gebhart/patrepeval huggingface dataset:
Discovery and analysis of inhibitors of the human immunodeficiency integrase. (1997)

An essential step in the replication of retroviruses is the integration of a DNA copy of the viral genome into the genome of the host cell. Integration encompasses a series of ordered endonucleolytic and DNA strand transfer reactions catalyzed by the viral enzyme, integrase. The requirement for integrase activity in the propagation of HIV-1 in cell culture defines the enzyme as a potential target for chemotherapeutic intervention. We have therefore developed a non-radioisotopic microtiter plate assay which can be used to identify novel inhibitors of integrase from random chemical screens and for the bioassay driven isolation of inhibitors from natural products. This assay uncouples various steps in the reaction pathway and therefore can be exploited to characterize inhibitors. In this monograph we describe a series of modifications to the method which facilitate such mechanistic studies using as an example a series of previously described integrase inhibitors.
GaN and AlGaN Devices: Field Effect Transistors and Photodetectors (2000)

A b stra c t........................................................................................... 48 1. In tro d u c tio n ................................................................................... 48 2. Material Parameters of GaN-based Semiconductors Importantfor Their Applications in FETs and Photodetectors.................... 49 3. Epitaxial Growth, Processing, Ohmic and Schottky Contactsand AlGaN/GaN/InN Band L in e u p s ............................................ 52 4. GaN-based Field Effect T ra n s is to rs ............................................ 554.1. Designs of GaN-based Field Effect Transistors ................ 55 4.2. High Temperature Performance and AlGaN/GaN DopedChannel H FE T s....................................... 58 4.3. Doped Channel H F E T ............................................................ 60 4.4. Role of Piezoelectric E ffec t.................................................... 62 4.5. Maximum Currents and Breakdown Voltages of GaN-basedHFETs ................................................................................... 65 4.6. Self-heating and GaN/AlGaN HFETs on SiC Substrates . . 65 4.7. GaN-based Heterojunction Bipolar Transistors.................... 675. GaN-based Photodetectors............................................................ 67 5.1. GaN and AlGaN Photodetector T y p e s ................................ 67 5.2. Photodetector Characteristics................................................ 69 R esponsivity ................................................................................... 69 Photoconductive G a i n .................................................................... 70Detectivity and Noise Equivalent Power ( N E P ) ................ 72 N o i s e ....................................................................................... 735.3. Photoconductive GaN and AlGaN Photodetectors . . . . 74 5.4. Schottky Barrier and p — n Junction GaN Photodetectors . 76 5.5. GaN Metal-Semiconductor-Metal Photodetectors . . . . 81 5.6. Avalanche Breakdown and Breakdown Luminescencein p-7r-n GaN D i o d e s ............................................................ 82 5.7. Gated Photodetector Based on GaN/AlGaN HeterostructureField Effect T ransisto r............................................................ 82 5.8. Emissive UV P hotodetecto rs................................................ 836. Challenges and Future Improvements in GaN Photodetector and FET Technology .................................................................... 85 Acknowledgm ent........................................................................... 85 R eferences....................................................................................... 86Recent improvements in material quality and contact technology for GaNbased materials system have led to a rapid progress in GaN devices. These devices include blue-green lasers [1], blue and green Light Emitting Diodes [2], Ultraviolet (UV) photodetectors [3,4] GaN Avalanche Photo Diodes [5], and AlGaN/GaN Heterostructure Field Effect Transistors [6-11].
Tuning the emission characteristics of top-emitting organic light-emitting devices by means of a dielectric capping layer: An experimental and theoretical study (2003)

The emission characteristics of top-emitting organic light-emitting devices (OLEDs) have been studied experimentally and theoretically to derive a quantitative understanding of the effect of a dielectric capping layer. We demonstrated that the angular intensity distribution and the spectral characteristics can be tuned and the light outcoupling enhanced simply by varying the optical thickness of a dielectric layer deposited on top of a semitransparent metal electrode. With the capping-layer concept, the outcoupled light intensity in forward direction was increased by a factor of 1.7, and concomitantly a high color purity achieved. An optical model based on a classical approach was used to calculate the emission characteristics. The excellent agreement between measured and simulated data shows that the capping layer controls the interplay between different interference effects such as wide-angle and multiple-beam interference occurring in top-emitting OLEDs. The strength of the capping layer concept is in particular that the optical and the electrical device performance can be optimized separately.
The Academic Achievement Game (2001)

