Liquidia Technologies (United States)

Large language models (LLMs) are increasingly applied in medical documentation and have been proposed for clinical decision support. We argue that the future for LLMs in medicine must be based on transparent and controllable open-source models. Openness enables medical tool developers to control the safety and quality of underlying AI models, while also allowing healthcare professionals to hold these models accountable. For these reasons, the future is open.

Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year. Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes. Instead of using whole-virus formulations, we are exploring the potentials for a particulate subunit vaccine, based on DENV E-protein displayed on nanoparticles that have been precisely molded using Particle Replication in Non-wetting Template (PRINT) technology. Here we describe immunization studies with a DENV2-nanoparticle vaccine candidate. The ectodomain of DENV2-E protein was expressed as a secreted recombinant protein (sRecE), purified and adsorbed to poly (lactic-co-glycolic acid) (PLGA) nanoparticles of different sizes and shape. We show that PRINT nanoparticle adsorbed sRecE without any adjuvant induces higher IgG titers and a more potent DENV2-specific neutralizing antibody response compared to the soluble sRecE protein alone. Antigen trafficking indicate that PRINT nanoparticle display of sRecE prolongs the bio-availability of the antigen in the draining lymph nodes by creating an antigen depot. Our results demonstrate that PRINT nanoparticles are a promising platform for delivering subunit vaccines against flaviviruses such as dengue and Zika.

<div class="section abstract"><div class="htmlview paragraph">The demand for lighter, smaller, more efficient, and more powerful engines calls for a rethinking of the traditional internal combustion engine (ICE). This paper describes development progress of LiquidPiston's small rotary engine, the XMv3, which operates on a Spark-Ignited (SI) variant of its patented High Efficiency Hybrid Cycle (HEHC). This thermodynamic cycle, which combines high compression ratio (CR), constant-volume combustion, and overexpansion, has a theoretical efficiency of up to 75 percent using air-standard assumptions and first-law analysis. XMv3 displaces 70cc (23cc per each of three working chambers) and is gasoline fueled. The engine is simple, having only two primary moving parts, which are balanced to prevent vibration. The ‘X’ engine geometry utilized by XMv3 can be considered an inverted ‘Wankel’, retaining the traditional Wankel' rotary advantages of high power density and smooth operation, while also overcoming some of Wankel's inherent performance limitations. These include inflexible combustion chamber shape, and lubrication and emissions challenges. At this stage of development, XMv3 produces 3.2 bhp at 10,000 rpm and weighs 1.7 kg. Indicated mean effective pressure (IMEP) and friction mean effective pressure (FMEP) are 5.0 bar and 1.0 bar respectively. The maximum tested engine speed is 15,000 rpm. Preliminary durability studies show no wear problems after 1 hour of running continuously at full load. This paper details both analytical and experimental studies carried out on the XMV3 prototype, including variation of compression ratio, combustion chamber shape, spark plug type, rotor port geometry, and supercharging. With further development, the engine is expected to produce 5 horsepower at up to 15,000 rpm, weighing in at < 1.5 kg. <figure id="F1" class="figure"><div class="graphic-wrapper"><img class="article-figure figure" src="2015-32-0719_fig0001.jpg" alt="XMv3 (left) and XMv2 (right) comparison"/></div><span class="label">Figure 1</span><figcaption class="caption"><span class="title">XMv3 (left) and XMv2 (right) comparison</span></figcaption></figure></div></div>

The top‐down, micromolding technique, referred to as Particle Replication in Nonwetting Templates (PRINT®), affords a new opportunity for the generation of inhalation therapeutics. Powders were fabricated with predetermined particle size and shape; when dispersed with a collision jet nebulizer, these particles resulted in monodisperse aerosols with geometric standard deviations well below 1.2. Dynamic shape factors for this novel set of uniformly shaped particles were determined by correcting the drag of nonspherical particles in the ultra‐Stokesian flow conditions of the aerodynamic particle sizer (APS). This convenient approach for shape factor determination agreed well with current literature approaches and allowed for the correction of APS results for particles with known volumes. Determined shape factor values of PRINT geometries were used to estimate the theoretical median aerodynamic diameters of individual aerosols, which were then compared to actual inhalation powders. © 2013 American Institute of Chemical Engineers AIChE J, 59: 3184–3194, 2013

Precision patterned optical films are key components of today's display technologies, serving as brightness enhancement films, diffuser films and patterned light guides, to name a few. In recent years, much attention has been given to methodologies for patterning optical films with nanoscale precision at the scale and economics required by the Flat Panel Display industry. With this work, we report a platform technology, Pattern Replication In Non-Wetting Templates (PRINT®), for polymer-tool based manufacturing of patterned optical films for the display industry. By using Fluorocur® mold materials, the PRINT® (Pattern Replication In Nonwetting Template) technology enables low cost manufacturing of precise micro and nanoscale features with single nanometer precision from virtually any material.

Elastomeric perfluoropolyether molds are applied to pattern arrays of sub-500 nm inorganic oxide features. This versatile soft-lithography technique can be used to pattern a wide range of materials; in this work inorganic oxides including TiO2 , SnO2 , ZnO, ITO, and BaTiO3 are patterned on a variety of substrates with different aspect ratios. An example of TiO2 posts is shown in the figure.