gebhart/patrepeval huggingface dataset:
Impact of lower body negative pressure induced hypovolemia on peripheral venous pressure waveform parameters in healthy volunteers (2014)

Lower body negative pressure (LBNP) creates a reversible hypovolemia by sequestrating blood volume in the lower extremities. This study sought to examine the impact of central hypovolemia on peripheral venous pressure (PVP) waveforms in spontaneously breathing subjects. With IRB approval, 11 healthy subjects underwent progressive LBNP (baseline, -30, -75, and -90 mmHg or until the subject became symptomatic). Each was monitored for heart rate (HR), finger arterial blood pressure (BP), a chest respiratory band and PVP waveforms which are generated from a transduced upper extremity intravenous site. The first subject was excluded from PVP analysis because of technical errors in collecting the venous pressure waveform. PVP waveforms were analyzed to determine venous pulse pressure, mean venous pressure, pulse width, maximum and minimum slope (time domain analysis) together with cardiac and respiratory modulations (frequency domain analysis). No changes of significance were found in the arterial BP values at -30 mmHg LBNP, while there were significant reductions in the PVP waveforms time domain parameters (except for 50% width of the respiration induced modulations) together with modulation of the PVP waveform at the cardiac frequency but not at the respiratory frequency. As the LBNP progressed, arterial systolic BP, mean BP and pulse pressure, PVP parameters and PVP cardiac modulation decreased significantly, while diastolic BP and HR increased significantly. Changes in hemodynamic and PVP waveform parameters reached a maximum during the symptomatic phase. During the recovery phase, there was a significant reduction in HR together with a significant increase in HR variability, mean PVP and PVP cardiac modulation. Thus, in response to mild hypovolemia induced by LBNP, changes in cardiac modulation and other PVP waveform parameters identified hypovolemia before detectable hemodynamic changes.
Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections (2022)

Molds are ubiquitous in the environment, and immunocompromised patients are at substantial risk of morbidity and mortality due to their underlying disease and the resistance of pathogenic molds to currently recommended antifungal therapies. This combination of weakened-host defense, with limited antifungal treatment options, and the opportunism of environmental molds renders patients at risk and especially vulnerable to invasive mold infections such as <i>Aspergillus</i> and members of the Order Mucorales. Currently, available antifungal drugs such as azoles and echinocandins, as well as combinations of the same, offer some degree of efficacy in the prevention and treatment of invasive mold infections, but their use is often limited by drug resistance mechanisms, toxicity, drug-drug interactions, and the relative paucity of oral treatment options. Clearly, there is a need for agents that are of a new class that provides adequate tissue penetration, can be administered orally, and have broad-spectrum efficacy against fungal infections, including those caused by invasive mold organisms. Ibrexafungerp, an orally bioavailable glucan synthase inhibitor, is the first in a new class of triterpenoid antifungals and shares a similar target to the well-established echinocandins. Ibrexafungerp has a very favorable pharmacokinetic profile for the treatment of fungal infections with excellent tissue penetration in organs targeted by molds, such as the lungs, liver, and skin. Ibrexafungerp has demonstrated in vitro activity against <i>Aspergillus</i> spp. as well as efficacy in animal models of invasive aspergillosis and mucormycosis. Furthermore, ibrexafungerp is approved for use in the USA for the treatment of women with vulvovaginal candidiasis. Ibrexafungerp is currently being evaluated in clinical trials as monotherapy or in combination with other antifungals for treating invasive fungal infections caused by yeasts and molds. Thus, ibrexafungerp offers promise as a new addition to the clinician's armamentarium against these difficult-to-treat infections.
A 28 GHz Hybrid PLL in 32 nm SOI CMOS (2014)

A hybrid PLL is introduced, which features a simple switched resistor analog proportional path filter in parallel with a highly digital integral path. The integral path control scheme for the LC-tank VCO includes a novel linearly scaled capacitor bank configuration. In addition to the analog proportional path, the PLL includes a set of digital proportional path controls, so that the two approaches can be experimentally compared. At 28 GHz the RMS jitter is 199 fs (1 MHz to 1 GHz), phase noise is -110 dBc/Hz at 10 MHz offset. The 14 × 160 μm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> 32 nm SOI CMOS PLL locks from 23.8 to 30.2 GHz, and draws 31 mA from a 1 V supply.
A computational tool to predict the evolutionarily conserved protein–protein interaction hot‐spot residues from the structure of the unbound protein (2013)

