Half-life Limit Research Articles

VEGF165b mutant with a prolonged half-life and enhanced anti-tumor potency in a mouse model

VEGF165b has been shown to be an effective anti-cancer agent; however, its short half-life limits further application in the clinical field. The development of a mutant VEGF165b with a prolonged half-life is urgently needed for its future application. A mutant VEGF165b was generated by inactivation of its plasmin cleavage site. The mutant and native VEGF165b proteins without purification tags were expressed via the Pichia pastoris expression system followed by purification with a HiTrap heparin affinity chromatography column through optimization of the purification conditions. Furthermore, its binding affinity with VEGF Receptors and its functions in vitro and in vivo were examined. Results showed that the half-life of mutant VEGF165b increased to approximately 10 times (Intravenous), 9.1 times (Intraperitoneal) and 5.4 times (Subcutaneous) greater than that of VEGF165b, and the mutation did not cause significant alteration of VEGFR1 and VEGFR2 binding affinity. Mutant VEGF165b inhibited the proliferation and migration of HUVECs in vitro, similar to the native VEGF165b. In a mouse melanoma model, mutant VEGF165b exhibited stronger anti-tumor activity in comparison with its native counterpart. These results indicate that the mutant VEGF165b had a prolonged half-life and retained the anti-angiogenic activity of the native VEGF165b, suggesting that this novel mutant VEGF165b may be a stronger anti-cancer agent.

First search for 2ε and εβ+ decay of 162Er and new limit on 2β− decay of 170Er to the first excited level of 170Yb

The first search for double electron capture (2ε) and electron capture with positron emission (εβ+) of 162Er to the ground state and to several excited levels of 162Dy was realized with 326 g of highly purified erbium oxide. The sample was measured over 1934 h by the ultra-low background HP Ge γ spectrometer GeCris (465 cm3) at the Gran Sasso underground laboratory. No effect was observed, the half-life limits were estimated at the level of yr. A possible resonant 0ν KL1 capture in 162Er to the 2+ 1 782.7 keV excited state of 162Dy is restricted as T1/2 ≥ 5.0 × 1017 yr at 90% C.L. A new improved half-life limit T1/2 ≥ 4.1 × 1017 yr was set on the 2β− decay of 170Er to the 2+ 84.3 keV first excited state of 170Yb.

2K-Capture in 124Хе: Results of Data Processing for an Exposure of 37.7 kg day

The results of the experimental search for two-neutrino $2K$-capture in $^{124}$Xe with a large copper proportional counter obtained by processing the data for an exposure of 37.7 kg$\times$day are presented. The experimental setup is located at the Underground Low-Background Laboratory of the Baksan Neutrino Observatory at a depth of 4900 m w.e. The combination of methods of selection of useful signals with a unique set of characteristics and the event topology taken into account allowed us to suppress the background in the energy region of interest. A new half-life limit for $2K(2\nu)$-capture in $^{124}$Xe was determined: T$_{1/2}\geq7.7\cdot10^{21}$ yrs (90\% C.L.).

An improved half-life limit of the double beta decay of 94Zr into the excited state of 94Mo

A search for the double beta decay transition of 94Zr into the first excited state of 94Mo has been performed at the Felsenkeller underground laboratory in Dresden, Germany. A 341.1 g zirconium sample with natural isotopic composition has been measured for 43.9 d in an ultra low background gamma spectroscopy setup. No signal has been observed and a new best lower half-life limit is set as 5.2 × 1019 yr (90% CI). This limit is valid for the 0νββ and 2νββ decay into excited states of 94Mo but cannot distinguish between the two modes. Existing limits are improved by 50%.

Fenobody: A Ferritin-Displayed Nanobody with High Apparent Affinity and Half-Life Extension.

