gebhart/patrepeval huggingface dataset:
Alterations in the activity and regulation of mammalian ribonucleotide reductase by chlorambucil, a DNA damaging agent. (1992)

Ribonucleotide reductase provides the four deoxyribonucleotides required for the synthesis of DNA. In this study, we examined the hypothesis that alterations in the regulation of ribonucleotide reductase activity may be necessary to provide the deoxyribonucleotides required for DNA repair, following exposure of mammalian cells to DNA damaging agents such as the antitumor agent chlorambucil. We observed a marked transient increase in ribonucleotide reductase activity within 2 h of exposing BALB/c 3T3 mouse cells to DNA damaging concentrations of chlorambucil. Northern blot analysis showed that elevations in activity were accompanied by transient increases in the mRNA levels of both genes (R1 and R2) that code for ribonucleotide reductase. Western blot analysis indicated that only the protein for the limiting component for enzyme activity, R2, was significantly elevated in chlorambucil treated cultures. The chlorambucil effects upon activity and regulation of ribonucleotide reductase occurred without any detectable changes in the rate of DNA synthesis, as would be expected if the elevation in enzyme activity is required for DNA repair. The chlorambucil-induced elevations in R1 and R2 message levels were blocked by treatment of cells with actinomycin D or the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, indicating the importance of the reductase transcriptional process in responding to the action of chlorambucil and providing evidence for the involvement of a protein kinase C pathway in the regulation of mammalian ribonucleotide reductase. In addition to the chlorambucil-induced elevations in enzyme activity, message, and protein levels, the drug was also shown to be an inhibitor of ribonucleotide reductase activity in cell-free preparations. Separation of ribonucleotide components on an affinity column followed by selective exposure of the protein components to chlorambucil showed that both R1 and R2 proteins were targets for chlorambucil, in keeping with the known alkylating abilities of the drug. These observations provide the first direct demonstration of a link between the regulation of mammalian ribonucleotide reductase and the process of DNA repair and contribute to our understanding of the mode of action of a class of drugs represented by chlorambucil, in which chemotherapeutic activity has been attributed to DNA damaging effects.
An algorithm for optimal service provisioning using resource pricing (2002)

The authors propose a microeconomic approach to service provisioning in ATM networks. The provisioning procedure consists of two algorithms, one executed by the network and the other by individual users. The network offers directly for rent its bandwidth and buffers. Users purchase freely resources to meet their desired quality based on their own traffic parameters and delay requirements. The network periodically adjusts resource prices based on user requests monitored in the previous period. They describe the networks adjustment scheme and users' decision rule, and show that under the proposed price adjustment scheme, in order to minimize their own service cost, individual users will indeed request amounts of resources that optimize a measure of overall network performance. Since this approach does not require the network to know user traffic and delay parameters, it does not mandate traffic policing on the part of the network.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Theoretical evaluation of the distributed power dissipation in biological cells exposed to electric fields (2000)

The paper deals with the power dissipation caused by exposure of biological cells to electric fields of various frequencies. With DC and sub-MHz AC frequencies, power dissipation in the cell membrane is of the same order of magnitude as in the external medium. At MHz and GHz frequencies, dielectric relaxation leads to dielectric power dissipation gradually increasing with frequency, and total power dissipation within the membrane rises significantly. Since such local increase can lead to considerable biochemical and biophysical changes within the membrane, especially at higher frequencies, the bulk treatment does not provide a complete picture of effects of an exposure. In this paper, we theoretically analyze the distribution of power dissipation as a function of field frequency. We first discuss conductive power dissipation generated by DC exposures. Then, we focus on AC fields; starting with the established first-order model, which includes only conductive power dissipation and is valid at sub-MHz frequencies, we enhance it in two steps. We first introduce the capacitive properties of the cytoplasm and the external medium to obtain a second-order model, which still includes only conductive power dissipation. Then we enhance this model further by accounting for dielectric relaxation effects, thereby introducing dielectric power dissipation. The calculations show that due to the latter component, in the MHz range the power dissipation within the membrane significantly exceeds the value in the external medium, while in the lower GHz range this effect is even more pronounced. This implies that even in exposures that do not cause a significant temperature rise at the macroscopic, whole-system level, the locally increased power dissipation in cell membranes could lead to various effects at the microscopic, single-cell level.
Algorithms for Nucleic Acid Sequence Design (2010)

