gebhart/patrepeval huggingface dataset:
Synthesis and biological activity of phosphonoacetate- and thiophosphonoacetate-modified 2′-O-methyl oligoribonucleotides (2011)

Chimeric 2'-O-methyl oligoribonucleotides (2'-OMe ORNs) containing internucleotide linkages which were modified with phosphonoacetate (PACE) or thiophosphonoacetate (thioPACE) were prepared by solid-phase synthesis. The modified 2'-OMe ORNs contained a central phosphate or phosphorothioate sequence with up to 4 PACE or thioPACE modifications, respectively, at either end of the ORN in a "gapmer" motif. Both PACE and thioPACE 2'-OMe ORNs formed stable duplexes with complementary RNA. The majority of these duplexes had higher thermal melting temperatures than an unmodified RNA:RNA duplex. The modified 2'-OMe ORNs were effective passenger strands with complementary, unmodified siRNAs, for inducing siRNA activity in a dual luciferase assay in the presence of a lipid transfecting agent. As single strands, thioPACE 2'-OMe ORNs were efficiently taken up by HeLa cells in the absence of a lipid transfecting agent. Furthermore, thioPACE modifications greatly improved the potency of a 2'-OMe phosphorothioate ORN as an inhibitor of microRNA-122 in Huh7 cells, without lipid transfection.
Prophylaxis of heterotopic ossification – an updated review (2009)

Heterotopic ossification (HO) is defined as the process by which trabecular bone forms outside of the skeletal structure, occupying space in soft tissue where it does not normally exist. The current popular prophylactic treatment modalities include non-steroidal anti-inflammatory drugs (NSAIDs) and radiation therapy, although the literature remains inconclusive as to which is superior. Additionally, both treatments can lead to adverse effects to the patient. Recently there have been several studies attempting to identify new aspects of the etiology of heterotopic bone formation and introduce new prophylactic modalities with increased efficacy and fewer side effects. For this review, we selectively retrieved articles from Medline published from 1958-2008 on the prophylaxis of HO with the aim of assisting readers in quickly grasping the current status of research and clinical aspects of HO prophylaxis.
Controlled Polymerization of a Cyclopentadithiophene–Phenylene Alternating Copolymer (2018)

The new conjugated poly(4,4-bis(2-ethylhexyl)cyclopentadithiophene-alt-p-phenylene) (PCPDTPP) has been synthesized in a controlled way via catalyst transfer condensative polymerization (CTCP) of the corresponding biaryl monomer. Therefore, a series of Ni catalysts as well as (new) Pd-PEPPSI catalysts were employed in different Kumada CTCPs (KCTCPs) and Negishi CTCPs (NCTCPs). A series of tests confirmed the absence of undesired transfer and termination reactions and, hence, the controlled character of the chain-growth polymerization with Ni(dppe)Cl2 as catalyst. This resulted in polymers with low dispersities (Đ = 1.2), M̅n of 33 kDa, and relatively good end-group control. Furthermore, formation of PCPDTPP-b-poly(3-octylthiophene) (P3OT) block copolymers was possible. Via optical analysis and DSC measurements, we demonstrated that the conjugated alternating PCPDTPP copolymer is an amorphous, strongly fluorescent polymer with a fluorescence quantum yield (ϕf) of 58% in chloroform.
A Pathologic Cascade Leading to Synaptic Dysfunction in -Synuclein-Induced Neurodegeneration (2010)

Several neurodegenerative diseases are typified by intraneuronal alpha-synuclein deposits, synaptic dysfunction, and dementia. While even modest alpha-synuclein elevations can be pathologic, the precise cascade of events induced by excessive alpha-synuclein and eventually culminating in synaptotoxicity is unclear. To elucidate this, we developed a quantitative model system to evaluate evolving alpha-synuclein-induced pathologic events with high spatial and temporal resolution, using cultured neurons from brains of transgenic mice overexpressing fluorescent-human-alpha-synuclein. Transgenic alpha-synuclein was pathologically altered over time and overexpressing neurons showed striking neurotransmitter release deficits and enlarged synaptic vesicles; a phenotype reminiscent of previous animal models lacking critical presynaptic proteins. Indeed, several endogenous presynaptic proteins involved in exocytosis and endocytosis were undetectable in a subset of transgenic boutons ("vacant synapses") with diminished levels in the remainder, suggesting that such diminutions were triggering the overall synaptic pathology. Similar synaptic protein alterations were also retrospectively seen in human pathologic brains, highlighting potential relevance to human disease. Collectively the data suggest a previously unknown cascade of events where pathologic alpha-synuclein leads to a loss of a number of critical presynaptic proteins, thereby inducing functional synaptic deficits.
Insulin resistance is associated with the pathology of Alzheimer disease (2010)

