gebhart/patrepeval huggingface dataset:
An influenza H1 hemagglutinin stem-only immunogen elicits a broadly cross-reactive B cell response in humans (2023)

Current yearly seasonal influenza vaccines primarily induce an antibody response directed against the immunodominant but continually diversifying hemagglutinin (HA) head region. These antibody responses provide protection against the vaccinating strain but little cross-protection against other influenza strains or subtypes. To focus the immune response on subdominant but more conserved epitopes on the HA stem that might protect against a broad range of influenza strains, we developed a stabilized H1 stem immunogen lacking the immunodominant head displayed on a ferritin nanoparticle (H1ssF). Here, we evaluated the B cell response to H1ssF in healthy adults ages 18 to 70 in a phase 1 clinical trial (NCT03814720). We observed both a strong plasmablast response and sustained elicitation of cross-reactive HA stem-specific memory B cells after vaccination with H1ssF in individuals of all ages. The B cell response was focused on two conserved epitopes on the H1 stem, with a highly restricted immunoglobulin repertoire unique to each epitope. On average, two-thirds of the B cell and serological antibody response recognized a central epitope on the H1 stem and exhibited broad neutralization across group 1 influenza virus subtypes. The remaining third recognized an epitope near the viral membrane anchor and was largely limited to H1 strains. Together, we demonstrate that an H1 HA immunogen lacking the immunodominant HA head produces a robust and broadly neutralizing HA stem-directed B cell response.
Properties of the slab modes in photonic crystal optical waveguides (2000)

We show that by placing a slab of semiconductor material between two photonic bandgap (PBG) mirrors, waveguide modes at frequencies out of the PBG can be obtained. These modes are similar to the modes of a conventional dielectric slab waveguide. Using these modes, we can obtain very good coupling between a PBG waveguide and a dielectric slab waveguide with similar slab properties. We discuss the properties of these slab modes and outline the guideline for the optimization of the PBG waveguides based on these properties.
Wafer-level electromigration for reliability monitoring: Quick-turn electromigration stress with correlation to package-level stress (2015)

Rapid, accurate and flexible reliability characterization capabilities are important tools in process development and monitoring. Electromigration evaluation has largely relied on packaged test structures given the need for high temperatures to provide sufficient acceleration. However, several Wafer-Level (WL) electromigration (EM) techniques and their correlation to Package-Level (PL) tests have been reported (e.g. SWEAT[1], [2], isothermal[3], tests). Presented in the this paper is a wafer-level electromigration test that addresses the PL correlation issues presented by quick-turn tests, but maintains the advantages of wafer-level and allows quick comparison to PL baseline with a significant advantage in time-to-data over PL-EM testing. Statistical matching of initial resistance (R0) and Time-to-Failure (TTF) between PL vs. WL electromigration tests on two concurrently stressed structures across sixteen reticle locations is demonstrated. This WL-EM stress technique provides equivalent TTF, with no reliance on extrapolations, whilst yielding an advantage in time-to-data relative to standard PL-EM tests.
Dual site-specific chemoenzymatic antibody fragment conjugation using CRISPR-based hybridoma engineering (2020)

I. Abstract Functionalized antibodies and antibody fragments have found applications in the fields of biomedical imaging, theragnostics, and antibody-drug conjugates (ADC). Antibody functionalization is classically achieved by coupling payloads onto lysine or cysteine residues. However, such stochastic strategies typically lead to heterogenous products, bearing a varying number of payloads. This affects bioconjugate efficacy and stability, as well as its in vivo biodistribution, and therapeutic index, while potentially obstructing the binding sites and leading to off-target toxicity. In addition, therapeutic and theragnostic approaches benefit from the possibility to deliver more than one type of cargo to target cells, further challenging stochastic labelling strategies. Thus, bioconjugation methods to reproducibly obtain defined homogenous conjugates bearing multiple different cargo molecules, without compromising target affinity, are in demand. Here, we describe a straightforward CRISPR/Cas9-based strategy to rapidly engineer hybridoma cells to secrete Fab’ fragments bearing two distinct site-specific labelling motifs, which can be separately modified by two different sortase A mutants. We show that sequential genetic editing of the heavy chain (HC) and light chain (LC) loci enables the generation of a stable cell line that secretes a dual tagged Fab’ molecule (DTFab’), which can be easily isolated in high yields. To demonstrate feasibility, we functionalized the DTFab’ with two distinct cargos in a site-specific manner. This technology platform will be valuable in the development of multimodal imaging agents, theragnostics, and next-generation ADCs.
High-Throughput Microfluidic Method To Study Biofilm Formation and Host-Pathogen Interactions in Pathogenic Escherichia coli (2015)

