gebhart/patrepeval huggingface dataset:
Diversity in the mechanisms of gene regulation by estrogen receptors (2002)

The sequencing of the human genome has opened the way for using bioinformatics to identify sets of genes controlled by specific regulatory signals. Here, we review the unexpected diversity of DNA response elements mediating transcriptional regulation by estrogen receptors (ERs), which control the broad physiological effects of estrogens. Consensus palindromic estrogen response elements are found in only a few known estrogen target genes, whereas most responsive genes contain only low-affinity half palindromes, which may also control regulation by other nuclear receptors. ERs can also regulate gene expression in the absence of direct interaction with DNA, via protein-protein interactions with other transcription factors or by modulating the activity of upstream signaling components, thereby significantly expanding the repertoire of estrogen-responsive genes. These diverse mechanisms of action must be taken into account in screening for potential estrogen-responsive sequences in the genome or in regulatory regions of target genes identified by expression profiling.
Rapid detection of the pandemic 2009 H1N1 virus M gene by real‐time and gel‐based RT‐PCR assays (2010)

The newly developed pH1N1-specific real-time and gel-based RT-PCR assays can be used to detect and differentiate the pH1N1 virus from currently circulating SIVs in North America. We suggest a combinational diagnostic approach where the real-time RT-PCR is used for high-throughput detection of influenza positive or suspect samples and the gel-based RT-PCR for confirmation and sequencing of the M-gene.
Possible contribution of CD44 variant 6 and nuclear ?-catenin expression to the formation of budding tumor cells in patients with T1 colorectal carcinoma (2001)

The current results suggest that the up-regulation of CD44 variant 6 through nuclear beta-catenin activation may contribute to the formation of tumor budding, and immunostaining of these two adhesion molecules may be useful in identifying those at high-risk for locoregional failure among patients with T1 colorectal carcinoma.
Effect of a noninvasive ventilatory support during exercise of a program in pulmonary rehabilitation in patients with COPD. (2007)

We conclude that IPS delivered by nasal mask can improve exercise tolerance and dyspnea in stable severe COPD patients and hence this mode of ventilatory support may be useful in respiratory rehabilitation programs.
Pathways of ubiquitin conjugation (1997)

The covalent attachment of the polypeptide ubiquitin to proteins marks them for degradation by the ubiquitin/26S proteasome-dependent degradation pathway. This pathway functions in regulating many fundamental processes required for cell viability. Phylogenetic analysis of ubiquitin sequences reveals greater variability among lower eukaryotes and defines essential residues, many of which are conserved among the three ubiquitin-like proteins known to undergo parallel ligation pathways. The hierarchical design of the ubiquitin conjugation mechanism provides great flexibility for the divergent evolution of new functions mediated by this posttranslational modification. Within this hierarchy, a single ubiquitin-activating enzyme provides charged intermediates to multiple targeting pathways defined by cognate ubiquitin carrier protein (E2)/ligase (E3) pairs. Sequence analysis of E2 isozymes shows that the E2 superfamily is composed of distinct function-specific families. The apparent lack of E2/E3 specificity suggested in the literature results from the presence of multiple isozymes within many E2 families and erroneous family assignments based on incomplete data sets. Other apparent inconsistencies are explained by interfamily sequence relationships among some E2 isoforms.
Codon Pair Utilization Biases Influence Translational Elongation Step Times (1995)

Two independent assays capable of measuring the relative in vivo translational step times across a selected codon pair in a growing polypeptide in the bacterium Escherichia coli have been employed to demonstrate that codon pairs observed in protein coding sequences more frequently than predicted (over-represented codon pairs) are translated slower than pairs observed less frequently than expected (under-represented codon pairs). These results are consistent with the findings that translational step times are influenced by codon context and that these context effects are related to the compatabilities of adjacent tRNA isoacceptor molecules on the surface of a translating ribosome. These results also support our previous suggestion that the frequency of one codon next to another has co-evolved with the structure and abundance of tRNA isoacceptors in order to control the rates of translational step times without imposing additional constraints on amino acid sequences or protein structures.
Preferential production of the IL‐12(p40)/IL‐23(p19) heterodimer by dendritic cells from human newborns (2005)

