gebhart/patrepeval huggingface dataset:
Aryl Hydrocarbon Nuclear Translocator (ARNT) Promotes Oxygen-independent Stabilization of Hypoxia-inducible Factor-1α by Modulating an Hsp90-dependent Regulatory Pathway (2004)

Hypoxia-inducible factor-1 (HIF-1) is a potent cellular survival factor contributing to tumorigenesis in a broad range of cancers. The functional transcription factor exists as a heterodimeric complex consisting of HIF-1 and the aryl hydrocarbon receptor nuclear translocator (ARNT). Association of HIF-1 with ARNT is required for its activity; however, no other role has been ascribed to this interaction. We demonstrated previously that pharmacologic inhibition of Hsp90 by geldanamycin (GA) impairs HIF transcription and promotes VHL (Von Hippel-Lindau)-independent degradation of the protein, thus implicating Hsp90 as an essential interacting partner for HIF. In this study, we further explore the physiological role for Hsp90 in HIF function. We establish that the PAS (Per-ARNT-Sim) domain of HIF is required both to promote association with Hsp90 and confer sensitivity to GA. Coincidentally, this domain also associates with ARNT. Overexpression of ARNT in a VHLdeficient background resulted in substantially increased HIF-1 protein concomitant with increased protein stability. Conversely, down-regulation of endogenous ARNT protein by RNA interference decreased the steady-state HIF protein. ARNT-mediated stabilization of HIF is specific for the Hsp90-dependent pathway, as ARNT was unable to protect HIF from VHL-mediated degradation. We establish that the ability of ARNT to up-regulate HIF and diminish HIF sensitivity to GA is due to its ability to compete for the Hsp90 binding site on HIF. These data elucidate novel functions for ARNT and Hsp90 in regulating HIF function and further illustrate that cofactor association may significantly impact upon the sensitivity of Hsp90 clients to chaperone inhibitors.
Treatment of recurrent squamous cell carcinoma of the head and neck with low doses of lnterleukin-2 injected periiymphatically (1988)

Ten patients with recurrent squamous cell carcinoma of the head and neck received daily injections of interleukin-2 (IL-2) from the Jurkat T-cell line purified by high pressure liquid chromatography for 10 days. Two hundred units of IL-2 in 0.5 ml were injected 1.5 cm from the insertion of the sternocleidomastoid muscle on the mastoid. When possible, courses were repeated at 45-day intervals. IL-2 was ineffective in two patients who had already undergone functional or radical neck dissection. By contrast, in six patients with contralateral or bilateral cervical lymph nodes, complete or partial disappearance of the tumor was observed. The injections were occasionally followed by moderate local swelling and lymph node pain, but no systemic disturbances.
Spinal cord herniation after multilevel anterior cervical corpectomy and fusion for ossification of the posterior longitudinal ligament of the cervical spine (2009)

The authors report the case of a 52-year-old man who had undergone resection of an ossified posterior longitudinal ligament via the anterior approach. The patient experienced postoperative neurological deterioration that may have been caused by a massive cord herniation associated with a dural defect at the corpectomy site. Spinal cord herniation may develop as a complication of anterior cervical decompression. Surgeons should be alert to this condition when planning to treat cervical ossification of the ossified posterior longitudinal ligament via the anterior approach.
S-Benzoxazolyl (SBox) Glycosides as Novel, Versatile Glycosyl Donors for Stereoselective 1,2-Cis Glycosylation (2003)

[reaction: see text] Novel glycosyl donors, S-benzoxazolyl (SBox) glycosides, have been synthesized, tested toward various protecting group manipulations, and applied to the highly stereoselective 1,2-cis glycosylation. These compounds fulfill the requirements for a modern glycosyl donor such as accessibility, high stability toward protecting group manipulations, and mild activation conditions. It was also demonstrated that SBox glycosides withstand other glycosyl donor activation conditions and therefore allow selective glycosylations of O-pentenyl and thioglycosides.
Radical-mediated dehydration reactions in anaerobic bacteria (2005)