Nanobodies consist of a single domain variable fragment of a camelid heavy-chain antibody. Nanobodies have potential applications in biomedical fields because of their simple production procedures and low cost. Occasionally, nanobody clones of interest exhibit low affinities for their target antigens, which, together with their short half-life limit bioanalytical or therapeutic applications. Here, we developed a novel platform we named fenobody, in which a nanobody developed against H5N1 virus is displayed on the surface of ferritin in the form of a 24mer. We constructed a fenobody by substituting the fifth helix of ferritin with the nanobody. TEM analysis showed that nanobodies were displayed on the surface of ferritin in the form of 6 × 4 bundles, and that these clustered nanobodies are flexible for antigen binding in spatial structure. Comparing fenobodies with conventional nanobodies currently used revealed that the antigen binding apparent affinity of anti-H5N1 fenobody was dramatically increased (∼360-fold). Crucially, their half-life extension in a murine model was 10-fold longer than anti-H5N1 nanobody. In addition, we found that our fenobodies are highly expressed in Escherichia coli, and are both soluble and thermo-stable nanocages that self-assemble as 24-polymers. In conclusion, our results demonstrate that fenobodies have unique advantages over currently available systems for apparent affinity enhancement and half-life extension of nanobodies. Our fenobody system presents a suitable platform for various large-scale biotechnological processes and should greatly facilitate the application of nanobody technology in these areas.

Tanshinol borneol ester on nanostructured lipid carriers has longer brain and systemic effector retention and better antioxidant activity in vivo.

BackgroundTanshinol borneol ester (DBZ) is a hybrid of danshensu (DSS) and borneol and has anti-ischemic activity in animals. However, its low water solubility and short half-life limit its clinical application.MethodsWe prepared polyethylene glycol (PEG)-modified and DBZ-loaded nanostructured lipid carriers (DBZ-PEG-NLC) and DBZ-NLC, and examined their physical characteristics, such as particle size, zeta potential, entrapment efficiency and drug loading. The in vitro stability and pharmacokinetics in rats as well as antioxidant activity of DBZ-PEG-NLC and DBZ-NLC in a C57BL/6 mouse model of ischemia/reperfusion-related brain injury were investigated. The levels of DBZ and its hydrolyzed DSS in rat plasma and brain microdialysates were determined by liquid chromatography–mass spectroscopy/mass spectroscopy analysis.ResultsWe found that the mean particle size and entrapment efficacy of DBZ-PEG-NLC were similar to that of DBZ-NLC. The DBZ-PEG-NLC, like DBZ-NLC, released DBZ in a biphasic manner with initially burst release and then prolonged slow release in vitro. Intravenous injection of DBZ-PEG-NLC resulted in significantly higher levels and longer retention periods of DBZ and DSS in plasma and the brains than DBZ-NLC and DBZ in rats. Finally, treatment with DBZ-PEG-NLC achieved a better antioxidant activity than DBZ or DBZ-NLC in mouse model of ischemia/reperfusion by reducing the levels of brain malondialdehyde, but increasing the levels of brain superoxide dismutase and glutathione.ConclusionDBZ-PEG-NLC is a preferable option to deliver DBZ for sustainable release of DSS and borneol in vivo, and may serve as a promising drug for effective therapy of ischemic cardiovascular and cerebrovascular diseases.

GERDA results and the future perspectives for the neutrinoless double beta decay search using 76Ge

The GERmanium Detector Array (GERDA) is a low background experiment at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN designed to search for the rare neutrinoless double beta decay ([Formula: see text]) of [Formula: see text]Ge. In the first phase (Phase I) of the experiment, high purity germanium diodes were operated in a “bare” mode and immersed in liquid argon. The overall background level of [Formula: see text] was a factor of ten better than those of its predecessors. No signal was found and a lower limit was set on the half-life for the [Formula: see text] decay of [Formula: see text]Ge [Formula: see text] yr (90% CL), while the corresponding median sensitivity was [Formula: see text] yr (90% CL). A second phase (Phase II) started at the end of 2015 after a major upgrade. Thanks to the increased detector mass and performance of the enriched germanium diodes and due to the introduction of liquid argon instrumentation techniques, it was possible to reduce the background down to [Formula: see text]. After analyzing 23.2 kg[Formula: see text]⋅[Formula: see text]yr of these new data no signal was seen. Combining these with the data from Phase I a stronger half-life limit of the [Formula: see text]Ge [Formula: see text] decay was obtained: [Formula: see text] yr (90% CL), reaching a sensitivity of [Formula: see text] yr (90% CL). Phase II will continue for the collection of an exposure of 100 kg[Formula: see text]yr. If no signal is found by then the GERDA sensitivity will have reached [Formula: see text] yr for setting a 90% CL. limit. After the end of GERDA Phase II, the flagship experiment for the search of [Formula: see text] decay of [Formula: see text]Ge will be LEGEND. LEGEND experiment is foreseen to deploy up to 1-ton of [Formula: see text]Ge. After ten years of data taking, it will reach a sensitivity beyond 10[Formula: see text] yr, and hence fully cover the inverted hierarchy region.

