gebhart/patrepeval huggingface dataset:
Poly(ethylene glycol)-Poly(ester-carbonate) Block Copolymers Carrying PEG-Peptidyl-Doxorubicin Pendant Side Chains:  Synthesis and Evaluation as Anticancer Conjugates (2005)

Water soluble polymer anticancer conjugates can improve the pharmacokinetics of covalently bound drugs by limiting cellular uptake to the endocytic route, thus prolonging plasma circulation time and consequently facilitating tumor targeting by the enhanced permeability and retention (EPR) effect. Many of the first generation antitumor polymer conjugates used nonbiodegradable polymeric carriers which limits the molecular weight that can be safely used to <40,000 g/mol. The aim of this ambitious study was to synthesize and evaluate a novel, prototype biodegradable polymeric system based on high molecular weight, water-soluble functionalized polyesters. The main polymeric platform was prepared from bis(4-hydroxy)butyl maleate (DBM) and poly(ethylene glycol) (PEG4000) blocks to give the polymer DBM2-PEG4000 containing biodegradable carbonate bonds and having a M(w) of 100,000-190,000 g/mol; M(n) of 37,000-53,000 g/mol, and M(w)/M(n) of 3.0-3.7. Using thioether linkages, this polymer was then grafted with HS-PEG3000-Gly-Phe-Lue-Gly doxorubicin (HS-PEG3000-GFLG-Dox) pendant side chains ( approximately 30 per DBM2-PEG chain). The final construct, DBM2-PEG4000-S-PEG3000-GFLG-Dox had a total Dox content of 3-4 wt % and a free Dox content of < or = 0.7% total Dox. During incubation with isolated lysosomal enzymes, the rate of Dox release from the polymer backbone was relatively slow (<5% release over 5 h) compared to that seen for PEG5000-GFLG-Dox alone (>20% over 5 h). The in vitro cytotoxicity was assessed using B16F10 murine melanoma (MTT assay). DBM2-PEG4000-S-PEG3000-GFLG-Dox was 10-20-fold less toxic than free Dox. In vivo antitumor activity of the DBM2-PEG4000-S-PEG3000-GFLG-Dox conjugates was assessed using a subcutaneous (s.c.) B16F10 murine melanoma model, and an intraperitoneal (i.p.) L1210 leukaemia model. The increased toxicity (attributed to poor solubility) and low antitumor activity of DBM2-PEG4000-S-PEG3000-GFLG-Dox conjugates compared to PEG5000-GFLG-Dox and HPMA copolymer-Dox conjugates was attributed to the slow rate of Dox release. The DBM2-PEG4000-S-PEG3000-GFLG-Dox conjugates were considered unfavorable as candidates for further development. However, the successful scale-up synthesis of DBM2-PEG4000-S-PEG3000 constructs suggest that they are worthy of further investigation as carriers for controlled release and targeting of less hydrophobic agents.
<title>Optimum cell duplication or replication for multicast applications</title> (1998)

Many multicast ATM switch architectures have been proposed which differ greatly in the method in which replication of cells is handled. Depending on the switch architecture, the processing overhead incurred due to the cell copy function may be non-negligible. We develop a queuing model for a multicast switching node which accounts for this overhead. In the model, the source sends some number of duplicate cells, each of which is replicated at the switch to yield the total number of required copies. We use constrained optimization to determine the optimal amount of source duplication which minimizes the mean response time of the system. It is found that higher resource duplication is favored when the copy function overhead is comparable to the service time of a single cell. The model is then enhanced to account for errors and retransmission for reliable multicast.
Digital Systems (2018)

Traditional programmable logic devices (PLD) and field programmable gate arrays allow circuit designers to implement logic circuits with fewer chips relative to standard gate level designs based on primitive gates and flip-flops. Design changes do not require physical changes to the printed circuit board as long as the revised functions fit onto the same programmable chip. The low cost of design revisions makes programmable chips very attractive for prototype design and low volume production. Designers often move up the design ladder once proven designs move into high volume production. Companies produce PLD devices in different technologies to meet varying design and market demands. &quot;Programming technology” refers to the physics of chip programming and affects ease of programming and the ability to reprogram or to reconfigure chips. The dominant technologies in PLD devices are bipolar and CMOS. The programming technologies used in PLDs are virtually the same as the programming technologies available for read-only memories.
Dispersion, aberration and deconvolution in multi‐wavelength fluorescence images (1996)

