Characterizing Microfluidic Operations Underlying an Electrowetting Heat Pipe on the International Space Station

Electrowetting heat pipes (EHPs) are a newly conceptualized class of heat pipes, wherein the adiabatic wick section is replaced by electrowetting-based pumping of the condensate (as droplets) to the evaporator. Specific advantages include the ability to transport high heat loads over long distances, low thermal resistance and power consumption, and the absence of moving mechanical parts. In this work, we describe characterization of key microfluidic operations (droplet motion and splitting) underlying the EHP on the International Space Station (ISS). The testing was performed under the Advanced Passive Thermal eXperiment (APTx) project, a project to test a suite of passive thermal control devices funded by the ISS Technology Demonstration Office at NASA JSC (Johnson Space Center). A rapid manufacturing method was used to fabricate the electrowetting device on a printed circuit board. Key device-related considerations were to ensure reliability and package the experimental hardware within a confined space. Onboard the ISS, experiments were conducted to study electrowetting-based droplet motion and droplet splitting, by imaging droplet manipulation operations via pre-programmed electrical actuation sequences. An applied electric field of 36 Volts per micron resulted in droplet speeds approaching 10 millimeters per second. Droplet splitting dynamics were observed and the time required to split droplets was quantified. Droplet motion data was analyzed to estimate the contact line friction coefficient. Overall, this demonstration is the first-ever electrowetting experiment in space. The obtained results are useful for future design of the EHP and other electrowetting-based systems for microgravity applications

Total and Active Rabbit Antithymocyte Globulin (rATG;Thymoglobulin®) Pharmacokinetics in Pediatric Patients Undergoing Unrelated Donor Bone Marrow Transplantation

AbstractRabbit antithymocyte globulin (rATG; Thymoglobulin®) is currently used to prevent or treat graft-versus-host disease (GVHD) during hematopoietic stem cell transplantation (HSCT). The dose and schedule of rATG as part of the preparative regimen for unrelated donor (URD) bone marrow transplantation (BMT) have not been optimized in pediatric patients. We conducted a prospective study of 13 pediatric patients with hematologic malignancies undergoing URD BMT at St. Jude Children's Research Hospital from October 2003 to March 2005, to determine the pharmacokinetics and toxicities of active and total rATG. The conditioning regimen comprised total body irradiation (TBI), thiotepa, and cyclophosphamide (Cy); cyclosporine (CsA) and methotrexate (MTX) were administered as GVHD prophylaxis. Patients received a total dose of 10 mg/kg rATG, and serial blood samples were assayed for total rATG by enzyme linked immunosorbent assay (ELISA) and active rATG by florescein activated cell sorting (FACS). We found that our weight-based dosing regimen for rATG was effective and well tolerated by patients. The half-lives of total and active rATG were comparable to those from previous studies, and despite high doses our patients had low maximum concentrations of active and total rATG. There were no occurrences of grade iii-iv GVHD even in patients having low peak rATG levels, and the overall incidence of grade II GVHD was only 15%. None of the patients had serious infections following transplantation. These data support the use of a 10 mg/kg dose of rATG in children with hematologic malignancies because it can be administered without increasing the risk of graft rejection, or serious infection in pediatric patients with a low rate of GVHD. These conclusions may not apply to patients with nonmalignant disorders

Factuality Challenges in the Era of Large Language Models

The emergence of tools based on Large Language Models (LLMs), such as OpenAI's ChatGPT, Microsoft's Bing Chat, and Google's Bard, has garnered immense public attention. These incredibly useful, natural-sounding tools mark significant advances in natural language generation, yet they exhibit a propensity to generate false, erroneous, or misleading content -- commonly referred to as "hallucinations." Moreover, LLMs can be exploited for malicious applications, such as generating false but credible-sounding content and profiles at scale. This poses a significant challenge to society in terms of the potential deception of users and the increasing dissemination of inaccurate information. In light of these risks, we explore the kinds of technological innovations, regulatory reforms, and AI literacy initiatives needed from fact-checkers, news organizations, and the broader research and policy communities. By identifying the risks, the imminent threats, and some viable solutions, we seek to shed light on navigating various aspects of veracity in the era of generative AI.Comment: Our article offers a comprehensive examination of the challenges and risks associated with Large Language Models (LLMs), focusing on their potential impact on the veracity of information in today's digital landscap

Influenza Virus Non-Structural Protein 1 (NS1) Disrupts Interferon Signaling

Type I interferons (IFNs) function as the first line of defense against viral infections by modulating cell growth, establishing an antiviral state and influencing the activation of various immune cells. Viruses such as influenza have developed mechanisms to evade this defense mechanism and during infection with influenza A viruses, the non-structural protein 1 (NS1) encoded by the virus genome suppresses induction of IFNs-α/β. Here we show that expression of avian H5N1 NS1 in HeLa cells leads to a block in IFN signaling. H5N1 NS1 reduces IFN-inducible tyrosine phosphorylation of STAT1, STAT2 and STAT3 and inhibits the nuclear translocation of phospho-STAT2 and the formation of IFN-inducible STAT1:1-, STAT1:3- and STAT3:3- DNA complexes. Inhibition of IFN-inducible STAT signaling by NS1 in HeLa cells is, in part, a consequence of NS1-mediated inhibition of expression of the IFN receptor subunit, IFNAR1. In support of this NS1-mediated inhibition, we observed a reduction in expression of ifnar1 in ex vivo human non-tumor lung tissues infected with H5N1 and H1N1 viruses. Moreover, H1N1 and H5N1 virus infection of human monocyte-derived macrophages led to inhibition of both ifnar1 and ifnar2 expression. In addition, NS1 expression induces up-regulation of the JAK/STAT inhibitors, SOCS1 and SOCS3. By contrast, treatment of ex vivo human lung tissues with IFN-α results in the up-regulation of a number of IFN-stimulated genes and inhibits both H5N1 and H1N1 virus replication. The data suggest that NS1 can directly interfere with IFN signaling to enhance viral replication, but that treatment with IFN can nevertheless override these inhibitory effects to block H5N1 and H1N1 virus infections

