gebhart/patrepeval huggingface dataset:
Synthesis and Antimicrobial Activity of Albicidin Derivatives with Variations of the Central Cyanoalanine Building Block (2016)

To investigate the pharmacophore regions of the antibiotic albicidin, derivatives with variations on the central amino acid were synthesized. Charged as well as uncharged residues were chosen to explore the influence of charge, chirality, and steric bulk. The bioactivity of the newly synthesized derivatives was determined by a microdilution technique to obtain minimum inhibitory concentrations (MIC) values. The compounds were also tested in a cell-free system to obtain information about their ability to inhibit their primary target, DNA gyrase. It was then shown that derivatives with uncharged side chains retain antibacterial activity, whereas incorporation of charged amino acid residues decreases the antibacterial activity dramatically, possibly due to restricted cell penetration of these derivatives. From the newly synthesized derivatives, the threonine derivative shows the most promising results in both tests. The information will help to develop the features of albicidin toward more drug-like structures.
Comprehensive Design of a Three-Phase Three-Switch Buck-Type PWM Rectifier (2007)

A three-phase three-switch buck-type pulsewidth modulation rectifier is designed for telecom applications in this paper. The rectifier features a constant 400-V output voltage and 5-kW output power at the three-phase 400-V mains. The principle of operation and the calculation of the relative on-times of the power transistors are described. Based on analytical relationships the stresses of the active and passive components are determined and the accuracy of the given calculations is verified by digital simulations. Exemplarily, a 5-kW power converter is then designed based on the analytical expressions and on switching loss measurements from a hardware prototype constructed with insulated gate bipolar transistor/diode power modules. The loss distribution of the components, the total efficiency, and the junction temperatures of the semiconductors are then evaluated in dependency on the operating point. Finally, the trade-off between the selected switching frequency and the admissible power range for the realized design is shown and a total efficiency of 95.0% is measured on the hardware prototype, where an excellent agreement with the theoretically evaluated efficiency is shown
Adsorption of Components of the Plasma Kinin-Forming System on the Surface of Porphyromonas gingivalis Involves Gingipains as the Major Docking Platforms (2010)

Enhanced production of proinflammatory bradykinin-related peptides, the kinins, has been suggested to contribute to the pathogenesis of periodontitis, a common inflammatory disease of human gingival tissues. In this report, we describe a plausible mechanism of activation of the kinin-generating system, also known as the contact system or kininogen-kallikrein-kinin system, by the adsorption of its plasma-derived components such as high-molecular-mass kininogen (HK), prekallikrein (PK), and Hageman factor (FXII) to the cell surface of periodontal pathogen Porphyromonas gingivalis. The adsorption characteristics of mutant strains deficient in selected proteins of the cell envelope suggested that the surface-associated cysteine proteinases, gingipains, bearing hemagglutinin/adhesin domains (RgpA and Kgp) serve as the major platforms for HK and FXII adhesion. These interactions were confirmed by direct binding tests using microplate-immobilized gingipains and biotinylated contact factors. Other bacterial cell surface components such as fimbriae and lipopolysaccharide were also found to contribute to the binding of contact factors, particularly PK. Analysis of kinin release in plasma upon contact with P. gingivalis showed that the bacterial surface-dependent mechanism is complementary to the previously described kinin generation system dependent on HK and PK proteolytic activation by the gingipains. We also found that several P. gingivalis clinical isolates differed in the relative significance of these two mechanisms of kinin production. Taken together, these data show the importance of this specific type of bacterial surface-host homeostatic system interaction in periodontal infections.
A Biocompatible Endothelial Cell Delivery System for in Vitro Tissue Engineering (2009)

