gebhart/patrepeval huggingface dataset:
Interleukin-6 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension (2010)

Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biologic activities in immune regulation, hematopoiesis, inflammation, and oncogenesis. Recent accumulating evidence indicates a pathologic role for IL-6 in promoting proliferation of both smooth muscle and endothelial cells in the pulmonary arterioles, resulting in development of pulmonary arterial hypertension (PAH). Here, we describe a patient with mixed connective tissue disease and severe, refractory PAH. Her functional activity and hemodynamic parameters dramatically responded to tocilizumab, a humanized monoclonal antibody to human IL-6 receptor, which was aimed at treating multicentric Castleman's disease. It appears that IL-6 blockade may hold promise as an adjunct drug in treatment of PAH in idiopathic form as well as in association with connective tissue disease.
Unique Biologic Properties of Recombinant AAV1 Transduction in Polarized Human Airway Epithelia (2006)

The choice of adeno-associated virus serotypes for clinical applications is influenced by the animal model and model system used to evaluate various serotypes. In the present study, we sought to compare the biologic properties of rAAV2/1, rAAV2/2, and rAAV2/5 transduction in polarized human airway epithelia using viruses purified by a newly developed common column chromatography method. Results demonstrated that apical transduction of human airway epithelia with rAAV2/1 was 100-fold more efficient than rAAV2/2 and rAAV2/5. This transduction profile in human airway epithelia (rAAV2/1 >> rAAV2/2 = rAAV2/5) was significantly different from that seen following nasal administration of these vectors to mouse lung (rAAV2/5 > rAAV2/1 >> rAAV2/2), emphasizing differences in transduction of these serotypes between these two species. In stark contrast to rAAV2/2 and rAAV2/5, rAAV2/1 transduced both the apical and basolateral membrane of human airway epithelia with similar efficiency. However, the overall level of transduction across serotypes did not correlate with vector internalization. We hypothesized that differences in post-entry processing of these serotypes might influence the efficiency of apical transduction. To this end, we tested the effectiveness of proteasome inhibitors to augment nuclear translocation and gene expression from the three serotypes. Augmentation of rAAV2/1 apical transduction of human polarized airway epithelia was 10-fold lower than that for rAAV2/2 and rAAV2/5. Cellular fractionation studies demonstrated that proteasome inhibitors more significantly enhanced rAAV2/2 and rAAV2/5 translocation to the nucleus than rAAV2/1. These results demonstrate that AAV1 transduction biology in human airway epithelia differs from that of AAV2 and AAV5 by virtue of altered ubiquitin/proteasome sensitivities that influence nuclear translocation.
Molecular Analysis of viviparous-1: An Abscisic Acid-Insensitive Mutant of Maize. (1989)

The viviparous-1 (vp1) gene in maize controls multiple developmental responses associated with the maturation phase of seed formation. Most notably, mutant embryos have reduced sensitivity to the hormone abscisic acid, resulting in precocious germination, and blocked anthocyanin synthesis in aleurone and embryo tissues. The Vp1 locus was cloned by transposon tagging, using the Robertson's Mutator element present in the vp1-mum1 mutant allele. Detection of DNA rearrangements in several spontaneous and transposable element-induced mutant vp1 alleles, including a partial deletion of the locus, confirmed the identity of the clone. The Vp1 gene encodes a 2500-nucleotide mRNA that is expressed specifically in embryo and endosperm tissues of the developing seed. This transcript is absent in seed tissues of vp1 mutant stocks. Expression of C1, a regulatory gene for the anthocyanin pathway, is selectively blocked at the mRNA level in vp1 mutant seed tissues, indicating the Vp1 may control the anthocyanin pathway by regulating C1. We suggest that the Vp1 gene product functions to potentiate multiple signal transduction pathways in specific seed tissues.
Clinical Study of Colorectal Cancer Found in Proctologic Hospital (2004)