Biofilm formation and host-pathogen interactions are frequently studied using multiwell plates; however, these closed systems lack shear force, which is present at several sites in the host, such as the intestinal and urinary tracts. Recently, microfluidic systems that incorporate shear force and very small volumes have been developed to provide cell biology models that resemble in vivo conditions. Therefore, the objective of this study was to determine if the BioFlux 200 microfluidic system could be used to study host-pathogen interactions and biofilm formation by pathogenic Escherichia coli. Strains of various pathotypes were selected to establish the growth conditions for the formation of biofilms in the BioFlux 200 system on abiotic (glass) or biotic (eukaryotic-cell) surfaces. Biofilm formation on glass was observed for the majority of strains when they were grown in M9 medium at 30 °C but not in RPMI medium at 37 °C. In contrast, HRT-18 cell monolayers enhanced binding and, in most cases, biofilm formation by pathogenic E. coli in RPMI medium at 37 °C. As a proof of principle, the biofilm-forming ability of a diffusely adherent E. coli mutant strain lacking AIDA-I, a known mediator of attachment, was assessed in our models. In contrast to the parental strain, which formed a strong biofilm, the mutant formed a thin biofilm on glass or isolated clusters on HRT-18 monolayers. In conclusion, we describe a microfluidic method for high-throughput screening that could be used to identify novel factors involved in E. coli biofilm formation and host-pathogen interactions under shear force.
Regulatory T Cells in Gynecologic Cancer (2018)

Increasing evidence supports that regulatory T cells (Tregs) within the tumor, tumor draining lymph nodes, ascites and peripheral blood of patients with cancer are associated with poor prognosis. Tregs are important mediators of active immune evasion in cancer. In this review, the potential mechanisms of Treg actions and the roles of Tregs specifically in the tumor microenvironment derived from three types of gynecological cancers, cervical, vulvar and ovarian, are described. The correlations between Tregs and clinical immunotherapeutic study outcomes are discussed. Successful modulation of Tregs would likely have significant impact on the effectiveness of immunotherapeutic treatments in cancer patients.
Silicon-on-Insulator Echelle Grating WDM Demultiplexers With Two Stigmatic Points (2009)

We present ultracompact integrated optical echelle grating wavelength-division-multiplexing (de)multiplexers for on-chip optical networks, fabricated using high-index-contrast silicon-on-insulator photonic waveguide technology. These devices are based on a design with two stigmatic points, which enables compact geometries with reduced aberrations. In the example presented here, this design allows us to achieve an eight-channel (de)multiplexer with 3.2-nm channel spacing, within an ultracompact footprint of 250 times 200 mum. The channel-to-channel isolation of the devices is 19 dB. The minimum insertion loss, relative to a straight waveguide, is 3 dB with a channel-to-channel variation of 0.5 dB.
Development of ultra-broadband UTC-PD module beyond 110 GHz without bias circuit (2015)

For future photonics devices, in addition to realizing improved performances at high baud rates, key factors that need to be addressed include high-density integration and the ability to realize miniaturization. High-baud rate optical devices that work at 40–100 Gbps in on-off-keying (OOK) systems have been reported [1]. A 3-dB bandwidth over 20–70 GHz band has also been reported; however, in this case, high-baud rate photonic intergradations were not considered. In this paper, in order to consider large-scale integration, we report a new ultra-broadband photodetector (PD) module beyond 110 GHz without any bias circuits.
Reduction of phonon resonant terahertz wave absorption in photoconductive switches using epitaxial layer transfer (2009)

