gebhart/patrepeval huggingface dataset:
Dynamics of localized and patterned structures in the Lugiato-Lefever equation determine the stability and shape of optical frequency combs (2014)

It has been recently uncovered that coherent structures in microresonators such as cavity solitons and patterns are intimately related to Kerr frequency combs. In this work, we present a general analysis of the regions of existence and stability of cavity solitons and patterns in the Lugiato-Lefever equation, a mean-field model that finds applications in many different nonlinear optical cavities. We demonstrate that the rich dynamics and coexistence of multiple solutions in the Lugiato-Lefever equation are of key importance to understanding frequency comb generation. A detailed map of how and where to target stable Kerr frequency combs in the parameter space defined by the frequency detuning and the pump power is provided. Moreover, the work presented also includes the organization of various dynamical regimes in terms of bifurcation points of higher codimension in regions of parameter space that were previously unexplored in the Lugiato-Lefever equation. We discuss different dynamical instabilities such as oscillations and chaotic regimes.
Proteolytic Processing in the Secretory Pathway (1999)

Many cellular processes, including embryogenesis (1-4), gene expression (5), cell cycle (6), programmed cell death (7), intracellular protein targeting (8) and endocrine/neural functions (9-13) are regulated by limited proteolysis of precursor proteins (14,15). These functions are carried out by proteolytic enzyme families that are strategically localized within cells or on cell surfaces (3,5-7, 9, 10). This review focuses on the serine proteases that process protein precursors (proproteins) traversing the secretory pathway (for recent reviews, see Refs.
Temperature-Sensitive Mutants for the Replication of Plasmids in Escherichia coli : Requirement for Deoxyribonucleic Acid Polymerase I in the Replication of the Plasmid ColE 1 (1973)

An Escherichia coli mutant (polA1), defective in deoxyribonucleic acid (DNA) polymerase I, (EC 2.7.7.7) is unable to maintain colicinogenic factor E1 (ColE1), whereas several sex factor plasmids are maintained normally in this strain. polA1 mutant strains containing these sex factor plasmids do not exhibit a readily detectable plasmid-induced polymerase activity. A series of E. coli mutants that are temperature sensitive for ColE1 maintenance, but able to maintain other plasmids, were isolated and shown to fall into two phenotypic groups. Mutants in one group are defective specifically in ColE1 maintenance at 43 C, but exhibit normal DNA polymerase I activity. Mutations in the second group map in the polA gene of E. coli, and bacteria carrying these mutations are sensitive to methylmethanesulfonate (MMS). Revertants that were selected either for MMS resistance or the ability to maintain ColE1 were normal for both properties. The DNA polymerase I enzyme of two of these mutants shows a pronounced temperature sensitivity when compared to the wild-type enzyme. An examination of the role of DNA polymerase I in ColE1 maintenance indicates that it is essential for normal replication of the plasmid. In addition, the presence of a functional DNA polymerase I in both the donor and recipient cell is required for the ColV-promoted conjugal transfer of ColE1 and establishment of the plasmid in the recipient cell.
Efficient folding of proteins with multiple disulfide bonds in the Escherichia coli cytoplasm (1999)

Under physiological conditions, the Escherichia coli cytoplasm is maintained in a reduced state that strongly disfavors the formation of stable disulfide bonds in proteins. However, mutants in which the reduction of both thioredoxins and glutathione is impaired (trxB gor mutants) accumulate oxidized, enzymatically active alkaline phosphatase in the cytoplasm. These mutants grow very poorly in the absence of an exogenous reductant and accumulate extragenic suppressors at a high frequency. One such suppressor strain, FA113, grows almost as rapidly as the wild type in the absence of reductant, exhibits slightly faster kinetics of disulfide bond formation, and has fully induced activity of the transcriptional activator, OxyR. FA113 gave substantially higher yields of properly oxidized proteins compared with wild-type or trxB mutant strains. For polypeptides with very complex patterns of disulfide bonds, such as vtPA and the full-length tPA, the amount of active protein was further enhanced up to 15-fold by co-expression of TrxA (thioredoxin 1) mutants with different redox potentials, or 20-fold by the protein disulfide isomerase, DsbC. Remarkably, higher yields of oxidized, biologically active proteins were obtained by expression in the cytoplasm of E. coli FA113 compared with what could be achieved via secretion into the periplasm of a wild-type strain, even under optimized conditions. These results demonstrate that the cytoplasm can be rendered sufficiently oxidizing to allow efficient formation of native disulfide bonds without compromising cell viability.
CTCF Is the Master Organizer of Domain-Wide Allele-Specific Chromatin at the H19/Igf2 Imprinted Region (2007)