Abstract Human newborns present impaired T helper type 1 cell responses, associated with a defect in the synthesis of IL‐12 by dendritic cells (DC). IL‐23 is a heterodimeric cytokine structurally related to IL‐12, implicated in protective and autoimmune responses. We recently showed that upon activation neonatal T cells up‐regulate a functional IL‐23 receptor and that this cytokine polarizes the differentiation of naive T cells. We therefore investigated the capacity of neonatal DC to secrete IL‐23. Lipopolysaccharide (LPS) stimulation induced the transcription of IL‐23(p19) mRNA in both adult and neonatal DC, in sharp contrast to the repressed IL‐12(p35) gene expression observed in neonatal cells. In comparison to adult DC, neonatal DC produced similar levels of IL‐23 protein, in reponse to Toll‐like receptor (TLR)‐2‐ and TLR‐3 ligands, and higher levels in response to TLR‐4‐ or TLR‐8 ligands. The same profile was observed in neonatal mononuclear cells. The supernatant of LPS‐stimulated DC induced the secretion of IL‐17 by polyclonally activated neonatal CD8 + T cells, confirming the IL‐23 bioactivity. Altogether, these observations strongly suggest that IL‐23 could play a role in the immune system of human newborns. In particular, a functional IL‐23/IL‐17 axis might compensate a suboptimal IL‐12/IFN‐γ pathway in early life.
Intercellular communication and maintenance of islet cell mass--implications for islet transplantation. (1993)

Pancreatic duct epithelium can stimulate islet cell proliferation in a paracrine manner.
Genomic divergence of an HIV-2 from a German AIDS patient probably infected in Mali (1990)

The complete nucleotide sequence of an HIV-2 isolate derived from a German AIDS patient with predominantly neurological symptoms is reported. The HIV-2BEN sequence is highly divergent from those of previously described HIV-2 and SIV strains. Evolutionary tree analysis of eight HIV-2 sequences reveals the existence of three HIV-2 groups. HIV-2BEN belongs to a group with two isolates from Ghana and The Gambia. Based on a comparison of HIV-2BEN with six HIV-2 isolates, SIVsmm and SIVmac, the variability of the structural env and gag proteins is similar within the HIV-2/SIVsmm/mac and HIV-1 groups. In contrast, the regulatory HIV-1 proteins are more highly conserved than those from HIV-2 strains. Multiple sequence alignments reveal that some domains of the envelope and regulatory proteins are well conserved among HIV-1, HIV-2/SIVsmm/mac, SIVagm and SIVmnd. The identification of conserved domains within the external glycoprotein could help to develop broadly active vaccines.
Equivalent circuits for electrically small antennas using LS-decomposition with the method of moments (1989)

As part of an investigation into methods for accelerating the process of filling the method-of-moments impedance matrix (Z), it was found that (Z) could be decomposed into three parts: a real inductance matrix (L) from the magnetostatic vector potential, a real elastance matrix (S) from the electrostatic static scalar potential, and a complex impedance matrix (z( omega )) of residual frequency-dependent contributions. By neglecting (z( omega )) at sufficiently low frequencies, static and quasi-static charge and current distributions were obtained. For electrically small antennas, a complete RLC circuit was obtained directly from a single quasi-static solution rather than as an approximate characterization of the impedance as a function of frequency. This gives a precise definition of the circuit parameters limiting the performance of electrically small antennas.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Self-immolative linkers in polymeric delivery systems (2010)

There has been significant interest in the methodologies of controlled release for a diverse range of applications spanning drug delivery, biological and chemical sensors, and diagnostics. The advancement in novel substrate-polymer coupling moieties has led to the discovery of self-immolative linkers. This new class of linker has gained popularity in recent years in polymeric release technology as a result of stable bond formation between protecting and leaving groups, which becomes labile upon activation, leading to the rapid disassembly of the parent polymer. This ability has prompted numerous studies into the design and development of self-immolative linkers and the kinetics surrounding their disassembly. This review details the main concepts that underpin self-immolative linker technologies that feature in polymeric or dendritic conjugate systems and outlines the chemistries of amplified self-immolative elimination.
Triple hydroxylation of tetracenomycin A2 to tetracenomycin C in Streptomyces glaucescens. Overexpression of the tcmG gene in Streptomyces lividans and characterization of the tetracenomycin A2 oxygenase. (1994)

