Core–shell nanostructures: perspectives towards drug delivery applications
Nanosystems have shown encouraging outcomes and substantial progress in the areas of drug delivery and biomedical applications.
Kumar, Raj↗
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Bacterial cellulose nanoparticles as a sustainable drug delivery platform for protein-based therapeutics
BCNPs prepared from a kombucha co-culture can serve as a sustainable delivery platform for protein-based drugs. The amorphous nanoparticles form a mesh-like fibrillar network that is thermally stable and can be produced at scale.
Balistreri, Gabrielle N.↗
The Open High Throughput Computing Content Delivery Network
LHC experiments make extensive use of web proxy caches, especially for software distribution via the CernVM File System and for conditions data via the Frontier Distributed Database Caching system. Since many jobs read the same data, cache hit rates are high and hence most of the traffic flows efficiently over Local Area Networks. However, it is not always possible to have local web caches, particularly for opportunistic cases whereexperiments have little control over site services. The Open High Throughput Computing (HTC) Content Delivery Network (CDN), openhtc.io, aims to address this by using web proxy caches from a commercial CDN provider. Cloudflare provides a simple interface for registering DNS aliases of any web server and does reverse proxy web caching on those aliases. The openhtc.io domain is hosted on Cloudflare's free tier CDN which has no bandwidth limit and makes use of data centers throughout the world, so the average performance for clients is much improved compared to reading from CERN or a Tier 1. The load on WLCG servers is also significantly reduced. WLCG Web Proxy Auto Discovery is used to select local web caches when they are available and otherwise select openhtc.io caching. This paper describes the Open HTC CDN in detail and provides initial results from its use for LHC@Home and USCMS opportunistic computing.
97 MATHEMATICS AND COMPUTING↗
Towards an Intelligent Data Delivery Service
The ATLAS Event Streaming Service (ESS) at the LHC is an approach to preprocess and deliver data for Event Service (ES) that has implemented a fine-grained approach for ATLAS event processing. The ESS allows one to asynchronously deliver only the input events required by ES processing, with the aim to decrease data traffic over WAN and improve overall data processing throughput. A prototype of ESS was developed to deliver streaming events to fine-grained ES jobs. Based on it, an intelligent Data Delivery Service (iDDS) is under development to decouple the "cold format" and the processing format of the data, which also opens the opportunity to include the production systems of other HEP experiments. Here we will at first present the ESS model view and its motivations for iDDS system. Then we will also present the iDDS schema, architecture and the applications of iDDS.
97 MATHEMATICS AND COMPUTING↗
Multiple-robot drug delivery strategy through coordinated teams of microswimmers
Untethered robotic microswimmers are very promising to significantly improve various types of minimally invasive surgeries by offering high accuracy at extremely small scales. A prime example is drug delivery, for which a large number of microswimmers is required to deliver sufficient dosages to target sites. For this reason, the controllability of groups of microswimmers is essential. In this paper, we demonstrate simultaneous control of multiple geometrically similar but magnetically different microswimmers using a single global rotating magnetic field. By exploiting the differences in their magnetic properties, we triggered different swimming behaviors from the microswimmers by controlling the frequency and the strength of the global field, for example, one swim and the other does not while exposed to the same control input. Our results show that the balance between the applied magnetic torque and the hydrodynamic torque can be exploited for simultaneous control of two microswimmers to swim in opposite directions, with different velocities, and with similar velocities. This work will serve to establish important concepts for future developments of control systems to manipulate multiple magnetically actuated microswimmers and a step towards using swarms of microswimmers as viable workforces for complex operations.
