gebhart/patrepeval huggingface dataset:
DNA-Directed Alkylating Agents. 7. Synthesis, DNA Interaction, and Antitumor Activity of Bis(hydroxymethyl)- and Bis(carbamate)-Substituted Pyrrolizines and Imidazoles (1998)

A series of bis(hydroxymethyl)-substituted imidazoles, thioimidazoles, and pyrrolizines and related bis(carbamates), linked to either 9-anilinoacridine (intercalating) or 4-(4-quinolinylamino)benzamide (minor groove binding) carriers, were synthesized and evaluated for sequence-specific DNA alkylation and cytotoxicity. The imidazole and thioimidazole analogues were prepared by initial synthesis of [(4-aminophenyl)alkyl]imidazole-, thioimidazole-, or pyrrolizine dicarboxylates, coupling of these with the desired carrier, and reduction to give the required bis(hydroxymethyl) alkylating moiety. The pyrrolizines were the most reactive alkylators, followed by the thioimidazoles, while the imidazoles were unreactive. The pyrrolizines and some of the thioimidazoles cross-linked DNA, as measured by agarose gel electrophoresis. Strand cleavage assays showed that none of the compounds reacted at purine N7 or N3 sites in the gpt region of the plasmid gpt2Eco, but the polymerase stop assay showed patterns of G-alkylation in C-rich regions. The corresponding thioimidazole bis(carbamates) were more selective than the bis(hydroxymethyl) pyrrolizines, with high-intensity bands at 5'-NCCN, 5'-NGCN and 5'-NCGN sequences in the PCR stopping assay ( indicates block sites). The data suggest that these targeted compounds, like the known thioimidazole bis(carbamate) carmethizole, alkylate exclusively at guanine residues via the 2-amino group, with little or no alkylation at N3 and N7 guanine or adenine sites. The cytotoxicities of the compounds correlated broadly with their reactivities, with the bis(hydroxymethyl)imidazoles being the least cytotoxic (IC50s >1 microM; P388 leukemia) and with the intercalator-linked analogues being more cytotoxic than the corresponding minor-groove-targeted ones. This was true also for the more reactive thioimidazole bis(carbamates) (IC50s 0.8 and 11 microM, respectively), but both were more active than the analogous "untargeted" carmethizole (IC50 20 microM). The bis(hydroxymethyl)pyrrolizine analogues were the most cytotoxic, with IC50s as low as 0.03 microM.
Molecular structure and chromosomal mapping of the human homolog of the agouti gene. (1994)

The agouti (a) locus in mouse chromosome 2 normally regulates coat color pigmentation. The mouse agouti gene was recently cloned and shown to encode a distinctive 131-amino acid protein with a consensus signal peptide. Here we describe the cloning of the human homolog of the mouse agouti gene using an interspecies DNA-hybridization approach. Sequence analysis revealed that the coding region of the human agouti gene is 85% identical to the mouse gene and has the potential to encode a protein of 132 amino acids with a consensus signal peptide. Chromosomal assignment using somatic-cell-hybrid mapping panels and fluorescence in situ hybridization demonstrated that the human agouti gene maps to chromosome band 20q11.2. This result revealed that the human agouti gene is closely linked to several traits, including a locus called MODY (for maturity onset diabetes of the young) and another region that is associated with the development of myeloid leukemia. Initial expression studies with RNA from several adult human tissues showed that the human agouti gene is expressed in adipose tissue and testis.
Antithrombotic Efficacy of a Novel Murine Antihuman Factor IX Antibody in Rats (1999)