Identifying hot-spot residues - residues that are critical to protein-protein binding - can help to elucidate a protein's function and assist in designing therapeutic molecules to target those residues. We present a novel computational tool, termed spatial-interaction-map (SIM), to predict the hot-spot residues of an evolutionarily conserved protein-protein interaction from the structure of an unbound protein alone. SIM can predict the protein hot-spot residues with an accuracy of 36-57%. Thus, the SIM tool can be used to predict the yet unknown hot-spot residues for many proteins for which the structure of the protein-protein complexes are not available, thereby providing a clue to their functions and an opportunity to design therapeutic molecules to target these proteins.
Catalytic enhancement of singlet oxygen for hybrid electric discharge oxygen-iodine laser systems (2010)

We are investigating catalytically enhanced production of singlet oxygen, O<sub>2</sub>(a1▵<sub>g</sub>), observed by reaction of O<sub>2</sub>/He discharge effluents on an iodine oxide film surface in a microwave discharge-flow reactor at 320 K. We have previously reported a two-fold increase in the O<sub>2</sub>(a) yields by this process, and corresponding enhancement of I(<sup>2</sup>P<sub>1/2</sub>) excitation and small-signal gain upon injection of I<sub>2</sub>. In this paper we report further observations of the effects of elevated temperature up to 410 K, and correlations of the catalytically generated O<sub>2</sub>(a) with atomic oxygen over a large range of discharge-flow conditions. We have applied a diffusion-limited reaction rate model to extrapolate the catalytic reaction rates to the highpressure, fast-flow conditions of the subsonic plenum of a supersonic EOIL test reactor. Using the model and the flow reactor results, we have designed and implemented a first-generation catalytic module for the PSI supersonic MIDJet/EOIL reactor. We describe preliminary tests with this module for catalyst coating deposition and enhancement of the small-signal gain observed in the supersonic flow. The observed catalytic effect could significantly benefit the development of high-power electrically driven oxygen-iodine laser systems.
Development of a Luminex-Based Multiplex Assay for Detection of Mutations Conferring Resistance to Echinocandins in Candida glabrata (2013)

Echinocandins are the recommended treatment for invasive candidiasis due to Candida glabrata. Resistance to echinocandins is known to be caused by nonsynonymous mutations in the hot spot-1 (HS1) regions of the FKS1 and FKS2 genes, which encode a subunit of the β-1,3-glucan synthase, the target of echinocandins. Here, we describe the development of a microsphere-based assay using Luminex MagPix technology to identify mutations in the FKS1 HS1 and FKS2 HS1 domains, which confer in vitro echinocandin resistance in C. glabrata isolates. The assay is rapid and can be performed with high throughput. The assay was validated using 102 isolates that had FKS1 HS1 and FKS2 HS1 domains previously characterized by DNA sequencing. The assay was 100% concordant with DNA sequencing results. The assay was then used for high-throughput screening of 1,032 C. glabrata surveillance isolates. Sixteen new isolates with mutations, including a mutation that was new to our collection (del659F), were identified. This assay provides a rapid and cost-effective way to screen C. glabrata isolates for echinocandin resistance.
Supported Ionic Liquid Catalysis Investigated for Hydrogenation Reactions. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Quantum cascade lasers: from tool to product (2015)

The quantum cascade laser (QCL) is an important laser source in the mid-infrared and terahertz frequency range. The past twenty years have witnessed its tremendous development in power, wall plug efficiency, frequency coverage and tunability, beam quality, as well as various applications based on QCL technology. Nowadays, QCLs can deliver high continuous wave power output up to 5.1 W at room temperature, and cover a wide frequency range from 3 to 300 μm by simply varying the material components. Broadband heterogeneous QCLs with a broad spectral range from 3 to 12 μm, wavelength agile QCLs based on monolithic sampled grating design, and on-chip beam QCL combiner are being developed for the next generation tunable mid-infrared source for spectroscopy and sensing. Terahertz sources based on nonlinear generation in QCLs further extend the accessible wavelength into the terahertz range. Room temperature continuous wave operation, high terahertz power up to 1.9 mW, and wide frequency tunability form 1 to 5 THz makes this type of device suitable for many applications in terahertz spectroscopy, imaging, and communication.
Efficacy and Safety of a Cell-Culture Live Virus Vaccine for Hemorrhagic Enteritis of Turkeys: Laboratory Studies (1984)