Engineering solid tissues, including cardiac muscle, requires the inclusion of a microvasculature. Prevascularization in vitro will likely be dependent upon coculturing parenchymal cells with vascular cells, on a matrix that is sufficiently porous to allow microvessel formation. In this study, we examined the behavior and function of endothelial cells on a highly porous elastomeric 3D poly(glycerol sebacate) (PGS) scaffold, to provide a flexible and biocompatible endothelial cell delivery system for developing cardiac engineered tissues with neovascularization potential. Both static and perfusion cell seeding methods were used, and the effects of surface treatment of the scaffold with various extracellular matrix components were examined. Endothelial cell adhesion and phenotype on the PGS scaffold under various flow conditions were also determined. Surface coating with laminin markedly improved the endothelial cell adhesion, survival, and proliferation. The anticoagulant phenotype of adhered endothelial cells was further regulated by the application of flow through regulation of nitric oxide expression. By providing a highly porous scaffolding that contains endothelium with anticoagulant properties, the endothelial cell-seeded PGS scaffold could provide a new basis for subsequent coculture studies with various cell types to develop complex engineered tissue constructs with vascularization capacity.
ADAPTIVE SPEED LIMIT FOR LAST MILE VEHICLES ON PUBLIC WALKWAYS (2017)

Foldable ultralight electric vehicles (E-ULV) are a promising key component for future sustainable traffic chains for urban regions with mountainous topography. While E-Bikes are prohibited in metropolitan public transport during rush-hours, foldable E-ULV are a real innovation for the "last mile" to the destination. This paper presents electric drive add-on kits for foldable scooters that can be used on public walkways, train stations and subway platforms. The key innovation of these very lightweight and powerful foldable scooters is the adaptive speed limitation based on an ultrasonic sensor that limits the maximum velocity on crowded walkways and permits a faster movement up to jogging velocity if the walkway is obstacle-free. The E-ULV has been tested legally in small fleets on public walkways in Stuttgart and Esslingen by special permission of the Ministry for Traffic and Infrastructure, Stuttgart. E-ULV for the "last mile" will reduce car kilometers and transfer them to the public transport system. Furthermore, parking lot search traffic can be avoided in crowded city centres with a E-ULV in the car trunk
ChemInform Abstract: Synthesis of Monohydroxylated 2‐Azabicyclo(2.2.1)heptan‐3‐ones. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Distributed fiber filter based on index-matched coupling between core and cladding (2005)

A new type of fiber for distributed filtering is proposed, designed to have resonant coupling between core and cladding at desired wavelengths. Design principles are illustrated with simulations of several fibers. A filter fiber was fabricated following this design strategy. Measured transmission spectra and imaging of mode output confirm the expected resonant coupling between core and cladding near 1100nm.
Development of MEMS Hot-Film Sensors (2012)

BAE Systems have been developing hot-film sensors for the detection and monitoring of laminar/turbulent flow on a wing. The sensors are constructed using silicon manufacturing techniques, with the ultimate aim of making them capable of being certified for flight. Primarily, this has involved looking at aspects of the sensor design, such as the robustness of the sensors to raindrop impacts and their resistance to environmental degradation. Tests done to date have shown that provided the sensors have a thin protective coating of a few microns thickness and are not installed close to the leading-edge of a wing they should be capable of being certified for flight.
Time domain comparison of pulse-width modulation schemes (2003)

This paper shows that classical space vector modulation (SVM) is functionally identical to double-sided uniform-sampled pulse width modulation (UPWM). Consequently, direct conclusions about harmonic distortion, losses, DC bus utilization, and ease of implementation are made that clarify some existing misconceptions about SVM. Since UPWM is conceptually simple and involves few steps, it is possible that computation may be reduced in practice. UPWM algorithms can avoid the sector and switch sequence tracking tasks in an SVM algorithm. The linear modulation range extension "inherent" to SVM is associated with triplen harmonic injection, and does not provide advantages over conventional third-harmonic injection techniques. The equivalence of SVM and UPWM means that SVM has spectral distortion in baseband as is known to occur in UPWM. This has implications for naturally-sampled sine-triangle PWM (NPWM)-which is known not to generate baseband distortion.
The Dynamics Of Image Processing Viewed As Damped Elastic Deformation (2009)

