Enhancement of osteoblast activity on nanostructured NiTi/hydroxyapatite coatings on additive manufactured NiTi metal implants by nanosecond pulsed laser sintering

Background: The osteoinductive behaviors of nitinol (NiTi)-based metal implants for bone regeneration are largely dependent on their surface composition and topology. Continuous-mode laser sintering often results in complete melting of the materials and aggregation of particles, which lack control of heat transfer, as well as microstructural changes during sintering of the nanocomposite materials. Methods: In the current study, in situ direct laser deposition was used to additively manufacture three-dimensional NiTi structures from Ni and Ti powders. The mechanical property of NiTi has been shown to be similar to bone. Nanosecond pulsed laser sintering process was then utilized to generate a nanoporous composite surface with NiTi alloy and hydroxyapatite (HA) by ultrafast laser heating and cooling of Ni, Ti, and HA nanoparticles mixtures precoated on the 3D NiTi substrates; HA was added in order to improve the biocompatibility of the alloy. We then studied the underlying mechanism in the formation of NiTi/HA nanocomposite, and the synergistic effect of the sintered HA component and the nanoporous topology of the composite coating. In addition, we examined the activity of bone-forming osteoblasts on the NiTi/HA surfaces. For this, osteoblast cell morphology and various biomarkers were examined to evaluate cellular activity and function. Results: We found that the nanoscale porosity delivered by nanosecond pulsed laser sintering and the HA component positively contributed to osteoblast differentiation, as indicated by an increase in the expression of collagen and alkaline phosphatase, both of which are necessary for osteoblast mineralization. In addition, we observed topological complexities which appeared to boost the activity of osteoblasts, including an increase in actin cytoskeletal structures and adhesion structures. Conclusion: These findings demonstrate that the pulsed laser sintering method is an effective tool to generate biocompatible coatings in complex alloy-composite material systems with desired composition and topology. Our findings also provide a better understanding of the osteoinductive behavior of the sintered nanocomposite coatings for use in orthopedic and bone regeneration applications

The role of pre-university education in the development of human capital

The role of education has evolved and undergone paradigm shifts, from that which focuses purely on imparting knowledge to the present one which encompasses career development of individuals to fulfil the needs of the global job market. The question that begs an answer is when (at what stage of education) does the aspect of career development or vocational awareness become significant, and how can educators better equip students at this stage? Looking at the developmental needs of young learners ? primary and secondary levels ? a broadbased curriculum approach is necessary in order to develop the academic aptitude, learning skills and create the body of knowledge necessary for the students to make the right choice in pursuing their tertiary or professional studies and perhaps disciplines of personal interests as well. Hence, we believe that pre-university level education has significant impact on shaping ?what? and ?how? students decide with regards to their career choices and this consequently impinges on the development of human capital in the country. This paper will document paradigm shifts that have taken place over time that have led to the present global trends, and review some critical thoughts and issues arising within the context of developing human capital in Malaysia. The national agenda for manpower development as outlined by the government shall also be considered. This paper will attempt to highlight the important role pre-university education can play in the development of employable graduates within the Malaysian context

ScanNet++: A High-Fidelity Dataset of 3D Indoor Scenes

We present ScanNet++, a large-scale dataset that couples together capture of high-quality and commodity-level geometry and color of indoor scenes. Each scene is captured with a high-end laser scanner at sub-millimeter resolution, along with registered 33-megapixel images from a DSLR camera, and RGB-D streams from an iPhone. Scene reconstructions are further annotated with an open vocabulary of semantics, with label-ambiguous scenarios explicitly annotated for comprehensive semantic understanding. ScanNet++ enables a new real-world benchmark for novel view synthesis, both from high-quality RGB capture, and importantly also from commodity-level images, in addition to a new benchmark for 3D semantic scene understanding that comprehensively encapsulates diverse and ambiguous semantic labeling scenarios. Currently, ScanNet++ contains 460 scenes, 280,000 captured DSLR images, and over 3.7M iPhone RGBD frames.Comment: ICCV 2023. Video: https://youtu.be/E6P9e2r6M8I , Project page: https://cy94.github.io/scannetpp

