gebhart/patrepeval huggingface dataset:
IL-1 and its receptor are translocated to the nucleus. (1990)

The internalization and intracellular transport of IL-1 and its receptor were examined in the murine T cell line EL-4. For 4 h after internalization intracellular 125I-IL-1 alpha remains bound to its receptor without degradation. Electron microscope autoradiography demonstrates that internalized IL-1 accumulates in purified nuclei. The IL-1 extracted from these nuclei is still bound to receptor. As no receptors for IL-1 were detected in untreated nuclei, these results suggest IL-1 driven translocation of the cell surface IL-1R complex to the nucleus. IL-1R internalization was correlated with IL-1 signal transduction events required to induce growth factor production from several subclones of EL-4 cells. The subsequent transport of the internalized IL-1R complex to the nucleus suggests the possibility for a nuclear site for IL-1R signaling.
Characterization of host response, resorption, and strength properties, and performance in the presence of bacteria for fully absorbable biomaterials for soft tissue repair (2017)

Host response, resorption, repair thickness, strength, and bacterial colonization suggest a more stable and favorable outcome for monofilament, macroporous devices such as Phasix™ relative to multifilament, microporous devices such as Bio-A<sup>®</sup> over time.
<title>Interference Filters With Irregular Spectral Transmittance Characteristics</title> (1974)

For many technological applications filters with rather complicated and irregular spectral transmittance curves are required. A number of numerical approaches to the design of all-dielectric interference filters with such characteristics have been described in the past. A brief outline is given of two different automatic thin film synthesis programs developed for this purpose by the author. With these it is possible to design filters with any desired spectral transmittance curve, providing that the range over which the latter is designed is not excessive. The resulting filter designs call for thin films whose refractive indexes are intermediate to those of known materials, and whose thicknesses may assume any value. A brief des-cription of the apparatus and procedures suitable for the experimental realization of such filters is given. The results obtained for a number of prototype filters are discussed.
Analytical model for absorption by lossy finite-length dipole antennas (2016)

Approximate analytical expression is presented for calculating the current flowing along a lossy finite-length dipole antenna illuminated by an obliquely-incident plane wave. This current is used to evaluate the total power absorbed, both by the lumped load connected across the antenna terminals and by the lossy material of which the antenna structure is made. An approximate value for the load impedance that maximizes the total absorbed power is then determined. The results are compared against results obtained using a Method of Moments (MoM) solution, and good agreement is found.
Predicting Mixing Volumes in Serial Transport in Pipelines (2002)

This paper presents a model for predicting the contaminated mixing volume arising in pipeline batch transfers without physical separators. The proposed technique represents an improvement over the existing methods since it takes into account time-dependent flow rates and accurate concentration-varying axial dispersion coefficients. The governing equation of the model forms a nonlinear boundary-value problem that is solved by a finite element method coupled to the Newton’s method. A comparison among the theoretical predictions of this method, a field test, and other classical procedures show that the proposed method exhibits the best estimate over the whole range of admissible concentrations investigated.
Innovation in insecticide discovery: Approaches to the discovery of new classes of insecticides (2022)

The continuing demand for agrochemical insecticides that can meet increasing grower, environmental, consumer and regulatory requirements creates the need for the development of new solutions for managing crop pest insects. The development of resistance to the currently available insecticidal products adds another critical driver for new insecticidal active ingredients (AIs). One avenue to meeting these challenges is the creation of new classes of insecticidal molecules to act as starting points and prototypes stimulating further spectrum, efficacy and environmental impact refinements. A new class of insecticides is foreshadowed by the first molecule exemplifying that class (first-in-class, FIC) and offers one measure of innovation within the agrochemical industry. Most insecticides owe their discovery to competitor-inspired (i.e. competitor patents/products) or next-generation (follow-on to a company's pre-existing product) strategies. In contrast, FIC insecticides primarily emerge from a bioactive hypothesis approach, with the largest segment resulting from the exploration of new areas of chemistry/heterocycles and underexploited motifs. Natural products also play an important role in the discovery of FIC insecticides. Understanding the origins of these FIC compounds and the approaches used in their discovery can provide insights into successful strategies for future FIC insecticides. This review analyses information on historic and recently introduced FIC insecticides. Its main objective has been to identify the most successful discovery strategies for identifying new agrochemical solutions to meet the challenge of minimizing crop losses resulting from insects. © 2022 Society of Chemical Industry.
Bipotential cell differentiation of KU-812: evidence of a hybrid cell line that differentiates into basophils and macrophage-like cells (1987)

