gebhart/patrepeval huggingface dataset:
Quantitative analysis of p53-targeted gene expression and visualization of p53 transcriptional activity following intratumoral administration of adenoviral p53 in vivo (2004)

Abstract To analyze the mechanism of the antitumor effect of an adenoviral vector expressing the p53 tumor suppressor (Ad-p53) in vivo, we quantitatively assessed p53-targeted gene expression and visualized transcriptional activity of p53 in tumors in nude mice treated with Ad-p53. Human lung cancer (H1299) xenografts established in nude mice were treated by intratumoral administration of Ad-p53. The levels of expression of exogenous p53 and p53-targeted genes p21, MDM2, Noxa, and p53AIP1 were quantified by real-time reverse transcription-PCR (RT-PCR) and induction of apoptosis was observed histochemically on days 1–3, 7, and 14 after treatment. Expression of mRNA of exogenous p53 and p53-targeted genes (except p53AIP1) was at its maximum 1 day after Ad-p53 treatment and then decreased rapidly; apoptosis was evident in situ 2–3 days after treatment. We developed a noninvasive and simple method for monitoring the transcriptional activity of exogenous p53 following intratumoral administration of Ad-p53 in nude mice. We established H1299 cells that express the green fluorescent protein (GFP) reporter gene under the control of p53-responsive p21 promoter (i.e., the p53R-GFP reporter system). Xenografts of these cells in nude mice were treated by intratumoral administration of Ad-p53, and the transcriptional activity of exogenous p53 could be visualized as intratumoral GFP expression in real time by 3-CCD camera. Expression of GFP was maximal 3 days after treatment and decreased remarkably by 7 days after treatment. We demonstrated that Ad-p53 treatment rapidly induced p53-targeted genes and apoptosis in tumors and succeeded in visualizing p53 transcriptional activity in vivo. We also found that Ad-p53 infection induced phosphorylation of p53 at Ser46 in p53-sensitive H1299 cells in vitro but not in p53-resistant H226Br cells, suggesting that phosphorylation of Ser46 is involved in p53-dependent apoptosis. Our data indicate that quantitative analysis of p53-targeted gene expression by real-time quantitative RT-PCR and visualization of p53 transcriptional activity in fresh xenografts by using the p53R-GFP reporter system may be useful in assessing the mechanisms of the antitumor effects of Ad-p53 and novel therapeutic approaches.
Auxin: Regulation, Action, and Interaction (2005)

Nearly six decades after the structural elucidation of IAA, many aspects of auxin metabolism, transport and signalling are well established; however, more than a few fundamental questions and innumerable details remain unresolved.
Highly ordered TiN nanotube arrays as counter electrodes for dye-sensitized solar cells (2009)

TiN nanotube arrays, prepared by the anodization of metallic Ti foil substrate and subsequent simple nitridation in an ammonia atmosphere, were investigated as low-cost counter electrodes in dye-sensitized solar cells for the first time. It is found that the highly ordered TiN nanotube arrays on the metallic Ti foil substrate show an excellent performance, comparable with typical Pt counter electrodes.
Absorbed fractions for electrons and beta particles in spheres of various sizes (1994)

The use of electron-emitting radionuclides in tumor imaging and therapy has presented some new challenges to conventional radiation dosimetry. The fraction of electron energy absorbed in most source regions has usually been assumed to be unity. In small structures such as localized tumors or isolated regions containing moderate to high energy electron emitters, however, this may not always be the case. Using an extension of Berger`s scaled absorbed dose distributions for point sources to represent a spherical geometry, absorbed fractions of electron energy for sources uniformly distributed in spheres of various sizes have been calculated. Beta particle and monoenergetic electron energies studied range from 0.025 to 4.0 MeV and sphere masses range from 0.01 to 1000 g. S values have also been calculated for {sup 90}Y, {sup 123}I and {sup 131}I based on the results of the absorbed fraction calculations. These calculated absorbed fractions are valuable in estimating electron energy loss from small spherical structures and may be useful in estimating the radiation dose to these small volumes. 9 refs., 2 figs., 3 tabs.
Scalable consistency maintenance in content distribution networks using cooperative leases (2003)

