gebhart/patrepeval huggingface dataset:
Development of a High-Throughput Screening Cancer Cell-Based Luciferase Refolding Assay for Identifying Hsp90 Inhibitors (2013)

The 90 kDa heat-shock protein (Hsp90) and other cochaperones allow for proper folding of nascent or misfolded polypeptides. Cancer cells exploit these chaperones by maintaining the stability of mutated and misfolded oncoproteins and allowing them to evade proteosomal degradation. Inhibiting Hsp90 is an attractive strategy for cancer therapy, as the concomitant degradation of multiple oncoproteins may lead to effective anti-neoplastic agents. Unfortunately, early clinical trials have been disappointing with N-terminal Hsp90 inhibitors, as it is unclear whether the problems that plague current Hsp90 inhibitors in clinical trials are related to on-target or off-target activity. One approach to overcome these pitfalls is to identify structurally diverse scaffolds that improve Hsp90 inhibitory activity in the cancer cell milieu. Utilizing a panel of cancer cell lines that express luciferase, we have designed an in-cell Hsp90-dependent luciferase refolding assay. The assay was optimized using previously identified Hsp90 inhibitors and experimental novobiocin analogues against prostate, colon, and lung cancer cell lines. This assay exhibits good interplate precision (% CV), a signal-to-noise ratio (S/N) of ≥7, and an approximate Z-factor ranging from 0.5 to 0.7. Novobiocin analogues that revealed activity in this assay were examined via western blot experiments for client protein degradation, a hallmark of Hsp90 inhibition. Subsequently, a pilot screen was conducted using the Prestwick library, and two compounds, biperiden and ethoxyquin, revealed significant activity. Here, we report the development of an in-cell Hsp90-dependent luciferase refolding assay that is amenable across cancer cell lines for the screening of inhibitors in their specific milieu.
Oxidative Desulfurization-Fluorination: A Facile Entry to a Wide Variety of Organofluorine Compounds Leading to Novel Liquid-Crystalline Materials (2001)

The oxidative desulfurization-fluorination reaction of organosulfur compounds using an N-haloimide and a fluoride source is demonstrated to be an effective and mild fluorinaton method that allows us to synthesize in high yields with high chemoselectivity various types of gem-difluoro compounds, trifluoromethyl-substituted (hetero)aromatics, trifluoromethyl ethers, and N-trifluoromethylanilines. Herein briefly summarized are the synthetic procedures as well as the scope and limitations of the reaction. The applicability of the reaction is demonstrated by the synthesis of a difluorinated glutamic acid and novel liquid-crystalline materials having an N-trifluoromethylamino, trifluoromethoxy, or 1,2-difluoroethylene group. The fluorine-containing liquid-crystalline materials are compared with the corresponding non-fluorinated materials in respect to phase transition behaviors and electro-optical properties and shown to be suitable for not only super twisted nematic (STN) but also for thin film transistor (TFT)-addressed liquid crystals displays. 1. Introduction 2. Fluorination Reactions 2.1 Fluorination of Sulfides and Thiols 2.2 Fluorination of Dithioacetals 2.3 Oxidative Desulfurization-Fluorination of Dithioester and Orthothioester 2.4 Synthesis of Trifluoromethyl Ethers from Dithiocarbonates 2.5 Oxidative Desulfurization-Fluorination of Thionesters and Thioncarbonates 2.6 Synthesis of Trifluoromethylamines from Dithiocarbamates 3. Synthesis and Electro-Optical Properties of Novel Fluorine-Containing Liquid Crystals 3.1 Synthesis and Electro-Optical Properties of N-Trifluoromethylamino-Substituted Liquid Crystals 3.2 Syntheses and Electro-Optical Properties of Liquid Crystals having Trifluoromethoxy Polar Functional Group 3.3 Synthesis and Properties of 3-Substituted Phenyl Trifluoromethyl Ethers 3.4 Synthesis and Electro-Optical Properties of Liquid Crystals with a vic-Difluoro-Olefinic Moiety
Orderly recruitment of motoneurons in an acute rabbit model (2002)