KU-812-F is a subclone of KU-812, which has cytological features similar to the parent clone, and which carries the Philadelphia chromosome. We studied the effects of various chemical agents and serum- free culture (SF-C) condition on its differentiation. The KU-812-F subclone differentiated into macrophage-like cells with phorbol myristate acetate (PMA), but not with other agents. Unexpectedly, under SF-C, KU-812-F cells differentiated into mature basophil-like cells, and the histamine content of cell lysates increased in proportion to maturation. The addition of the condensed supernatant of SF-C promoted the cloning efficiency of KU-812-F cells in semisolid SF-C, whereas the cloning efficiency was reduced in SF-C alone. KU-812-F cells expressed myelomonocytic antigens. Additionally, My4 was induced with PMA and SF- C, but less often. HLA-DR was not expressed in any culture conditions, despite blastic morphology of KU-812-F cells or macrophage-like cells induced with PMA. The IgE receptor could not be demonstrated under any conditions. Correspondingly, immature and mature KU-812-F cells did not respond to anti-IgE or concanavalin A (con A), while histamine release was induced with PMA. In conclusion, KU-812-F belongs to the myeloid cell lineage and is at least a bipotential cell that can differentiate into basophils and macrophage-like cells. Although the functions appear to be dissimilar to those of normal basophils, the KU-812-F cell line may be a good model for basophil differentiation. Moreover, KU-812-F cells may provide new insights because they grow in semisolid culture by an autostimulating mechanism.
A taxonomy based semantic similarity of documents using the cosine measure (2009)

In this paper, we present a new method for calculating semantic similarities between documents. This method is based on cosine similarity calculation between concept vectors of documents obtained from a taxonomy of words that captures IS-A relations. The calculation of semantic similarities between documents is a very time consuming task, since it is necessary first to calculate semantic similarities between each pair of words that appear on different documents. In this paper, we present a new method to calculate semantic similarities between documents which results in faster computational time. Both a taxonomy based semantic similarity and cosine similarity are employed. First, the concept vectors of documents are obtained by extending the terms in the document vectors with their corresponding IS-A concepts. Cosine similarity is then calculated between those concept vectors of documents. Thus, the overall similarity between documents is a combination of cosine similarity and semantic similarity. The proposed semantic similarity is tested in document clustering problem. The experimental results show that our method achieves a good performance.
Preclinical pharmacokinetics and pharmacodynamics of DCLL9718A: An antibody-drug conjugate for the treatment of acute myeloid leukemia (2018)