1995～2001年に所沢肛門病院で経験した大腸癌症例の検討を行った.7年間に38,212例の大腸内視鏡検査が施行され,762例の大腸癌(進行癌498例,早期癌264例)が発見された.これは検査総数の約2.0%に達していた.進行癌では,男性の直腸癌が有意に多かった(p<0.01).平均年齢は進行癌(62.4歳)が早期癌(59.8歳)に比べ2.6歳高かった(p<0.002).当院の第一紹介病院である防衛医大第1外科で1995～99年に施行された大腸癌初回手術例743例を,当院から紹介した257例とその他の施設から紹介された476例に分け,両群の特徴を比較検討した.当院から紹介した症例では,主訴が出血である症例の割合が高く,腫瘍占拠部位では有意に直腸癌が多かった(p<0.0001).平均年齢は当院で有意に若年であるものの(p=0.02),臨床病期は有意に高く(p=0.01),痔疾患のある患者は出血しても痔からの出血と考え放置している可能性が示唆され注意が必要と考えられた.
Cannabinoids Biology: The Search for New Therapeutic Targets (2006)

Cannabinoids, in the form of marijuana plant extracts, have been used for thousands of years for a wide variety of medical conditions, ranging from general malaise and mood disorders to more specific ailments, such as pain, nausea, and muscle spasms. The discovery of tetrahydrocannabinol, the active principal in marijuana, and the identification and cloning of two cannabinoid receptors (i.e., CB1 and CB2) has subsequently led to biomedical appreciation for a family of endocannabinoid lipid transmitters. The biosynthesis and catabolism of the endocannabinoids and growing knowledge of their broad physiological roles are providing insight into potentially novel therapeutic targets. Compounds directed at one or more of these targets may allow for cannabinoid-based therapeutics with limited side effects and abuse liability.
The Effects of Receptor Density and cell Shape on Epidermal Growth Factor Binding (1992)

In this paper we describe the effects of receptor density and cell shape on the binding of epidermal growth factor (EGF) to its receptor. Association kinetics of EGF binding to cells with a high receptor density was done using A431 cells. The association rate of EGF binding was apparently independent of the EGF concentration, most likely due to diffusion limited EGF binding as result of high receptor density. The effect of receptor density on EGF association rate was examined by reducing the number of functional EGF receptors on A431 cells. Preincubation of the cells with a monoclonal antibody directed against the EGF receptor and isolation of the cytoskeletons of A431 cells which both leaves only EGF binding to high affinity receptors revealed an EGF concentration dependent association rate. These results were confirmed in HeLa cells with 40 times less receptor numbers than A431 cells demonstrating the effect of receptor density on EGF binding. The influence of shape of the cell on EGF binding was examined by comparing the EGF association to monolayer cells with that of suspension cells. EGF association to suspended A431 cells was EGF concentration dependent. In conclusion we have shown that binding of EGF to A431 cells is dependent not only on the intrinsic rate constants but in addition on both receptor numbers per cell and the shape of cells. These results are in agreement with the hypothesis that EGF binding can be restricted by limited diffusion.
Scatter rejection methods in megavoltage imaging with an amorphous-silicon flat-panel array (2000)

X-ray scattering in megavoltage portal imaging becomes more of an issue when quantitative results are needed. This is the case in megavoltage computed tomography (MVCT) and transit dosimetry, where the absorbed dose delivered to the patient is to be reconstructed. Although sensor arrays based on amorphous silicon (a-Si) photodiodes show promising results for this application, the scatter problem has so far not been examined. In this paper portal scatter distributions are calculated by means of Monte-Carlo (MC) simulations for typical clinical parameters. The aim of the MC simulations is to design a detector which is able to reject photons and electrons scattered by the phantom. As expected the analysis of the spectrum shows that multiply scattered photons can be differentiated from singly scattered photons by means of their energy. The MC results indicate that by using a detector with a high-Z conversion plate combined with a moderately thick phosphor screen a significant fraction of low energy scattered photons and most electrons can be rejected. However, to reduce the scatter signal further a software correction method based on a dedicated scatter model is still necessary.
Patterned Metallization of Porous Silicon from Electroless Solution for Direct Electrical Contact (2000)

The excitation of the triplet exciton leading to the "long‐lived" photoluminescence characteristic of a porous silicon (PS) surface has been used to selectively enhance the highly efficient, controlled, and patterned plating of copper and silver metal from electroless solutions. The basis of this method lies in the use of the "long‐lived" excited state to promote an enhanced reduction at the PS surface. Excited fluorophors, created at the PS surface, using a Xe arc lamp or HeNe laser, exhibit an interaction and reduction capability absent without optical pumping. The thickness of the metal deposit is proportional to the time and intensity of exposure and the contact resistance can be made less than 500 Ω. © 2000 The Electrochemical Society. All rights reserved.
Cloning, sequence determination, and expression in transfected cells of the coding sequence for the tox 176 attenuated diphtheria toxin A chain. (1987)

