concentrations were maintained after repeated dosing. Oral dosing of ENDX resulted in substantially higher ENDX concentrations than a similar dose of TAM. These data support the ongoing development of ENDX to overcome the limitations associated with CYP2D6-mediated metabolism of TAM in humans. SIGNIFICANCE STATEMENT: This study presents for the first time the pharmacokinetics and bioavailability of endoxifen and three key tamoxifen metabolites following repeated oral dosing in female rats and dogs. This study reports that endoxifen has high oral bioavailability, and therapeutic concentrations were maintained after repeated dosing. On the basis of these data, Z-endoxifen (Z-ENDX) was developed as a drug based upon the hypothesis that oral administration of Z-ENDX would overcome the limitations of CYP2D6 metabolism required for full metabolic activation of tamoxifen.

Decomposition and nutrient release patterns of municipal solid waste compost in two agro-ecological zones of Uganda

BackgroundDeteriorating soil fertility is a major constraint to agricultural production and food security among smallholder farmers in Uganda and throughout sub-Saharan Africa, where the majority of the population relies on subsistence farming for its livelihoods.Unfortunately, inorganic fertiliser used as a significant soil nutrient replenishment is unsustainable, causing adverse environmental effects, including soil acidification and pollution of water bodies. Therefore, finding alternative, more sustainable, low-cost nutrient management systems is vital. This study assessed the decomposition and nutrient release patterns of municipal solid waste compost (MSWC) in a 36 weeks litter bag experiment under field conditions in two agro-ecological zones (AEZs) of Uganda.ResultsWe found a higher rate of decomposition in the South-western Grass Farmlands (SGF) agro-ecological zone (0.041 week−1, with 20% of initial compost mass remaining after 36 weeks of decay) compared to Southern and Eastern Lake Kyoga Basin (SEKB) (0.043 week−1, 32% of initial litter mass remaining). The half-life values were 16 and 17 weeks for SGF and SEKB AEZs, respectively. The nutrient release rates differed between the two study sites. The macronutrient release pattern in both sites followed the order K > P > N. The secondary macronutrients release followed the order Ca > Mg in the SGF, while in SEKB, the order was reversed. The micronutrients followed the order Cu > Mn > Fe > Zn and Cu > Mn > Zn > Fe in SGF and SEKB AEZs, respectively. The MSWC mass loss during decomposition was negatively correlated with rainfall in both AEZs and with temperature in SGF AEZ, while it was positively correlated with temperature in SEKB AEZ. However, the relationship with nutrient release rates was inconsistent in both AEZs.ConclusionsOur results showed consistent release of nutrients in all AEZs throughout the study period, which coincides with the two cropping seasons in Uganda, suggesting that smallholder farmers can use MSWC as a soil amendment to address soil fertility decline and improve crop productivity. However, because most nutrients were released almost right away in both AEZs, planting should be done at the beginning of high rainfall months when soil moisture is high to synchronise nutrient release from MSWC with crop demand and maximise nutrient uptake by crops while minimising losses to the environment. Furthermore, the inconsistent relationships between the climatic variables and nutrient release suggest that other factors, such as site-specific microbial composition, influenced MSWC nutrient release. Therefore, long-term research is needed to examine other factors affecting nutrient release in these AEZs.

Validation of simple and efficient analytical methodology for estimation of forchlorfenuron residues

A simple and efficient analytical methodology was standardised for the estimation of forchlorfenuron residues in rice leaves, grains, husk, straw and soil using LC-MS/MS. The methodology was validated in terms selectivity, sensitivity, linearity, limit of detection, limit of quantification, matrix effect, repeatability and reproducibility. The limit of detection and limit of quantification of forchlorfenuron in rice leaves, grains, straw, husk and soil were worked out to be 0.003 and 0.01mgkg-1, respectively. Recoveries ranged between 81.54 and 99.05% with RSDr below 4.57 and RSDR below 4.19%. This validated method was applied for the determination of forchlorfenuron residues in paddy leaves after foliar application. The residues persisted for 0, 3 and 7days after application of forchlorfenuron 0.12% EC @ 1.25, 2.50 and 5.00ppm a.i. The half-life values were estimated to be 1.91 and 2.11days for 2.50 and 5.00ppm a.i. concentration. The residues were found to be below the limit of quantification of 0.01mgkg-1 in straw, grain, husk and soil samples collected at harvest time.

