Tandem Act Research Articles

Solid lipid nanoparticles and nanostructured lipid carriers of dual functionality at emulsion interfaces. Part II: active carrying/delivery functionality

The utilisation of lipid nanostructures that can in tandem act as Pickering emulsion stabilisers and as active carrier/delivery systems, could potentially enable the development of liquid (emulsion-based) formulations with the capacity for multi-active encapsulation and delivery. Part I of this work focused on the first aspect of this two-fold functionality by investigating the capacity of both solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) to act as effective Pickering particles in o/w emulsions. Herein, attention shifts to the secondary functionality, with part II of this study assessing both SLNs and NLCs in terms of their capacity to act as carriers and release regulators for curcumin, a model hydrophobic active. The previously established Pickering functionality and physical properties in terms of particle size, zeta potential and interfacial tension of the lipid particles remained unaffected after encapsulation of curcumin. In emulsions, loss of crystalline (solid lipid) matter and particle interfacial presence were specifically investigated, as these aspects can impact upon the particles’ active carrying and delivery performance. Low solid matter losses were recorded for all emulsions (ranging between 0% and 15%), with increasing liquid lipid fraction in the particles (SLNs to NLCs) resulting in relatively higher depletion of crystallinity. Removal of unadsorbed surfactant (remnant from the particle formation processing step) prior to emulsification led to higher particle interfacial occupancy. Despite said changes, the lipid particles’ curcumin carrying capacity, expressed as encapsulation efficiency and loading capacity, did not differ between an emulsion and dispersion setting. Although the active carrying capacity was retained, it was shown that the presence of the particles at the emulsion interfaces affects the curcumin release rate. Partial migration of curcumin to the oil droplet and creation of an additional release-inducing potential to the particles in close proximity to the droplet interface are proposed to be responsible for the overall faster active expulsion. What is more, the curcumin release profile from either SLNs or NLCs (also) stabilising an emulsion microstructure, was shown to persist after storage; either storage of the particles (up to 4 months) prior to emulsification, or storage of emulsions (up to 3 months) stabilised by ‘freshly’ formed lipid particles. Overall, the present study provides evidence that the two-fold functionality of the lipid particles can be indeed realised, markedly demonstrating that their concurrency does not compromise one another.

Structural insight into the arginine-binding specificity of CASTOR1 in amino acid-dependent mTORC1 signaling.

The mechanistic Target Of Rapamycin Complex 1 (mTORC1) is central to the cellular response to changes in nutrient signals such as amino acids. CASTOR1 is shown to be an arginine sensor, which plays an important role in the activation of the mTORC1 pathway. In the deficiency of arginine, CASTOR1 interacts with GATOR2, which together with GATOR1 and Rag GTPases controls the relocalization of mTORC1 to lysosomes. The binding of arginine to CASTOR1 disrupts its association with GATOR2 and hence activates the mTORC1 signaling. Here, we report the crystal structure of CASTOR1 in complex with arginine at 2.5 Å resolution. CASTOR1 comprises of four tandem ACT domains with an architecture resembling the C-terminal allosteric domains of aspartate kinases. ACT1 and ACT3 adopt the typical βαββαβ topology and function in dimerization via the conserved residues from helices α1 of ACT1 and α5 of ACT3; whereas ACT 2 and ACT4, both comprising of two non-sequential regions, assume the unusual ββαββα topology and contribute an arginine-binding pocket at the interface. The bound arginine makes a number of hydrogen-bonding interactions and extensive hydrophobic contacts with the surrounding residues of the binding pocket. The functional roles of the key residues are validated by mutagenesis and biochemical assays. Our structural and functional data together reveal the molecular basis for the arginine-binding specificity of CASTOR1 in the arginine-dependent activation of the mTORC1 signaling.