Using the notion of design developed as part of the New London Group's Multiliteracies Project, this qualitative multicase study examines undergraduate academic literacy as a multimodal achievement game. Retrospective interviews and textual analyses revealed a series of operations on course content that constituted moves in the game. The goal of the game was to find, move, and display content, including not only facts but also concepts and forms of situated knowledge that would gain the highest points on assessments. Better “players” were more aware than their lower achieving counterparts of the game as specific activity different from learning. They also had more nuanced and planned versions of the operations that began with what was expected on assessments and moved backwards toward sources. Findings support forms of preparing students for academic success through the multiliteracies pedagogy that combines consciousness raising through overt instruction with forms of immersion and critical analysis.
Inhibition of the Mitotic Kinesin Eg5 Up-regulates Hsp70 through the Phosphatidylinositol 3-Kinase/Akt Pathway in Multiple Myeloma Cells (2006)

The microtubule-dependent motor protein Eg5 plays a critical role in spindle assembly and maintenance in mitosis. Herein we show that the suppression of Eg5 by a specific inhibitor arrested mitosis, induced apoptosis, and up-regulated Hsp70 in human multiple myeloma cells. Mechanistically, Hsp70 induction occurred at the transcriptional level via a cis-regulatory DNA element in Hsp70 promoter and was mediated by the phosphatidylinositol 3-kinase/Akt pathway. Eg5 inhibitor-mediated Hsp70 up-regulation is cytoprotective because blocking Hsp70 induction directly by antisense or small interfering RNA or indirectly by inhibiting the phosphatidylinositol 3-kinase/Akt pathway significantly increased Eg5 inhibitor-induced apoptosis. Furthermore, a farnesyltransferase inhibitor interacted synergistically with the Eg5 inhibitor in inducing apoptosis through disrupting the Akt/Hsp70 signaling axis. These findings provide the first evidence for Eg5 inhibitor activity in hematologic malignancy and identify Hsp70 up-regulation as a critical mechanism responsible for modulating myeloma cell sensitivity to Eg5 inhibitors. In addition, these findings suggest that a combination of Eg5 inhibitors with agents abrogating Hsp70 induction would be useful for myeloma therapy in the clinic.
IL-6 and TNF-α promote metastasis of lung cancer by inducing epithelial-mesenchymal transition (2017)

The characteristics of cancer cells, such as invasiveness, are affected by the tumor microenvironment. Studies have shown that interleukin (IL)-6 and tumor necrosis factor (TNF)-α regulate the proliferation of lung cancer. However, few studies have focused on the effects of IL-6 and TNF-α on metastasis of lung cancer. The present study was designed to investigate whether IL-6 and TNF-α can promote metastasis of non-small cell lung cancer (NSCLC). Sixty-five tumor and matched adjacent tissue samples from patients with NSCLC and corresponding serum samples were collected. Thirty serum samples from healthy subjects were selected as controls. Real-time PCR and western blot analysis were used to measure IL-6, TNF-α, vimentin, E-cadherin, and N-cadherin expression in tissue samples; ELISA was used to measure IL-6 and TNF-α expression in serum samples. The correlation of serum levels of IL-6 and TNF-α with the clinical stage was analyzed; the correlation of IL-6 and TNF-α levels in serum with these tissues was analyzed; the correlation of serum levels of IL-6 and TNF-α with lymph node metastasis and distant metastasis was analyzed. Expression of IL-6 and TNF-α were significantly increased compared with controls in both serum and tissue; IL-6 and TNF-α levels were positively correlated with lymph node metastasis and distant metastasis; IL-6 and TNF-α levels were negatively correlated with E-cadherin level and were positively correlated with N-cadherin and vimentin levels. In conclusion, IL-6 and TNF-α can induce epithelial-mesenchymal transition, and subsequently promote metastasis of lung cancer. Anti-inflammation should be considered for the treatment of lung cancer.
Tobacco mosaic virus infection stimulates the phosphorylation of a plant protein associated with double-stranded RNA-dependent protein kinase activity. (1988)