Publication in the conference proceedings of EUSIPCO, Glasgow, Scotland, 2009
Cavity Optomechanics with Silicon Nitride Membrane Gratings (2011)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text U. Kemiktarak, M. Metcalfe, M. Durand, and J. Lawall, "Cavity Optomechanics with Silicon Nitride Membrane Gratings," in Frontiers in Optics 2011/Laser Science XXVII, OSA Technical Digest (Optica Publishing Group, 2011), paper FTuN4. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19 (2022)

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log<sub>10</sub> at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.
Micro reactors for the optimisation of reaction conditions in asymmetric metal catalysis (2005)

Two types of micro reactors were employed for enantioselective metal catalysed reactions. In the first type of reactor, an electroosmotic flow was used, whereas the second type of reactor used a pressure driven flow. The purpose of the study is to develop tools for rapid and efficient optimization of reactions, utilising minimum amounts of reagents.
Chemoprevention Gene Therapy (CGT) of Pancreatic Cancer Using Perillyl Alcohol and a Novel Chimeric Serotype Cancer Terminator Virus (2014)

Conditionally replication competent adenoviruses (Ads) that selectively replicate in cancer cells and simultaneously express a therapeutic cytokine, such as melanoma differentiation associated gene- 7/Interleukin-24 (mda-7/IL-24), a Cancer Terminator Virus (CTV-M7), hold potential for treating human cancers. To enhance the efficacy of the CTV-M7, we generated a chimeric Ad.5 and Ad.3 modified fiber bipartite CTV (Ad.5/3-CTV-M7) that can infect tumor cells in a Coxsackie Adenovirus receptor (CAR) independent manner, while retaining high infectivity in cancer cells containing high CAR. Although mda-7/IL-24 displays broad-spectrum anticancer properties, pancreatic ductal adenocarcinoma (PDAC) cells display an intrinsic resistance to mda-7/IL-24-mediated killing due to an mda-7/IL-24 mRNA translational block. However, using a chemoprevention gene therapy (CGT) approach with perillyl alcohol (POH) and a replication incompetent Ad to deliver mda-7/IL-24 (Ad.mda-7) there is enhanced conversion of mda-7/IL-24 mRNA into protein resulting in pancreatic cancer cell death in vitro and in vivo in nude mice containing human PDAC xenografts. This combination synergistically induces mda-7/IL-24-mediated cancer-specific apoptosis by inhibiting anti-apoptotic Bcl-xL and Bcl-2 protein expression and inducing an endoplasmic reticulum (ER) stress response through induction of BiP/GRP-78, which is most evident in chimeric-modified non-replicating Ad.5/3- mda-7- and CTV-M7-infected PDAC cells. Moreover, Ad.5/3-CTV-M7 in combination with POH sensitizes therapy-resistant MIA PaCa-2 cell lines over-expressing either Bcl-2 or Bcl-xL to mda-7/IL-24-mediated apoptosis. Ad.5/3-CTV-M7 plus POH also exerts a significant antitumor 'bystander' effect in vivo suppressing both primary and distant site tumor growth, confirming therapeutic utility of Ad.5/3-CTV-M7 plus POH in PDAC treatment, where all other current treatment strategies in clinical settings show minimal efficacy.
Large‐scale purification and preliminary x‐ray diffraction studies of human aspartylglucosaminidase (1996)