A paternally methylated imprinting control region (ICR) directs allele-specific expression of the imprinted H19 and Igf2 genes. CTCF protein binding in the ICR is required in the maternal chromosome for insulating Igf2 from the shared enhancers, initiation of the H19 promoter transcription, maintaining DNA hypomethylation, and chromosome loop formation. Using novel quantitative allele-specific chromatin immunoprecipitation-single-nucleotide primer extension assays, we measured the chromatin composition along the H19/Igf2 imprinted domain in cells with engineered mutations at the four ICR-CTCF binding sites. Abolishing CTCF binding in the ICR reduced normally maternal allele-specific H3K9 acetylation and H3K4 methylation at the H19 ICR and promoter/gene body and maternal allele-specific H3K27 trimethylation at the Igf2 P2 promoter and Igf2 differentially methylated regions (DMRs). Paternal H3K27 trimethylation and macroH2A1 became biallelic in the mutant cells at the H19 promoter while paternal H3K9 acetylation and H3K4 methylation became biallelic at the Igf2 DMRs. We provide evidence that CTCF is the single major organizer of allele-specific chromatin composition in this domain. This finding has important implications: (i) for mechanisms of insulation since CTCF regulates chromatin at a distance, involving repression by H3K27 trimethylation at the Igf2 locus independently of repression by DNA hypermethylation; and (ii) for mechanisms of genomic imprinting since point mutations of CTCF binding sites cause domain-wide "paternalization" of the maternal allele's chromatin composition.
The quinolones: decades of development and use (2003)

The discovery of nalidixic acid in 1962, and its introduction for clinical use in 1967, marks the beginning of five decades of quinolone development and use. It was not until the discovery and licensing of the fluoroquinolones in the 1970s and 1980s that these drugs began to establish their place in the armamentarium of clinically useful antimicrobials. At the beginning of the 21st century, in their fifth decade of discovery and use, our understanding of structure-function relationships has improved, and better compounds, in terms of both spectrum of antimicrobial cover and pharmacokinetics, have been developed. The clinical utility of this expanding class of antimicrobial agents, and the lower propensity for the development of resistance with the "newer" fluoroquinolones will need to be continually monitored in the changing therapeutic environment. Antibiotic drug choice will remain difficult in the presence of increasing resistance, but the introduction of the new fluoroquinolones has created a new and exciting era in antimicrobial treatment. The role of these agents has already been acknowledged in a number of clinical guidelines, and appropriate use of these agents may help to preserve their clinical utility, enabling them to realize their full therapeutic potential.
A Potent Anti-Carcinoma and Anti-Acute Myeloblastic Leukemia Agent, AG490 (2008)

Proteins with tyrosine kinase activity are recognized as key regulators of cellular processes including growth and differentiation. Tyrosine kinase receptors e.g. EGFR and soluble tyrosine kinase proteins e.g. JAK-2, have emerged as essentials in cell survival for cervical carcinoma and acute myeloblastic leukemia, respectively. These receptors and soluble cytoplasm networks have been studied in detail and finally pharmacological agents, targeted at key molecules, could be produced. Tyrphostins are kinases inhibitors synthesized on the basic structure of erbstatin a natural kinase inhibitor. The JAK-2 specific inhibitor, Tyrphostin AG490 is used to inhibit phosphorylation of EGFR and signal transducer and activator of transcription 3 [STAT-3], and subsequently reduce invasion and adhesion potential of malignant cells. This review summarizes experiments providing a detailed picture of how hematopoietic cancer c-Kit+, Jak-2+ and non hematopoietic tumors c-Kit+, HER-2+, JAK-2+ can be inhibited by the chemosensitizing agent AG490 causing programmed cell death. Furthermore, studies presented herein analyzed several cellular targets that can be modified by the same death effector. The highly conserved JAK-2/STAT-3, c-Kit, and HER-2 signaling pathways play pleiotropic roles during embryonic development and are important for the regulation of self-renewing tissues. The physiological functions of these signaling cascades range from stem cell maintenance and influencing cell fate decisions of progenitor cells, to the induction of terminal differentiation processes, all of which have been found to be recapitulated in different forms of cancers. Inhibiting their action by AG490 represents a therapeutic approach for the treatment of individual types of cancer and several broad-spectrum.
Expression of Constitutive and Tissue-Specific Acyl Carrier Protein Isoforms in Arabidopsis (1992)