We argue that cache consistency mechanisms designed for stand-alone proxies do not scale to the large number of proxies in a content distribution network and are not flexible enough to allow consistency guarantees to be tailored to object needs. To meet the twin challenges of scalability and flexibility, we introduce the notion of cooperative consistency along with a mechanism, called cooperative leases, to achieve it. By supporting /spl Delta/-consistency semantics and by using a single lease for multiple proxies, cooperative leases allow the notion of leases to be applied in a flexible, scalable manner to CDNs. Further, the approach employs application-level multicast to propagate server notifications to proxies in a scalable manner. We implement our approach in the Apache Web server and the Squid proxy cache and demonstrate its efficacy using a detailed experimental evaluation. Our results show a factor of 2.5 reduction in server message overhead and a 20 percent reduction in server state space overhead when compared to original leases albeit at an increased interproxy communication overhead.
Anti-Cancer Therapy: Targeting the Mevalonate Pathway (2006)

The mevalonate pathway has become an important target for anti-cancer therapy. Manipulation of this pathway results in alteration of malignant cell growth and survival in cell culture and animal models, with promising potential for application in human cancers. Mevalonate is synthesized from 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA). Mevalonate is further metabolized to farnesyl pyrophosphate (FPP), which is the precursor for sterols. In addition, the farnesyl moiety from FPP is utilized for post-translational modification of proteins including small GTPases, such as Ras and Ras related proteins, which play a role in malignant transformation of cells. FPP is a precursor for geranylgeranyl pyrophosphate (GGPP), which is similarly involved in post-translational modification of proteins. There has been intense interest in manipulating the pathway through HMG-CoA reductase inhibition. More recently, the focus has been on manipulating the pathway by post-translational modification of key regulatory proteins through farnesyl prenyl transferase (FPTase) or geranylgeranyl prenyl transferase (GGPTase) inhibition. This review focuses on the mevalonate pathway and the application of rational drug therapies to manipulate this pathway. Included in the review are a summary of agents demonstrating success in preclinical investigations such as; farnesyl transferase inhibitors, geranylgeranyl transferase inhibitors, dual inhibitors, statins, bisphosphonates, histone deacetylase inhibitors and other compounds. While these agents have shown preclinical success, translation to success in clinical trials has been more difficult. These clinical trials are reviewed along with evaluation of some of the potential problems with these agents in their clinical application.
Biochemical Characterization of Glycyrrhizin as an Effective Inhibitor for Hyaluronidases from Bovine Testis. (1997)

The inhibitory effects of several anti-inflammatory agents, including glycyrrhizin (GL), on the activities of hyaluronidases (HAses) purified from bovine testes and Streptomyces were investigated in vitro. It was found that (i) GL inhibits the activity of HAse (p55) from bovine testes in a dose-dependent manner, but does not affect HAse from Streptomyces; (ii) GL was the most effective of the compounds tested on bovine testis HAse activity (50% inhibition with approx. 3 microM GL); and (iii) glycyrrhetinic acid (GA), a derivative (oGA) of GA and diglucuronic acid had no detectable effects on HAse activity at 9.0 microM. The GL-induced inhibition of HAse activity is uncompetitive for its substrates. Data are provided to support the contentions that (i) bovine testis HAse (p55) is a GL-binding protein; and (ii) GL acts as a potent inhibitor of HAse in vitro.
Calculations of ZnO properties using the Heyd-Scuseria-Ernzerhof screened hybrid density functional (2009)

The Heyd-Scuseria-Ernzerhof (HSE) screened hybrid density functional has been proven to yield lattice constants and energy gaps of semiconductors in better agreement with experiment than standard local and semilocal exchange correlation functionals. The latter underestimate the band gaps of many semiconductors severely, i.e., in the case of ZnO the underestimation amounts to 75% of the experimental value. In this work, we report on the structure optimization and the study of the electronic band gap of ZnO in the wurtzite phase performed within density-functional theory using the semilocal Perdew-Burke-Ernzerhof as well as the HSE functional. Furthermore, the phonon-dispersion relations of ZnO and the dielectric and piezoelectric properties are calculated with both functionals and are compared to experimental findings.
An internally controlled peripheral biomarker for Alzheimer’s disease: Erk1 and Erk2 responses to the inflammatory signal bradykinin (2006)