Aspartylglucosaminidase (AGA) is a lysosomal asparaginase that takes part in the ordered degradation of glycoproteins and a deficiency of which results in a lysosomal accumulation disease aspartylglucosaminuria in human. The mature enzyme consists of 24-kDa and 17-kDa subunits, which are both heterogeneously glycosylated. Activation of the enzyme from a single precursor polypeptide into two subunits is accomplished in the endoplasmic reticulum (ER). The relative lack of this proteolytic capacity in several tested high-producing expression systems has complicated the production of active recombinant enzyme in high quantities, which would be an alternative for purification of this molecule for crystallization. Consequently, the AGA enzyme has to be purified directly from cellular or tissue sources for crystallographic analysis. Here we describe a large-scale purification method to produce milligram amounts of homogeneous AGA from human leukocytes. The purified AGA enzyme represents a heterogeneous pool of molecules not only due to glycosylation, but also heterogeneity at the polypeptide level, as demonstrated here. We were able to isolate a homogeneous polypeptide pool that was successfully crystallized and preliminary X-ray data collected from the crystals. The crystals diffract well to 2.0 Å and are thus suitable for determination of the crystal structure of AGA.
Implementing a micro-operation cache with compaction (2023)

Systems, apparatuses, and methods for compacting multiple groups of micro-operations into individual cache lines of a micro-operation cache are disclosed. A processor includes at least a decode unit and a micro-operation cache. When a new group of micro-operations is decoded and ready to be written to the micro-operation cache, the micro-operation cache determines which set is targeted by the new group of micro-operations. If there is a way in this set that can store the new group without evicting any existing group already stored in the way, then the new group is stored into the way with the existing group(s) of micro-operations. Metadata is then updated to indicate that the new group of micro-operations has been written to the way. Additionally, the micro-operation cache manages eviction and replacement policy at the granularity of micro-operation groups rather than at the granularity of cache lines.
Automatic Text Summarization and Classification (2018)

In this tutorial, we consider important aspects (algorithms, approaches, considerations) for tagging both unstructured and structured text for downstream use. This includes summarization, in which text information is compressed for more efficient archiving, searching, and clustering. In the tutorial, we focus on the topic of automatic text summarization, covering the most important milestones of the six decades of research in this area.
Active control of interior noise in a large scale cylinder using piezoelectric actuators (1991)

The noise reduction effectiveness of two types of control force actuator models has been analytically investigated: (1) a point actuator, and (2) an in-plane, piezoelectric actuator. The actuators were attached to the wall of a simply supported, elastic cylinder closed with rigid end caps. Control inputs to the actuators were determined such that the integrated square of the pressure over the interior of the vibrating cylinder was a minimum. Significant interior noise reductions were achieved for all actuator configurations, but especially for the structurally dominated response. Noise reduction of 9 dB to 26 dB were achieved using point force actuators, as well as localized and extended piezoelectric actuators. Control spillover was found to limit overall performance for all cases. However, the use of extended piezoelectric actuators was effective in reducing control spillover, without increasing the number of control degrees of freedom.
Endothelial cell signature in muscle stem cells validated by VEGFA-FLT1-AKT1 axis promoting survival of muscle stem cell (2021)

Abstract Endothelial and skeletal muscle lineages arise from common embryonic progenitors. Despite their shared developmental origin, adult endothelial cells (ECs) and muscle stem cells (MuSCs) (satellite cells) have been thought to possess distinct gene signatures and signaling pathways. Here we shift this paradigm by uncovering how adult MuSC behavior is affected by the expression of a subset of EC transcripts. We used several computational analyses including single-cell RNAseq to show that MuSCs express low levels of canonical EC markers. We demonstrate that MuSC survival is regulated by one such prototypic endothelial signaling pathway (VEGFA-FLT1). Using pharmacological and genetic gain- and loss-of-function studies, we identify the FLT1-AKT1 axis as the key effector underlying VEGFA-mediated regulation of MuSC survival. All together, our data support that the VEGFA-FLT1-AKT1 pathway promotes MuSC survival during muscle regeneration, and highlights how the minor expression of select transcripts is sufficient for affecting cell behavior.
211 SQZ™ eAPCs generated from PBMCs by delivery of multiple mRNAs encoding for antigens, costimulatory proteins, and engineered cytokines (2021)