The results of this study suggest that hyperinsulinemia and hyperglycemia caused by insulin resistance accelerate NP formation in combination with the effects of APOE epsilon4.
A 6 MJ spherical hohlraum target for heavy ion inertial fusion (1999)

A new target option for energy applications of heavy ion inertial fusion is analysed. It has a spherical hohlraum and is irradiated by ion beams along the directions of the zeros of the fourth Legendre polynomial P4. The target performance is simulated with a 1-D three temperature hydrodynamics code and with a 2-D view factor code. Its efficiency is shown to depend crucially on the structure of the hohlraum wall, which, simultaneously, plays the role of the X ray converter. For an optimized pulse power profile, a 1-D energy gain of G = 78 is calculated with an input energy of Edr = 6.1 MJ in the form of 5 GeV 209Bi ions focused on the target sphere with an outer radius of R = 6.37 mm.
Treatment of X-Linked Hypophosphatemia with Calcitriol and Phosphate Increases Circulating Fibroblast Growth Factor 23 Concentrations (2010)

Treating XLH with phosphate and calcitriol was associated with concurrent increases in circulating FGF23 concentrations, which may diminish therapeutic effect or contribute to complications of therapy. Because it is unknown whether the degree of FGF23 elevation correlates with disease severity in XLH, further study is needed to determine whether adjusting therapy to minimize effects on FGF23 concentration is warranted.
Cytokine control of inflammation and repair in the pathology of multiple sclerosis. (2012)

Cytokines are secreted signaling proteins that play an essential role in propagating and regulating immune responses during experimental autoimmune encephalomyelitis (EAE), the mouse model of the neurodegenerative, autoimmune disease multiple sclerosis (MS). EAE pathology is driven by a myelin-specific T cell response that is activated in the periphery and mediates the destruction of myelin upon T cell infiltration into the central nervous system (CNS). Cytokines provide cell signals both in the immune and CNS compartment, but interestingly, some have detrimental effects in the immune compartment while having beneficial effects in the CNS compartment. The complex nature of these signals will be reviewed.
Association of a pH-sensitive peptide with membrane vesicles: role of amino acid sequence (1990)

The solution properties and bilayer association of two synthetic 30 amino acid peptides, GALA and LAGA, have been investigated at pH 5 and 7.5. These peptides have the same amino acid composition and differ only in the positioning of glutamic acid and leucine residues which together compose 47% of each peptide. Both peptides undergo a similar coil to helix transition as the pH is lowered from 7.5 to 5.0. However, GALA forms an amphipathic alpha-helix whereas LAGA does not. As a result, GALA partitions into membranes to a greater extent than LAGA and can initiate leakage of vesicle contents and membrane fusion which LAGA cannot (Subbarao et al., 1987; Parente et al., 1988). Membrane association of the peptides has been studied in detail with large phosphatidylcholine vesicles. Direct binding measurements show a strong association of the peptide GALA to vesicles at pH 5 with an apparent Ka around 10(6). The single tryptophan residue in each peptide can be exploited to probe peptide motion and positioning within lipid bilayers. Anisotropy changes and the quenching of tryptophan fluorescence by brominated lipids in the presence of vesicles also indicate that GALA can interact with uncharged vesicles in a pH-dependent manner. By comparison to the peptide LAGA, the membrane association of GALA is shown to be due to the amphipathic nature of its alpha-helical conformation at pH 5.
FGF19-induced Hepatocyte Proliferation Is Mediated through FGFR4 Activation (2009)