The influence of tobacco mosaic virus (TMV) infection on nucleotide binding and phosphorylation of an Mr 68,000 host-encoded protein (p68) was examined. The phosphorylation of p68 in homogenates from TMV-infected tissues was 4-fold greater than in homogenates from mock inoculated tissues. Phosphorylation of p68 in extracts from mock inoculated tissues was enhanced by the addition of double-stranded (ds) RNA. Nucleotide photoaffinity labeling experiments indicate that p68 contains an ATP binding site with characteristics consistent with protein kinase activity. Antiserum raised against a dsRNA-dependent protein kinase activity. Antiserum raised against a dsRNA-dependent protein kinase from interferon-treated human cells immunoprecipitated p68 from extracts of TMV-infected tissue, and p68-containing immunocomplexes catalyzed the phosphorylation of endogenous p68. These data suggest that p68 may be an autophosphorylating, dsRNA-dependent protein kinase involved in viral pathogenesis. Based upon analogous functions demonstrated for dsRNA-dependent protein kinases in mammalian systems, p68 may have a role in the regulation of protein synthesis and viral replication in infected cells.
Surface-Charge-Governed Ion Transport in Nanofluidic Channels (2004)

A study of ion transport in aqueous-filled silica channels as thin as 70 nm reveals a remarkable degree of conduction at low salt concentrations that departs strongly from bulk behavior: In the dilute limit, the electrical conductances of channels saturate at a value that is independent of both the salt concentration and the channel height. Our data are well described by an electrokinetic model parametrized only by the surface-charge density. Using chemical surface modifications, we further demonstrate that at low salt concentrations, ion transport in nanochannels is governed by the surface charge.
Lyt-23+ cyclophosphamide-sensitive T cells regulate the activity of an interleukin 2 inhibitor in vivo. (1981)

Sera of thymus-bearing normal mice contain high levels of Interleukin 2 (II-2) inhibitor, whereas sera of athymic nu/nu mice do not. Evidence is presented that cyclophosphamide-sensitive Lyt-23+ T cells induce high II-2 inhibitor activity in the recipient nu/nu mice in the course of a graft-vs.-host reaction. The II-2 inhibitor has an approximately 50,000 mol wt. Its function is neither antigen specific nor H-2 restricted. During ontogeny, its activity parallels the development of T cell reactivity, i.e., it is absent both in the amniotic fluid and in sera of unborn mice, but increases to high levels during the early postnatal phase. The II-2 inhibitor described is viewed as an example of a T cell-dependent, in vivo regulatory mechanism able to effectively counteract the nonspecific activity of the Lyt-1+ helper T cell-derived II-2. Because the II-2 inhibitor activity is rather high in vivo, II-2 activity will exist only in close proximity to its producer cell, thereby maintaining specificity during the in vivo induction of cytotoxic T lymphocytes
Use of the RAPD Technique for Identification ofFusarium oxysporumf. sp.dianthifrom Carnation (1994)

The random amplified polymorphic DNA (RAPD) method was used to distinguish among pathogenic and nonpathogenic isolates of Fusarium oxysporum recovered from carnation. Fifty-eight isolates, which were isolated in Israel from different cultivars of carnation, included 42 pathogenic isolates of race 2, one pathogenic isolate of race 4, and 15 nonpathogenic isolates. These isolates were examined for RAPD patterns with 30 arbitrary primers of 10 bases. The RAPD patterns generated by each of 22 primers enabled us to distinguish clearly between pathogenic and nonpathogenic isolates from carnation. The amplification patterns of race 2 isolates were identical for all the primers examined [...]
Pteridine, LXVIII. Überführung von Biopterin in Sepiapterin und absolute Konfiguration des Sepiapterins (1979)

