gebhart/patrepeval huggingface dataset:
MR of cis-platinum-induced optic neuritis. (1994)

Right-sided blindness developed in a patient after three intraarterial treatments with cis-platinum for a right temporal glioblastoma multiforme. MR showed an enlarged and enhancing optic chiasm. Because of the history of remote radiation therapy and the fact that the tumor was located distal to the optic chiasm, we postulate that the clinical and imaging findings were related to the chemotoxicity.
Electronic-resonance-enhanced coherent anti-Stokes Raman spectroscopy of nitric oxide (2003)

A dual-pump, electronic-resonance-enhanced coherent anti-Stokes Raman spectroscopy (CARS) technique for the measurement of minor species concentrations has been demonstrated. The frequency difference between a visible Raman pump beam and Stokes beam is tuned to a vibrational Q-branch Raman resonance of nitric oxide (NO) to create a Raman polarization in the medium. The second pump beam is tuned into resonance with rotational transitions in the (1,0) band of the A2Σ+–X2Π electronic transition at 236 nm, and the CARS signal is thus resonant with transitions in the (0,0) band. We observe significant resonant enhancement of the NO CARS signal and have obtained good agreement between calculated and experimental spectra.
High intensity focused ultrasound: surgery of the future? (2003)

For 50 years, high intensity focused ultrasound (HIFU) has been a subject of interest for medical research. HIFU causes selective tissue necrosis in a very well defined volume, at a variable distance from the transducer, through heating or cavitation. Over the past decade, the use of HIFU has been investigated in many clinical settings. This literature review aims to summarize recent advances made in the field. A Medline-based literature search (1965-2002) was conducted using the keywords "HIFU" and "high intensity focused ultrasound". Additional literature was obtained from original papers and published meeting abstracts. The most abundant clinical trial data comes from studies investigating its use in the treatment of prostatic disease, although early research looked at applications in neurosurgery. More recently horizons have been broadened, and the potential of HIFU as a non-invasive surgical tool has been demonstrated in many settings including the treatment of tumours of the liver, kidney, breast, bone, uterus and pancreas, as well as conduction defects in the heart, for surgical haemostasis, and the relief of chronic pain of malignant origin. Further clinical evaluation will follow, but recent technological development suggests that HIFU is likely to play a significant role in future surgical practice.
Extending the scope of pooled analyses of individual patient biomarker data from heterogeneous laboratory platforms and cohorts using merging algorithms (2016)

We demonstrate the feasibility of merging PlGF concentrations from different analytical platforms. Overall BRC identification of HDP performed at least as well as platform-specific curves. Our method can be extended to any set of biomarkers obtained from different laboratory platforms in any field. Merged biomarker data from multiple studies will improve statistical power and enlarge our understanding of the pathophysiology and management of medical syndromes.
Interaction of α-Agglutinin and a -Agglutinin, Saccharomyces cerevisiae Sexual Cell Adhesion Molecules (2001)

alpha-Agglutinin and a-agglutinin are complementary cell adhesion glycoproteins active during mating in the yeast Saccharomyces cerevisiae. They bind with high affinity and high specificity: cells of opposite mating types are irreversibly bound by a few pairs of agglutinins. Equilibrium and surface plasmon resonance kinetic analyses showed that the purified binding region of alpha-agglutinin interacted similarly with purified a-agglutinin and with a-agglutinin expressed on cell surfaces. At 20 degrees C, the K(D) for the interaction was 2 x 10(-9) to 5 x 10(-9) M. This high affinity was a result of a very low dissociation rate ( approximately 2.6 x 10(-4) s(-1)) coupled with a low association rate (= 5 x 10(4) M(-1) s(-1)). Circular-dichroism spectroscopy showed that binding of the proteins was accompanied by measurable changes in secondary structure. Furthermore, when binding was assessed at 10 degrees C, the association kinetics were sigmoidal, with a very low initial rate. An induced-fit model of binding with substantial apposition of hydrophobic surfaces on the two ligands can explain the observed affinity, kinetics, and specificity and the conformational effects of the binding reaction.
Thermal conductivity of simple and tubular nanowire composites in the longitudinal direction (2005)