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Enhancing the cooling capacity of heat pipes : wicking in micropillar arrays and electrowetting-based droplet pumping

Thermal management is an important consideration for many technologies, ranging from electronic devices to solar thermal energy. Heat pipes transfer heat by cyclically evaporating and condensing a working fluid, and their main benefits are high thermal conductance and little to no power consumption. In a standard heat pipe, an internal wicking structure utilizes capillary action to drive fluid circulation. Heat transfer capacity is limited by the maximum fluid velocity the wick can sustain, among other factors. Because viscous pressure losses increase with distance, the maximum heat transfer capacity of a heat pipe decreases over extended distances. This work explores two ways to increase the maximum cooling capacity of heat pipes: first, by designing an alternative wicking geometry, and second, by removing the wick entirely and replacing it with electrowetting-based droplet pumping technology. The capillary limit is largely determined by the permeability and driving capillary pressure of the wick. These two factors typically depend on the same geometric parameter, such that the two are inseparable and inversely related. Micropillar arrays are wicking materials where the distances between pillars are independent and variable, which could lead to a decoupled capillary pressure and permeability. The first half of this dissertation work designs, optimizes, manufactures, and tests micropillar wicks for use in a heat pipe. To accomplish this, an analytical model for fluid flow through a micropillar array with independent x- and y- dimensions is developed, enabling the exploration of non-symmetrical pillar arrangements. For pillar dimensions outside of the range of the analytical model, numerical simulations are employed. Using these models, the dimensions of pillar arrays are optimized for maximum fluid flow rate. The findings indicate that arrays where the pillars are arranged in a rectangular pattern exhibit the ability to maintain high capillary pressures even at high porosities, which increases the overall cooling capacity above square arrays by 1.5x in the absence of gravity and 5x – 7x in the presence of gravity. To verify the maximum fluid velocities predicted by modeling, a range of pillar configurations are manufactured and tested. However, conclusions about the fluid velocity are obscured because atmospheric conditions of the experimental apparatus allow the boiling limit to occur before the capillary limit. Electrowetting is a microfluidic pumping technique which operates by applying a voltage across a liquid droplet to change the surface energy balance of the liquid/solid interface. If several electrodes are placed in succession, a discrete droplet can be pulled along a surface. Replacing the internal wick of a heat pipe with an electrowetting system reduces the viscous pressure losses of a long pipe, potentially revolutionizing heat transfer over long distances. The second half of this dissertation work explores the feasibility of replacing the internal wick in a heat pipe with electrowetting-based droplet pumping to create an electrowetting heat pipe (EHP) with water as the working fluid. First-order models show that an EHP with a cross-sectional area of 10 cm x 4 mm can transport 1.6 kW over extended distances (1 m) using only 1.2 mW of power. Compared to three heat pipes and one thermosyphon of similar dimensions, the EHP can transport more than twice the maximum heat capacity of other devices while offering a low thermal resistance of 0.01 K/W, comparable to wicked heat pipes. Compared to pumped microchannel systems of equivalent cooling capacity, the EHP achieves lower thermal resistances than both single- and two-phase pumped microchannels. The EHP offers lower power requirements than a single-phase pumped system and similar power requirements compared to a two-phase system. To experimentally prove the feasibility of an EHP condenser, this work first develops a novel, rapid manufacturing method for an electrowetting droplet pumping platform, then demonstrates droplet generation from an open liquid source. This work therefore constitutes a starting point for the development of a new class of electrically controlled thermal management devices for long-distance heat transport.Chemical Engineerin

Heat pipes with electrical pumping of condensate

A heat pipe with electrical pumping. The heat pipe includes a condenser to condense vapor into liquid droplets and an evaporator for the liquid-vapor conversion. Furthermore, the heat pipe includes liquid conduits for carrying the liquid droplets, where every liquid conduit includes electrodes for moving the liquid droplets along the liquid conduits. Additionally, the heat pipe includes vapor conduits for carrying the vapor. After the liquid is condensed and droplets are formed, they are electrically pumped towards the evaporator by sequentially actuating a series of electrodes in the liquid conduits. By implementing electrical pumping instead of wick-based pumping, the heat transport capacity over long distances is greatly increased. Additionally, since the electrical force is greater than gravity, it is possible to develop orientation independent long heat pipes. Other benefits include planar form factors, noiselessness, high reliability due to the absence of moving mechanical parts and ultralow power consumption.Board of Regents, University of Texas Syste

Interview with Renee Hale (FA 769)

Oral interview with Renee Hale, conducted by Lisa K. Miller on 22 July 2014. This interview was part of the Evelyn Thurman Oral History Project. The audio interview can be accessed by clicking the Download button. This download may take several minutes. A photograph of the interviewee can be accessed by clicking on Additional Files