gebhart/patrepeval huggingface dataset:
Inhibition of Grape Crown Gall by<i>Agrobacterium vitis</i>F2/5 Requires Two Nonribosomal Peptide Synthetases and One Polyketide Synthase (2015)

Agrobacterium vitis nontumorigenic strain F2/5 is able to inhibit crown gall disease on grapevines. The mechanism of grape tumor inhibition (GTI) by F2/5 has not been fully determined. In this study, we demonstrate that two nonribosomal peptide synthetase (NRPS) genes (F-avi3342 and F-avi5730) and one polyketide synthase gene (F-avi4330) are required for GTI. Knockout of any one of them resulted in F/25 losing GTI capacity. We previously reported that F-avi3342 and F-avi4330 but not F-avi5730 are required for induction of grape tissue necrosis and tobacco hypersensitive response. F-avi5730 is predicted to encode a single modular NRPS. It is located in a cluster that is homologous to the siderophore vicibactin biosynthesis locus in Rhizobium species. Individual disruption of F-avi5730 and two immediate downstream genes, F-avi5731 and F-avi5732, all resulted in reduced siderophore production; however, only F-avi5730 was found to be required for GTI. Complemented F-avi5730 mutant (ΔF-avi5730(+)) restored a wild-type level of GTI activity. It was determined that, over time, populations of ΔF-avi4330, ΔF-avi3342, and ΔF-avi5730 at inoculated wound sites on grapevine did not differ from those of ΔF-avi5730(+) indicating that loss of GTI was not due to reduced colonization of wound sites by mutants.
Polarization mode dispersion compensation by phase diversity detection (1997)

A phase diversity detection method is described for compensating for polarization mode dispersion (PMD) in optical fiber at 10 Gb/s. The PMD distorted received signal is separated into its two constituent principal states of polarization (PSP) by maximizing the measured phase difference between the two pseudorandom data streams. The PMD is inferred from the measured phase and the two data streams are resynchronized by introducing appropriate delay/advance in their respective paths prior to merging in a combiner. The PMD source is a specially constructed three-sectioned polarization maintaining fiber that provides a controlled amount of PMD in the range of 1.6-42 ps.
<title>Optical property measurements in turbid media using frequency-domain photon migration</title> (1991)

In frequency-domain photon migration (FDPM), amplitude-modulated light is launched into a turbid medium, e.g., tissue, which results in the propagation of density waves of diffuse photons. Variations in the optical properties of the medium perturb the phase velocity and amplitude of the diffusing waves. These parameters can be determined by measuring the phase delay and demodulation amplitude of the waves with respect to the source. More specifically, the damped spherical-wave solutions to the homogeneous form of the diffusion equation yield expressions for phase ((phi) ) and demodulation (m) as a function of source distance, modulation frequency, absorption coefficient ((Beta) ), and effective scattering coefficient ((sigma) eff). In this work, analytical expressions for the variable dependence of (phi) and m on modulation frequency are presented. A simple method for extracting absorption coefficients from (phi) and m vs. frequency plots is applied to the measurement of tissue phantoms. Using modulation frequencies between 5 MHz and 250 MHz, absorption coefficients as low as 0.024 cm-1 are measured in the presence of effective scattering coefficients as high as 144 cm-1. The results underscore the importance of employing multiple modulation frequencies for the quantitative determination of optical properties.
Turning Defense into Offense: Defensin Mimetics as Novel Antibiotics Targeting Lipid II (2013)

We have previously reported on the functional interaction of Lipid II with human alpha-defensins, a class of antimicrobial peptides. Lipid II is an essential precursor for bacterial cell wall biosynthesis and an ideal and validated target for natural antibiotic compounds. Using a combination of structural, functional and in silico analyses, we present here the molecular basis for defensin-Lipid II binding. Based on the complex of Lipid II with Human Neutrophil peptide-1, we could identify and characterize chemically diverse low-molecular weight compounds that mimic the interactions between HNP-1 and Lipid II. Lead compound BAS00127538 was further characterized structurally and functionally; it specifically interacts with the N-acetyl muramic acid moiety and isoprenyl tail of Lipid II, targets cell wall synthesis and was protective in an in vivo model for sepsis. For the first time, we have identified and characterized low molecular weight synthetic compounds that target Lipid II with high specificity and affinity. Optimization of these compounds may allow for their development as novel, next generation therapeutic agents for the treatment of Gram-positive pathogenic infections.
Fluorescent peptidyl chemosensors for the measurement of divalent metal cation concentrations (2012)