This work establishes a generic model to study phonon transport and the thermal conductivity of periodic two-dimensional nanocomposites in the longitudinal direction (along the wire axis direction). More specifically, the generic model is applied to study the thermal conductivity of silicon-germanium composites with simple silicon nanowire and tubular silicon nanowire inclusions in a germanium matrix, and cylindrical nanoporous silicon materials. The results show that the effective thermal conductivity changes not only with the volumetric fraction of the constituents but also with the radius of the nanowires and cylindrical pores due to the nature of the ballistic phonon transport. The smaller the wire/pore diameter, the smaller is the thermal conductivity of the periodic two-dimensional nanocomposites for a given volumetric fraction. Composites with tubular nanowire inclusions have a lower effective thermal conductivity than simple nanowire composites due to the introduction of additional surface scattering through the pores associated with tubular nanowires. Results of this study can be used to direct the development of both high-efficiency thermoelectric materials and thermal interface material containing high-thermal-conductivity particle or wire inclusions.
Boosting CRISPR/Cas9 multiplex editing capability with the endogenous tRNA-processing system (2015)

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9) system is being harnessed as a powerful tool for genome engineering in basic research, molecular therapy, and crop improvement. This system uses a small guide RNA (gRNA) to direct Cas9 endonuclease to a specific DNA site; thus, its targeting capability is largely constrained by the gRNA-expressing device. In this study, we developed a general strategy to produce numerous gRNAs from a single polycistronic gene. The endogenous tRNA-processing system, which precisely cleaves both ends of the tRNA precursor, was engineered as a simple and robust platform to boost the targeting and multiplex editing capability of the CRISPR/Cas9 system. We demonstrated that synthetic genes with tandemly arrayed tRNA-gRNA architecture were efficiently and precisely processed into gRNAs with desired 5' targeting sequences in vivo, which directed Cas9 to edit multiple chromosomal targets. Using this strategy, multiplex genome editing and chromosomal-fragment deletion were readily achieved in stable transgenic rice plants with a high efficiency (up to 100%). Because tRNA and its processing system are virtually conserved in all living organisms, this method could be broadly used to boost the targeting capability and editing efficiency of CRISPR/Cas9 toolkits.
Abstract 3626: Development of inhibitors of the fibroblast growth factor receptor (FGFR) kinase using a fragment based approach (2010)

Abstract Recent data in a number of tumour types has implicated Fibroblast Growth Factor (FGF) and Fibroblast Growth Factor receptor (FGFR) signalling as being key to the molecular pathology of cancer. FGFR is a receptor tyrosine kinase which activates the extracellular signal-regulated kinase / mitogen-activated protein kinase and the protein kinase B / Akt pathways which promote cell growth and survival. Amplification, over-expression or activating mutations of fibroblast growth factor receptors have been associated with bladder tumours, multiple myeloma, hormone-refractory prostate cancer and breast cancer. Multiple lead series of FGFR inhibitors were developed using Astex's fragment based medicinal chemistry approach, Pyramid™, linked to high throughput X-ray Crystallography. We describe here the characterisation of some examples of these lead molecules. In particular we detail the pharmacological profile of a compound from one of these lead series that demonstrated activity against FGFR 1-4 with an IC50 &amp;lt;100nM in an isolated kinase assay. This compound inhibited FGFR1-4 kinase activity in BaF3 cell lines engineered to express the relevant kinase fusion proteins and proliferation and survival of a panel of FGFR-dependent human tumour cell lines derived from several different tissues. The cytotoxic activity was &amp;gt;10 fold lower in cell lines lacking FGFR expression. We demonstrate inhibition of FGFR 2 and 3 phosphorylation in gastric and multiple myeloma cell lines respectively with associated inhibition of downstream signalling pathways. This lead molecule has an excellent pharmacokinetic profile and high oral bioavailibility in mice and rats. In xenograft models in mice where aberrant FGF signalling underlies tumour pathology, tumour growth inhibition is observed at doses of 100mg/kg /day orally for 21 days. This xenograft efficacy was observed in several models, with significantly lower activity in models where aberrant FGF signalling is not involved in tumour pathology. This suggests that the mechanism of action is consistent with FGFR inhibition. The pharmacological profile in these models is also distinct from other broader spectrum receptor tyrosine kinase inhibitors. The pre-clinical data shown here suggests that such compounds warrant further investigation pre-clinically and may benefit patients whose disease is driven by FGFR activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3626.
Determination of Cannabinoids in Water and Human Saliva by Solid-Phase Microextraction and Quadrupole Ion Trap Gas Chromatography/Mass Spectrometry (1998)