<h3>Background</h3> Antigen-specific CD8+ T cells are critical components of mounting an effective immune response against tumors. Generation of antigen-specific T cells require interactions with multiple signals produced by antigen presenting cells (APCs). These signals are comprised of three components: (signal 1) the peptide-MHC complex binding to the T cell receptor, (signal 2) costimulatory molecules on the surface of APCs, and (signal 3) inflammatory cytokines binding to cognate receptors on T cells. <h3>Methods</h3> To engineer all major cell subsets of human peripheral blood mononuclear cells (PBMCs) to become enhanced APCs (eAPCs), we used Cell Squeeze® technology to deliver multiple mRNA encoding for non-self-antigens (signal 1), CD86 (signal 2), and/or membrane-bound cytokines (signal 3). The signal 3 molecules, membrane-bound IL-12 (mbIL-12) and membrane-bound IL-2 (mbIL-2), are chimeric proteins designed to increase the localized concentration of the cytokines and limit off-target effects. Flow cytometry and western blots were used to confirm the translation of each of the delivered mRNA. The increased capabilities of these enhanced APCs were assessed in vitro by culturing the APCs with antigen-specific T cells for multiple days before measuring the functionality of antigen-specific T cells via intracellular cytokine staining or ELISA. <h3>Results</h3> We demonstrate that Cell Squeeze® processing of PBMCs with mRNA encoding for signals 1, 2, and 3 results in highly effective enhanced APCs in vitro. In a single squeeze process, efficient delivery and translation of up to five mRNA is observed in all major PBMC cell subsets including T cells, B cells, NK cells, and monocytes. Once translated, the chimeric mbIL-2 and mbIL-12 can bind to their cognate receptors and exhibit minimal shedding from the surface. We show that enhanced APCs can present antigenic peptides derived from mRNA encoding for a foreign antigen on MHC complexes in an HLA agnostic manner, which drives antigen-specific T cell responses. The addition of CD86, mbIL-2, and mbIL-12 further enhance the activation and potency of antigen-specific T cells, as measured by an increase in the secretion of inflammatory cytokines upon restimulation (i.e. IFNγ). <h3>Conclusions</h3> Cell squeezing of human PBMCs with mRNA encoding for signals 1, 2, and 3 has the potential to generate enhanced APCs that drive robust CD8+ T cell response against multiple targets across several disease areas. The versatility of the Cell Squeeze® technology potentially enables rapid exchange of mRNA to other antigens or T cell activation signals.
Electrochemical Characterization of LiCoO2 Composite Particles by Single Particle Measurement (2014)

Active materials for rechargeable lithium-ion batteries are generally coated with polymer binder and conductive carbon on a current collector and evaluated as a porous composite electrode. However, the use of composite electrode makes it difficult to understand the intrinsic electrochemical properties of active material since the electrode structural factors such as porosity and thickness are included in the electrochemical response of composite electrode. In order to prevent such misunderstanding, single particle measurement is one of useful tools. In the case of single particle measurement, a micro current collector is used to establish electrical connection to an active material particle. Thus, the structural factors of composite electrode can be neglected, resulting in precise understanding the intrinsic electrochemical properties of active materials. In this study, LiCoO 2 was focused and its electrochemical properties, particularly the cycleability at high temperatures was investigated by single particle measurement. Furthermore, the cluster particle of LiCoO 2 composite electrode was also evaluated in order to investigate the effects of PVdF binder and conductive carbon on the cycleability of LiCoO 2 . As shown in Figure 1, the rate capability of cluster particle was low compared with LiCoO 2 single particle, namely the discharge capacity was decreased at high discharge rates. This difference is expected to be due to the blocking effect of PVdF binder on Li + diffusion to LiCoO 2 particle from an electrolyte solution. In contrast, the capacity retention in charge-discharge cycle test (Figure 2) was significantly improved in the cluster particle. This result suggests that LiCoO 2 is stabilized by PVdF binder and conductive carbon.