Weldon City Schools

Neural population dynamics during behavior occur across various spatial and temporal scales. Current neural recording methods, however, are primarily acute and do not lend themselves to optimal long-term multimodal recordings with combined high temporal and spatial mapping capabilities. This methodological bottleneck has hindered comprehensive longitudinal studies of neural dynamics. Here, we introduce a novel chronic multimodal platform that enables simultaneous high-density electrophysiological recording and two-photon (2P) calcium imaging over several months. We present a detailed multimodal analysis pipeline to demonstrate the platform's utility in investigating neural dynamics during month-long motor learning, which was previously inaccessible.

<div><p>Immune checkpoint blockade therapy, one of the most promising cancer immunotherapies, has shown remarkable clinical impact in multiple cancer types. Despite the recent success of immune checkpoint blockade therapy, however, the response rates in patients with cancer are limited (∼20%–40%). To improve the success of immune checkpoint blockade therapy, relevant preclinical animal models are essential for the development and testing of multiple combination approaches and strategies. Companion dogs naturally develop several types of cancer that in many respects resemble clinical cancer in human patients. Therefore, the canine studies of immuno-oncology drugs can generate knowledge that informs and prioritizes new immuno-oncology therapy in humans. The challenge has been, however, that immunotherapeutic antibodies targeting canine immune checkpoint molecules such as canine PD-L1 (cPD-L1) have not been commercially available. Here, we developed a new cPD-L1 antibody as an immuno-oncology drug and characterized its functional and biological properties in multiple assays. We also evaluated the therapeutic efficacy of cPD-L1 antibodies in our unique caninized PD-L1 mice. Together, these <i>in vitro</i> and <i>in vivo</i> data, which include an initial safety profile in laboratory dogs, support development of this cPD-L1 antibody as an immune checkpoint inhibitor for studies in dogs with naturally occurring cancer for translational research. Our new therapeutic antibody and caninized PD-L1 mouse model will be essential translational research tools in raising the success rate of immunotherapy in both dogs and humans.</p>Significance:<p>Our cPD-L1 antibody and unique caninized mouse model will be critical research tools to improve the efficacy of immune checkpoint blockade therapy in both dogs and humans. Furthermore, these tools will open new perspectives for immunotherapy applications in cancer as well as other autoimmune diseases that could benefit a diverse and broader patient population.</p></div>

A Modified Pill-shaped ultra-wideband THz antenna is designed with a $45 \mu \mathrm{m}$ thick FR-4 substrate material having a dielectric constant of 4.3. Power from the source is coupled to the patch using a thin microstrip line and a quarterwave transformer. The partial ground plane reduces the back radiations of the antenna and introduces additional reactance which is responsible for wideband response and providing circular polarization over a wide frequency range. The designed antenna offers ultrawideband impedance bandwidth (IMBW) in the frequency range from 0.24THz to 2.1 THz(159 %), axial ratio bandwidth (3-dB $A R B W$) in the frequency range of 0.66THz to 1.6 THz(83.18 %) peak gain 8.17dBi and radiation efficiency approximately 87 %. Due to its compactness and ultrawideband response, this antenna can be used for spectroscopic detection and diagnosis, imaging system, sensing, biomedical imaging, and indoor wireless communication system.

In cell migration, polarization is the process by which a stationary cell breaks symmetry and initiates motion. Although a lot is known about the mechanisms involved in cell polarization, the role played by myosin contraction remains unclear. In addition, cell polarization by mechanical impact has received little attention. Here, we study the influence of myosin activity on cell polarization and the initiation of motion induced by mechanical cues using a computational model for keratocytes. The model accounts for cell deformation, the dynamics of myosin and the signaling protein RhoA (a member of the Rho GTPases family), as well as the forces acting on the actomyosin network. Our results show that the attainment of a steady polarized state depends on the strength of myosin down- or up-regulation and that myosin upregulation favors cell polarization. Our results also confirm the existence of a threshold level for cell polarization, which is determined by the level of polarization of the Rho GTPases at the time the external stimuli vanish. In all, this paper shows that capturing the interactions between the signaling proteins (Rho GTPases for keratocytes) and the compounds of the motile machinery in a moving cell is crucial to study cell polarization.