A broadband terahertz time-domain spectroscopy (TDS) system for frequencies of up to 15 THz, including the phonon resonance frequency range, has been developed using a transferred thin-film photoconductive switch (PCS) detector. The thin-film PCSs, based on low-temperature-grown GaAs, were fabricated using epitaxial layer transfer onto high-resistivity Si substrates. We observed a reduction of phonon resonant absorption, including between 7 and 10 THz, in a forward radiation configuration. Numerically calculated absorption spectra show good agreement with our experimental results. This technique will provide compact, broadband TDS systems.
Effects of MAP kinase cascade inhibitors on the MKK5/ERK5 pathway (2001)

Antibodies that recognise the active phosphorylated forms of mitogen-activated protein kinase (MAPK) kinase 5 (MKK5) and extracellular signal-regulated kinase 5 (ERK5) in untransfected cells have been exploited to show that the epidermal growth factor (EGF)-induced activation of MKK5 and ERK5 occurs subsequent to the activation of ERK1 and ERK2 in HeLa cells. The drugs U0126 and PD184352, which prevent the activation of MKK1 (and hence the activation of ERK1/ERK2), also prevent the activation of MKK5, although higher concentrations are required. Our studies define physiological targets of the MKK5/ERK5 pathway as proteins whose phosphorylation is largely prevented by 10 microM PD184352, but unaffected by 2 microM PD184352. Surprisingly, 2 microM PD184352 prolongs the activation of MKK5 and ERK5 induced by EGF or H(2)O(2), indicating negative control of the MKK5/ERK5 pathway by the classical MAPK cascade. Our results also indicate that ERK5 is not a significant activator of MAPK-activated protein kinase-1/RSK in HeLa cells.
Cryogenic Transmission Electron Microscopy Investigation of Carbon Nanothreads (2021)

The ability of the element carbon to form many types of chemical bonds enables it to exist as a variety of allotropes, including diamond, graphite/graphene, and fullerenes Recently, a new class of hydrocarbon materials has been discovered, called carbon nanothreads Nanothreads have been created by the controlled compression of aromatic molecules, such as benzene and its derivatives, and the resulting structure consists largely of one-dimensional sp3-bonded carbon networks saturated with hydrogen.
Hiding Data in Plain Sight: Undetectable Wireless Communications Through Pseudo-Noise Asymmetric Shift Keying (2019)

Undetectable wireless transmissions are fundamental to avoid eavesdroppers. To address this issue, wireless steganography hides covert information inside primary information by slightly modifying the transmitted waveform such that primary information will still be decodable, while covert information will be seen as noise by agnostic receivers. Since the addition of covert information inevitably decreases the SNR of the primary transmission, key challenges in wireless steganography are: i) to assess the impact of the covert channel on the primary channel as a function of different channel conditions; and ii) to make sure that the covert channel is undetectable. Existing approaches are protocol-specific, also we notice that existing wireless technologies rely on phase-keying modulations that in most cases do not use the channel up to its Shannon capacity. Therefore, the residual capacity can be leveraged to implement a wireless system based on a pseudo-noise asymmetric shift keying (PN-ASK) modulation, where covert symbols are mapped by shifting the amplitude of primary symbols. This way, covert information will be undetectable, since a receiver expecting phase-modulated symbols will see their shift in amplitude as an effect of channel/path loss degradation. We first investigate the SER of PN-ASK as a function of the channel; then, we find the optimal PN-ASK parameters that optimize primary and covert throughput under different channel condition. We evaluate the throughput performance and undetectability of PN-ASK through extensive simulations and on an experimental testbed based on USRP N210 software-defined radios. We show that PN-ASK improves the throughput by more than 8x with respect to prior art. Finally, we demonstrate through experiments that PN-ASK is able to transmit covert data on top of IEEE 802.11g frames, which are correctly decoded by an off-the-shelf laptop WiFi.
Echo cancellation in mono and stereo using the conjugate gradient method (2001)

