gebhart/patrepeval huggingface dataset:
Local delivery of photosensitizing drugs in arteries: a novel approach to photodynamic therapy for the prevention of intimal hyperplasia (1995)

The long-term benefit of coronary or peripheral vascular interventions is limited by restenosis, due to intimal hyperplasia (IH). Photodynamic therapy (PDT) with systematic delivery of the photosensitizing drug, performed either at the time or shortly after vascular injury, has been demonstrated to effectively inhibit the development of experimental IH. However, in order to deliver large quantities of the photosensitizer, but avoid systematic photosensitization, local delivery of the drug appears to be an advantageous option. An experimental model was therefore developed to deliver benzporphyrin derivative (BPD-MA) directly into isolated segments of balloon-injured rat common carotid arteries, and to study the uptake in serum and arterial tissue by means of spectrofluorometry. Furthermore, early effects of local versus systematic drug delivery and subsequent PDT treatment, were investigated with light microscopy and morphometric analysis. Local delivery of BPD lead to effective drug concentrations in the artery with complete depletion of endothelial and smooth muscle cells, already 24 h after PDT. The media appeared compacted and acellular. No thrombosis or occlusion were observed. Serum concentrations of BPD, after local delivery, were at the detection threshold, whereas systematic application resulted in significantly higher serum but equivalent tissue drug concentrations. In conclusion, these data demonstrate that local delivery of BPD results in tissue concentrations, appropriate to perform an efficient vascular PDT treatment of the arterial wall.
Characterization of structurally distinct, isoform-selective phosphoinositide 3′-kinase inhibitors in combination with radiation in the treatment of glioblastoma (2008)

The phosphoinositide 3'-kinase (PI3K)-mediated signaling pathway plays a key role in fundamental cellular functions important in normal cellular homeostasis and malignant transformation. Deregulated signaling through this pathway contributes to development of gliomas and their resistance to radiation and chemotherapy. Targeting the PI3K signaling pathway has thus emerged as a promising approach to successful treatment of gliomas. We assessed the radiosensitizing potential of four small-molecule inhibitors that differ in their activities against specific isoforms of the PI3K 110-kDa catalytic subunit (p110). p110alpha inhibitors blocked phosphorylation of both protein kinase B/Akt and S6 in all cell lines examined, effectively decreased cellular proliferation, and produced additive cytotoxic effects in combination with radiation therapy. The p110beta inhibitor exhibited limited biochemical effects and failed to decrease cellular proliferation or viability as either a single agent or in combination with radiation or rapamycin. In vivo studies examining the effects of the p110alpha inhibitor in combination with radiation indicated a significant reduction in tumor growth rate induced by the combined treatment compared with each treatment modality alone. This translated into a trend toward prolonged time-to-failure for mice in the combination treatment group. In conclusion, PI3K inhibitors are promising agents in the treatment of glioblastomas, especially when used in combination with ionizing radiation.
The effectiveness of GIOSS for the text database discovery problem (1994)

The popularity of on-line document databases has led to a new problem: finding which text databases (out of many candidate choices) are the most relevant to a user. Identifying the relevant databases for a given query is the text database discovery problem. The first part of this paper presents a practical solution based on estimating the result size of a query and a database. The method is termed GlOSS—Glossary of Servers Server. The second part of this paper evaluates the effectiveness of GlOSS based on a trace of real user queries. In addition, we analyze the storage cost of our approach.
Induction of speech arrest and counting errors with rapid‐rate transcranial magnetic stimulation (1991)

Six adult epileptic patients underwent rapid-rate transcranial magnetic stimulation (rTMS) at stimulation rates of up to 25 Hz with an 11-cm water-cooled round coil held flat on the scalp, centered over 15 different positions on each side of the scalp. The trains of stimuli were for 10 seconds while the patients counted aloud. rTMS centered over D5 or D7 induced reproducible speech arrest in all patients and counting errors in three when applied at lower intensities. There were no such speech disturbances by rTMS centered over the different positions on the right side. Intracarotid amobarbital test (IAT) demonstrated left hemispheric language dominance in all patients. Lateralization of speech arrest induced by rTMS correlated with the IAT results and may be helpful for noninvasive determination of hemispheric language dominance.
Interleukin-12 from Intrinsic Cells Is an Effector of Renal Injury in Crescentic Glomerulonephritis (2001)