Pteridines, LXVIII. Transformation of Biopterin into Sepiapterin and Absolute Configuration of Sepiapterin A new synthesis of the Drosophila pigment sepiapterin ( 10 ) has been found in the pH‐dependent autoxidation of 5,6,7,8‐tetrahydrobiopterin ( 1 ). Most sepiapterin is formed at pH4 leading to a 20% yield. Autoxidation of 1 at pH 7.5 caused a more severe degradation with preferential formation of 7,8‐dihydroxanthopterin ( 11 ). The absolute configuration of the chiral center in 10 has been established and this natural product characterized as 6‐[(S)‐lactoyl]‐7,8‐dihydropterin. The photochemical degradation of 10 yielded pterin‐6‐carboxylic acid (5).
Pharmacotherapy of Acute Lung Injury and Acute Respiratory Distress Syndrome (2008)

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are characterized by rapid-onset respiratory failure following a variety of direct and indirect insults to the parenchyma or vasculature of the lungs. Mortality from ALI/ARDS is substantial, and current therapy primarily emphasizes mechanical ventilation and judicial fluid management plus standard treatment of the initiating insult and any known underlying disease. Current pharmacotherapy for ALI/ARDS is not optimal, and there is a significant need for more effective medicinal chemical agents for use in these severe and lethal lung injury syndromes. To facilitate future chemical-based drug discovery research on new agent development, this paper reviews present pharmacotherapy for ALI/ARDS in the context of biological and biochemical drug activities. The complex lung injury pathophysiology of ALI/ARDS offers an array of possible targets for drug therapy, including inflammation, cell and tissue injury, vascular dysfunction, surfactant dysfunction, and oxidant injury. Added targets for pharmacotherapy outside the lungs may also be present, since multiorgan or systemic pathology is common in ALI/ARDS. The biological and physiological complexity of ALI/ARDS requires the consideration of combined-agent treatments in addition to single-agent therapies. A number of pharmacologic agents have been studied individually in ALI/ARDS, with limited or minimal success in improving survival. However, many of these agents have complementary biological/biochemical activities with the potential for synergy or additivity in combination therapy as discussed in this article.
Prospective multiaxial motion correction for fMRI (2000)

Corruption of the image time series due to interimage head motion limits the clinical utility of functional MRI. This paper presents a method for real-time prospective correction of rotation and translation in all six degrees of rigid body motion. By incorporating an orbital navigator (ONAV) echo for each of the sagittal, axial, and coronal planes into the fMRI pulse sequence, rotation and translation can be measured and the spatial orientation of the image acquisition sequence that follows can be corrected prospectively in as little as 160 msec. Testing of the method using a computerized motion phantom capable of performing complex multiaxial motion showed subdegree rotational and submillimeter translational accuracy over a range of +/-8 degrees and +/-8 mm of motion. In vivo images demonstrate correction of simultaneous through-plane and in-plane motion and improved detection of fMRI activation in the presence of head motion.
Novel modulated-master injection-locked 1.55-µm VCSELs (2006)

We report a novel optical injection-locking configuration using a directly-modulated master VCSEL to injection-lock a slave VCSEL. We demonstrate an interesting RF modulation response for the modulated master laser. An RF gain up to 30 dB is attained for frequencies greater than a certain critical frequency f(c), which is approximatelty 10 GHz here and increases with the injection power. In addition, an RF phase change of 2 pi is achieved above f(c) by varying the wavelength detuning. The slope of phase-frequency curve represents an equivalent slow or fast light attained through the slave laser. We incorporate an amplifier model to explain this novel modulated-master injection-locked VCSEL configuration. Simulations show good qualitative agreement with the experimental results.
Structural genes encoding the thermophilic alpha-amylases of Bacillus stearothermophilus and Bacillus licheniformis (1986)

The genes encoding the thermostable alpha-amylases of Bacillus stearothermophilus and B. licheniformis were cloned in Escherichia coli, and their DNA sequences were determined. The coding and deduced polypeptide sequences are 59 and 62% homologous to each other, respectively. The B. stearothermophilus protein differs most significantly from that of B. licheniformis in that it possesses a 32-residue COOH-terminal tail. Transformation of E. coli with vectors containing either gene resulted in the synthesis and secretion of active enzymes similar to those produced by the parental organisms. A plasmid was constructed in which the promoter and the NH2-terminal two-thirds of the B. stearothermophilus coding sequence was fused out of frame to the entire mature coding sequence of the B. licheniformis gene. Approximately 1 in 5,000 colonies transformed with this plasmid was found to secrete an active amylase. Hybridization analysis of plasmids isolated from these amylase-positive colonies indicated that the parental coding sequences had recombined by homologous recombination. DNA sequence analysis of selected hybrid genes revealed symmetrical, nonrandom distribution of loci at which the crossovers had resolved. Several purified hybrid alpha-amylases were characterized and found to differ with respect to thermostability and specific activity.
A pilot investigation of new superparamagnetic iron oxide (ferumoxytol) as a contrast agent for cardiovascular MRI (2003)