Most dehydratases catalyse the elimination of water from beta-hydroxy ketones, beta-hydroxy carboxylic acids or beta-hydroxyacyl-CoA. The electron-withdrawing carbonyl functionalities acidify the alpha-hydrogens to enable their removal by basic amino acid side chains. Anaerobic bacteria, however, ferment amino acids via alpha- or gamma-hydroxyacyl-CoA, dehydrations of which involve the abstraction of a beta-hydrogen, which is ostensibly non-acidic (pK ca. 40). Evidence is accumulating that beta-hydrogens are acidified via transient conversion of the CoA derivatives to enoxy radicals by one-electron transfers, which decrease the pK to 14. The dehydrations of (R)-2-hydroxyacyl-CoA to (E)-2-enoyl-CoA are catalysed by heterodimeric [4Fe-4S]-containing dehydratases, which require reductive activation by an ATP-dependent one-electron transfer mediated by a homodimeric protein with a [4Fe-4S] cluster between the two subunits. The electron is further transferred to the substrate, yielding a ketyl radical anion, which expels the hydroxyl group and forms an enoxy radical. The dehydration of 4-hydroxybutyryl-CoA to crotonyl-CoA involves a similar mechanism, in which the ketyl radical anion is generated by one-electron oxidation. The structure of the FAD- and [4Fe-4S]-containing homotetrameric dehydratase is related to that of acyl-CoA dehydrogenases, suggesting a radical-based mechanism for both flavoproteins.
Interactions among Bipolar Spheres in an Electrolytic Cell (1994)

The bipolar behavior of an arbitrary finite assemblage of spherical particles in an electrolytic cell is considered. The particles are allowed to differ in radius, in electric conductivity, and in electrochemical properties. A linear polarized electrode kinetics is assumed for the electrochemical reaction occurring at the particle surfaces. Using a boundary collocation technique, the governing equations for the electrical potential field are solved, and the interaction effects among the particles are calculated for various cases. The current enhancement factor of a particle is increased or decreased by the presence of a second neighboring particle, depending on the relative conductivities with respect to the surrounding medium, electrode reaction parameters, and orientation of the particles. The interaction effects between particles can be significant when the distance between particle surfaces approaches zero. The influence of particle interactions is stronger on the smaller particle than on the larger one. The current enhancement factors of linear chains of three spheres have been calculated, showing that the existence of the third particle can enhance the two‐particle interaction effect significantly. Finally, our numerical results for the interaction between two spheres are used to find the effect of volume fractions of particles of each type on the effective electric conductivity in a dilute dispersion.
Phase II study of mitomycin C and 5 fluorouracil in platinum resistant ovarian cancer. (1992)

Fourteen patients with relapsing ovarian cancer were treated with Mitomycin C (Mit C) and 5 Fluorouracil (5-FU). All but one patient (one responder) were defined as platinum resistant. The drug dosaging was Mit C 10 mg/m2 IV day 1 every 6 weeks, and 5-FU 500 mg/m2 IV days 1-3, every 3 weeks. Therapy was evaluated clinically and with ultrasound every 6 weeks. Toxicity was graded using the Gynecologic Oncology Group adverse criteria. All patients had been previously treated with platinum containing chemotherapeutic regimens with a mean cumulative total dose of 418 mg/m2 and 1308 mg/m2 of cisplatin and carboplatin, respectively. The mean time interval from completion of the last platinum containing regimen to entry in this study was 3.6 months. There were 4 responders, 1 complete, and 3 partial. The duration of the responses were 13 weeks for the complete responder, and 6, 6, and 12 weeks for the partial responders. No factor was identified which was predictive for response. Grade 3/4 granulocytopenia and thrombocytopenia were experienced by 43% and 21% of all patients respectively. Despite our documented response rate of 29%, the short duration of responses and high incidence of severe and life threatening hematologic toxicity preclude this regimen from being of any significant benefit to relapsing platinum resistant ovarian cancer patients.
Cellular Events Mediated by Lipopolysaccharide-stimulated Toll-like Receptor 4 (2000)

