gebhart/patrepeval huggingface dataset:
Reactions and significance of cytochrome P-450 enzymes (1991)

complex has a characteristic absorption maximum (Soret band) near 450 nm due to axial ligation with a cysteine thiolate of the protein (with or without substrate present). This cysteine residue is present in a relatively well conserved region, -80% into the protein from the N terminus. Collectively there are thousands of potential substrates for the P-450s; each of the P-450s may have a rather strict limitation of catalytic specificity
Real time detection of DNA⋅RNA hybridization in living cells (1998)

Demonstrating hybridization between an antisense oligodeoxynucleotide and its mRNA target has proven to be extremely difficult in living cells. To address this fundamental problem in antisense research, we synthesized "molecular beacon" (MB) reporter oligodeoxynucleotides with matched fluorescent donor and acceptor chromophores on their 5' and 3' ends. In the absence of a complementary nucleic acid strand, the MB remains in a stem-loop conformation where fluorescence resonance energy transfer prevents signal emission. On hybridization with a complementary sequence, the stem-loop structure opens increasing the physical distance between the donor and acceptor moieties thereby reducing fluorescence resonance energy transfer and allowing a detectable signal to be emitted when the beacon is excited by light of the appropriate wavelength. Solution hybridization studies revealed that in the presence of a complementary strand targeted MB could yield up to a 60-fold increase in fluorescence intensity in comparison to control MB. By using a fluorescence microscope fitted with UV fluoride lenses, the detection limit of preformed MB/target sequence duplexes microinjected into cells was found to be >/=1 x 10(-1) ag of MB, or approximately 10 molecules of mRNA. On the basis of this exquisite sensitivity, real-time detection of MB/target mRNA hybridization in living cells was attempted by microinjecting MB targeted to the vav protooncogene, or control MB, into K562 human leukemia cells. Within 15 min, confocal microscopy revealed fluorescence in cells injected with targeted, but not control, MB. These studies suggest that real-time visualization and localization of oligonucleotide/mRNA interactions is now possible. MB could find utility in studying RNA processing, trafficking, and folding in living cells. We hypothesize that MB may also prove useful for finding targetable mRNA sequence under physiologic conditions.
Protein fold recognition using sequence‐derived predictions (1996)

In protein fold recognition, one assigns a probe amino acid sequence of unknown structure to one of a library of target 3D structures. Correct assignment depends on effective scoring of the probe sequence for its compatibility with each of the target structures. Here we show that, in addition to the amino acid sequence of the probe, sequence-derived properties of the probe sequence (such as the predicted secondary structure) are useful in fold assignment. The additional measure of compatibility between probe and target is the level of agreement between the predicted secondary structure of the probe and the known secondary structure of the target fold. That is, we recommend a sequence-structure compatibility function that combines previously developed compatibility functions (such as the 3D-1D scores of Bowie et al. [1991] or sequence-sequence replacement tables) with the predicted secondary structure of the probe sequence. The effect on fold assignment of adding predicted secondary structure is evaluated here by using a benchmark set of proteins (Fischer et al., 1996a). The 3D structures of the probe sequences of the benchmark are actually known, but are ignored by our method. The results show that the inclusion of the predicted secondary structure improves fold assignment by about 25%. The results also show that, if the true secondary structure of the probe were known, correct fold assignment would increase by an additional 8-32%. We conclude that incorporating sequence-derived predictions significantly improves assignment of sequences to known 3D folds. Finally, we apply the new method to assign folds to sequences in the SWISSPROT database; six fold assignments are given that are not detectable by standard sequence-sequence comparison methods; for two of these, the fold is known from X-ray crystallography and the fold assignment is correct.
Carcinoma-Associated Fibroblast–Like Differentiation of Human Mesenchymal Stem Cells (2008)