The wavelength dependence of the incoherent point spread function in a wide-field microscope was investigated experimentally. Dispersion in the sample and optics can lead to significant changes in the point spread function as wavelength is varied over the range commonly used in fluorescence microscopy. For a given sample, optical conditions can generally be optimized to produce a point spread function largely free of spherical aberration at a given wavelength. Unfortunately, deviations in wavelength from this value will result in spherically aberrated point spread functions. Therefore, when multiple fluorophores are used to localize different components in the same sample, the image of the distribution of at least one of the fluorophores will be spherically aberrated. This aberration causes a loss of intensity and resolution, thereby complicating the localization and analysis of multiple components in a multi-wavelength image. We show that optimal resolution can be restored to a spherically aberrated image by constrained, iterative deconvolution, as long as the spherical aberration in the point spread function used for deconvolution matches the aberration in the image reasonably well. The success of this method is essentially independent of the initial degree of spherical aberration in the image. Deconvolution of many biological images can be achieved by collecting a small library of spherically aberrated and unaberrated point spread functions, and then choosing a point spread function appropriate for deconvolving each image. The co-localization and relative intensities of multiple components can then be accurately studied in a multi-wavelength image.
Supplementary Figure Legends from MEK Inhibition, Alone or in Combination with BRAF Inhibition, Affects Multiple Functions of Isolated Normal Human Lymphocytes and Dendritic Cells (2023)

&lt;p&gt;PDF file - 79K&lt;/p&gt;
Current Steering Creates Additional Pitch Percepts in Adult Cochlear Implant Recipients (2007)

These results indicate that additional pitch percepts can be created using current steering.
Determination of pyrimidine cyclobutane dimers by electrospray ionization/ion trap mass spectrometry (1992)

A straightforward approach for determining the cyclobutane pyrimidine dimers, thymine-thymine, uracil-thymine, and uracil-uracil, based upon electrospray ionization/ion trap mass spectrometry is described. These compounds are detected as the sodiated molecules, [M + Na]+, the response for which is maximized by adding low concentrations of sodium salts to the electrospray solutions. Under these conditions subnanogram levels of the dimers are determined by flow injection analysis. Structural information is obtained by collision-induced dissociation of the lithium adducts, [M + Li]+, which are formed by adding lithium salts to the solvents.
RADIUS: Model-Based Optimization (1998)

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources gathering and maintaining the data needed, and completing and reviewing the collection of information.
Prospective observational cohort study on grading the severity of postoperative complications in global surgery research (2019)

Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally.
Rituximab in the treatment of non-Hodgkin&amp;rsquo;s lymphoma (2008)

Beate Hauptrock, Georg HessHematology/Oncology, Johannes Gutenberg-University, Mainz, GermanyAbstract: Besides traditional cytostatic drugs the introduction of monoclonal antibodies has substantially influenced current treatment concepts of non-Hodgkin&amp;amp;rsquo;s lymphoma (NHL). &amp;amp;nbsp;Rituximab, a monoclonal anti-CD20 chimeric antibody, now has been widely evaluated in the various B-cell lymphatic neoplasms. Large phase III studies helped to prove the value of this drug in follicular lymphoma as part of induction or relapse treatment as well as maintenance treatment. The addition of rituximab to the well established CHOP regimens has increased achievable cure rates in diffuse large cell lymphoma, and this combination is now accepted worldwide as standard of care. Although conflicting results are available, rituximab is widely used for the treatment of mantle cell lymphoma. For the less frequent lymphoma entities phase 2 studies show a considerable efficiency for most of these B-NHL variants. Current research focuses on combined chemoimmunotherapy approaches, optimization of dosing regimens, and combination with novel agents.Keywords: non-Hodgkin&amp;amp;rsquo;s lymphoma, rituximab, monoclonal-antibody, targeted therapy
IGF-Binding Protein-1 Levels Are Related to Insulin-Mediated Glucose Disposal and Are a Potential Serum Marker of Insulin Resistance (2007)