A murine antihuman factor IX monoclonal antibody (BC2) has been generated and evaluated for its capacity to prolong the activated partial thromboplastin time (aPTT) in vitro and ex vivo and to prevent arterial thrombosis in a rat model in vivo. BC2 extended aPTT to a maximum of 60 to 80 seconds at 100 to 1000 nmol/L in vitro (rat and human plasma, respectively) and ex vivo (rat) after dosing of rats up to 6 mg/kg in vivo. BC2, administered as bolus (1 to 6 mg/kg) followed by infusion (0.3 to 2 mg x kg(-1) x h(-1)), dose-dependently prevented thrombosis of an injured rat carotid artery (FeCl(3)-patch model), increased time to artery occlusion, and reduced incidence of vessel occlusion. BC2 efficacy in preventing arterial thrombosis exceeded that of heparin (bolus 15 to 120 U/kg followed by infusion 0.5 to 4.0 U x kg(-1) x min(-1)), whereas the latter rendered the blood incoagulable (aPTT>1000 seconds). BC2 demonstrated complete antithrombotic efficacy also as a single bolus given either as prevessel or postvessel injury as evidenced by reduction of thrombus mass (from 4.18+/-0.49 to 1.80 +/-0.3 mg, P<0.001), increasing vessel patency time (from 14.9+/-0.9 minutes to 58.3+/-1.7 minutes, P<0.001) and decreasing incidence of vessel occlusion from 100% to 0% in vehicle- versus BC2-treated rats, respectively. BC2 (3 mg/kg, IV) administered in a single bolus resulted in 50% reduction in thrombus mass (P<0.01), extended vessel patency time (P<0.001), extended aPTT only 4-fold, and had no effect on blood loss via a tail surgical wound; heparin, at doses that reduced thrombus mass to a similar extent, extended aPTT beyond 1000 seconds (over 500-fold) and increased blood loss from 1.8+/-0.7 to 3.3 +/-0.6 mL (P<0.001). These data suggest that BC2 may provide enhanced therapeutic efficacy in humans at lesser interference with blood hemostasis than heparin.
The Role of Phonological Processing in Early Reading Ability: What We Can Learn From Chinese (1998)

Research has demonstrated that there is a strong relation between children's phonological processing skills and their ability to learn to read an alphabetic orthography. It is unclear whether this relation is specific to an alphabetic orthography or whether it extends as well to logographic orthographies such as Chinese. In this study, a group of Chinese 1st graders were administered three measures of phonological processing, including phonological memory, phonological awareness, and phonological retrieval. A visual memory task was also included. Two weeks later, the children were administered 2 reading tasks. One assessed their ability to read familiar and less familiar words printed in the Chinese alphabet. The other assessed their ability to read familiar and less familiar Chinese characters. Results showed that children's performance on the visual memory task was not related to their performance on either of the reading measures. In contrast, performance on the phonological measures was related to performance on both reading tasks. These results suggest that the relation between phonological processing skills and early reading ability is not specific to reading an alphabetic orthography. This relation extends to a logographic orthography as well.
[Identification of vertical transmission of hepatitis B virus from mother to children by direct sequencing a segment of surface gene of hepatitis B virus]. (1996)

This study revealed the vertical transmission linkage of HBV between the mother and children in a molecular level, and also first described a codon 145 immune escape mutant in Chinese vaccinated children.
Effects of crosslink density on mechanical properties of high glass transition temperature polycyanurate networks (1997)

Polycyanurate networks of different architecture were synthesized using different curing cycles. Networks with a variable extent of reaction were obtained; the small variation of the cyanate conversion (0.8 to 1) corresponds to a large variation of glass transition temperature (150–290°C) and crosslink density. The mechanical behavior at small and large deformations and the fracture toughness were examined at room temperature and related to the network structural parameters. To explain the puzzling variation of the yield stress and yield strain with the cyanate conversion, recovery experiments were conducted to discriminate anelastic deformation from plastic deformation. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 65: 2471–2479, 1997
Buddyguard: A buddy system for fast and reliable detection of IP prefix anomalies (2012)

Due to operational malpractice or security attacks, an IP prefix (i.e., a block of IP addresses) can undergo many types of routing anomalies. Perhaps the most well-known of such anomalies is prefix hijacking, where an attacker hijacks traffic meant to reach the legitimate user of a prefix. Anomalies can also easily occur through route leaks, which can disrupt traffic for numerous prefixes at once. While various solutions have been proposed to detect such anomalies, these solutions are limited and susceptible to attacker countermeasures. In this paper we present Buddyguard, a new approach to detecting prefix anomalies including prefix hijacking and route leaks. Buddyguard compares the behavior of a monitored prefix with the behavior of a set of numerous buddy prefixes. The system detects anomalies when the behavior of the monitored prefix significantly diverges from that of its buddies. Our evaluation results show that Buddyguard provides fast, accurate and lightweight monitoring of IP prefix anomalies, and its introduction and use of buddy prefixes enables it to be resilient against resourceful attackers.
INFLUENCE OF GENETIC FACTORS ON THE MAGNITUDE AND THE HETEROGENEITY OF THE IMMUNE RESPONSE IN THE RABBIT (1971)