FGF19 and FGF21, unique members of the fibroblast growth factor (FGF) family, are hormones that regulate glucose, lipid, and energy homeostasis. Increased hepatocyte proliferation and liver tumor formation have also been observed in FGF19 transgenic mice. Here, we report that, in contrast to FGF19, FGF21 does not induce hepatocyte proliferation in vivo. To identify the mechanism for FGF19-induced hepatocyte proliferation, we explored similarities and differences in receptor specificity between FGF19 and FGF21. We find that although both are able to activate FGF receptors (FGFRs) 1c, 2c, and 3c, only FGF19 activates FGFR4, the predominant receptor in the liver. Using a C-terminal truncation mutant of FGF19 and a series of FGF19/FGF21 chimeric molecules, we determined that amino acids residues 38-42 of FGF19 are sufficient to confer both FGFR4 activation and increased hepatocyte proliferation in vivo to FGF21. These data suggest that activation of FGFR4 is the mechanism whereby FGF19 can increase hepatocyte proliferation and induce hepatocellular carcinoma formation.
4Calcium(2+).cntdot.troponin C forms dimers in solution at neutral pH that dissociate upon binding various peptides: Small-angle x-ray scattering studies of peptide-induced structural changes (1992)

Small-angle X-ray scattering data have been measured for rabbit skeletal muscle troponin C and its complexes with the venom peptides melittin and mastoparan as well as synthetic peptides based on regions of the troponin I sequence implicated in troponin C binding. At the neutral pH used in this study (pH 6.8), troponin C shows a tendency to form dimers in the presence of 4 mol equiv of Ca2+, but is monomeric in solution when 2 or less mol equiv of Ca2+ is present. The 4Ca2+.troponin C dimers dissociate upon binding melittin, mastoparan, and peptides based on residues 96-115, 1-30, and 1-40 in the troponin I sequence. This result suggests that the peptide-binding sites overlap with the regions of contact between troponin C molecules forming a dimer. Like the structurally homologous calcium-binding protein calmodulin, troponin C shows conformational flexibility upon binding different peptides. Upon binding melittin, troponin C contracts in a similar manner to calmodulin when it binds peptides known to form amphiphilic helices (e.g., melittin, mastoparan, or MLCK-I). In contrast, mastoparan binding to troponin C does not result in a contracted structure. The scattering data indicate troponin C also remains in an extended structure upon binding the inhibitory peptides having the same sequence as residues 96-115 in troponin I.
Immune response to a differentiation antigen induced by altered antigen: A study of tumor rejection and autoimmunity (1996)

Recognition of self is emerging as a theme for the immune recognition of human cancer. One question is whether the immune system can actively respond to normal tissue autoantigens expressed by cancer cells. A second but related question is whether immune recognition of tissue autoantigens can actually induce tumor rejection. To address these issues, a mouse model was developed to investigate immune responses to a melanocyte differentiation antigen, tyrosinase-related protein 1 (or gp75), which is the product of the brown locus. In mice, immunization with purified syngeneic gp75 or syngeneic cells expressing gp75 failed to elicit antibody or cytotoxic T-cell responses to gp75, even when different immune adjuvants and cytokines were included. However, immunization with altered sources of gp75 antigen, in the form of either syngeneic gp75 expressed in insect cells or human gp75, elicited autoantibodies to gp75. Immunized mice rejected metastatic melanomas and developed patchy depigmentation in their coats. These studies support a model of tolerance maintained to a melanocyte differentiation antigen where tolerance can be broken by presenting sources of altered antigen (e.g., homologous xenogeneic protein or protein expressed in insect cells). Immune responses induced with these sources of altered antigen reacted with various processed forms of native, syngeneic protein and could induce both tumor rejection and autoimmunity.
The tandem repeat domain in the Listeria monocytogenes ActA protein controls the rate of actin-based motility, the percentage of moving bacteria, and the localization of vasodilator-stimulated phosphoprotein and profilin. (1996)

The ActA protein is responsible for the actin-based movement of Listeria monocytogenes in the cytosol of eukaryotic cells. Analysis of mutants in which we varied the number of proline-rich repeats (PRR; consensus sequence DFPPPPTDEEL) revealed a linear relationship between the number of PRRs and the rate of movement, with each repeat contributing approximately 2-3 microns/min. Mutants lacking all functional PRRs (generated by deletion or point mutation) moved at rates 30% of wild-type. Indirect immunofluorescence indicated that the PRRs were directly responsible for binding of vasodilator-stimulated phosphoprotein (VASP) and for the localization of profilin at the bacterial surface. The long repeats, which are interdigitated between the PRRs, increased the frequency with which actin-based motility occurred by a mechanism independent of the PRRs, VASP, and profilin. Lastly, a mutant which expressed low levels of ActA exhibited a phenotype indicative of a threshold; there was a very low percentage of moving bacteria, but when movement did occur, it was at wild-type rates. These results indicate that the ActA protein directs at least three separable events: (1) initiation of actin polymerization that is independent of the repeat region; (2) initiation of movement dependent on the long repeats and the amount of ActA; and (3) movement rate dependent on the PRRs.
Enhancing Efficacy of Recombinant Anticancer Vaccines With Prime/Boost Regimens That Use Two Different Vectors (1997)

