gebhart/patrepeval huggingface dataset:
Disruption of p53 function in immortalized human cells does not affect survival or apoptosis after taxol or vincristine treatment. (1998)

In the present study, we report our findings on the impact of p53 disruption on the sensitivity of human cell lines to the antimitotic agents Taxol and vincristine. Comparisons of cell survival and apoptosis were made with y-irradiation and, in some cases, several other DNA-damaging chemotherapeutic agents. Studies in eight Burkitt's lymphoma and lymphoblastoid cell lines (four wild-type p53 and four mutant p53 cell lines) revealed that the DNA-damaging agents assayed tended to exhibit less growth inhibition in the mutant p53 cell lines compared to the wild-type p53 cell lines. In contrast, no significant correlation was apparent between p53 gene status and the growth-inhibitory potency of Taxol or vincristine in these eight cell lines. We also found that contrary to gamma-irradiation, Taxol and vincristine could induce apoptosis in lymphoma cell lines harboring p53 mutations. These observations were explored further in lymphoblastoid VDSO cells (wild-type p53) from a normal individual and stably transfected VDSO derivatives lacking p53 function due to expression of the human papillomavirus type-16 E6 gene. We found that p53 disruption in VDSO/E6 cells blocked y-ray-induced apoptosis and afforded a survival advantage to VDSO/E6 cells compared to control-transfected cells. In contrast, p53 disruption did not affect Taxol- or vincristine-induced apoptosis or survival in VDSO cells. The effect of p53 disruption on Taxol sensitivity was explored further in the breast carcinoma MCF-7 and colon carcinoma HCT-116 cell lines that had been stably transfected with either the human papillomavirus type-16 E6 gene or a dominant-negative mutant p53 gene. Again, in these cell model systems, we found that p53 disruption did not affect the growth-inhibitory potency of Taxol. Taken together, our results suggest that p53 status is not a dominant factor in the mechanism by which antimitotic agents induce apoptosis and reduce survival in immortalized human cell lines.
Multiple Signaling Pathways Involving ATM (2000)

Cellular responses to DNA damage have become central to the two major issues in the field of cancer biology:(1) How do cancers start and progress? (2) What determines the sensitivity of tumors to therapeutic interventions? Bacteria possess elaborate mechanisms to dealwith various types of DNA damage. In general, these response mechanisms appear to enhance survival and minimize genetic instability (unless the genetic instabilitywould enhance survival). Although many of the generalsteps involved have been relatively well conservedthroughout evolution, DNA damage response pathwayshave predictably become even more complex in eukaryotes. In terms of cancer causation, the critical role forDNA damage responses is demonstrated by the fact thata number of human cancer susceptibility syndromes arecaused by inherited mutations affecting proteins involvedin DNA damage responses. For example, inherited mutations in damage-response genes can lead to skin cancers(xeroderma pigmentosum genes), leukemias and lymphomas (ATM, Fanconi anemia genes), breast and ovarian cancers (p53, Brca1, Brca2), colon cancers (mismatchrepair genes), and brain tumors (p53). The epidemiologicobservation that exposure to environmental DNA damaging agents contributes to at least 80% of all human cancers (Doll and Peto 1981) further illustrates the importance of these responses in cancer causation. Since manyof our cancer therapeutic interventions attempt to kill tumor cells via targeting the DNA, gene products involvedin DNA damage response pathways are also predictablycritical for determining therapeutic outcomes. Thus, elucidation of the mechanisms involved in DNA damage response pathways for both understanding cancer causationand eliciting cancer cures has obvious importance. Thep53 and ATM gene products are critical in cellular responses to DNA damage, particularly DNA strand breakssuch as those induced by ionizing irradiation, and are thefocus of this discussion...
Colon Microflora in Infants Fed Formula with Galacto- and Fructo-Oligosaccharides: More Like Breast-Fed Infants (2004)

