gebhart/patrepeval huggingface dataset:
Gene Expression-Based Chemical Genomics Identifies Potential Therapeutic Drugs in Hepatocellular Carcinoma (2011)

Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis. Currently, only sorafenib is approved by the FDA for advanced HCC treatment; therefore, there is an urgent need to discover candidate therapeutic drugs for HCC. We hypothesized that if a drug signature could reverse, at least in part, the gene expression signature of HCC, it might have the potential to inhibit HCC-related pathways and thereby treat HCC. To test this hypothesis, we first built an integrative platform, the "Encyclopedia of Hepatocellular Carcinoma genes Online 2", dubbed EHCO2, to systematically collect, organize and compare the publicly available data from HCC studies. The resulting collection includes a total of 4,020 genes. To systematically query the Connectivity Map (CMap), which includes 6,100 drug-mediated expression profiles, we further designed various gene signature selection and enrichment methods, including a randomization technique, majority vote, and clique analysis. Subsequently, 28 out of 50 prioritized drugs, including tanespimycin, trichostatin A, thioguanosine, and several anti-psychotic drugs with anti-tumor activities, were validated via MTT cell viability assays and clonogenic assays in HCC cell lines. To accelerate their future clinical use, possibly through drug-repurposing, we selected two well-established drugs to test in mice, chlorpromazine and trifluoperazine. Both drugs inhibited orthotopic liver tumor growth. In conclusion, we successfully discovered and validated existing drugs for potential HCC therapeutic use with the pipeline of Connectivity Map analysis and lab verification, thereby suggesting the usefulness of this procedure to accelerate drug repurposing for HCC treatment.
The zone of comfort: Predicting visual discomfort with stereo displays (2011)

Recent increased usage of stereo displays has been accompanied by public concern about potential adverse effects associated with prolonged viewing of stereo imagery. There are numerous potential sources of adverse effects, but we focused on how vergence-accommodation conflicts in stereo displays affect visual discomfort and fatigue. In one experiment, we examined the effect of viewing distance on discomfort and fatigue. We found that conflicts of a given dioptric value were slightly less comfortable at far than at near distance. In a second experiment, we examined the effect of the sign of the vergence-accommodation conflict on discomfort and fatigue. We found that negative conflicts (stereo content behind the screen) are less comfortable at far distances and that positive conflicts (content in front of screen) are less comfortable at near distances. In a third experiment, we measured phoria and the zone of clear single binocular vision, which are clinical measurements commonly associated with correcting refractive error. Those measurements predicted susceptibility to discomfort in the first two experiments. We discuss the relevance of these findings for a wide variety of situations including the viewing of mobile devices, desktop displays, television, and cinema.
Volumes to Learn: Advancing Therapeutics with Innovative Computed Tomography Image Data Analysis (2010)

Semi-automated methods for calculating tumor volumes from computed tomography images are a new tool for advancing the development of cancer therapeutics. Volumetric measurements, relying on already widely available standard clinical imaging techniques, could shorten the observation intervals needed to identify cohorts of patients sensitive or resistant to treatment.
Mechanochemical manipulation of hepatocyte aggregation can selectively induce or repress liver-specific function (2000)

Controlled activation of hepatocyte aggregation is critical to three-dimensional (3D) multicellular morphogenesis during native regeneration of liver as well as tissue reconstruction therapies. In this work, we quantify the stimulatory effects of two model hepatotrophic activators, epidermal growth factor (EGF) and hepatocyte growth factor (HGF), on the aggregation kinetics and liver-specific function of hepatocytes cultured on organotypic substrates with differing mechanical resistivity. Substrate-specific morphogenesis of cultured hepatocytes is induced on a tissue basement membrane extract, Matrigel, formulated at two distinct levels of mechanical compliance (storage modulus G', at oscillatory shear rate 1 rad/s, was 34 Pa for basal Matrigel and 118 Pa for crosslinked Matrigel). Overall, we report that growth factor stimulation selectively promotes the kinetics of aggregation in the form of two-dimensional corded aggregates on basal Matrigel and three-dimensional spheroidal aggregates on crosslinked Matrigel. Our analysis also indicates that costimulation with EGF and HGF (20 ng/mL each) cooperatively maximizes the kinetics of aggregation in a substrate-specific manner. In addition, we show that the role of growth factor stimulation on hepatocyte function is sensitively governed by the mechanical compliance of the substrate. In particular, on matrices with high compliance, costimulatory aggregation is shown to elicit a marked increase in albumin secretion rate, whereas on matrices with low compliance aggregation results in effective functional repression to basal, unstimulated levels. Thus, our studies highlight a novel interplay of physicochemical parameters of the culture microenvironment, leading to selective enhancement or repression of differentiated functions of hepatocytes, in concert with the activation of cellular morphogenesis.
Glycine and other amino compounds prevent chromatin precipitation at physiological ionic strength (1989)