Cognitive impairment has recently been found to correlate with changes in peripheral inflammatory signals such as TNF-alpha and IL-1beta. PKC isozymes regulate levels of TNF-alpha and IL-6 and the release of other cytokines and also show deficits in Alzheimer's disease (AD) brains and skin fibroblasts. Here, we investigate MAPK Erk1 and Erk2 phosphorylation in response to the inflammatory agonist bradykinin, which activates PKC pathways. An internally controlled comparison of Erk1 and Erk2 produced an AD index that accurately distinguished fibroblasts of AD from those of normal controls and of non-AD dementias. This accuracy was demonstrated for Coriell Cell Repository (Coriell Institute of Medical Research, Camden, NJ) samples, as well as for samples analyzed on gels with autopsy diagnostic confirmation. AD Erk1 and Erk2 index values were inversely correlated with disease duration, suggesting maximal efficacy for early diagnosis. Finally, the results also demonstrate that, when the AD index agreed with the clinical diagnosis on the presence of AD, there was a high probability of accuracy based on autopsy validation. Thus, this peripheral molecular biomarker, based on differential Erk1 and Erk2 phosphorylation, could have important clinical utility for providing increased certainty in the positive diagnosis of AD, particularly in the early phase of disease progression.
Production of Recombinant Human Von Willebrand Factor in the Milk of Transgenic Pigs (2009)

Von Willebrand factor (vWF), a large multimeric glycoprotein present in blood plasma, is a blood protein of the coagulation system. It is defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura-hemolytic uremic syndrome and heyde's syndrome. We have developed a line of transgenic swine harboring recombinant human von Willebrand factor (rhvWF) cDNA through microinjection of fertilized one-cell pig zygotes. Expression of rhvWF in the mammary gland and secretion of rhvWF into the milk of the transgenic swine were confirmed by immunohistochemical and western blot analyses, respectively, and rhvWF proteins were detected in milk from all lactating founder females at concentrations that were 28- to 56-folds greater than that in circulating human plasma. The amino acid sequence of rhvWF protein in the transgenic pig milk matched that of vWF produced from human blood plasma. This study provides evidence that production of rhvWF from transgenic pig milk is a potentially valuable technology and can be used as a cost-effective alternative in clinical applications.
Multiple Scale Faster-RCNN Approach to Driver’s Cell-Phone Usage and Hands on Steering Wheel Detection (2016)

In this paper, we present an advanced deep learning based approach to automatically determine whether a driver is using a cell-phone as well as detect if his/her hands are on the steering wheel (i.e. counting the number of hands on the wheel). To robustly detect small objects such as hands, we propose Multiple Scale Faster-RCNN (MSFRCNN) approach that uses a standard Region Proposal Network (RPN) generation and incorporates feature maps from shallower convolution feature maps, i.e. conv3 and conv4, for ROI pooling. In our driver distraction detection framework, we first make use of the proposed MS-FRCNN to detect individual objects, namely, a hand, a cell-phone, and a steering wheel. Then, the geometric information is extracted to determine if a cell-phone is being used or how many hands are on the wheel. The proposed approach is demonstrated and evaluated on the Vision for Intelligent Vehicles and Applications (VIVA) Challenge database and the challenging Strategic Highway Research Program (SHRP-2) face view videos that was acquired to monitor drivers under naturalistic driving conditions. The experimental results show that our method archives better performance than Faster R-CNN on both hands on wheel detection and cell-phone usage detection while remaining at similar testing cost. Compare to the state-of-the-art cell-phone usage detection, our approach obtains higher accuracy, is less time consuming and is independent to landmarking. The groundtruth database will be publicly available.
Management of Patients Refractory to Platelet Transfusion (2007)

This article discusses the causes and management of platelet refractoriness. Improvements in the quality of platelets and leukoreduction have reduced the morbidity and mortality related to alloimmunization and refractoriness of patients to platelet transfusion. Alloimmunization can be distinguished from other causes of poor post-transfusion platelet increments by the measurement of platelet alloantibodies. Options for managing platelet refractoriness caused by alloimmunization include platelet transfusion from human leukocyte antigen-matched or donor-recipient cross-matched platelets. Prevention strategies include efforts to limit recipients' exposure to human leukocyte antigen specificities by using single-donor platelets, filtration to reduce the number of human leukocyte antigen-bearing leukocytes, and pretransfusion ultraviolet B irradiation to decrease their immunogenicity. For appropriate management of patients refractory to platelets, close cooperation and good communication are necessary between clinicians and blood centers.
Cadherin-11-mediated interactions with bone marrow stromal/osteoblastic cells support selective colonization of breast cancer cells in bone (2008)