Lipopolysaccharide (LPS) stimulates multiple signaling events, including nuclear factor-kappaB (NF-kappaB) activity and the mitogen-activated protein (MAP) kinases, ERK, JNK, and p38 in LPS-responsive cells, resulting in transcriptional activation and cytokine generation. LPS-induced signaling via toll-like receptor 4 (TLR4) results in the activation of the transcription factor NF-kappaB. Since LPS activates other signaling cascades in responsive cells, the objective of this study was to determine whether such events are mediated by TLR4 in response to LPS. We generated human embryonic kidney cells (HEK293) that stably express TLR4 (HEK-TLR4) and examined their responsiveness to LPS by measuring NF-kappaB activity and production of interleukin-8 (IL-8). A trans-reporting system was used to measure the activity of Elk-1, an ETS-domain transcription factor targeted by MAP kinase pathways. LPS stimulated NF-kappaB reporter activity and IL-8 production but not Elk-1 activity in HEK-TLR4 cells. When MD-2, a protein associated with the extracellular domain of TLR4, was expressed in these cells, there was a marked increase in Elk-1 activity as well as ERK, JNK, and p38 MAP kinase phosphorylation in response to LPS. TLR4-mediated NF-kappaB reporter activity and IL-8 production was enhanced by the expression of MD-2. This study demonstrates that expression of both TLR4 and MD-2 is required for LPS to activate or augment the MAP kinase pathways, Elk-1 stimulation, and IL-8 generation.
Structural and Dynamic Aspects of the Sequence Specific Binding of Netropsin and Its Bis-Imidazole Analogue on the Decadeoxyribonucleotide d-[CGCAATTGCG]2 (1988)

High field 1H-NMR techniques have been used to examine the sequence dependent binding of a lexitropsin, the bis-imidazole analogue of netropsin 1, to the decadeoxyribonucleotide d-[CGCAATTGCG]2. The non-exchangeable and imino protons of the 1:1 lexitropsin:DNA complex are assigned by 1D-NOE difference and COSY methods. Addition of 1 to the DNA resulted in marked drug induced chemical shift changes of both the non-exchangeable and imino protons of A(4,5) and T(6,7). These results suggest that the lexitropsin is located in the minor groove along A(4) to T(7) of the DNA. Weaker chemical shift changes are observed for C(3) and G(8) which suggest that the bisimidazole moiety of 1 can also accept G.C sites. Specific NOEs seen between the lexitropsin (H2, H14 and H15) and DNA (AH2(4) and AH2(5] confirmed that the N to C-terminii of 1 is, on average, bound centrally to the sequence in the direction 5'-AATT-3'. However, netropsin 2 is shown to bind tightly only to the AATT sequence. Exchange NMR effects permit the estimate of the rate of exchange of the lexitropsin 1 between the two equivalent sites on the DNA to be approximately 160s and 24s for netropsin under comparable conditions. Several factors contributing to the sequence specificity of lexitropsin binding are discussed.
The ATPase activity of N-ethylmaleimide-sensitive fusion protein (NSF) is regulated by soluble NSF attachment proteins. (1994)

N-Ethylmaleimide-sensitive fusion protein (NSF) is an ATPase required in multiple stages of the secretory and endocytic pathways. NSF requires other proteins for its action in vesicular transport including the soluble NSF attachment proteins (SNAPs), which act to bind NSF to integral membrane proteins. We have investigated the ATPase activity of NSF and its modulation by alpha- and gamma-SNAPs using His6-tagged recombinant proteins. His6-NSF possessed ATPase activity, which was enhanced in a dose-dependent manner by immobilized (i.e. plastic-adsorbed) but not soluble His6-tagged SNAPs. NSF displayed complex enzyme kinetics consistent with the possession of two ATPase domains with different affinities for ATP. SNAPs apparently enhanced NSF ATPase activity primarily by decreasing the Km of its low affinity site 100-fold. In vivo this effect would be predicted to sensitize the low affinity site to physiological ATP concentrations. Thus SNAPs could act as a molecular switch by "turning on" the normally dormant low affinity ATPase site of NSF.
Very deep convolutional networks for end-to-end speech recognition (2017)

Sequence-to-sequence models have shown success in end-to-end speech recognition. However these models have only used shallow acoustic encoder networks. In our work, we successively train very deep convolutional networks to add more expressive power and better generalization for end-to-end ASR models. We apply network-in-network principles, batch normalization, residual connections and convolutional LSTMs to build very deep recurrent and convolutional structures. Our models exploit the spectral structure in the feature space and add computational depth without overfitting issues. We experiment with the WSJ ASR task and achieve 10.5% word error rate without any dictionary or language model using a 15 layer deep network.
Autophagic removal of micronuclei (2012)