We appreciate the interest of van Haeflen et al. (1) in our article (2) concerning IGF-binding protein (IGFBP)-1 as a maker of insulin resistance in healthy nondiabetic subjects. In contrast to our study, they did not find a strong a correlation between insulin action as determined …
7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects (2019)

<i>Mitragyna speciosa</i>, more commonly known as kratom, is a plant native to Southeast Asia, the leaves of which have been used traditionally as a stimulant, analgesic, and treatment for opioid addiction. Recently, growing use of the plant in the United States and concerns that kratom represents an uncontrolled drug with potential abuse liability, have highlighted the need for more careful study of its pharmacological activity. The major active alkaloid found in kratom, mitragynine, has been reported to have opioid agonist and analgesic activity in vitro and in animal models, consistent with the purported effects of kratom leaf in humans. However, preliminary research has provided some evidence that mitragynine and related compounds may act as atypical opioid agonists, inducing therapeutic effects such as analgesia, while limiting the negative side effects typical of classical opioids. Here we report evidence that an active metabolite plays an important role in mediating the analgesic effects of mitragynine. We find that mitragynine is converted in vitro in both mouse and human liver preparations to the much more potent mu-opioid receptor agonist 7-hydroxymitragynine and that this conversion is mediated by cytochrome P450 3A isoforms. Further, we show that 7-hydroxymitragynine is formed from mitragynine in mice and that brain concentrations of this metabolite are sufficient to explain most or all of the opioid-receptor-mediated analgesic activity of mitragynine. At the same time, mitragynine is found in the brains of mice at very high concentrations relative to its opioid receptor binding affinity, suggesting that it does not directly activate opioid receptors. The results presented here provide a metabolism-dependent mechanism for the analgesic effects of mitragynine and clarify the importance of route of administration for determining the activity of this compound. Further, they raise important questions about the interpretation of existing data on mitragynine and highlight critical areas for further research in animals and humans.
Direct Measurement of Optical Force Induced by Near-Field Plasmonic Cavity Using Dynamic Mode AFM (2015)

Plasmonic nanostructures have attracted much attention in recent years because of their potential applications in optical manipulation through near-field enhancement. Continuing experimental efforts have been made to develop accurate techniques to directly measure the near-field optical force induced by the plasmonic nanostructures in the visible frequency range. In this work, we report a new application of dynamic mode atomic force microscopy (DM-AFM) in the measurement of the enhanced optical force acting on a nano-structured plasmonic resonant cavity. The plasmonic cavity is made of an upper gold-coated glass sphere and a lower quartz substrate patterned with an array of subwavelength gold disks. In the near-field when the sphere is positioned close to the disk array, plasmonic resonance is excited in the cavity and the induced force by a 1550 nm infrared laser is found to be increased by an order of magnitude compared with the photon pressure generated by the same laser light. The experiment demonstrates that DM-AFM is a powerful tool for the study of light induced forces and their enhancement in plasmonic nanostructures.
Role of Cross-Linking Agents in Determining the Biochemical and Pharmacokinetic Properties of Mgr6−Clavin Immunotoxins (1998)

