gebhart/patrepeval huggingface dataset:
siRNA Design Principles and Off-Target Effects (2013)

Short interfering RNAs (siRNAs) are a major research tool that allows for knock-down of target genes via selective mRNA destruction in almost all eukaryotic organisms. siRNAs typically consist of a synthetic ∼21 nucleotide (nt) RNA-duplex where one strand is designed with perfect complementarity to the target mRNA. Although siRNAs were initially thought to be very target-specific because of their design, it turned out during the last years that all siRNAs have a more or less pronounced intrinsic off-target activity which can make the interpretation of data from siRNA experiments difficult. Here we describe essential rules for siRNA design that should be taken into account in order to obtain potent siRNAs with minimal off-target activity. In addition, we describe how to control for off-target activity in siRNA experiments.
Tobramycin resistance of Pseudomonas aeruginosa cells growing as a biofilm on urinary catheter material (1985)

When disks of urinary catheter material were exposed to the flow of artificial urine containing cells of Pseudomonas aeruginosa, a thick adherent biofilm, composed of these bacteria and of their exopolysaccharide products, developed on the latex surface within 8 h. After this colonization, sterile artificial urine containing 1,000 micrograms of tobramycin per ml was flowed past this established biofilm, and a significant proportion of the bacterial cells within the biofilm were found to be still viable after 12 h of exposure to this very high concentration of aminoglycoside antibiotic. Planktonic (floating) cells taken from the test system just before the exposure of the biofilm to the antibiotic were completely killed by 50 micrograms of tobramycin per ml. The MIC of tobramycin for cells taken from the seeding cultures before colonization of the catheter material, and for surviving cells recovered directly from the tobramycin-treated biofilm, was found to be 0.4 micrograms/ml when dispersed cells were assayed by standard methods. These data indicate that growth within thick adherent biofilms confers a measure of tobramycin resistance on cells of P. aeruginosa.
NTCIR-5 Patent Retrieval Experiments at RICOH (2015)

Focusing on the IPC (International Patent Classi-cation) of patent, two retrieval methods were exam-ined. One is to use the IPC code of the query patent and the other is to exploit the codes assigned to top-N retrieved patents in a similar manner of pseudo-relevance feedback. In both methods, the codes were used as constraint on retrieval results. As a result, we found the former is clearly effective and the latter’s effect is positive but small. Another point of our ex-periments is exploitation of synonyms, which were au-tomatically collected from a machine-readable dictio-nary for each query term.
Issues on Building an MPI Cluster on Microblaze (2010)

MPI is the traditional paradigm to parallelize applications for High Performance Computing environments. AzequiaMPI is an implementation of the MPI-1.3 standard. Its thread-based architecture enables it to run on high-end HPC machines as well as on embedded environments as soft-core processor in FPGAs. This article describes the experience of building a maintainable cluster of fourteen popular Xilinx XUP2-Pro FPGA development boards around the PetaLinux/Micro blaze base. Figures on the AzequiaMPI performance are given.
Expression of an <i>engrailed</i>-related protein is induced in the anterior neural ectoderm of early <i>Xenopus</i> embryos (1989)

We have used a monoclonal antibody directed against the C-terminus of the Drosophila invected homeodomain to detect a nuclear protein in brain cells of Xenopus laevis embryos. We refer to this antigen as the Xenopus EN protein. The EN protein is localized at midneurula stage to a band of cells in the anterior portion of the neural plate, on each side of the neural groove. Later in development, the expression coincides with the boundary of the midbrain and hindbrain, and persists at least to the swimming tadpole stage. These properties make the EN protein an excellent molecular marker for anterior neural structures. In embryos where inductive interactions between mesodermal and ectodermal tissues have been perturbed, the expression of the EN protein is altered; in embryos that have been anterodorsalized by LiCl treatment, the region that expresses the EN protein is expanded, but still well organized. In ventralized UV-irradiated embryos, the absence of the protein is correlated with the absence of anterior neural structures. In extreme exogastrulae, where the contacts between head mesoderm and prospective neurectoderm are lost, the EN protein is not expressed.
Polymer Coatings for Optical Fibers (1985)