Glycine, proline and taurine, when present in the range 0.1-0.60 M, inhibit chromatin precipitation by sodium chloride. Histone gel electrophoresis revealed that the linker histones H1 and H5 were largely depleted from the supernatant chromatin fraction at 0.2 M NaCl, while this depletion was absent in the presence of glycine. These observations are discussed in relation with the various factors which may be involved in the precipitation process.
InterPay: Managing Multiple Payment Mechanisms in Digital Libraries. (1995)

We propose an architecture called InterPay for managing financial interactions with for-pay digital library services. The approach accommodates multiple payment mechanisms, interaction models, and charging policies. Key components of our model are payment agents and payment capabilities that encapsulate payment policy and the details of payment on behalf of the user. Collection agents and collection capabilities provide similar encapsulation for the service provider. The architecture supports interactions ranging from individual users directly interacting with the service provider to institutional users accessing information brokers via a corporate library. We also describe a prototype system that implements the InterPay architecture, allowing access to real services under varying payment policies. 1 Introduction In an ideal world, access to information and services would be free. However, collecting and providing access to information and services is expensive and these costs must b...
BnWRI1 coordinates fatty acid biosynthesis and photosynthesis pathways during oil accumulation in rapeseed (2014)

Photosynthesis in "green" seeds, such as rapeseed, soybean, and Arabidopsis, plays a substantial role in the improved efficiency of oil accumulation. However, the molecular mechanism underpinning the coordinated expression of fatty acid (FA) biosynthesis- and photosynthesis-related genes in such developing seeds remains to be elucidated. Here, we found that seed-specific overexpression of BnWRI1, a WRI1 homolog from rapeseed (Brassica napus cv. ZGY2), results in enhanced chlorophyll content in developing seeds and increased oil content and seed mass in matured seeds. BnWRI1 was co-expressed with BnBCCP and BnCAB, two marker genes of FA biosynthesis and photosynthesis during seed development, respectively. Overexpression of BnWRI1 increased expression of both marker genes. Further, the nuclear-localized BnWRI1 protein was found to act as a transcription activator. It could bind to the GT1-element and/or GCC-box, which are widespread in the upstream regions of genes involved in FA biosynthesis and photosynthesis pathways. Accordingly, BnWRI1 could interact with promoters of BCCP2 and LHB1B2 in vivo. These results suggested that BnWRI1 may coordinate FA biosynthesis and photosynthesis pathways in developing seeds via directly stimulating expression of GT1-element and/or GCC-box containing genes.
CONDITIONING FILM DEPOSITION ON URETERAL STENTS AFTER IMPLANTATION (1998)

Three types of ureteral stents were used in a study of 53 patients. Following extracorporeal shock wave lithotripsy, the stents were implanted and retained for periods of between 3 and 40 days. Each patient received daily antibiotic therapy with either ciprofloxacin or trimethoprim. After removal, the devices were analyzed for adherent bacteria and encrustations. The study showed that a conditioning film became deposited onto the stents upon implantation, changing the surface characteristics of the biomaterials. Dense encrustations were found to be least on a low surface energy device. No differences were found related to patient age and gender or duration of stent insertion. Flakiness and apparent sloughing of the stent surfaces was observed in some devices, raising concerns as to what actually happens to medical devices when exposed to the host urinary tract. Bacteria were recovered from the urine of three patients and the stents of four patients treated with trimethoprim. Five stents had bacterial biofilms detected by SEM. The actual clinical end-point was not the focus of this study, but no patients became septic. Our goal was to demonstrate conclusively in humans that medical devices do develop conditioning films upon implantation, and that they can be susceptible to bacterial colonization even during antibiotic treatments. The kidneys of stented patients are clearly at risk of infection, and only by proper selection of a stent type and appropriate antibiotic coverage can this risk be significantly reduced.
Cross-Dressing the Virion: the Transcapsidation of Adeno-Associated Virus Serotypes Functionally Defines Subgroups (2004)