Selective breeding of rabbits immunized with Group C and Group A streptococcal vaccines was employed to reveal genetic influences on the magnitude and on the restriction in heterogeneity of the immune response to the group-specific carbohydrates. After two generations of selective breeding, complete segregation was achieved between a high-response population (>18 mg precipitins/ml serum, average 33 mg/ml) and a low-response population (<13 mg precipitins/ml serum, average 7.5 mg/ml) to Group C carbohydrate. This suggests that a limited number of genes controls the magnitude of the immune response to this antigen. Selective breeding of rabbits which were representative of heterogeneous, restricted, and monoclonal responses revealed that the degree of antibody heterogeneity in the parental rabbits is reflected in the offspring. More than 95% of the offspring derived from rabbits which had a heterogeneous immune response developed heterogeneous antibodies. 33% of the offspring derived from rabbits which had restricted and monoclonal immune responses developed monoclonal antibodies. This suggests that the degree of heterogeneity of the antibody response to the streptococcal carbohydrates is under genetic control. The degree of heterogeneity and the magnitude of the immune response appear to be independent variables.
Synthesis of 2′-Deoxyuridine Nucleosides with Appended 5-Position Carbonyl Cross-Linking Groups (1994)

Abstract A simple modification of Stille type carbonylative coupling conditions resulted in high yield reactions giving new carbonyl appended 2′-deoxyuridine derivatives useful for chemical cross-linking.
Combined vascular and extracellular pH imaging of solid tumors (2002)

The unique physiological environment of solid tumors, frequently characterized by areas of poor flow, hypoxia, high lactate and low extracellular pH (pHe), influences vascularization, invasion and metastasis. Thus, vascularization and the physiological and metabolic environment play permissive (and conversely preventive) roles in invasion and metastasis. By using a multi-parametric approach of combined vascular and spectroscopic imaging, we can begin to evaluate which combinations of vascular, metabolic and physiological regions in a solid tumor represent the highest 'metastatic threat'. Here, we present measurements of pHe, vascular volume and permeability from co-localized regions within a solid tumor. These studies were performed for a group of metastatic (MDA-MB-231) and non-metastatic (MCF-7) human breast cancer xenografts. In this study, we have demonstrated the feasibility of such an approach, and presented methods of analyses to detect differences in patterns of combined parameters obtained from spatially co-registered regions in a solid tumor.
Administration of α 1 -Proteinase Inhibitor Ameliorates Bleomycin-induced Pulmonary Fibrosis in Hamsters (1992)

The effect of alpha 1-proteinase inhibitor (alpha 1Pi) administration on the acute lung injury and subsequent fibrosis induced by bleomycin (BLM) was examined in hamsters. Pulmonary lesions were quantitatively reduced in alpha 1Pi-administered BLM-treated (BLM-alpha 1Pi) animals compared with animals treated by BLM alone (BLM-control) at both 7 days (acute stage) and 30 days (fibrotic stage) after BLM treatment. Analysis of intraalveolar cells from bronchoalveolar lavage (BAL) fluid revealed that neutrophils and lymphocytes were significantly decreased in the BLM-alpha 1Pi animals at 7 days after BLM treatment and that 30 days after BLM treatment macrophages as well as neutrophils and lymphocytes were remarkably decreased in the BLM-alpha 1Pi animals. The elastase activity in supernatants of BAL fluid during 7 days following BLM treatment was detected, but there was no difference between the two groups. In vitro studies on neutrophil responsiveness to stimulation of BAL fluid at 3 days after BLM treatment revealed noticeable chemotaxis and generation of superoxide anion of isolated neutrophils, but alpha 1Pi did not show any inhibitory effects on neutrophil responsiveness. We suggest that alpha 1Pi administration ameliorates pulmonary fibrosis preceded by acute lung injury induced by BLM treatment in hamsters and that the inhibitory effects of alpha 1Pi on lung injury may not be brought about by altered elastase activity, chemotaxis, or superoxide generation in neutrophils. Alternative mechanisms are discussed.
<title>Depth from focus using a compact camera arrangement</title> (1996)