Solid-phase microextraction (SPME) is applied to the determination of cannabidiol, delta 8-tetrahydrocannabinol (delta 8-THC), delta 9-tetrahydrocannabinol (delta 9-THC), and cannabinol in pure water and human saliva. The inherent extraction behavior of the cannabinoids in pure water is evaluated along with optimization of the method in human saliva. The commercially available poly(dimethylsiloxane) (PDMS) SPME fibers were found to be the best class for the cannabinoid analysis. Partition coefficients were found to be extremely large for all of the cannabinoids (log K > 4.0). Equilibrium times for the 7- and 30-micron PDMS fibers were 50 and 240 min, respectively. A shorter extraction time of 10 min with the 30-micron PDMS fiber may be used for multiple extractions from the same vial, thus conserving the sample necessary for analysis and speeding up the total analysis time. Recoveries for the cannabinoids in saliva, relative to pure water, were dramatically improved by a method developed in our laboratory involving addition of glacial acetic acid to the sample vial prior to performing SPME. Using this method, recoveries relative to SPME in pure water ranged from 21 to 47% depending on the cannabinoid. The linear range for spiked saliva samples was established at 5-500 ng/mL (r2 > 0.994) with precisions between 11 and 20% RSD. The ultimate level of detection by SPME for the cannabinoids in saliva was 1.0 ng/mL, with signal-to-noise values of > or = 12. A saliva sample collected 30 min after marijuana smoking was subject to SPME and traditional liquid-liquid extraction analysis. Internal standard quantitation results for delta 9-THC by both methods yielded comparable results, indicating that the SPME method of analysis is highly accurate and precise. The level of delta 9-THC by SPME was found to be 9.54 ng/mL for the saliva sample.
Palladium-Catalyzed Suzuki-Type Self-Coupling of Arylboronic Acids. A Mechanistic Study (1996)

Symmetrical biaryls are formed from arylboronic acids both under tetrakis(triphenylphosphine)palladium and under palladium(II) acetate catalysis. The principal mechanistic features of these self-couplings have been determined.
MULTIPLE EFFECTS ON DRUG-SENSITIVITY, GENOME STABILITY AND MALIGNANT POTENTIAL BY COMBINATIONS OF H-RAS, C-MYC AND MUTANT P53 GENE OVEREXPRESSION (1995)

Activation of specific oncogenes and inactivation of tumor suppressor genes play major roles in mechanisms leading to neoplastic transformation. The potential involvement of these genes in determining genome stability is an important issue. To examine the relationships between altered oncogene expression and the effects on genome stability, we have investigated the drug sensitivity properties of mouse 10T1/2 fibroblasts transfected with combinations of H-ras, c-myc and the proline 193 mutant form of p53. The relative colony forming efficiencies of these cells were investigated in the absence or presence of various concentrations of the chemotherapeutic agents, methotrexate, N-(phosphonacetyl)-L-aspartate (PALA) or hydroxyurea. The effects of altered oncogene expression were found to be drug and locus specific, and to lead to increased drug resistance (e.g. H-ras transfectants were significantly resistant to methotrexate or PALA), decreased drug resistance (e.g. H-ras/-myc transfectants were significantly less resistant to PALA or hydroxyurea than H-ras transfected cells), or to no significant change in drug sensitivity (e.g. H-ras transfected cells were not significantly different in sensitivity to hydroxyurea than non-transfected cells). Gene amplification was an important but not the only mechanism for drug resistance. Cells that were transfected with p53 (H-ras/p53 or H-ras/c-myc/p53) exhibited the greatest drug resistance properties with all three chemotherapeutic agents, in keeping with the important role of p53 in DNA repair and DNA amplification mechanisms. Although both H-ras/p53 and H-ras/c-myc/p53 groups exhibited very similar genome stability characteristics as determined by drug sensitivity results, they were significantly different in their abilities to produce transformed foci in vitro and lung metastases in vivo. The H-ras/c-myc/p53 transfected cells formed significantly higher numbers of transformed foci and exhibited a greater malignant potential. These results are consistent with observations that H-ras expression directly correlates with malignant potential, and that H-ras/c-myc/p53 transfected cells have higher H-ras expression than H-ras/p53 transfected cells. Alterations in genomic integrity through changes in onocogene expression play important roles in mechanisms determining drug sensitivity; in addition to genome destabilization, other events are critically involved in regulating transformed and malignant characteristics.
Showing your ID: intrinsic disorder as an ID for recognition, regulation and cell signaling (2005)