The addition of the prebiotic GOS/FOS mixture to an infant formula has a stimulating effect on the growth of bifidobacteria and on the metabolic activity of the total intestinal flora. The changes in short chain fatty acids, lactate and pH in the prebiotic group represent a fermentation profile that is closer to that observed in breast-fed infants compared to infants fed control formula.
Femoral Arterial Hemostasis Using a Collagen Plug After Coronary Artery Stent Implantation (1992)

We have investigated the safety and efficacy of sealing the femoral arterial puncture site using purified bovine collagen in the catheter laboratory immediately after coronary stent implantation. Ten consecutive patients, mean age 64.6 years, pretreated with heparin, aspirin, and dextran underwent the insertion of a collagen plug immediately after coronary stent implantation. The mean activated clotting time was 512 seconds (range 320-999). Femoral arterial hemostasis was achieved before leaving the catheterization laboratory in nine of ten patients. Seven of these patients received additional mild groin compression with an air cushion compression device after hemostasis was successful. One of ten patients had persistent bleeding after delivery of the collagen plug and later required blood transfusion. The collagen plug may be a useful adjunct to obtaining hemostasis following coronary stent implantation, but further trials are required to test its reliability in fully anticoagulated patients.
Incipient fault diagnosis of chemical processes via artificial neural networks (1989)

Abstract Artificial neural networks have capacity to learn and store information about process faults via associative memory, and thus have an associative diagnostic ability with respect to faults that occur in a process. Knowledge of the faults to be learned by the network evolves from sets of data, namely values of steady‐state process variables collected under normal operating condition and those collected under faulty conditions, together with information about the degree of the faults and their causes. Here, we describe how to apply artificial neural networks to fault diagnosis. A suitable two‐stage multilayer neural network is proposed as the network to be used for diagnosis. The first stage of the network discriminates between the causes of faults when fed the noisy process measurements. Once the fault is identified, the second stage of the network estimates the degree of the fault. Thus, the diagnosis of incipient faults becomes possible.
Quantitative Detection of Hepatitis C Virus RNA by Light Cycler PCR and Comparison with Two Different PCR Assays (2001)

The new Light Cycler technology was adapted to the detection of hepatitis C virus (HCV) RNA in clinical samples. Sera from 81 patients were tested by Light Cycler PCR, AMPLICOR HCV Monitor assay, and in-house PCR. Our data demonstrate that Light Cycler is a fast and reliable method for the detection and quantitation of HCV RNA.
Improving the quality of BIACORE-based affinity measurements. (2003)

Although the BIACORE technology has become the standard method for measuring the affinity of antigen-antibody interactions, many users of the technology do not apply the most advanced experimental design and data processing methods that are now available. In addition, many published reports fail to provide the experimental details that are necessary to assess the reliability of the affinity data that are presented. This review describes the experimental conditions that should be used to ensure that reliable biosensor data are collected. There is little justification for the belief that ELISA methods provide in principle more reliable affinity parameters than biosensor technology.
Synthesis and Self-Association of an Imine-Containing m-Phenylene Ethynylene Macrocycle (2001)

The purpose of this study was to test the suitability of the imine bond as a structural unit within the backbone of phenylene ethynylene macrocycles and oligomers by determining the ability of m-phenylene ethynylene macrocycle 1 to form pi-stacked aggregates in both solution and the solid state. Macrocycle 1, with two imine bonds, was synthesized in high yield from diamine 4 and dialdehyde 5. The imine-forming macrocyclization step was carried out under a variety of conditions, with the best yield obtained simply by refluxing the reactants in methanol. The self-association behavior of 1 in various solvents was probed by (1)H NMR. The association constants (K(E)) in acetone-d(6) and tetrahydrofuran-d(8) were determined by fitting the concentration-dependent chemical shifts with indefinite self-association models. The results showed that solvophobically driven intermolecular pi-pi stacking could be preserved in the imine-containing m-phenylene ethynylene macrocycles. Interestingly, in acetone macrocycle 1 exhibited a stronger tendency to form a dimer rather than higher aggregates. We postulate that this behavior may be due to electrostatic attraction between dipolar imine groups. The solid-state packing of 1 was studied by wide- and small-angle X-ray powder diffraction (WAXD and SAXD). Bragg reflections of 1 were consistent with a hexagonal packing motif similar to our previous studies on m-phenylene ethynylene macrocycles that formed columnar liquid crystal phases.
Inhibitors of Protein Kinases and Phosphatases Alter Root Morphology and Disorganize Cortical Microtubules (1997)