In this paper an approximation to the sliding window Recursive Least Squares (RLS) algorithm with filter estimate updates using the conjugate gradient algorithm is applied to the Acoustic Echo Canc ...
The Potassium‐Assisted P‐Type Characteristics of Tin Oxide in Solution‐Processed High‐Performance Metal Oxide Thin‐Film Transistors (2021)

Developing high‐performance p‐type metal‐oxide semiconductors comparable to n‐type ones has opened a new window for the realization of transparent, flexible, and low‐power integrated circuits in large‐area electronics. Herein, the fabrication of solution‐processed p‐type metal‐oxide thin‐film transistors (TFTs) with excellent device performance at low temperatures using a novel material is reported. Potassium (K) content is introduced into the tin oxide precursor solution to stabilize the tin (II) oxide (SnO) phase rather than the tin (IV) oxide (SnO 2 ) phase during thin‐film formation. The optimized K‐doped SnO (K‐SnO) TFTs exhibit outstanding electrical performance, with a maximum Hall mobility of 51 cm 2 V −1 s −1 and a field‐effect hole mobility of 2.3 cm 2 V −1 s −1 . The achievement of the solution‐processed K‐SnO TFTs not only provides a significant step toward the development of complementary metal‐oxide semiconductor circuits, but also represents a feasible approach for low‐cost flexible p‐type metal‐oxide electronics.
Preparation of biologically active 32P-labeled human relaxin. Displaceable binding to rat uterus, cervix, and brain. (1990)

Relaxin is a member of the insulin family of polypeptide hormones and is known to exert its biological effects on various parts of the mammalian reproductive system. Biologically active human relaxin has been chemically synthesized based on the nucleotide sequence obtained from an ovarian cDNA clone. In the present study synthetic human relaxin was radiolabled by phosphorylation with cAMP-dependent protein kinase and [gamma-32P]ATP to a specific activity of 5000 Ci/mmol. The phosphorylated relaxin was purified on cation exchange high performance liquid chromatography and was shown to co-migrate with relaxin on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Mass spectrometry revealed a single phosphorylated site on the B chain of relaxin. The 32P-relaxin was able to bind to a goat anti-relaxin antibody, and this binding could be displaced by unlabeled relaxin in a concentration-dependent manner. A comparison of the concentration responses of cellular cAMP production stimulated by relaxin and phosphorylated relaxin in a primary human uterine cell line showed that phosphorylation did not affect the in vitro biological efficacy of relaxin. This made it suitable for in situ autoradiographic localization of relaxin binding sites in rat uterine, cervical, and brain tissue sections. Displacement of the binding of 100 pM 32P-relaxin by 100, 10, and 3 nM unlabeled relaxin, but not by 100 nM insulin, insulin-like growth factor-I, and an insulin-like growth factor-I analog, demonstrated the high affinity and specificity of such binding. We conclude that 32P-labeled human relaxin is biologically and immunologically active and that this novel probe binds reversibly and with high affinity to classical (e.g. uterus) and unpredicted (e.g. brain) tissues.
Structured packing in air distillation (1993)

An economic analysis has been performed to establish when it is advantageous to use structured packing in air separation plant. A model of a low pressure cycle was developed to calculate the power saved when packing is used, and cost models were developed for the columns and cold box. The rate of return was calculated on the extra investment required for a packed plant based on the annual power saving. Structured packing was found to be economic only in larger plants, where economies of scale mean that the increased capital cost becomes less significant compared with the power saved. It was also found that different sized plants favour different packings. The analysis identified that the packing variable with the biggest impact on the economic balance was the efficiency and that increasing the efficiency of current packings could enhance their balance in air distillation. A new packing was therefore developed to have a higher efficiency than conventional ones. The vapour phase resistance was targeted for reduction, since most packing models predict this to be dominant. The final shape was chosen as the easiest and most economic to make. It has converging and diverging channels and was manufactured in two specific areas and with two block heights by Tianjin University Packing Factory. A 0.3 m diameter distillation column test rig was designed, built and commissioned with the standard Sulzer Mellapak 500YW. It was then used to test the new packing alongside some standard ones. Because the packings had different specific areas, correlations of published results were developed to allow a true comparison to be made. The test results show that, unexpectedly, the packings with 0.1 m high blocks have an efficiency about 8% greater than the standard 0.2 m blocks. The new shape as implemented in the 350Y packing shows an additional 7% greater efficiency, so it is 15% better than a standard packing with the same area. It has a better efficiency than the Mellapak 500YW and the higher capacity associated with its lower area. The new 500Y did not show a significant advantage.
Studies on the In-vitro Percutaneous Penetration of Indomethacin from Gel Systems in Hairless Mice (1995)