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
Utilization of bio-degradable fermented tapioca to synthesized low toxicity of carbon nanotubes for drug delivery applications
Carbon nanotubes (CNT) have potential biomedical applications, and investigations are shifting towards the production of such nanotubes using renewable natural sources. CNTs were synthesized at various temperatures of 700, 750, 800, 850 and 900 °C, respectively, using a local fermented food known as “tapai ubi” or fermented tapioca as a precursor. The liquid part of this fermented food was heated separately at 80°C and channeled directly into the furnace system that employs the thermal chemical vapor deposition (CVD) method. Ferrocene, which was the catalyst was placed in furnace 1 in the thermal CVD process. The resulting CNTs produced from the process were studied using field emission scanning electron microscopy (FESEM) and Raman spectroscopy. The FESEM images showed the growth morphology of the CNTs at the different temperatures employed. It was observed that the higher the synthesis temperature up to a point, the diameter of CNTs produced, after which the diameter increased. CNTs with helical structures were observed at 700 °C with a diameter range of 111 - 143 nm. A more straightened structure was observed at 750 °C with a diameter range of 59 - 121 nm. From 800 °C onwards, the diameters of the CNTs were less than 60 nm. Raman analysis revealed the present of D, G and G’ peak were observed at 1227-1358, 1565-1582, and 2678-2695 cm{sup −1}, respectively. The highest degree of crystallity of the carbon nanotubes synthesized were obtained at 800 °C. The radial breathing mode (RBM) were in range between 212-220 and 279-292 cm{sup −1}. Carbon nanotubes also being functionalized with Polyethylene bis(amine) Mw2000 (PEG 2000-NH2) and showed highly cells viability compared to non-functionalized CNT. The nanotubes synthesized will be applied as drug delivery in future study.
77 NANOSCIENCE AND NANOTECHNOLOGY↗
The system with zwitterionic lactose-based surfactant for complexation and delivery of small interfering ribonucleic acid—A structural and spectroscopic study
Systems suitable for the effective preparation of complexes with siRNA (small interfering RNA) are at the center of interest in the area of research work on the delivery of the RNA-based drugs (RNA-therapeutics). This article presents results of a study on the structural effects associated with siRNA complexation by a surfactant comprising a lactose group (N-(3-propanesulfone)-N-dodecyl-amino-beta-D-lactose hydrochloride, LA12). The double stranded siRNA oligomer (21 base pairs) used in this study is responsible for silencing a gene that can be important in the therapy of myotonic dystrophy type 1. The obtained siRNA/LA12 lipoplexes were studied using the methods of small angle scattering of synchrotron radiation, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, and electrophoretic mobility tests. Lipoplexes form in solution stable lamellar or cubic phases. The surfactant selected for the study shows much lower cytotoxicity and good complexation abilities of siRNA than dicationic or polycationic surfactants.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
Noncontact microsurgery and delivery of substances into stem cells by means of femtosecond laser pulses
We have studied the efficiency of microsurgery of a cell membrane in mesenchymal stem cells and the posterior cell viability under the localised short-time action of femtosecond IR laser pulses aimed at noncontact delivery of specified substances into the cells. (extreme light fields and their applications)
46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
The elaborate route for UDP-arabinose delivery into the Golgi of plants
Significance Nucleotide sugars, the activated sugar donors essential for processes such as cell wall biosynthesis and protein and lipid glycosylation are predominantly made in the cytosol. However, a highly diverse range of glycosyltransferases that are located within the Golgi lumen, mediate the above-mentioned glycosylation reactions. Thus, transport of nucleotide sugars across the Golgi membrane into the lumen is crucial for growth and development of many species including microorganisms, plants, and humans. In this study, we identify and functionally characterize four UDP-arabinofuranose transporters from Arabidopsis that are responsible for the delivery of activated arabinose, a critical sugar of plant cell walls, glycoproteins, and signaling peptides.