The poor efficacy of homologous boosting regimens with viral vectors was probably a consequence of the induction of a strong antiviral antibody response. Heterologous boosting augmented antitumor immunity by generating a strong antigen-specific cytotoxic T-lymphocyte response. These data suggest that heterologous boosting strategies may be useful in increasing the efficacy of recombinant DNA anticancer vaccines that have now entered clinical trials.
An optimum design of a soft heating system for local hyperthermia (1987)

The hybrid heater based on Soft Heating method is miniaturized without reducing heating power density. A prototype heating system for local hyperthermia is designed. The temperature distribution established in a phantom is measured.
Stat3 and Stat4: members of the family of signal transducers and activators of transcription. (1994)

The deduced amino acid sequence of two members of the signal transducers and activators of transcription (STAT) family from the mouse are described. Comparison with the deduced protein sequence of the two previously described genes (Stat91 and Stat113), discovered because of their activation as transcription factors after interferon-induced tyrosine phosphorylation, shows several highly conserved regions, including the putative SH3 and SH2 domains. The conserved amino acid stretches likely point to conserved domains that enable these proteins to carry out the several required functions they are known and proposed to carry out. While Stat1 and Stat3 are widely expressed, Stat4 expression is restricted to testis, thymus, and spleen. Antiserum to Stat3 detects a major approximately 92-kDa protein and a minor approximately 89-kDa protein, while antiserum to Stat4 precipitates one major protein of approximately 89 kDa.
Notch signaling: switching an oncogene to a tumor suppressor (2014)

The Notch signaling pathway is a regulator of self-renewal and differentiation in several tissues and cell types. Notch is a binary cell-fate determinant, and its hyperactivation has been implicated as oncogenic in several cancers including breast cancer and T-cell acute lymphoblastic leukemia (T-ALL). Recently, several studies also unraveled tumor-suppressor roles for Notch signaling in different tissues, including tissues where it was before recognized as an oncogene in specific lineages. Whereas involvement of Notch as an oncogene in several lymphoid malignancies (T-ALL, B-chronic lymphocytic leukemia, splenic marginal zone lymphoma) is well characterized, there is growing evidence involving Notch signaling as a tumor suppressor in myeloid malignancies. It therefore appears that Notch signaling pathway's oncogenic or tumor-suppressor abilities are highly context dependent. In this review, we summarize and discuss latest advances in the understanding of this dual role in hematopoiesis and the possible consequences for the treatment of hematologic malignancies.
MAVID multiple alignment server (2003)

MAVID is a multiple alignment program suitable for many large genomic regions. The MAVID web server allows biomedical researchers to quickly obtain multiple alignments for genomic sequences and to subsequently analyse the alignments for conserved regions. MAVID has been successfully used for the alignment of closely related species such as primates and also for the alignment of more distant organisms such as human and fugu. The server is fast, capable of aligning hundreds of kilobases in less than a minute. The multiple alignment is used to build a phylogenetic tree for the sequences, which is subsequently used as a basis for identifying conserved regions in the alignment. The server can be accessed at http://baboon.math.berkeley.edu/mavid/.
Matrix Metalloproteinase Activity Inactivates the CXC Chemokine Stromal Cell-derived Factor-1 (2001)

Chemokines provide directional cues for leukocyte migration and activation that are essential for normal leukocytic trafficking and for host responses during processes such as inflammation, infection, and cancer. Recently we reported that matrix metalloproteinases (MMPs) modulate the activity of the CC chemokine monocyte chemoattractant protein-3 by selective proteolysis to release the N-terminal tetrapeptide. Here we report the N-terminal processing, also at position 4-5, of the CXC chemokines stromal cell-derived factor (SDF)-1alpha and beta by MMP-2 (gelatinase A). Robustness of the MMP family for chemokine cleavage was revealed from identical cleavage site specificity of MMPs 1, 3, 9, 13, and 14 (MT1-MMP) toward SDF-1; selectivity was indicated by absence of cleavage by MMPs 7 and 8. Efficient cleavage of SDF-1alpha by MMP-2 is the result of a strong interaction with the MMP hemopexin C domain at an exosite that overlaps the monocyte chemoattractant protein-3 binding site. The association of SDF-1alpha with different glycosaminoglycans did not inhibit cleavage. MMP cleavage of SDF-1alpha resulted in loss of binding to its cognate receptor CXCR-4. This was reflected in a loss of chemoattractant activity for CD34(+) hematopoietic progenitor stem cells and pre-B cells, and unlike full-length SDF-1alpha, the MMP-cleaved chemokine was unable to block CXCR-4-dependent human immunodeficiency virus-1 infection of CD4(+) cells. These data suggest that MMPs may be important regulatory proteases in attenuating SDF-1 function and point to a deep convergence of two important networks, chemokines and MMPs, to regulate leukocytic activity in vivo.
Equivalent circuit modelling of p-i-n photodiodes for 40 Gb/s receivers (2003)

