gebhart/patrepeval huggingface dataset:
Stereochemical aspects of the interaction between steroidal diamines and DNA (1975)

A complete series of stereoisomeric quaternised diaminoandrostanes, differing in their stereochemistry at the 3,5 and 17 positions, has been examined for effects on the thermal denaturation of calf thymus DNA and for the ability to remove and reverse the supercoiling of closed circular duplex PM2 DNA. In both types of test the eight isomers rank in the same order of effectiveness. The preferred stereochemistry for the quaternary substituents at positions 3 and 17 is beta; of these the orientation of the 17- substituent is more critical. Folding of the steroid skeleton between the A and B rings, as in 5beta-androstanes, diminishes effectiveness but does not necessarily abolish the effect on supercoiling. The over-riding importance of the C-D ring end of the steroid nucleus bearing a 17beta-amino substituent is confirmed by a comparison of the effects of five mon-amino androstanes. Relative helix=unwinding angles per bound steroidal diamine molecule have been determined for four of the isomers; for three 17beta compounds the estimated values are similar to that previously reported for irehdiamine A. For a fourth isomer the angle is 0.22 times that of ethidium, the lowest yet determined for any DNA-binding drug. The results lend further support to the argument that intercalation can be reled out, and alternative models for the binding mechanism are discussed.
Heterodyne interferometric polarization coherent anti‐Stokes Raman scattering (HIP‐CARS) spectroscopy (2010)

Abstract We demonstrate a new technique that combines polarization sensitivity of the coherent anti‐Stokes Raman scattering (CARS) response with heterodyne amplification for background‐free detection of CARS signals. In this heterodyne interferometric polarization CARS (HIP‐CARS), the major drawbacks of polarization and heterodyne CARS are rectified. Using a home‐built picosecond optical parametric oscillator, we are able to address vibrational stretches between 600 and 1650 cm −1 and record continuous high‐resolution Raman equivalent HIP‐CARS spectra. Copyright © 2010 John Wiley &amp; Sons, Ltd.
ChemInform Abstract: Efficient Synthesis of Differentiated syn‐1,2‐Diol Derivatives by Asymmetric Transfer Hydrogenation—Dynamic Kinetic Resolution of α‐Alkoxy‐Substituted β‐Ketoesters. (2015)

Abstract Title compounds (II), (IV), and (VI) are formed in the presence of chiral Ru‐catalyst using a mixture of HCOOH and triethylamine as hydrogen source in high diastereo‐ and enantioselectivities.
Imaging endocarditis with Tc-99m-labeled antibody--an experimental study: concise communication. (1982)

The sensitivity and specificity of Tc-99m-labeled antibacterial antibody (Tc-99m Ab) for detecting bacterial endocarditis were evaluated in an experimental model. Rabbit-produced antistaphylococcal antibody was extracted using Rivanol and chemically labeled with Tc-99m. This Tc-99m Ab was injected intravenously in New Zealand rabbits 24 hr after producing Staphylococcus aureus endocarditis of the aortic valve. Imaging and tissue analyses were performed on the following day. All 11 animals developed S. aureus aortic-valve vegetations and showed increased uptake of Tc-99m Ab at the aortic valve, 118 times higher than at the uninfected tricuspid valve. Although high hepatic radioactivity and anatomic uncertainties interfered with in vivo delineation of these lesions, images of the excised hearts showed all affected valves. Two rabbits inoculated with Escherichia coli did not develop endocarditis and had little uptake of Tc-99m Ab, while six rabbits with enterococcal endocarditis had no uptake of the Tc-99m Ab in their vegetations. The findings suggest potential value of Tc-99m Ab on the rapid diagnosis of endocarditis.
Authorized manufacturing changes for therapeutic monoclonal antibodies (mAbs) in European Public Assessment Report (EPAR) documents (2016)