59 BASIC BIOLOGICAL SCIENCES↗
A requirement for an active proton delivery network supports a compound I-mediated C–C bond cleavage in CYP51 catalysis
CYP51 enzymes (sterol 14α-demethylases) are cytochromes P450 that catalyze multistep reactions. The CYP51 reaction occurs in all biological kingdoms and is essential in sterol biosynthesis. It removes the 14α-methyl group from cyclized sterol precursors by first forming an alcohol, then an aldehyde, and finally eliminating formic acid with the introduction of a Δ14–15 double bond in the sterol core. The first two steps are typical hydroxylations, mediated by an electrophilic compound I mechanism. The third step, C–C bond cleavage, has been proposed to involve either compound I (i.e. FeO 3+ ) or, alternatively, a proton transfer-independent nucleophilic ferric peroxo anion (compound 0, i.e. Fe 3+ O 2 – ). In this work, using comparative crystallographic and biochemical analyses of WT human CYP51 (CYP51A1) and its D231A/H314A mutant, whose proton delivery network is destroyed (as evidenced in a 1.98-Å X-ray structure in complex with lanosterol), we demonstrate that deformylation of the 14α-carboxaldehyde intermediate requires an active proton relay network to drive the catalysis. These results indicate a unified, compound I-based mechanism for all three steps of the CYP51 reaction, as previously established for CYP11A1 and CYP19A1. We anticipate that our approach can be applied to mechanistic studies of other P450s that catalyze multistep reactions, such as C–C bond cleavage.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
VOLATILE DELIVERY TO PLANETS FROM WATER-RICH PLANETESIMALS AROUND LOW-MASS STARS
Most models of volatile delivery to accreting terrestrial planets assume that the carriers for water are similar in water content to the carbonaceous chondrites in our solar system. Here we consider how the water content of planetesimals may be higher in many planetary systems, as they could lack the short-lived radionuclides that drove water loss in carbonaceous chondrites in our solar system. Using N-body simulations, we explore how planetary accretion would be different if bodies beyond the water line contained a water-mass fraction consistent with chemical equilibrium calculations, and more similar to comets, as opposed to the more traditional water-depleted values. We apply this model to consider planet formation around stars of different masses and identify trends in the properties of habitable zone planets and planetary system architecture that could be tested by ongoing exoplanet census data collection. Comparison of such data with the model-predicted trends will serve to evaluate how well the N-body simulations and the initial conditions used in studies of planetary accretion can be used to understand this stage of planet formation.
79 ASTRONOMY AND ASTROPHYSICS↗
Magnetic properties of γ-Fe 2 O 3 nanoparticles in a porous SiO 2 shell for drug delivery
A method is presented for synthesizing core–shell nanoparticles with a magnetic core and a porous shell suitable for drug delivery and other medical applications. The core contains multiple γ -Fe 2 O 3 nanoparticles (~15 nm) enclosed in a SiO 2 (~100–200 nm) matrix using either methyl (denoted TMOS- γ -Fe 2 O 3 ) or ethyl (TEOS- γ -Fe 2 O 3 ) template groups. Low-temperature Mössbauer spectroscopy showed that the magnetic nanoparticles have the maghemite structure, γ -Fe 2 O 3 , with all the vacancies in the octahedral sites. Saturation magnetization measurements revealed that the density of γ -Fe 2 O 3 was greater in the TMOS- γ -Fe 2 O 3 nanoparticles than TEOS- γ -Fe 2 O 3 nanoparticles, presumably because of the smaller methyl group. Magnetization measurements showed that the blocking temperature is around room temperature for the TMOS- γ -Fe 2 O 3 and around 250 K for the TEOS- γ -Fe 2 O 3 . Three dimensional topography analysis shows clearly that the magnetic nanoparticles are not only at the surface but have penetrated deep in the silica to form the core–shell structure.
Physics↗
Beam delivery and final focus systems for multi-TeV advanced linear colliders
The Beam Delivery System (BDS) is a critical component of a high-energy linear collider. It transports the beam from the accelerator and brings it to a focus at the Interaction Point. The BDS system includes diagnostic sections for measuring the beam energy, emittance, and polarization, as well as collimators for machine protection. The length of the BDS increases with collision energy. Higher collision energies also require higher luminosities, and this is a significant constraint on the design for energy-frontier machines. Here, we review BDS designs based on traditional quadrupole magnets and examine the challenges involved in extending these to the Multi-TeV regime consistent with requirements for advanced accelerator concepts.
43 PARTICLE ACCELERATORS↗
Beam delivery and beamstrahlung considerations for ultra-high energy linear colliders
As part of the Snowmass'21 community planning excercise, the Advanced Accelerator Concepts (AAC) community proposed future linear colliders with center-of-mass energies up to 15 TeV and luminosities up to 50 × 1034 cm -2 s -1 in a compact footprint. In addition to being compact, these machines must also be energy efficient. We identify two challenges that must be addressed in the design of these machines. First, the Beam Delivery System (BDS) must not add significant length to the accelerator complex. Second, beam parameters must be chosen to mitigate beamstrahlung effects and maximize the luminosity-per-power of the machine. In this paper, we review advances in plasma lens technology that will help to reduce the length of the BDS system, and we detail new Particle-in-Cell simulation studies that will provide insight into beamstrahlung mitigation techniques. We apply our analysis to both $e$ + $e$ - and $γγ$ colliders. The challenges and solutions described in this paper are considered independently. In conclusion, a unified, self-consistent concept for a BDS system for a 15 TeV linear collider will be the subject of future work.