Interleukin-12 (IL-12) directs the cognate nephritogenic T helper type 1 responses that initiate renal injury in murine crescentic glomerulonephritis (GN). The recent demonstration of IL-12 production by intrinsic renal cells, including mesangial and proximal tubular cells, raises the possibility that IL-12 from nonimmune cells may contribute to inflammatory renal injury. To address this possibility, the development of sheep anti-mouse glomerular basement membrane globulin-induced crescentic GN was studied in C57BL/6 wild-type (WT), IL-12-deficient (IL-12 -/-), and IL-12 "chimeric" mice. IL-12 chimeric mice were produced by transplantation of WT bone marrow into IL-12 -/- mice to restore IL-12 production by immune cells, while leaving them deficient in renal IL-12 production. WT and "sham" chimeric mice (normal bone marrow transplanted into WT mice) developed crescentic GN with glomerular T-cell and macrophage recruitment and impaired renal function (elevated proteinuria and serum creatinine) 10 d after initiation of GN. IL-12 -/- mice showed significant protection from GN. Chimeric IL-12 mice showed significant attenuation of crescent formation, glomerular T-cell and macrophage accumulation, and renal impairment, compared with WT and sham chimeric mice, but were not protected to the same extent as IL-12 -/- mice. IL-12 chimeric mice showed no attenuation of their systemic cognate immune response to the nephritogenic antigen (sheep globulin), indicated by antigen-specific circulating antibody and cutaneous delayed-type hypersensitivity. These studies indicate that IL-12 produced by non-bone marrow derived intrinsic renal cells contributes to immune renal injury. They provide the first in vivo demonstration of a proinflammatory role for an intrinsic renal cell-derived cytokine in renal inflammation.
Nitric Oxide Suppresses Apoptosis via Interrupting Caspase Activation and Mitochondrial Dysfunction in Cultured Hepatocytes (1999)

Nitric oxide (NO) is a potent inhibitor of apoptosis in many cell types, including hepatocytes. We and others have described NO-dependent decreases in caspase activity in cells undergoing apoptosis. However, previous work has not determined whether NO disrupts the proteolytic processing and thus the activation of pro-caspases. Here we report that NO suppresses proteolytic processing and activation of multiple pro-caspases in intact cells, including caspase-3 and caspase-8. We found that both exogenous NO as well as endogenously produced NO via adenoviral inducible NO synthase gene transfer protected hepatocytes from tumor necrosid factor (TNF) alpha plus actinomycin D (TNFalpha/ActD)-induced apoptosis. Affinity labeling with biotin-VAD-fmk of all active caspase species in TNFalpha-mediated apoptosis identified four newly labeled spots (activated caspases) present exclusively in TNFalpha/ActD-treated cells. Both NO and the caspase inhibitor, Ac-DEVD-CHO, prevented the appearance of the four newly labeled spots or active caspases. Immunoanalysis of affinity labeled caspases demonstrated that caspase-3 was the major effector caspase. Western blot analysis also identified the activation of caspase-8 in the TNFalpha/ActD-treated cells, and the activation was suppressed by NO. Furthermore, NO inhibited several other events associated with caspase activation in cells, including release of cytochrome c from mitochondria, decrease in mitochondrial transmembrane potential, and cleavage of poly(ADP-ribose) polymerase in TNFalpha/ActD-treated cells. These findings indicate the involvement of multiple caspases in TNFalpha-mediated apoptosis in hepatocytes and establish the capacity of NO to inhibit not only active caspases but also caspase activation.
Acid-degradable polymers for drug delivery: a decade of innovation (2012)

Polymers that start degrading under acidic conditions are increasingly investigated as a pathway to trigger the release of drugs once the drug carrier reached the slightly acidic tumour environment or after the drug carrier has been taken up by cells, resulting in the localization of the polymer in the acidic endosomes and lysosomes. The advances in the design of acid-degradable polymers and drug delivery systems have been summarized and discussed in this review article. Various acid-labile groups such as acetals, orthoester, hydrazones, imines and cis-aconityl, that can undergo cleavage in slightly acidic conditions, have been employed to create polymer architectures or polymer-drug conjugates that can degrade under lysosomal and endosomal conditions, triggering the fast release of drugs or DNA.
Therapeutic Options in the Treatment of Clozapine‐Induced Sialorrhea (2000)