Regulation, recognition and cell signaling involve the coordinated actions of many players. To achieve this coordination, each participant must have a valid identification (ID) that is easily recognized by the others. For proteins, these IDs are often within intrinsically disordered (also ID) regions. The functions of a set of well-characterized ID regions from a diversity of proteins are presented herein to support this view. These examples include both more recently described signaling proteins, such as p53, alpha-synuclein, HMGA, the Rieske protein, estrogen receptor alpha, chaperones, GCN4, Arf, Hdm2, FlgM, measles virus nucleoprotein, RNase E, glycogen synthase kinase 3beta, p21(Waf1/Cip1/Sdi1), caldesmon, calmodulin, BRCA1 and several other intriguing proteins, as well as historical prototypes for signaling, regulation, control and molecular recognition, such as the lac repressor, the voltage gated potassium channel, RNA polymerase and the S15 peptide associating with the RNA polymerase S-protein. The frequent occurrence and the common use of ID regions in important protein functions raise the possibility that the relationship between amino acid sequence, disordered ensemble and function might be the dominant paradigm for the molecular recognition that serves as the basis for signaling and regulation by protein molecules.
Membrane association and release of wild-type and pathological tau from organotypic brain slice cultures (2017)

The spatiotemporal transmission of pathological tau in the brain is characteristic of Alzheimer's disease. Release of both soluble and abnormal tau species from healthy neurons is increased upon stimulation of neuronal activity. It is not yet understood whether the mechanisms controlling soluble tau release from healthy neurons is the same as those involved in the spread of pathological tau species. To begin to understand these events, we have studied tau distribution and release using organotypic brain slice cultures. The slices were cultured from postnatal wild-type and 3xTg-AD mice for up to 1 month. Tau distribution in subcellular compartments was examined by western blotting, and tau release into culture medium was determined using a sensitive sandwich ELISA. We show here that 3xTg-AD cultures have an accelerated development of pathological tau abnormalities including the redistribution of tau to synaptic and membrane compartments. The 3xTg-AD slice cultures show elevated basal tau release relative to total tau when compared with wild-type cultures. However, tau release from 3xTg-AD slices cannot be further stimulated when neuronal activity is increased with potassium chloride. Moreover, we report that there is an increased pool of dephosphorylated membrane-associated tau in conditions where tau release is increased. These data suggest that there may be differential patterns of tau release when using integrated slice culture models of wild-type and transgenic mouse brain, although it will be important to determine the effect of tau overexpression for these findings. These results further increase our knowledge of the molecular mechanisms underlying tau release and propagation in neurodegenerative tauopathies.
Borrelia BurgdorferiUpregulates the Adhesion Molecules E-selectin, P-selectin, ICAM-1 and VCAM-1 on Mouse Endothelioma Cellsin vitro (1994)

