The 5f localization/delocalization in square and hexagonal americium monolayers: A FP-LAPW electronic structure study

The electronic and geometrical properties of bulk americium and square and hexagonal americium monolayers have been studied with the full-potential linearized augmented plane wave (FP-LAPW) method. The effects of several common approximations are examined: (1) non-spin polarization (NSP) vs. spin polarization (SP); (2) scalar-relativity (no spin-orbit coupling (NSO)) vs. full-relativity (i.e., with spin-orbit (SO) coupling included); (3) local-density approximation (LDA) vs. generalized-gradient approximation (GGA). Our results indicate that both spin polarization and spin orbit coupling play important roles in determining the geometrical and electronic properties of americium bulk and monolayers. A compression of both americium square and hexagonal monolayers compared to the americium bulk is also observed. In general, the LDA is found to underestimate the equilibrium lattice constant and give a larger total energy compared to the GGA calculations. While spin orbit coupling shows a similar effect on both square and hexagonal monolayer calculations regardless of the model, GGA versus LDA, an unusual spin polarization effect on both square and hexagonal monolayers is found in the LDA results as compared with the GGA results. The 5f delocalization transition of americium is employed to explain our observed unusual spin polarization effect. In addition, our results at the LDA level of theory indicate a possible 5f delocalization could happen in the americium surface within the same Am II (fcc crystal structure) phase, unlike the usually reported americium 5f delocalization which is associated with crystal structure change. The similarities and dissimilarities between the properties of an Am monolayer and a Pu monolayer are discussed in detail.Comment: 22 pages, 8 figure

Microscopic theory of quadrupolar ordering in TmTe

We have calculated the crystal electric field of TmTe (T>T_Q) and have obtained that the ground state of a Tm 4f hole is the $\Gamma_7$ doublet in agreement with Mossbauer experiments. We study the quadrupole interactions arising from quantum transitions of 4f holes of Tm. An effective attraction is found at the L point of the Brillouin zone, $\vec{q}_L$. Assuming that the quadrupolar condensation involves a single arm of $\vec{q}_L$ we show that there are two variants for quadrupole ordering which are described by the space groups C2/c and C2/m. The Landau free energy is derived in mean-field theory. The phase transition is of second order. The corresponding quadrupole order parameters are combinations of $T_{2g}$ and $E_g$ components. The obtained domain structure is in agreement with observations from neutron diffraction studies for TmTe. Calculated lattice distortions are found to be different for the two variants of quadrupole ordering. We suggest to measure lattice displacements in order to discriminate between those two structures.Comment: 10 pages, 2 figures, 5 tables; accepted by PR

Investigation of localized delivery of diclofenac sodium from poly(D,L-lactic acid-co-glycolic acid)/ poly(ethylene glycol) scaffolds using an in vitro osteoblast inflammation model

Nonunion fractures and large bone defects are significant targets for osteochondral tissue engineering strategies. A major hurdle in the use of these therapies is the foreign body response of the host. Herein, we report the development of a bone tissue engineering scaffold with the ability to release anti-inflammatory drugs, in the hope of evading this response. Porous, sintered scaffolds composed of poly(D,L-lactic acid-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) were prepared with and without the anti-inflammatory drug diclofenac sodium. Analysis of drug release over time demonstrated a profile suitable for the treatment of acute inflammation with ∼80% of drug released over the first 4 days and a subsequent release of around 0.2% per day. Effect of drug release was monitored using an in vitro osteoblast inflammation model, comprised of mouse primary calvarial osteoblasts stimulated with proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Levels of inflammation were monitored by cell viability and cellular production of nitric oxide (NO) and prostaglandin E2 (PGE2). The osteoblast inflammation model revealed that proinflammatory cytokine addition to the medium reduced cell viability to 33%, but the release of diclofenac sodium from scaffolds inhibited this effect with a final cell viability of ∼70%. However, releasing diclofenac sodium at high concentrations had a toxic effect on the cells. Proinflammatory cytokine addition led to increased NO and PGE2 production; diclofenac-sodium-releasing scaffolds inhibited NO release by ∼64% and PGE2 production by ∼52%, when the scaffold was loaded with the optimal concentration of drug. These observations demonstrate the potential use of PLGA/PEG scaffolds for localized delivery of anti-inflammatory drugs in bone tissue engineering applications

Pharmacokinetics of Teriparatide (rhPTH[1–34]) and Calcium Pharmacodynamics in Postmenopausal Women with Osteoporosis

