gebhart/patrepeval huggingface dataset:
Using EPR To Compare PEG-branch-nitroxide “Bivalent-Brush Polymers” and Traditional PEG Bottle–Brush Polymers: Branching Makes a Difference (2012)

Attachment of poly(ethylene glycol) (PEG) to polymeric nanostructures is a general strategy for sterically shielding and imparting water solubility to hydrophobic payloads. In this report, we describe direct graft-through polymerization of branched, multifunctional macromonomers that possess a PEG domain and a hydrophobic nitroxide domain. Electron paramagnetic resonance (EPR) spectroscopy was used to characterize microenvironments within these novel nanostructures. Comparisons were made to nitroxide-labeled, traditional bottle-brush random and block copolymers. Our results demonstrate that bivalent bottle-brush polymers have greater microstructural homogeneity compared to random copolymers of similar composition. Furthermore, we found that compared to a traditional brush polymer, the branched-brush, “pseudo-alternating” microstructure provided more rotational freedom to core-bound nitroxides, and greater steric shielding from external reagents. The results will impact further development of multivalent bottle-brush materials as nanoscaffolds for biological applications.
Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 5. SkQ1 prolongs lifespan and prevents development of traits of senescence (2008)

Very low (nano- and subnanomolar) concentrations of 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) were found to prolong lifespan of a fungus (Podospora anserina), a crustacean (Ceriodaphnia affinis), an insect (Drosophila melanogaster), and a mammal (mouse). In the latter case, median lifespan is doubled if animals live in a non-sterile vivarium. The lifespan increase is accompanied by rectangularization of the survival curves (an increase in survival is much larger at early than at late ages) and disappearance of typical traits of senescence or retardation of their development. Data summarized here and in the preceding papers of this series suggest that mitochondria-targeted antioxidant SkQ1 is competent in slowing down execution of an aging program responsible for development of age-related senescence.
Mechanical Interactions Among Cytoskeletal Filaments (1998)

Mechanical properties of the cells are important in controlling cell shape, cell migration, and other functions. To understand how cytoskeletal (CSK) filaments interact with one another mechanically, mechanical properties of adherent endothelial cells were analyzed after treatment with CSK-disrupting drugs. CSK stiffness (the ratio of applied stress to strain, a measure of cell resistance to shape deformation), viscosity (an index of intracellular structural damping), and permanent deformation (a measure of "plasticity") were measured with magnetic twisting cytometry, by which rotational stress was applied directly to integrin receptors with ferromagnetic beads coated with RGD-containing peptide. Treatment with cytochalasin D, which disrupts actin microfilaments inhibited stiffness by 50% and decreased permanent deformation from 70% to 50% but had almost no effect on viscosity. In contrast, nocodazole, a microtubule disrupter, had very little effect on inhibition of CSK stiffness, decreased viscosity by 25%, and had no effects on permanent deformation. Acrylamide, an intermediate filament disrupter, had little effect on inhibition of CSK stiffness, little effect on viscosity, and no effect on permanent deformation. Taxol, a drug that facilitates microtubule polymerization, increased stiffness by 10%, increased viscosity by 10%, and decreased permanent deformation from 70% to 50%. Combinations of cytochalasin D and nocodazole, cytochalasin D and acrylamide, or all three drugs resulted in a synergistic effect on inhibition of CSK stiffness and viscosity but not in permanent deformation. Inhibition of oxidative metabolism with potassium cyanide had no effects on stress-induced stiffening response. Inhibition of tyrosine phosphatase with phenylarsine oxide had no effect on stress-induced stiffening response. We conclude that higher order mechanical interactions of CSK filaments are important in determining the mechanical properties of the cell.
Design of a Composite Ethidium–Netropsin–Anilinoacridine Molecule for DNA Recognition (2003)