Studies toward the production of fluorescent chemosensors for trace divalent metal ions have been conducted, with emphasis placed on the attainment of sufficient analyte selectivity and sensitivity for the measurement of environmental or biomedical samples. One technique that has historically been applied for the design of selective metal ion sensors is to prepare biosensors, devices that exploit proteins for their unmatched specificity in the recognition of small molecules. Alternately, the construction of abiotic chemosensors has been favored by other researchers, but the synthetic simplicity and enhanced durability exhibited by these agents comes at the expense of analyte-detection selectivity. By applying a strategy that is a hybrid of these approaches, selective and sensitive chemosensors for divalent zinc, copper, and nickel have been prepared. These devices combine the advantageous aspects of biosensors within a peptidyl architecture that by virtue of its synthetic origin contains an expanded repertoire of amino acids for metal ion binding and signaling. Fluorescent chemosensors for Zn(II) have been prepared that are based upon the zinc finger domains and enable the quantitation of sub-micromolar concentrations of that ion in the presence of many other divalent ions. In addition, other fluorosensors have been prepared that employ nonnatural alpha-amino acid derivatives that contain the bidentate metal binding functionality of oxine (8-hydroxyquinoline). These also enable the selective detection of sub-micromolar concentrations of Zn(II), but require only seven amino acid residues as opposed to the 25 present in the zinc finger-based sensors. By exploiting the metal binding properties of the amino terminal Cu(II)- and Ni(II)-binding (ATCUN) motif of the serum albumins, sensors have been prepared which enable the selective determination of sub-micromolar concentrations of the Cu(II) ion, even in the presence of elevated concentrations of Ni(II). Sensors for Ni(II) that employ a fluorescence resonance energy transer (FRET) mechanism for analyte detection have also been prepared. In addition, studies have been performed to convert these solution based chemosensing reagents into solid phase-attached devices, in order to perform realtime measurements with regenerable sensing materials.
P4‐226: Crystal structure of the amyloid precursor protein intracellular domain in complex with Fe65‐PTB2 (2009)

Amyloidogenic processing of the amyloid precursor protein (APP) is a key event in Alzheimer disease pathogenesis. It creates the amyloid-beta peptide (A-beta) which aggregates and forms the disease characteristic cerebral plaques and liberates the C-terminal APP intracellular domain (AICD) into the cytosol. While A-beta is in the limelight from the beginnings of Alzheimer research, the AICD slowly but surely enters the stage as an important player of the tragedy. Physiologically, the APP C-terminus is involved in APP internalization, transport and signal transduction by interacting with a variety of adaptor and signaling proteins. The interaction with the brain-enriched adaptor protein Fe65 is important for all of these processes. However, it plays as well a significant role for pathogenic APP processing and A-beta secretion. The structural basis of this central complex in APP metabolism and Alzheimer disease pathogenesis has so far been unknown. X-ray crystallography, Nuclear Magnetic Resonance (NMR), Isothermal Titration Calorimetry (ITC), Site Directed Mutagenesis. Here we present the crystal structure of the AICD of human APP695 in complex with the C-terminal phosphotyrosine binding domain of Fe65 (Fe65-PTB2) at 2.1 å resolution. In contrast to classical PTB domain/peptide interactions focusing on the NPX(p)Y consensus motif of the peptide, the AICD/Fe65-PTB2 complex involves two surrounding alpha-helices resulting in a three times enlarged and unique interface. The N-terminal helix of the AICD is capped by threonine 668, which upon phosphorylation regulates complex dissociation and its increased phosphorylation is an important pathologic trait of Alzheimer disease. The crystallographic analysis is complemented by NMR, ITC, and site directed mutagenesis data. The three-dimensional structure of the AICD/Fe65-PTB2 complex gives a detailed view on a central protein complex involved in APP physiology and Alzheimer disease pathology. An impressive number of cell biological, molecular biological, and biochemical data can now be integrated in a solid mechanistic model for complex regulation by the Alzheimer disease relevant phosphorylation of threonine 668 within the AICD. The knowledge of the AICD/Fe65-PTB2 complex structure and of its regulation sets the basis for a new structure based approach in the treatment of Alzheimer disease.
Raman Spectroscopy in Combination with Background Near‐infrared Autofluorescence Enhances the <i>In Vivo</i> Assessment of Malignant Tissues (2005)

The diagnostic ability of optical spectroscopy techniques, including near-infrared (NIR) Raman spectroscopy, NIR autofluorescence spectroscopy and the composite Raman and NIR autofluorescence spectroscopy, for in vivo detection of malignant tumors was evaluated in this study. A murine tumor model, in which BALB/c mice were implanted with Meth-A fibrosarcoma cells into the subcutaneous region of the lower back, was used for this purpose. A rapid-acquisition dispersive-type NIR Raman system was employed for tissue Raman and NIR autofluorescence spectroscopic measurements at 785-nm laser excitation. High-quality in vivo NIR Raman spectra associated with an autofluorescence background from mouse skin and tumor tissue were acquired in 5 s. Multivariate statistical techniques, including principal component analysis (PCA) and linear discriminant analysis (LDA), were used to develop diagnostic algorithms for differentiating tumors from normal tissue based on their spectral features. Spectral classification of tumor tissue was tested using a leave-one-out, cross-validation method, and the receiver operating characteristic (ROC) curves were used to further evaluate the performance of diagnostic algorithms derived. Thirty-two in vivo Raman, NIR fluorescence and composite Raman and NIR fluorescence spectra were analyzed (16 normal, 16 tumors). Classification results obtained from cross-validation of the LDA model based on the three spectral data sets showed diagnostic sensitivities of 81.3%, 93.8% and 93.8%; specificities of 100%, 87.5% and 100%; and overall diagnostic accuracies of 90.6%, 90.6% and 96.9% respectively, for tumor identification. ROC curves showed that the most effective diagnostic algorithms were from the composite Raman and NIR autofluorescence techniques.
Synthesis and Evaluation of Bombesin Derivatives on the Basis of Pan-Bombesin Peptides Labeled with Indium-111, Lutetium-177, and Yttrium-90 for Targeting Bombesin Receptor-Expressing Tumors (2004)