Searching Neutrinoless Double Beta Decay with Gerda Phase II

An observation of neutrinoless double beta ([Formula: see text]) decay would allow to shed light onto the nature of neutrinos. Gerda (GERmanium Detector Array) aims to discover this process in a background-free search using [Formula: see text]Ge. The experiment is located at the Laboratori Nazionali del Gran Sasso (LNGS) of the Istituto Nazionale di Fisica Nucleare (INFN) in Italy. Bare, isotopically enriched, high purity germanium detectors are operated in liquid argon. Gerda follows a staged approach. In Phase II 35.6 kg of enriched germanium detectors are operated since December 2015. The application of active background rejection methods, such as a liquid argon scintillation light read-out and pulse shape discrimination of germanium detector signals, allows to reduce the background index to the intended level of [Formula: see text] cts/(keV⋅kg⋅yr). No evidence for the [Formula: see text] decay has been found in 23.2 kg⋅yr of Phase II data, and together with data from Phase I the up-to-date most stringent half-life limit for this process in [Formula: see text]Ge has been established, at a median sensitivity of 5.8⋅10[Formula: see text][Formula: see text]yr the 90[Formula: see text]% C.L. lower limit is 8.0⋅10[Formula: see text][Formula: see text]yr.

Discovery of ^{72}Rb: A Nuclear Sandbank Beyond the Proton Drip Line.

In this Letter, the observation of two previously unknown isotopes is presented for the first time: ^{72}Rb with 14 observed events and ^{77}Zr with one observed event. From the nonobservation of the less proton-rich nucleus ^{73}Rb, we derive an upper limit for the ground-state half-life of 81ns, consistent with the previous upper limit of 30ns. For ^{72}Rb, we have measured a half-life of 103(22)ns. This observation of a relatively long-lived odd-odd nucleus, ^{72}Rb, with a less exotic odd-even neighbor, ^{73}Rb, being unbound shows the diffuseness of the proton drip line and the possibility of sandbanks to exist beyond it. The ^{72}Rb half-life is consistent with a 5^{+}→5/2^{-} proton decay with an energy of 800-900keV, in agreement with the atomic mass evaluation proton-separation energy as well as results from the finite-range droplet model and shell model calculations using the GXPF1A interaction. However, we cannot explicitly exclude the possibility of a proton transition between 9^{+}(^{72}Rb)→9/2^{+}(^{71}Kr) isomeric states with a broken mirror symmetry. These results imply that ^{72}Kr is a strong waiting point in x-ray burst rp-process scenarios.

New limits on $2 \varepsilon$ 2 ɛ , $\varepsilon \beta^{+}$ ɛ β + and $2 \beta^{+}$ 2 β + decay of 136Ce and 138Ce with deeply purified cerium sample

A search for double electron capture ($2\varepsilon$), electron capture with positron emission ($\varepsilon\beta^+$), and double positron emission $2\beta^+$) in $^{136}$Ce and $^{138}$Ce was realized with a 465 cm$^3$ ultra-low background HP Ge $\gamma$ spectrometer over 2299 h at the Gran Sasso underground laboratory. A 627 g sample of cerium oxide deeply purified by liquid-liquid extraction method was used as a source of $\gamma$ quanta expected in double $\beta$ decay of the cerium isotopes. New improved half-life limits were set on different modes and channels of double $\beta$ decay of $^{136}$Ce and $^{138}$Ce at the level of $T_{1/2}>10^{17}-10^{18}$ yr.

Search for the decay of nature's rarest isotopeTa180m

$^{\rm {180m}}$Ta is the rarest naturally occurring quasi-stable isotope and the longest lived metastable state which is known. Its possible decay via the $\beta^-$ or the electron capture channel has never been observed. This article presents a search for the decay of $^{\rm {180m}}$Ta with an ultra low background Sandwich HPGe gamma spectrometry setup in the HADES underground laboratory. No signal is observed and improved lower partial half-life limits are set with a Bayesian analysis to $5.8\cdot10^{16}$ yr for the $\beta^-$ channel and $2.0\cdot10^{17}$ yr for the electron capture channel (90% credibility). The total half-life of $^{\rm {180m}}$Ta is longer than $4.5\cdot10^{16}$ yr. This is more than a factor of two improvement compared to previous searches.

