gebhart/patrepeval huggingface dataset:
Structural requirements of N-glycosylation of proteins. Studies with proline peptides as conformational probes (1983)

Conformational aspects of N-glycosylation have been investigated with a series of proline-containing peptides as molecular probes. The results demonstrate that, depending on the position of the imino acid in the peptide chain, dramatic alterations of glycosylation rates are produced, pointing to a critical contribution of the amino acids framing the 'marker sequence' triplet Asn-Xaa-Thr(Ser) on the formation of a potential sugar-attachment site. No glycosyl transfer at all was detectable to those peptides containing a proline residue either in position Xaa or in the next position beyond the threonine of the Asn-sequon on the C-terminal side, whereas the hexapeptide Pro-Asn-Gly-Thr-Ala-Val was glycosylated at a high rate. (Emboldened residues denote the 'marker sequence' that is identical in all the peptides; italicized residues distinguish the positions of proline in the various peptides.) Studies with space-filling models reveal that the lack of glycosyl-acceptor capabilities of Ala(Pro)-Asn-Gly-Thr-Pro-Val might be directly related to their inability to adopt and/or stabilize a turn or loop conformation which permits the catalytically essential interaction between the hydroxy amino acid and the asparagine residue within the 'marker sequence' [Bause & Legler (1981) Biochem. J. 195, 639-644]. This conclusion is supported by circular-dichroism spectroscopic data, which suggest structure-forming potentials in this type of non-acceptor peptides dominating over those that favour the induction of an appropriate sugar-attachment site in the acceptor peptides. The lack of acceptor properties of Tyr-Asn-Pro-Thr-Ser-Val indicates that even small modifications in the 'recognition' pattern are not tolerated by the N-glycosyltransferases.
noise in polymer thick-film resistors (1998)

noise properties of carbon black/polyesterimide and (carbon )/polyesterimide thick-film resistors are studied. In resistive inks either high-structure carbon black or medium-structure carbon black was used. The influence of the content p of carbon black and graphite in resistive inks and curing temperature on sheet resistance and noise intensity C is considered. It is shown that a higher curing temperature causes a decrease in the resistor's volume and influences and C indirectly, via changes of the parameter p. It is then found that an increase in p leads to a simultaneous decrease of sheet resistance and noise intensity C. The relation is found in this case for all measured resistors. The values of noise exponent are estimated and a comparison with the noise properties of conventional cermet thick-film resistors is made. It is shown that the noise intensities of carbon black/polyesterimide resistors are comparable to those of cermet resistors.
LCAT Modulates Atherogenic Plasma Lipoproteins and the Extent of Atherosclerosis Only in the Presence of Normal LDL Receptors in Transgenic Rabbits (2000)

Elevated low density lipoprotein cholesterol (LDL-C) and reduced high density lipoprotein cholesterol (HDL-C) concentrations are independent risk factors for coronary heart disease. We have previously demonstrated that overexpression of an enzyme with a well established role in HDL metabolism, lecithin:cholesterol acyltransferase (LCAT), in New Zealand White rabbits not only raises HDL-C concentrations but reduces those of LDL-C as well, ultimately preventing diet-induced atherosclerosis. In the present study, the human LCAT gene (hLCAT) was introduced into LDL receptor (LDLr)-deficient (Watanabe heritable hyperlipidemic) rabbits to (1) investigate the role of the LDLr pathway in the hLCAT-mediated reductions of LDL-C and (2) determine the influence of hLCAT overexpression on atherosclerosis susceptibility in an animal model of familial hypercholesterolemia. Heterozygosity or homozygosity for the LDLr defect was determined by polymerase chain reaction, and 3 groups of hLCAT-transgenic (hLCAT+) rabbits that differed in LDLr status were established: (1) LDLr wild-type (LDLr+/+), (2) LDLr heterozygotes (LDLr+/-), and (3) LDLr homozygotes (LDLr-/-). Data for hLCAT+ rabbits were compared with those of nontransgenic (hLCAT-) rabbits of the same LDLr status. Plasma HDL-C concentrations were significantly elevated in the hLCAT+ animals of each LDLr status. However, LDL-C levels were significantly reduced only in hLCAT+/LDLr+/+ and hLCAT+/LDLr+/- rabbits but not in hLCAT+/LDLr-/- rabbits (405+/-14 versus 392+/-31 mg/dL). Metabolic studies revealed that the fractional catabolic rate (FCR, d(-1)) of LDL apolipoprotein (apo) B-100 was increased in hLCAT+/LDLr+/+ (26+/-4 versus 5+/-0) and hLCAT+/LDLr+/- (4+/-1 versus 1+/-0) rabbits, whereas the FCR of LDL apoB-100 in both groups of LDLr-/- rabbits was nearly identical (0.16+/-0.02 versus 0.15+/-0.02). Consistently, neither aortic lipid concentrations nor the extent of aortic atherosclerosis was significantly different between hLCAT+/LDLr-/- and hLCAT-/LDLr-/- rabbits. Significant correlations were observed between the percent of aortic atherosclerosis and both LDL-C (r=0.985) and LDL apoB-100 FCR (-0.745), as well as between LDL-C and LDL apoB-100 FCR (-0.866). These data are the first to establish that LCAT modulates LDL metabolism via the LDLr pathway, ultimately influencing atherosclerosis susceptibility. Moreover, LCAT's antiatherogenic effect requires only a single functional LDLr allele, identifying LCAT as an attractive gene therapy candidate for the majority of dyslipoproteinemic patients.
Infectivity, disease patterns, and serologic profiles of reovirus serotypes 1, 2, and 3 in infant and weanling mice. (1993)

