gebhart/patrepeval huggingface dataset:
Efficient isolation of specific genomic regions and identification of associated proteins by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using CRISPR (2013)

Isolation of specific genomic regions retaining molecular interactions is necessary for their biochemical analysis. Here, we established a novel method, engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP), for purification of specific genomic regions retaining molecular interactions. We showed that enChIP using the CRISPR system efficiently isolates specific genomic regions. In this form of enChIP, specific genomic regions are immunoprecipitated with antibody against a tag(s), which is fused to a catalytically inactive form of Cas9 (dCas9), which is co-expressed with a guide RNA (gRNA) and recognizes endogenous DNA sequence in the genomic regions of interest. enChIP-mass spectrometry (enChIP-MS) targeting endogenous loci identified associated proteins. enChIP using the CRISPR system would be a convenient and useful tool for dissecting chromatin structure of genomic regions of interest.
Thermo-responsive self-immolative nanoassemblies: direct and indirect triggering (2017)

A thermo-responsive end-cap based on a retro-Diels-Alder and subsequent furan elimination reaction was developed. It was used to cap poly(ethyl glyoxylate), allowing end-to-end depolymerization upon thermal triggering. Using block copolymers, thermo-responsive micelles and vesicles were prepared and shown to disassemble upon heating. Thermal degradation could also be triggered indirectly by magnetic field hyperthermia after incorporation of iron oxide nanoparticles into the assemblies.
Nucleic acid-based nanoengineering: novel structures for biomedical applications (2011)

Nanoengineering exploits the interactions of materials at the nanometre scale to create functional nanostructures. It relies on the precise organization of nanomaterials to achieve unique functionality. There are no interactions more elegant than those governing nucleic acids via Watson-Crick base-pairing rules. The infinite combinations of DNA/RNA base pairs and their remarkable molecular recognition capability can give rise to interesting nanostructures that are only limited by our imagination. Over the past years, creative assembly of nucleic acids has fashioned a plethora of two-dimensional and three-dimensional nanostructures with precisely controlled size, shape and spatial functionalization. These nanostructures have been precisely patterned with molecules, proteins and gold nanoparticles for the observation of chemical reactions at the single molecule level, activation of enzymatic cascade and novel modality of photonic detection, respectively. Recently, they have also been engineered to encapsulate and release bioactive agents in a stimulus-responsive manner for therapeutic applications. The future of nucleic acid-based nanoengineering is bright and exciting. In this review, we will discuss the strategies to control the assembly of nucleic acids and highlight the recent efforts to build functional nucleic acid nanodevices for nanomedicine.
Heterocyclic Ureas:  Inhibitors of Acyl-CoA:Cholesterol O-Acyltransferase as Hypocholesterolemic Agents (1996)

A series of diaryl-substituted heterocyclic ureas was prepared, and their ability to inhibit acyl-CoA: cholesterol O-acyltransferase (ACAT) in vitro and to lower plasma total cholesterol in cholesterol-fed animal models in vivo was examined. N-(2,6-Diisopropylphenyl)-N'-tetrazole or isoxazole-substituted heterocyclic ureas proved optimal. A carbon chain of 11-14 carbons substituted 1,3 with respect to the amine provided the optimal side chain. Substitution of the alkyl chain generally lowered activity. Tetrazole urea 2i dosed at 3 mg/kg lowered plasma total cholesterol (TC) 67% in an acute, cholesterol-fed (C-fed) rat model of hypercholesterolemia and 47% in C-fed dogs. Tetrazole 2i, dosed at 10 mg/kg, also lowered TC 52% and raised HDL cholesterol 113% in rats with pre-established hypercholesterolemia.
High-Mannose Glycans are Elevated during Breast Cancer Progression (2010)