Motivated by a growing field of research focused on programming function into biomolecules, we seek to decrease the cost of high-quality rational nucleic acid sequence design while increasing its versatility and availability. We begin by describing an algorithm for designing the sequence of one or more interacting nucleic acid strands intended to adopt a target secondary structure at equilibrium. Using ensemble defect optimization, we seek to minimize the average number of incorrectly paired nucleotides at equilibrium, calculated over the entire ensemble of unpseudoknotted secondary structures. Empirically, the algorithm exhibits asymptotic optimality and costs 4/3 the time of a single objective function evaluation for large structures. We then extend this algorithm to design multi-state systems with an arbitrary number of linked targets and demonstrate its efficacy on systems invented by molecular engineers. To improve the ease of use and availability of nucleic acid analysis and design tools, we present NUPACK, a web application already in wide use that allows the international research community to share a high-performance compute cluster for the analysis and design of systems of interacting nucleic acids.
Passive compliance versus active compliance in robot‐based automated assembly systems (1998)

Industrial robots have found great potential in applications to assembly‐line automation. Programmable robot‐based assembly systems are often needed, in particular for circumstances in which special assembly equipments is not available or well‐trained operators could not be employed economically. Robots with enough compliance can perform not only classic automation tasks, such as spot welding, cargo carrying, etc., but also can operate those tasks which demand the compliant motion capacity of robots. Therefore, the research on robot compliance is especially important for parts assembly by robots, where robot compliant motions and manipulations are essential requirements. This paper presents a number of important issues in robot compliance research, including the specification of robot end‐effector compliance; properties of a robot compliance matrix at its end‐effector; discussions on passive compliance and active compliance and their comparisons; and derivation of the compliance at the end‐effector required for tasks.
4-Amido-2-carboxytetrahydroquinolines. Structure-activity relationships for antagonism at the glycine site of the NMDA receptor (1992)

trans-2-Carboxy-5,7-dichloro-4-amidotetrahydroquinolines, evolved from the lead 5,7-dichlorokynurenic acid, have been synthesized and tested for in vitro antagonist activity at the glycine site on the N-methyl-D-aspartate (NMDA) receptor. Optimization of the 4-substituent has provided antagonists having nanomolar affinity, including the urea trans-2-carboxy-5,7-dichloro-4[[(phenylamino)carbonyl]amino]-1,2,3, 4-tetrahydroquinoline (35; IC50 = 7.4 nM vs [3H]glycine binding; Kb = 130 nM for block of NMDA responses in the rat cortical slice), which is one of the most potent NMDA antagonists yet found. The absolute stereochemical requirements for binding were found to be 2S,4R, showing that, in common with other glycine-site NMDA receptor ligands, the unnatural configuration at the alpha-amino acid center is required. The preferred conformation of the trans-2,4-disubstituted tetrahydroquinoline system, as shown by X-ray crystallography and 1H NMR studies, places the 2-carboxyl pseudoequatorial and the 4-substituent pseudoaxial. Modifications of the 4-amide show that bulky substituents are tolerated and reveal the critical importance for activity of correct positioning of the carbonyl group. The high affinity of trans-2-carboxy-5,7-dichloro-4-[1-(3-phenyl-2-oxoimidazolidinyl)]- 1,2,3,4-tetrahydroquinoline (55; IC50 = 6 nM) suggests that the Z,Z conformer of the phenyl urea moiety in 35 is recognized by the receptor. Molecular modeling studies show that the 4-carbonyl groups of the kynurenic acids, the tetrahydroquinolines, and related antagonists based on N-(chlorophenyl)glycine, can interact with a single putative H-bond donor on the receptor. The results allow the establishment of a three-dimensional pharmacophore of the glycine receptor antagonist site, incorporating a newly defined bulk tolerance/hydrophobic region.
Effects of SM-215 on Hair Growth by Hair Follicle Stimulation (2015)

Although hair growth medications have been developed, these medications have some side effects and usability problems. Recently there has been a growing interest in hair loss remedies from natural materials. This Study was carried out to investigate the effect of SM-215 on hair growth by hair follicle stimulation. We divided the 8-week-old ICR mice into a Control Group (CG), a Non-Treatment Group (NTG), and a SM-215 application Group (SMG). 100μl/day of SM 215 was applied for 3 weeks to SMG. After 3 weeks, we found a change to the sebaceous gland, the capillaries around the hair follicles (Vascularity and Vasodilation of capillaries), and changes in the hair follicle activity (Growth-promoting hormones, Neurotransmitters) in a tissue sample excised from the dorsal skin. A large number of hair and hair follicles in the subcutaneus layer of SMG was observed as compared to the NTG. Sebum secretions around the hair follicles and sebaceous gland distribution of SMG were observed more clearly than in NTG. A large number of capillaries, especially in the hip region versus the neck region in SMG, were also observed compared to the NTG as noted through external capillaries observation. Positive responses of IGF-1, serotonin, and neuropeptide Y in SMG were increased compared to the NTG in immunohistochemistry. Based on these studies and analysis, we suppose that SM-215 improves a hair growth activity by increasing the distribution of the sebaceous glands, capillaries around the hair follicles, and the vasodilation to assist in forming the necessary environment for hair growth, thereby promoting hair growth by stimulating at hair follicles. Keywords: Hair Growth, IGF-1, Neuropeptide Y, Serotonin, SM-215
Communication and Control in Electric Power Systems: Applications of Parallel and Distributed Processing (2003)