Extracellular matrix (ECM) mechanical stiffness and its dynamic change is one of the main cues that directly affects the differentiation and proliferation of normal cells as well as the progression of disease processes such as fibrosis and cancer. Recent advancements in biomaterials have enabled a wide range of polymer matrices that could mimic the ECM of different tissues for a wide range of in vitro basic research and drug discovery. However, most of the technologies utilized to quantify the stiffness of such ECM are either destructive or expensive, and therefore are unsuitable for the in situ, long-term monitoring of variations in ECM stiffness for on-chip cell culture applications. This work demonstrates a novel noninvasive on-chip platform for characterization of ECM stiffness in vitro, by monitoring ultrasonic wave attenuation through the targeted material. The device is composed of a pair of millimeter scale ultrasonic transmitter and receiver transducers with the test medium placed in between them. The transmitter generates an ultrasonic wave that propagates through the material, triggers the piezoelectric receiver and generates a corresponding electrical signal. The characterization reveals a linear (r2 = 0.86) decrease in the output voltage of the piezoelectric receiver with an average sensitivity of -15.86 μV kPa-1 by increasing the stiffnesses of hydrogels (from 4.3 kPa to 308 kPa made with various dry-weight concentrations of agarose and gelatin). The ultrasonic stiffness sensing is also demonstrated to successfully monitor dynamic changes in a simulated in vitro tissue by gradually changing the polymerization density of an agarose gel, as a proof-of-concept towards future use for 3D cell culture and drug screening. In situ long-term ultrasonic signal stability and thermal assessment of the device demonstrates its high robust performance even after two days of continuous operation, with negligible (<0.5 °C) heating of the hydrogel in contact with the piezoelectric transducers. In vitro biocompatibility assessment of the device with mammary fibroblasts further assures that the materials used in the platform did not produce a toxic response and cells remained viable under the applied ultrasound signals in the device.

While identifying acute HIV infection is critical to providing prompt treatment to HIV-positive individuals and preventing transmission, existing laboratory-based testing methods are too complex to perform at the point of care. Specifically, molecular techniques can detect HIV RNA within 8–10 days of transmission but require laboratory infrastructure for cold-chain reagent storage and extensive sample preparation performed by trained personnel. Here, we demonstrate our point-of-care microfluidic rapid and autonomous analysis device (microRAAD) that automatically detects HIV RNA from whole blood. Inside microRAAD, we incorporate vitrified amplification reagents, thermally-actuated valves for fluidic control, and a temperature control circuit for low-power heating. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) products are visualized using a lateral flow immunoassay (LFIA), resulting in an assay limit of detection of 100 HIV-1 RNA copies when performed as a standard tube reaction. Even after three weeks of room-temperature reagent storage, microRAAD automatically isolates the virus from whole blood, amplifies HIV-1 RNA, and transports amplification products to the internal LFIA, detecting as few as 3 × 105 HIV-1 viral particles, or 2.3 × 107 virus copies per mL of whole blood, within 90 minutes. This integrated microRAAD is a low-cost and portable platform to enable automated detection of HIV and other pathogens at the point of care.

Complex biomolecules, including carbohydrates, frequently have molecular surface footprints larger than those in broadly utilized standing phase alkanethiol self-assembled monolayers, yet would benefit from structured orientation and clustering interactions promoted by ordered monolayer lattices. Striped phase monolayers, in which alkyl chains extend across the substrate, have larger, more complex lattices: nm-wide stripes of headgroups with 0.5 or 1nm lateral periodicity along the row, separated by wider (∼5 nm) stripes of exposed alkyl chains. These anisotropic interfacial patterns provide a potential route to controlled clustering of complex functional groups such as carbohydrates. Although the monolayers are not covalently bound to the substrate, assembly of functional alkanes containing an internal diyne allows such monolayers to be photopolymerized, increasing robustness. Here, we demonstrate that, with appropriate modifications, microcontact printing can be used to generate well-defined microscopic areas of striped phases of both single-chain and dual-chain amphiphiles (phospholipids), including one (phosphoinositol) with a carbohydrate in the headgroup. This approach generates hierarchical molecular-scale and microscale interfacial clustering of functional ligands, prototyping a strategy of potential relevance for glycobiology.

The development of new active biocompatible materials and devices is a current need for their implementation in multiple fields, including the fabrication of implantable devices for biomedical applications and sustainable devices for bio-optics and bio-optoelectronics. This paper describes a simple strategy to use designed proteins to develop protein-based functional materials. Using simple proteins as self-assembling building blocks as a platform for the fabrication of new optically active materials takes previous work one step further towards the design of materials with defined structures and functions using naturally occurring protein materials, such as silk. The proposed fabrication strategy generates thin and flexible nanopatterned protein films by letting the engineered protein elements self-assemble over the surface of an elastomeric stamp with nanoscale features. These nanopatterned protein films are easily transferred onto 3D objects (flat and curved) by moisture-induced adhesion. Additionally, flexible nanopatterned protein films are prepared by incorporating a thin polymeric layer as a back support. Finally, taking advantage of the tunability of the selected protein scaffold, the flexible protein-based surfaces are endowed with optical functions, achieving efficient lasing features. As such, this work enables the simple and cost-effective production of flexible and nanostructured, protein-based, optically active biomaterials and devices over large areas toward emerging applications.