Teriparatide (rhPTH[1–34]) affects calcium metabolism in a pattern consistent with the known actions of endogenous parathyroid hormone (PTH). This report describes the pharmacokinetics and resulting serum calcium response to teriparatide in postmenopausal women with osteoporosis. Pharmacokinetic samples for this analysis were obtained from 360 women who participated in the Fracture Prevention Trial. Postmenopausal women with osteoporosis received daily subcutaneous injections of either teriparatide 20 μg (4.86 μmol) or placebo, median 21 months’ treatment. Serum teriparatide and calcium concentrations were measured throughout the study. An indirect-response model was developed to describe the pharmacokinetic–pharmacodynamic relationship between teriparatide concentrations and serum calcium response. The pharmacokinetics of teriparatide were characterized by rapid absorption (maximum concentration achieved within 30 min) and rapid elimination (half-life of 1 h), resulting in a total duration of exposure to the peptide of approximately 4 h. Teriparatide transiently increased serum calcium, with the maximum effect observed at approximately 4.25 h (median increase 0.4 mg/dl [0.1 mmol/l]). Calcium concentrations returned to predose levels by 16–24 h after each dose. Persistent hypercalcemia was not observed; one teriparatide 20 μg-treated patient had a predose serum calcium value above the normal range but <11.0 mg/dl (2.75 mmol/l). Following once-daily subcutaneous administration, teriparatide produces a modest but transient increase in serum calcium, consistent with the known effects of endogenous PTH on mineral metabolism. The excursion in serum calcium is brief, due to the short length of time that teriparatide concentrations are elevated

Numerical methods for the design and description of in vitro expansion processes of human mesenchymal stem cells

Human mesenchymal stem cells (hMSCs) are a valuable source of cells for clinical applications (e.g., treatment of acute myocardial infarction or inflammatory diseases), especially in the field of regenerative medicine. However, for autologous (patient-specific) and allogeneic (off-the-shelf) hMSC-based therapies, in vitro expansion is necessary prior to the clinical application in order to achieve the required cell numbers. Safe, reproducible, and economic in vitro expansion of hMSCs for autologous and allogeneic therapies can be problematic because the cell material is restricted and the cells are sensitive to environmental changes. It is beneficial to collect detailed information on the hydrodynamic conditions and cell growth behavior in a bioreactor system, in order to develop a so called “Digital Twin” of the cultivation system and expansion process. Numerical methods, such as Computational Fluid Dynamics (CFD) which has become widely used in the biotech industry for studying local characteristics within bioreactors or kinetic growth modelling, provide possible solutions for such tasks. In this review, we will present the current state-of-the-art for the in vitro expansion of hMSCs. Different numerical tools, including numerical fluid flow simulations and cell growth modelling approaches for hMSCs, will be presented. In addition, a case study demonstrating the applicability of CFD and kinetic growth modelling for the development of an microcarrier-based hMSC process will be shown

Scale-up of an intensified bioprocess for the expansion of bovine adipose-derived stem cells (bASCs) in stirred tank bioreactors

Cultivated meat is an emerging field, aiming to establish the production of animal tissue for human consumption in an in vitro environment, eliminating the need to raise and slaughter animals for their meat. To realise this, the expansion of primary cells in a bioreactor is needed to achieve the high cell numbers required. The aim of this study was to develop a scalable, microcarrier based, intensified bioprocess for the expansion of bovine adipose-derived stem cells as precursors of fat and muscle tissue. The intensified bioprocess development was carried out initially in spinner flasks of different sizes and then translated to fully controlled litre scale benchtop bioreactors. Bioprocess intensification was achieved by utilising the previously demonstrated bead-to-bead transfer phenomenon and through the combined addition of microcarrier and medium to double the existing surface area and working volume in the bioreactor. Choosing the optimal time point for the additions was critical in enhancing the cell expansion. A significant fold increase of 114.19 ± 1.07 was obtained at the litre scale in the intensified bioprocess compared to the baseline (**p < .005). The quality of the cells was evaluated pre- and post-expansion and the cells were found to maintain their phenotype and differentiation capacity

Novel probes for pH and dissolved oxygen measurements in cultivations from millilitre to benchtop scale

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)pH value and the concentration of dissolved oxygen (DO) are key parameters to monitor and control cell growth in cultivation studies. Reliable, robust and accurate methods to measure these parameters in cultivation systems in real time guarantee high product yield and quality. This mini-review summarises the current state of the art of pH and DO sensors that are applied to bioprocesses from millilitre to benchtop scale by means of a short introduction on measuring principles and selected applications. Special emphasis is placed on single-use bioreactors, which have been increasingly employed in bioprocess development and production in recent years. Working principles, applications and the particular requirements of sensors in these cultivation systems are given. In such processes, optical sensors for pH and DO are often preferred to electrochemical probes, as they allow semi-invasive measurements and can be miniaturised to micrometre scale or lower. In addition, selected measuring principles of novel sensing technologies for pH and DO are discussed. These include solid-state sensors and miniaturised devices that are not yet commercially available, but show promising characteristics for possible use in bioprocesses in the near future