In order to obtain more information on processes leading to Borrelia burgdorferi-induced inflammation in the host, we have developed an in vitro model to study the upregulation of cell surface expression of adhesion molecules on endothelial cells by spirochetes. A mouse endothelioma cell line, derived from brain capillaries, bEnd3, was used as indicator population. bEnd3 cells were incubated with preparations of viable, inactivated or sonicated spirochetes and the expression of E-selectin, P-selectin, ICAM-1 and VCAM-1 was monitored by immunocytochemistry and quantified by cell surface ELISA. We show that all three spirochetal preparations are able to upregulate cell surface expression of E-selectin, P-selectin, ICAM-1 and VCAM-1 on bEnd 3 cells in a dose-dependent manner. The kinetics of cell surface expression of the individual adhesion molecules in the presence of Borrelia burgdorferi showed maxima at about 50 h of incubation or later; this was distinct from results obtained with sonicated-preparations of Escherichia coli bacteria or with enterobacterial LPS where peak expression was observed between 4 h and 16 h. The fact that Borrelia burgdorferi does not contain conventional LPS suggests that the mode of induction of adhesion molecules on endothelial cells is influenced by the phenotype of bacteria. At the peak of spirochete-induced cell surface expression of adhesion molecules (approximately 50 h), bEnd3 cells were found to bind cells of a VLA-4+ B lymphoma line (L1-2) much more efficiently than untreated control cells. The binding of L1-2 cells to presensitized bEnd3 cells was significantly inhibited (more than 75%) in the presence of monoclonal antibodies to both VLA-4 and its endothelial counterreceptor VCAM-1. These findings demonstrate that Borrelia burgdorferi organisms are able to induce functionally active adhesion molecules on endothelial cells in vitro and suggest that E-selectin, P-selectin, ICAM-1 and VCAM-1 play an important role in the pathogenesis of spirochetal infection.
CREB: a Ca 2+ -Regulated Transcription Factor Phosphorylated by Calmodulin-Dependent Kinases (1991)

The mechanism by which Ca2+ mediates gene induction in response to membrane depolarization was investigated. The adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB) was shown to function as a Ca(2+)-regulated transcription factor and as a substrate for depolarization-activated Ca(2+)-calmodulin-dependent protein kinases (CaM kinases) I and II. CREB residue Ser133 was the major site of phosphorylation by the CaM kinases in vitro and of phosphorylation after membrane depolarization in vivo. Mutation of Ser133 impaired the ability of CREB to respond to Ca2+. These results suggest that CaM kinases may transduce electrical signals to the nucleus and that CREB functions to integrate Ca2+ and cAMP signals.
The calcium-binding properties of bovine factor V. (1980)

The calcium-binding properties of the coagulation cofactor, Factor V, have been investigated using atomic absorption spectrophotometry, equilibrium dialysis, and chemical exchange experiments. Two classes of binding sites have been observed: one site containing a single Ca2+ ion bound with an unusually high affinity (Kd less than 10(-8) M), and a second site in which 2 mol of calcium are bound/mol of Factor V with an association constant Ka = 1.7 +/- 0.52 x 10(4) M-1 (Kd = 5.9 +/- 1.9 x 10(-5) M). The binding of the dissociable Ca2+ ions is apparently noncooperative. The single high affinity Ca2+ ion may be removed readily by EDTA under native conditions with an immediate loss of Factor V activity, and the activity of the Factor V can be restored by the addition of a molar excess of calcium. The high affinity Ca2+ ion will exchange with radiolabeled calcium in solution, and Factor V labeled in this way was used to provide an independent measure of the stoichiometry of this high affinity binding site, and to observe directly the interaction of calcium in this site with EDTA. In addition, elemental analyses of solid lyophilized samples of Factor V revealed that no transition metals are present and that no phosphorus (or phospholipid) is retained by the Factor V after purification.
Synthesis and Characterization of Nanometric Iron and Iron-Titanium Oxides by Mechanical Milling: (2005)

Nanometric mixed iron-titanium oxides were prepared by mechanical milling with a view to determining their ability to act as anodic materials in lithium cells. At a mole ratio of 0.4, a solid-state reaction occurs that leads to the formation of , which possesses a spinel-like structure; at lower ratios, however, the structure retains the hematite framework. cells exhibit poor electrochemical reversibility; by contrast, Ti-containing electrodes possess improved cycling properties. Changes in the electrodes upon cycling were examined by X-ray photoelectron spectroscopy (XPS). XPS data confirm the participation of electrolyte in the electrochemical reaction and the different type of electrochemical reversibility exhibited by samples. Both processes were influenced by the presence of titanium. Titanium dioxide, in the presence of iron oxides, seems to be inactive to the electrochemical process. Based on the step potential electrochemical spectroscopy (SPES) curves and photoelectron spectra obtained, the presence of Ti increases the reversibility of the redox reactions undergone by the electrolyte during discharge/charge processes. The increased active-material/electrolyte/inactive-material interaction which is reported here offers new perspectives for the use of well-known transition oxides as anode materials in Li-ion batteries.