Control of gene expression is a cherished goal of cancer chemotherapy. Small ligand molecules able to bind tightly to DNA in a well-defined configuration are being actively searched for. With this goal in mind, we have designed and synthesized the trifunctional molecule R-132, which combines a bispyrrole skeleton for minor groove DNA recognition and two different chromophores, anilinoacridine and ethidium. The affinity and mode of binding of R-132 to DNA were studied by a combination of complementary biochemical and biophysical techniques, which included absorption and fluorescence spectroscopy and circular and linear dichroism. A surface plasmon resonance biosensor analysis was also performed to quantify the kinetic parameters of the drug-DNA interaction process. Altogether, the results demonstrate that the three moieties of the hybrid molecule are engaged in the interaction process, thus validating the rational design strategy. At the biological level, R-132 stabilizes topoisomerase-II-DNA covalent complexes and displays potent cytotoxic activities, which are attributable to its DNA-binding properties. R-132 easily enters and accumulates in cell nuclei, as evidenced by confocal microscopy. R-132 therefore provides a novel lead compound for the design of gene-targeted anticancer agents.
Detection and Parallel Execution of Independent Instructions (1970)

For a single instruction stream–single data stream organization the problem of simultaneously issuing several instructions is studied.
Near-Infrared Studies of the Structure of Water. I. Pure Water (1963)

The absorption bands of water in the 1.1-to-1.3-μ region have been measured. From the extinction coefficients, concentrations of water species involving 2,1, and 0 hydrogen bonds per molecule were calculated. The temperature dependence of these concentrations yielded a value of 3.7–4.5 kcal for the energy involved in breaking one mole of hydrogen bonds in water. On melting, 46% of the hydrogen bonds originally present in ice are broken; by 72°C the percentage broken has increased to 61. Further, the results were used in conjunction with the flickering cluster model of Frank and Wen to obtain an upper limit for the average size of the water polymers of 90 molecules of H2O at 20°C.
Contextualising Water Use in Residential Settings: A Survey of Non-Intrusive Techniques and Approaches (2016)

Water monitoring in households is important to ensure the sustainability of fresh water reserves on our planet. It provides stakeholders with the statistics required to formulate optimal strategies in residential water management. However, this should not be prohibitive and appliance-level water monitoring cannot practically be achieved by deploying sensors on every faucet or water-consuming device of interest due to the higher hardware costs and complexity, not to mention the risk of accidental leakages that can derive from the extra plumbing needed. Machine learning and data mining techniques are promising techniques to analyse monitored data to obtain non-intrusive water usage disaggregation. This is because they can discern water usage from the aggregated data acquired from a single point of observation. This paper provides an overview of water usage disaggregation systems and related techniques adopted for water event classification. The state-of-the art of algorithms and testbeds used for fixture recognition are reviewed and a discussion on the prominent challenges and future research are also included.
Hoechst 33258 Tethered by a Hexa(ethylene glycol) Linker to the 5‘-Termini of Oligodeoxynucleotide 15-Mers:  Duplex Stabilization and Fluorescence Properties (1997)

A fluorescent Hoechst 33258 derivative has been prepared in which a hexa(ethylene glycol) linker is attached to the terminal phenol residue. Conjugation of this derivative to DNA sequences is accomplished by a reversed coupling protocol, one in which the 5'-terminal nucleoside residue of a fully protected DNA sequence is converted to a terminal phosphoramidite. In the presence of the Hoechst derivative and tetrazole the final coupling reaction is achieved to generate the conjugated nucleic acid. After deprotection and cleavage of the conjugate from the support, HPLC analysis indicates that the conjugation reaction proceeds with yields as high as 75%. The presence of the conjugated Hoechst derivative increases the stability of DNA duplexes typically by 10-16 degrees C. A variety of sequence variants indicate that the tether length is sufficient to reach beyond the terminus of the DNA duplex and bind to internal A-T rich target sequences as far away as four base pairs from the site of attachment. A four base pair binding site appears to be necessary for effective helix stabilization by the conjugate, but in some cases can include a G-C base pair, which is consistent with a previous X-ray diffraction study regarding the binding of Hoechst 33258 to duplex DNA. When A-T base pairs alternate with G-C base pairs, a small but discernible increase is T(m) is observed (3.6 degrees C), indicating that binding to this sequence still occurs, but not in the same manner as to A-T rich sequences. Upon formation of the conjugated duplex, an enhanced quantum yield for the fluorescence emission spectrum of the tethered Hoechst derivative is observed. When an A-T rich binding site is present, the enhanced quantum yield increases by at least 16- and in some cases to nearly 30-fold relative to the value obtained for the single-stranded DNA-Hoechst conjugate.
Exogenous High-Mobility Group Box 1 Protein Induces Myocardial Regeneration After Infarction via Enhanced Cardiac C-Kit + Cell Proliferation and Differentiation (2005)