Poults free from hemorrhagic enteritis (HE) antibody were vaccinated by gavage at 1 day or 2 weeks of age with a live HE vaccine virus that had been propagated in a Marek's disease (MD)-induced B-lymphoblastoid cell line of turkey origin. Vaccinated and unvaccinated poults were challenged with a virulent HE virus at various times postvaccination. One hundred tissue-culture-infectious doses of the vaccine virus per poult were sufficient to induce a serological response as well as to protect poults against HE lesions and mortality. Vaccinated poults were protected against the disease as early as 1 week and as late as 8 weeks PV. The vaccine was efficacious by several routes of application. The vaccine virus spread horizontally from vaccinated to contact-exposed poults, as indicated by seroconversion and resistance of contact-exposed poults to challenge. The vaccine had no detectable harmful effects on the humoral immune response to particulate antigens or on weight gain of vaccinated poults. The vaccine proved to be free from MD virus, as indicated by the absence of MD lesions and antibody in 8-week-old chickens inoculated intra-abdominally with the vaccine at hatching. These findings indicate that the cell-culture-propagated HE vaccine is efficacious and safe.
Inhibition of tumor cell induced platelet aggregation by prostacyclin and carbacyclin: an ultrastructural study. (1987)

Prostacyclin and its synthetic analog carbacyclin were compared as to their abilities to inhibit tumor cell-platelet interactions. Aggregation of rat platelets was induced in vitro by homologous rat Walker 256 carcinosarcoma cells. The extent of cellular interactions was examined ultrastructurally. The ultrastructural data presented here indicate that the tumor cell-platelet interactions began with individual platelets which initiated platelet chain formation in focal association with tumor cell surfaces. By mid-phase aggregation large homotypic platelet aggregates had formed with tumor cells positioned on the external surfaces of the emboli. Tumor cell-platelet interactions became progressively more extensive as tumor cells became enmeshed with growing platelet aggregates. Prostacyclin and carbacyclin inhibited tumor cell platelet interactions in a dose-dependent manner. Carbacyclin inhibition of tumor cell induced platelet aggregation was longer in duration but carbacyclin was 10-fold less effective than was prostacyclin. We report here that prostacyclin and carbacyclin inhibit both aggregation and the ultrastructural changes associated with tumor cell-platelet interactions.
Wetting and Dispersing Agents (2002)

The incorporation of inorganic and organic particles into liquid resin media is an important process step in the paint, graphic arts and plastics industries. Various classes of wetting and dispersing agents are used for this purpose. The physical principles, chemistry and stabilisation mechanisms for both water- and solvent-based applications are described. A focus is directed towards the molecular architecture of high molecular weight dispersants, which exhibit superior and more universal characteristics than low molecular weight wetting agents. A preview of future developments in this field completes this overview.
Metal‐Free Synthesis of Pharmaceutically Important Biaryls by Photosplicing (2018)

Many pharmaceuticals feature biaryl motifs that are crucial for their binding to the target. Yet, benchmark methods for selective cross-couplings rely on highly toxic heavy metal catalysts, which are unfavorable in the synthesis of pharmaceuticals. Metal-free coupling reactions, on the other hand, may require harsh conditions and lack selectivity. We report a novel, metal-free cross-coupling reaction that involves the tethering of two phenyl groups by a temporary, traceless sulfonamide linker that directs a photochemical aryl fusion into a single coupling product. The perfect regio- and chemoselectivity of the reaction could be rationalized by a cyclic intermediate, which fragments into the biaryl and volatile side products. Using a flow reactor, we synthesized numerous substituted biaryl building blocks for important therapeutics in high yields, such as antibiotics, antitumor, neuroprotective and cholesterol-lowering agents as well as antiarthritic non-steroidal antiinflammatory drugs (NSAIDs). The new method was successfully employed in a total synthesis of cannabinol, an important analgesic and antiemetic therapeutic. We also report a metal-free synthesis of key building blocks used for the preparation of sartans, antihypertensive agents that rank among the top blockbuster drugs worldwide. This safe and convenient protocol is a valuable alternative for the widely used metal-dependent aryl cross-coupling methods.
Design and fabrication of high aspect ratio fine pitch interconnects for wafer level packaging (2003)