Artificial muscle activation by electrical stimulation of motor nerves is characterized by poor force gradation and a relative fast onset of muscle fatigue. Muscle force gradation would improve and the onset of muscle fatigue would be delayed by mimicking the physiological recruitment order by primarily activating the small-diameter motoneurons. In this study selective anodal blocking has been used in an acute animal model to investigate the advantages of orderly recruitment. The results show that primarily activating the smaller motor units results in a reduced steepness of the recruitment curve. At low forces the twitch width increases, so a lower stimulation frequency is needed to obtain a fused contraction.
A novel suture‐based method for efficient transplantation of stem cells (2012)

Advances in regenerative medicine have improved the potential of using cellular therapy for treating several diseases. However, the effectiveness of new cellular therapies is largely limited by low cell engraftment and inadequate localization. To improve on these limitations, we developed a novel delivery mechanism using cell-seeded biological sutures. We demonstrate the ability of cell-seeded biological sutures to efficiently implant human mesenchymal stem cells (hMSCs) to specific regions within the beating heart; a tissue known to have low cell retention and engraftment shortly after delivery. Cell-seeded biological sutures were developed by bundling discrete microthreads extruded from extracellular matrix proteins, attaching a surgical needle to the bundle and seeding the bundle with hMSCs. During cell preparation, hMSCs were loaded with quantum dot nanoparticles for cell tracking within the myocardium. Each biological suture contained an average of 5903 ± 1966 hMSCs/cm suture length. Delivery efficiency was evaluated by comparing cell-seeded biological suture implantation with intramyocardial (IM) cell injections (10,000 hMSCs in 35 μL) into the left ventricle of normal, noninfarcted rat hearts after 1 h. Delivery efficiency of hMSCs by biological sutures (63.6 ± 10.6%) was significantly higher than IM injection (11.8 ± 6.2%; p < 0.05). Cell-tracking analysis indicated suture-delivered hMSCs were found throughout the thickness of the ventricular myocardium: along the entire length of the biological suture track, localizing closely with native myocardium. These results suggest cell-seeded biological sutures can deliver cells to the heart more efficiently than conventional methods, demonstrating an effective delivery method for implanting cells in soft tissue.
A mobile phone based alarm system for supervising vital parameters in free moving rats (2012)

Study protocols involving experimental animals often require the monitoring of different parameters not only in anesthetized, but also in free moving animals. Most animal research involves small rodents, in which continuously monitoring parameters such as temperature and heart rate is very stressful for the awake animals or simply not possible. Aim of the underlying study was to monitor heart rate, temperature and activity and to assess inflammation in the heart, lungs, liver and kidney in the early postoperative phase after experimental cardiopulmonary bypass involving 45 min of deep hypothermic circulatory arrest in rats. Besides continuous monitoring of heart rate, temperature and behavioural activity, the main focus was on avoiding uncontrolled death of an animal in the early postoperative phase in order to harvest relevant organs before autolysis would render them unsuitable for the assessment of inflammation. We therefore set up a telemetry-based system (Data Science International, DSI™) that continuously monitored the rat's temperature, heart rate and activity in their cages. The data collection using telemetry was combined with an analysis software (Microsoft excel™), a webmail application (GMX) and a text message-service. Whenever an animal's heart rate dropped below the pre-defined threshold of 150 beats per minute (bpm), a notification in the form of a text message was automatically sent to the experimenter's mobile phone. With a positive predictive value of 93.1% and a negative predictive value of 90.5%, the designed surveillance and alarm system proved a reliable and inexpensive tool to avoid uncontrolled death in order to minimize suffering and harvest relevant organs before autolysis would set in. This combination of a telemetry-based system and software tools provided us with a reliable notification system of imminent death. The system's high positive predictive value helped to avoid uncontrolled death and facilitated timely organ harvesting. Additionally we were able to markedly reduce the drop out rate of experimental animals, and therefore the total number of animals used in our study. This system can be easily adapted to different study designs and prove a helpful tool to relieve stress and more importantly help to reduce animal numbers.
Effects of Thyroxine as Compared with Thyroxine plus Triiodothyronine in Patients with Hypothyroidism (1999)