DNA including the coding sequence for the A chain of the mutant diphtheria toxin tox 176 was cloned. The cloned mature A-chain coding sequence showed a G-to-A transition at nucleotide 383 as the only difference from the wild-type sequence. This resulted in replacement of the glycine at position 128 by aspartic acid in the predicted amino acid sequence. A eucaryotic cell expression plasmid, pTH1-176, was constructed in which the tox 176 A-chain coding sequence was attached to a truncated metallothionein promoter. The toxicity of this construct, compared with that of the corresponding wild-type diphtheria toxin A-chain plasmid, pTH1, was assessed after transfection into the human 293 cell line by an indirect transient expression assay (I. H. Maxwell, F. Maxwell, and L. M. Glode, Cancer Res. 46:4660-4664, 1986). For the same effect, 15- to 30-fold more pTH1-176 than pTH1 was required, a result consistent with previous in vitro estimates of the diminished activity of the tox 176 A chain. Controlled expression of the cloned tox 176 A-chain coding sequence may provide a means of eliminating specific cell populations in an organism, for which purpose the wild-type diphtheria toxin A chain might prove too toxic.
Plasma Gelsolin is Decreased and Correlates with Rate of Decline in Alzheimer's Disease (2010)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder where definite diagnosis can only be made postmortem, and for which the most promising peripheral markers of disease state and severity have been found in the cerebrospinal fluid. However, recent results suggest that differences in the levels of certain plasma proteins do exist between AD patients and non-demented controls (NDC). Herein, we undertook an untargeted discovery study using isobaric mass tagging to compare the plasma protein levels between slow cognitive declining AD patients, rapid cognitive declining AD patients (RCD) and NDC subjects. Subsequent relative quantification and statistical analysis identified a list of candidate proteins able to distinguish RCD from NDC groups based on multivariate analysis. Selected proteins were then validated by western blot analysis in an independent sample set of 60 AD and 35 NDC subjects. In this cohort, AD patients displayed significantly lower plasma gelsolin levels compared to NDC subjects. Additionally, gelsolin levels correlated with disease progression rate estimated by Mini-Mental Status Examination decline per year. In order to further investigate gelsolin expression, three different brain regions from an additional cohort of 23 subjects and their respective plasma samples were analysed. No significant change in brain gelsolin levels could be established between AD and control subjects. Interestingly, this study reveals yet another condition where plasma gelsolin levels are decreased and our findings, together with the reported interaction of gelsolin and amyloid-beta, makes plasma gelsolin an attractive candidate for further studies targeted at better understanding disease progression in AD.
Reverse electrowetting as a new approach to high-power energy harvesting (2011)

Over the last decade electrical batteries have emerged as a critical bottleneck for portable electronics development. High-power mechanical energy harvesting can potentially provide a valuable alternative to the use of batteries, but, until now, a suitable mechanical-to-electrical energy conversion technology did not exist. Here we describe a novel mechanical-to-electrical energy conversion method based on the reverse electrowetting phenomenon. Electrical energy generation is achieved through the interaction of arrays of moving microscopic liquid droplets with novel nanometer-thick multilayer dielectric films. Advantages of this process include the production of high power densities, up to 10(3) W m(-2); the ability to directly utilize a very broad range of mechanical forces and displacements; and the ability to directly output a broad range of currents and voltages, from several volts to tens of volts. These advantages make this method uniquely suited for high-power energy harvesting from a wide variety of environmental mechanical energy sources.
Synthesis of optically active α-amino acids (1989)

Asymmetric derivatization of glycine. Homologation of the beta-carbon. Electrophilic amination of enolates. Nucleophilic amination of alpha-substituted acids. Asymmetric Strecker syntheses. Asymmetric hydrogenation of dehydroamino acids. Enzymatic syntheses of alpha-amino acids. Miscellaneous methods. Total synthesis of complex amino acids. Author index. Subject index.
Greenhouse Gas Carbon Dioxide Mitigation (1998)

Any mention of the "greenhouse effect" tends to ignite controversy. While the rising atmospheric concentrations of greenhouse gases-especially carbon dioxide- are certainly among the most pressing issues today, theoretical and perceived consequences have been subject to conjecture and misinformation.That raging debate has obscured an important
Synthesis of Ge nanocrystals embedded in a Si host matrix (1994)