Few treatment options are available for acute myeloid leukemia (AML) patients. DCLL9718A is an antibody-drug conjugate that targets C-type lectin-like molecule-1 (CLL-1). This receptor is prevalent on monocytes, neutrophils, and AML blast cells, and unlike CD33, is not expressed on hematopoietic stem cells, thus providing possible hematopoietic recovery. DCLL9718A comprises an anti-CLL-1 IgG1 antibody (MCLL0517A) linked to a pyrrolobenzodiazepine (PBD) dimer payload, via a cleavable disulfide-labile linker. Here, we characterize the in vitro and in vivo stability, the pharmacokinetics (PK) and pharmacodynamics (PD) of DCLL9718A and MCLL0517A in rodents and cynomolgus monkeys. Three key PK analytes were measured in these studies: total antibody, antibody-conjugated PBD dimer and unconjugated PBD dimer. In vitro, DCLL9718A, was stable with most (> 80%) of the PBD dimer payload remaining conjugated to the antibody over 96 hours. This was recapitulated in vivo with antibody-conjugated PBD dimer clearance estimates similar to DCLL9718A total antibody clearance. Both DCLL9718A and MCLL0517A showed linear PK in the non-binding rodent species, and non-linear PK in cynomolgus monkeys, a binding species. The PK data indicated minimal impact of conjugation on the disposition of DCLL9718A total antibody. Finally, in cynomolgus monkey, MCLL0517A showed target engagement at all doses tested (0.5 and 20 mg/kg) as measured by receptor occupancy, and DCLL9718A (at doses of 0.05, 0.1 and 0.2 mg/kg) showed strong PD activity as evidenced by notable reduction in monocytes and neutrophils.
Repressive gene regulation synchronizes development with cellular metabolism (2019)

ABSTRACT Metabolic conditions affect the developmental tempo of most animal species. Consequently, developmental gene regulatory networks (GRNs) must faithfully adjust their dynamics to a variable time scale. We find evidence that layered weak repression of genes provides the necessary coupling between GRN output and cellular metabolism. Using a mathematical model that replicates such a scenario, we find that lowering metabolism corrects developmental errors that otherwise occur when different layers of repression are lost. Through mutant analysis, we show that gene expression dynamics are unaffected by loss of repressors, but only when cellular metabolism is reduced. We further show that when metabolism is lowered, formation of a variety of sensory organs in Drosophila is normal despite loss of individual repressors of transcription, mRNA stability, and protein stability. We demonstrate the universality of this phenomenon by experimentally eliminating the entire microRNA family of repressors, and find that all microRNAs are rendered unnecessary when metabolism is reduced. Thus, layered weak repression provides robustness through error frequency suppression, and may provide an evolutionary route to a shorter reproductive cycle.
Protein surface recognition by synthetic agents: Design and structural requirements of a family of artificial receptors that bind to cytochrome C (1998)

The design, synthesis, and evaluation of a novel series of receptors for protein surface recognition are described. The design of these agents is based around the attachment of four constrained peptide loops onto a central calix[4]arene scaffold. This arrangement mimics the role of the hypervariable loops in antibody combining regions and defines a large surface area for binding to a complementary region of the exterior of a target protein. Using affinity and gel filtration chromatographies we show that one particular receptor binds strongly to the surface of cytochrome c. The site of binding is presumably close to the heme edge region, which contains several charged lysine residues. This is supported by the observation that the receptor inhibits the reduction of Fe(III) cytochrome c to its Fe(II) form. We also show that binding is strongly dependent on the nature of the substituents on the lower rim of the calixarene. The nmr and computational studies suggest that this effect may be due to conformational differences among the differently substituted receptors.
Potential Applications in Electric Power and Electronics Sectors (2017)

Polymer nanocomposites have been developed for practical use in electric power applications. For example, epoxy-based nanomicrocomposites have been developed for solid insulated switch-gear (SIS). This kind of switchgear is environmentally friendly and uses solid insulation systems instead of sulfur hexafluoride (SF6) gas insulation systems. Moreover, cross-linked polyethylene nanocomposite has been developed to prevent space charge accumulation and is used in insulation systems in DC power cables. With the development of power electronics technology toward recent promotion of energy saving, many inverter-fed motors are used in electric vehicles or hybrid vehicles. As compactness and high performance of electronic devices progress, there is an increasing demand for high-density mounting of electronic components. In high-performance electronic devices, high-density mounting of components is adopted. This chapter describes nanocomposites and nano-microcomposites for use in the field of information science, or specifically as sealing resins for semiconductor devices and packaging, underfill materials used in semiconductor flip-chip mounting, and capacitor materials.
Role of lipoprotein-X in the pathogenesis of cholestatic hypercholesterolemia. Uptake of lipoprotein-X and its effect on 3-hydroxy-3-methylglutaryl coenzyme A reductase and chylomicron remnant removal in human fibroblasts, lymphocytes, and in the rat. (1984)