Macroautophagy is known to participate in the quality control and turnover of cytoplasmic organelles, yet there is little evidence that macroautophagy targets nuclei in mammalian cells. Here, we investigated whether autophagy may target micronuclei, which arise as a result of deficient bipolar chromosome segregation in cells exposed to cell cycle perturbations. After removal of several distinct cell cycle blockers (nocodazole, cytochalasin D, hydroxyurea or SP600125), cells manifested an increase in the frequency of micronuclei (positive for histone H2B-RFP) as well as an increase in autophagic puncta (positive for GFP-LC3) over several days. A small but significant percentage of micronuclei co-localized with GFP-LC3 in autophagy-competent cells and this co-localization was lost after knockdown of ATG5 or ATG7. Electron microscopy analyses confirmed autophagic sequestration of micronuclei. "Autophagic micronuclei" (GFP-LC3+) were also decorated with p62/SQSTM1, while non-autophagic (GFP-LC3-) micronuclei where p62/SQSTM1 negative. In addition, GFP-LC3+ micronuclei exhibited signs of envelope degradation and γH2AX+ DNA damage foci, yet stained less intensively for chromatin markers, whereas GFP-LC3- micronuclei were surrounded by an intact envelope and rarely exhibited markers or DNA damage. These results indicate that micronuclei can be subjected to autophagic degradation. Moreover, it can be speculated that removal of micronuclei may contribute to the genome-stabilizing effects of autophagy.
A Chimeric Influenza Virus Expressing an Epitope of Outer Membrane Protein F ofPseudomonas aeruginosaAffords Protection against Challenge withP. aeruginosain a Murine Model of Chronic Pulmonary Infection (1998)

The ability of a chimeric influenza virus containing, within the antigenic B site of its hemagglutinin, an 11-amino-acid (AEGRAINRRVE) insert from the peptide 10 epitope of outer membrane (OM) protein F of Pseudomonas aeruginosa to serve as a protective vaccine against P. aeruginosa was tested by using the murine chronic pulmonary infection model. Mice immunized with the chimeric virus developed antibodies that reacted in an enzyme-linked immunosorbent assay with peptide 10, with purified protein F, and with whole cells of various immunotype strains of P. aeruginosa but failed to react with a protein F-deficient strain of P. aeruginosa. The chimeric-virus antisera reacted specifically with protein F alone when immunoblotted against proteins extracted from cell envelopes of each of the seven Fisher-Devlin immunotype strains and had significantly greater in vitro opsonic activity for P. aeruginosa than did antisera from wild-type influenza virus-immunized mice. Subsequent to intratracheal challenge with agar-encased cells of P. aeruginosa, chimeric-virus-immunized mice developed significantly fewer severe lung lesions than did control mice immunized with the wild-type influenza virus. Furthermore, the chimeric influenza virus-immunized group had a significantly smaller percentage of mice with >5 x 10(3) CFU of P. aeruginosa in their lungs upon bacterial quantitation than did the control group. These data indicate that chimeric influenza viruses expressing epitopes of OM protein F warrant continued development as vaccines to prevent pulmonary infections caused by P. aeruginosa.
Improvement of carrier diffusion length in silicon nanowire arrays using atomic layer deposition (2013)

To achieve a high-efficiency silicon nanowire (SiNW) solar cell, surface passivation technique is very important because a SiNW array has a large surface area. We successfully prepared by atomic layer deposition (ALD) high-quality aluminum oxide (Al2O3) film for passivation on the whole surface of the SiNW arrays. The minority carrier lifetime of the Al2O3-depositedSiNW arrays with bulk silicon substrate was improved to 27 μs at the optimum annealing condition. To remove the effect of bulk silicon, the effective diffusion length of minority carriers in the SiNW array was estimated by simple equations and a device simulator. As a result, it was revealed that the effective diffusion length in the SiNW arrays increased from 3.25 to 13.5 μm by depositing Al2O3 and post-annealing at 400°C. This improvement of the diffusion length is very important for application to solar cells, and Al2O3 deposited by ALD is a promising passivation material for a structure with high aspect ratio such as SiNW arrays.
Two paradigms of metabolic engineering applied to amino acid biosynthesis (1995)