In patients with hypothyroidism, partial substitution of triiodothyronine for thyroxine may improve mood and neuropsychological function; this finding suggests a specific effect of the triiodothyronine normally secreted by the thyroid gland.
Cytotoxicity of interleukin 2-toxin toward lymphocytes from patients with adult T-cell leukemia. (1989)

The inhibitory effect of a diphtheria toxin-related interleukin 2 fusion protein, IL-2-toxin, on protein synthesis in adult T-cell leukemia/lymphoma (ATL) cells was examined in vitro. Peripheral blood ATL cells from 12 patients (six acute type, four chronic type, and two smoldering type ATL) and the lymph node cells from three ATL patients (two acute type and one lymphoma type ATL) were examined. At a concentration of 10(-8) M, IL-2-toxin inhibited protein synthesis by 60 to 98% in lymph node ATL cells, whereas protein synthesis in peripheral blood ATL cells was inhibited from 20 to 57% in acute type, and from 3 to 13% in chronic type. In contrast, IL-2-toxin had no measurable effect on T-cells from either patients with smoldering type ATL or normal controls. The cytopathic effects of IL-2-toxin were blocked by the addition of anti-CD25 monoclonal antibody, suggesting that the inhibition of protein synthesis in target cells was mediated by the IL-2 receptor (IL-2R). The degree of inhibition of protein synthesis, however, was not closely correlated with expression of CD25 antigen (low-affinity Mr 55,000 glycoprotein, IL-2R, Tac antigen) on ATL cells. There was an apparent correlation between the degree of inhibition and the rate of protein synthesis in ATL cells. We demonstrate that ATL cells from patients with acute or lymphoma type disease were more sensitive to IL-2-toxin than cells from chronic or smoldering disease. These findings suggest that the high affinity IL-2R present on acute and lymphoma type ATL cells may serve as a target for therapy with this recombinant chimeric toxin.
The Rapidly Evolving Centromere-Specific Histone Has Stringent Functional Requirements inArabidopsis thaliana (2010)

Centromeres control chromosome inheritance in eukaryotes, yet their DNA structure and primary sequence are hypervariable. Most animals and plants have megabases of tandem repeats at their centromeres, unlike yeast with unique centromere sequences. Centromere function requires the centromere-specific histone CENH3 (CENP-A in human), which replaces histone H3 in centromeric nucleosomes. CENH3 evolves rapidly, particularly in its N-terminal tail domain. A portion of the CENH3 histone-fold domain, the CENP-A targeting domain (CATD), has been previously shown to confer kinetochore localization and centromere function when swapped into human H3. Furthermore, CENP-A in human cells can be functionally replaced by CENH3 from distantly related organisms including Saccharomyces cerevisiae. We have used cenh3-1 (a null mutant in Arabidopsis thaliana) to replace endogenous CENH3 with GFP-tagged variants. A H3.3 tail domain-CENH3 histone-fold domain chimera rescued viability of cenh3-1, but CENH3's lacking a tail domain were nonfunctional. In contrast to human results, H3 containing the A. thaliana CATD cannot complement cenh3-1. GFP-CENH3 from the sister species A. arenosa functionally replaces A. thaliana CENH3. GFP-CENH3 from the close relative Brassica rapa was targeted to centromeres, but did not complement cenh3-1, indicating that kinetochore localization and centromere function can be uncoupled. We conclude that CENH3 function in A. thaliana, an organism with large tandem repeat centromeres, has stringent requirements for functional complementation in mitosis.
Stabilization of antibody fragments in adverse environments (1998)