Nucleotide sequence analysis of the tcmG gene has suggested that the TcmG protein is responsible for the triple-hydroxylation of tetracenomycin (Tcm) A2 to Tcm C in Streptomyces glaucescens (Decker, H., Motamedi, H., and Hutchinson, C.R. (1993) J. Bacteriol. 175, 3876-3886). The heterologous expression of the tcmG gene in Streptomyces lividans and the purification and characterization of TcmG protein, which we have named Tcm A2 oxygenase, are described here. NH2-terminal amino acid analysis of the purified enzyme led to the revision of the translational start site of tcmG to a TTG, 33 base pairs downstream of the GTG site assigned initially on the basis of nucleotide sequence analysis. Tcm A2 oxygenase is a monomeric protein in solution and contains 1 mol of non-covalently bound FAD; the apoenzyme can be partially reconstituted in vitro by addition of FAD. Tcm A2 oxygenase exhibits an optimal pH of 9.0-9.5 and prefers NADPH over NADH as an electron donor. The apparent K'm of the enzyme for Tcm A2, NADH, and NADPH are 1.81 +/- 0.38, 260 +/- 19, and 82.1 +/- 17 microM, respectively, and the apparent V'max for the reaction is 14.7 +/- 1.1 nmol Tcm C/min.mg. Purification and characterization of Tcm A2 oxygenase provide direct evidence to support the notion that the angular hydroxy groups of naphthacenequinones like Tcm C are introduced from 18O2 via a mono- or dioxygenase process.
Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo (2012)

Foxp3(+) CD4(+) T helper cells called regulatory T (T reg) cells play a key role in controlling reactivity to self-antigens and onset of autoimmunity. T reg cells either arise in thymus and are called natural T reg (nT reg) cells or are generated in the periphery through induction of Foxp3 and are called inducible T reg (iT reg) cells. The relative contributions of iT reg cells and nT reg cells in peripheral tolerance remain unclear as a result of an inability to separate these two subsets of T reg cells. Using a combination of novel TCR transgenic mice with a defined self-antigen specificity and conventional mouse models, we demonstrate that a cell surface molecule, neuropilin-1 (Nrp-1), is expressed at high levels on nT reg cells and can be used to separate nT reg versus iT reg cells in certain physiological settings. In addition, iT reg cells generated through antigen delivery or converted under homeostatic conditions lack Nrp-1 expression. Nrp-1(lo) iT reg cells show similar suppressive activity to nT reg cells in controlling ongoing autoimmune responses under homeostatic conditions. In contrast, their activity might be compromised in certain lymphopenic settings. Collectively, our data show that Nrp-1 provides an excellent marker to distinguish distinct T reg subsets and will be useful in studying the role of nT reg versus iT reg cells in different disease settings.
Lipid Bilayer Disruption by Polycationic Polymers:  The Roles of Size and Chemical Functional Group (2005)

Polycationic polymers are used extensively in biology to disrupt cell membranes and thus enhance the transport of materials into the cell. The highly polydisperse nature of many of these materials makes obtaining a mechanistic understanding of the disruption processes difficult. To design an effective mechanistic study, a monodisperse class of polycationic polymers, poly(amidoamine) (PAMAM) dendrimers, has been studied in the context of supported dimyristoylphosphatidylcholine (DMPC) lipid bilayers using atomic force microscopy (AFM). Aqueous solutions of amine-terminated generation 7 (G7) PAMAM dendrimers caused the formation of 15-40-nm-diameter holes in lipid bilayers. This effect was significantly reduced for smaller G5 dendrimers. For G3, no hole formation was observed. In addition to dendrimer size, surface chemistry had a strong influence on dendrimer-lipid bilayer interactions. In particular, acetamide-terminated G5 did not cause hole formation in bilayers. In all instances, the edges of bilayer defects proved to be points of highest dendrimer activity. A proposed mechanism for the removal of lipids by dendrimers involves the formation of dendrimer-filled lipid vesicles. By considering the thermodynamics, interaction free energy, and geometry of these self-assembled vesicles, a model that explains the influence of polymer particle size and surface chemistry on the interactions with lipid membranes was developed. These results are of general significance for understanding the physical and chemical properties of polycationic polymer interactions with membranes that lead to the transport of materials across cell membranes.
IN VIVO MEASUREMENTS OF INTRADISCAL PRESSURE. DISCOMETRY, A METHOD FOR THE DETERMINATION OF PRESSURE IN THE LOWER LUMBAR DISCS. (1964)

In an effort to obtain more information about the mechanics of the lumbar discs and about the production of low-back pain, direct in vivo measurements of lumbar intradiscal pressures were made under various conditions. A needle with a pressure-sensitive polyethylene membrane at its tip was constructed for this purpose.

