To enhance the strength-to-weight ratio of a material, one may try to either improve the strength or lower the density, or both. The lightest solid materials have a density in the range of 1,000 kg/m ...³; only cellular materials, such as technical foams, can reach considerably lower values. However, compared with corresponding bulk materials, their specific strength generally is significantly lower. Cellular topologies may be divided into bending- and stretching-dominated ones. Technical foams are structured randomly and behave in a bending-dominated way, which is less weight efficient, with respect to strength, than stretching-dominated behavior, such as in regular braced frameworks. Cancellous bone and other natural cellular solids have an optimized architecture. Their basic material is structured hierarchically and consists of nanometer-size elements, providing a benefit from size effects in the material strength. Designing cellular materials with a specific microarchitecture would allow one to exploit the structural advantages of stretching-dominated constructions as well as size-dependent strengthening effects. In this paper, we demonstrate that such materials may be fabricated. Applying 3D laser lithography, we produced and characterized micro-truss and -shell structures made from alumina–polymer composite. Size-dependent strengthening of alumina shells has been observed, particularly when applied with a characteristic thickness below 100 nm. The presented artificial cellular materials reach compressive strengths up to 280 MPa with densities well below 1,000 kg/m ³.
In 1903, Alexander Graham Bell developed a design principle to generate lightweight, mechanically robust lattice structures based on triangular cells; this has since found broad application in ...lightweight design. Over one hundred years later, the same principle is being used in the fabrication of nanolattice materials, namely lattice structures composed of nanoscale constituents. Taking advantage of the size‐dependent properties typical of nanoparticles, nanowires, and thin films, nanolattices redefine the limits of the accessible material‐property space throughout different disciplines. Herein, the exceptional mechanical performance of nanolattices, including their ultrahigh strength, damage tolerance, and stiffness, are reviewed, and their potential for multifunctional applications beyond mechanics is examined. The efficient integration of architecture and size‐affected properties is key to further develop nanolattices. The introduction of a hierarchical architecture is an effective tool in enhancing mechanical properties, and the eventual goal of nanolattice design may be to replicate the intricate hierarchies and functionalities observed in biological materials. Additive manufacturing and self‐assembly techniques enable lattice design at the nanoscale; the scaling‐up of nanolattice fabrication is currently the major challenge to their widespread use in technological applications.
Nanolattices are highly ordered three‐dimensional architectures composed of nanoscale constituents, and have, in the recent past, redefined the limits of the accessible material‐property space throughout different disciplines. The exceptional mechanical properties of nanolattices, including their ultrahigh strength, damage tolerance, and stiffness, are reviewed, and their potential for multifunctional applications beyond mechanics, relevant fabrication methods, and future directions are discussed.
Introduction
A retrospective observational study of the short‐term efficacy and safety of using glue embolization, namely n‐butyl‐2‐cyanoacrylate (NBCA), in bronchial artery embolization (BAE) and ...comparison with the literature. The main aim of the study is to display the safety of this embolic material through standardization of interventional procedure for consideration of NBCA as a possible primary embolic agent in cases of BAE.
Methods
A total of 35 BAE was performed in 31 patients with acute haemoptysis after failure of bronchoscopic therapy using NBCA. The mean age was 56 years with 22 male patients. Pre‐interventional bronchoscopy and computed tomographic angiography were performed. In 35 cases, embolization was performed exclusively with NBCA. One patient in combination with coils and one with particles and coils. The 1:4 NBCA‐to‐Lipiodol mixture was most commonly used. Post‐interventional bronchoscopy was performed after 24 h.
Results
Technical success was possible in all cases. Clinical success was achieved in 94.3%. There was a mortality rate of 6.5% within 48 h. No other embolization related major complications were noticed. A minor complication of temporary ischaemia of the bronchial mucosa. No reperfusion of the embolized vessel, however with rebleeding in four patients from different primarily not embolized bronchial arteries.
Conclusion
Despite previous concerns about its safety based on previous reports and in line with recent studies, we conclude that NBCA is a safe and effective embolic agent to perform BAE in cases of acute haemoptysis if performed according to a clear standard operating procedure as described with a possible superiority over embolic agents. Further blinded prospective comparative studies are necessary.
Though beam-based lattices have dominated mechanical metamaterials for the past two decades, low structural efficiency limits their performance to fractions of the Hashin-Shtrikman and Suquet upper ...bounds, i.e. the theoretical stiffness and strength limits of any isotropic cellular topology, respectively. While plate-based designs are predicted to reach the upper bounds, experimental verification has remained elusive due to significant manufacturing challenges. Here, we present a new class of nanolattices, constructed from closed-cell plate-architectures. Carbon plate-nanolattices are fabricated via two-photon lithography and pyrolysis and shown to reach the Hashin-Shtrikman and Suquet upper bounds, via in situ mechanical compression, nano-computed tomography and micro-Raman spectroscopy. Demonstrating specific strengths surpassing those of bulk diamond and average performance improvements up to 639% over the best beam-nanolattices, this study provides detailed experimental evidence of plate architectures as a superior mechanical metamaterial topology.
Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it ...has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires.
Suspected osteopathology in chronically ill children often necessitates the assessment of bone mineral density. The most frequently used methods are dual-energy X-ray-absorption (DXA) and peripheral ...quantitative computed tomography (pQCT). The BoneXpert software provides an automated radiogrammatic method to assess skeletal age from digitalized X-rays of the left hand. Furthermore, the program calculates the Bone Health Index (BHI), a measure of cortical thickness and mineralization, which is obtained from indices of three metacarpal bones. In our study, we analyzed the manner in which BHI information provided by BoneXpert compares with DXA or pQCT measurements in youths.