The new superparamagnetic iron oxide colloid ferumoxytol is a promising blood pool agent especially for cardiac, aorta and pulmonary imaging.
Sacral-neuromodulation CT-guided. (2005)

Thirty patients were subjected to PNE under CT guidance for a total of 38 centerings. Eight patients underwent the PNE procedure on both the S3 foramina. The sacral foramen was centred at the first attempt in 36 out of 38 cases. Two cases required several attempts to centre correctly the foramen. In 4 patients out of 30 a second electrode was implanted. In one patient who had a nonconsolidated sacral fracture, CT guidance enabled insertion of the electrode inside the only practicable foramen, a manoeuvre that would have been impossible with fluoroscopical guidance. Only once was the electrode placed in a wrong location but promptly repositioned after a CT control. During the whole trial period we had a positive response to the PNE test in 18 out of 30 patients (60%), a partial response in 4 out of 30 patients and a negative response in the remaining 8 patients. None of the patients who underwent the PNE test had infectious complications and the procedure was well tolerated by all. The procedure lasted about 45 minutes.
Leukemia inhibitory factor and interleukin‐6 are produced by diseased and regenerating skeletal muscle (1996)

The process of skeletal muscle regeneration following injury or disease involves locally produced growth factors which control cellular proliferation and differentiation. Leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) have previously been shown to promote the proliferation of myoblasts in vitro, and thus may be involved in muscle regeneration. In the present investigation, the in vivo expression of these two myogenic growth factors was examined in regenerating muscle after a crush injury of wild-type mice, and in diseased skeletal muscle and diaphragm of the mdx mouse. Using reverse transcription polymerase chain reaction we have demonstrated that while normal muscle rarely expresses mRNA for these two molecules, there is significant up-regulation following injury, coinciding with the active period of muscle regeneration. This suggests these molecules act as locally produced trauma factors. This observation is reinforced in mdx mouse muscle, which is undergoing a cycle of degeneration and regeneration, and expresses both LIF and IL-6. Using in situ hybridization, we have localized mRNA for LIF expression in the mdx diaphragm, suggesting that local production of these molecules by regenerating muscle itself, as well as by other cells in muscle, plays an important role in muscle regeneration. © 1996 John Wiley & Sons, Inc.
WST11, A Novel Water-soluble Bacteriochlorophyll Derivative; Cellular Uptake, Pharmacokinetics, Biodistribution and Vascular-targeted Photodynamic Activity Using Melanoma Tumors as a Model¶ (2005)

WST11 is a novel negatively charged water-soluble palladium-bacteriochlorophyll derivative that was developed for vascular-targeted photodynamic therapy (VTP) in our laboratory. The in vitro results suggest that WST11 cellular uptake, clearance and phototoxicity are mediated by serum albumin trafficking. In vivo, WST11 was found to clear rapidly from the circulation (t1/2=1.65 min) after intravenous bolus injection in the mouse, whereas a longer clearance time (t1/2=7.5 min) was noted in rats after 20 min of infusion. The biodistribution of WST11 in mouse tissues indicates hepatic clearance (t1/2=20 min), with minor (kidney, lung and spleen) or no intermediary accumulation in other tissues. As soon as 1 h after injection, WST11 had nearly cleared from the body of the mouse, except for a temporal accumulation in the lungs from which it cleared within 40 min. On the basis of these results, we set the VTP protocol for a short illumination period (5 min), delivered immediately after WST11 injection. On subjecting M2R melanoma xenografts to WST11-VTP, we achieved 100% tumor flattening at all doses and a 70% cure with 9 mg/kg and a light exposure dose of 100 mW/cm2. These results provide direct evidence that WST11 is an effective agent for VTP and provide guidelines for further development of new candidates.