gebhart/patrepeval huggingface dataset:
265 Empowering iPSC-derived iNK cells with multiple gene edits to improve persistence and anti-tumor efficacy (2022)

<h3>Background</h3> A unique attribute of iPSCs is the ability to perform sequential gene edits thus enabling development of highly engineered cell therapies. Here, we describe our next generation platform for iPSC-derived NK cells (iNK cells) that include genetic enhancements for improved allo-evasion, cell fitness, tumor targeting, in vivo imaging, and safety. By adopting a common progenitor strategy, an engineered iPSC master cell bank will be used as the starting point for future therapies across diverse indications. <h3>Methods</h3> Clinical grade iPSC lines were engineered using Mad7 CRISPR endonuclease. β2 microglobulin was disrupted and a bicistronic transgene encoding both HLA-E and HLA-G was inserted. The gene encoding CIITA was disrupted and a bicistronic transgene encoding HSV-TK and PSMA ectodomain was inserted. A transgene encoding IL-15/IL-15Ra was delivered into the NKG2A locus, and a bicistronic transgene encoding CD16 and NKG2D was delivered into the CD70 locus. <h3>Results</h3> iNK cells exhibited uniform expression of each transgene. Functional studies demonstrated that HLA-E/G enabled evasion of allogenic NK cells; IL-15/IL-15RA enhanced persistence of iNK cells both in vitro and in vivo; PSMA expression on the cell surface was confirmed through binding of a PSMA-specific fluorescent tracer; HSV-TK enabled the elimination of iNK cells in culture in the presence of ganciclovir; NKG2D enhanced elimination of tumor lines expressing the stress ligands MICA/MICB; and high-affinity CD16 enabled ADCC-mediated killing of CD20-expressing target cells in the presence of rituximab. HLA-A/B/C, HLA-DR/DP/DQ, NKG2A, and CD70 were absent from iNK cells. <h3>Conclusions</h3> A clonal iPSC line was derived with eleven total genetic modifications to improve allogeneic cell therapy for cancer. Future iNK cell therapies will be derived from the common progenitor by addition of a CAR(s) for indication-specific tumor targeting.
A cost effective PoP structure with high I/O density (2014)

Package-on-package (PoP) structure is widely used in smart phones and tablets in which memory package is directly attached to the top of the application processor. As the market demands more speed and bandwidth, memory devices need more than 1000 I/Os to support future requirements. However← since the package size also becomes smaller and smaller, finer I/O pitch is absolutely required. Although using some new technology can achieve finer I/O pitch, it increases the manufacturing cost. Using traditional mature technology can reduce manufacturing cost, but has limitation in finer I/O pitch. So, it demands a reasonable balance between design, process and cost to develop an applicable PoP structure. In this paper we proposed a novel and cost effective PoP interconnection structure and a multi-layer PoP model. The PoP interconnection was formed by the solder ball on the top package connected to the solder bumps on the bottom package. The solder bump was made of a smaller solder ball attached on a Cu stud bump on the top of bottom substrate. The Cu stud bump was made through wire bonding machines and was coined so that the small solder ball can be attached to it. Using film assist molding technology, a half of the solder ball is exposed outside of molding compound, which can be connected with the solder ball of the top package through reflow process. This PoP interconnection structure was named solder bump through molding (BTM). A three layer PoP vehicle package was designed in our experiments. The top package was a wire bonding BGA, the middle and bottom packages were both flip chip BGA with BTM interconnection structure. The package size of these three packages was 10×10mm2 and ball pitch was 0.4mm. The assembly process of top package was as normal as other wire bonding BGA. The assembly processes of middle and bottom packages were as follows: The Cu stud bumps were first bonded to the top surface of the substrate using wire bonding machines. Small solder balls were attached to the top of Cu stud bumps using stencil tool and then reflowed. After solder bumps were made, all chips were flip bonded to the substrates. Then, using film assist molding and MUF technology, the chips were encapsulated and Cu stud bumps were half exposed. After all the packages were ready, the package stacking and reflow was performed one by one from top to the bottom and the overall three layer PoP was formed. C-scan test and cross section analysis showed that the encapsulation had no voids in most samples. Electrical test results showed the interconnection was good. Reliability study will be also discussed in this paper, which is still in research now. In BTM structure, both Cu stud and solder ball attach can be easily realized. The ball pitch can be 0.4mm or smaller and the process is also applicable for more layer PoP. Thus, BTM PoP structure provides a good solution considering the balance among cost, performance and manufacturing for 3D package. Acknowledgments The authors acknowledge the support of National Science and Technology Major Project (Project numberï¼š2013ZX02501003).
Solder self-alignment for optical MEMS (2003)