Towards a no-lose theorem for naturalness

We derive a phenomenological no-lose theorem for naturalness up to the TeV scale, which applies when quantum corrections to the Higgs mass from top quarks are canceled by perturbative BSM particles (top partners) of similar multiplicity due to to some symmetry. Null results from LHC searches already seem to disfavor such partners if they are colored. Any partners with SM charges and ~TeV masses will be exhaustively probed by the LHC and a future 100 TeV collider. Therefore, we focus on neutral top partners. While these arise in Twin Higgs theories, we analyze neutral top partners as model-independently as possible using EFT and Simplified Model methods. We classify all perturbative neutral top partner structures in order to compute their irreducible low-energy signatures at proposed future lepton and hadron colliders, as well as the irreducible tunings suffered in each scenario. Central to our theorem is the assumption that SM-charged BSM states appear in the UV completion of neutral naturalness, which is the case in all known examples. Direct production at the 100 TeV collider then allows this scale to be probed at the ~10 TeV level. We find that proposed future colliders probe any such scenario of naturalness with tuning of 10% or better. This provides very strong model-independent motivation for both new lepton and hadron colliders, which in tandem act as discovery machines for general naturalness. We put our results in context by discussing other possibilities for naturalness, including "swarms" of top partners, inherently non-perturbative or exotic physics, or theories without SM-charged states in the UV completion. Realizing a concrete scenario which avoids our arguments while still lacking experimental signatures remains an open model-building challenge.

Design and fabrication of spectrally selective TiAlC/TiAlCN/TiAlSiCN/TiAlSiCO/TiAlSiO tandem absorber for high-temperature solar thermal power applications

A new nanostructured TiAlC/TiAlCN/TiAlSiCN/TiAlSiCO/TiAlSiO tandem absorber has been designed for high-temperature solar thermal power applications. The first three layers in this tandem act as an absorbing layer, whereas, TiAlSiCO and TiAlSiO act as semi-transparent and anti-reflecting layers. The tandem absorber was deposited on stainless steel substrates using a four-cathode reactive direct current unbalanced magnetron sputtering system. The composition and thicknesses of the individual component layers have been optimized by adjusting the reactive flow rate of C2H2, N2, O2, and also Al, Ti and Si target power densities to achieve high absorptance (0.961) and low emittance (0.07 at 82°C). The reflectance data showed that the absorptance increases gradually with shift of reflectance minimum to higher wavelengths from first layer to last layer (i.e., TiAlC to TiAlSiO). The thickness of optimized tandem absorber was calculated from the cross-sectional field-emission scanning electron microscopy images and confirmed using transmission electron microscopy. The performance evaluation of the tandem absorber has been evaluated by heating it in air and vacuum under cycling conditions at different temperatures. These results showed that the tandem absorber was stable up to 325°C in air for 400h and up to 650°C in vacuum for 100h, thus demonstrating its suitability for high-temperature solar thermal power generation applications.

Crystal structure of tandem ACT domain‐containing protein ACTP from Galdieria sulphuraria

The ACT domain is a structurally conserved small molecule binding domain which is mostly involved in amino acid and purine metabolism. Here, we report the crystal structure of a tandem ACT domain-containing protein (ACTP) from Galdieria sulphuraria. The two ACTP monomers in the asymmetric unit form a dimer with a non-crystallographic twofold axis in a domain-swapped manner, showing a horseshoe-like structure with a central crevice. This structure contributes to expand our knowledge on the structural diversity of ACT domain-containing proteins.

Did Overzealous Activists Destroy Housing Affordability in San Francisco?

In this article, I use time-series models of construction and price levels in the San Francisco housing market to test claims that implementation of more strict zoning controls restricts housing construction and artificially inflates housing prices. The results do not support these claims. I argue that the primary barrier to new housing construction derives from the interaction of financial market variables, household search behavior, and the unique characteristics of urban land markets that in tandem act to constrain new construction to high-end luxury segments of the local housing market. Increasing the supply of affordable housing in San Francisco will therefore require large-scale public subsidies to compensate for the failure of the market to meet the pressing housing needs of low-to-moderate-income households.

Coherence-tuned interrogation of a remote elliptical-core, dual-mode fiber strain sensor

Two dual-mode fibers in tandem act as unbalanced sensor and recovery interferometers. We investigate how coherence-tuned interrogation of the remote sensor fiber is affected by the coherence properties of the multimode laser diode source and the modal group index difference of the dual-mode fibers. The parameters for optimized sensor performance are ascertained. We focus particularly on the recovery of small optical phase modulations induced by periodic strain. Using homodyne phase tracking, stability of the detected ac signal is achieved to within /spl plusmn/10/sup -3/ in the presence of additional, quasistatic phase drifts of large amplitude. The minimum detectable differential modal phase modulation is 5 /spl mu/rad rms//spl radic/Hz at 70 Hz. As an example, remote interrogation of a piezoelectric quartz high-voltage transducer is demonstrated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>