Modification of Taxifolin Properties by Spray Drying

Taxifolin is known as an active pharmaceutical ingredient (API) and food supplement due to its high antioxidant activity, multiple pharmacological effects, and good safety profile. Previously, taxifolin spheres (TS) were obtained from industrially produced API taxifolin in Russia (RT). In our work, we perform a pharmaceutical analysis of this new taxifolin material versus RT. TS is an amorphous material; however, it is stable without the polymer carrier, as confirmed by Fourier transform infrared spectroscopy. Both RT and TS demonstrate high safety profiles and are assigned to Class 1 of the Biopharmaceutical Classification System based on the results of experiments with MDCK cells. The water solubility of the new taxifolin form was 2.225 times higher compared with RT. Hausner ratios for RT and TS were 1.421 and 1.219, respectively, while Carr indices were 29.63% and 19.00%, respectively. Additionally, TS demonstrated sustained release from tablets compared with RT: the half-life values of tablets were 14.56 min and 20.63 min for RT and TS, respectively. Thus, TS may be a promising object for developing oral antiseptics in the form of orally dispersed tablets with sustained release patterns because of its anti-inflammatory, -protozoal, and -viral activities.

Molecular Characterization of a Stable and Robust L-Asparaginase from Pseudomonas sp. PCH199: Evaluation of Cytotoxicity and Acrylamide Mitigation Potential

L-asparaginase is an important industrial enzyme widely used to treat acute lymphoblastic leukemia (ALL) and to reduce acrylamide formation in food products. In the current study, a stable and robust L-asparaginase from Pseudomonas sp. PCH199, with a high affinity for L-asparagine, was cloned and expressed in Escherichia coli BL21(DE3). Recombinant L-asparaginase (Pg-ASNase II) was purified with a monomer size of 37.0 kDa and a native size of 148.0 kDa. During characterization, Pg-ASNase II exhibited 75.8 ± 3.84 U/mg specific activities in 50.0 mM Tris-HCl buffer (pH 8.5) at 50 °C. However, it retained 80 and 70% enzyme activity at 37 °C and 50 °C after 60 min, respectively. The half-life and kd values were 625.15 min and 1.10 × 10−3 min−1 at 37 °C. The kinetic constant Km, Vmax, kcat, and kcat/Km values were 0.57 mM, 71.42 U/mg, 43.34 s−1, and 77.90 ± 9.81 s−1 mM−1 for L-asparagine, respectively. In addition, the enzyme has shown stability in the presence of most metal ions and protein-modifying agents. Pg-ASNase II was cytotoxic towards the MCF-7 cell line (breast cancer) with an estimated IC50 value of 0.169 U/mL in 24 h. Further, Pg-ASNase II treatment led to a 70% acrylamide reduction in baked foods. These findings suggest the potential of Pg-ASNase II in therapeutics and the food industry.

Enhanced acidic stability of a Bacillus 1,3-1,4-β-glucanase through pH-based molecular dynamics simulation for efficient application in brewing industry

This study aimed to enhance the acidic stability of a Bacillus β-glucanase through pH-based MD simulation without the sacrifice of enzymatic catalytic properties. Based on the analysis of enzymatic flexibility and internal interactions, nine single-site variants and seven multi-site variants were constructed and their enzymatic properties were characterized. The optimal pH of G12N/D22N/T187A variant was 0.5 pH lower than that of wild-type. Its acidic stability is also significantly enhanced since the half-life values of the triple-site variant at pH4.5, pH5.0 and pH5.5 were 104.1 mins, 98.1 mins and 116.8 mins longer than those of wild-type. Moreover, the specific activities and kcat/Km value of the triple-site variant were also higher than those of wild-type. The computational and structural analysis indicated that the change of enzymatic surface charge and more stable hydrogen bonds might be the reason for the improvement of acidic stability of β-glucanase. The application of G12N/D22N/T187A variant in Congress mashing showed its strong ability to reduce the filtration time of mash and the wort viscosity, indicating that this variant might have potential value to apply in brewing industry.