New limit for the half-life of double beta decay of 94Zr to the first excited state of 94Mo

Neutrinoless Double Beta Decay is a phenomenon of fundamental interest in particle physics. The decay rates of double beta decay transitions to the excited states can provide input for Nuclear Transition Matrix Element calculations for the relevant two neutrino double beta decay process. It can be useful as supplementary information for the calculation of Nuclear Transition Matrix Element for the neutrinoless double beta decay process. In the present work, double beta decay of $^{94}$Zr to the $2^{+}_{1}$ excited state of $^{94}$Mo at 871.1 keV is studied using a low background $\sim$ 230 cm$^3$ HPGe detector. No evidence of this decay was found with a 232 g.y exposure of natural Zirconium. The lower half-life limit obtained for the double beta decay of $\rm^{94}Zr$ to the $2^{+}_{1}$ excited state of $\rm^{94}Mo$ is $T_{1/2} (0\nu + 2\nu)> 3.4 \times 10^{19}$ y at 90% C.L., an improvement by a factor of $\sim$ 4 over the existing experimental limit at 90\% C.L. The sensitivity is estimated to be $T_{1/2} (0\nu + 2\nu) > 2.0\times10^{19}$ y at 90% C.L. using the Feldman-Cousins method.

High precision half-life measurement of Sm147α decay from thin-film sources

An investigation of the {\alpha}-decay of $^{147}$Sm was performed using an ultra low-background Twin Frisch-Grid Ionisation Chamber (TF-GIC). Four natural samarium samples were produced using pulsed laser deposition in ultra high vacuum. The abundance of the $^{147}$Sm isotope was mea- sured using inductively coupled plasma mass spectrometry. A combined half-life value for 147Sm of $1.079(26)\times{}10^{11}$ years was measured. A search for the {\alpha}-decay into the first excited state of $^{143}$Nd has been performed using $\gamma$-spectroscopy, resulting in a lower half-life limit of $T_{1/2} > 3.1 \times{}10^{18}$ years (at 90% C.L.).

Double beta decays into excited states in 110Pd and 102Pd

A search for double beta decays of and into excited states of the daughter nuclides has been performed using three ultra-low background gamma-spectrometry measurements in the Felsenkeller laboratory, Germany, the HADES laboratory, Belgium and at the LNGS, Italy. The combined Bayesian analysis of the three measurements sets improved half-life limits for the 2νββ and 0νββ decay modes of the , and transitions in to yr, yr and yr, respectively, and in to yr, yr and yr, respectively, with 90% credibility.

Preparation and evaluation of HPMC-based pirfenidone solution in vivo

Context: Pirfenidone (PFD) has exhibited therapeutic potential in the treatment of cell proliferative disorders. The previously developed 0.5% water-based PFD eye drops by our team exhibited antiscarring effectiveness and ocular safety but with a limit of short half-life and poor bioavailability.Objective: To increase bioavailability of the water-based PFD eye drops, we prepared a viscous solution by adding hydroxypropyl methylcellulose (HPMC, F4M), which acted as a viscosity-enhancer. Subsequently, we compared the HPMC-based PFD solution with the water-based PFD eye drops.Materials and methods: PFD solution with 1% HPMC (w/v) was prepared, and the viscosities at different shear rates were measured to investigate its rheology. PFD concentrations in the tear, aqueous humor, conjunctiva, cornea, and sclerae of New Zealand rabbits were detected at different time points with high-performance liquid chromatography (HPLC) following single instillation of the 0.5% PFD (w/v) water-based eye drops or HPMC-based solution.Results: Compared with the 0.5% water-based PFD eye drops, the HPMC-based solution increased the PFD levels in tears and prolonged the residence time from 10 to more than 20 min (p < .01). Consequently, the concentrations of PFD in aqueous humor, conjunctiva, cornea, and sclera were elevated to varying degrees until 90 min after topical administration.Conclusions: The developed formulation possesses a same readily administration and simple preparation as the PFD eye drops; however, the HPMC-based solution exhibited the higher bioavailability.