For all adeno-associated virus (AAV) serotypes, 60 monomers of the Vp1, Vp2, and Vp3 structural proteins assemble via an unknown mechanism to form an intact capsid. In an effort to better understand the properties of the capsid monomers and their role in viral entry and infection, we evaluated whether monomers from distinct serotypes can be mixed to form infectious particles with unique phenotypes. This transcapsidation approach consisted of the transfection of pairwise combinations of AAV serotype 1 to 5 helper plasmids to produce mosaic capsid recombinant AAV (rAAV). All ratios (19:1, 3:1, 1:1, 1:3, and 1:19) of these mixtures were able to replicate the green fluorescent protein transgene and to produce capsid proteins. A high-titer rAAV was obtained with mixtures that included either serotype 1, 2, or 3, whereas an rAAV of intermediate titer was obtained from serotype 5 mixtures. Only mixtures containing the AAV4 capsid exhibited reduced packaging capacity. The binding profiles of the mixed-virus preparations to either heparin sulfate (HS) or mucin agarose revealed that only AAV3-AAV5 mixtures at the 3:1 ratio exhibited duality in binding. All other mixtures displayed either an abrupt shift or a gradual alteration in the binding profile to the respective ligand upon increase of a capsid component that conferred either HS or mucin binding. The transduction of cell lines was used to further evaluate the phenotypes of these transcapsidated virions. Three transduction profiles were observed: (i) small to no change regardless of ratio, (ii) a gradual increase in transduction consistent with titration of a second capsid component, or (iii) an abrupt increase in transduction (threshold effect) dependent on the specific ratios used. Interestingly, an unexpected synergistic effect in transduction was observed when AAV1 helper constructs were combined with type 2 or type 3 recipient helpers. Further studies determined that at least two components contributed to this observed synergy: (i) heparin-mediated binding from AAV2 and (ii) an unidentified enhancement activity from AAV1 structural proteins. Using this procedure of mixing different AAV helper plasmids to generate "cross-dressed" AAV virions, we propose an additional means of classifying new AAV serotypes into subgroups based on functional approaches to analyze AAV capsid assembly, receptor-mediated binding, and virus trafficking. Exploitation of this approach in generating custom-designed AAV vectors should be of significant value to the field of gene therapy.
Effects of Oxygenated Fuel and Cetane Improver on Exhaust Emission from Heavy-Duty DI Diesel Engines (1994)

&lt;div class="htmlview paragraph"&gt;Smoke emission from single-cylinder DI and IDI diesel engines was shown to strongly depend on oxygen content in fuel regardless of oxygenate molecular structure. Thus, with cetane improver and oxygenate used in combination in a proportion determined from blending properties and potential cost for modern heavy-duty DI diesel engines were assessed. The combined use of nitrate type cetane improver with glycol ether type oxygenate reduced particulate, HC, and CO emission but not that of NOx. Particulate reduction depended on oxygenate content. Oxygenate at less than 5% with cetane improver seldom worsened volume-based fuel economy compared with the base hydrocarbon fuel.&lt;/div&gt;
4-Azasteroidal 5 alpha-reductase inhibitors without affinity for the androgen receptor. (1984)