The influence of co-solvents on the in-vitro percutaneous penetration of indomethacin from gel systems was studied using a simplex lattice experimental design. Gel formulations were prepared by gelling the vehicle mixture of water, either alcohol or isopropanol and either propylene glycol or PEG 400 with 1% w/w Carbomer 940. Hairless mouse skin was employed as the barrier in a Franz-type diffusion cell. The penetration rates at steady state for seven formulations were fitted to a polynomial equation based on this simple lattice method and a three-dimensional plot was constructed. The formulation having the maximal penetration rate was determined to be the vehicle with a solvent ratio of water: alcohol: propylene glycol equal to 15:33:52, and which possessed a solubility parameter of 15 and a drug solubility of around 10 mg mL-1. When the solubility parameter of the vehicle was > 15, the drug solubility increased. However, the penetration rate decreased with an increasing solubility parameter. For those vehicles with a solubility parameter < 15, both the drug solubility and the penetration rate decreased with a decrease in the solubility parameter. There was shown to be an approximately 20-fold increase in the relative enhancement factor when using both alcohol and isopropanol, but only a threefold increase for both propylene glycol and PEG 400, when compared with water.
Transient Elastic Thermal Stress Development During Laser Scribing of Ceramics (2000)

Lsaers are emerging as a valuable tool for shaping and cutting hard and brittle ceramics. Unfortunately, the large, concentrated heat flux rates that allow the laser to efficiently cut and shape the ceramic also result in large localized thermal stresses in a small heat-affected zone. These notable thermal stresses can lead to micro-cracks, a decrease in strength and fatigue life, and possibly catastrophic failure. In order to assess where, when, and what stresses occur during laser scribing, an elastic stress model has been incorporated into a three-dimensional scribing and cutting code. First, the code predicts the temporal temperature fields and the receding surface of the ceramic. Then, using the scribed geometry and temperature field, the elastic stress fields are calculated as they develop and decay during the laser scribing process. The analysis allows the prediction of stresses during continuous wave and pulsed laser operation, a variety of cutting speeds and directions, and various shapes and types of ceramic material. The results of the analysis show substantial tensile stresses develop over a thick layer below and parallel to the surface, which may be the cause of experimentally observed subsurface cracks.
Coactivator condensation at super-enhancers links phase separation and gene control (2018)

Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density of the transcriptional apparatus to drive robust expression of genes with prominent roles in cell identity. Here we demonstrate that the SE-enriched transcriptional coactivators BRD4 and MED1 form nuclear puncta at SEs that exhibit properties of liquid-like condensates and are disrupted by chemicals that perturb condensates. The intrinsically disordered regions (IDRs) of BRD4 and MED1 can form phase-separated droplets, and MED1-IDR droplets can compartmentalize and concentrate the transcription apparatus from nuclear extracts. These results support the idea that coactivators form phase-separated condensates at SEs that compartmentalize and concentrate the transcription apparatus,
Responsive and patterned polymer brushes (2013)

ABSTRACT While polymer brush systems continue to grow in popularity, so does their complexity and sophistication. Advances in polymerization and specific functionalization methods have led to novel applications in diverse research fields. The marriage of top‐down lithography with bottom‐up brush processing is becoming increasingly important in the development and progress of nanotechnology. The aim of this review is to examine different approaches taken to generate tailored polymer brush systems through surface‐initiated polymerizations as well as patterning techniques. Detaching polymer brushes to create free‐standing membranes is also highlighted and discussed in terms of methods and characterization. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013 , 51 , 1457–1472