To investigate molecular mechanisms controlling plant morphogenesis, we examined the morphology of primary roots of Arabidopsis thaliana and the organization of cortical microtubules in response to inhibitors of serine/threonine protein phosphatases and kinases. We found that cantharidin, an inhibitor of types 1 and 2A protein phosphatases, as previously reported for okadaic acid and calyculin A (R.D. Smith, J.E. Wilson, J.C. Walker, T.I. Baskin [1994] Planta 194: 516-524), inhibited elongation and stimulated radial expansion. Of the protein kinase inhibitors tested, chelerythrine, 6-dimethylaminopurine, H-89, K252a, ML-9, and staurosporine all inhibited elongation, but only staurosporine appreciably stimulated radial expansion. To determine the basis for the root swelling, we examined cortical microtubules in semithin sections of material embedded in butyl-methyl-methacrylate. Chelerythrine and 100 nM okadaic acid, which inhibited elongation without causing swelling, did not change the appearance of cortical arrays, but calyculin A, cantharidin, and staurosporine, which caused swelling, disorganized cortical microtubules. The stability of the microtubules in the aberrant arrays was not detectably different from those in control arrays, as judged by similar sensitivity to depolymerization by cold or oryzalin. These results identify protein phosphorylation and dephosphorylation as requirements in one or more steps that organize the cortical array of microtubules.
Mechanism of C−F Reductive Elimination from Palladium(IV) Fluorides (2010)

The first systematic mechanism study of C-F reductive elimination from a transition metal complex is described. C-F bond formation from three different Pd(IV) fluoride complexes was mechanistically evaluated. The experimental data suggest that reductive elimination occurs from cationic Pd(IV) fluoride complexes via a dissociative mechanism. The ancillary pyridyl-sulfonamide ligand plays a crucial role for C-F reductive elimination, likely due to a kappa(3) coordination mode, in which an oxygen atom of the sulfonyl group coordinates to Pd. The pyridyl-sulfonamide can support Pd(IV) and has the appropriate geometry and electronic structure to induce reductive elimination.
Transgenic and Null Mutant Animals for Psychosomatic Research (1996)

While genetically altered animals have revolutionized the understanding of single gene disorders, their promise has not yet been fulfilled for multigenic behavioral disorders. Newer techniques to allow control of the tissue and stage of development at which a gene is expressed are likely to enhance the usefulness of these models for psychosomatic research. New models of disease for testing psychological impacts on illness and specific ways altering neurotransmitter function will be discovered. While these models will be extremely useful to psychosomatic medicine, the nature of this discipline of necessity involves emphasis on individual experience, and thus will never be amenable to exclusively genetic analysis.
Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains. (1988)

The nucleotide sequence of the ret proto-oncogene has been determined from cDNA clones isolated from a cDNA library of a THP-1 human monocytic leukemia cell line. Analysis of this sequence indicates that it encodes a protein which is structurally related to transmembrane receptors with a cytoplasmic tyrosine kinase domain. Unlike most growth factor receptors, it contains two hydrophobic regions which are potential transmembrane domains. Comparison of the sequence of the ret proto-oncogene with that of the ret transforming gene revealed that, in addition to the amino-terminal truncation, the last 51 carboxy-terminal amino acids of the ret proto-oncogene were replaced with 9 unrelated amino acids of the ret transforming gene. The focus forming activity of the ret cDNA, containing both amino-terminal and caboxy-terminal truncations, was approximately 13-fold higher than that of cDNA containing only the amino-terminal truncation. This suggests a possible role for the carboxy-terminal sequence in activation of transforming potential of the ret proto-oncogene. When transcription of the ret proto-oncogene was examined in a variety of mouse tissues, we detected its transcription in normal mouse spinal cord and lymphadenopathy of C3H/HeJ-gld/gld and MRL/Mp-lpr/lpr mice.
Determination of blood glucose concentration by using wavelet transform and neural networks. (2013)