Cell adhesion molecules have been implicated in the selective colonization of cancer in distant organs. Breast cancer has a strong predilection for spreading to bone. Cadherin-11, which is one of the classical type-2 cadherin family members and mediates homophilic cell-cell adhesion, is constitutively expressed in stromal and osteoblastic cells in bone marrow. Elevated cadherin-11 expression is also found in aggressive human breast cancers. Here, we investigated the role of the interactions between breast cancer cells and bone marrow stromal/osteoblastic cells via cadherin-11 in the selective spread to bone. The bone-seeking clone of the MDA-MB-231 human breast cancer cells showed greater cadherin-11 expression than the parental and the brain-seeking clone. Cadherin-11 overexpression in MDA-MB-231 cells increased bone metastases with promoted bone resorption, while the natural variant form of cadherin-11 that is unable to establish cell-cell adhesion did not. Of note, introduction of cadherin-11 showed no effects on lung metastases. Fluorescence-activated cell sorter analysis using the fluorescent dye-labeled cancer cells showed that early colonization in bone marrow was increased by cadherin-11. Co-cultures with the MC3T3-E1 osteoblastic cells that constitutively expressed cadherin-11 caused an up-regulation of parathyroid hormone-related protein (PTH-rP) production in MDA-MB-231 cells overexpressing cadherin-11. The conditioned medium of the co-cultures increased osteoclastogenesis, which was blocked by a neutralizing antibody to PTH-rP. In conclusion, our results suggest that cadherin-11 promotes homing and migration to bone and osteoclastogenesis through mediating the homophilic interactions of breast cancer cells with marrow stromal/osteoblastic cells, thereby enhancing bone metastases.
Photoluminescence from Single Semiconductor Nanostructures (1999)

We review some recent results in the spectroscopy of single CdSe nanocrystal quantum dots. By eliminating the effects of inhomogeneous broadening and ensemble averaging, single nanocrystal spectroscopy has revealed many new and previously unexpected physical phenomena. Among those discussed in this review are ultra-narrow emission lineshapes (∼600× narrower than ensemble spectra), a highly polarizable emitting state in the presence of strong local electric fields, line broadening as a result of environmental fluctuations, and shifting of the emission spectra over a wide range of energies (from less than 300 μeV to 80 meV). In addition, polarization spectroscopy of single nanocrystals has revealed the presence of a theoretically predicted two-dimensional transition dipole moment oriented in the xy plane of the nanocrystals. As a result, it is, in principle, possible to use polarization spectroscopy to determine the three-dimensional orientation of individual nanocrystals. These and other studies of single quantum dots have provided us with significant insight into the detailed physics and dynamics of this unique and fascinating physical system.
Chimeric Receptors of the Human C3a Receptor and C5a Receptor (CD88) (1999)

Chimeras were generated between the human anaphylatoxin C3a and C5a receptors (C3aR and C5aR, respectively) to define the structural requirements for ligand binding and discrimination. Chimeric receptors were generated by systematically exchanging between the two receptors four receptor modules (the N terminus, transmembrane regions 1 to 4, the second extracellular loop, and transmembrane region 5 to the C terminus). The mutants were transiently expressed in HEK-293 cells (with or without Galpha-16) and analyzed for cell surface expression, binding of C3a and C5a, and functional responsiveness (calcium mobilization) toward C3a, C5a, and a C3a as well as a C5a analogue peptide. The data indicate that in both anaphylatoxin receptors the transmembrane regions and the second extracellular loop act as a functional unit that is disrupted by any reciprocal exchange. N-terminal substitution confirmed the two-binding site model for the human C5aR, in which the receptor N terminus is required for high affinity binding of the native ligand but not a C5a analogue peptide. In contrast, the human C3a receptor did not require the original N terminus for high affinity binding of and activation by C3a, a result that was confirmed by N-terminal deletion mutants. This indicates a completely different binding mode of the anaphylatoxins to their corresponding receptors. The C5a analogue peptide, but not C5a, was an agonist of the C3aR. Replacement of the C3aR N terminus by the C5aR sequence, however, lead to the generation of a true hybrid C3a/C5a receptor, which bound and functionally responded to both ligands, C3a and C5a.
Negative charge, barrier heights, and the conduction-band discontinuity in AlxGa1−xAs capacitors (1985)