We have characterized the occurrence and expression of multiple acyl carrier protein (ACP) isoforms in Arabidopsis thaliana (L.) Heynh ecotype Columbia. Immunoblot analysis of ACPs from Arabidopsis tissues separated by native polyacrylamide gel electrophoresis and 1 molar urea polyacrylamide gel electrophoresis revealed a complex pattern of multiple ACP isoforms. All tissues examined (leaves, roots, and seeds) expressed at least three forms of ACP. The immunoblot identifications of ACP bands were confirmed by acylation of ACP extracts with Escherichia coli acyl-ACP synthetase. A full-length cDNA clone has been isolated that has 70% identity with a previously characterized Arabidopsis genomic ACP clone (ACP-1) (MA Post-Beittenmiller, A Hlousek-Radojcić, JB Ohlrogge [1989] Nucleic Acids Res 17: 1777). Based on RNA blot analysis, the cDNA clone represents an ACP that is expressed in leaves, seeds, and roots. In order to identify the protein products of each known ACP gene, their mature coding sequences have been expressed in E. coli. Using polymerase chain reactions, exons II and III of the genomic ACP-1 clone and the mature coding sequences of the ACP-2 cDNA clone were subcloned into E. coli expression vectors. Site-directed mutagenesis was used to convert the amino acid sequence of the ACP-2 cDNA clone to that of the A2 clone of Lamppa and Jacks ([1991] Plant Mol Biol 16: 469-474), ACP-3. The three E. coli-expressed proteins have different mobilities on polyacrylamide gel electrophoresis gels and each comigrates with a different Arabidopsis ACP isoform expressed in leaves, seeds, and roots. Thus, all of the three cloned ACPs appear to be constitutively expressed Arabidopsis ACPs. In addition to these three ACP isoforms, protein blots indicate that seed, leaf, and root each express one or more tissue-specific isoforms.
Genome-wide sequencing data reveals virulence factors implicated in banana Xanthomonas wilt (2010)

Banana Xanthomonas wilt is a newly emerging disease that is currently threatening the livelihoods of millions of farmers in East Africa. The causative agent is Xanthomonas campestris pathovar musacearum (Xcm), but previous work suggests that this pathogen is much more closely related to species Xanthomonas vasicola than to X. campestris. We have generated draft genome sequences for a banana-pathogenic strain of Xcm isolated in Uganda and for a very closely related strain of X. vasicola pathovar vasculorum, originally isolated from sugarcane, that is nonpathogenic on banana. The draft sequences revealed overlapping but distinct repertoires of candidate virulence effectors in the two strains. Both strains encode homologues of the Pseudomonas syringae effectors HopW, HopAF1 and RipT from Ralstonia solanacearum. The banana-pathogenic and non-banana-pathogenic strains also differed with respect to lipopolysaccharide synthesis and type-IV pili, and in at least several thousand single-nucleotide polymorphisms in the core conserved genome. We found evidence of horizontal transfer between X. vasicola and very distantly related bacteria, including members of other divisions of the Proteobacteria. The availability of these draft genomes will be an invaluable tool for further studies aimed at understanding and combating this important disease.
GLOBAL STABILITY IN HOPFIELD NEURAL NETWORKS WITH DISTRIBUTED TIME DELAYS (2001)

In this paper, without assuming the boundedness, monotonicity and differentiability of the activation functions, the conditions ensuring existence, uniqueness, and global asymptotical stability of the equilibrium point of Hopfield neural network models with distributed time delays are studied. Using M-matrix theory and constructing proper Liapunov functionals, the sufficient conditions for global asymptotic stability are obtained.
Human interferons: structure and function. (1987)