Several immunotoxins (ITs) were synthesized by the attachment of clavin, a recombinant toxic protein derived from Aspergillus clavatus, to the monoclonal antibody Mgr6 that recognizes an epitope of the gp185(HER-2) extracellular domain expressed on breast and ovarian carcinoma cells. Conjugation and purification parameters were analyzed in an effort to optimize the antitumor activity and stability of the ITs in vivo. To modulate the in vitro and in vivo properties of the immunotoxins, different coupling procedures were used and both disulfide and thioether linkages were obtained. Unhindered and hindered disulfide with a methyl group linkage ethyl S-acetyl 3-mercaptopropionthioimidate ester hydrochloride (AMPT) or ethyl S-acetyl 3-mercaptobutyrothioimidate ester hydrochloride (M-AMPT) were obtained by reaction with recombinant clavin, while the monoclonal antibody Mgr6 was derivatized with ethyl 3-[(4-carboxamidophenyl)dithio]propionthioimidate ester hydrochloride (CDPT). To achieve higher hindrance (a disulfide bond with a geminal dimethyl group), Mgr6 was derivatized with the N-hydroxysuccinimidyl 3-methyl-3-(acetylthio)butanoate (SAMBA) and clavin with CDPT. To evaluate the relevance of the disulfide bond in the potency and pharmacokinetic behavior of the ITs, a conjugate consisting of a stable thioether bond was also prepared by derivatizing Mgr6 with the N-hydroxysuccinimidyl ester of iodoacetic acid (SIA) and clavin with AMPT. The immunotoxins were purified and characterized using a single-step chromatographic procedure. Specificity and cytotoxicity were assayed on target and unrelated cell lines. The data indicate that the introduction of a hindered disulfide linkage into ITs has little or no effect on antitumor activity and suggest that disulfide cleavage is essential for activity; indeed, the intracellularly unbreakable thioether linkage produced an inactive IT. Analysis of IT stability in vitro showed that the release of mAb by incubation with glutathione is proportional to the presence of methyl groups and increases exponentially with the increase in steric hindrance. Analysis of the pharmacokinetic behavior of ITs in Balb/c mice given intravenous bolus injections indicated that ITs with higher in vitro stability were eliminated more slowly; i.e., the disulfide bearing a methyl group doubled the beta-phase half-life (from 3.5 to 7.1 h) compared with that of the unhindered, while a geminal dimethyl protection increased the elimination phase to 24 h. The thioether linkage showed its intrinsic stability with a beta-phase half-life of 46 h. The thioether linkage also increased the distribution phase from 17 to 32 min. The in vitro characteristics and in vivo stability of Mgr6-clavin conjugates composed of a methyl and dimethyl steric hindered disulfide suggest clinical usefulness.
Modeling of the angular tolerancing of an effective medium diffractive lens using combined finite difference time domain and radiation spectrum method algorithms (2010)

A new rigorous vector-based design and analysis approach of diffractive lenses is presented. It combines the use of two methods: the Finite-Difference Time-Domain for the study in the near field, and the Radiation Spectrum Method for the propagation in the far field. This approach is proposed to design and optimize effective medium cylindrical diffractive lenses for high efficiency structured light illumination systems. These lenses are realised with binary subwavelength features that cannot be designed using the standard scalar theory. Furthermore, because of their finite and high frequencies characteristics, such devices prevent the use of coupled wave theory. The proposed approach is presented to determine the angular tolerance in the cases of binary subwavelength cylindrical lenses by calculating the diffraction efficiency as a function of the incidence angle.
Proton NMR characterization of Chromatium gracile high-potential iron protein and its ruthenium-modified derivatives. Modulation of the reduction potentials in low- and high-potential [Fe4S4] ferredoxins (1989)

The NMR spectra of the high-potential iron protein from the photosynthetic bacterium Chromatium gracile and its ruthenium-labeled (His-42 and His-20) derivatives are reported. The isotropically shifted resonances in both the oxidized and reduced forms show a complex pH dependence due to the presence of three ionizable residues (Glu-44, His-20, and His-42). Assignments have been made to specific residues and the spectral features compared to those of other bacterial HiPIP's. The decrease in the reduction potential with increasing pH for this class of proteins is attributed to stabilization of the oxidized state of the cluster by delocalization of electron density onto the neighboring Tyr-19 residue.
Supplementary Figure 4 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase (2023)

&lt;p&gt;MaXFISH coregistry of sequenced tumors&lt;/p&gt;
Molecular cloning and sequence analysis of the gene coding for the 57-kDa major soluble antigen of the salmonid fish pathogenRenibacterium salmoninarum (1992)