Alteration in glycosylation has been observed in cancer. However, monitoring glycosylation changes during breast cancer progression is difficult in humans. In this study, we used a well-characterized transplantable breast tumor mouse model, the mouse mammary tumor virus-polyoma middle T antigen, to observe early changes in glycosylation. We have previously used the said mouse model to look at O-linked glycosylation changes with breast cancer. In this glycan biomarker discovery study, we examined N-linked glycan variations during breast cancer progression of the mouse model but this time doubling the number of mice and blood draw points. N-glycans from total mouse serum glycoproteins were profiled using matrix-assisted laser desorption/ionization Fourier transform-ion cyclotron resonance mass spectrometry at the onset, progression, and removal of mammary tumors. We observed four N-linked glycans, m/z 1339.480 (Hex(3)HexNAc), 1485.530 (Hex(3)HexNAc(4)Fuc), 1809.639 (Hex(5)HexNAc(4)Fuc), and 1905.630 (Man(9)), change in intensity in the cancer group but not in the control group. In a separate study, N-glycans from total human serum glycoproteins of breast cancer patients and controls were also profiled. Analysis of human sera using an internal standard showed the alteration of the low-abundant high-mannose glycans, m/z 1419.475, 1581.528, 1743.581, 1905.634 (Man(6-9)), in breast cancer patients. A key observation was the elevation of a high-mannose type glycan containing nine mannoses, Man(9), m/z 1905.630 in both mouse and human sera in the presence of breast cancer, suggesting an incompletion of the glycosylation process that normally trims back Man(9) to produce complex and hybrid type oligosaccharides.
Aligning two sequences within a specified diagonal band (1992)

We describe an algorithm for aligning two sequences within a diagonal band that requires only O(NW) computation time and O(N) space, where N is the length of the shorter of the two sequences and W is the width of the band. The basic algorithm can be used to calculate either local or global alignment scores. Local alignments are produced by finding the beginning and end of a best local alignment in the band, and then applying the global alignment algorithm between those points. This algorithm has been incorporated into the FASTA program package, where it has decreased the amount of memory required to calculate local alignments from O(NW) to O(N) and decreased the time required to calculate optimized scores for every sequence in a protein sequence database by 40%. On computers with limited memory, such as the IBM-PC, this improvement both allows longer sequences to be aligned and allows optimization within wider bands, which can include longer gaps.
Metabolic Engineering of Tropane Alkaloid Biosynthesis in Plants (2005)

Abstract: Over the past decade, the evolving commercial importance of so-called plant secondary metabolites has resulted in a great interest in secondary metabolism and, particularly, in the possibilities to enhance the yield of fine metabolites by means of genetic engineering. Plant alkaloids, which constitute one of the largest groups of natural products, provide many pharmacologically active compounds. Several genes in the tropane alkaloids biosynthesis pathways have been cloned, making the metabolic engineering of these alkaloids possible. The content of the target chemical scopolamine could be significantly increased by various approaches, such as introducing genes encoding the key biosynthetic enzymes or genes encoding regulatory proteins to overcome the specific rate-limiting steps. In addition, antisense genes have been used to block competitive pathways. These investigations have opened up new, promising perspectives for increased production in plants or plant cell culture. Recent achievements have been made in the metabolic engineering of plant tropane alkaloids and some new powerful strategies are reviewed in the present paper. ( Managing editor: Wei WANG)
Posterior sub-Tenon's injections of corticosteroids in uveitis patients with cystoid macular edema. (1988)

Cystoid macular edema (CME) is a major cause of visual impairment and is thought to be due to abnormal perifoveal capillary permeability. Posterior sub-Tenon's corticosteroid injections are used to improve the visual acuity in CME, although their mechanism of action is uncertain. In this study, visual acuity, blood retinal barrier (BRB) permeability, and fluorescein angiograms were recorded immediately before and one and four weeks after the administration of steroid injections. Ten patients (12 treated eyes) with CME secondary to uveitis were studied. Visual improvement, defined as an increase in at least two lines of Snellen visual acuity, was seen in half of the treated eyes. In some patients, these improvements were not directly related to changes in the BRB permeability or the amount of macular fluid. Posterior sub-Tenon's corticosteroid injections do not consistently affect blood retinal barrier permeability.
Development and evaluation of an in-house multimedia desktop conference system (1990)