Background The quality of biologicals, including biosimilars, is subject to change as a result of manufacturing process modifications following initial authorization. It is important that such product changes have no adverse impact on product efficacy or safety, including immunogenicity. Objectives The aim of this study was to investigate the number and types of manufacturing changes for originator mAbs (the reference for the comparability exercise to confirm biosimilarity) according to European Public Assessment Report (EPAR) documentation and to ascertain the level of risk these changes might impart. The extensive body of evidence contained in the EPAR documents can help support the EMA during the EC marketing authorization approval process for biosimilars, since it provides a broad base of scientific experience. Research designs and methods For EPAR-listed mAbs, details of all changes listed chronologically in the EPAR were evaluated and described. Based on these descriptions the manufacturing changes can be categorized by risk status (low, moderate or high). Results Entries for 29 mAbs with publicly available EPAR reports were reviewed. These contained details of 404 manufacturing changes authorized by the European Medicines Agency (EMA): 22 were categorized as high risk, 286 as moderate risk and 96 as low risk manufacturing changes. A limitation of this analysis is that it only summarizes publicly available data from EPAR documents. Conclusions Manufacturing change data indicate that the EMA has significant experience of process changes for originator mAbs, and the impact they may have on the efficacy and safety of biologicals. This experience will be useful in biosimilar product development to ensure adherence to sound scientific principles. Compared with the established manufacturing process for a reference product, the production of biosimilars will usually be different. Consequently, in addition to a comprehensive comparative functional and physicochemical characterization analysis, clinical data is required to confirm mAb biosimilarity.
Scrabble (2018)

Interoperability in the Internet of Things relies on a common data model that captures the necessary semantics for vendor independent application development and data exchange. However, traditional systems such as those in building management are vertically integrated and do not use a standard schema. A typical building can consist of thousands of data points. Third party vendors who seek to deploy applications like fault diagnosis need to manually map the building information into a common schema. This mapping process requires deep domain expertise and a detailed understanding of intricacies of each building's system. Our framework -Scrabble -reduces the mapping effort significantly by using a multi-stage active learning mechanism that exploits the structure present in a standard schema and learns from buildings that have already been mapped to the schema. Scrabble uses conditional random fields with transfer learning to represent unstructured building information in a reusable intermediate representation. This reusable representation is mapped to the schema using a multilayer perceptron. Our novel semantic model based active learning mechanism requires only minimal input from domain experts to interpret esoteric, idiosyncratic data points. We have evaluated Scrabble on five buildings with thousands of different entities and our method outperforms prior work by 59%/162% higher Accuracy/Macro-averaged-F1 in a building when 10 examples are provided by an expert in both cases. Scrabble achieves 99% Accuracy with 100-160 examples for buildings with thousands of points while the other baselines cannot.
Combination Small Molecule MEK and PI3K Inhibition Enhances Uveal Melanoma Cell Death in a Mutant GNAQ- and GNA11 -Dependent Manner (2012)

MEK + PI3K inhibition may be an effective combination therapy in uveal melanoma, given the inherent reciprocal activation of these pathways within these cells.
Follow up of fetal outcome in cases of maternal phenylketonuria in Northern Ireland: Table 1 (2002)

Most problems occurred when dietary control was not established until after the 2nd trimester. As the cohort of young women with treated PKU is growing steadily, maternal PKU is going to become an even greater cause for concern.
Characterization of engineered hepatitis C virus NS3 protease inhibitors affinity selected from human pancreatic secretory trypsin inhibitor and minibody repertoires (1997)

Given the extent of hepatitis C virus (HCV) infection as a worldwide health problem and the lack of effective treatment, the development of anti-HCV drugs is an important and pressing objective. Previous studies have indicated that proteolytic events mediated by the NS3 protease of HCV are fundamental to the generation of an active viral replication apparatus, as unequivocably demonstrated for flaviviruses. As a result, the NS3 protease has become a major target for discovering anti-HCV drugs. To gain further insight into the biochemical and biophysical properties of the NS3 enzyme binding pocket(s) and to generate biological tools for developing antiviral strategies, we decided to engineer macromolecular ligands of the NS3 protease domain. Phage-displayed repertoires of minibodies ("minimized" antibody-like proteins) and human pancreatic secretory trypsin inhibitor were sampled by using the recombinant NS3 protease domain as a ligate molecule. Two protease inhibitors were identified and characterized biochemically. These inhibitors show marked specificity for the viral protease and potency in the micromolar range but display different mechanisms of inhibition. The implications for prospective development of low-molecular-weight inhibitors of this enzyme are discussed.
Down-regulation of Androgen Receptor by 3,3′-Diindolylmethane Contributes to Inhibition of Cell Proliferation and Induction of Apoptosis in Both Hormone-Sensitive LNCaP and Insensitive C4-2B Prostate Cancer Cells (2006)