In efforts to develop potent 5 alpha-reductase inhibitors without affinity for the androgen receptor, synthetic 3-oxo-5 alpha-steroids were tested for their ability to inhibit 5 alpha-reductase, using [14C]testosterone as the substrate, and for their ability to inhibit the binding of [3H]5 alpha-dihydrotestosterone to the androgen receptor of rat prostate cytosol. 2',3' alpha-Tetrahydrofuran-2'-spiro-17-(5 alpha-androstan-3-one) is not an inhibitor of 5 alpha-reductase and has a high affinity for the androgen receptor; substitution of the -CH2- at the 4-position with N-H resulted in a good inhibitor of 5 alpha-reductase. The 4-N-CH3 derivative is even more active, whereas the N-CH2-CH3 derivative is inactive. These 4-aza derivatives have much lower affinity for the androgen receptor than the parent compound. The 4-N-H derivatives of several 3-oxo-5 alpha-steroids were found to be 20-100% as potent as their corresponding 4-N-CH3 analogs as inhibitors of 5 alpha-reductase, whereas their androgen receptor affinities were at least 40-fold lower than their 4-N-CH3 analogs. Their 5 beta-isomers did not inhibit either 5 alpha-reductase or the androgen receptor binding of [3H]5 alpha-dihydrotestosterone. Two of these 4-N-H steroids, 17 beta-N,N-diethylcarbamoyl-4-aza-5 alpha-androstan-3-one and 17 beta-N, N-diisopropylcarbamoyl-4-aza-5 alpha-androstan-3-one, are potent 5 alpha-reductase inhibitors with Ki values equal to 29.2 +/- 1.7 and 12.6 +/- 0.8 nM, respectively, but have little affinity for the androgen receptor. The inhibition of 5 alpha-reductase by both compounds is competitive with testosterone. When [3H]testosterone was incubated with minced rat prostate in the presence of either of these two 4-azasteroids, the nuclear concentration of 5 alpha-dihydrotestosterone decreased and that of testosterone increased. The total nuclear uptake of testosterone plus 5 alpha-dihydrotestosterone was not significantly affected. These 4-azasteroids should be useful for investigating the importance of 5 alpha-reductase in androgen action in vivo.
Measurements and Modeling of Distributed Antenna Systems in Railway Tunnels (2007)

This paper covers some of the work carried out in the planning of the global system for mobile communication for railway (GSM-R) of the tunnels on the new high-speed trains in Spain. Solutions based on distributed antenna systems have been tested by installing several 900-MHz transmitters inside and outside of a 4000-m tunnel and measuring the propagation in different conditions. The measurements have been used to model the effects of tunnel propagation, including curves, trains passing from the outside to the inside, and the effect of two trains passing inside the tunnel. All cases have been tested by comparing solutions using isofrequency and multifrequency distributed transmitters inside the tunnel. The improvements of signal-to-noise ratio and the reduction of the blocking effects of two trains passing have demonstrated the advantages of using isofrequency distributed antenna systems in tunnels. Finally, a complete propagation model combining both modal analysis and ray tracing has been applied to predict the propagation loss inside and outside these tunnels, and results have been compared with the measurements. The model has proven to be very useful for radio planning in new railway networks.
PQTable: Fast Exact Asymmetric Distance Neighbor Search for Product Quantization Using Hash Tables (2015)

We propose the product quantization table (PQTable), a product quantization-based hash table that is fast and requires neither parameter tuning nor training steps. The PQTable produces exactly the same results as a linear PQ search, and is 102 to 105 times faster when tested on the SIFT1B data. In addition, although state-of-the-art performance can be achieved by previous inverted-indexing-based approaches, such methods do require manually designed parameter setting and much training, whereas our method is free from them. Therefore, PQTable offers a practical and useful solution for real-world problems.
Semi-automatic photo annotation strategies using event based clustering and clothing based person recognition (2007)