Clozapine is an effective atypical antipsychotic drug, but its use may be compromised by its side effects. Agranulocytosis may be fatal, but sialorrhea occurs more frequently and plays a major role in patients' noncompliance. A MEDLINE search from 1975-2000 revealed that treatment of clozapine-induced sialorrhea is predominantly based on case reports. Due to its elusive mechanism, physicians have attempted to treat this side effect with agents that counteract clozapine's adrenergic and muscarinic properties. We evaluated reported treatment options and other possible strategies from a pharmacologic standpoint. Antimuscarinic agents and alpha-receptor agonists are both viable options but must be administered and monitored cautiously in patients with psychiatric disorders. Although not yet available in the United States, pirenzepine, a selective muscarinic receptor antagonist, has the most promising mechanism. Other selective, peripherally acting agents must be investigated in controlled clinical trials to determine their efficacy as possible alternatives.
Microfluidic transwell inserts for generation of tissue culture-friendly gradients in well plates (2013)

Gradients of biochemical molecules play a key role in many physiological processes such as axon growth, tissue morphogenesis, and trans-epithelium nutrient transport, as well as in pathophysiological phenomena such as wound healing, immune response, bacterial invasion, and cancer metastasis. In this paper, we report a microfluidic transwell insert for generating quantifiable concentration gradients in a user-friendly and modular format that is compatible with conventional cell cultures and with tissue explant cultures. The device is simply inserted into a standard 6-well plate, where it hangs self-supported at a distance of ~250 μm above the cell culture surface. The gradient is created by small microflows from the device, through an integrated track-etched porous membrane, into the cell culture well. The microfluidic transwell can deliver stable, quantifiable gradients over a large area with extremely low fluid shear stress to dissociated cells or tissue explants cultured independently on the surface of a 6-well plate. We used finite-element modeling to describe the porous membrane flow and molecular transport and to predict gradients generated by the device. Using the device, we applied a gradient of the chemotactic peptide N-formyl-met-leu-phe (fMLP) to a large population of HL-60 cells (a neutrophil cell line) and directly observed the migration with time-lapse microscopy. On quantification of the chemotactic response with an automated tracking algorithm, we found 74% of the cells moving towards the gradient. Additionally, the modular design and low fluid shear stress made it possible to apply gradients of growth factors and second messengers to mouse retinal explant cultures. With a simplified interface and well-defined gradients, the microfluidic transwell device has potential for broad applications to gradient-sensing biology.
Communication Efficient Secret Sharing (2016)

A secret sharing scheme is a method to store information securely and reliably. Particularly, in a threshold secret sharing scheme, a secret is encoded into n shares, such that any set of at least t <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> shares suffice to decode the secret, and any set of at most t <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> <; t <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> shares reveal no information about the secret. Assuming that each party holds a share and a user wishes to decode the secret by receiving information from a set of parties; the question we study is how to minimize the amount of communication between the user and the parties. We show that the necessary amount of communication, termed “decoding bandwidth”, decreases as the number of parties that participate in decoding increases. We prove a tight lower bound on the decoding bandwidth, and construct secret sharing schemes achieving the bound. Particularly, we design a scheme that achieves the optimal decoding bandwidth when d parties participate in decoding, universally for all t <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> ≤ d ≤ n. The scheme is based on a generalization of Shamir's secret sharing scheme and preserves its simplicity and efficiency. In addition, we consider the setting of secure distributed storage where the proposed communication efficient secret sharing schemes not only improve decoding bandwidth but further improve disk access complexity during decoding.
Glial Contribution to Seizure: Carbonic Anhydrase Activity in Epileptic Mammalian Brain (1991)