Increased degradation of acetochlor in soil by mixed culture of P. fluorescens KT3 and B. subtilis 2M6E

The herbicide of acetochlor has been widely applied to control weeds in agricultural sector, but it is responsible for numerous environmental hazards. In the current study, we investigated the effects of the herbicide on bacteria and microfungi communities in soil. The research findings revealed that acetochlor used at 1.24 mg/kg inhibited the growth of both bacteria and microfungi. Moreover, the degradation half-life values were greater at higher acetochlor concentrations in soil, from 12.3 ± 1.2 days at the concentration of 1.0× to 24.5 ± 2.5 days at 2.0×. The augmentation of P. fluorescens KT3 and amendment with peat in soil increased the degradation rates. Besides, the cultivation of peanut enhanced degradation of the compound, and stimulated the growth of bacteria and microfungi. This study showed a process to enhance the remediation of acetochlor in soil by augmentation of P. fluorescens KT3 and cultivation of peanut.

Half-life prediction of some neutron-rich exotic nuclei prior to peak A = 130

β-decay is amongst the key properties of nuclei required for the modeling of r-process nucleosynthesis. It also governs the flow of abundances among neighboring isotopic chains of high-mass elements. In the present work, a simple proton-neutron quasi particle random phase approximation (p–n-QRPA) model has been used for the calculation of β-decay half-lives of Rb, Sr, Y and Zr neutron-rich isotopes. For 97−103Rb, 98−107Sr, 101−109Y and 104−112Zr, where the experimental data were available, the half-life values are reproduced with reasonable accuracy. The same set of model parameters are later used to predict half-lives for few neutron-rich nuclei (104−112Rb, 108−113Sr, 110−114Y and 113−115Zr) where measured data is not available. The p–n-QRPA results (including only allowed transitions) are compared with previous calculations (allowed plus forbidden) and exhibit agreement within a factor of 2.0 when compared with the recent available experimental data.

Half-life measurement of 44Sc and 44mSc

The half-lives of 44Sc and 44mSc were measured by following their decay rate using several measurement systems: two ionization chambers and three γ-spectrometry detectors with digital and/or analogue electronics. For 44Sc, the result was the combination of seven half-life values giving a result of 4.042(7) h, which agrees with the last reported value of 4.042(3) h and confirms the near to 2% deviation from the recommended half-life of 3.97(4) h. Scandium-44 is present as an impurity in the production of 44Sc by cyclotron proton irradiation. Its half-life was determined by measurements performed a few days after End of Bomardment (EoB), so that the 44Sc decayed down to a negligible level. Seven measurements were combined to obtain an average of 58.7(3) h, which is in agreement with the recommended value of 58.6(1) h.

Dl-Serine Covalently Ornamented and Ln3+-Incorporated Arsenotungstates with Fast-Responsive Photochromic and Photoinduced Luminescent Switchable Behaviors.

Three isostructural dl-serine covalently functionalized and multinuclear lanthanide (Ln3+)-embedded arsenotungstates, K2[{As4W44O137(OH)18(H2O)2(dl-Ser)2}{Ln2(H2O)4(dl-Ser)}2{Ln(H2O)7}2]·70H2O (Ln = Sm (1), Eu (2), and Gd (3); dl-Ser = C3H7NO3), were prepared, where the centrosymmetric [{As4W44O137(OH)18(H2O)2(dl-Ser)2}{Ln2(H2O)4(dl-Ser)}2]8- polyanion consists of two {As2W19O59(OH)8(H2O)}6- fragments, integrated with a two-dl-serine-ornamented [W6O23(OH)2(dl-Ser)2{Ln2(H2O)4}2]8- segment. In addition, the photochromic transformation of solid-state compounds 1-3 was observed from colorless to blue after a UV illumination of 4 min, and the decay process lasted as long as ∼20 h in the dark. The coloration kinetic half-life (t1/2) values of compounds 1, 2, and 3 were calculated to be 0.597, 0.920, and 0.723 min, respectively. Furthermore, the luminescent properties and energy migration from arsenotungstates and organic chromophores to Sm3+ and Eu3+ ions in 1 and 2 have been intensively investigated. Further analysis manifests that 1 possesses an effective luminescent switchable behavior, triggered by its fast-responsive photochromism effect.