An in-house computer-supported desk-to-desk conference system that allows a group of users to conduct a meeting in real time from their telephone-attached personal computers is described. Participants can jointly view and edit relevant multimedia information, including text, graphics, images, and handwritten information distributed through a local area network. Participants can also simultaneously communicate by voice to discuss the information they are sharing. The system's design principle, i.e. the group communication architecture, and the protocol for conference coordination are discussed. The system configuration, service functions, and related control mechanisms are presented. User experiences and the results of feasibility evaluations are examined. The system has proved to be applicable to a wide variety of cooperative work, such as distributed software development, joint authoring, and group decision support.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Palladium‐Catalyzed Asymmetric Allylation of Prochiral Nucleophiles: Synthesis of 3‐Allyl‐3‐Aryl Oxindoles (2004)

Excellent yields and enantioselectivies are attained in the synthesis of 3-alkyl-3-aryl oxindoles based on the Pd-catalyzed asymmetric allylic alkylation (AAA) reaction. This approach utilizes a nonbasic hydroxylic additive in the transformation of 3-aryl oxindoles into complex, synthetically valuable oxindoles (see scheme). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z460335_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The Important Molecular Markers on Chromosome 17 and Their Clinical Impact in Breast Cancer (2011)

Abnormalities of chromosome 17 are important molecular genetic events in human breast cancers. Several famous oncogenes (HER2, TOP2A and TAU), tumor suppressor genes (p53, BRCA1 and HIC-1) or DNA double-strand break repair gene (RDM1) are located on chromosome 17. We searched the literature on HER2, TOP2A, TAU, RDM1, p53, BRCA1 and HIC-1 on the Pubmed database. The association of genes with chromosome 17, biological functions and potential significance are reviewed. In breast cancer, the polysomy 17 (three or more) is the predominant numerical aberration. HER2 amplification is widely utilized as molecular markers for trastuzumab target treatment. Amplified TOP2A, TAU and RDM1 genes are related to a significant response to anthracycline-based chemotherapy, taxane or cisplatin, respectively. In contrast, p53, BRCA1 and HIC-1 are important tumor suppressor genes related to breast carcinogenesis. This review focused on several crucial molecular markers residing on chromosome 17. The authors consider the somatic aberrations of chromosome 17 and associated genes in breast cancer.
On-line Q-learning Using Connectionist Systems (1994)

Reinforcement learning algorithms are a powerful machine learning technique. However, much of the work on these algorithms has been developed with regard to discrete finite-state Markovian problems, which is too restrictive for many real-world environments. Therefore, it is desirable to extend these methods to high dimensional continuous state-spaces, which requires the use of function approximation to generalise the information learnt by the system. In this report, the use of back-propagation neural networks (Rumelhart, Hinton and Williams 1986) is considered in this context. We consider a number of different algorithms based around Q-Learning (Watkins 1989) combined with the Temporal Difference algorithm (Sutton 1988), including a new algorithm (Modified Connectionist Q-Learning), and Q() (Peng and Williams 1994). In addition, we present algorithms for applying these updates on-line during trials, unlike backward replay used by Lin (1993) that requires waiting until the end of each t...
Immunoglobulin Production: Method for Quantitatively Detecting Variant Myeloma Cells (1970)

Mouse myeloma cells in continuous culture were cloned in soft agar. The clones were assayed for their ability to synthesize heavy and light chains of gamma globulin by immunoprecipitation directly in the agar. A minor population secreting only light chains was identified. The two cell types were recloned and a low incidence of conversion of 7S to light-chain production was demonstrated. This technique can be used to isolate rare variants of cells secreting specific macromolecules.
Phosphatidylinositol 3-Kinase and NF-κB/Rel Are at the Divergence of CD40-Mediated Proliferation and Survival Pathways (2000)