Optical fiber technology, developed during the 1970s, has ushered in the lightwave telecommunications era of the 1980s wherein the implementation of commercial systems has begun. The optical fiber, shown schematically in Figure 1, represents the medium over which light signals, consisting of streams of digital pulses that comprise voice, video, or data information, are transmitted. The fiber consists of a central core, usually composed of a highly transparent glass, and surrounded by cladding of lower refractive index that confines the light energy to propagate within the core by total internal reflection. The cladding material is commonly another glass, but polymer-clad fibers have also been developed for short to medium distance applications. The outstanding requirement for the glass core is high transparency so that light propagation will occur with very little energy loss by absorption or scattering processes. Losses below 0.5dB/km at selected transmission wavelengths have now been routinely achieved (1,
Enhancement of Hypoxia-Induced Tumor Cell Death <b> <i>In vitro</i> </b> and Radiation Therapy <b> <i>In vivo</i> </b> by Use of Small Interfering RNA Targeted to Hypoxia-Inducible Factor-1α (2004)

Hypoxia-inducible factor-1alpha (HIF-1alpha) is an important transcriptional factor that is activated when mammalian cells experience hypoxia, a tumor microenvironmental condition that plays pivotal roles in tumor progression and treatment. In this study, we examined the idea of down-regulating HIF-1alpha in tumor cells for therapeutic gain. We show that the expression levels of HIF-1alpha can be significantly attenuated by use of the recently established small interfering RNA technology in combination with adenovirus-mediated gene transfer. Down-regulation of the HIF-1alpha protein enhanced hypoxia-mediated tumor cell apoptosis in vitro. Subcutaneous tumor growth was also prevented from cells with attenuated HIF-1alpha expression. In addition, intratumoral injection of adenovirus encoding the HIF-1alpha-targeted small interfering RNA had a small but significant effect on tumor growth when combined with ionizing radiation. Therefore, our results provide proof of HIF-1alpha as an effective target for anticancer therapy. They also suggest that an adenovirus-based small interfering RNA gene transfer approach may be a potentially effective adjuvant strategy for cancer treatment.
Methotrexate chemosensitivity by ATP luminescence in human leukemia cell lines and in breast cancer primary cultures (1995)

Chemosensitivity assays are widely used to predict the ability of tumor cell lines to respond to potential or existing cytotoxic drugs. In this study we have compared the cell cloning assay first described by Salmon and Hamburger with a recently developed assay which measures viable cell number by ATP luminescence. Methotrexate (MTX) was chosen as the test agent, since cell lines with varying degrees of sensitivity to this agent were readily available. The results shown good correlation between the two assays, both of which are able to discriminate between the various cell lines used. MTX inhibition of primary breast carcinomas and cell lines shows a steep dose-response curve with a threshold concentration above which increasing dose does not increase sensitivity. In solid tumors, the plateau is usually reached at a level well below 100% inhibition. The ATP luminescence assay allows discrimination of MTX sensitivity between breast carcinomas and has considerable technical advantages over the cloning assay.
Inhibition and induction of CYP enzymes in humans: an update (2020)

The cytochrome P450 (CYP) enzyme family is the most important enzyme system catalyzing the phase 1 metabolism of pharmaceuticals and other xenobiotics such as herbal remedies and toxic compounds in the environment. The inhibition and induction of CYPs are major mechanisms causing pharmacokinetic drug-drug interactions. This review presents a comprehensive update on the inhibitors and inducers of the specific CYP enzymes in humans. The focus is on the more recent human in vitro and in vivo findings since the publication of our previous review on this topic in 2008. In addition to the general presentation of inhibitory drugs and inducers of human CYP enzymes by drugs, herbal remedies, and toxic compounds, an in-depth view on tyrosine-kinase inhibitors and antiretroviral HIV medications as victims and perpetrators of drug-drug interactions is provided as examples of the current trends in the field. Also, a concise overview of the mechanisms of CYP induction is presented to aid the understanding of the induction phenomena.
pTAC2, -6, and -12 Are Components of the Transcriptionally Active Plastid Chromosome That Are Required for Plastid Gene Expression (2005)