We have combined current-voltage (I-V) and capacitance-voltage (C-V) measurements on n− GaAs–Al0.4Ga0.6As–n+ GaAs capacitors with different thicknesses of Al0.4Ga0.6As to determine the conduction-band discontinuity at the Al0.4Ga0.6As–n+ GaAs interface. Undoped AlxGa1−xAs deposited by molecular-beam epitaxy contains negative charge. We calculate the effect of band bending in undoped AlxGa1−xAs due to negative charge on measured barrier heights and on C-V curves. The temperature dependence of I-V curves is analyzed in terms of thermionic emission to derive barrier heights at the n+ GaAs–Al0.4Ga0.6As interface φG. Measured values of φG are proportional to the square of the insulator thickness, w, showing that negative charge is uniformly distributed through undoped Al0.4Ga0.6As. Combining values of Fermi energy and band bending at zero bias with φG at zero Al0.4Ga0.6As thickness, we find that the value of the barrier discontinuity for n+ GaAs–Al0.4Ga0.6As is ∼0.30 V. This corresponds to a ratio of conduction-band discontinuity ΔEC to band-gap difference ΔEG of 0.63±0.03, which is appreciably less than the value 0.85±0.03 that is widely accepted. We find that the dielectric constant of Al0.4Ga0.6As is more temperature dependent than that of GaAs between 77 and 250 K.
Integrated feature scale modeling of plasma processing of porous and solid SiO2. I. Fluorocarbon etching (2004)

Increases in RC delay times in interconnect wiring for microelectronics as feature sizes decrease have motivated investigations into the use of low-dielectric constant insulators, and in particular, porous silicon-dioxide (PS). Profile evolution and maintenance of critical dimensions during plasma etching of PS are problematic due to the exposure of open pores. To investigate these issues, reaction mechanisms for fluorocarbon plasma etching of SiO2 in C2F6, CHF3, and C4F8 chemistries have been developed and incorporated into the Monte Carlo Feature Profile Model which was modified to address these two-phase systems. The reaction mechanism was validated by comparison to experiments by others for etching of PS and solid SiO2 (SS). We found that the etch rates for PS are generally higher than that of SS due to the inherently lower mass fraction. Mass corrected etch rates of PS can be larger or smaller than those for SS depending on the degree of pore filling by polymer and the degree of ion activated chemical sputtering. Pore filling is particularly important for PS having open networks with large pores and high porosities. We found little dependence of the taper of high aspect ratio profiles on the average pore radius and porosity. However, the profile changes from tapered to bowed as the interconnectivity of the porous network increases. Scaling laws for profile shapes are otherwise similar for both SS and PS.
Chromosome site for Epstein-Barr virus DNA in a Burkitt tumor cell line and in lymphocytes growth-transformed in vitro. (1983)

The Epstein-Barr virus (EBV) genome stably persists in latently infected Burkitt tumor cells and growth-transformed B lymphocytes. These cells usually contain multiple copies of episomal viral DNA. Cytological hybridization of recombinant viral DNA fragments to metaphase chromosomes of two latently infected cell lines demonstrates that viral DNA localizes to both chromatids of one homologue of chromosome 1 in Namalwa, a Burkitt tumor cell line, and to both chromatids of one homologue of chromosome 4 in IB4, a cell line with transformed growth properties in vitro. The site of chromosome association remains stable in a clone of IB4 cells. Probes from five separate regions of the EBV genome hybridize to the same chromosome regions. A previously undescribed achromatic site is identified within the region of EBV chromosome cytological hybridization. These observations suggest that most or all of the EBV genome is integrated into the chromosomal DNA of Namalwa and IB4 cells. Although the chromosomal sites of EBV DNA association are among those regions with homology to the EBV IR3 repeated DNA sequence, EBV IR3 did not mediate recombination between EBV and chromosomal DNA.