The oronasal median infectious doses of reovirus serotypes 1, 2, and 3 were established in infant and weanling Sencar mice on the basis of disease expression and seroconversion. Infant mice were susceptible to infection with low doses of all three serotypes, whereas weanling mice were comparatively resistant to infection. Uniform transmission of virus to cagemates or mothers of infants did not occur, indicating low contagiousness of all three virus serotypes. The comparative susceptibility of 2-day-old Sencar mice to disease was examined following oronasal inoculation with reovirus 1, 2, or 3. Tissues were collected on days 3, 5, 7, 9, 14, 16, and 21 after inoculation for virus isolation, histologic examination, and serologic analysis. Disease patterns in infant mice were distinctly different among reovirus serotypes. Reovirus 3 induced severe disease, with focal myocarditis, hepatitis, diffuse encephalitis, and generalized lymphoid depletion, whereas reovirus 1 induced a similar pattern, but much milder disease. In contrast, reovirus 2 induced mild transient enteritis without lesions in other organs. Sera from experimentally infected mice were tested in virus serotype-specific enzyme immunoassays. Cross reactivity of antibody among the three virus serotypes was found, but antibody titers were always highest with the homologous antigen. These studies confirm that infant laboratory mice are susceptible to infection with all three serotypes of virus; weanling mice are comparatively resistant to infection and disease; the viruses induce different patterns of disease in infant mice; and infecting virus serotypes can be distinguished serologically by enzyme immunoassay.
The Behavior and Significance of Slow‐Binding Enzyme Inhibitors (1988)

Introduction Characteristics of Progress Curves for Slow-Binding Inhibitors Specific Cases of Slow-Binding Inhibition Concluding REmarks
Invited Review: Arteriolar smooth muscle mechanotransduction: Ca2+signaling pathways underlying myogenic reactivity (2001)

The smooth muscle of arterioles responds to an increase in intraluminal pressure with vasoconstriction and with vasodilation when pressure is decreased. Such myogenic vasoconstriction provides a level of basal tone that enables arterioles to appropriately adjust diameter in response to neurohumoral stimuli. Key in this process of mechanotransduction is the role of changes in intracellular Ca(2+). However, it is becoming clear that considerable complexity exists in the spatiotemporal characteristics of the Ca(2+) signal and that changes in intracellular Ca(2+) may play roles other than direct effects on the contractile process via activation of myosin light-chain phosphorylation. The involvement of Ca(2+) may extend to modulation of ion channels and release of Ca(2+) from the sarcoplasmic reticulum, alterations in Ca(2+) sensitivity, and coupling between cells within the vessel wall. The purpose of this brief review is to summarize the current literature relating to Ca(2+) and the arteriolar myogenic response. Consideration is given to coupling of Ca(2+) changes to the mechanical stimuli, sources of Ca(2+), involvement of ion channels, and spatiotemporal aspects of intracellular Ca(2+) signaling.
Induction of Interleukin-10 Producing Dendritic Cells As a Tool to Suppress Allergen-Specific T Helper 2 Responses (2018)