High-mobility group box 1 protein (HMGB1) is a chromatin protein that is released by inflammatory and necrotic cells. Extracellular HMGB1 signals tissue damage, stimulates the secretion of proinflammatory cytokines and chemokines, and modulates stem cell function. The present study examined exogenous HMGB1 effect on mouse left-ventricular function and myocyte regeneration after infarction. Myocardial infarction was induced in C57BL/6 mice by permanent coronary artery ligation. After 4 hours animals were reoperated and 200 ng of purified HMGB1 was administered in the peri-infarcted left ventricle. This intervention resulted in the formation of new myocytes within the infarcted portion of the wall. The regenerative process involved the proliferation and differentiation of endogenous cardiac c-kit+ progenitor cells. Circulating c-kit+ cells did not significantly contribute to HMGB1-mediated cardiac regeneration. Echocardiographic and hemodynamic parameters at 1, 2, and 4 weeks demonstrated a significant recovery of cardiac performance in HMGB1-treated mice. These effects were not observed in infarcted hearts treated either with the unrelated protein glutathione S-transferase or a truncated form of HMGB1. Thus, HMGB1 appears to be a potent inducer of myocardial regeneration following myocardial infarction.
Microfluidic Chips for Plasma Isolation from Whole Blood (2012)

Since most conventional clinical assays are performed on cell-free serum or plasma, plasma isolation is a necessary step in the processing of whole blood sample pretreatment. Traditional technologies for plasma isolation are based on centrifugation or membrane filtration, which are time and cost intensive processes. Microfluidic chips for whole blood plasma isolation are attractive alternatives, which lead to more gentle, fast, and consistent manipulation of the whole blood samples, and therefore more accurate and better quality of plasma isolation. In this chapter, a variety of microfluidic devices for blood plasma separation are reviewed and compared. Two specific examples of plasma isolation leveraging MEMS technologies are included for further concept demonstration in which design, fabrication and testing of these microfluidic devices are covered in detail. These plasma isolation microfluidic devices can be easily connected with other microfluidic components to form micro total analysis systems for blood testing with the advantages of continuous and real time separation of plasma from whole blood samples.
New sources of soybean seed meal and oil composition traits identified through TILLING (2009)

The oligosaccharide phenotype controlled by the novel RS2 allele is similar to previously observed seed oligosaccharide phenotypes in RS2 mutant (PI 200508) allele-containing lines. Due to the anti-nutritional characteristics of raffinose and stachyose, this represents a positive change in seed composition. The fatty acid phenotype controlled by the novel FAD2-1A allele controls an increase in oleic acid in the seed oil, a phenotype also observed in a line previously characterized to have a null allele of the FAD2-1A gene. Molecular marker assays were developed to reliably detect the inheritance of the mutant alleles and can be used in efficient breeding for these desired seed phenotypes. Our results serve as the first demonstration of the identification of soybean mutants controlling seed phenotypes discovered through the reverse genetics technique TILLING.
From in vitro Experiments to in vivo and Clinical Studies; Pros and Cons (2016)

Biomedical investigators use different methods including experimental animals, tissue, and cell cultures as well as computational simulations and clinical studies finding the ways to treat human diseases and disorders. All the mentioned procedures have their own advantages and disadvantages. For instance although animal models provide some drawbacks like difference in biokinetics parameters or extrapolation of results to human, they are more reliable than in vitro tests. The disadvantage of the in vitro procedures is that they are mostly performed on cancerous cell lines that have a substantially abnormal function. Furthermore, although in vitro models are fruitfully used in biological fields, finding an end point, the initial aim of chemical attack, and extrapolation of the effects to the human are some real weaknesses. Absence of biokinetics in in vitro methods may lead to a misinterpretation of the data. The present review has criticized the pros and cons of both methods, especially in the fields of pharmacology, toxicology, and medical sciences.
Modeling Conversational Speech for Speech Recognition (1996)