Antibody fragments have the potential to be used as sensitive and specific binding agents in a broad range of industrial applications. Genetic manipulation has been used to design a series of antibody fragment configurations with a flexible linker and/or a disulphide bond between the heavy chain and light chain of an antibody fragment against the herbicide atrazine. The thermostability and stability to a range of denaturants, polar and non-polar solvents, surfactants and proteases have been compared. It has been found that a novel antibody fragment construct (STAB: stabilized antibody) containing both a flexible linker and a disulphide bond can be effectively produced and shows greatly improved stability in these diverse environments. These STABs should be useful in environmental diagnostics and remediation, and may provide a generic approach for stabilizing antibody fragments in formulations containing detergents and penetrants for topical application in the pharmaceutical and cosmetic industries.
LISA—machine description language for cycle-accurate models of programmable DSP architectures (1999)

Article LISA—machine description language for cycle-accurate models of programmable DSP architectures Share on Authors: Stefan Pees Integrated Signal Processing Systems, Aachen University of Technology, Aachen, Germany Integrated Signal Processing Systems, Aachen University of Technology, Aachen, GermanyView Profile , Andreas Hoffmann Integrated Signal Processing Systems, Aachen University of Technology, Aachen, Germany Integrated Signal Processing Systems, Aachen University of Technology, Aachen, GermanyView Profile , Vojin Zivojnovic AXYS Design Automation, Inc., 135 Santa Louisa, Irvine, CA AXYS Design Automation, Inc., 135 Santa Louisa, Irvine, CAView Profile , Heinrich Meyr Integrated Signal Processing Systems, Aachen University of Technology, Aachen, Germany Integrated Signal Processing Systems, Aachen University of Technology, Aachen, GermanyView Profile Authors Info & Claims DAC '99: Proceedings of the 36th annual ACM/IEEE Design Automation ConferenceJune 1999 Pages 933–938https://doi.org/10.1145/309847.310101Online:01 June 1999Publication History 75citation943DownloadsMetricsTotal Citations75Total Downloads943Last 12 Months17Last 6 weeks3 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Electronic and Photonic Applications of Polymers (1988)

The application of polymers to selected areas of electronics and photonics is reviewed. These areas include microlithography, packaging, conducting polymers, molecular electronics, optical fiber coatings, integrated optics, nonlinear optics, and optical recording. This chapter provides an overview of the various technologies and highlights the advantages offered by the unique properties of polymers in meeting the material requirements of each technology.
Host and non‐host pathogens elicit different jasmonate/ethylene responses in Arabidopsis (2004)

Arabidopsis does not support the growth and asexual reproduction of the barley pathogen, Blumeria graminis f. sp. hordei Bgh). A majority of germlings fail to penetrate the epidermal cell wall and papillae. To gain additional insight into this interaction, we determined whether the salicylic acid (SA) or jasmonate (JA)/ethylene (ET) defence pathways played a role in blocking barley powdery mildew infections. Only the eds1 mutant and NahG transgenics supported a modest increase in penetration success by the barley powdery mildew. We also compared the global gene expression patterns of Arabidopsis inoculated with the non-host barley powdery mildew to those inoculated with a virulent, host powdery mildew, Erysiphe cichoracearum. Genes repressed by inoculations with non-host and host powdery mildews relative to non-inoculated control plants accounted for two-thirds of the differentially expressed genes. A majority of these genes encoded components of photosynthesis and general metabolism. Consistent with this observation, Arabidopsis growth was inhibited following inoculation with Bgh, suggesting a shift in resource allocation from growth to defence. A number of defence-associated genes were induced during both interactions. These genes likely are components of basal defence responses, which do not effectively block host powdery mildew infections. In addition, genes encoding defensins, anti-microbial peptides whose expression is under the control of the JA/ET signalling pathway, were induced exclusively by non-host pathogens. Ectopic activation of JA/ET signalling protected Arabidopsis against two biotrophic host pathogens. Taken together, these data suggest that biotrophic host pathogens must either suppress or fail to elicit the JA/ET signal transduction pathway.
Laser ranging: a critical review of usual techniques for distance measurement (2001)