The BHI was retrospectively obtained using digitalized X-rays of the left hand and compared with the results of 203 corresponding DXA readings (Lunar Prodigy, GE Healthcare) of the lumbar vertebrae and femur as well as 117 pQCT readings (XCT 900, Stratec) of the distal radius.
The BHI values showed a strong positive correlation with the DXA readings at each and all lumbar vertebrae (L1 -L4: r = 0.73; P < 0.0001). The age-adjusted Z-score of L1 -L4 and the height-adjusted score showed a positive correlation with the BHI-SDS (standard deviation score, r = 0.23; P < 0.002 and r = 0.27; P < 0.001, respectively). Total bone mineral density, as assessed via pQCT, also positively correlated with the BHI (r = 0.39; P < 0.0001), but the trabecular values displayed only a weak correlation.
The BHI obtained using BoneXpert can be a useful parameter in the assessment of bone health in children in most cases. This technique provides observer-independent information on cortical thickness and mineralization based on X-ray imaging of the hands.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Biomedical applications require substrata that allow for the grafting, colonization and control of eukaryotic cells. Currently available materials are often limited by insufficient possibilities for ...the integration of biological functions and means for tuning the mechanical properties. We report on tailorable nanocomposite materials in which silica nanoparticles are interwoven with carbon nanotubes by DNA polymerization. The modular, well controllable and scalable synthesis yields materials whose composition can be gradually adjusted to produce synergistic, non-linear mechanical stiffness and viscosity properties. The materials were exploited as substrata that outperform conventional culture surfaces in the ability to control cellular adhesion, proliferation and transmigration through the hydrogel matrix. The composite materials also enable the construction of layered cell architectures, the expansion of embryonic stem cells by simplified cultivation methods and the on-demand release of uniformly sized stem cell spheroids.
The transition process from paediatric/adolescent to adult medical care settings is of utmost importance for the future health of adolescents with chronic diseases and poses even more difficulties in ...the context of rare diseases (RDs). Paediatric care teams are challenged to deliver adolescent-appropriate information and structures. Here we present a structured transition pathway which is patient-focused and adoptable for different RDs.
The transition pathway for adolescents 16 years and older was developed and implemented as part of a multi-centre study in 10 university hospitals in Germany. Key elements of the pathway included: assessment of patients' disease-related knowledge and needs, training/educational and counselling sessions, a structured epicrisis and a transfer appointment jointly with the paediatric and adult specialist. Specific care coordinators from the participating university hospitals were in charge of organization and coordination of the transition process.
Of a total of 292 patients, 286 completed the pathway. Deficits in disease-specific knowledge were present in more than 90% of participants. A need for genetic or socio-legal counselling was indicated by > 60%. A mean of 2.1 training sessions per patient were provided over a period of almost 1 year, followed by the transfer to adult care in 267 cases. Twelve patients remained in paediatric care as no adult health care specialist could be identified. Targeted training and counselling resulted in improved disease-specific knowledge and contributed to empowering of patients.
The described transition pathway succeeds to improve health literacy in adolescents with RDs and can be implemented by paediatric care teams in any RD specialty. Patient empowerment was mainly achieved by individualized training and counselling.
The DNAJB1-PRKACA fusion transcript is the oncogenic driver in fibrolamellar hepatocellular carcinoma, a lethal disease lacking specific therapies. This study reports on the identification, ...characterization, and immunotherapeutic application of HLA-presented neoantigens specific for the DNAJB1-PRKACA fusion transcript in fibrolamellar hepatocellular carcinoma. DNAJB1-PRKACA-derived HLA class I and HLA class II ligands induce multifunctional cytotoxic CD8
and T-helper 1 CD4
T cells, and their cellular processing and presentation in DNAJB1-PRKACA expressing tumor cells is demonstrated by mass spectrometry-based immunopeptidome analysis. Single-cell RNA sequencing further identifies multiple T cell receptors from DNAJB1-PRKACA-specific T cells. Vaccination of a fibrolamellar hepatocellular carcinoma patient, suffering from recurrent short interval disease relapses, with DNAJB1-PRKACA-derived peptides under continued Poly (ADP-ribose) polymerase inhibitor therapy induces multifunctional CD4
T cells, with an activated T-helper 1 phenotype and high T cell receptor clonality. Vaccine-induced DNAJB1-PRKACA-specific T cell responses persist over time and, in contrast to various previous treatments, are accompanied by durable relapse free survival of the patient for more than 21 months post vaccination. Our preclinical and clinical findings identify the DNAJB1-PRKACA protein as source for immunogenic neoepitopes and corresponding T cell receptors and provide efficacy in a single-patient study of T cell-based immunotherapy specifically targeting this oncogenic fusion.
Immunotherapeutic approaches, including allogeneic stem cell transplantation and donor lymphocyte infusion, have significantly improved the prognosis of leukemia patients. Further efforts are now ...focusing on the development of immunotherapies that are able to target leukemic cells more specifically, comprising monoclonal antibodies, chimeric antigen receptor (CAR) T cells, and dendritic cell- or peptide-based vaccination strategies. One main prerequisite for such antigen-specific approaches is the selection of suitable target structures on leukemic cells. In general, the targets for anti-cancer immunotherapies can be divided into two groups: (1) T-cell epitopes relying on the presentation of peptides via human leukocyte antigen (HLA) molecules and (2) surface structures, which are HLA-independently expressed on cancer cells. This review discusses the most promising tumor antigens as well as the underlying discovery and selection strategies for the development of anti-leukemia immunotherapies.
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