Other relevant areas of research regarding the structure and function of IFNs include the study of IFN fragments and hybrid IFN molecules prepared by recombinant DNA technology, and monoclonal antibodies against IFNs have also made major contributions to our knowledge of IFN structure and function. However, these topics have been addressed in a number of recent reviews (Zoon and Wetzel, 1984; Langer and Pestka, 1985). We are now awaiting the crystal structure of several human IFNs. Once this knowledge has been acquired, we can proceed to envisage at the three-dimensional level how these molecules interact with their receptors to produce their numerous biological activities.
Oligonucleotide Conjugated to Linear and Branched High Molecular Weight Polyethylene Glycol as Substrates for RNase H (1999)

Two conjugates of an anti-HIV oligonucleotide (ODN) with different high molecular weight monomethoxy polyethylene glycols (MPEGs) have been tested for their activity as substrate towards RNase H. The MPEG does not impede the formation of the regular hybrid duplex with the target RNA sequence as pointed out by the persistence of the RNase H activity; thus, these derivatives stimulate the hydrolysis of RNA by the enzyme at the same site and with the same extent of cleavage as the native sequence.
Dense coding for continuous variables (2000)

A scheme to achieve dense quantum coding for the quadrature amplitudes of the electromagnetic field is presented. The protocol utilizes shared entanglement provided by nondegenerate parametric down-conversion in the limit of large gain to attain high efficiency. For a constraint in the mean number of photons $\mathrm{n\ifmmode \bar{}\else \={}\fi{}}$ associated with modulation in the signal channel, the channel capacity for dense coding is found to be $\mathrm{ln}(1+\mathrm{n\ifmmode \bar{}\else \={}\fi{}}+{n}^{2}),$ which always beats coherent-state communication and surpasses squeezed-state communication for $\mathrm{n\ifmmode \bar{}\else \={}\fi{}}&gt;1.$ For $\mathrm{n\ifmmode \bar{}\else \={}\fi{}}\ensuremath{\gg}1,$ the dense coding capacity approaches twice that of either scheme.
Auditory Nerve and Brainstem Responses in Newborn Infants with Hyperbilirubinemia (1985)

To assess early bilirubin toxicity, a study was made of auditory brainstem responses in relation to total bilirubin levels as well as unbound bilirubin levels in 56 hyperbilirubinemic infants (total bilirubin greater than or equal to 15.0 mg/dL) and 24 infants who did not have jaundice. The latencies of wave I at 85 dB HL (hearing level) in hyperbilirubinemic infants were significantly greater than those in the control group. The latencies of wave I and V in hyperbilirubinemic infants with unbound bilirubin levels greater than or equal to 1.0 microgram/dL (group C) were greater than those in the control group and in the hyperbilirubinemic infants with unbound bilirubin levels less than 0.5 microgram/dL (group A) and with unbound bilirubin levels less than 1.0 microgram/dL (group B). There were no significant differences of the wave I-V interpeak latency between the control infants and the hyperbilirubinemic infants. Thirty of the 80 infants showed prolonged peak latencies (greater than the mean +/- 2 SD for the control infants) of wave I and/or V in one or both ears. The incidences of the prolonged peak latencies in group B (42%) and group C (89%) were significantly greater than that in the control group (12%). The serial determinations of auditory brainstem responses in infants treated with exchange transfusions revealed that the prolonged peak latencies before exchange transfusion improved at 48 and 96 hours after the procedure for wave I, and at 24, 48, and 96 hours after the procedure for wave V. The interpeak latency of wave I-V did not change with exchange transfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Soybean nodulation and grain yield as influenced by N-fertilizer rate, plant population density and cultivar in southern Quebec (1992)

Optimum soybean (Glycine max (L) Merr.) production requires information on the interaction between cultivars, population densities and fertilizer nutrients as related to climate and region. Consequently, field experiments were conducted to determine the effects of N-fertilizer rate, plant population and cultivar on soybean nodulation and grain yield on two soils in southern Quebec. N-fertilizer application consistently depressed soybean nodulation, but it improved soybean growth where initial soil inorganic-N levels were low. High plant population densities had little effect on individual plant nodulation, but they increased fresh nodule mass per unit area. Grain yields were increased with high plant population densities. The two cultivars tested, Apache and Maple Arrow, generally produced similar grain yields on the Ste. Rosalie soil, where yields were low due to moisture stress or low initial inorganic-N levels. On the more productive Ormstown soil, Apache produced higher grain yields than Maple Arrow.Key words: Glycine max (L.) Merr., N fertilization, plant population, nodulation, grain yield
The Crystal Structure ofEscherichia coliGroup 4 Capsule Protein GfcC Reveals a Domain Organization Resembling That of Wza (2011)