DropIT: Dropping Intermediate Tensors for Memory-Efficient DNN Training

A standard hardware bottleneck when training deep neural networks is GPU memory. The bulk of memory is occupied by caching intermediate tensors for gradient computation in the backward pass. We propose a novel method to reduce this footprint - Dropping Intermediate Tensors (DropIT). DropIT drops min-k elements of the intermediate tensors and approximates gradients from the sparsified tensors in the backward pass. Theoretically, DropIT reduces noise on estimated gradients and therefore has a higher rate of convergence than vanilla-SGD. Experiments show that we can drop up to 90% of the intermediate tensor elements in fully-connected and convolutional layers while achieving higher testing accuracy for Visual Transformers and Convolutional Neural Networks on various tasks (e.g. classification, object detection).Our code and models are available at https://github.com/chenjoya/dropitComment: 16 pages. DropIT can save memory & improve accuracy, providing a new perspective of dropping in activation compressed training than quantizatio

Exploring Membrane Binding Targets of Disordered Human Tau Aggregates on Lipid Rafts Using Multiscale Molecular Dynamics Simulations

The self-aggregation of tau, a microtubule-binding protein, has been linked to the onset of Alzheimer’s Disease. Recent studies indicate that the disordered tau aggregates, or oligomers, are more toxic than the ordered fibrils found in the intracellular neurofibrillary tangles of tau. At present, details of tau oligomer interactions with lipid rafts, a model of neuronal membranes, are not known. Using molecular dynamics simulations, the lipid-binding events, membrane-damage, and protein folding of tau oligomers on various lipid raft surfaces were investigated. Tau oligomers preferred to bind to the boundary domains (Lod) created by the coexisting liquid-ordered (Lo) and liquid-disordered (Ld) domains in the lipid rafts. Additionally, stronger binding of tau oligomers to the ganglioside (GM1) and phosphatidylserine (PS) domains, and subsequent protein-induced lipid chain order disruption and beta-sheet formation were detected. Our results suggest that GM1 and PS domains, located exclusively in the outer and inner leaflets, respectively, of the neuronal membranes, are specific membrane domain targets, whereas the Lod domains are non-specific targets, of tau oligomers binding to neurons. The molecular details of these specific and non-specific tau bindings to lipid rafts may provide new insights into understanding membrane-associated tauopathies leading to Alzheimer’s Disease

Counting of enzymatically amplified affinity reactions in hydrogel particle-templated drops.

Counting of numerous compartmentalized enzymatic reactions underlies quantitative and high sensitivity immunodiagnostic assays. However, digital enzyme-linked immunosorbent assays (ELISA) require specialized instruments which have slowed adoption in research and clinical labs. We present a lab-on-a-particle solution to digital counting of thousands of single enzymatic reactions. Hydrogel particles are used to bind enzymes and template the formation of droplets that compartmentalize reactions with simple pipetting steps. These hydrogel particles can be made at a high throughput, stored, and used during the assay to create ∼500 000 compartments within 2 minutes. These particles can also be dried and rehydrated with sample, amplifying the sensitivity of the assay by driving affinity interactions on the hydrogel surface. We demonstrate digital counting of β-galactosidase enzyme at a femtomolar detection limit with a dynamic range of 3 orders of magnitude using standard benchtop equipment and experiment techniques. This approach can faciliate the development of digital ELISAs with reduced need for specialized microfluidic devices, instruments, or imaging systems

Quantitative Multi-Parametric Evaluation of Centrosome Declustering Drugs: Centrosome Amplification, Mitotic Phenotype, Cell Cycle and Death

Unlike normal cells, cancer cells contain amplified centrosomes and rely on centrosome clustering mechanisms to form a pseudobipolar spindle that circumvents potentially fatal spindle multipolarity (MP). Centrosome clustering also promotes lowgrade chromosome missegregation, which can drive malignant transformation and tumor progression. Putative ‘centrosome declustering drugs’ represent a cancer cell-specific class of chemotherapeutics that produces a common phenotype of centrosome declustering and spindle MP. However, differences between individual agents in terms of efficacy and phenotypic nuances remain unexplored. Herein, we have developed a conceptual framework for the quantitative evaluation of centrosome declustering drugs by investigating their impact on centrosomes, clustering, spindle polarity, cell cycle arrest, and death in various cancer cell lines at multiple drug concentrations over time. Surprisingly, all centrosome declustering drugs evaluated in our study were also centrosome-amplifying drugs to varying extents. Notably, all declustering drugs induced spindle MP, and the peak extent of MP positively correlated with the induction of hypodiploid DNA-containing cells. Our data suggest acentriolar spindle pole amplification as a hitherto undescribed activity of some declustering drugs, resulting in spindle MP in cells that may not have amplified centrosomes. In general, declustering drugs were more toxic to cancer cell lines than non-transformed ones, with some exceptions. Through a comprehensive description and quantitative analysis of numerous phenotypes induced by declustering drugs, we propose a novel framework for the assessm