Despite the initial efficacy of androgen deprivation therapy, most patients with advanced prostate cancer eventually progress to hormone-refractory prostate cancer, for which there is no curative therapy. Previous studies from our laboratory and others have shown the antiproliferative and proapoptotic effects of 3,3'-diindolylmethane (DIM) in prostate cancer cells. However, the molecular mechanism of action of DIM has not been investigated in androgen receptor (AR)-positive hormone-responsive and -nonresponsive prostate cancer cells. Therefore, we investigated the effects of B-DIM, a formulated DIM with greater bioavailability, on AR, Akt, and nuclear factor kappaB (NF-kappaB) signaling in hormone-sensitive LNCaP (AR+) and hormone-insensitive C4-2B (AR+) prostate cancer cells. We found that B-DIM significantly inhibited cell proliferation and induced apoptosis in both cell lines. By Akt gene transfection, reverse transcription-PCR, Western blot analysis, and electrophoretic mobility shift assay, we found a potential crosstalk between Akt, NF-kappaB, and AR. Importantly, B-DIM significantly inhibited Akt activation, NF-kappaB DNA binding activity, AR phosphorylation, and the expressions of AR and prostate-specific antigen, suggesting that B-DIM could interrupt the crosstalk. Confocal studies revealed that B-DIM inhibited AR nuclear translocation, leading to the down-regulation of AR target genes. Moreover, B-DIM significantly inhibited C4-2B cell growth in a severe combined immunodeficiency-human model of experimental prostate cancer bone metastasis. These results suggest that B-DIM-induced cell proliferation inhibition and apoptosis induction are partly mediated through the down-regulation of AR, Akt, and NF-kappaB signaling. These observations provide a rationale for devising novel therapeutic approaches for the treatment of hormone-sensitive, but more importantly, hormone-refractory prostate cancer by using B-DIM alone or in combination with other therapeutics.
Structure/Function Analysis of p55 Tumor Necrosis Factor Receptor and Fas-associated Death Domain (2000)

Tumor necrosis factor (TNF) induces a typical apoptotic cell death program in various cell lines by interacting with the p55 tumor necrosis factor receptor (TNF-R55). In contrast, triggering of the fibrosarcoma cell line L929sA gives rise to characteristic cellular changes resulting in necrosis. The intracellular domain of TNF-R55 can be subdivided into two parts: a membrane-proximal domain (amino acids 202-325) and a C-terminal death domain (DD) (amino acids 326-413), which has been shown to be necessary and sufficient for apoptosis. Structure/function analysis of TNF-R55-mediated necrosis in L929sA cells demonstrated that initiation of necrotic cell death, as defined by swelling of the cells, rapid membrane permeabilization, absence of nuclear condensation, absence of DNA hypoploidy, and generation of mitochondrial reactive oxygen intermediates, is also confined to the DD. The striking synergistic effect of the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone on TNF-induced necrosis was also observed with receptors solely containing the DD. TNF-R55-mediated necrosis is not affected by the dominant negative deletion mutant of the Fas-associated death domain (FADD-(80-205)) that lacks the N-terminal death effector domain. Moreover, overexpression of FADD-(80-205) in L929sA is cytotoxic and insensitive to CrmA, while the cytotoxicity due to overexpression of the deletion mutant FADD-(1-111) lacking the DD is prevented by CrmA. These results demonstrate that the death domain of FADD can elicit an active necrotic cell death pathway.
Increasing the cyclodextrin complexation of drugs and drug biovailability through addition of water-soluble polymers. (1998)

For a variety of reasons, including cost, production capabilities and toxicology, the amounts of cyclodextrin (CD) that can be included in drug formulations is limited and, thus, it is important to develop methods which can be applied to enhance the complexation efficacy. Moreover, bioavailability of drugs in CD containing vehicles can be rather limited resulting in less than optimal drug delivery. Addition of small amounts of a water-soluble polymer to the aqueous complexation media enhances the CD complexation of drugs. Thus, less CD is needed to dissolve a given amount of drug when a polymer is present than when it is not present in the aqueous complexation media. Furthermore, the bioavailability of drugs is enhanced through addition of polymers. In general, the water-soluble polymers improve both pharmaceutical and biological properties of drug-CD complexes. This polymer enhancement of drug complexation and bioavailability is independent of the physiochemical properties of the drug. Thermodynamic studies and other physicochemical observations indicate that the polymers participate directly in the drug-CD complexation.
송대(宋代) 림제종(臨濟宗)에서의 종밀(宗密) 비판(批判) -종밀(宗密)에 대한 각범(覺範)의 비판을 중심으로 (2002)