In language modeling for speech recognition the goal is to constrain the search of the speech recognizer by providing a model which can, a context, indicate what the next most likely word will be. In this paper, we explore how the addition of information to the text, in particular part of speech and dysfluency annotations, can be used to,build more complex language models. In particular, we ask two questions. First, in conversational speech, where there is a less clear notion of than in written text, does segmenting the text into linguistically or semantically based units contribute to a better language model than merely segmenting based on broad acoustic information, such as pauses. Second, is the sentence itself a good unit to be modeling, or should we look at smaller units, for example, dividing a sentence into a given and new portion and segmenting out acknowledgments and replies. To answer these questions, we present a variety of kinds of analysis, from vocabulary distributions to perplexities on language models. The next step will be modeling conversations and incorporating those models into a speech recognizer.
Phase II study of recombinant human tumor necrosis factor in colorectal carcinoma. (1990)

Fifteen patients with colorectal carcinoma received a 30-min intravenous infusion of recombinant human tumor necrosis factor (rHuTNF) to investigate the value of rHuTNF in the treatment of colorectal carcinoma. Patients received 5 x 10(5) U/m2 (217 micrograms/m2) on day 1, and in the absence of serious side effects 10 x 10(5) U/m2 (435 micrograms/m2) on day 3 and 15 x 10(5) U/m2 (652 micrograms/m2) on day 5. The cycle was repeated on day 28. Full dose escalation was possible in all patients. There was a minor response in one patient (disappearance of retroperitoneal lymph nodes). All other patients showed progressive disease. At the dose and schedule used, rHuTNF had minimal therapeutic activity in colorectal carcinoma.
Targeting T cells against brain tumors with a bispecific ligand‐antibody conjugate (1998)

High-affinity receptors expressed on the surface of some tumors can be exploited by chemically conjugating the ligand for the receptor and an antibody against immune effector cells, thus redirecting their cytolytic potential against the tumor. Ovarian carcinomas and some brain tumors express the high-affinity folate receptor (FR). In this report, a transgenic mouse model that generates endogenously arising choroid plexus tumors was used to show that folate/anti- T-cell receptor antibody conjugates can direct infiltration of T cells into solid brain tumor masses. An engineered single-chain Fv form of the anti-T-cell receptor antibody KJ16 was conjugated with folate, to produce a bispecific agent that was substantially smaller than most previously characterized bispecific antibodies. Folate conjugation to the antibody increased T-cell infiltration into the tumors by 10- to 20-fold, and significantly prolonged survival of the mice. Int. J. Cancer 76:761–766, 1998.© 1998 Wiley-Liss, Inc.
Novel Sm‐like proteins with long C‐terminal tails and associated methyltransferases (2004)

Sm and Sm-like proteins of the Lsm (like Sm) domain family are generally involved in essential RNA-processing tasks. While recent research has focused on the function and structure of small family members, little is known about Lsm domain proteins carrying additional domains. Using an integrative bioinformatics approach, we discovered five novel groups of Lsm domain proteins (Lsm12-16) with long C-terminal tails and investigated their functions. All of them are evolutionarily conserved in eukaryotes with an N-terminal Lsm domain to bind nucleic acids followed by as yet uncharacterized C-terminal domains and sequence motifs. Based on known yeast interaction partners, Lsm12-16 may play important roles in RNA metabolism. Particularly, Lsm12 is possibly involved in mRNA degradation or tRNA splicing, and Lsm13-16 in the regulation of the mitotic G2/M phase. Lsm16 proteins have an additional C-terminal YjeF_N domain of as yet unknown function. The identification of an additional methyltransferase domain at the C-terminus of one of the Lsm12 proteins also led to the recognition of three new groups of methyltransferases, presumably dependent on S-adenosyl-l-methionine. Further computational analyses revealed that some methyltransferases contain putative RNA-binding helix-turn-helix domains and zinc fingers.
Multicast routing in internetworks and extended LANs (1988)