Dendritic cells (DCs) are gatekeepers of the immune system that control induction and polarization of primary, antigen-specific immune responses. Depending on their maturation/activation status, the molecules expressed on their surface, and the cytokines produced DCs have been shown to either elicit immune responses through activation of effector T cells or induce tolerance through induction of either T cell anergy, regulatory T cells, or production of regulatory cytokines. Among the cytokines produced by tolerogenic DCs, interleukin 10 (IL-10) is a key regulatory cytokine limiting und ultimately terminating excessive T-cell responses to microbial pathogens to prevent chronic inflammation and tissue damage. Because of their important role in preventing autoimmune diseases, transplant rejection, allergic reactions, or in controlling chronic inflammation DCs have become an interesting tool to modulate antigen-specific immune responses. For the treatment of allergic inflammation, the aim is to downregulate allergen-specific T helper 2 (Th2) responses and the associated clinical symptoms [allergen-driven Th2 activation, Th2-driven immunoglobulin E (IgE) production, IgE-mediated mast cell and basophil activation, allergic inflammation]. Here, combining the presentation of allergens by DCs with a pro-tolerogenic, IL-10-producing phenotype is of special interest to modulate allergen-specific immune responses in the treatment of allergic diseases. This review discusses the reported strategies to induce DC-derived IL-10 secretion for the suppression of allergen-specific Th2-responses with a focus on IL-10 treatment, IL-10 transduction, and the usage of both whole bacteria and bacteria-derived components. Interestingly, while IL-10-producing DCs induced either by IL-10 treatment or IL-10 transduction are arrested in an immature/semi-mature state, treatment of DCs with live or killed bacteria as well as isolated bacterial components results in the induction of both anti-inflammatory IL-10 and pro-inflammatory, Th1-promoting IL-12 secretion often paralleled by an enhanced expression of co-stimulatory molecules on the stimulated DCs. By the secretion of DC-derived exosomes or CC-chemokine ligand 18, as well as the expression of inhibitory molecules like cytotoxic T lymphocyte-associated antigen 4, TNF receptor superfamily member 4, Ig-like transcript-22/cluster of differentiation 85, or programmed death-1, IL-10-producing DCs have been repeatedly shown to suppress antigen-specific Th2-responses. Therefore, DC-based vaccination approaches hold great potential to improve the treatment of allergic diseases.
Molecular cloning of matrin F/G: A DNA binding protein of the nuclear matrix that contains putative zinc finger motifs. (1991)

We have isolated a 2.7-kilobase rat liver cDNA clone that contains the entire 544-amino acid coding sequence for matrin F/G. This protein has previously been localized to the internal, fibrogranular areas of the nuclear matrix and shown to bind to DNA on nitrocellulose blots. The predicted amino acid sequence from the coding region of this cDNA shows that this protein contains approximately 50% hydrophobic amino acids with secondary structure predictions suggesting a large percentage of beta-sheet regions. No significant homologies were found with any other known proteins, including the nuclear lamins. The predicted amino acid sequence was also searched for DNA binding motifs. Two putative zinc finger motifs were found. In addition, a 7-mer palindromic sequence (Ser-Ser-Thr-Asn-Thr-Ser-Ser) was discovered within one of these zinc finger DNA binding regions. A possible regulatory role for this element is discussed.
A review of pulmonary arterial hypertension: role of ambrisentan. (2007)