The activity of carbonic anhydrase (CA), a glial enzyme, was measured in the epileptic cortex of audiogenic DBA/2 mice and of cats with a freeze lesion. In mice, the activity increased with age from birth to 24 days, but were always higher in audiogenic mice than in normal C57/BL mice, reflecting species differences. The difference between the two strains increased sharply from 25 to 40 days of age, after the period of maximal audiogenic susceptibility. Acetazolamide, a CA-specific inhibitor, greatly decreased the seizure severity score of DBA/2 mice after a single intraperitoneal (i.p.) administration (150 mg/kg). After 24 days of age, when CA activities were high, the effect of acetazolamide was less important, suggesting that the increased cortical CA activity might reflect a protective mechanism. In cats with a freeze lesion, no significant changes in CA activities were observed in the actively discharging primary and secondary foci as compared with the nonepileptogenic perifocal cortex and the control cortex of sham-operated animals. The results indicate that the cortex of genetically susceptible audiogenic mice has an increased CA activity. The hypothesis of an adaptive glial mechanism, relating to the age-dependent decrease of seizure susceptibility in DBA/2 mice, is postulated.
Activation of GLUT1 by metabolic and osmotic stress: potential involvement of AMP-activated protein kinase (AMPK) (2002)

In the rat liver epithelial cell line Clone 9, the V(max) for glucose uptake is acutely increased by inhibition of oxidative phosphorylation and by osmotic stress. By using a membrane-impermeant photoaffinity labelling reagent together with an isoform-specific antibody, we have, for the first time, provided direct evidence for the involvement of the GLUT1 glucose transporter isoform in this response. Transport stimulation was found to be associated with enhanced accessibility of GLUT1 to its substrate and with photolabelling of formerly 'cryptic' exofacial substrate binding sites in GLUT1 molecules. The total amount of cell surface GLUT1 remained constant. The precise mechanism for this binding site 'unmasking' is unclear but appears to involve AMP-activated protein kinase: in the current study, osmotic and metabolic stresses were found to result in activation of the alpha 1 isoform of AMP-activated protein kinase, and transport stimulation could be mimicked both by 5-aminoimidazole-4-carboxamide ribonucleoside and by infection of cells with a recombinant adenovirus encoding constitutively active AMP-activated protein kinase. The effect of 5-aminoimidazole-4-carboxamide ribonucleoside, as for metabolic stress, was on the V(max) rather than on the K(m) for transport and did not affect the cell-surface concentration of GLUT1. The relevant downstream target(s) of AMP-activated protein kinase have not yet been identified, but stimulation of transport by inhibition of oxidative phosphorylation or by 5-aminoimidazole-4-carboxamide ribonucleoside was not prevented by either inhibitors of conventional and novel protein kinase C isoforms or inhibitors of nitric oxide synthase. These enzymes, which have been implicated in stress-regulated pathways in other cell types, are therefore unlikely to play a role in transport regulation by stress in Clone 9 cells.
2010년 한국어교육 국제학술회의 : 다문화 시대의 문학과 대중문화 ; 다문화사회: 한국문학과 대중문화의 대응 (2010)

한국 사회의 다문화적 현상은 다른 어느 나라와 비교해도 다양하다. 다른 나라의 경우에는 인종, 종교 언어, 성, 사회계층 등의 문제가 중심이지만, 우리의 경우에는 이 외에도 국내로 들어온 북한이탈주민 재외동포들도 다문화사회의 한 구성원이다. 그리고 이와 같은 한국의 다문화사회적 특정은 우리 사회가 해결해야 할 과제이고, 이 문제의 해결은 지금까지처럼 소수자에게 베푸는 시혜 보다는 다수자의 의식을 변화시키는 데 초점을 맞추어야 한다. 이런 맥락에서 최근의 한국문학과 대중문화는 단편적인 현상보다는 총체적인 측면에서 문제의 본질을 드러내려고 노력하고 있다. 특히 최근의 문학 작품과 대중문화는 이들을 또 다른 우리, 다수자인 우리와 별로 다르지 않다는 사실을 보여주고 있으며, 이런 문학, 문화의 형상화 노력은 단편 소설이나 단편의 인권 영화를 중심으로 문제의식을 부각시키는 데 초점이 맞추어졌던 것에 비하여 장편 소설이나 장편의 독립 영화를 통해서 문제의 해결책이나 대안을 찾아내려는 노력으로 번화하고 있다는 사실이다. 그리고 이 외에도 애니메이션, 연극, 시, 만화 등에서도 다문화사회의 다양성이라는 특정과 과제를 본격적으로 다루고 있다.
Rapid Identification of the Bacterial Pathogens Responsible for Urinary Tract Infections Using Direct Injection CE (2000)