The Packaging Research Center (PRC) at Georgia Tech has been exploring and evaluating novel compliant nano interconnect designs to enable high density I/O architecture for the next generation chip assembly. Most of the compliant interconnects that are currently being developed have inductance and resistance higher than desirable. We propose high aspect ratio interconnects as a solution that can support both electrical and mechanical requirements. The fabrication of these interconnects is similar to the standard IC fabrication and involves only one additional step beyond the standard CMOS wafer processing, thus making it a cost effective wafer level process. Extensive modeling was carried out to design 40 /spl mu/m pitch interconnects with optimized electrical and mechanical properties. The fabrication of fine-pitch copper interconnects with aspect ratio of 1:5 was demonstrated as a low-cost wafer level process. Results show that these interconnects provide the optimal combination of electrical and mechanical requirements and hence provides a viable solution for next-generation electronic packaging that can support extremely high I/O density.
Serum Deprivation of Mesenchymal Stem Cells Improves Exosome Activity and Alters Lipid and Protein Composition (2019)

Exosomes can serve as delivery vehicles for advanced therapeutics. The components necessary and sufficient to support exosomal delivery have not been established. Here we connect biochemical composition and activity of exosomes to optimize exosome-mediated delivery of small interfering RNAs (siRNAs). This information is used to create effective artificial exosomes. We show that serum-deprived mesenchymal stem cells produce exosomes up to 22-fold more effective at delivering siRNAs to neurons than exosomes derived from control cells. Proteinase treatment of exosomes stops siRNA transfer, indicating that surface proteins on exosomes are involved in trafficking. Proteomic and lipidomic analyses show that exosomes derived in serum-deprived conditions are enriched in six protein pathways and one lipid class, dilysocardiolipin. Inspired by these findings, we engineer an "artificial exosome," in which the incorporation of one lipid (dilysocardiolipin) and three proteins (Rab7, Desmoplakin, and AHSG) into conventional neutral liposomes produces vesicles that mimic cargo delivering activity of natural exosomes.
Development of Selective Inhibitors for Aldehyde Dehydrogenases Based on Substituted Indole-2,3-diones (2014)

Aldehyde dehydrogenases (ALDH) participate in multiple metabolic pathways and have been indicated to play a role in several cancerous disease states. Our laboratory is interested in developing novel and selective ALDH inhibitors. We looked to further work recently published by developing a class of isoenzyme-selective inhibitors using similar indole-2,3-diones that exhibit differential inhibition of ALDH1A1, ALDH2, and ALDH3A1. Kinetic and X-ray crystallography data suggest that these inhibitors are competitive against aldehyde binding, forming direct interactions with active-site cysteine residues. The selectivity is precise in that these compounds appear to interact directly with the catalytic nucleophile, Cys243, in ALDH3A1 but not in ALDH2. In ALDH2, the 3-keto group is surrounded by the adjacent Cys301/303. Surprisingly, the orientation of the interaction changes depending on the nature of the substitutions on the basic indole ring structure and correlates well with the observed structure-activity relationships for each ALDH isoenzyme.
TU‐F‐BRF‐09: Feasibility Study of Spatial and Temporal Fractionation Using a Table‐Top Image‐Guided MRT System (2014)