We report the 1.9 Å resolution crystal structure of enteropathogenic Escherichia coli GfcC, a periplasmic protein encoded by the gfc operon, which is essential for assembly of group 4 polysaccharide capsule (O-antigen capsule). Presumed gene orthologs of gfcC are present in capsule-encoding regions of at least 29 genera of Gram-negative bacteria. GfcC, a member of the DUF1017 family, is comprised of tandem β-grasp (ubiquitin-like) domains (D2 and D3) and a carboxyl-terminal amphipathic helix, a domain arrangement reminiscent of that of Wza that forms an exit pore for group 1 capsule export. Unlike the membrane-spanning C-terminal helix from Wza, the GfcC C-terminal helix packs against D3. Previously unobserved in a β-grasp domain structure is a 48-residue helical hairpin insert in D2 that binds to D3, constraining its position and sequestering the carboxyl-terminal amphipathic helix. A centrally located and invariant Arg115 not only is essential for proper localization but also forms one of two mostly conserved pockets. Finally, we draw analogies between a GfcC protein fused to an outer membrane β-barrel pore in some species and fusion proteins necessary for secreting biofilm-forming exopolysaccharides.
P-glycoprotein deficiency at the blood-brain barrier increases amyloid- deposition in an Alzheimer disease mouse model (2005)

Accumulation of amyloid-beta (Abeta) within extracellular spaces of the brain is a hallmark of Alzheimer disease (AD). In sporadic, late-onset AD, there is little evidence for increased Abeta production, suggesting that decreased elimination from the brain may contribute to elevated levels of Abeta and plaque formation. Efflux transport of Abeta across the blood-brain barrier (BBB) contributes to Abeta removal from the brain. P-glycoprotein (Pgp) is highly expressed on the luminal surface of brain capillary endothelial cells and contributes to the BBB. In Pgp-null mice, we show that [I]Abeta40 and [I]Abeta42 microinjected into the CNS clear at half the rate that they do in WT mice. When amyloid precursor protein-transgenic (APP-transgenic) mice were administered a Pgp inhibitor, Abeta levels within the brain interstitial fluid significantly increased within hours of treatment. Furthermore, APP-transgenic, Pgp-null mice had increased levels of brain Abeta and enhanced Abeta deposition compared with APP-transgenic, Pgp WT mice. These data establish a direct link between Pgp and Abeta metabolism in vivo and suggest that Pgp activity at the BBB could affect risk for developing AD as well as provide a novel diagnostic and therapeutic target.
Metabolism of Ca and Sr in Late Adult Life (1990)

Data are presented on the metabolism of Ca and Sr in a healthy male volunteer who, in a series of investigations conducted between the ages of 53 and 82 y, received controlled intakes of 45Ca, 47Ca, or 85Sr. No age-related trends were established, either in factors affecting the skeletal deposition of the tracers or in their subsequent retention studied for up to 462 d after intake. The data thus lend support to an important working postulate in the ICRP's model of alkaline earth metabolism.
Convening on the influenza human viral challenge model for universal influenza vaccines, Part 2: Methodologic considerations (2019)

In response to global interest in the development of a universal influenza vaccine, the Bill & Melinda Gates Foundation, PATH, and the Global Funders Consortium for Universal Influenza Vaccine Development convened a meeting of experts (London, UK, May 2018) to assess the role of a standardized controlled human influenza virus infection model (CHIVIM) towards the development of novel influenza vaccine candidates. This report (in two parts) summarizes those discussions and offers consensus recommendations. Part 1 covers challenge virus selection, regulatory and ethical considerations, and issues concerning standardization, access, and capacity. This article (Part 2) summarizes the discussion and recommendations concerning CHIVIM methods. The panelists identified an overall need for increased standardization of CHIVIM trials, in order to produce comparable results that can support universal vaccine licensure. Areas of discussion included study participant selection and screening, route of exposure and dose, devices for administering challenge, rescue therapy, protection of participants and institutions, clinical outcome measures, and other considerations. The panelists agreed upon specific recommendations to improve the standardization and usefulness of the model for vaccine development. Experts agreed that a research network of institutions working with a standardized CHIVIM could contribute important data to support more rapid development and licensure of novel vaccines capable of providing long-lasting protection against seasonal and pandemic influenza strains.