Transcription in plastids is mediated by a plastid-encoded multimeric (PEP) and a nuclear-encoded single-subunit RNA polymerase (NEP) and a still unknown number of nuclear-encoded factors. By combining gel filtration and affinity chromatography purification steps, we isolated transcriptionally active chromosomes from Arabidopsis thaliana and mustard (Sinapis alba) chloroplasts and identified 35 components by electrospray ionization ion trap tandem mass spectrometry. Eighteen components, called plastid transcriptionally active chromosome proteins (pTACs), have not yet been described. T-DNA insertions in three corresponding genes, ptac2, -6, and -12, are lethal without exogenous carbon sources. Expression patterns of the plastid-encoded genes in the corresponding knockout lines resemble those of Deltarpo mutants. For instance, expression of plastid genes with PEP promoters is downregulated, while expression of genes with NEP promoters is either not affected or upregulated in the mutants. All three components might also be involved in posttranscriptional processes, such as RNA processing and/or mRNA stability. Thus, pTAC2, -6, and -12 are clearly involved in plastid gene expression.
Combined optical and electronic analysis of cells with the AMAC transducers. (1977)

Free accessAbstractFirst published July 1977Combined optical and electronic analysis of cells with the AMAC transducers.R A Thomas, T A Yopp, […], B D Watson, D H Hindman, B F Cameron, S B Leif, R C Leif, L Roque, and W Britt+6-6View all authors and affiliationsVolume 25, Issue 7https://doi.org/10.1177/25.7.330732
Development of a long-life three-phase flywheel UPS using an electrolytic capacitorless converter/inverter (1999)

A long-life three-phase flywheel (FW) uninterruptible power supply (UPS) using an electrolytic capacitorless converter/inverter and a transformerless isolating system rating of 200 V and 5 kW–1min is described. The UPS has the following characteristics: (1) electrolytic capacitorless converter/inverter configuration for long life and smaller size (2) transformerless isolating system to realize small size and correct weight (3) batteryless system for maintenance-free long life of about 20 years The electrolytic capacitorless converter/inverter has a small-film capacitor value of 1/50 times of a conventional one. The converter/inverter is controlled by a current and voltage follow-up method using PWM control. Charging and discharging abilities of the FW energy is achieved only by controlling the instantaneous slip frequency of the induction machine. The UPS has obtained excellent test results, such as an input power factor of 99.8%, a small output voltage distortion of 1.03%, and 93.8% efficiency at full load. © 1999 Scripta Technica, Electr Eng Jpn, 127(3): 25–32, 1999
Predrill pore-pressure prediction using seismic data (2002)

Abstract A predrill estimate of pore pressure can be obtained from seismic velocities using a velocity-to–pore-pressure transform, but the seismic velocities need to be derived using methods having sufficient resolution for well planning purposes. For a deepwater Gulf of Mexico example, significant differences are found between the velocity field obtained using reflection tomography and that obtained using a conventional method based on the Dix equation. These lead to significant differences in the predicted pore pressure. Parameters in the velocity-to–pore-pressure transform are estimated using seismic interval velocities and pressure data from nearby calibration wells. The uncertainty in the pore pressure prediction is analyzed by examining the spread in the predicted pore pressure obtained using parameter combinations which sample the region of parameter space consistent with the available well data. If calibration wells are not available, the ideas proposed in this paper can be used with measurements made while drilling to predict pore pressure ahead of the bit based on seismic velocities.
Differentiation of Human Induced Pluripotent Stem Cells into Brown and White Adipocytes: Role of Pax3 (2013)