We review some usual laser range finding techniques for in- dustrial applications. After outlining the basic principles of triangulation and time of flight (pulsed, phase-shift and frequency modulated continu- ous wave (FMCW)), we discuss their respective fundamental limitations. Selected examples of traditional and new applications are also briefly presented. © 2001 Society of Photo-Optical Instrumentation Engineers.
Prospects for Telediagnosis Using Ultrasound (1996)

Ultrasound imaging is currently used as a primary diagnostic tool in cardiology, abdominal disorders, pulmonary medicine, trauma, and obstetrics. Because of its relatively low capital and operating costs as well as its growth potential, it represents one of the major diagnostic modalities of future health care. However, the use of ultrasonography as a mobile and powerful modality is controlled by the availability of a highly skilled technician to acquire the images and an experienced physician to interpret them. This paper discusses the technology required to increase the availability of a diagnosing physician by employing telerobotics. With this technology, the physician can guide the motion of the transducer by the technician from a remote location. Thus, the physician controls the examination and renders the diagnosis. It is shown that communication lines at 1.5 Mbits/s (T-1 speed) can, with appropriate compression, support both real-time viewing of the ultrasound images and telerobotic manipulation of the transducer. The incremental costs of telediagnosis for an examination are estimated to be a small fraction of the base charges and significantly less than the expense of bringing a physician to a remote location or transporting a patient to a regional medical center. Telediagnosis can, in addition, provide benefits from immediate interpretation and consultation that cannot be duplicated using store-and-forward scenarios.
Gas Extraction and Risk of Subsidence: the Case of the Northern Adriatic Gas Fields, Technical Issues (1998)

Abstract The exploitation of offshore gas fields in the Northern Adriatic Sea (Italy) has been jeopardized by a growing sensitivity of the public opinion to an allegedly possible subsidence impact on the heavily urbanized coast. The proximity of the city of Venice, with its invaluable legacy of historical monuments and masterpieces has made the debate even harsher. A detailed procedure of environmental impact assessment is currently undertaken by the central Italian government. Considerable energy and resources have been expended by Agip in its effort to show that the project has no actual consequence on the stability and elevation of the coast. A large number of lab tests and in-situ compaction measurements have been collected in an area that spans the whole Northern Adriatic offshore of the Italian coast. New lab techniques have been devised to reconcile in-situ and lab compressibility, the latter one being consistently biased towards higher values. The geology of the area is known in great detail thanks to a large 3-D seismic survey performed in recent years. Extensive and detailed modeling of the whole area has shown that no tangible risk exists of subsidence affecting the Venetian lagoon area and the Po river delta. For extra safety, a water injection plan has been set up to prevent the depressurization from propagating through the lateral aquifers away from the gas fields. We present the state of the situation from a technical viewpoint, while it is clear that also political, economical and social aspects play a fundamental role in cases like this.
Structural and idiotypic characterization of the L chains of human IgM autoantibodies with different specificities. (1989)

We have determined the V region amino acid sequence and/or serologic markers (kIIIb, PSL2, and PSL3) of 24 IgM monoclonal autoantibodies with specificities of anti-gamma-globulin (RF), anti-I (cold agglutinin), anti-low density lipoprotein and anti-intermediate filaments. The data emphasize the overwhelming selection of the HumKv325/VkIIIb L chain for this family of autoantibodies. The few amino acid substitutions found within the VL regions were mainly concentrated in the complementarity-determining region 1. JK and CK genes did not show the same pattern of restriction. There is a good correlation between the amino acid sequence and the presence of the kIIIb marker. The idiotypic marker PSL2 was present in 34 out of 35 kIIIb L chains analyzed (97%) and the PSL3 in 27 (80%). Moreover, the hydrophilicity and antigenic profiles of these L chains corroborate the presence of the epitopes detected by the anti-CRI. These results demonstrate a restricted selection of the Vk genes used by a family of self reacting proteins, and an unusual evolutionary conservation of the idiotypic structure that may be involved in the network regulation.