Short Communication: Flexure delicacies

Flexures are nowadays enjoying a new boom in numerous high-precision and extreme-environment applications. The paper presents some delicate issues concerning stiffness compensation, large reduction ratios, as well as rectilinear and circular movements in compliant mechanisms. Novel concrete technical solutions to these well-known issues are described, giving a glimpse into the vast and still largely unexploited potential of flexure mechanisms manufactured by wire-electrical-discharge machining

Device for converting a first motion into a second motion responsive to said first motion under a demagnification scale

The present invention discloses a device (CD) for converting a first motion (x s ) into a second motion ( y) responsive to said first movement (x s ) under a demagnification scale (i), comprising: a) an input portion (IP) being drivable in a rectilinear translation in a first direction (x) by an actuator (AC) causing said first motion (x s ); b) an output portion (OP) being movable by a converting blade (CB) causing said second motion ( y) responsive to said first motion (x s ) in a second direction (y) substantially perpendicular to said first direction (x); and c) a converting section (CS) connecting said input portion (IP) to said output portion (OP); said converting section (CS) comprising an intermediate spring portion (ITP) and the converting blade (CB), c1) wherein said intermediate spring portion (ITP) comprises at least two parallel flexure blades (FB1, FB2); and c2) wherein said converting blade (CB) being substantially identical in shape to the a least two parallel flexure blades (FB1, FB2) and being offset from its neutral position by a predetermined amount (x 0 ) in the first direction (x) as compared to the neutral position of the at least two parallel flexure blades (FB1, FB2). This device has a flexure-based structure that allows combining the advantages of classical actuators with accuracies in the micrometer range and the advantages of flexures to achieve nanometer accuracy

Preclinical challenges for developing long acting intravitreal medicines

The majority of blinding conditions arise due to chronic pathologies in the retina. During the last two decades, antibody-based medicines administered by intravitreal injection directly into the back of the eye have revolutionised the treatment of chronic retinal diseases characterised by uncontrolled blood vessel growth, e.g. wet age-related macular degeneration (wAMD), diabetic retinopathy (DR) and choroidal neovascularisation. Although intravitreal injections have become a commonly performed ophthalmic procedure that provides a reproducible dose to maximise drug exposure in the back of the eye, there is a need to minimise the frequency and cumulative number of intravitreal injections. Developing longer-acting intraocular therapies is one key strategy that is being pursued. Pharmaceutical preclinical development of intraocular medicines is heavily reliant on the use of animal models to determine ocular tolerability, pharmacokinetics, biodistribution and drug stability. Animal eyes are different from human eyes, such as the anatomy, organisation of vitreous macromolecular structure, aqueous outflow and immune response; all which impacts the ability to translate preclinical data into a clinical product. The development of longer acting protein formulations using animals is also limited because animals reject human proteins. Preclinical strategies also do not account for differences in the vitreous due to ageing and whether a vitrectomy has been performed. Intraocular formulations must reside and clear from the vitreous body, so there is a need for the formulation scientist to have knowledge about vitreous structure and physiology to facilitate preclinical development strategies. Preclinical pharmaceutical development paradigms used to create therapies for other routes of administration (e.g. oral and intravenous) are grounded on the use of preclinical in vitro models. Analogous pharmaceutical strategies with appropriately designed in vitro models that can account for intraocular mass transfer to estimate pharmacokinetic profiles can be used to develop in vitro-in vivo correlations (IVIVCs) to accelerate the preclinical optimisation of long acting intraocular formulations. Data can then inform preclinical in vivo and clinical studies. With the now widespread use of intravitreal injections, it has also important early in preclinical studies to ensure there is a viable regulatory pathway for new therapies. Knowledge of these factors will help in the development of long acting intravitreal medicines, which is rapidly evolving into a distinct pharmaceutical discipline

Correcteur d'isochromisme pour échappement horloger et échappement muni d'un tel correcteur

The present invention provides an image forming apparatus (210) as well as a developing cartridge (240) for use in an image forming apparatus, wherein a contact plate of an electrode (247) of the developing catridge is disposed to contact a bias terminal (258) coupled to a first wall (251a) of a drum unit (250) when the developing cartridge is installed in a developing cartridge installation portion (250a), and wherein a position where the electrode contacts the bias terminal when the developing cartridge is installed in a developing cartridge installation portion is inside an outer shape of the driven coupling (248a1) when viewed in a direction of the developing roller shaft (244a)

Gravity insensitive flexure pivots for watch oscillators

Classical pivots have frictional losses leading to the limited quality factor of oscillators used as time bases in mechanical watches. Flexure pivots address these issues by greatly reducing friction. However, they have drawbacks such as gravity sensitivity and limited angular stroke. This paper analyses these problems for the cross-spring flexure pivot and presents an improved version addressing these issues. We first show that the cross spring pivot cannot be both insensitive to gravity and have a long stroke. A 10 ppm sensitivity to gravity acceptable for watchmaking applications occurs only when the leaf springs cross at about 87.3 % of their length, but the stroke is only 30.88 % of the stroke of the symmetrical cross-spring pivot. For the symmetrical pivot, gravity sensitivity is of the order of 104 ppm. Our solution is to introduce the co-differential concept which we show to be gravity insensitive. We then use the co-differential to build a gravity insensitive flexure pivot with long stroke. The design consists of a main rigid body, two co-differentials and a torsional beam. We show that our pivot is gravity insensitive and achieves 100 % of the stroke of symmetrical pivots

Effects of communication and utility-based decision making in a simple model of evacuation

We present a simple cellular automaton based model of decision making during evacuation. Evacuees have to choose between two different exit routes, resulting in a strategic decision making problem. Agents take their decisions based on utility functions, these can be revised as the evacuation proceeds, leading to complex interaction between individuals and to jamming transitions. The model also includes the possibility to communicate and exchange information with distant agents, information received may affect the decision of agents. We show that under a wider range of evacuation scenarios performance of the model system as a whole is optimal at an intermediate fraction of evacuees with access to communication.Comment: 9 pages, 9 figure

Hydrodynamics of Intravitreal Injections into Liquid Vitreous Substitutes

Intravitreal injections have become the cornerstone of retinal care and one of the most commonly performed procedures across all medical specialties. The impact of hydrodynamic forces of intravitreal solutions when injected into vitreous or vitreous substitutes has not been well described. While computational models do exist, they tend to underestimate the starting surface area of an injected bolus of a drug. Here, we report the dispersion profile of a dye bolus (50 µL) injected into different vitreous substitutes of varying viscosities, surface tensions, and volumetric densities. A novel 3D printed in vitro model of the vitreous cavity of the eye was designed to visualize the dispersion profile of solutions when injected into the following vitreous substitutes-balanced salt solution (BSS), sodium hyaluronate (HA), and silicone oils (SO)-using a 30G needle with a Reynolds number (Re) for injection ranging from approximately 189 to 677. Larger bolus surface areas were associated with faster injection speeds, lower viscosity of vitreous substitutes, and smaller difference in interfacial surface tensions. Boluses exhibited buoyancy when injected into standard S1000. The hydrodynamic properties of liquid vitreous substitutes influence the initial injected bolus dispersion profile and should be taken into account when simulating drug dispersion following intravitreal injection at a preclinical stage of development, to better inform formulations and performance