Carcinoma-associated fibroblasts (CAF) have recently been implicated in important aspects of epithelial solid tumor biology, such as neoplastic progression, tumor growth, angiogenesis, and metastasis. However, neither the source of CAFs nor the differences between CAFs and fibroblasts from nonneoplastic tissue have been well defined. In this study, we show that human bone marrow-derived mesenchymal stem cells (hMSCs) exposed to tumor-conditioned medium (TCM) over a prolonged period of time assume a CAF-like myofibroblastic phenotype. More importantly, these cells exhibit functional properties of CAFs, including sustained expression of stromal-derived factor-1 (SDF-1) and the ability to promote tumor cell growth both in vitro and in an in vivo coimplantation model, and expression of myofibroblast markers, including alpha-smooth muscle actin and fibroblast surface protein. hMSCs induced to differentiate to a myofibroblast-like phenotype using 5-azacytidine do not promote tumor cell growth as efficiently as hMSCs cultured in TCM nor do they show increased SDF-1 expression. Furthermore, gene expression profiling revealed similarities between TCM-exposed hMSCs and CAFs. Taken together, these data suggest that hMSCs are a source of CAFs and can be used in the modeling of tumor-stroma interactions. To our knowledge, this is the first report showing that hMSCs become activated and resemble carcinoma-associated myofibroblasts on prolonged exposure to conditioned medium from MDAMB231 human breast cancer cells.
In situhigh-pressure synchrotron x-ray diffraction study ofSc2W3O12at up to 10 GPa (2005)

${\mathrm{Sc}}_{2}{\mathrm{W}}_{3}{\mathrm{O}}_{12}$ is known to display both negative thermal expansion and significant ${\mathrm{Sc}}^{3+}$ conductivity. Monochromatic synchrotron x-ray powder diffraction was used to study ${\mathrm{Sc}}_{2}{({\mathrm{WO}}_{4})}_{3}$ at pressures up to 10 GPa in diamond anvil cells. Nitrogen and isopropanol were both used as pressure transmitting media. A phase transition from orthorhombic (Pnca) to monoclinic $(\mathrm{P}{2}_{1}∕a)$ symmetry was observed at $\ensuremath{\sim}0.3\phantom{\rule{0.3em}{0ex}}\mathrm{GPa}$ with a volume reduction of $\ensuremath{\sim}1.7%$. A second crystalline to crystalline phase transition was seen at $\ensuremath{\sim}2.8\phantom{\rule{0.3em}{0ex}}\mathrm{GPa}$. The latter was not reversible on decompression. The orthorhombic phase displays highly anisotropic compressibility, but that of the monoclinic phase is almost isotropic [orthorhombic in isopropanol ${\ensuremath{\beta}}_{\mathrm{a}}=6.32(16)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}3}\phantom{\rule{0.3em}{0ex}}{\mathrm{GPa}}^{\ensuremath{-}1}$, ${\ensuremath{\beta}}_{\mathrm{b}}=1.76(21)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}2}\phantom{\rule{0.3em}{0ex}}{\mathrm{GPa}}^{\ensuremath{-}1}$, ${\ensuremath{\beta}}_{\mathrm{c}}=6.84(32)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}3}\phantom{\rule{0.3em}{0ex}}{\mathrm{GPa}}^{\ensuremath{-}1}$; monoclinic in isopropanol ${\ensuremath{\beta}}_{\mathrm{a}}=1.85(3)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}2}\phantom{\rule{0.3em}{0ex}}{\mathrm{GPa}}^{\ensuremath{-}1}$, ${\ensuremath{\beta}}_{\mathrm{b}}=1.78(3)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}2}\phantom{\rule{0.3em}{0ex}}{\mathrm{GPa}}^{\ensuremath{-}1}$, ${\ensuremath{\beta}}_{\mathrm{c}}=1.69(9)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}2}\phantom{\rule{0.3em}{0ex}}{\mathrm{GPa}}^{\ensuremath{-}1}$]. ${\mathrm{Sc}}_{2}{({\mathrm{WO}}_{4})}_{3}$ is very soft even when compared to most other NTE phases. Fitting a Birch-Murnaghan equation of state to data from the experiment in isopropanol gave a bulk modulus $({K}_{0})$ of 31(3) for the orthorhombic and 14(1) GPa for the monoclinic phase. This reduction in bulk modulus at the phase transition and the reduction in volume per formula unit is almost entirely associated with changes in the orthorhombic $a$ and $c$ directions. The variation of ${b}_{\mathrm{ortho}}$ and its monoclinic equivalent lattice constant is essentially continuous through the transition. The pressure of the orthorhombic to monoclinic phase transition in ${A}_{2}{M}_{3}{\mathrm{O}}_{12}$ compounds does not have a strong dependence on the identity of the ${A}^{3+}$ cation. Amorphization did not occur in the pressure range studied.
First Fluorescent Photoinduced Electron Transfer (PET) Reagent for Hydroperoxides (2003)