The use of high-performance capillary electrokinetic techniques for the separation, identification, and quantitation of intact microbes represents a new frontier for separation science. In this work, it is demonstrated that pathogens most responsible for urinary tract infections can be distinguished from one another after direct injection of untreated urine. High efficiencies (often exceeding 1000000 plates/m) and short analysis times (< 10 min) are characteristics of this approach. The concentration of the urine matrix appears to be able to cause a small, but definite, change in the electroosmotic flow velocity. This high-efficiency separation-based approach could prove to be invaluable for the diagnosis and tracking of certain diseases. It also could form the basis for a variety of rapid microbial assays.
Quantitative Estimation of Soil Salinity Using UAV-Borne Hyperspectral and Satellite Multispectral Images (2019)

Soil salinization is a global issue resulting in soil degradation, arable land loss and ecological environmental deterioration. Over the decades, multispectral and hyperspectral remote sensing have enabled efficient and cost-effective monitoring of salt-affected soils. However, the potential of hyperspectral sensors installed on an unmanned aerial vehicle (UAV) to estimate and map soil salinity has not been thoroughly explored. This study quantitatively characterized and estimated field-scale soil salinity using an electromagnetic induction (EMI) equipment and a hyperspectral camera installed on a UAV platform. In addition, 30 soil samples (0~20 cm) were collected in each field for the lab measurements of electrical conductivity. First, the apparent electrical conductivity (ECa) values measured by EMI were calibrated using the lab measured electrical conductivity derived from soil samples based on empirical line method. Second, the soil salinity was quantitatively estimated using the random forest (RF) regression method based on the reflectance factors of UAV hyperspectral images and satellite multispectral data. The performance of models was assessed by Lin’s concordance coefficient (CC), ratio of performance to deviation (RPD), and root mean square error (RMSE). Finally, the soil salinity of three study fields with different land cover were mapped. The results showed that bare land (field A) exhibited the most severe salinity, followed by dense vegetation area (field C) and sparse vegetation area (field B). The predictive models using UAV data outperformed those derived from GF-2 data with lower RMSE, higher CC and RPD values, and the most accurate UAV-derived model was developed using 62 hyperspectral bands of the image of the field A with the RMSE, CC, and RPD values of 1.40 dS m−1, 0.94, and 2.98, respectively. Our results indicated that UAV-borne hyperspectral imager is a useful tool for field-scale soil salinity monitoring and mapping. With the help of the EMI technique, quantitative estimation of surface soil salinity is critical to decision-making in arid land management and saline soil reclamation.
Synthesis of ethyl 6-substituted-chroman- and -chromone-2-carboxylates. Comparative structure-activity study employing the 6-phenyl and phenoxy analogs in the triton hyperlipidemic rat model (1975)

To explore the effect of lipophilicity on antilipidemic activity in the Triton WR-1339 induced hyperlipidemic rat model we synthesized the 6-cyclohexyl, phenyl, and phenoxy analogs of ethyl chroman-2-carboxylate. Results obtained were analyzed in light of the biological activity observed for the 6-chloro-substituted and unsubstituted chromans, the 6-chlorochroman-4-one ester, and the 6-chloro-, phenyl-, and phenoxychromone esters. The suggestion is made that chromones likely exert their antilipidemic effects by a somewhat different set of mechanisms than do the chromans and clofibrate. Whereas the 6-chlorochromanone ester is inactive, the 6-chlorochromone ester is active in both normal and hyperlipidemic Sprague-Dawley rats. The major differential effect was observed for ethyl 6-cyclohexylchroman-2-carboxylate which did not lower cholesterol levels but returned triglyceride levels to normal in hyperlipidemic rats.
Reporter Gene Imaging (2013)

In molecular biology, many reporter genes have been developed for monitoring cellular processes. Development of controlled gene delivery systems promotes construction of various types of reporter genes for monitoring the level of a gene expression, promoter activity, and protein-protein interaction. When an imaging reporter gene is placed under the control of a promoter, the amount of reporter protein can be dynamically visualized in vivo. Instrumental advances in molecular imaging have increased the sensitivity and resolution of in vivo reporter imaging. Though several types of reporters and multimodal imaging instruments are currently available, more efficient multimodal reporter gene systems and detectors compatible with several imaging modalities are needed.