CD40 receptor ligation evokes several crucial outcomes for the fate of an activated B cell, including proliferation and survival. Although multiple signaling molecules in the CD40 pathways have been identified, their specific roles in regulating proliferation and maintaining cell viability are still obscure. In this report, we demonstrate that the activation of both phosphatidylinositol 3-kinase (PI-3K) and NF-kappaB/Rel transcription factors is crucial for CD40-mediated proliferation. Furthermore, our data indicate that PI-3K is indispensable for CD40-mediated NF-kappaB/Rel activation. This is achieved via activation of AKT and the degradation of IkappaBalpha. Furthermore, we show that PI-3K activity is necessary for the degradation of cyclin-dependent kinase inhibitor p27kip. Therefore, both of these events comprise the mechanism by which PI-3K controls cell proliferation. In contrast to the absolute requirement of PI-3K and NF-kappaB/Rel for proliferation, these signaling molecules are only partially responsible for CD40-mediated survival, as blocking of PI-3K activity did not lead to apoptosis of anti-CD40-treated cells. However, the PI-3K/NF-kappaB pathway is still required for CD40-induced Bcl-X gene expression. Taken together, our data indicate that multiple survival pathways are triggered via this receptor, whereas NF-kappaB/Rel and PI-3K are crucial for CD40-induced proliferation.
The Effects of Frequent Nonoxynol-9 Use on the Vaginal and Cervical Mucosa (1991)

The authors conducted a single-dose phase I local toxicity study of the effects of frequent insertion of nonoxynol-9 (N-9) on the lower genital tract to determine whether a phase II dose-ranging study is warranted. Fourteen women used 150 mg of N-9 cumulatively four times a day for 14 days. Epithelial disruption of the cervix and vagina, the main outcome of interest, occurred in 43% (95% CI, 18-71%) of women on this high-frequency use schedule. None of the women experienced symptoms that prompted them to discontinue the study. This preliminary study indicates that a phase II study to examine the local toxicity of different use schedules is needed to provide further safety information about the use of N-9.
Multiple sclerosis flares associated with recombinant granulocyte colony-stimulating factor (2000)

Four of 10 patients who were enrolled on protocols of high-dose immunosuppression with peripheral blood stem cell rescue for MS experienced neurologic worsening while receiving recombinant human granulocyte colony-stimulating factor. There was improvement when methylprednisolone was given to three of the patients, but one patient died of respiratory failure. The mechanism of the neurologic worsening is uncertain.
Process issue improvement of surface image transfer technique: Depth-of-focus characteristics and their comparison with simulation results (1993)

There are several disadvantages concerning surface image transfer technique for contact hole fabrication in KrF excimer laser lithography utilizing absorbing photoresist SAL601 (Shipley, chemically amplified negative type). A long development time (MF622, Shipley, 10 min) is the first disadvantage, but this can be improved by using concentrated developer (MF312-CD38, Shipley) without loss of focus margin. Pattern transfer thicknesses limited to an oxide layer of less than 0.2 μm is the second disadvantage, but this can be improved to a thickness of 0.8 μm by using more anisotropic etching conditions. Small depth of focus (DOF) is the third and the most critical disadvantage, and this can be improved by employing low numerical aperture (NA) and high σ (coherency factor) exposure conditions (NA=0.35, σ=0.9). Comparison between the DOF characteristics for a 0.4 μm contact hole using SAL601 and a two-dimensional photointensity simulation has resulted in a simple metric to predict the DOF by mask edge intensity loss from perfect focus to defocus. Although the correlation between the loss and the DOF is weak, the loss is ∼0.025–0.045. The observed DOF results for 0.35 and 0.32 μm contact holes were in the range of the prediction obtained by the metric except NA=0.45 and σ=0.3 with 0.35 μm contact hole case.
Magnetic resonance imaging of convection in laser-polarized xenon (2000)

We demonstrate nuclear magnetic resonance (NMR) imaging of the flow and diffusion of laser-polarized xenon (129Xe) gas undergoing convection above evaporating laser-polarized liquid xenon. The large xenon NMR signal provided by the laser-polarization technique allows more rapid imaging than one can achieve with thermally polarized gas-liquid systems, permitting shorter time-scale events such as rapid gas flow and gas-liquid dynamics to be observed. Two-dimensional velocity-encoded imaging shows convective gas flow above the evaporating liquid xenon, and also permits the measurement of enhanced gas diffusion near regions of large velocity variation.
Multitubular reactors with immobilized L-phenylalanine ammonia-lyase for use in extracorporeal shunts. (1980)