A novel fluorescent reagent for hydroperoxides, 4-(2-diphenylphosphinoethylamino)-7-nitro-2,1,3-benzoxadiazole (1), was developed on the basis of the method for designing photoinduced electron transfer (PET) reagents having a benzofurazan skeleton. Compound 1 was quantitatively reacted with hydroperoxides to give its fluorescent derivative, 2. In acetonitrile, the Phi value (0.44) of 2 was 31 times greater than that of 1. The long excitation (458 nm) and emission (520 nm) wavelengths of 2 are suitable for the determination of hydroperoxides, especially in biosamples. [structure: see text]
Imprint/Photo Hybrid Lithography Using Conventional Contact Aligner (2004)

Fine patterns were fabricated by a combination of imprint lithography and photo-lithography using a conventional contact aligner. A resist film was pressed at an atmospheric pressure. Since it was difficult to press the mold mask onto the resist film completely, the residual resist was removed by a photolithography process. An image reversal process is used. It was important that the press was carried out on an unbaked resist. Patterns were exposed to a mercury lamp without a monochromatic filter during the atmospheric pressure press. After the photolithography no residual resist could be found. Good patterns can be obtained up to approximately 0.5 µm. A 0.35 µm line and 0.65 µm space pattern can also be fabricated, but the resist thickness of the fabricated pattern is less than the initial resist thickness.
Bone Morphogenetic Protein-4 Acts as an Ovarian Follicle Survival Factor and Promotes Primordial Follicle Development (2003)

The growth and development of follicles within the ovary are highly dependent on autocrine and paracrine signaling involving growth factors from granulosa cells, theca cells, stromal interstitial cells, and the oocytes. The growth factor bone morphogenetic protein-4 (BMP-4) and its receptor (BMPR-IB) have been detected in ovaries, and a mutation in BMPR-IB has been associated with abnormal ovulation rate. The objective of the current study was to examine the role that BMP-4 plays in the early stages of primordial follicle development. Ovaries from 4-day-old rats were placed into a whole-ovary organ culture system for 2 wk to investigate the effect that treatment with exogenous BMP-4 has on early follicle development. BMP-4-treated ovaries had a significantly higher proportion of developing primary follicles and fewer arrested primordial follicles than did untreated controls. This indicates that BMP-4 promotes primordial follicle development and the primordial-to-primary follicle transition. Ovaries were also treated with neutralizing antibody against BMP-4 to determine effects of removing endogenously produced BMP-4. Interestingly, ovaries treated with BMP-4 antibody were markedly smaller than controls. This was associated with a progressive loss of oocytes and primordial follicles, a progressive increase in cellular apoptosis, and an accompanying loss of normal ovarian tissue morphology over time. Immunocytochemistry localized BMP-4 protein to isolated stromal cell populations, selected stromal cells (i.e., pretheca cells) associated with developing primordial follicles, and the basement membrane of follicles. Ovaries were treated with BMP-4 and RNA collected after organ culture to determine whether BMP-4 signaling affects expression of other growth factors. Kit ligand and basic fibroblast growth factor expression was unchanged, but TGFalpha expression was decreased in whole ovaries. Taken together, these data suggest that BMP-4 plays an important role in promoting the survival and development of primordial follicles in the neonatal ovary.
Towards a real-time distributed systems annex in Ada (2001)