Pressure values were obtained in eighteen normal third and fourth lumbar discs of sixteen subjects. The sitting position was used in all cases; other positions and factors studied included standing, reclining, holding total weights of 9.1 and 22.7 kilograms, performing the Valsalva maneuver, and wearing an inflatable corset.

High intradiscal pressures (ten to fifteen kilograms per square centimeter) were found in the normal discs with the subject in the sitting position. In all cases, pressures were highest in the sitting position, about 30 per cent less in the standing position, and about 50 per cent less in the reclining than in the sitting position.

It was found that the lower lumbar discs have to support total loads of as much as 100 to 175 kilograms when the subject is seated. For the standing position total loads of between ninety and 120 kilograms were calculated from the pressure values obtained.

It was calculated that, in the normal discs tensile forces of considerable magnitude (sixty to eighty kilograms per square centimeter) exist in the posterior part of the annulus; this fact gives strong support to the mechanical theory of the production of ruptures of the posterior annulus.

The Valsalva maneuver generally increased the intradiscal pressure, but the results were variable. The inflatable corset decreased the pressure in the examined discs by about 25 per cent.

The loads on discs spanned by a posterior fusion in two patients were approximately 30 per cent less than would have been anticipated. In the one with a pseudarthrosis, further loading increased the intradiscal pressure to a value similar to that in subjects without fusion. In the one with a successful fusion demonstrated by surgical exploration, the force on the disc was proportionately reduced with further loading.

The data support and help to explain such observations as increased pain in sitting as compared with standing and reclining in patients with low-back pain, pain during the Valsalva maneuver, and the codfish appearance of osteoporotic spines with relatively normal discs.

Lumbar discometry is suggested as a means not only of determining the basic mechanics of the disc in different positions and under different conditions of stress but also of evaluating therapeutic measures such as posterior fusion and the wearing of corsets and braces.
Stöber Synthesis of Nitric Oxide-Releasing S-Nitrosothiol-Modified Silica Particles (2011)

We report the synthesis of S-nitrosothiol-modified silica particles capable of nitric oxide (NO) release. The thiol precursor modification to form S-nitrosothiol NO donors was introduced into the silica network via co-condensation of mercaptosilane and alkoxysilane precursors. Both the concentrations of reactants (i.e., water, ammonia, and silane) and the silane feed rate into the reaction proved important in the yield of monodisperse, spherical particles with tunable diameters ranging from 241-718 nm. Subsequent nitrosation resulted in NO storage approaching ~4.40 μmol NO mg(-1), as determined by total NO release. Behaving similar to low molecular weight S-nitrosothiol NO donors, the NO release from the macromolecular silica vehicles was influenced by light, temperature, and metal ions.
Interleukin-6 Overcomes p21WAF1 Upregulation and G1 Growth Arrest Induced by Dexamethasone and Interferon-γ in Multiple Myeloma Cells (1997)