Purpose: Microbeam radiation therapy is a promising experimental radiotherapy method for cancer treatment. Synchrotron studies have shown that MRT can preferentially ablate tumors while mostly preserving the surrounding normal tissues. Our purpose is to develop a compact microbeam irradiator that can be accessible for laboratory research on MRT's therapeutic mechanism, with the ultimate goal of translating this technique for clinical applications. Utilizing a carbon nanotube field emission X‐ray source array, our lab has developed a first of its kind table‐top microbeam irradiator. The purpose of this study is to investigate the possibility of increasing the total dose to the tumor region using spatial and temporal fractionation. Methods: MRI and CT scans were acquired and registered to locate both the target region and the landmark in the treatment coordinate space. A crossbeam treatment configuration was planned to achieve the desired dosage and tumor coverage. One array of 300 μm‐thick microbeams was delivered to the target on the first day. Another array, perpendicular to the first one, was delivered the next day targeting the same region. The feasibility of this image‐guided MRT procedure was evaluated using a phantom. Gafchromic EBT2 film was employed to characterize the targeting accuracy and the delivered tumor dose. Results: The preliminary phantom study showed that a cross‐pattern of microbeam arrays was successfully delivered with sub‐millimeter targeting accuracy. The delivered dose in the target region was doubled. The fraction of tumor volume that received the peak dose was increased. Conclusion: Temporal fractionation of crosspatterned microbeams can be delivered to the same target region. The feasibility of this procedure was investigated with a phantom study. Once implemented, this procedure has the potential of increasing the tumor control effect of MRT and of achieving better normal tissue recovery.
Abstract 921: Combination of antibody-targeted amanitin conjugates (ATAC) with immune checkpoint inhibitors shows synergistic therapeutic effect <i>in vitro</i> and <i>in vivo</i> (2021)

Abstract Background: Antibody-targeted amanitin conjugates (ATACs) are a new class of antibody-drug conjugates (ADCs) using amanitin as a toxic payload. Amanitin binds to the RNA polymerase II and thereby efficiently inhibits the cellular transcription process. The present study highlights the benefit of combining ATACs with immune checkpoint inhibitors. The combination of these two modalities leads to an induction of immunogenic cell death (ICD) in vitro and a synergistic anti-tumor effect in vivo. Hence, the combination of ATACs with immune checkpoint inhibitors (ICI) provides a promising approach for potential further cancer treatment. Material and methods: Cell lines: BT-474 (breast ductal carcinoma); BJAB, Raji, (Burkitt lymphoma) Antibody: engineered monoclonal antibody produced at Heidelberg Pharma Toxic warhead: Cysteine reactive amanitin-linker constructs were synthesized at Heidelberg Pharma and conjugated site-specifically to the antibody. Animal models: Raji cells with/without human peripheral blood mononuclear cells (PBMCs) were implanted subcutaneously in mice. Treatment: ADC (ATAC): single dose i.v.; immune checkpoint inhibitor: Q3D x6. Results: The treatment of target-positive cell lines (e.g., BT-474 and BJAB) with corresponding ATACs led to the induction of three ICD hallmarks in vitro. In addition to increased surface expression of calreticulin (CRT), ATAC-treated tumor cells secreted adenosine triphosphate (ATP) and released high-mobility group box 1 protein (HMGB1). In contrast, this was not observed when the same cells were treated with a non-targeting ATAC. In a subcutaneous CDX model, mixed with human PBMCs, the combined administration of target specific ATACs with an immune checkpoint inhibitor led to an increased anti-tumor effect indicated by significant tumor growth inhibition as compared to single treatment with ATAC or ICI. This synergistic effect was not observed in mice bearing tumors without human PBMCs. Conclusions: Antibody-targeted amanitin conjugates (ATACs) induced immunogenic cell death in vitro and resulted in an increased anti-tumor effect in combination with an immune checkpoint inhibitor in a subcutaneous CDX model if human PBMCs were present. Consequently, the data presented provide a rationale to the use of ATACs in combination therapy with immune checkpoint inhibitors. Citation Format: Kristin Decker, Irina Dranova, Christian Orlik, Aniko Palfi, Christoph Mueller, Ram Kumar Singh, Robert Z. Orlowski, Torsten Hechler, Andreas Pahl, Michael Kulke. Combination of antibody-targeted amanitin conjugates (ATAC) with immune checkpoint inhibitors shows synergistic therapeutic effect in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 921.
Optical control of photon tunneling through an array of nanometer scale cylindrical channels (2003)

Photon tunneling gated by light at a different wavelength in an artificially created array of nanometer scale cylindrical channels in a thick gold film is described. This observation suggests the possibility of building a new class of "gated" photon tunneling devices for massive parallel all-optical signal and image processing.