We have described a back-illuminated photodetector with an 0.62 A/W responsivity, a typical dark current of 3 nA at -5 V bias, a failure rate of less than 1 FIT at 40/spl deg/C, and a bandwidth (into a 50 ohm load) as high as 39 GHz. By inserting a tunnelling element into an otherwise standard equivalent circuit model, we have shown that this model is capable of self-consistently fitting photodiode S-parameter data and explaining a broad range of behavior including low frequency tailing. The physically-based equivalent circuit model and parameter extraction allows an understanding of detector performance and improved control of device processing. The detector is suitable for operation in 40 Gb/s receivers.
Radio-frequency losses of YBa2Cu3O7-δcomposite superconductors (1988)

YBa2Cu3O7- delta multi-crystalline ceramics were shaped into one-turn coils. The RF performance of the coils was evaluated by measuring the Q-value at 77 K from 1.3 to 270 MHz and comparing it with that of a Cu coil of the same geometry. The coils were also tested as NMR detection coils. In a poorly magnetically shielded environment the multicrystalline YBa2Cu3O7- delta performed less well than Cu in the frequency range studied. Q was significantly lowered by applying a magnetic field. The temperature dependence of the Q-value also was measured at 100 MHz, from 77 K to well above the superconducting phase transition temperature.
Mutations in the Second Cytoplasmic Loop of the Rat Parathyroid Hormone (PTH)/PTH-related Protein Receptor Result in Selective Loss of PTH-stimulated Phospholipase C Activity (1997)

To define the structural requirements of the parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor necessary for activation of phospholipase C (PLC), receptors with random mutations in their second cytoplasmic loop were synthesized, and their properties were assessed. A mutant in which the wild type (WT) rat PTH/PTHrP receptor sequence EKKY (amino acids 317-320) was replaced with DSEL had little or no PTH-stimulated PLC activity when expressed transiently in COS-7 cells, but it retained full capacity to bind ligand and to generate cAMP. This phenotype was confirmed in LLC-PK1 cells stably expressing the DSEL mutant receptor, where both PTH-stimulated PLC activity and sodium-dependent phosphate co-transport were essentially abolished. Individual mutations of these four residues point to a critical role for Lys-319 in receptor-G protein coupling. PTH-generated IPs were reduced to 27 +/- 13% when K319E, compared with the WT receptor, and PLC activation was fully recovered in a receptor revertant in which Glu-319 in the DSEL mutant cassette was restored to the WT residue, Lys. Moreover, the WT receptor and a mutant receptor in which K319R had indistinguishable properties, thus suggesting that a basic amino acid at this position may be important for PLC activation. All of these receptors had unimpaired capacity to bind ligand and to generate cAMP. To ensure adequacy of Galphaq-subunits for transducing the receptor signal, Galphaq was expressed in HEK293 and in LLC-PK1 cells together with either WT receptors or receptors with the DSEL mutant cassette. PTH generated no inositol phosphates (IPs) in either HEK293 or LLC-PK1 cells, when they expressed DSEL mutant receptors together with Galphaq. In contrast, PTH generated 2- and 2. 5-fold increases in IPs, respectively, when these cells co-expressed both the WT receptor and Galphaq. Thus, generation of IPs by the activated PTH/PTHrP receptor can be selectively abolished without affecting its capacity to generate cAMP, and Lys-319 in the second intracellular loop is critical for activating the PLC pathway. Moreover, alpha-subunits of the Gq family, rather than betagamma-subunits, transduce the signal from the activated receptor to PLC, and the PLC, rather than the adenylyl cyclase, pathway mediates sodium-dependent phosphate co-transport in LLC-PK1 cells.