Pharmacokinetic evaluation of radiolabeled intraocular anti-CLEC14a antibody in preclinical animal species and application in humans.

Anti-angiogenic antibodies are widely used in the treatment of neovascular macular degeneration. Human antibody targeting C-type lectin domain family 14 member A (CLEC14a) is potential therapeutic agents owing to its antiangiogenic activity. In the present study, we aimed to predict the human intraocular pharmacokinetic (PK) properties of an anti-CLEC14a antibody. I-125 labeled aflibercept and anti-CLEC14a antibody were intravitreally injected into mice, rats, and rabbits. Single photon emission computed tomography/computed tomography imaging was performed, and the intraocular radioactivity concentration (%ID/ml) was obtained. The PK parameters in those three animal species were obtained by compartmental analysis. The PK parameters in humans were estimated by allometric scaling of the animal PK parameters with consideration of the hydrodynamic radius of the antibody. The mean half-life values of intraocular I-125-labeled aflibercept in mice, rats, and rabbits were 1.13 days, 1.25 days, and 4.91 days, respectively, by analysis with a one-compartment model. The predicted human half-life of intraocular aflibercept was 5.75 days based on vitreal volume by allometric scaling. The half-life values of intraocular I-125-labeled anti-CLEC14a in mice, rats and rabbits were 1.05 days, 1.84 days, and 6.37 days, respectively, by analysis with a one-compartment model. The predicted human half-life of intraocular anti-CLEC14a was 10.29 days based on vitreal volume. According to the hydrodynamic volume of the anti-CLEC14a, the predicted human half-life of intraocular anti-CLEC14a was 9.81 days. The PK characteristics of the intraocular anti-CLEC14a antibody were evaluated noninvasively in animals using I-125 labeling, and the intraocular PK characteristics in humans were predicted using these animal data. This methodology can be applied for the development of new antiangiogenic antibodies to treat macular degeneration.

Beta decay and electron capture rates of manganese isotopes in astrophysical environments

The isotopes of manganese in the mass range of A=53−63 are abundant in the core materials of high-mass stars and they are considered to be of prime importance in the progression of the pre-collapse phases. During these late evolutionary phases, nuclear processes associated with weak interactions, including β−-decay and electron capture (EC) of these isotopes, significantly alter the lepton to baryon ratio (Ye) in the core’s composition. The temporal change in this parameter is one of the basic elements used to simulate a successful explosion. Hence, the β−-decay and EC rates of manganese (Mn) nuclides may serve as important inputs in the simulation codes for core-collapse supernova. In this study, we investigated the weak decay characteristics of 55−63Mn nuclides. The strength distributions of Gamow–Teller transitions in the directions of β−-decay and EC were calculated for these isotopes using the proton–neutron quasi-particle random-phase approximation (pn-QRPA) model. The β-decay half-life values of Mn isotopes under terrestrial conditions were computed and compared with measured data and previous calculations. The pn-QRPA estimated half-lives were in good agreement with the experimental values. The β− and EC rates were then calculated over a large range of stellar temperatures (0.01−30)×109K and densities (10−1011) g/cm3. The computed rates were compared with previous calculations performed using the large-scale shell model (LSSM) and independent particle model (IPM). For most of the isotopes, in high temperature and density regimes, the pn-QRPA calculated β−-decay rates were smaller than the LSSM and IPM rates by up to an order of magnitude. By contrast, the EC rates were larger by up to an order of magnitude (factor of 3−10) at high temperature compared with the LSSM (IPM) results.