Multicasting is used within local-area networks to make distributed applications more robust and more efficient. The growing need to distribute applications across multiple, interconnected networks, and the increasing availability of high-performance, high-capacity switching nodes and networks, lead us to consider providing LAN-style multicasting across an internetwork. In this paper, we propose extensions to two common internetwork routing algorithms—distance-vector routing and link-state routing—to support low-delay datagram multicasting. We also suggest modifications to the single-spanning-tree routing algorithm, commonly used by link-layer bridges, to reduce the costs of multicasting in large extended LANs. Finally, we show how different link-layer and network-layer multicast routing algorithms can be combined hierarchically to support multicasting across large, heterogeneous internetworks.
A New Regioselective Synthesis of 1,2,5-Trisubstituted 1H-Imidazoles and Its Application to the Development of Eprosartan (1997)

A new method is presented for the preparation of 1,2-disubstitued-1H-imidazole-5-carboxaldehydes by the reaction of N-monosubstituted amidines with 2-halo-3-alkoxy-2-propenals. The reaction is highly regioselective with ratios of 1,2,5:1,2,4-imidazolecarboxaldehydes ranging from 85:15 to 100:0. This methodology could be extended with similar results to the synthesis of imidazole-5-nitriles by the reaction of 2-bromo-3-methoxy-2-propenenitrile with N-monosubstituted amidines.
Functional reentry in cultured monolayers of neonatal rat cardiac cells (2003)

Previous studies of reentrant arrhythmias in the heart have been performed in computer models and tissue experiments. We hypothesized that confluent monolayers of cardiac cells can provide a simple, controlled, and reproducible experimental model of reentry. Neonatal rat ventricular cells were cultured on 22-mm-diameter coverslips and stained with the voltage-sensitive dye RH-237. Recordings of transmembrane potentials were obtained from 61 sites with the use of a contact fluorescence imaging system. An electrical field stimulus, followed by a point stimulus, induced 39 episodes of sustained reentry and 21 episodes of nonsustained reentry. Sustained reentry consisted of single-loop (n = 18 monolayers) or figure-of-eight (n = 4) patterns. The cycle length, action potential duration at 80% repolarization, and conduction velocity were (in means +/- SE) 358 +/- 33 ms, 118 +/- 12 ms, and 12.9 +/- 1.0 cm/s for single loop and 311 +/- 78 ms, 137 +/- 18 ms, and 7.8 +/- 1.3 cm/s for figure-of-eight, respectively. Electrical termination by 6- to 13-V/cm field pulses or 15- to 20-V point stimuli was successful in 60% of the attempts. In summary, highly stable reentry can be induced, sustained for extensive periods of time, and electrically terminated in monolayers of cultured neonatal rat cardiac myocytes.
Longitudinal evaluation of a fibrosis index combining MMP‐1 and PIIINP compared with MMP‐9, TIMP‐1 and hyaluronic acid in patients with chronic hepatitis C treated by interferon‐alpha and ribavirin (2006)

We have recently described a fibrosis index combining serum procollagen type III N-terminal peptide (PIIINP) and matrix metalloproteinase 1 (MMP-1) concentrations for evaluating the amount of liver fibrosis in chronic hepatitis C patients. The aims of the present study were to validate this score in another cohort of patients and to assess its variations along those of TIMP-1, hyaluronic acid (HA) and MMP-9 during antiviral treatment. Seventy-nine patients treated by interferon-alpha and ribavirin for 24 or 48 weeks were included. A liver biopsy was performed within the 6 months before the start of treatment. Serum markers were measured in serum collected the day of the liver biopsy, at start of treatment, and every 3 months during treatment and a 6-month follow-up period. The PIIINP/MMP-1 index was significantly correlated to the METAVIR fibrosis (r = 0.68, P < 0.001). Its overall diagnostic value defined by the area under the receiver operating characteristics curves was 0.77 for discriminating F1 vs F2F3F4, and 0.81 for discriminating F1F2 vs F3F4, and was better than that observed for HA and TIMP-1. At the end of follow-up, the PIIINP/MMP-1 index significantly decreased in responders and remained stable in nonresponder patients. This decrease occurred early and continued regularly during the treatment period. This variation was because of both a decrease of PIIINP and an increase of MMP-1 concentrations. HA and TIMP-1 serum concentrations were also significantly lower at the end of follow-up in responder patients, but early changes were minimal and not influenced by the response to treatment. Our study shows that a noninvasive index combining PIIINP and MMP-1 is a useful tool to follow-up fibrosis change during and after antiviral therapy chronic hepatitis C patients.