In the Sung dynasty, the criticism of Lin-Chi school against Tsung-mi`s assertion can divide into two parts. One is the problem of dharma-lineage in the history of Sean Sect. The other is the understanding and practise on our Mind. This criticism was formed in the Sung dynasty by Hui-hung Chueh-fan(慧洪覺範, 1071-1128) who belonged to Lin-Chi school or especially to the Huang-lung branch(黃龍派). He criticized the Ho-tse school of the thought of ``Accordance of Ch`an and Teachings`` in his lin-chien-lu(林間錄). For Tsung-mi(宗密)`s assertion about four schools of Ch`an thought, he said that Tsung-mi advocated Shen-hui(神會) as a legitimate heir of Hui-Neng`s Teachings and abused Huai-Jang(懷讓) as a side line of Dharma. He denied the assertion that the genuine religious tradition of Hui-Neng was inherited to Shen-hui, but presumed that It was transmitted to Huai-Jang who had been a teacher of Ma-tsu. This view, regardless of the personal thought and historical background of Shen-Hui and Huai-Jang, became the standard to differ the direct line from the collateral since then. The Lin-Chi school in the Sung dynasty judged Shen-Hui as ``an adherent of the conceptual knowledge and interpretation`` And this problem was important to the Lin-Chi school which tried to confirm its legitimacy, in opposition to the Ho-tse school or the Fa-yen school which aimed at the thought of ``the Accordance of Ch`an and the Sutra``. It emphasized on the thought of ``Not Bounded to Scripture`` and ``Teachings Apart from the Sutra``, and took as a standard of approval method not The Platform Sutra but Enlightenment based on ``Buddhahood by Seeing the Real Nature of Things``. This inclination of thought was more intense in the Yang-ch`i branch than in the Huang-lung branch, so this trend in its turn gave birth to ``the meditation through observing the Topic(看話禪)``.
Microbubbles-overlapping mode for laser killing of cancer cells with absorbing nanoparticle clusters (2005)

Laser-induced bubble formation around nanoparticles may play a crucial role in selective laser nanophotothermolysis of cancer cells targeted with nanoparticles. In this paper, we propose theoretically, and confirm experimentally, a new dynamic mode for selective cancer treatment that involves the overlapping of bubbles inside the cell volume. This bubbles-overlapping mode (BOM) can dramatically increase the efficiency of cancer treatment by laser-heated nanoparticles as a result of the large damage range. On the basis of nanoparticle optics below the diffraction limit and the kinetic model of bubble dynamics, we found the criteria and conditions (interparticle distance and particle size and concentration) for BOM initiation in cancer cells by laser radiation. Using MDA-MB-231 breast cancer cells, we showed that the optimal size range of the gold nanoparticles for effective laser initiation of BOM is 30–40 nm and the lower concentration limit is n ≈ 2.44 × 10 11 cm –3 (i.e. the absolute number of particles homogeneously distributed inside a tumour cell is n ≈ 430). It was demonstrated that the formation of nanoclusters on the cell surface with sizes larger than the sizes of individual nanoparticles, may further increase the efficiency of the laser treatment of cancer.
A Ligand-Based Approach To Identify Quantitative Structure−Activity Relationships for the Androgen Receptor (2004)

We examined the three-dimensional quantitative structure-activity relationship (QSAR) of a group of endogenous and synthetic compounds for the androgen receptor (AR) using comparative molecular field analysis (CoMFA). The goal of these studies was to identify structural features necessary for high binding affinity and optimization of selective androgen receptor modulators (SARMs). A homology model of the AR was used as a scaffold to align six lead compounds that served as templates for alignment of the remaining 116 structures prior to CoMFA modeling. The conventional r(2) and cross-validated q(2) relating observed and predicted relative binding affinity (RBA) were 0.949 and 0.593, respectively. Comparison of predicted and observed RBA for a test set of 10 compounds resulted in an r(2) of 0.954, demonstrating the excellent predictive ability of the model. These integrated homology modeling and CoMFA studies identified critical amino acids for SARM interactions and provided QSAR data as the basis for mechanistic studies of AR structure, function, and design of optimized SARMs.
116 cases of coronary angina pectoris treated with powder composed of radix ginseng, radix notoginseng and succinum. (1997)