The synthesis of a composite material consisting of Ge nanoclusters (≥2 nm in diameter) embedded in a Si host matrix is reported. The Ge nanoparticles are produced by pulsed laser ablation and are codeposited in a Si film simultaneously grown by chemical beam epitaxy using disilane. Scanning transmission electron microscopy, combined with energy-dispersive x-ray measurements, show that discrete Ge particles (≥2 nm diameter) are deposited within a polycrystalline Si host matrix. High-resolution transmission electron microscopy reveals that the particles are crystalline with a lattice spacing corresponding to that of Ge. The enhancement of Si deposition rates from silanes in the presence of Ge, previously demonstrated in chemical vapor deposition of Si1−xGex alloys, is shown to facilitate the growth of a Si layer around the Ge nanocrystals. The overall composition of the Ge cluster/Si host composite material is determined by Rutherford backscattering measurements.
Increased resolution and penetration from a towed dual-sensor streamer (2007)

David Carlson, Andrew Long, Walter Söllner, Hocine Tabti, Rune Tenghamn, and Nils Lunde discuss the theory behind a towed dual-sensor developed by Petroleum Geo-Services to operate at deeper depths and deliver de-ghosted data.
Contrasting behaviour of related palladium complex-derived resolving agents. 8-H conformational locking of the 1-naphthyl side-chain (1995)

The X-ray crystal structures of palladium complexes 4 and 6 derived from (R)-N,N-dimethyl-1-(1-naphthyl)ethylamine and (S)-N,N-dimethyl-1-phenylethylamine, respectively, are reported; in the latter case two diastereoisomers differing both in the ligand configuration and the conformation of the C,N-chelate ring cocrystallise as a quasiracemate.
Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease: implications for neuronal damage (2011)

The purpose of our study was to better understand the relationship between mitochondrial structural proteins, particularly dynamin-related protein 1 (Drp1) and amyloid beta (Aβ) in the progression of Alzheimer's disease (AD). Using qRT-PCR and immunoblotting analyses, we measured mRNA and protein levels of mitochondrial structural genes in the frontal cortex of patients with early, definite and severe AD and in control subjects. We also characterized monomeric and oligomeric forms of Aβ in these patients. Using immunoprecipitation/immunoblotting analysis, we investigated the interaction between Aβ and Drp1. Using immunofluorescence analysis, we determined the localization of Drp1 and intraneuronal and oligomeric Aβ in the AD brains and primary hippocampal neurons from Aβ precursor protein (AβPP) transgenic mice. We found increased expression of the mitochondrial fission genes Drp1 and Fis1 (fission 1) and decreased expression of the mitochondrial fusion genes Mfn1 (mitofusin 1), Mfn2 (mitofusin 2), Opa1 (optic atrophy 1) and Tomm40. The matrix gene CypD was up-regulated in AD patients. Results from our qRT-PCR and immunoblotting analyses suggest that abnormal mitochondrial dynamics increase as AD progresses. Immunofluorescence analysis of the Drp1 antibody and the Aβ antibodies 6E10 and A11 revealed the colocalization of Drp1 and Aβ. Drp1 immunoprecipitation/immunoblotting analysis of Aβ antibodies 6E10 and A11 revealed that Drp1 interacts with Aβ monomers and oligomers in AD patients, and these abnormal interactions are increased with disease progression. Primary neurons that were found with accumulated oligomeric Aβ had lost branches and were degenerated, indicating that oligomeric Aβ may cause neuronal degeneration. These findings suggest that in patients with AD, increased production of Aβ and the interaction of Aβ with Drp1 are crucial factors in mitochondrial fragmentation, abnormal mitochondrial dynamics and synaptic damage. Inhibiting, these abnormal interactions may be a therapeutic strategy to reduce mitochondrial fragmentation, neuronal and synaptic damage and cognitive decline in patients with AD.
Intradiscal transplantation of synovial mesenchymal stem cells prevents intervertebral disc degeneration through suppression of matrix metalloproteinase-related genes in nucleus pulposus cells in rabbits (2010)

Synovial MSCs injected into the nucleus pulposus space promoted synthesis of the remaining nucleus pulposus cells to type II collagen and inhibition of expressions of degradative enzymes and inflammatory cytokines, resulting in maintaining the structure of the intervertebral disc being maintained.
Cannabis Use in Patients with Fibromyalgia: Effect on Symptoms Relief and Health-Related Quality of Life (2011)