Robust range estimation is one of the most important tasks in mobile robotics. This paper presents a new optical arrangement for utilizing the previously known 'depth from defocus' principle. The arrangement makes it possible to apply standard video lenses and camera modules for making a compact range camera system. Real-time processing is made possible with a single-board DSP card.
Disruption of BASIGIN decreases lactic acid export and sensitizes non-small cell lung cancer to biguanides independently of the LKB1 status (2014)

Most cancers rely on aerobic glycolysis to generate energy and metabolic intermediates. To maintain a high glycolytic rate, cells must efficiently export lactic acid through the proton-coupled monocarboxylate transporters (MCT1/4). These transporters require a chaperone, CD147/BASIGIN (BSG) for trafficking to the plasma membrane and function.To validate the key role of these transporters in lung cancer, we first analysed the expression of MCT1/4 and BSG in 50 non-small lung cancer (NSCLC) cases. These proteins were specifically upregulated in tumour tissues. We then disrupted BSG in three NSCLC cell lines (A549, H1975 and H292) via 'Zinc-Finger Nucleases'. The three homozygous BSG-/- cell lines displayed a low MCT activity (10- to 5-fold reduction, for MCT1 and MCT4, respectively) compared to wild-type cells. Consequently, the rate of glycolysis, compared to the wild-type counterpart, was reduced by 2.0- to 3.5-fold, whereas the rate of respiration was stimulated in BSG-/- cell lines. Both wild-type and BSG-null cells were extremely sensitive to the mitochondria inhibitor metformin/phenformin in normoxia. However, only BSG-null cells, independently of their LKB1 status, remained sensitive to biguanides in hypoxia in vitro and tumour growth in nude mice. Our results demonstrate that inhibiting glycolysis by targeting lactic acid export sensitizes NSCLC to phenformin.
Role of Nicotinamide in DNA Damage, Mutagenesis, and DNA Repair (2010)

Nicotinamide is a water-soluble amide form of niacin (nicotinic acid or vitamin B3). Both niacin and nicotinamide are widely available in plant and animal foods, and niacin can also be endogenously synthesized in the liver from dietary tryptophan. Nicotinamide is also commercially available in vitamin supplements and in a range of cosmetic, hair, and skin preparations. Nicotinamide is the primary precursor of nicotinamide adenine dinucleotide (NAD(+)), an essential coenzyme in ATP production and the sole substrate of the nuclear enzyme poly-ADP-ribose polymerase-1 (PARP-1). Numerous in vitro and in vivo studies have clearly shown that PARP-1 and NAD(+) status influence cellular responses to genotoxicity which can lead to mutagenesis and cancer formation. This paper will examine the role of nicotinamide in the protection from carcinogenesis, DNA repair, and maintenance of genomic stability.
Molecular cloning and sequence of cDNA encoding the plasma membrane proton pump (H+-ATPase) of Arabidopsis thaliana. (1989)

In plants, the transport of solutes across the plasma membrane is driven by a proton pump (H+-ATPase) that produces an electric potential and pH gradient. We have isolated and sequenced a full-length cDNA clone that encodes this enzyme in Arabidopsis thaliana. The protein predicted from its nucleotide sequence encodes 959 amino acids and has a molecular mass of 104,207 Da. The plant protein shows structural features common to a family of cation-translocating ATPases found in the plasma membrane of prokaryotic and eukaryotic cells, with the greatest overall identity in amino acid sequence (36%) to the H+-ATPase observed in the plasma membrane of fungi. The structure predicted from a hydropathy plot contains at least eight transmembrane segments, with most of the protein (73%) extending into the cytoplasm and only 5% of the residues exposed on the external surface. Unique features of the plant enzyme include diverged sequences at the amino and carboxyl termini as well as greater hydrophilic character in three extracellular loops.
Scheduling algorithms for unpredictably heterogeneous CMP architectures (2008)