Pulmonary arterial hypertension (PAH) is a rare fatal disease. Current disease-specific therapeutic interventions in PAH target 1 of 3 established pathways in disease pathobiology: prostacyclin, nitric oxide, and endothelin-1. Endothelin receptor antagonists (ERAs) act on the endothelin pathway by blocking binding of endothelin-1 to its receptors (endothelin type-A [ET(A)] and/or type-B [ET(B)]) on the surface of endothelial and smooth muscle cells. Ambrisentan is an oral, once-daily, ET(A)-selective ERA in development for the treatment of PAH. In Phase 3 clinical trials in patients with PAH, ambrisentan (2.5-10 mg orally once-daily) improved exercise capacity, Borg dyspnea index, time to clinical worsening, WHO functional class, and quality of life compared with placebo. Ambrisentan provided durable (at least 2 years) improvement in exercise capacity in a Phase 2 long-term extension study. Ambrisentan was well tolerated with a lower incidence and severity of liver function test abnormalities compared with the ET(A)/ET(B) ERA, bosentan, and the ET(A)-selective ERA, sitaxsentan. Ambrisentan does not induce or inhibit P450 enzymes; therefore, ambrisentan is unlikely to affect the pharmacokinetics of P450-metabolized drugs. The demonstration of clinical efficacy, low incidence of acute hepatic toxicity, and low risk of drug-drug interactions support the role of ambrisentan for the treatment of PAH.
Corneal hydration control in Fuchs' dystrophy. (1989)

Corneal hydration control was tested in 22 patients with Fuchs' dystrophy, and eight subjects of similar age without the disease, by measuring the corneal thickness recovery from swelling induced by hypoxia or following overnight sleep. Measurement precision was enhanced by using a modified optical pachometer and conducting two test procedures which were analyzed by a coupled exponential model. We have identified three parameters of the recovery from corneal swelling which may be used to describe hydration control: percent recovery per hour (PRPH) (mean 25.4% for Fuchs' and 34.2% for normals), time for 95% of corneal thickness recovery (mean 10.2 hr for Fuchs' and 7.1 hr for normals), and the open-eye steady-state thickness (mean 562 microns for Fuchs' and 537 microns for normals.) A PRPH of 17.1%/hr was identified as the minimum below which the cornea could not regain its open-eye steady state during the entire day and approaches decompensation. Our test procedure quantifies the corneal hydration control mechanism and may provide a test of endothelial function which can be used to monitor the progression of Fuchs' disease and guide decisions related to corneal surgery.
Sustained Gene Expression in Retrovirally Transduced, Engrafting Human Hematopoietic Stem Cells and Their Lympho-Myeloid Progeny (1998)

Inefficient retroviral-mediated gene transfer to human hematopoietic stem cells (HSC) and insufficient gene expression in progeny cells derived from transduced HSC are two major problems associated with HSC-based gene therapy. In this study we evaluated the ability of a murine stem cell virus (MSCV)-based retroviral vector carrying the low-affinity human nerve growth factor receptor (NGFR) gene as reporter to maintain gene expression in transduced human hematopoietic cells. CD34(+) cells lacking lineage differentiation markers (CD34(+)Lin-) isolated from human bone marrow and mobilized peripheral blood were transduced using an optimized clinically applicable protocol. Under the conditions used, greater than 75% of the CD34(+) cell population retained the Lin- phenotype after 4 days in culture and at least 30% of these expressed a high level of NGFR (NGFR+) as assessed by fluorescence-activated cell sorter analysis. When these CD34(+)Lin-NGFR+ cells sorted 2 days posttransduction were assayed in vitro in clonogenic and long-term stromal cultures, sustained reporter expression was observed in differentiated erythroid and myeloid cells derived from transduced progenitors, and in differentiated B-lineage cells after 6 weeks. Moreover, when these transduced CD34(+)Lin-NGFR+ cells were used to repopulate human bone grafts implanted in severe combined immunodeficient mice, MSCV-directed NGFR expression could be detected on 37% +/- 6% (n = 5) of the donor-type human cells recovered 9 weeks postinjection. These findings suggest potential utility of the MSCV retroviral vector in the development of effective therapies involving gene-modified HSC.
The first synthesis of a tricyclic homodetic peptide employing coordinated orthogonal protection (1996)

In an effort to cause significant conformational distortion and thereby possibly generate a pure SRIF antagonist, we undertook the synthesis of 2, the first homodetic tricyclic peptide. This required five dimensional orthogonal amino protection and three carboxyl protecting groups to allow the selective closure of the three rings and to differentiate the ε-amino groups of the two lysines. We also exploited acid catalyzed removal from the resin to achieve selective deprotection of a side chain carboxyl moiety simultaneously with its partner amino group for subsequent cyclization.
An in-flight radiography platform to measure hydrodynamic instability growth in inertial confinement fusion capsules at the National Ignition Facility (2014)