116 cases of coronary angina pectoris were treated with a powder composed of Radix Ginseng, Radix Notoginseng and Succinum, which was an empirical prescription of Dr. Yue Meizhong ([symbol: see text]), and compared with patients treated Fufang Danshen Tablet (a compound prescription of Radix Salviae Miltiorrhizae) as the control group. Results indicated that the curative effects and ECG in the treated group were better than that in the control group (P < 0.01), so were improvement of general symptoms, physical strength as well as changes of lipid metabolism and microcirculation of nail fold.
THE SQUAMOCOLUMNAR TRANSITIONAL ZONE OF THE CERVIX UTERI (1959)

Department of Obstetrics and Gynecology, Stanford University School of Medicine, San Francisco, California
High quality two-dimensional photonic crystal slab cavities (2001)

We have fabricated and characterized donor-mode nanocavities formed by a single defect cavity defined within a two-dimensional photonic crystal slab. Quantum dots emitting in the 1.1–1.3 micron range were used as luminescence sources, and a design using fractional edge dislocations was used to demonstrate well-confined dipole modes with high quality factors. By applying the fractional dislocation geometry, the measured quality factor could be increased to values as high as 2800. This compares with typical quality factors of around 1500 measured from more conventional shallow donor mode cavities with larger mode volumes.
Latent semantic models for collaborative filtering (2004)

Collaborative filtering aims at learning predictive models of user preferences, interests or behavior from community data, that is, a database of available user preferences. In this article, we describe a new family of model-based algorithms designed for this task. These algorithms rely on a statistical modelling technique that introduces latent class variables in a mixture model setting to discover user communities and prototypical interest profiles. We investigate several variations to deal with discrete and continuous response variables as well as with different objective functions. The main advantages of this technique over standard memory-based methods are higher accuracy, constant time prediction, and an explicit and compact model representation. The latter can also be used to mine for user communitites. The experimental evaluation shows that substantial improvements in accucracy over existing methods and published results can be obtained.
Effects of Conjugated Linoleic Acid (CLA) on Swine Performance and Body Composition (1998)

Market animals fed conjugated linoleic acid (CLA) could be leaner, have less fat and more muscle, and an increased rate of gain and improved feed efficiency. Improvement of these three production variables–improved lean, rate of gain, and feed efficiency–would offer significant economic advantages in swine production. Moreover, consumers would have available a leaner, more healthful meat product because consumption of the product could potentially help prevent obesity, cancer, and heart disease. Coupling both production efficiencies and the consumption of a more healthful meat product would mean significant enhancement economically for the pork industry. This project taken in total offers economic incentives to produce lean meat animals at the farm level and a more healthful product for consumption.
Ajulemic acid, a synthetic cannabinoid, increases formation of the endogenous proresolving and anti‐inflammatory eicosanoid, lipoxin A4 (2009)

Ajulemic acid (AjA), a synthetic nonpsychoactive cannabinoid, and lipoxin A(4) (LXA(4)), an eicosanoid formed from sequential actions of 5- and 15-lipoxygenases (LOX), facilitate resolution of inflammation. The purpose of this study was to determine whether the ability of AjA to limit the progress of inflammation might relate to an increase in LXA(4), a known anti-inflammatory and proresolving mediator. Addition of AjA (0-30 microM) in vitro to human blood and synovial cells increased production of LXA(4) (ELISA) 2- to 5-fold. Administration of AjA to mice with peritonitis resulted in a 25-75% reduction of cells invading the peritoneum, and a 7-fold increase in LXA(4) identified by mass spectrometry. Blockade of 12/15 LOX, which leads to LXA(4) synthesis via 15-HETE production, reduced (>90%) the ability of AjA to enhance production of LXA(4) in vitro. These results suggest that AjA and other agents that increase endogenous compounds that facilitate resolution of inflammation may be useful for conditions characterized by inflammation and tissue injury.