This paper discusses the use of solder self-alignment to assemble novel three-dimensional MEMS and package MEMS with other optical devices with precision alignment. Soldering is a predominant technology for electronics assembly, and is being developed for optoelectronic passive alignment. Using solder, hundreds or thousands of precision alignments can be accomplished with a single batch reflow process, and the cost/alignment can be reduced by orders of magnitude.
A Comparison of Drug Delivery into Skin Using Topical Solutions, Needle Injections and Jet Injections (2019)

Abstract Drug diffusion within the skin with a needle-free micro-jet injection (NFI) device was compared with two well-established delivery methods: topical application and solid needle injection. A permanent make-up (PMU) machine, normally used for dermal pigmentation, was utilized as a solid needle injection method. For NFIs a continuous wave (CW) laser diode was used to create a bubble inside a microfluidic device containing a light absorbing solution. Each method delivered two different solutions into ex-vivo porcine skin. The first solution consisted of a red dye (direct red 81) and rhodamine B in water. The second solution was direct red 81 and rhodamine B in water and glycerol. For PMU experiments, the skin samples were kept stationary and the diffusion depth, width and surface area were measured. The NFI has a higher vertical dispersion velocity of 3 × 10 5 μm /s compared to topical (0.1 μm/s) and needle injection (53 μm /s). The limitations and advantages of each method are discussed, and we conclude that the micro-jet injector represents a fast and minimally invasive injection method, while the solid needle injector causes notably tissue damage. In contrast, the topical method had the slowest diffusion rate but causes no visible damage to the skin.
Dietary approaches to the prevention of food allergy (2008)

Although there is evidence for the primary dietary prevention of eczema and possible respiratory allergies, data on food allergy prevention have, so far, remained less convincing. Further prospective research is needed to clarify the effectiveness of dietary interventions in primary food allergy prevention.
Utilizing nonlinear behavior of microbubbles in medical ultrasound (2007)

Abstract Microbubbles exposed to ultrasound exhibit extremely nonlinear conspicuous behaviors. Medical imaging makes wide use of the pulse inversion method, in which only this nonlinear component is extracted by adding the received signals obtained by sending the phase inverted ultrasonic pulses twice. Further, there have been research efforts to use this nonlinear behavior for sonochemical healing of tumors by the efficient generation of acoustic cavitation by illumination with the second harmonic superimposed on the fundamental wave. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 90(8): 63–69, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/ecjc.20259
Selective Regulation of Somatostatin Receptor Subtype Signaling: Evidence for Constitutive Receptor Activation (2007)

Anterior pituitary hormone secretion is under tonic suppression by hypothalamic somatostatin signaling through somatostatin receptor subtypes (SSTs). Because some hormonal axes are known to be abnormally regulated by ligand-independent constitutively active G protein-coupled receptors, we tested pituitary SSTs for selective constitutive signaling. We therefore differentially silenced endogenous SST2, SST3, and SST5 in somatostatin-sensitive ACTH-secreting mouse AtT-20 pituitary corticotroph cells using small inhibitory RNA (siRNA) and analyzed downstream SSTs-regulated pathways. Transfection with siRNA reduced specific receptor subtype mRNA expression up to 82%. Specificity of receptor silencing was validated against negative controls with different gene-selective siRNAs, concordance of mRNA and cAMP changes, reduced potency of receptor-selective agonists, and phenotype rescue by overexpression of the silenced receptor. Mouse SST3 > SST5 > SST2 knockdown increased basal cAMP accumulation (up to 200%) and ACTH secretion (up to 60%). SST2- and SST5-selective agonist potencies were reduced by SST3- and SST5-silencing, respectively. SST5 > SST2 = SST3 silencing also increased basal levels of ERK1/2 phosphorylation. SST3- and SST5-knockdown increased cAMP was only partially blocked by pertussis toxin. The results show that SST2, SST3, and SST5 exhibit constitutive activity in mouse pituitary corticotroph cells, restraining adenylate cyclase and MAPK activation and ACTH secretion. SST3 mainly inhibits cAMP accumulation and ACTH secretion, whereas SST5 predominantly suppresses MAPK pathway activation. Therefore, SST receptor subtypes control pituitary cell function not only through somatostatin binding to variably expressed cell membrane receptor subtypes, but also by differential ligand-independent receptor-selective constitutive action.
Discovery of Encequidar, First-in-Class Intestine Specific P-glycoprotein Inhibitor (2021)