Identification of molecular mechanisms involved in generation of different types of adipocytes is progressing substantially in mice. However, much less is known regarding characterization of brown (BAP) and white adipocyte progenitors (WAPs) in humans, highlighting the need for an in vitro model of human adipocyte development. Here, we report a procedure to selectively derive BAP and WAPs from human-induced pluripotent stem cells. Molecular characterization of APs of both phenotypes revealed that BMP4, Hox8, Hoxc9, and HoxA5 genes were specifically expressed in WAPs, whereas expression of PRDM16, Dio2, and Pax3 marked BAPs. We focused on Pax3 and we showed that expression of this transcription factor was enriched in human perirenal white adipose tissue samples expressing UCP1 and in human classical brown fat. Finally, functional experiments indicated that Pax3 was a critical player of human AP fate as its ectopic expression led to convert WAPs into brown-like APs. Together, these data support a model in which Pax3 is a new marker of human BAPs and a molecular mediator of their fate. The findings of this study could lead to new anti-obesity therapies based on the recruitment of APs and constitute a platform for investigating in vitro the developmental origins of human white and brown adipocytes.
Glucocorticoid Receptor Recruitment of Histone Deacetylase 2 Inhibits Interleukin-1β-Induced Histone H4 Acetylation on Lysines 8 and 12 (2000)

We have investigated the ability of dexamethasone to regulate interleukin-1beta (IL-1beta)-induced gene expression, histone acetyltransferase (HAT) and histone deacetylase (HDAC) activity. Low concentrations of dexamethasone (10(-10) M) repress IL-1beta-stimulated granulocyte-macrophage colony-stimulating factor (GM-CSF) expression and fail to stimulate secretory leukocyte proteinase inhibitor expression. Dexamethasone (10(-7) M) and IL-1beta (1 ng/ml) both stimulated HAT activity but showed a different pattern of histone H4 acetylation. Dexamethasone targeted lysines K5 and K16, whereas IL-1beta targeted K8 and K12. Low concentrations of dexamethasone (10(-10) M), which do not transactivate, repressed IL-1beta-stimulated K8 and K12 acetylation. Using chromatin immunoprecipitation assays, we show that dexamethasone inhibits IL-1beta-enhanced acetylated K8-associated GM-CSF promoter enrichment in a concentration-dependent manner. Neither IL-1beta nor dexamethasone elicited any GM-CSF promoter association at acetylated K5 residues. Furthermore, we show that GR acts both as a direct inhibitor of CREB binding protein (CBP)-associated HAT activity and also by recruiting HDAC2 to the p65-CBP HAT complex. This action does not involve de novo synthesis of HDAC protein or altered expression of CBP or p300/CBP-associated factor. This mechanism for glucocorticoid repression is novel and establishes that inhibition of histone acetylation is an additional level of control of inflammatory gene expression. This further suggests that pharmacological manipulation of of specific histone acetylation status is a potentially useful approach for the treatment of inflammatory diseases.
Genetic alterations in streptomycin-resistant Mycobacterium tuberculosis: mapping of mutations conferring resistance (1994)

We report on the identification of mutations associated with streptomycin resistance in Mycobacterium tuberculosis. Two isolates (3656 and 3976) showed a wild-type ribosomal protein, S12, but exhibited a single point mutation at 16S rRNA position 491 (C-->T) or 512 (C-->T), respectively. Sequence analysis of a third isolate (2438) revealed a single base change at 16S rRNA position 904 (A-->G). This position is equivalent to invariant position 913 of the Escherichia coli 16S rRNA gene, an A-->G transition of which has been shown previously to impair streptomycin binding and streptomycin-induced misreading in vivo. Surprisingly, strain 2438 harbors an additional mutation in the ribosomal protein S12 (Lys-88-->Gln).
Controlled Synthesis and Luminescence of Lanthanide Doped NaYF<sub>4</sub> Nanocrystals (2007)

A range of nearly monodispersed NaYF4 single-crystal nanorods, hexagonal nanoplates, and nanoparticles have been successfully prepared via a facile wet chemical technology. Varying the dopants leads to different luminescence. These as-prepared nanocrystals not only present novel room-temperature downconversion (DC) and upconversion (UC) fluorescence but can also be transparently dispersed in cyclohexane. The effects of reaction temperature and time, doped ion concentration, ratio of NaF to Ln(NO3)3, and the reactant content on the shape, size, and crystal phase purity of the as-prepared nanocrystals have been investigated in detail. The fluorescence photos, spectra, luminescence mechanism, and the formation mechanism of the nanorods have also been demonstrated. For the next biolabel applications, the colloidal nanoparticles dispersed in cyclohexane have also been transferred into water by surface silane modification. For their unique DC and UC luminescence and high processability, these nanocrystals will open new avenues in biolabels, light-emitting diodes (LEDs), color displays, anti-counterfeiting, and solid-state lasers.
Interaction of the anthracycline 4'-iodo-4'-deoxydoxorubicin with amyloid fibrils: inhibition of amyloidogenesis. (1995)