Hollow fiber cartridges of improved design have been loaded with L-phenylalanine ammonia-lyase [EC 4.3.1.5.] from Rhodotorula glutinis in order to prepare multitubular enzyme reactors for removal of L-phenylalanine from blood. The kinetics of the enzyme in free solution was investigated and the results showed a behavior similar to that reported for L-phenylalanine ammonia-lyase from other sources. On the other hand kinetic data with the reactors were obtained in a recirculating system by measuring the increase in trans-cinnamate concentration in the perfusate. The effect of changing the enzyme load in the hollow fiber cartridge, the length of the cartridge, the substrate concentration, pH as well as the flow rate and the temperature have been investigated. The results showed that the overall kinetics of the enzymic reaction in the multitubular reactor is not the same as that in free solution and the difference can be attributed to diffusion resistances in the hollow fiber system.
Direct measurement of oligonucleotide substrate binding to wild-type and mutant ribozymes from Tetrahymena. (1990)

Like protein enzymes, RNA enzymes (ribozymes) provide specific binding sites for their substrates. We now show that equilibrium dissociation constants for complexes between the Tetrahymena ribozyme and its RNA substrates and products can be directly measured by electrophoresis in polyacrylamide gels containing divalent cations. Binding is 10(3)- to 10(4)-fold tighter (4-5 kcal/mol at 42 degrees C) than expected from base-pairing interactions alone, implying that tertiary interactions also contribute to energetic stabilization. Binding decreases with single base changes in the substrate, substitution of deoxyribose sugars, and lower Mg2+ concentration. Ca2+, which enables the ribozyme to fold but is unable to mediate efficient RNA cleavage, promotes weaker substrate binding than Mg2+. This indicates that Mg2+ has special roles in both substrate binding and catalysis. Mutagenesis of a region near the internal guide sequence disrupts substrate binding, whereas binding is not significantly affected by a mutation of the guanosine-binding site. This approach should be generally useful for analysis of ribozyme variants independent of their catalytic activities.
Unbounded page-based transactional memory (2006)

Exploiting thread level parallelism is paramount in the multicore era. Transactions enable programmers to expose such parallelism by greatly simplifying the multi-threaded programming model. Virtualized transactions (unbounded in space and time) are desirable, as they can increase the scope of transactions' use, and thereby further simplify a programmer's job. However, hardware support is essential to support efficient execution of unbounded transactions. In this paper, we introduce Page-based Transactional Memory to support unbounded transactions. We combine transaction bookkeeping with the virtual memory system to support fast transaction conflict detection, commit, abort, and to maintain transactions' speculative data.
Reconstruction of Endometrium from Human Endometrial Side Population Cell Lines (2011)

Endometrial regeneration is mediated, at least in part, by the existence of a specialized somatic stem cell (SSC) population recently identified by several groups using the side population (SP) technique. We previously demonstrated that endometrial SP displays genotypic, phenotypic and the functional capability to develop human endometrium after subcutaneous injection in NOD-SCID mice. We have now established seven human endometrial SP (hESP) cell lines (ICE 1-7): four from the epithelial and three from the stromal fraction, respectively. SP cell lines were generated under hypoxic conditions based on their cloning efficiency ability, cultured for 12-15 passages (20 weeks) and cryopreserved. Cell lines displayed normal 46XX karyotype, intermediate telomerase activity pattern and expressed mRNAs encoding proteins that are considered characteristic of undifferentiated cells (Oct-4, GDF3, DNMT3B, Nanog, GABR3) and those of mesodermal origin (WT1, Cardiac Actin, Enolase, Globin, REN). Phenotype analysis corroborated their epithelial (CD9+) or stromal (vimentin+) cell origin and mesenchymal (CD90+, CD73+ and CD45⁻) attributes. Markers considered characteristic of ectoderm or endoderm were not detected. Cells did not express either estrogen receptor alpha (ERα) or progesterone receptor (PR). The hESP cell lines were able to differentiate in vitro into adipocytes and osteocytes, which confirmed their mesenchymal origin. Finally, we demonstrated their ability to generate human endometrium when transplanted beneath the renal capsule of NOD-SCID mice. These findings confirm that SP cells exhibit key features of human endometrial SSC and open up new possibilities for the understanding of gynecological disorders such as endometriosis or Asherman syndrome. Our cell lines can be a valuable model to investigate new targets for endometrium proliferation in endometriosis.