The proposed non-invasive optical glucose monitoring system is able to predict the glucose concentration by proving that there is a definite variation in hematological distribution between patients with DM and those without DM.
Transmembrane movement of heme. (1990)

Evidence for CO-heme partitioning into and across lipid bilayers was obtained by kinetic and chromatographic studies. Biphasic time courses were observed when CO-heme was rapidly mixed with unilamellar lipid vesicles in a stopped-flow spectrometer. The initial rapid phase depended linearly on lipid concentration and was assigned to heme partitioning between the external solvent phase and the outer lipid layer of the membranes. The rate of the second, much slower phase was independent of both heme and lipid concentration. The fraction of absorbance change associated with this slower phase increased with increasing heme to lipid ratios and reached a maximum of approximately 45%. A similar slow phase was observed when membrane-bound heme was reacted with apomyoglobin. In the presence of excess globin, all of the CO-heme was extracted from the membranes to form native CO myoglobin. Under these conditions, the fractional amount of absorbance change associated with the slow dissociation phase was approximately 45%, regardless of the heme to lipid ratio. These results suggest strongly that the slow phases represent transmembrane movement of heme, from the outer to the inner lipid layer in the association reactions and from the inner to the outer layer in dissociation reactions. The temperature dependence of the rate of CO-heme binding to the outer lipid layer was markedly different from that of transmembrane movement. The rate of the latter, slower process decreased greatly with increasing acyl chain length, whereas the rate of the initial binding process varied little with vesicle composition, as long as the membranes were examined above their melting temperatures. Finally, the two kinetically distinct bound heme fractions could be isolated directly by column chromatography.
Biochemical properties of the kringle 2 and protease domains are maintained in the refolded t-PA deletion variant BM 06.022 (1992)

BM 06.022 is a t-PA deletion variant which comprises the kringle 2 and the protease domain. Production of BM 06.022 in Escherichia coli leads to the formation of inactive inclusion bodies, which have to be refolded by an in vitro refolding process to achieve activity and proper structure of the domains. We analysed the biochemical properties of BM 06.022 to obtain some information about the structure of kringle 2 and the protease as compared with the structure of these domains in the intact t-PA molecule. The kinetic analysis of the amidolytic activity of BM 06.022 and CHO-t-PA yielded similar values for kcat (13.9 s-1 and 11.4 s-1 for the single chain forms and 33.9 s-1 and 27.1 s-1 for the two chain forms of BM 06.022 and CHO-t-PA, respectively) and for Km (2.5 mM and 2.1 mM for the single chains forms and 0.5 mM and 0.3 mM for the two chain forms of BM 06.022 and CHO-t-PA, respectively). BM 06.022 and CHO-t-PA have the same plasminogenolytic activity in the absence of CNBr fragments of fibrinogen. However, BM 06.022 has a lower plasminogenolytic activity in the presence of CNBr fragments of fibrinogen and a lower affinity to fibrin as compared with CHO-t-PA. The affinity of BM 06.022 for fibrin is completely suppressed by 0.3 mM epsilon-aminocaproic acid, while the intact t-PA has a residual affinity of approximately 30%. The dissociation constants for the interaction with the lysine analogue epsilon-aminocaproic acid are 0.10 mM and 0.09 mM for BM 06.022 and the intact t-PA, respectively. Furthermore, BM 06.022 and CHO-t-PA are inhibited by PAI-1 in a similar manner.
An Improved Model of Blocking Probability in All-Optical Networks (1995)

We have developed a model of blocking probability in an All-Optical Network (AON) without wavelength changers and tested this model against simulations. The new model is an improvement of a model first proposed in [l].
High‐dose gamma irradiation for soft tissue allografts: High margin of safety with biomechanical integrity (2006)