Managing a large number of digital photos is a challenging task for casual users. Personal photos often don’t have rich metadata, or additional information associated with them. However, available metadata can play a crucial role in managing photos. Labeling the semantic content of photos (i.e., annotating them), can increase the amount of metadata and facilitate efficient management. However, manual annotation is tedious and labor intensive while automatic metadata extraction techniques often generate inaccurate and irrelevant results. This paper describes a semi-automatic annotation strategy that takes advantage of human and computer strengths. The semi-automatic approach enables users to efficiently update automatically obtained metadata interactively and incrementally. Even though automatically identified metadata are compromised with inaccurate recognition errors, the process of correcting inaccurate information can be faster and easier than manually adding new metadata from scratch. In this paper, we introduce two photo clustering algorithms for generating meaningful photo groups: (1) Hierarchical event clustering; and (2) Clothing based person recognition, which assumes that people who wear similar clothing and appear in photos taken in one day are very likely to be the same person. To explore our semi-automatic strategies, we designed and implemented a prototype called SAPHARI (Semi-Automatic PHoto Annotation and Recognition Interface). The prototype provides an annotation framework which focuses on making bulk annotations on automatically identified photo groups. The prototype automatically creates photo clusters based on events, people, and file metadata so that users can easily bulk annotation photos. We performed a series of user studies to investigate the effectiveness and usability of the semi-automatic annotation techniques when applied to personal photo collections. The results show that users were able to make annotations significantly faster with event clustering using SAPHARI. We also found that users clearly preferred the semi-automatic approaches.
Pharmacological sensitivity of ATP release triggered by photoliberation of inositol‐1,4,5‐trisphosphate and zero extracellular calcium in brain endothelial cells (2003)

Recently, ATP has gained much interest as an extracellular messenger involved in the communication of calcium signals between cells. The mechanism of ATP release is, however, still a matter of debate. In the present study we investigated the possible contribution of connexin hemichannels or ion channels in the release of ATP in GP8, a rat brain endothelial cell line. Release of ATP was triggered by photoactivation of InsP(3) or by reducing the extracellular calcium concentration. Both trigger protocols induced ATP release significantly above baseline. InsP(3)-triggered ATP release was completely blocked by alpha-glycyrrhetinic acid (alpha-GA), the connexin mimetic peptides gap 26 and 27, and the trivalent ions gadolinium and lanthanum. ATP release triggered by zero calcium was, in addition to these substances, also blocked by flufenamic acid (FFA), niflumic acid, and NPPB. Gap 27 selectively blocked zero calcium-triggered ATP release in connexin-43 transfected HeLa cells, while having no effect in wild-type and connexin-32 transfected cells. Of all the agents used, only alpha-GA, FFA and NPPB significantly reduced gap junctional coupling. In conclusion, InsP(3) and zero calcium-triggered ATP release show major similarities but also some differences in their sensitivity to the agents applied. It is suggested that both stimuli trigger ATP release through the same mechanism, which is connexin-dependent, permeable in both directions, potently blocked by connexin mimetic peptides, and consistent with the opening of connexin hemichannels.
Carbonic Anhydrase IX Expression in Clear Cell Renal Cell Carcinoma (2008)

Carbonic anhydrase IX (CAIX)-a protein maintaining intracellular and extracellular pH-reportedly also influences regulation of cell proliferation, oncogenesis, and tumor progression. Its expression is von Hippel-Lindau-hypoxia inducible factor pathway dependent. Immunohistochemical (IHC) studies show that CAIX is diffusely overexpressed in clear cell renal cell carcinoma (CRCC), making it a potentially important differential diagnostic marker. Prognostically, low CAIX expression reportedly indicates poor survival and low response to interleukin therapy in CRCC. Most IHC studies have used clone M75 as the primary antibody, which is not commercially available. We evaluated a new commercially available antibody (clone NB100-417) to assess its expression in CRCC and compared its results with M75. On a tissue microarray of CRCC, IHC staining was performed using both antibodies. The immunoreactivity was graded as 0; 1+, 1% to 25%; 2+, 26% to 50%; and 3+, >50% tumor cells immunoreactive. Ninety-one out of ninety-five (96%) cases showed similar staining grade with excellent agreement (kappa=0.65, weighted kappa=0.75). Grade 3+ expression of CAIX was observed in 89 (94%) cases each, with both antibodies. Both antibodies produced intense membrane-predominant expression, limited to tumor cells. More than 95% of the tumors with low nuclear grade, compared with 84% and 88% of tumors with high nuclear grade, showed 3+ expression using both antibodies. Thus, most CRCC show strong and diffuse expression of CAIX, and the expression is comparable using both antibodies. Therefore, similar to the clone M75, NB100-417 can be used as a diagnostic and potentially a prognostic marker in CRCC, with the advantage of its commercial availability.