The complete sequence coding for the 57-kDa major soluble antigen of the salmonid fish pathogen, Renibacterium salmoninarum, was determined. The gene contained an opening reading frame of 1671 nucleotides coding for a protein of 557 amino acids with a calculated Mr value of 57190. The first 26 amino acids constituted a signal peptide. The deduced sequence for amino acid residues 27–61 was in agreement with the 35 N-terminal amino acid residues determined by microsequencing, suggesting the protein in synthesized as a 557-amino acid precursor and processed to produce a mature protein of Mr 54505. Two regions of the protein contained imperfect direct repeats. The first region contained two copies of an 81-residue repeat, the second contained five copies of an unrelated 25-residue repeat. Also, a perfect inverted repeat (including three in-frame UAA stop codons) was observed at the carboxyl-terminus of the gene.
Separation of harmonic sound sources using sinusoidal modeling (2002)

In this paper, an approach for the separation of harmonic sounds is described. The overall system consists of three components. Sinusoidal modeling is first used to analyze the mixed signal and to obtain the frequencies and amplitudes of sinusoidal spectral components. Then a new method is proposed for the calculation of the perceptual distance between pairs of sinusoidal trajectories, according to the implications of psychoacoustic knowledge. A procedure for classifying the sinusoids into separate sound sources is presented. The system is not designed to separate sounds that have the same fundamental frequencies. However, a solution to detect single colliding sinusoids is given.
Convolutional Extreme Learning Machines: A Systematic Review (2021)

Much work has recently identified the need to combine deep learning with extreme learning in order to strike a performance balance with accuracy, especially in the domain of multimedia applications. When considering this new paradigm—namely, the convolutional extreme learning machine (CELM)—we present a systematic review that investigates alternative deep learning architectures that use the extreme learning machine (ELM) for faster training to solve problems that are based on image analysis. We detail each of the architectures that are found in the literature along with their application scenarios, benchmark datasets, main results, and advantages, and then present the open challenges for CELM. We followed a well-structured methodology and established relevant research questions that guided our findings. Based on 81 primary studies, we found that object recognition is the most common problem that is solved by CELM, and CCN with predefined kernels is the most common CELM architecture proposed in the literature. The results from experiments show that CELM models present good precision, convergence, and computational performance, and they are able to decrease the total processing time that is required by the learning process. The results presented in this systematic review are expected to contribute to the research area of CELM, providing a good starting point for dealing with some of the current problems in the analysis of computer vision based on images.
Pegylation of charged polymer-photosensitiser conjugates: effects on photodynamic efficacy (2003)

Conjugates between photosensitisers (PS) and charged polymeric carriers are under investigation for photodynamic therapy of cancer and may allow targeting to certain cell types or compartments in tumours. Covalent attachment of polyethylene glycol to macromolecules (pegylation) may alter their pharmacokinetics, cell type targeting, and photophysical properties. Macrophages may take up large amounts of aggregated PS, thus lessening the selectivity for cancer cells in tumours. We investigated the effect of pegylation on the uptake and phototoxicity of poly-L-lysine chlorin(e6) conjugates with either cationic or anionic charges in two cell lines, human ovarian cancer cells and mouse macrophages. The cationic conjugate after pegylation became less aggregated, consumed less oxygen and had reduced cellular uptake. However, the phototoxicity corrected for cellular uptake increased three- to five-fold. In contrast, the anionic succinylated conjugate on pegylation became more aggregated, consumed similar amounts of oxygen, and had higher cellular uptake. The anionic conjugate showed the highest relative phototoxicity towards both the cell lines (compared to the other three conjugates) and it decreased most towards the macrophages after pegylation. Pegylation reduced the amount of oxygen consumed per chlorin(e6) molecule when photosensitised cells were illuminated. These in vitro studies suggest that pegylation alters the phototoxicity of PS conjugates depending on the effect produced on the aggregation state.