Screening and processing methods currently in place have made the risk of bacterial and viral infections from allograft tissues extremely low. However, the development of a terminal sterilization method that does not adversely affect tissue function would provide an added safety to tissues for transplantation. We assessed whether high-dose gamma irradiation could be used as an effective terminal sterilization method for allografts without impairing the preimplantation mechanical integrity of the tissues. Semitendinosus tendons were pretreated with a radioprotectant solution and then irradiated to 50 kGy under well-defined conditions that included a tight dose range and maintained low temperatures. Maximum force, strain, stress, modulus, and strain energy density for tendons irradiated to 50 kGy were compared to nonirradiated control tendons and tendons irradiated to 18 kGy by a commercial tissue bank using their existing method. The preimplantation biomechanical properties of the 50-kGy group compared favorably to the nonirradiated and 18 kGy groups. A study to evaluate the postimplantation mechanical and biological performance of grafts irradiated to 50 kGy is ongoing. Pathogen inactivation was also quantified following 50 kGy of irradiation, with > or =4.5 logs of Sindbis virus and 4.9 logs of parvovirus kill achieved. Analysis of Clostridium sordellii inactivation kinetics indicated that a 16 log10 reduction is predicted with 50 kGy of irradiation. A high dose of gamma irradiation using the described conditions can reduce infectious risks associated with soft tissue allografts while maintaining the preimplantation biomechanical performance of the tissues.
One-Pot Synthesis of Hierarchically Structured Ceramic Monoliths with Adjustable Porosity (2010)

Hierarchically porous oxides are used in a variety of applications within the energy sector (e.g., fuel cells, batteries), biology (e.g., scaffolds, biocatalysis), separations, and catalysis. This article describes a reproducible one-step method for the preparation of metal oxides with controllable hierarchical pore architectures. The preparation is demonstrated for a wide range of materials, specifically silica, titania, zirconia, aluminum titanium oxide, titanium zirconium oxide, and yttrium zirconium oxide monoliths. The samples were prepared by exploiting the polymerization and phase separation of furfuryl alcohol to produce a colloidal dispersion of poly(furfuryl alcohol) particles. The gelation in the sol−gel process occurred after the in situ formation of the template. The removal of the polymer template led to the formation of macropores, whereas inclusion of an amphiphilic block copolymer (Pluronic F127) assisted mesopore formation, either by templating or by stabilizing the inorganic building blocks. The macropore and mesopore morphology could be altered by varying the synthesis conditions. This control over the pore structure was demonstrated in the silica, titania, and titanium zirconium oxide materials.
Tomotherapy: A new concept for the delivery of dynamic conformal radiotherapy (1993)

Tomotherapy, literally "slice therapy," is a proposal for the delivery of radiation therapy with intensity-modulated strips of radiation. The proposed method employs a linear accelerator, or another radiation-emitting device, which would be mounted on a ring gantry like a CT scanner. The patient would move through the bore of the gantry simultaneously with gantry rotation. The intensity modulation would be performed by temporally modulated multiple independent leaves that open and close across the slit opening. At any given time, any leaf would be (1) closed, covering a portion of the slit, (2) open, allowing radiation through, or (3) changing between these states. This method would result in the delivery of highly conformal radiation. Overall treatment times should be comparable with contemporary treatment delivery times. The ring gantry would make it convenient to mount a narrow multisegmented megavoltage detector system for beam verification and a CT scanner on the treatment unit. Such a treatment unit could become a powerful tool for treatment planning, conformal treatment, and verification using tomographic images. The physical properties of this treatment delivery are evaluated and the fundamental design specifications are justified.
Si-based interband tunneling devices for high-speed logic and low power memory applications (2002)

This study extends the preliminary work of the authors, presenting improved epitaxially grown Si/Si/sub 0.5/Ge/sub 0.5//Si resonant interband tunnel diodes (RITDs) with current densities which exceed any previously reported for a Si-based NDR device. For the first time, the needs of Si-based TDTL circuits are beginning to be addressed, Two new classes of Si-based NDR devices are also reported here: Si-only RITDs and Si/Si/sub 0.5/Ge/sub 0.5/ heterojunction Esaki tunnel diodes with a digitally graded superlattice (DG-SL).