In this paper we address the problem of combining two issues that are standardized separately in two Ada 95 annexes: Real-Time Systems (Annex D) and Distributed Systems (Annex E). With these annexes it is possible to build applications with real-time requirements, or alternatively distributed applications; but real-time distributed applications are not directly supported. In this paper we propose extensions to the Distributed Systems Annex that would provide support for developing distributed real-time applications in Ada. The paper proposes an interface for assigning priorities to the messages in the interconnection networks, and also to the tasks executing remote operations, in a way that avoids priority inversions. It also addresses the issues of configuration of the RPC handler tasks and non blocking asynchronous remote procedure calls.
Machine translation : a view from the lexicon (1993)

so begins a preliminary discussion of translation divergences, such as the lexical-semantic categorial type as in the English I am hungry, in which the predicate hungry is adjectival, compared with the German Ich habe Hunger (&amp;apos;I have hunger&amp;apos;), in which the corresponding Hunger is nominal. Chapters 2 and 3 form the part dealing with the syntactic component. The former discusses the implementation of GB modules coupled with the parameters particular for each of English, Spanish, and German. The latter deals with the two-level morphological processor used in UNITRAN for analysis and generation. Chapter 4, the first in the part dealing with the lexical-semantic component, is to a large extent a variant of Dorr (1993a). It describes the interlingual representation of UNITRAN. The chosen interlingua is an extended version of LCS, used also as a representation of lexical entries. Dorr justifies this choice as follows: [It] is suitable to the task of translating between divergent struct
Mitigation of intra-channel nonlinearities using a frequency-domain Volterra series equalizer (2012)

We address the issue of intra-channel nonlinear compensation using a Volterra series nonlinear equalizer based on an analytical closed-form solution for the 3rd order Volterra kernel in frequency-domain. The performance of the method is investigated through numerical simulations for a single-channel optical system using a 20 Gbaud NRZ-QPSK test signal propagated over 1600 km of both standard single-mode fiber and non-zero dispersion shifted fiber. We carry on performance and computational effort comparisons with the well-known backward propagation split-step Fourier (BP-SSF) method. The alias-free frequency-domain implementation of the Volterra series nonlinear equalizer makes it an attractive approach to work at low sampling rates, enabling to surpass the maximum performance of BP-SSF at 2× oversampling. Linear and nonlinear equalization can be treated independently, providing more flexibility to the equalization subsystem. The parallel structure of the algorithm is also a key advantage in terms of real-time implementation.
Pulsed DC electric fields couple to natural NAD(P)H oscillations in HT-1080 fibrosarcoma cells (2001)

Previously, we have demonstrated that NAD(P)H levels in neutrophils and macrophages are oscillatory. We have also found that weak ultra low frequency AC or pulsed DC electric fields can resonate with, and increase the amplitude of, NAD(P)H oscillations in these cells. For these cells, increased NAD(P)H amplitudes directly signal changes in behavior in the absence of cytokines or chemotactic factors. Here, we have studied the effect of pulsed DC electric fields on HT-1080 fibrosarcoma cells. As in neutrophils and macrophages, NAD(P)H levels oscillate. We find that weak (approximately 10(-5) V/m), but properly phased DC (pulsed) electric fields, resonate with NAD(P)H oscillations in polarized and migratory, but not spherical, HT-1080 cells. In this instance, electric field resonance signals an increase in HT-1080 pericellular proteolytic activity. Electric field resonance also triggers an immediate increase in the production of reactive oxygen metabolites. Under resonance conditions, we find evidence of DNA damage in HT-1080 cells in as little as 5 minutes. Thus the ability of external electric fields to effect cell function and physiology by acting on NAD(P)H oscillations is not restricted to cells of the hematopoietic lineage, but may be a universal property of many, if not all polarized and migratory eukaryotic cells.
Orphan nuclear receptor Nurr1 directly transactivates the promoter activity of the tyrosine hydroxylase gene in a cell‐specific manner (2003)