Many chemotherapeutics, such as paclitaxel, are administered intravenously as they suffer from poor oral bioavailability, partly because of efflux mechanism of P-glycoprotein in the intestinal epithelium. To date, no drug has been approved by the U.S. Food and Drug Administration (FDA) that selectively blocks this efflux pump. We sought to identify a compound that selectively inhibits P-glycoprotein in the gastrointestinal mucosa with poor oral bioavailability, thus eliminating the issues such as bone marrow toxicity associated with systemic inhibition of P-glycoprotein. Here, we describe the discovery of highly potent, selective, and poorly orally bioavailable P-glycoprotein inhibitor <b>14</b> (encequidar). Clinically, encequidar was found to be well tolerated and minimally absorbed; and importantly, it enabled the oral delivery of paclitaxel.
Cannabinoid receptor 2 (CB2) agonists and antagonists: a patent update (2016)

Structural diversity of CB2 modulator scaffolds characterized the patent literature. Several CB2 agonists reached clinical Phase II for pain management and inflammation. Other therapeutic applications need to be explored such as neuroprotection and/or neurodegeneration.
Hybrid Turbulence Model for Unsteady Boundary Layers (1998)

A hybrid model is developed and evaluated for a single data set. For a broader perspective, the results of algebraic, one-equation, and two-equation models are also presented. The algebraic model was composed of the van Driest near-wall mixing length with the Cebeci-Keller unsteady modification and the Cebeci-Smith outer-layer eddy viscosity. The one-equation model was based on the Norris-Reynolds Prandtl-energy model with a prescribed mixing length. The two-equation model was based on that of Jones and Launder, making use of wall functions for computional efficiency
New Semi-Blind Channel Estimation for LDM-LSI (2019)

Local content insertion and viewer segmentation with proximity service information is a critical business case for broadcasting operators. This personalized service delivery will open up an opportunity for new use cases, such as local service delivery, local advertisement insertion and local emergency warning. In practice, single frequency networks (SFNs) offer a better spectrum efficiency when compared with traditional Multiple Frequency Network (MFN) approaches. Nevertheless, the addition of local content delivery can dramatically reduce that efficiency. Recently, the Layered Division Multiplexing (LDM) based Local Service Insertion (LSI) solution has been proposed as an interesting alternative for including local content in single frequency networks. Nonetheless, the required channel estimation procedure has been considered a major drawback for its successful implementation. In this work, a new semi-blind channel estimation algorithm is proposed. The algorithm takes advantage of the LDM structure and it is based on the statistical properties of the time domain Orthogonal Frequency Division Multiplexing (OFDM) frame. It proposes a solution for the major challenges that have remain unsolved so far. The paper also includes the first simulation results for this new approach.
Progress in Top Surface Imaging Process (2000)

A top surface imaging (TSI) process is one of the approaches for 0.10 µm or smaller pattern fabrication using photolithography. We have been evaluating the different types of bilayer resist processes, such as a bilayer silylation process, a bilayer process using a Si-containing resist and an improved silylation process which applies vapor phase silylation treatment after alkaline wet development (SILYAL). In this paper, we review the current status of these processes, specifically focusing on the progress in the bilayer silylation process. In addition, we evaluated the critical dimension (CD) controllability of the bilayer silylation process for 193 nm lithography and found that this process can already be compared with the wet-development single-layer resist process. We found that the resist stripping technique, which has been the main problem of the TSI process, is practically feasible with the application of a plasma ashing treatment followed by a subsequent wet cleaning using a fluorine-containing chemical stripper. We also evaluated the characteristic properties using a 157 nm frame exposure tool and confirmed that this process is extendible to 157 nm lithography.
Robust Antigen-Specific T Cell Activation within Injectable 3D Synthetic Nanovaccine Depots (2021)