Preface.1. Introduction.2. Parallel and Distributed Processing of Power Systems.3. Information System for Control Centers.4. Common Information Model and Middleware for Integration.5. Parallel and Distributed Load Flow Computation.6. Parallel and Distributed Load Flow of Distribution Systems.7. Parallel and Distributed State Estimation.8. Distributed Power System Security Analysis.9. Hierarchical and Distributed Control of Voltage/VAR.10. Transmission Congestion Management Based on Multi-Agent Theory.11. Integration, Control, and Operation of Distributed Generation.12. Special Topics in Power System Information System.Appendix A. Example System Data.Appendix B. Measurement Data for Distributed State Estimation.Appendix C. IEEE-30 Bus System Data.Appendix D. Acronyms.Bibliography.Index.
Self-testing graph states (2010)

We give a construction for a self-test for any connected graph state. In other words, for each connected graph state we give a set of non-local correlations that can only be achieved (quantumly) by that particular graph state and certain local measurements. The number of correlations considered is small, being linear in the number of vertices in the graph. We also prove robustness for the test.
Micro-Computed Tomography Evaluation of Human Fat Grafts in Nude Mice (2012)

Studies assessing the fate of autologous fat grafts in animals have focused on nonimaging modalities, including histological and biochemical analyses, which require euthanasia of the animals. In this study, we have demonstrated the ability to employ micro-CT for 3D reconstruction and volumetric analysis of human fat grafts in a mouse model. Importantly, this model provides a platform for subsequent study of fat manipulation and soft tissue engineering.
Overcoming neurite‐inhibitory chondroitin sulfate proteoglycans in the astrocyte matrix (2013)

Acute trauma to the central nervous system (CNS) can result in permanent damage and loss of function related to the poor regeneration of injured axons. Injured axons encounter several barriers to regeneration, such as the glial scar at the injury site. The glial scar contains extracellular matrix (ECM) macromolecules deposited by reactive astrocytes in response to injury. The scar ECM is rich in chondroitin sulfate proteoglycans (CSPGs), macromolecules that inhibit axonal growth. CSPGs consist of a core protein with attachment sites for glycosaminoglycan (GAG) chains. An extensive literature demonstrates that enzymatic removal of the GAG chains by chondroitinase ABC permits some axonal regrowth; however, the remaining intact core proteins also possess inhibitory domains. Because metalloproteinases can degrade core proteins of CSPGs, we have evaluated five matrix metalloproteinases (MMPs) and a related protease-a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4)-for their capacity to overcome CSPG inhibition of neuritic growth in culture. The metalloproteinases were selected for their known expression after CNS injuries. Of the MMPs, MMP-3, -7 and -8 reduced or abolished inhibition of neurite outgrowth on a purified CSPG substrate and on an astrocyte-derived ECM. ADAMTS-4 also attenuated CSPG inhibition of neurites and had the additional benefits of neither degrading laminin nor causing neurotoxicity. The efficacy of ADAMTS-4 matched that of blocking the EGFR signaling previously reported to mediate CSPG inhibition. These findings highlight ADAMTS-4 as a superior protease for overcoming CSPG inhibition of axonal regeneration in the CNS.
Cover Picture: Angew. Chem. Int. Ed. 9/2002 (2002)

The cover picture shows adamantane-2,6-dione encapsulated within a hydrogen-bonded capsule made up of four identical subunits. The ketone functionality of the guest molecule (CPK model, red) participates in the structural seam at each end of the capsule through bifurcated hydrogen bonds. Find out more about encapsulating complexes in the review by Rebek, Jr., et al. on p. 1488 ff.
Lipofection reagents prepared by a simple ethanol injection technique. (1995)

Cationic liposomes are being utilized for the delivery of DNA into mammalian cells both in vitro and in vivo. In this report, we describe a rapid, simple injection method for the preparation of cationic liposomes that requires no special equipment. We demonstrate that, using this injection method, liposomes prepared with a commercially available cationic lipid (dimethyldioctadecylammonium bromide, DDAB) or a synthetic cationic cholesterol derivative, along with a neutral lipid (dioleoyl-L-alpha-phosphatidylethanolamine, DOPE), effectively transfect a variety of cell lines in vitro. The transfection activity of liposomes prepared by this method was comparable to that obtained with liposomes prepared by the standard evaporation/sonication procedure and to that of a commercial reagent, Lipofectamine.
Engineered hapten‐binding antibody derivatives for modulation of pharmacokinetic properties of small molecules and targeted payload delivery (2016)