All types of amyloidosis are structurally characterized by the cross beta-pleated sheet conformation of the fibrils, irrespective of their biochemical composition. The clinical observation that the anthracycline 4'-iodo-4'-deoxy-doxorubicin (IDOX) can induce amyloid resorption in patients with immunoglobulin light chain amyloidosis was the starting point for this investigation of its possible mechanism of action. IDOX binds strongly to all five types of natural amyloid fibrils tested: immunoglobulin light chains, amyloid A, transthyretin (methionine-30 variant), beta-protein (Alzheimer), and beta 2-microglobulin. Quantitative binding studies showed that IDOX, but not doxorubicin, binds strongly to amyloid fibrils. This binding is saturable and involves two apparently distinct binding sites with Kd values of 5.9 x 10(-11) M and 3.4 x 10(-9) M. IDOX inhibited in vitro insulin amyloid fibrillogenesis. In vivo studies using the experimental amyloid murine model confirmed the specific targeting of IDOX to amyloid deposits. Preincubation of amyloid enhancing factor with IDOX significantly reduced the formation of amyloid deposits. It is hypothesized that IDOX exerts its beneficial effects through the inhibition of fibril growth, thus increasing the solubility of existing amyloid deposits and facilitating their clearance. IDOX may represent the progenitor of a class of amyloid-binding agents that could have both diagnostic and therapeutic potential in all types of amyloidoses.
Fetal granulocytes in maternal venous blood detected by <i>in situ</i> hybridization (1992)

Fetal male cells from maternal venous blood were detected by a non-radioactive in situ hybridization method using the biotinylated Y-specific DNA probe pY431. The hybridizations were performed on Ficoll-Paque-isolated nucleated blood cells obtained from 11 pregnant women in the seventh to 31st week of gestation. A Y-specific signal was detected in both granulocytes and lymphocyte-like cells in seven of the 11 women studied. These women gave birth to boys. In one of the four remaining cases, a Y-specific signal was detected in the lymphocyte-like cells but not in the granulocytes. This woman gave birth to a girl. The other three women had no cells with a Y-specific signal and all three gave birth to girls. Altogether, 83,500 nucleated cells were analysed. One hundred and three cells showed a Y-specific signal. Of these Y-specific cells, 62 per cent were granulocytes and 38 per cent lymphocyte-like cells. Our results suggest that fetomaternal transfer of granulocytes is common and that it occurs as early as in the seventh week of gestation. None of the ten non-pregnant female control samples showed positive cells with the Y-chromosome-specific probe; approximately 97 per cent of the cells from the five adult male controls showed a Y-specific signal. Our results indicate that in situ hybridization using a Y-specific DNA probe performed on granulocytes in maternal blood can be used for fetal male sex determination.
Genetically Engineered Mouse Models of Pancreatic Cancer (2012)

Pancreatic ductal adenocarcinoma is the 10th most common cancer and the fourth leading cause of cancer-related death in the United States. Despite great effort, the prognosis for patients with this disease remains dismal with a 5-year survival rate of just 4% to 6%. Although several important advances have improved our understanding of the underlying biology of pancreatic cancer, this knowledge has not translated into novel therapeutic approaches and effective systemic or targeted therapies. Pancreatic cancer is one of the malignancies most difficult to treat, with remarkable intrinsic resistance to both standard and targeted chemotherapy as well as ionizing radiation. Surgical intervention remains the only potentially curative approach. However, most patients present with inoperable and/or metastatic disease and are therefore excluded from surgery. Accordingly, new therapeutic options are desperately needed. In vivo models to study innovative and alternative treatment approaches are of major importance. A variety of genetically engineered mouse models of pancreatic cancer have been developed over the last decade. However, these models display different characteristics, and not all of them are suited for preclinical studies. In this review, we aim to review the mouse models available, their experimental use, their clinical relevance and limitations, and future directions.