32 research outputs found
Holographic tracking and sizing of optically trapped microprobes in diamond anvil cells
We demonstrate that Digital Holographic Microscopy can be used for accurate 3D tracking and sizing of a colloidal probe trapped in a diamond anvil cell (DAC). Polystyrene beads were optically trapped in water up to Gigapascal pressures while simultaneously recording in-line holograms at 1 KHz frame rate. Using Lorenz-Mie scattering theory to fit interference patterns, we detected a 10% shrinking in the beadâs radius due to the high applied pressure. Accurate bead sizing is crucial for obtaining reliable viscosity measurements and provides a convenient optical tool for the determination of the bulk modulus of probe material. Our technique may provide a new method for pressure measurements inside a DAC
The very long range nature of capillary interactions in liquid films
Micron-sized objects confined in thin liquid films interact through forces
mediated by the deformed liquid-air interface. This capillary interactions
provide a powerful driving mechanism for the self-assembly of ordered
structures such as photonic materials or protein crystals. Direct probing of
capillary interactions requires a controlled force field to independently
manipulate small objects while avoiding any physical contact with the
interface. We demonstrate how optical micro-manipulation allows the direct
measurement of capillary interactions between two micron sized spheres in a
free standing liquid film. The force falls off as an inverse power law in
particles separation. We derive and validate an explicit expression for this
exponent whose magnitude is mainly governed by particles size. For micron-sized
objects we found an exponent close to, but smaller than one, making capillary
interactions a unique example of strong and very long ranged forces in the
mesoscopic world
A transition to stable one-dimensional swimming enhances E. coli motility through narrow channels
Living organisms often display adaptive strategies that allow them to move efficiently even in strong confinement. With one single degree of freedom, the angle of a rotating bundle of flagella, bacteria provide one of the simplest examples of locomotion in the living world. Here we show that a purely physical mechanism, depending on a hydrodynamic stability condition, is responsible for a confinement induced transition between two swimming states in E. coli. While in large channels bacteria always crash onto confining walls, when the cross section falls below a threshold, they leave the walls to move swiftly on a stable swimming trajectory along the channel axis. We investigate this phenomenon for individual cells that are guided through a sequence of micro-fabricated tunnels of decreasing cross section. Our results challenge current theoretical predictions and suggest effective design principles for microrobots by showing that motility based on helical propellers provides a robust swimming strategy for exploring narrow spaces
Synthesis and biological evaluation of phosphonated dihydroisoxazole nucleosides
Phosphonated isoxazolinyl nucleosides have been prepared via 1,3-dipolar cycloaddition reaction of nitrile oxides with
corresponding vinyl or allyl nucleobases for antiviral studies. The cytotoxicity, the anti-HSV activity and the RT-inhibitory activity
of the obtained compounds were evaluated and compared with those of AZT and diethyl{(10SR,40RS)-10-[[(5-methyl-2,4-dioxo-3,4-
dihydropyrimidin-1(2H)-yl)]-30-methyl-20-oxa-30-azacyclopent-40-yl]}methylphosphonate, a saturated phosphonated dihydroisoxazole
nucleoside analogue
A transition to stable one-dimensional swimming enhances E. coli motility through narrow channels
Living organisms often display adaptive strategies that allow them to move efficiently even in strong confinement. With one single degree of freedom, the angle of a rotating bundle of flagella, bacteria provide one of the simplest examples of locomotion in the living world. Here we show that a purely physical mechanism, depending on a hydrodynamic stability condition, is responsible for a confinement induced transition between two swimming states in E. coli. While in large channels bacteria always crash onto confining walls, when the cross section falls below a threshold, they leave the walls to move swiftly on a stable swimming trajectory along the channel axis. We investigate this phenomenon for individual cells that are guided through a sequence of micro-fabricated tunnels of decreasing cross section. Our results challenge current theoretical predictions and suggest effective design principles for microrobots by showing that motility based on helical propellers provides a robust swimming strategy for exploring narrow spaces. © 2020, The Author(s)
Synthesis of phosphonated carbocyclic 2 '-oxa-3 '-aza-nucleosides: Novel inhibitors of reverse transcriptase
Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides have been synthesized in good yields by 1,3-dipolar cycloaddition methodology. The cytotoxicity and the reverse transcriptase inhibitory activity of the obtained compounds have been investigated. Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides, while showing low levels of cytotoxicity, exert a specific inhibitor activity on two different reverse transcriptases, which is comparable with that of AZT, opening new perspectives on their possible use as therapeutic agents, in anti-retroviral and anti-HBV chemotherapy
Four-directional stereo-microscopy for 3D particle tracking with real-time error evaluation
High-speed video stereo-microscopy relies on illumination from two distinct angles to create two views of a sample from different directions. The 3D trajectory of a microscopic object can then be reconstructed using parallax to combine 2D measurements of its position in each image. In this work, we evaluate the accuracy of 3D particle tracking using this technique, by extending the number of views from two to four directions. This allows us to record two independent sets of measurements of the 3D coordinates of tracked objects, and comparison of these enables measurement and minimisation of the tracking error in all dimensions. We demonstrate the method by tracking the motion of an optically trapped microsphere of 5 ÎŒm in diameter, and find an accuracy of 2â5 nm laterally, and 5â10 nm axially, representing a relative error of less than 2.5% of its range of motion in each dimension
Haloarchaea swim slowly for optimal chemotactic efficiency in low nutrient environments
Archaea have evolved to survive in some of the most extreme environments on earth. Life in extreme, nutrient-poor conditions gives the opportunity to probe fundamental energy limitations on movement and response to stimuli, two essential markers of living systems. Here we use three-dimensional holographic microscopy and computer simulations to reveal that halophilic archaea achieve chemotaxis with power requirements one hundred-fold lower than common eubacterial model systems. Their swimming direction is stabilised by their flagella (archaella), enhancing directional persistence in a manner similar to that displayed by eubacteria, albeit with a different motility apparatus. Our experiments and simulations reveal that the cells are capable of slow but deterministic chemotaxis up a chemical gradient, in a biased random walk at the thermodynamic limit
Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer
Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies