gebhart/patrepeval huggingface dataset:
Design, Synthesis, and Structure–Activity Relationship Studies of Tryptanthrins As Antitubercular Agents (2013)

The natural product tryptanthrin (1a) represents a potential lead for new tuberculosis (TB) drugs since tryptanthrin and its synthetic analogues possess potent in vitro activity against Mycobacterium tuberculosis (Mtb). However, in spite of their in vitro activity, none of these agents have been shown to be efficacious in vivo against animal models of TB. Described herein are syntheses of new tryptanthrin analogues together with a systematic investigation of their in vitro antitubercular activity and ADME properties followed by pharmacokinetic characterization in rodents for the most promising compounds. Those with the best potency and oral bioavailability were progressed to evaluations of efficacy against acute murine TB. The work aimed to prove the concept that this compound class can limit growth of Mtb during infection as well as to establish the SAR for in vitro activity against Mtb and the range of in vitro ADME parameters for this class of natural products. Novel C-11-deoxy (5b) and A-ring-saturated (6) tryptanthrin analogues were discovered that maintained activity against Mtb and showed improved solubility compared to tryptanthrin as well as evidence of oral bioavailability in rodents. However, neither 5b nor 6 demonstrated efficacy against acute murine TB following administration at doses up to 400 mg/kg daily for 4 weeks. Although 5b and 6 failed to inhibit replication or kill Mtb in vivo, they illuminate a path to new structural variations of the tryptanthrin scaffold that may maximize the potential of this class of compounds against TB.
Pathology Review of Cases Presenting to a Multidisciplinary Pigmented Lesion Clinic (2002)

Pathology review of primary melanocytic lesions, within the context of a multidisciplinary pigmented lesion clinic, results in changes in diagnosis in a significant proportion of cases. These changes have important implications for clinical decision making, patient outcome, and research data collection.
Amino acid residues 56 to 69 of HLA-A2 specify an antigenic determinant shared by HLA-A2 and HLA-B17. (1986)

The mouse monoclonal antibody MA2.1 was previously used to define an epitope shared by native HLA-A2 and HLA-B17 molecules and amino acid sequence comparison of nine HLA-A,B,C molecules identified residues 62 to 65 as the region most likely to form this epitope. An unabsorbed rabbit antiserum raised against a peptide corresponding to residues 56 to 69 of HLA-A2 gives highly specific reactions with HLA-A2 and HLA-B17 heavy chains in Western blots. No interactions with native HLA-A2 and B17 molecules were detected in a variety of assays. Although the topographic relationship between the epitopes recognized by the rabbit antiserum and the monoclonal antibody could not be determined, the results show that residues 56 to 69 of HLA-A2 can form epitopes with specificity for HLA-A2 and HLA-B17.
Motion Mechanism Analysis of a Two-Degree-of-Freedom Spherical Motor (2010)

The working principle of a two-degree-of-freedom piezoelectric spherical motor using only one piezoelectric element was analyzed. The resonance frequencies of the motor's plate type piezoelectric vibrator were calculated by finite element method. The computer simulation was executed to analyze the motion trajectory of the four contact points between the stator and the sphere. Simulation results verified that the four contact points can form timing reasonable elliptical trajectories which re designed to drive the sphere to form two rotation degrees of freedom. The conclusion indicated the formation of two-dimensional movement mechanism of the spherical motor.
Isolation of a cDNA clone for the human muscle specific carbonic anhydrase, CAIII (1985)

The molecular cloning of cDNA for the human muscle specific carbonic anhydrase CAIII is described. The recombinant was isolated from a human muscle cDNA library prepared in the expression vector lambda gt11, and was characterized by hybridization selection and immunoprecipitation. A comparison of insert cDNA and mRNA sizes suggests that the cDNA is full length and includes extensive untranslated sequences. Preliminary sequence data have confirmed the authenticity of this clone and Southern blotting of human and rodent DNA indicates that it will be a useful probe in the analysis of somatic cell hybrids.
Pitavastatin prevents NMDA‐induced retinal ganglion cell death by suppressing leukocyte recruitment (2006)

Excitotoxicity is a major cause of retinal ganglion cell (RGC) death during ischemic diseases such as vessel occlusion and diabetic retinopathy. However, the underlying mechanisms are not well understood. Statins, inhibitors of the HMG-CoA reductase, have neuroprotective effects in addition to their original role in lowering cholesterol. We hypothesize that pitavastatin, a recently introduced potent statin, is protective against N-methyl-d-aspartic acid (NMDA)-induced RGC death. Pitavastatin, administered by gavage, abolished NMDA-induced loss of RGCs. To elucidate the mechanisms underlying the neuroprotective effect of pitavastatin, we investigated its impact on inflammation. NMDA increased the expression of interleukin-1beta and TNF-alpha, and endothelial adhesion molecules, including ICAM-1, and induced leukocyte accumulation in the retinal vessels. Pitavastatin significantly reduced NMDA-induced leukocyte accumulation and up-regulation of endothelial adhesion molecules, whereas cytokine expression was unaffected. Systemic blockade of ICAM-1 in wild-type mice or absence of CD18 in gene-deficient (CD18(-/-)) mice significantly suppressed NMDA-induced leukocyte accumulation and RGC death. These findings suggest a novel and causative role for inflammatory leukocyte recruitment in NMDA-induced excitotoxicity. Furthermore, we show the novel neuroprotective effect of statins against excitotoxicity-induced RGC death. Statins or other anti-inflammatory agents may thus have therapeutic benefits in excitotoxicity-associated neuronal diseases through blockade of leukocyte recruitment.
The design of Chebyshev band-pass filter (2010)

Using Chebyshev filter designs a 50~60 MHz band-pass filter,the testing result is also given.
Review of palivizumab in the prophylaxis of respiratory syncytial virus (RSV) in high-risk infants (2008)

In respiratory syncytial virus (RSV) disease the balance between the innate and adaptive immune responses determines the expression of the pathological phenotype favoring the development of acute bronchiolitis, and in certain children the development of recurrent wheezing. While humoral antibody plays a major role in protection against disease, T-cell immunity targeted to viral proteins appears to terminate viral infection. At the moment, treatment modalities for acute RSV infection do not effectively modify the course of the disease, and RSV vaccine development has shown conflicting results. To date, however, passive immunoprophylaxis with monoclonal antibodies is the only strategy that has demonstrated consistent efficacy in reducing RSV hospitalizations in high-risk children. The potential benefit of new strategies for prevention and treatment of RSV infections should be evaluated with respect to both the acute infection as well as the chronic respiratory manifestations induced by RSV.
Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci (2015)

The interplay between genetic and epigenetic variation is only partially understood. One form of epigenetic variation is methylation at CpG sites, which can be measured as methylation quantitative trait loci (meQTL). Here we report that in a panel of lymphocytes from 1,748 individuals, methylation levels at 1,919 CpG sites are correlated with at least one distal (trans) single-nucleotide polymorphism (SNP) (P<3.2 × 10(-13); FDR<5%). These trans-meQTLs include 1,657 SNP-CpG pairs from different chromosomes and 262 pairs from the same chromosome that are >1 Mb apart. Over 90% of these pairs are replicated (FDR<5%) in at least one of two independent data sets. Genomic loci harbouring trans-meQTLs are significantly enriched (P<0.001) for long non-coding transcripts (2.2-fold), known epigenetic regulators (2.3-fold), piwi-interacting RNA clusters (3.6-fold) and curated transcription factors (4.1-fold), including zinc-finger proteins (8.75-fold). Long-range epigenetic networks uncovered by this approach may be relevant to normal and disease states.
Mutual relevance feedback for multimodal query formulation in video retrieval (2005)

Video indexing and retrieval systems allow users to find relevant video segments for a given information need. A multimodal video index may include speech indices, a text-from-screen (OCR) index, semantic visual concepts, content-based image features, audio features and more. Formulating an efficient multimodal query for a given information need is much less intuitive and more challenging for the user than of composing a text query in document search. This paper describes a video retrieval system that uses mutual relevance feedback for multimodal query formulation. Through an iterative search and browse session, the user provides relevance feedback on system's output and the system provides the user a mutual feedback which leads to better query and better retrieval results. Official evaluation at the NIST TRECVID 2004 Search Task is provided for both Manual and Interactive search. It is shown that in the Manual task the queries result from the mutual feedback on the training data significantly improve the retrieval performances. A further improvement over the manual search is achieved in the interactive task by using both browsing and mutual feedback on the test set.
Price-Based Distributed Offloading for Mobile-Edge Computing With Computation Capacity Constraints (2017)

Mobile-edge computing is a promising technology to enable real-time information transmission and computing by offloading computation tasks from wireless devices to network edge. In this letter, we propose a price-based distributed method to manage the offloaded computation tasks from users. A Stackelberg game is formulated to model the interaction between the edge cloud and users, where the edge cloud sets prices to maximize its revenue subject to its finite computation capacity, and for given prices, each user locally makes offloading decision to minimize its own cost which is defined as latency plus payment. Depending on the edge cloud's knowledge of the network information, we develop the uniform and differentiated pricing algorithms, which can both be implemented in distributed manners. Simulation results validate the effectiveness of the proposed schemes.
Antibody-induced receptor loss. Different fates for asialoglycoproteins and the asialoglycoprotein receptor in HepG2 cells. (1986)

The human asialoglycoprotein receptor (ASGP-R) is a membrane glycoprotein which participates in receptor-mediated endocytosis and delivery of its ligands to lysosomes for degradation. In order to examine the pathways and mechanisms responsible for the turnover and degradation of the ASGP-R we have followed the fate of the ASGP-R in HepG2 cells during exposure to anti-receptor antibody as well as inhibitors of lysosomal processing and receptor recycling. Incubation of cells at 37 degrees C with anti-ASGP-R antibody results in the rapid (t 1/2 30 min) loss of mature 46,000-Da ASGP-R (control, t 1/2 20 h). This process requires whole IgG, since Fab fragments do not induce loss of receptor. Furthermore, this antibody-induced loss is specific, since incubation with antibody to the transferrin receptor does not alter cellular ASGP-R content. Of note, weak bases (e.g. primaquine) abrogate this antibody-induced loss of ASGP-R. Inhibitors of lysosomal proteases (EC64 and leupeptin) do not alter this antibody-mediated loss. Furthermore, this effect occurs at 18 degrees C, a temperature at which delivery of ligand to the lysosome is blocked. Thus, the present observations suggest a unique pathway for antibody-induced ASGP-R loss which is distinct from the pathway of lysosomal delivery of ligand.
Concise Review: Telomere Biology in Normal and Leukemic Hematopoietic Stem Cells (2007)

The measurement of telomere length can give an insight into the replicative history of the cells in question. Much of the observed telomere loss occurs at the stem and progenitor cell level, even though these populations express the enzyme telomerase. Telomerase-transfected hematopoietic stem cells (HSC), although able to maintain telomere length, are still limited in terms of ability to undergo sequential transplantation, and other factors require to be addressed to achieve optimal levels of stem cell expansion. Unchecked telomere loss by HSC, meanwhile, would appear to play a significant role in the pathogenesis of bone marrow failure, as observed in the condition dyskeratosis congenita. This heterogeneous inherited condition appears to exhibit telomerase dysfunction as a common final pathogenic mechanism. Although less well-established for acquired marrow failure syndromes, mutations in key telomerase components have been described. The identification of the leukemic stem cell (LSC), along with the desire to target this population with anti-leukemia therapy, demands that telomerase biology be fully understood in this cell compartment. Future studies using primary selected LSC-rich samples are required. A better understanding of telomerase regulation in this population may allow effective targeting of the telomerase enzyme complex using small molecule inhibitors or additional novel approaches. Disclosure of potential conflicts of interest is found at the end of this article.
Abstract P240: Mitochondrial Reactive Oxygen Species Regulate the Cardiac Na <sup>+</sup> Channel in Heart Failure (2011)

Background: Previously, we have shown that elevated intracellular NADH causes a decrease in cardiac Na + current ( I Na ) signaled by an increase in mitochondrial reactive oxygen species (ROS). The decrease in I Na can be ameliorated by NAD + or a mitochondrial specific anti-oxidant, mitoTEMPO. It is known that cardiomyopathy is associated with reduced I Na . Therefore, we tested whether the NADH-mitochondrial ROS pathway was involved in the reduction in I Na in cardiomyopathic mice. Methods: Nonischemic cardiomyopathy was induced in C57BL/6 mice 6 weeks after unilateral nephrectomy, deoxycorticosterone acetate (DOCA) pellet implantation, and salt water substitution. Sham operated mice were used as controls. Ventricular myocytes isolated from mice were utilized for whole-cell patch clamp recording, intracellular NADH/NAD + level measurements, and mitochondrial ROS monitoring with confocal microscopy. Results: Compared to the sham mice, the left ventricular volume was significantly enlarged (105.5 ± 4.4 µL vs. 91.6 ± 4.0 µL, P<0.05), and the ejection fraction was significantly reduced (39.2 ± 1.6% vs. 48.7 ± 1.6%, P<0.05) in DOCA mice. Intracellular NADH level was increased (2.78-fold; P<0.01), and I Na was decreased (62±8%; P<0.01) in myocytes of DOCA mice vs. sham. NAD + (500 μ M) and mitoTEMPO (10 μ M) recovered I Na (90±9% and 103±9% of sham, respectively, P>0.05). Mitochondrial ROS overproduction was observed with DOCA mice myocytes by MitoSOX Red (∼4.8-fold of sham; P<0.01). NAD + and mitoTEMPO decreased ROS in DOCA mice myocytes (∼20±6% of DOCA for both, P<0.01). Conclusions: NADH and mitochondrial ROS were elevated, and I Na was decreased in nonischemic cardiomyopathy. Maneuvers that reduced mitochondrial ROS restored I Na . Since reduced I Na and the subsequent slow conduction velocity are thought to contribute to arrhythmic risk in this condition, NAD + and mitochondrial anti-oxidants may have anti-arrhythmic activity in cardiomyopathy.
Advanced Microscopic Imaging by Spatial Control of Light and Multi-Image Reconstruction (2012)

According to the industrial requirement for optical imaging, particularly in microscopic imaging, resolution improvement is one of the most important issues. In digital microscopic imaging, resolution of an optical system is limited by both optical parameters such as light wavelength and the objective lens numerical aperture and by spatial sampling such as pixel size of charge-coupled device camera. Focused on exceeding these limits and improving the resolution of optical imaging, spatial control of light is useful. In this study, spatial control of illumination with sub-wavelength accuracy improves resolution in diffraction limited imaging; besides spatial control of imaging path with sub-pixel accuracy improves resolution determined by the spatial sampling. High-resolution image can be reconstructed by using multiple images acquired with spatial control of light. This paper includes theoretical discussions, numerical simulations, and experimental verifications of some techniques proposed in our related works.
Kinetics of the Reaction of Nitric Oxide with Oxygen in Aqueous Solutions (1994)

An understanding of the rate of reaction of nitric oxide (NO) with oxygen in aqueous solutions is needed in assessing the various actions of NO in the body. A novel approach was developed for studying the kinetics of this reaction, which permitted simultaneous and continuous measurements of the concentrations of NO and the principal product, nitrite (NO2-). Nitric oxide was measured using a chemiluminescence detector, with continuous sampling achieved by diffusion of NO through a membrane fitted into the base of a small, stirred reactor. The results with various initial NO and O2 concentrations confirmed that the rate of reaction is second-order in NO and first-order in O2. The rate of reaction of NO was described by the expression 4k1 [NO]2[O2], where k1 was (2.1 +/- 0.4) x 10(6) M-2 s-1 at 23 degrees C and (2.4 +/- 0.3) x 10(6) M-2 s-1 at 37 degrees C. The value of k1 was the same at pH 4.9 and 7.4. The rate of formation of NO2- equaled the rate of reaction of NO (within experimental uncertainty of a few percent), and there was no detectable formation of nitrate (NO3-). This confirmed that NO and NO2- were the only NOx species present in significant amounts and supported the validity of pseudo-steady-state assumptions for NO2 and N2O3, which are intermediates in the conversion of NO to NO2-.(ABSTRACT TRUNCATED AT 250 WORDS)
Deposition Of Diamond-like Carbon Films With Intense Ion Beams (1994)

Thin film deposition by ion beam evaporation is being studied at Los Alamos with an intense light ion beam generated in a focused applied-Br magnetically-insulated ion diode. H, C, and O ions are extracted from the Lucite flashover anode. The diode is powered directly by a Marx generator. For these first experiments, typical beam parameters are: 0.4 MV, 35 kA, 0.5-{mu}s pulsewidth. The beam is being used to produce and evaluate carbon films for use in field-emissive flat-panel displays. The films have been prepared by ablation of graphite targets with a 4 kJ ion beam focused to 30 {+-} 15 J/cm{sup 2}. Approximately 10 mg of material is ablated per pulse roughly consistent with a 1-D deposition and heat transport model. Films are deposited onto Si (100) and glass substrates. The films are fairly smooth with deposition rates as high as 50 nm/pulse. Four-point measurements give electrical resistivities of 10 to 100 {Omega}-cm, 10{sup 4} to 10{sup 5} times higher than graphite. Current-voltage measurements show good electron emission with Fowler-Nordheim scaling. X-ray diffraction shows no crystalline structure, while scanning electron microscopy reveals 100-nm feature sizes with a few 1-{mu}m particles. Raman spectroscopy and electron energy loss spectroscopy indicate that themore » films contain significant sp{sup 3} bonding. Glassy carbon is also produced under some conditions. Time-resolved photographs of ablation plume expansion will be presented. Also, time-resolved measurements of plume energy input to the substrates, using thin-film platinum resistive elements, have been made and will be presented.« less
Blood velocity measurements using laser speckle imaging (2005)

Blood velocity measurements in the skin of pigs are reported. Measurements were obtained using laser speckle contrast analysis with a multiple scattering correction. Laser speckle contrast analysis is a rapid technique for obtaining a velocity mapping of perfused tissue. Measurements of blood velocity in pig skin were obtained using a laser and a monochrome digital camera. Blood velocities were measured in tissue prior to and after elevation of flaps. The effect of Iloprost and nitroglycerine on local blood velocity was also examined in nonexcised tissue.
MAL hypermethylation is a tissue-specific event that correlates with MAL mRNA expression in esophageal carcinoma (2013)

MAL promoter hypermethylation was examined in 260 human esophageal specimens using real-time quantitative methylation-specific PCR (qMSP). MAL hypermethylation showed highly discriminative ROC curve profiles which clearly distinguished esophageal adenocarcinomas (EAC) from both esophageal squamous cell carcinomas (ESCC) and normal esophagus (NE). Both MAL methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett's esophagus (BE), dysplastic BE, and EAC than in ESCC or in NE. Among matched NE and EAC samples, MAL NMVs in EAC were significantly higher than in corresponding NE. There was a significant correlation between MAL hypermethylation and BE segment length. Treatment with 5-aza-2'-deoxycytidine reversed MAL methylation and reactivated MAL mRNA expression in OE33 EAC cells. MAL mRNA levels in EACs with unmethylated MAL were significantly higher than in EACs with methylated MAL. MAL hypermethylation is a common, tissue-specific event in human EAC and correlates with clinical neoplastic progression risk factors.
Light scattering from a sphere arbitrarily located in a Gaussian beam, using a Bromwich formulation (1988)

We present a theoretical description of the scattering of a Gaussian beam by a spherical, homogeneous, and isotropic particle. This theory handles particles with arbitrary size and nature having any location relative to the Gaussian beam. The formulation is based on the Bromwich method and closely follows Kerker’s formulation for plane-wave scattering. It provides expressions for the scattered intensities, the phase angle, the cross sections, and the radiation pressure.
ARCHETYPES IN MILTON'S EARTHLY PARADISE (1980)

Research Article| January 01 1980 ARCHETYPES IN MILTON'S EARTHLY PARADISE Joseph E. Duncan Joseph E. Duncan Search for other works by this author on: This Site Google Milton Studies (1980) 14: 25–58. https://doi.org/10.2307/44645347 Cite Icon Cite Share Icon Share Twitter Permissions Search Site Citation Joseph E. Duncan; ARCHETYPES IN MILTON'S EARTHLY PARADISE. Milton Studies 1 January 1980; 14 25–58. doi: https://doi.org/10.2307/44645347 Download citation file: Zotero Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All Scholarly Publishing CollectivePenn State University PressMilton Studies Search Advanced Search The text of this article is only available as a PDF. Copyright © 1980 by The Pennsylvania State University. All rights reserved.1980The Pennsylvania State University Article PDF first page preview Close Modal You do not currently have access to this content.
Advanced microprocessor test strategy and methodology (1997)

This paper describes the overall test methodology used in implementing the S/390® microprocessor and the associated L2 cache array in shared multiprocessor designs, the design-for-test implementations, and the test software used in creating the test patterns and in measuring test effectiveness. Microprocessor advances in architectural complexity, circuit density, cycle time, and technology-related issues, coupled with IBM's high requirements for quality, reliability, and diagnosability, have made it necessary to develop testing methods and attain quality levels that far exceed what others have approached.