Synthetic cancer vaccines may boost anticancer immune responses by co-delivering tumor antigens and adjuvants to dendritic cells (DCs). The accessibility of cancer vaccines to DCs and thereby the delivery efficiency of antigenic material greatly depends on the vaccine platform that is used. Three-dimensional scaffolds have been developed to deliver antigens and adjuvants locally in an immunostimulatory environment to DCs to enable sustained availability. However, current systems have little control over the release profiles of the cargo that is incorporated and are often characterized by an initial high-burst release. Here, an alternative system is designed that co-delivers antigens and adjuvants to DCs through cargo-loaded nanoparticles (NPs) incorporated within biomaterial-based scaffolds. This creates a programmable system with the potential for controlled delivery of their cargo to DCs. Cargo-loaded poly(d,l-lactic-<i>co</i>-glycolic acid) NPs are entrapped within the polymer walls of alginate cryogels with high efficiency while retaining the favorable physical properties of cryogels, including syringe injection. DCs cultured within these NP-loaded scaffolds acquire strong antigen-specific T cell-activating capabilities. These findings demonstrate that introduction of NPs into the walls of macroporous alginate cryogels creates a fully synthetic immunostimulatory niche that stimulates DCs and evokes strong antigen-specific T cell responses.
Impact of Hydrothermally Grown ZnO Nanorods on External Quantum Efficiency of 32 × 32 Pixelated InGaN/GaN Micro-LED Array (2018)

We systematically examined the growth parameters of the hydrothermally grown ZnO nanorods and studied their effects on the external quantum efficiency of 32 × 32 pixelated InGaN/GaN microlight-emitting diodes (μ-LEDs). The growth temperature increased the growth rate of the hydrothermally grown ZnO nanorods in the c-axis direction but not in the a-axis direction. On the other hand, the concentration of reaction solution increased the growth rate in the c-axis direction as well as the lateral growth rate of ZnO nanorods. The pressure of autoclave reactor had little influence on ZnO growth. The external quantum efficiency and light output power of the 32 × 32 pixelated InGaN/GaN μ-LEDs with the hydrothermally grown ZnO nanorods on the sapphire substrate were enhanced by 16.4% and 16.0% at 83 A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , respectively, compared to those of the μ-LEDs without the ZnO nanorods, which can be attributed to increased light extraction due to the ZnO nanorods.
Multi-fingered exoskeleton haptic device using passive force feedback for dexterous teleoperation (2003)

A novel control methodology for master-slave systems using passive force feedback has been proposed by the authors. The methodology solves the conventional problems of previously developed master-slave systems with force feedback, such as oscillations, complex structures and complicated control algorithm. In the present paper a multi-fingered exoskeleton haptic device (master hand) with passive force feedback function is developed. First, the exoskeleton master hand with three fingers (12 degrees of freedom) is designed and implemented. Each finger of the master hand consists of a link mechanism with elastic-shaft joints and clutches. Using link mechanisms, the master hand measures fingertip positions and angles of index finger middle finger and thumb. Furthermore, it also enables passive force feedback to an operator by the same link mechanism used for the geometric measurements. Then, a virtual reality system of human hand is constructed using the master hand and the control methodology. Using the system, sensory evaluations are conducted on human subjects to confirm the usability of the developed master hand and the possibility of the control methodology in the virtual reality system. As a result, the subjects possibly recognize the stiffness of the objects in the virtual environment.
Genetic confirmation for a central role for TNFα in the direct action of thyroid stimulating hormone on the skeleton (2013)