Tyrosine hydroxylase (TH) catalyzes the first and rate-limiting step of catecholamine synthesis and its expression is necessary for neurotransmitter specification of all catecholaminergic neurons, while dopamine beta-hydroxylase (DBH) is essential for the noradrenergic phenotype. In the present study, we show that Nurr1, an orphan nuclear receptor critical for dopaminergic (DA) neuron development, directly transactivates the promoter activity of the TH gene in a cell type-dependent manner, while it does not regulate the DBH promoter. Consistent with these results, only the TH promoter contains multiple sequence motifs homologous to the known Nurr1-binding motif, NBRE. TH promoter deletional analysis indicates that < 1.0 kb upstream sequences, encompassing three NBRE-like motifs (i.e. NL1, NL2 and NL3) are mostly responsible for the effects of Nurr1. Among these potential motifs, site-directed mutational analysis showed that NL1, residing from - 35 to - 28 bp, was most critical for mediating the transactivation by Nurr1. Strikingly, however, both DNase I footprinting and electrophoretic mobility shift assays showed that NL3, but not NL1 or NL2, has high binding affinity to Nurr1. To determine whether the proximity of these motifs may be important for transactivation by Nurr1 in the transient transfection assay, we generated reporter gene constructs in which NL3 is immediately proximal to the TATA box. Indeed, NL3 was more efficient in this position than NL1 or NL2 for mediating the transactivation by Nurr1. Our results suggest that Nurr1 may play a direct role for specification of DA neurotransmitter identity by activating TH gene transcription in a cell context-dependent manner.
Enhancing Effect of IL-17 on IL-1-Induced IL-6 and Leukemia Inhibitory Factor Production by Rheumatoid Arthritis Synoviocytes and Its Regulation by Th2 Cytokines (1998)

IL-17 is a cytokine produced by CD4 T cells that activates the production of inflammatory mediators by synoviocytes. To study the contribution of soluble factors in the interaction between T cells and synoviocytes in rheumatoid arthritis (RA), we looked at the effect of IL-17 on these cells in the presence of cytokines classified as pro (IL-1)- and anti-inflammatory (IL-4, IL-13, IL-10). Both human rIL-1beta and rIL-17 induced IL-6 and leukemia inhibitory factor (LIF) production by synovial fibroblasts in a dose-dependent manner. After 7 days of culture, optimal concentrations of IL-1beta increased IL-6 (33-fold) and LIF (10-fold) production by synoviocytes, while IL-17 showed a lesser effect on IL-6 (17-fold) and LIF (4-fold) production. Using low concentrations of IL-17 and IL-1beta in combination, a synergistic effect was observed on the production of IL-6, whereas an additive effect was observed for LIF production. Production of biologically active IL-17 was demonstrated in RA synovium supernatants with the use of a blocking anti-IL-17 Ab. Both IL-4 and IL-13 had a modest stimulatory effect on IL-1- and IL-17-induced production of IL-6, but inhibited that of LIF. In contrast, IL-10 had a limited inhibitory effect on IL-6 production and no effect on that of LIF. These findings indicate that low levels of cytokines produced by monocytes (IL-1) and T cells (IL-17) can act together on synoviocytes. Thus, some RA synovium T cells producing IL-17 can activate mesenchymal cells leading to an increased proinflammatory pattern sensitive to Th2 cytokine regulation.
REGULATION AND EXPRESSION OF THE ADAPTIVE RESPONSE TO ALKYLATING AGENTS (1988)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Fine-Tuning Antitumor Responses Through the Control of Galectin–Glycan Interactions: An Overview (2010)

In recent years, we have witnessed critical advances in genomics and proteomics which contributed to delineate the "tumor progression signature". This includes the altered expression of genes and proteins not only in tumor cells, but also in tumor-associated stromal, endothelial, and immune cells. Adding more complexity to this bewildering information, efforts are being made to define the "glycosylation signature" of the tumor microenvironment, which results from the abnormal expression and activity of glycosyltransferases, glycosidases, and enzyme chaperons. The multiple combinatorial possibilities of glycan structures expressed by neoplastic versus normal tissue provide enormous potential for information display and expand potential therapeutic opportunities. The responsibility of deciphering the biological information encoded by the tumor-associated glycome is partially assigned, to distinct families of endogenous glycan-binding proteins or lectins, whose expression and function are regulated in cancerous tissues. Galectins, a family of evolutionarily conserved glycan-binding proteins, can control tumor progression by directly influencing tumor growth or by modulating cell migration, angiogenesis, and tumor-immune escape. In this review, we will highlight recent findings on how galectin-glycan lattices control the dialogue between tumor and immune cells and how these interactions could be exploited for therapeutic purposes.
The development of endometrial hyperplasia in aged PD-1-deficient female mice (2014)

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5809067461223905.