A new in-flight radiography platform has been established at the National Ignition Facility (NIF) to measure Rayleigh–Taylor and Richtmyer–Meshkov instability growth in inertial confinement fusion capsules. The platform has been tested up to a convergence ratio of 4. An experimental campaign is underway to measure the growth of pre-imposed sinusoidal modulations of the capsule surface, as a function of wavelength, for a pair of ignition-relevant laser drives: a “low-foot” drive representative of what was fielded during the National Ignition Campaign (NIC) [Edwards et al., Phys. Plasmas 20, 070501 (2013)] and the new high-foot [Dittrich et al., Phys. Rev. Lett. 112, 055002 (2014); Park et al., Phys. Rev. Lett. 112, 055001 (2014)] pulse shape, for which the predicted instability growth is much lower. We present measurements of Legendre modes 30, 60, and 90 for the NIC-type, low-foot, drive, and modes 60 and 90 for the high-foot drive. The measured growth is consistent with model predictions, including much less growth for the high-foot drive, demonstrating the instability mitigation aspect of this new pulse shape. We present the design of the platform in detail and discuss the implications of the data it generates for the on-going ignition effort at NIF.
Developmental Seizure Susceptibility of Kv1.1 Potassium Channel Knockout Mice (1999)

Potassium channels play a critical role in limiting neuronal excitability. Mutations in certain voltage-gated potassium channels have been associated with hyperexcitable phenotypes in both humans and animals. However, only recently have mutations in potassium channel genes (i.e. KCNQ2 and KCNQ3) been discovered in a human epilepsy, benign familial neonatal convulsions. Recently, it has been reported that mice lacking the voltage-gated Shaker-like potassium channel Kv1.1 alpha-subunit develop recurrent spontaneous seizures early in postnatal development. The clinical relevance of the Kv1.1 knockout mouse has been underscored by a recent report of epilepsy occurring in a family affected by mutations in the KCNA1 locus (the human homologue of Kv1.1) which typically cause episodic ataxia and myokymia. Here we summarize preliminary studies characterizing the developmental changes in seizure susceptibility and neuronal activation in the three genotypes of Kv1.1 mice (-/-, +/-, +/+). Using behavioral and immediate-early gene indicators of regional brain excitability, we have found that a seizure-sensitive predisposition exists in Kv1.1 -/- animals at a very young age (P10), before either spontaneous seizure activity or changes in c-fos mRNA expression can be demonstrated. Kv1.1 +/- mice, although behaviorally indistinguishable from wild types, also have an increased susceptibility to seizures at a similar early age. The Kv1. 1 knockout mouse possesses many features desirable in a developmental animal epilepsy model and represents a clinically relevant model of early-onset epilepsies.
New and Redesigned pRS Plasmid Shuttle Vectors for Genetic Manipulation of Saccharomyces cerevisiae (2012)

We have constructed a set of 42 plasmid shuttle vectors based on the widely used pRS series for use in the budding yeast Saccharomyces cerevisiae and the bacterium Escherichia coli. This set of pRSII plasmids includes new shuttle vectors that can be used with histidine and adenine auxotrophic laboratory yeast strains carrying mutations in the genes HIS2 and ADE1, respectively. Our pRSII plasmids also include updated versions of commonly used pRS plasmids from which common restriction sites that occur within their yeast-selectable biosynthetic marker genes have been removed to increase the availability of unique restriction sites within their polylinker regions. Hence, our pRSII plasmids are a complete set of integrating, centromere and 2μ episomal plasmids with the biosynthetic marker genes ADE2, HIS3, TRP1, LEU2, URA3, HIS2, and ADE1 and a standardized selection of at least 16 unique restriction sites in their polylinkers. Additionally, we have expanded the range of drug selection options that can be used for PCR-mediated homologous replacement using pRS plasmid templates by replacing the G418-resistance kanMX4 cassette of pRS400 with MX4 cassettes encoding resistance to phleomycin, hygromycin B, nourseothricin, and bialaphos. Finally, in the process of generating the new plasmids, we have determined several errors in existing publicly available sequences for several commonly used yeast plasmids. Using our updated sequences, we constructed pRS plasmid backbones with a unique restriction site for inserting new markers to facilitate future expansion of the pRS series.