Clinical data showing correlations between low thyroid-stimulating hormone (TSH) levels and high bone turnover markers, low bone mineral density, and an increased risk of osteoporosis-related fractures are buttressed by mouse genetic and pharmacological studies identifying a direct action of TSH on the skeleton. Here we show that the skeletal actions of TSH deficiency are mediated, in part, through TNFα. Compound mouse mutants generated by genetically deleting the Tnfα gene on a Tshr(-/-) (homozygote) or Tshr(+/-) (heterozygote) background resulted in full rescue of the osteoporosis, low bone formation, and hyperresorption that accompany TSH deficiency. Studies using ex vivo bone marrow cell cultures showed that TSH inhibits and stimulates TNFα production from macrophages and osteoblasts, respectively. TNFα, in turn, stimulates osteoclastogenesis but also enhances the production in bone marrow of a variant TSHβ. This locally produced TSH suppresses osteoclast formation in a negative feedback loop. We speculate that TNFα elevations due to low TSH signaling in human hyperthyroidism contribute to the bone loss that has traditionally been attributed solely to high thyroid hormone levels.
Bragg gratings made with ultrafast radiation in crystal waveguides: lithium niobate, sapphire and YAG Bragg gratings (2007)

We present results of Bragg gratings inscription in several crystalline optical weveguiding structures. Using infrared femtosecond radiation and the phase mask method, Bragg gratings were inscribed in multimode crystalline sapphire fiber, RPE lithium niobate waveguides and large area core multimode YAG fibers. It was shown that Bragg grating structures could be created in all these crystalline substrates with comparable IR- intensities. The spectral characteristics and the thermal stability of these Bragg gratings is also presented.
Reducing Aerosol-Related Risk of Transmission in the Era of COVID-19: An Interim Guidance Endorsed by the International Society of Aerosols in Medicine (2020)

National and international guidelines recommend droplet/airborne transmission and contact precautions for those caring for coronavirus disease 2019 (COVID-19) patients in ambulatory and acute care settings. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, an acute respiratory infectious agent, is primarily transmitted between people through respiratory droplets and contact routes. A recognized key to transmission of COVID-19, and droplet infections generally, is the dispersion of bioaerosols from the patient. Increased risk of transmission has been associated with aerosol generating procedures that include endotracheal intubation, bronchoscopy, open suctioning, administration of nebulized treatment, manual ventilation before intubation, turning the patient to the prone position, disconnecting the patient from the ventilator, noninvasive positive-pressure ventilation, tracheostomy, and cardiopulmonary resuscitation. The knowledge that COVID-19 subjects can be asymptomatic and still shed virus, producing infectious droplets during breathing, suggests that health care workers (HCWs) should assume every patient is potentially infectious during this pandemic. Taking actions to reduce risk of transmission to HCWs is, therefore, a vital consideration for safe delivery of all medical aerosols. Guidelines for use of personal protective equipment (glove, gowns, masks, shield, and/or powered air purifying respiratory) during high-risk procedures are essential and should be considered for use with lower risk procedures such as administration of uncontaminated medical aerosols. Bioaerosols generated by infected patients are a major source of transmission for SARS CoV-2, and other infectious agents. In contrast, therapeutic aerosols do not add to the risk of disease transmission unless contaminated by patients or HCWs.
CORPORATE WELFARE FOR THE RAL INDUSTRY: THE DEBT INDICATOR, IRS SUBSIDY, AND TAX FRAUD (2005)

• The debt indicator has helped boost RAL profitability. The IRS terminated the debt indicator in 1994 due to RAL fraud, and the price of RALs rose significantly, from $29$35 to $29-$89. The IRS reinstated the debt indicator in 1999 partly to lower RAL prices. RAL prices dipped for a year in 2000, but have gone back up to pre-indicator levels. Meanwhile, the amount of RAL fraud has multiplied since the debt indicator was reinstated.
Descriptions of the Larva and Pupa of Callirhopalus (subg. Pseudocneorhinus)bifasciatus, the Twobanded Japanese Weevil, with New Host Plant Records1 (1979)

The mature larva and pupa of the twobanded Japanese weevil, Callirhopalus bifasciatus (Roelofs), are described and illustrated. New host plants reported for the adults of the species are species of Abelia, Viburnum, Acer, Morus, Populus, Sedum, Lythrum, Campsis, Thunbergia, and Coleus.