In future large-scale multi-core microprocessors, hard errors and process variations will create dynamic heterogeneity, causing performance and power characteristics to differ among the cores in an unanticipated manner. Under this scenario, naive assignments of applications to cores degraded by various faults and variations may result in large performance losses and power inefficiencies. We propose scheduling algorithms based on the Hungarian Algorithm and artificial intelligence (AI) search techniques that account for this future uncertainty in core characteristics. These thread assignment policies effectively match the capabilities of each degraded core with the requirements of the applications, achieving an ED <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> only 3.2% and 3.7% higher, respectively, than a baseline eight core chip multiprocessor with no degradation, compared to over 22% for a round robin policy.
Electrowetting-based actuation of droplets for integrated microfluidicsElectronic supplementary information (ESI) available: six videos showing droplet flow, droplet dispensing and electrowetting. See http://www.rsc.org/suppdata/lc/b1/b110474h/ (2002)

The serviceability of microfluidics-based instrumentation including 'lab-on-a-chip' systems critically depends on control of fluid motion. We are reporting here an alternative approach to microfluidics based upon the micromanipulation of discrete droplets of aqueous electrolyte by electrowetting. Using a simple open structure, consisting of two sets of opposing planar electrodes fabricated on glass substrates, positional and formational control of microdroplets ranging in size from several nanoliters to several microliters has been demonstrated at voltages between 15-100 V. Since there are no permanent channels or structures between the plates, the system is highly flexible and reconfigurable. Droplet transport is rapid and efficient with average velocities exceeding 10 cm s(-1) having been observed. The dependence of the velocity on voltage is roughly independent of the droplet size within certain limits, thus the smallest droplets studied (approximately 3 nl) could be transported over 1000 times their length per second. Formation, mixing, and splitting of microdroplets was also demonstrated using the same microactuator structures. Thus, electrowetting provides a means to achieve high levels of functional integration and flexibility for microfluidic systems.
A protein kinase C isozyme is translocated to cytoskeletal elements on activation. (1990)

Protein kinase C (PKC)1 isozymes comprise a family of related cytosolic kinases that translocate to the cell particulate fraction on stimulation. The activated enzyme is thought to be on the plasma membrane. However, phosphorylation of protein substrates occurs throughout the cell and is inconsistent with plasma membrane localization. Using an isozyme-specific monoclonal antibody we found that, on activation, this PKC isozyme translocates to myofibrils in cardiac myocytes and to microfilaments in fibroblasts. Translocation of this activated PKC isozyme to cytoskeletal elements may explain some of the effects of PKC on cell contractility and morphology. In addition, differences in the translocation site of individual isozymes--and, therefore, phosphorylation of different substrates localized at these sites--may explain the diverse biological effects of PKC.
Remote Telemetry: New Twists for Old Technology (1995)

Availability of telemetry beds was increased cost-effectively by providing telemetry on medical/surgical units with remote monitoring at designated critical care areas. Guidelines were developed for patient selection, education, clinical policy and procedure. A two-hour inservice was completed by all medical/surgical nurses and after a pilot study the system was implemented on three medical/surgical units.
Aptamer-Conjugated Gold Nanoparticles for Bioanalysis (2013)

Aptamers are single-stranded oligonucleotides synthesized through an in vitro selection and amplification process that involves systematic evolution of ligands by exponential enrichment. Based on their high binding affinity and specificity towards other molecules, aptamers generated during the final rounds of selection can be utilized in applications ranging from biosensing to diagnostics and therapeutics. Meanwhile, advances in nanotechnology have led to new and improved materials for biomedical applications. Specifically, nanoparticles can readily interact with both intra- and extra-cellular biomolecules to yield improved signal amplification and target recognition. By combining both technologies, aptamer-conjugated nanoparticles, especially gold nanoparticles (Apt–AuNPs), offer great promise for applications in bioanalysis and biomedicine, including early diagnosis and drug delivery. This review summarizes recent methodologies that have increased the application of Apt–AuNPs in biomedicine, and discusses the potential of Apt–AuNPs in bioanalysis.
A cooperative approach to user mobility (2001)

We propose a networking model that treats a user's set of personal devices as a MObile grouPEd Device, a MOPED, which appears as a single entity to the rest of the Internet. All communication for a user is directed to this point of presence. As the user moves through different environments, the devices cooperate to provide the user with access to all available communication resources. We present the basic networking functionality necessary to enable the operation of MOPEDs and their integration into the Internet. We introduce a middleware layer to extend IP routing to work with MOPEDs and a lightweight IP encapsulation protocol, Multipath Routing enCAPsulation (MRCAP), used to implement that middleware.