The use of cannabis was associated with beneficial effects on some FM symptoms. Further studies on the usefulness of cannabinoids in FM patients as well as cannabinoid system involvement in the pathophysiology of this condition are warranted.
Role of endotoxin in acute inflammation induced by gram-negative bacteria: specific inhibition of lipopolysaccharide-mediated responses with an amino-terminal fragment of bactericidal/permeability-increasing protein (1995)

A recombinant 23-kDa amino-terminal fragment of human bactericidal/permeability-increasing protein (rBPI23), a potent lipopolysaccharide (LPS)-binding/neutralizing protein, was used as a probe to assess the role of endotoxin in the acute inflammatory responses elicited by gram-negative bacteria in rat subcutaneous air pouches. In initial experiments, rBPI23 prevented the Escherichia coli O111:B4 LPS-induced accumulation of polymorphonuclear leukocytes (PMN), tumor necrosis factor alpha (TNF-alpha), and nitrite (a stable end product of nitric oxide formation) in exudate fluids. Significant inhibition of TNF-alpha production was still evident when rBPI23 treatment was delayed for 30 min after LPS instillation. In subsequent experiments, rBPI23 also prevented the nitrite and early (2-h) TNF-alpha accumulation induced by three different strains of formaldehyde-killed gram-negative bacteria (E. coli O7:K1, E. coli O111:B4, and Pseudomonas aeruginosa 12.4.4) but did not inhibit the PMN or late (6-h) TNF-alpha accumulation induced by these bacteria. As with LPS challenge, a significant inhibition of early TNF-alpha production was still evident when rBPI23 treatment was delayed for 30 to 60 min after instillation of killed bacteria. The results indicate that in this experimental model the NO and early TNF-alpha responses to gram-negative bacterial challenge are mediated predominantly by endotoxin, whereas the PMN and late TNF-alpha responses may be mediated by other bacterial components. Moreover, the results indicate that rBPI23 can inhibit the bacterially induced production of certain potentially harmful mediators (TNF-alpha and NO) without entirely blocking the host defense, i.e., PMN response, against the bacteria.
Tunable coupling between three qubits as a building block for a superconducting quantum computer (2011)

Large-scale quantum computers will consist of many interacting qubits. In this paper we expand the two flux qubit coupling scheme first devised by P. Plourde et al. [Phys. Rev. B 70, 140501 (2004)] and realized by T. Hime et al. [Science 314, 1427 (2006)] to a three-qubit, two-coupler scenario. We study L-shaped and line-shaped coupler geometries, and show how the interaction strength between qubits changes in terms of the couplers' dimensions. We explore two cases: the ``on-state'' where the interaction energy between two nearest-neighbor qubits is high, and the ``off-state'' where it is turned off. In both situations we study the undesirable crosstalk with the third qubit. Finally, we use the grape algorithm to find efficient pulse sequences for two-qubit gates subject to our calculated physical constraints on the coupling strength.
<title>1.3-in. active matrix liquid crystal spatial light modulator with 508-dpi resolution</title> (1996)

Optical signal processing systems frequently use Fourier transform techniques for correlation, filtering, etc. In practical applications the complex-valued filters placed in the frequency domain plane are often realized by a liquid crystal spatial light modulator (LCSLM). The requirements for such LCSLMs are very demanding, as they should offer a high resolution, high uniformity, low fluctuation in time and an increased number of grayscales or phase steps. We designed and manufactured an active matrix LCSLM (AMLCSLM) and the appropriate driving system meeting these requirements. The AMLCSLM consists of 480 by 480 pixels, each containing an amorphous silicon thin film transistor (aSi-TFT). Although the pixel size is only 50 by 50 micrometer squared, corresponding to a resolution of 508 dpi, an optical aperture of more than 40 percent is achieved. By the use of a transparent storage capacitor the pixel capacitance was greatly increased, resulting in a reduction of the fluctuation in time. The driving circuitry is capable of driving up to 256 grayscales at a frame rate of 100 Hz in dual scan driving mode. For the row scanning the commonly used rectangular impulse shape was substituted by a shortened trapezoidal impulse. As a result a very good uniformity over the area with an overall phase change error of less than 6 percent is obtained.