Cholestasis is accompanied by the appearance of lipoprotein-X (LP-X) in plasma. This lipoprotein has a high content of unesterified cholesterol and phospholipids and appears to be ineffective in suppressing the enhanced hepatic cholesterogenesis of cholestasis. Its role as a possible causative factor for cholestatic hypercholesterolemia was investigated. When 125I-LP-X was injected into rats, it disappeared rapidly from the circulation. Calculated on the basis of gram wet weight, spleen took up more LP-X than liver. Prior ligation of the bile duct reduced the uptake in spleen. Experiments with isolated perfused rat liver showed that nonparenchymal cells (NPC) took up over eightfold more 125I-LP-X than hepatic parenchymal cells (PC). Incubation of PC, NPC, human lymphocyte suspensions, or fibroblast cultures with LP-X showed that NPC bound more LP-X than PC or fibroblasts. Lymphocytes took up 20-fold more LP-X than PC and the activity of 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase was depressed by LP-X. Lymphocytes isolated from cholestatic patients showed low activity of this enzyme. The activity was increased by LP-X in isolated perfused livers, but suppressed in isolated microsomes. LP-X competitively inhibited the uptake of chylomicron remnants in isolated perfused livers and hepatocytes. In contrast, degradation of LDL by perfused livers, which were isolated from ethinyl estradiol-treated rats or human fibroblast cultures, remained unchanged in the presence of LP-X. The results indicate that cholesterol transported by LP-X is mainly taken up by the cells of the reticuloendothelial system. It increases the activity of hepatic HMG-CoA reductase and suppresses remnant uptake, thus emphasizing a major role of LP-X in cholestatic hypercholesterolemia.
Effects of dopamine in lung‐transplanted pigs at 32°C (1999)

The results suggest that dopamine may be used to increase cardiac output after lung transplantation in moderate hypothermia as well as in normothermia, but one should be aware that dopamine may cause a substantial decrease in blood pressure, depending on the prevailing hemodynamic conditions at the start of its administration.
Spatial Variation in Frequency and Intensity of Antibiotic Interactions among Streptomycetes from Prairie Soil (2004)