Interleukin-6 (IL-6) is a growth factor for multiple myeloma (MM) cells and can inhibit MM cell apoptosis. Our recent studies show that IL-6 facilitates MM cell growth via phosphorylation of retinoblastoma protein (pRB); however, the effects of IL-6 on those cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CDIs) that are known to regulate phosphorylation of pRB have not been defined in MM cells. In the present report, we cultured MM cell lines and patient cells with IL-6 and/or dexamethasone (Dex) and characterized changes in cell cycle; expression and association of cyclins, CDKs, and CDIs; and phosphorylation of pRB. Dex induced G1 growth arrest in MM cells, whereas IL-6 facilitated G1 to S phase transition; moreover, the effect of Dex was blocked by IL-6. p21WAF1 (p21) protein was constitutively expressed in the majority of MM cells independent of the status of p53. Its expression was upregulated by Dex and downregulated by IL-6; again, IL-6 inhibited the increase in p21 triggered by Dex. These alterations in p21 expression in MM cells were associated with changes in p21 binding to CDK2, CDK4, and CDK6; CDK2, CDK4, and CDK6 kinase activities; and phosphorylation of pRB. In contrast, expression of G1 cell cycle regulatory proteins, including p27KIP1, cyclin D2, and cyclin E, was not altered in MM cells cultured with Dex and/or IL-6. Finally, interferon-γ (IFN-γ) also induced G1 growth arrest and upregulated p21 protein expression; as with Dex, affects of IFN-γ were inhibited by IL-6. Our results therefore show that changes in cell cycle distribution in MM cells triggered by Dex, IL-6, and IFN-γ correlate with changes in p21 protein expression and implicate p21 in the coupling of Dex-, IL-6–, and IFN-γ–related signals to G1 cell cycle regulation in MM cells.
Single-molecule spectroelectrochemical cross-correlation during redox cycling in recessed dual ring electrode zero-mode waveguides (2017)

The ability of zero-mode waveguides (ZMW) to guide light into subwavelength-diameter nanoapertures has been exploited for studying electron transfer dynamics in zeptoliter-volume nanopores under single-molecule occupancy conditions. In this work, we report the spectroelectrochemical detection of individual molecules of the redox-active, fluorogenic molecule flavin mononucleotide (FMN) freely diffusing in solution. Our approach is based on an array of nanopore-confined recessed dual ring electrodes, wherein repeated reduction and oxidation of a single molecule at two closely spaced annular working electrodes yields amplified electrochemical signals. We have articulated these structures with an optically transparent bottom, so that the nanopores are bifunctional, exhibiting both nanophotonic and nanoelectrochemical behaviors allowing the coupling between electron transfer and fluorescence dynamics to be studied under redox cycling conditions. We also investigated the electric field intensity in electrochemical ZMWs (E-ZMW) through finite-element simulations, and the amplification of fluorescence by redox cycling agrees well with predictions based on optical confinement effects inside the E-ZMW. Proof-of-principle experiments are conducted showing that electrochemical and fluorescence signals may be correlated to reveal single molecule fluctuations in the array population. Cross-correlation of single molecule fluctuations in amperometric response and single photon emission provides unequivocal evidence of single molecule sensitivity.
Circulating MicroRNAs: a novel class of biomarkers to diagnose and monitor human cancers (2010)

Abstract Specific and sensitive non‐invasive biomarkers for the detection of human epithelial malignancies are urgently required to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are 19–24 nt noncoding RNAs that are frequently dysregulated in cancer and have shown great promise as tissue‐based markers for cancer classification. Once thought to be unstable RNA molecules, miRNAs are now shown to be stably expressed in serum, plasma, urine, saliva, and other body fluids. Moreover, the unique expression patterns of these circulating miRNAs are correlated with certain human diseases, including various types of cancer. Therefore, tumor‐derived miRNAs in serum or plasma are emerging as novel blood‐based fingerprints for the detection of human cancers, especially at an early stage. This review presented newly uncovered cellular and molecular mechanisms of the sources and stability of circulating miRNAs, revealing their great potential as a class of highly specific and sensitive biomarkers for tumor classification and prognostication. Meanwhile, this review also addressed certain critical issues that hinder the wide application of this new approach. Some potential challenges for the transition of circulating miRNAs from a research setting to a clinical application were also highlighted, with a future perspective of the incorporation of circulating miRNAs in the field of clinical oncology, especially their great potential from diagnostic to prognostic and predictive applications. © 2010 Wiley Periodicals, Inc. Med Res Rev
Pelican DHCP Automated Self-Registration System: Distributed Registration and Centralized Management (2001)

Pelican is an automated DHCP client self-registration tool. Unlike other popular self-registration tools, the Pelican registration system runs on an independent server with no access to the DHCP daemon's lease data or configuration files. It derives MAC addresses by SNMP-querying network devices and periodically generating and pushing updated configuration files to all participating DHCP servers. This allows Pelican to scale more effectively than most other existing automated registration systems. Pelican also tracks lease allocation on participating DHCP servers, providing administrators with a central repository of data for simplified administration and troubleshooting.