Multilayer Network Analysis of Nuclear Reactions.

The nuclear reaction network is usually studied via precise calculation of differential equation sets, and much research interest has been focused on the characteristics of nuclides, such as half-life and size limit. In this paper, however, we adopt the methods from both multilayer and reaction networks, and obtain a distinctive view by mapping all the nuclear reactions in JINA REACLIB database into a directed network with 4 layers: neutron, proton, 4He and the remainder. The layer names correspond to reaction types decided by the currency particles consumed. This combined approach reveals that, in the remainder layer, the β-stability has high correlation with node degree difference and overlapping coefficient. Moreover, when reaction rates are considered as node strength, we find that, at lower temperatures, nuclide half-life scales reciprocally with its out-strength. The connection between physical properties and topological characteristics may help to explore the boundary of the nuclide chart.

Host–guest inclusion complexation of β-cyclodextrin and hecogenin acetate to enhance anti-hyperalgesic effect in an animal model of musculoskeletal pain

Abstract Hecogenin acetate (HA), a steroidal acetylated-sapogenin, has an analgesic profile already assigned, but its low water solubility and short half-life limit its use in chronic conditions. β-cyclodextrin (β-CD) can improve the chemical and pharmacological property of nonpolar compounds such as HA. Therefore, a HA complexed with β-CD (HA-CD) was prepared and characterized by thermal, morphological and spectroscopic analysis. A model of chronic musculoskeletal pain was induced by means of two injections of pH 4.0 saline (20 μL) into the left gastrocnemius 5 days apart was used. After confirming hyperalgesia, male mice were treated with HA, HA-CD (20 mg/kg; p.o.) or vehicle (saline 0.9%, p.o.). Motor coordination tests, substance P (SP) levels in a lumbosacral (L4-S2) spinal cord sample and a docking study were equally assessed to check for a possible action on the opioid receptors. Oral pretreatment with HA or HA-CD produced a significant antinociceptive (p

Double electron capture searches in 74Se

A search for various double electron capture modes of 74Se has been performed using an ultralow background Ge-detector in the Felsenkeller laboratory, Germany. Especially for the potentially resonant transition into the 1204.2 keV excited state of 74Ge a lower half-life limit of yr (90% credibility) has been obtained. Serious concerns are raised about the validity of obtained 74Se limits in some recent publications.

Background constrains of the SuperNEMO experiment for neutrinoless double beta-decay searches

The SuperNEMO experiment is a new generation of experiments dedicated to the search for neutrinoless double beta-decay, which if observed, would confirm the existence of physics beyond the Standard Model. It is based on the tracking and calorimetry techniques, which allow the reconstruction of the final state topology, including timing and kinematics of the double beta-decay transition events, offering a powerful tool for background rejection. While the basic detection strategy of the SuperNEMO detector remains the same as of the NEMO-3 detector, a number of improvements were accomplished for each of detector main components. Upgrades of the detector technologies and development of low-level counting techniques ensure radiopurity control of construction parts of the SuperNEMO detector. A reference material made of glass pellets has been developed to assure quality management and quality control of radiopurity measurements. The first module of the SuperNEMO detector (Demonstrator) is currently under construction in the Modane underground laboratory. No background event is expected in the neutrinoless double beta-decay region in 2.5 years of its operation using 7kg of 82Se. The half-life sensitivity of the Demonstrator is expected to be >6.5·1024 y, corresponding to an effective Majorana neutrino mass sensitivity of |0.2−0.4|eV (90% C.L.). The full SuperNEMO experiment comprising of 20 modules with 100kg of 82Se source should reach an effective Majorana neutrino mass sensitivity of |0.04−0.1| eV, and a half-life limit 1·1026 y.

A search for the radiative neutrinoless double-electron capture of 58Ni

A search for the radiative neutrinoless double-electron capture with single γ-ray emission has been performed in 58Ni. Gamma radiation from a nickel sample in natural isotope composition was measured for with an ultra-low background HPGe detector in the Felsenkeller underground laboratory in Dresden, Germany. A new lower half-life limit of yr ( CL) was obtained for this decay mode. This half-life limit is two orders of magnitude higher than the existing limit for 58Ni and among the best half-life limits for neutrinoless double-electron capture decays.