Dissipation of Lambda-cyhalothrin 5% EC on Brinjal Fruit Grown in Gurugram, Haryana

Background: The introduction of synthetic pesticides Lambda-cyhalothrinin for crop protection in general has significantly contributed to increased productivity. Lambda-cyhalothrin have been reported to cause toxic effects on humans, ranging from short-term effects such as headaches and nausea to chronic effects like cancer, reproductive damage and endocrine disruption. Lambda-cyhalothrin is a type-II highly active synthetic pyrethroid insecticide which contains a-cyano group. Lambda-cyhalothrin applied at the rate of 30 g a.i. ha-1 was found to be effective against shoot and fruit borer on brinjal. Methods: The analytical method for the determination of Lambda-cyhalothrin 5% EC (Test Item) on brinjal was validated as per DG-SANTE 2019 guideline. The field trails including the dissipation study and final residue study were conducted in a randomized block design in open field. As per recommendation, dose of test item (T1= 15 g a.i/ha; T2 = 30 g a.i/ha) were 500 L/hectare for Trial. Lambda-cyhalothrin residues of brinjal samples were determined at 0, 1, 3, 5, 7 and 10 days at both application of recommended and double the recommended dose of test item. Result: The analytical method employed for determination of persistence residues of Lambda-cyhalothrin in brinjal was validated and found accurate and precise. The per cent dissipation of Lambda-cyhalothrin for the treatment T1 was 37.22% after 1 day which increased to 96.66% by 10th day, similarly for the double dose (T2) the initial dissipation was 57.14%, which increased to 99.7 % after 10th day. The half-life (T1/2) values of Lambda-cyhalothrin on brinjal were found to be 2.06 and 2.13 days for T1 and T2, respectively.

Measurements of the 252Cf half-life

Data from manganese bath measurements of the neutron emission rates from commercial 252Cf sources over a period of 40 years have been used to derive an accurate value for the 252Cf half-life. Particular care was taken to account for the presence of other californium and curium isotopes in the sources, and the resulting value has an uncertainty of 0.05%. The present value has been compared with earlier measurements in a review of this important half-life.

Multianalytical Approach for Deciphering the Specific MS/MS Transition and Overcoming the Challenge of the Separation of a Transient Intermediate, Quinonoid Dihydrobiopterin.

Despite recent technological developments in analytical chemistry, separation and direct characterization of transient intermediates remain an analytical challenge. Among these, separation and direct characterization of quinonoid dihydrobiopterin (qH2Bip), a transient intermediate of tetrahydrobiopterin (H4Bip)-dependent hydroxylation reactions, essential in living organisms, with important and varied human pathophysiological impacts, are a clear illustration. H4Bip regeneration may be impaired by competitive nonenzymatic autoxidation reactions, such as isomerization of qH2Bip into a more stable 7,8-H2Bip (H2Bip) isomer, and subsequent nonenzymatic oxidation reactions. The quinonoid qH2Bip intermediate thus plays a key role in H4Bip-dependent hydroxylation reactions. However, only a few experimental results have indirectly confirmed this finding while revealing the difficulty of isolating qH2Bip from H4Bip-containing solutions. As a result, no current H4Bip assay method allows this isomer to be quantified even by liquid chromatography-tandem mass spectrometry (MS/MS). Here, we report isolation, structural characterization, and abundance of qH2Bip formed upon H4Bip autoxidation using three methods integrated into MS/MS. First, we characterized the structure of the two observed H2B isomers using IR photodissociation spectroscopy in conjunction with quantum chemical calculations. Then, we used differential ion mobility spectrometry to fully separate all oxidized forms of H4Bip including qH2Bip. These data are consistent and show that qH2Bip can also be unambiguously identified thanks to its specific MS/MS transition. This finding paves the way for the quantification of qH2Bip with MS/MS methods. Most importantly, the half-life value of this intermediate is nearly equivalent to that of H4Bip (tens of minutes), suggesting that an accurate method of H4Bip analysis should include the quantification of qH2Bip.