47 OTHER INSTRUMENTATION↗
High voltage delivery and distribution for the NEXT-100 Time Projection Chamber
A critical element in the realization of large liquid andgas time projection chambers (TPCs) is the delivery and distributionof high voltages into and around the detector. Such experimentsrequire of order tens of kilovolts to enable electron drift overmeter-scale distances. This paper describes the design andoperation of the cathode feedthrough and high voltage distributionthrough the field cage of the NEXT-100 experiment, an undergroundTPC that will search for neutrinoless double beta decay0νββ. The feedthrough has been demonstrated to holdpressures up to 20 bar and sustain voltages as high as -65 kV.The TPC is operating stably at its design high voltages. The systemhas been realized within the constraints of a stringent radiopuritybudget and is now being used to execute a suite of sensitive doublebeta decay analyses.
Adams, C. [Argonne]↗
Extracellular Matrix-Inspired Growth Factor Delivery Systems for Skin Wound Healing
Blood vessel growth plays a key role in regenerative medicine, both to restore blood supply to ischemic tissues and to ensure rapid vascularization of clinical-size tissue-engineered grafts. For example, vascular endothelial growth factor (VEGF) is the master regulator of physiological blood vessel growth and is one of the main molecular targets of therapeutic angiogenesis approaches. However, angiogenesis is a complex process and there is a need to develop rational therapeutic strategies based on a firm understanding of basic vascular biology principles, as evidenced by the disappointing results of initial clinical trials of angiogenic factor delivery. In particular, the spatial localization of angiogenic signals in the extracellular matrix (ECM) is crucial to ensure the proper assembly and maturation of new vascular structures. Here, we discuss the therapeutic implications of matrix interactions of angiogenic factors, with a special emphasis on VEGF, as well as provide an overview of current approaches, based on protein and biomaterial engineering that mimic the regulatory functions of ECM to optimize the signaling microenvironment of vascular growth factors.
59 BASIC BIOLOGICAL SCIENCES↗
Heritable, multinucleotide deletions in plants using viral delivery of a repair exonuclease and guide RNAs
Abstract CRISPR/Cas9-mediated mutagenesis typically results in short insertion/deletion mutations, which are often too small to disrupt the function of cis-acting regulatory elements. Here, we describe a highly efficient in planta gene editing approach called VirTREX2-HLDel that achieves heritable multinucleotide deletions in both protein-coding genes and noncoding DNA regulatory elements. VirTREX2-HLDel uses RNA viruses to deliver both the 3 prime repair exonuclease 2 (TREX2) and single-guide RNAs. Our method enables recovery of multiplexed heritable deletions and increases the heritable gene editing frequency at poorly edited sites. We identified functional conservation and divergence of MICRORNA164 (miR164) in Nicotiana benthamiana and tomato (Solanum lycopersicum) using VirTREX2-HLDel and observed previously uncharacterized phenotypes in plants with large deletions at this locus. Our viral delivery method reduces the need for tissue culture and will accelerate the understanding of protein-coding and regulatory regions in plants.
59 BASIC BIOLOGICAL SCIENCES↗
5G Service Value Chain and Network Slicing Framework using Ecosystem Modeling, Agile Delivery, and User-Story Automation
The 5G technology allows telecommunication operators to provide services beyond data broadband for consumers, employing tailored use-cases for enterprise and vertical markets. As a result, there is an increasing need for a collaborative service development through a de-centralized value-chain, along with new business models and shorter time-to-market. In this paper, a novel, use-case driven framework for a modular 5G service design and delivery is proposed. The framework implements agile and as-a-service principles to provide 5G use-case customers access not only to service usage, but also to design and operation. The framework integrates with the 3rd Generation Partnership Project (3GPP) specifications by mapping network-slicing procedures to the designed ecosystem lifecycle operations. The framework allows for any-technology deployment, utilizing the available foundations for domain-specific automation. A structured collaboration between a 5G operator and a use-case user allows for the customization and improvement of the targeted use-case, where 5G network assets are updated with customer’s vertical components through programmable user-stories. Laboratory testing of a 5G network-slicing for a private-telephony and merchandise-tracking service is performed to validate the effectiveness of the proposed approach for real-world applications.
97 MATHEMATICS AND COMPUTING↗