Antibiotic interactions are believed to be significant to microbial fitness in soil, yet little is known of the frequency, intensity, and diversity of antibiotic inhibition and resistance among indigenous microbes. To begin to address these issues, we studied the abilities of streptomycete isolates from prairie soil to inhibit growth and display resistance to antibiotics produced by a test collection of 10 streptomycete isolates. Wide variations in antibiotic inhibition and resistance for prairie isolates among three locations and four soil depths within a 1-m2 plot were revealed. Fewer than 10% of 153 prairie isolates inhibited all 10 test isolates, while more than 40% of the isolates did not inhibit any of the test isolates. No field isolate was resistant to all of the test isolates, nor was any isolate susceptible to all of the test isolates. No correlation between inhibition and resistance phenotypes was found, suggesting that inhibition and resistance are under independent selection. The significant spatial variation in the frequency and intensity of antibiotic inhibition implies that the fitness benefits of antibiotic production are not the same among locations in soil. In contrast, the consistency of resistance over space indicates that its significance to fitness across locations is stable or the costs of maintaining resistance in the absence of selection are small or nonexistent. The spatial clustering of antibiotic inhibitory activity suggests a variable matrix of selection pressures and microbial responses across the soil landscape.
Data from Allogeneic Human Double Negative T Cells as a Novel Immunotherapy for Acute Myeloid Leukemia and Its Underlying Mechanisms (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; To explore the potential of &lt;i&gt;ex vivo&lt;/i&gt; expanded healthy donor–derived allogeneic CD4 and CD8 double-negative cells (DNT) as a novel cellular immunotherapy for leukemia patients.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Clinical-grade DNTs from peripheral blood of healthy donors were expanded and their antileukemic activity and safety were examined using flow cytometry–based &lt;i&gt;in vitro&lt;/i&gt; killing assays and xenograft models against AML patient blasts and healthy donor–derived hematopoietic cells. Mechanism of action was investigated using antibody-mediated blocking assays and recombinant protein treatment assays.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Expanded DNTs from healthy donors target a majority (36/46) of primary AML cells, including 9 chemotherapy-resistant patient samples &lt;i&gt;in vitro&lt;/i&gt;, and significantly reduce the leukemia load in patient-derived xenograft models in a DNT donor–unrestricted manner. Importantly, allogeneic DNTs do not attack normal hematopoietic cells or affect hematopoietic stem/progenitor cell engraftment and differentiation, or cause xenogeneic GVHD in recipients. Mechanistically, DNTs express high levels of NKG2D and DNAM-1 that bind to cognate ligands preferentially expressed on AML cells. Upon recognition of AML cells, DNTs rapidly release IFNγ, which further increases NKG2D and DNAM-1 ligands’ expression on AML cells. IFNγ pretreatment enhances the susceptibility of AML cells to DNT-mediated cytotoxicity, including primary AML samples that are otherwise resistant to DNTs, and the effect of IFNγ treatment is abrogated by NKG2D and DNAM-1–blocking antibodies.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; This study supports healthy donor–derived allogeneic DNTs as a therapy to treat patients with chemotherapy-resistant AML and also reveals interrelated roles of NKG2D, DNAM-1, and IFNγ in selective targeting of AML by DNTs. &lt;i&gt;Clin Cancer Res; 24(2); 370–82. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Techniques for fluorescence detection of protoporphyrin IX in skin cancers associated with photodynamic therapy (2013)

Photodynamic therapy (PDT) is a treatment modality that uses a specific photosensitizing agent, molecular oxygen, and light of a particular wavelength to kill cells targeted by the therapy. Topically administered aminolevulinic acid (ALA) is widely used to effectively treat cancerous and precancerous skin lesions, resulting in targeted tissue damage and little to no scarring. The targeting aspect of the treatment arises from the fact that ALA is preferentially converted into protoporphyrin IX (PpIX) in neoplastic cells. To monitor the amount of PpIX in tissues, techniques have been developed to measure PpIX-specific fluorescence, which provides information useful for monitoring the abundance and location of the photosensitizer before and during the illumination phase of PDT. This review summarizes the current state of these fluorescence detection techniques. Non-invasive devices are available for point measurements, or for wide-field optical imaging, to enable monitoring of PpIX in superficial tissues. To gain access to information at greater tissue depths, multi-modal techniques are being developed which combine fluorescent measurements with ultrasound or optical coherence tomography, or with microscopic techniques such as confocal or multiphoton approaches. The tools available at present, and newer devices under development, offer the promise of better enabling clinicians to inform and guide PDT treatment planning, thereby optimizing therapeutic outcomes for patients.
High Strength Low Alloy Steels in Naval Construction (1986)

The Naval Sea Systems Command has recently certified a lower-cost alternative steel to the HY-80 steel presently used in construction of naval surface ships. This alternative steel is based on the commercial development of high strength low alloy (HSLA) steels originally directed to the offshore oil exploration platform and gas line transmission industries. The certification is a result of an ongoing research and development program begun in 1980. This paper addresses several aspects of the HSLA steel development effort, including a discussion of the properties and metallurgy of this steel, and the cost savings which are achievable. Finally, the status of the current and planned Navy HSLA usage and the R&amp;D program is described.
Modified amino acids as useful tool for peptide synthesis and their measurement in complex matrices (2012)

Dottorato di Ricerca in Methodologies for the Development of Molecules of Pharmacological Interest, Ciclo XXV, a.a. 2011-2012