Hapten-binding antibodies have for more than 50 years played a pivotal role in immunology, paving the way to antibody generation (as haptens are very important and robust immunogens), to antibody characterization (as the first structures generated more than 40 years ago were those of hapten binders), and enabled and expanded antibody engineering technologies. The latter field of engineered antibodies evolved over many years and many steps resulting in recombinant humanized or human-derived antibody derivatives in multiple formats. Today, hapten-binding antibodies are applied not only as reagents and tools (where they still play an important part) but evolved also to engineered targeting and pretargeting vehicles for disease diagnosis and therapy. Here we describe recent applications of hapten-binding antibodies and of engineered mono- and bispecific hapten-binding antibody derivatives. We have designed and applied these molecules for the modulation of the pharmacokinetic properties of small compounds or peptides. They are also integrated as additional binding entities into bispecific antibody formats. Here they serve as non-covalent or covalent coupling modules to haptenylated compounds, to enable targeted payload delivery to disease tissues or cells.
Biological considerations and clinical applications of new HER2-targeted agents (2010)

Over the past two decades, since the discovery of the human EGF receptor 2 (HER2) oncogene, the oncoprotein has become one of the best known and intensively studied tumor targets in oncology. In fact, laboratory findings were the basis for clinical proof-of-principle studies, whose results not only confirmed the relationship between gene amplification and an aggressive tumor phenotype but also demonstrated that the poor prognosis associated with receptor overexpression could be improved. Indeed, the success in treating patients with HER2-positive breast cancer extends to those with early as well as advanced disease. Nonetheless, not all tumors respond to treatment targeting the receptor; disease progression also occurs after initially responding to anti-HER2 therapy. This article focuses on the biology of HER2 and three novel agents currently in clinical trials that target HER2 beyond disease progression.
Interactions between extracellular matrix and growth factors in wound healing (2009)

Dynamic interactions between growth factors and extracellular matrix (ECM) are integral to wound healing. These interactions take several forms that may be categorized as direct or indirect. The ECM can directly bind to and release certain growth factors (e.g., heparan sulfate binding to fibroblast growth factor-2), which may serve to sequester and protect growth factors from degradation, and/or enhance their activity. Indirect interactions include binding of cells to ECM via integrins, which enables cells to respond to growth factors (e.g., integrin binding is necessary for vascular endothelial growth factor-induced angiogenesis) and can induce growth factor expression (adherence of monocytes to ECM stimulates synthesis of platelet-derived growth factor). Additionally, matrikines, or subcomponents of ECM molecules, can bind to cell surface receptors in the cytokine, chemokine, or growth factor families and stimulate cellular activities (e.g., tenascin-C and laminin bind to epidermal growth factor receptors, which enhances fibroblast migration). Growth factors such as transforming growth factor-beta also regulate the ECM by increasing the production of ECM components or enhancing synthesis of matrix degrading enzymes. Thus, the interactions between growth factors and ECM are bidirectional. This review explores these interactions, discusses how they are altered in difficult to heal or chronic wounds, and briefly considers treatment implications.
Characterization and Evaluation of C18 HPLC Stationary Phases Based on Ethyl-Bridged Hybrid Organic/Inorganic Particles (2003)

The characterization and evaluation of three novel 5-microm HPLC column packings, prepared using ethyl-bridged hybrid organic/inorganic materials, is described. These highly spherical hybrid particles, which vary in specific surface area (140, 187, and 270 m(2)/g) and average pore diameter (185, 148, and 108 A), were characterized by elemental analysis, SEM, and nitrogen sorption analysis and were chemically modified in a two-step process using octadecyltrichlorosilane and trimethylchlorosilane. The resultant bonded materials had an octadecyl surface concentration of 3.17-3.35 micromol/m(2), which is comparable to the coverage obtained for an identically bonded silica particle (3.44 micromol/m(2)) that had a surface area of 344 m(2)/g. These hybrid materials were shown to have sufficient mechanical strength under conditions normally employed for traditional reversed-phase HPLC applications, using a high-pressure column flow test. The chromatographic properties of the C(18) bonded hybrid phases were compared to a C(18) bonded silica using a variety of neutral and basic analytes under the same mobile-phase conditions. The hybrid phases exhibited similar selectivity to the silica-based column, yet had improved peak tailing factors for the basic analytes. Column retentivity increased with increasing particle surface area. Elevated pH aging studies of these hybrid materials showed dramatic improvement in chemical stability for both bonded and unbonded hybrid materials compared to the C(18) bonded silica phase, as determined by monitoring the loss in column efficiency through 140-h exposure to a pH 10 triethylamine mobile phase at 50 degrees C.