Conference Article| May 01 1995 Two paradigms of metabolic engineering applied to amino acid biosynthesis T. W. Simpson; T. W. Simpson 1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar G. E. Colón; G. E. Colón 1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar G. Stephanopoulos G. Stephanopoulos * 1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, U.S.A. *To whom correspondence should be addressed. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1995) 23 (2): 381–387. https://doi.org/10.1042/bst0230381 Article history Received: November 16 1994 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation T. W. Simpson, G. E. Colón, G. Stephanopoulos; Two paradigms of metabolic engineering applied to amino acid biosynthesis. Biochem Soc Trans 1 May 1995; 23 (2): 381–387. doi: https://doi.org/10.1042/bst0230381 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: ASA, dl-aspartic-β-semialdehyde, CHR, chorismate, FCC, Flux Control Coefficient, G3P, glyceraldehyde 3-phosphate, G6P, glucose 6-phosphate, HD, homoserine dehydrogenase, HK, homoserine kinase, HS, homoserine, IPTG, isopropyl β-d-thiogalactoside, MCA, Metabolic Control Analysis This content is only available as a PDF. © 1995 Biochemical Society1995 Article PDF first page preview Close Modal You do not currently have access to this content.
Prostaglandin E2 Exerts Catabolic Effects in Osteoarthritis Cartilage: Evidence for Signaling via the EP4 Receptor (2008)

Elevated levels of PGE(2) have been reported in synovial fluid and cartilage from patients with osteoarthritis (OA). However, the functions of PGE(2) in cartilage metabolism have not previously been studied in detail. To do so, we cultured cartilage explants, obtained from patients undergoing knee replacement surgery for advanced OA, with PGE(2) (0.1-10 muM). PGE(2) inhibited proteoglycan synthesis in a dose-dependent manner (maximum 25% inhibition (p < 0.01)). PGE(2) also induced collagen degradation, in a manner inhibitable by the matrix metalloproteinase (MMP) inhibitor ilomastat. PGE(2) inhibited spontaneous MMP-1, but augmented MMP-13 secretion by OA cartilage explant cultures. PCR analysis of OA chondrocytes treated with PGE(2) with or without IL-1 revealed that IL-1-induced MMP-13 expression was augmented by PGE(2) and significantly inhibited by the cycolooygenase 2 selective inhibitor celecoxib. Conversely, MMP-1 expression was inhibited by PGE(2), while celecoxib enhanced both spontaneous and IL-1-induced expression. IL-1 induction of aggrecanase 5 (ADAMTS-5), but not ADAMTS-4, was also enhanced by PGE(2) (10 muM) and reversed by celecoxib (2 muM). Quantitative PCR screening of nondiseased and end-stage human knee OA articular cartilage specimens revealed that the PGE(2) receptor EP4 was up-regulated in OA cartilage. Moreover, blocking the EP4 receptor (EP4 antagonist, AH23848) mimicked celecoxib by inhibiting MMP-13, ADAMST-5 expression, and proteoglycan degradation. These results suggest that PGE(2) inhibits proteoglycan synthesis and stimulates matrix degradation in OA chondrocytes via the EP4 receptor. Targeting EP4, rather than cyclooxygenase 2, could represent a future strategy for OA disease modification.
Rapamycin Destabilizes Interleukin-3 mRNA in Autocrine Tumor Cells by a Mechanism Requiring an Intact 3′ Untranslated Region (1997)

We analyzed the effect of rapamycin on autocrine mast cell tumor lines with abnormally stable interleukin-3 (IL-3) transcripts due to a defect in mRNA degradation. Rapamycin inhibited IL-3 mRNA expression specifically, while transcripts of IL-4 and IL-6 were not affected. As indicated by the use of the transcriptional inhibitor actinomycin D or by reporter constructs, inhibition was posttranscriptional and resulted from destabilization of the mRNA. Transcripts from transgenes lacking the AU-rich 3' untranslated region were refractory to drug-induced degradation, suggesting that these 3' sequences contain the target of the rapamycin effect. Rapamycin did not promote IL-3 mRNA degradation in cells of a tumor variant lacking expression of FKBP12, the binding protein of rapamycin. Experiments with wortmannin indicated that rapamycin does not act via p70S6 kinase. FK-506, another ligand of FKBP12 affecting the phosphatase calcineurin, did not antagonize but shared the effect of rapamycin. Our data fit a model whereby both FKBP12 and calcineurin target an unknown regulator of IL-3 mRNA turnover.
Stochastic Response of Storage Function Model (2) (1997)

The observed rainfall is described as a random step function whose step height belongs to some stochastic process. On the other hand, the theoretical equations to calculate the first four moments of discharge require stochastic properties of rainfall defined as continuous function. In this paper, it is assumed that the observed rainfall is approximated by the first order autoregressive process. In this paper, authors strictly derive the auto-covariance function for rainfall defined as continuous function and theoretical equations which give the first four moments of discharge based on storage function model.