Bombesin receptors are overexpressed on a variety of human tumors like prostate, breast, and lung cancer. The aim of this study was to develop radiolabeled (Indium-111, Lutetium-177, and Yttrium-90) bombesin analogues with affinity to the three bombesin receptor subtypes for targeted radiotherapy. The following structures were synthesized: diethylenetriaminepentaacetic acid-gamma-aminobutyric acid-[D-Tyr6, beta-Ala11, Thi13, Nle14] bombesin (6-14) (BZH1) and 1,4,7,10-tetraazacyclododecane-N,N',N",N"' -tetraacetic acid-gamma-aminobutyric acid-[D-Tyr6, beta-Ala11, Thi13, Nle14] bombesin (6-14) (BZH2). [111In]-BZH1 and in particular [90Y]-BZH2 were shown to have high affinity to all three human bombesin receptor subtypes with binding affinities in the nanomolar range. In human serum metabolic cleavage was found between beta-Ala11 and His12 with an approximate half-life of 2 hours. The metabolic breakdown was inhibited by EDTA and beta-Ala11-His12 (carnosine) indicating that carnosinase is the active enzyme. Both 111In-labeled peptides were shown to internalize into gastrin-releasing peptide-receptor-positive AR4-2J and PC-3 cells with similar high rates, which were independent of the radiometal. The biodistribution studies of [111In]-BZH1 and [111In]-BZH2 ([177Lu]-BZH2) in AR4-2J tumor-bearing rats showed specific and high uptake in gastrin-releasing peptide-receptor-positive organs and in the AR4-2J tumor. A fast clearance from blood and all of the nontarget organs except the kidneys was found. These radiopeptides were composed of the first pan-bombesin radioligands, which show great promise for the early diagnosis of tumors bearing not only gastrin-releasing peptide-receptors but also the other two bombesin receptor subtypes and may be of use in targeted radiotherapy of these tumors.
Real Time Observation and Quantification of Shear-Induced Collagen Self-Assembly (2009)

Collagen is the most abundant protein in the extracellular matrix (ECM) of vertebrates and is distributed widely throughout connective tissues. Fibrillar collagen is the principal load-bearing molecule in vertebrates (e.g. type I in tendon and ligament and type II in cartilage). Its inherent biocompatibility makes collagen an attractive scaffolding material candidate for tissue engineering. Although use of 2-D or 3-D collagen networks as a substrate for cell culturing have provided invaluable information about cell-ECM interactions, it has not been very successful in producing load-bearing tissue-engineered constructs. We attribute the fundamental problem to the use of disorganized collagen which may interfere with the ability of cells to generate organization. Several research groups have developed methods to produce organized layer(s) of collagen fibrils de novo (often with the intention of using them for guiding cell culture systems). Methods employed to influence collagen fibril organization during self-assembly include, electro-spinning [1], the use of strong magnetic fields [2–4], electrical gradients [5], flows through a microfluidic channel [6, 7], a combination of fluid flow and magnetic field [8], dip-pen nanolithography [9], cholesteric methods [10], and even freezing and thawing [11]. Although there has been some progress in controlling the alignment of collagen fibrils in vitro, there are many unknown factors which govern directed collagen self-assembly.
Identification and partial characterization by chemical cross-linking of a binding protein for tissue-type plasminogen activator (t-PA) on rat hepatoma cells. A plasminogen activator inhibitor type 1-independent t-PA receptor. (1992)

Plasma tissue-type plasminogen activator (t-PA) is cleared rapidly in vivo by the liver. Previous studies with the human hepatoma cell line HepG2 have identified a clearance system for t-PA modulated by plasminogen activator inhibitor type 1 (PAI-1). In the present study, a rat hepatoma cell line MH1C1 is shown to contain a PAI-1-independent t-PA clearance system. At 4 degrees C, binding of 125I-t-PA to MH1C1 cells was rapid, specific, and saturable. Scatchard analysis of the binding data yielded a mean estimate of 105,000 high affinity binding sites per cell (Kd = 4.1 nM). When the bound ligand was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the majority (about 90%) of the specific binding was in the form of uncomplexed 125I-t-PA. This is in contrast to HepG2 cells in which specific binding was mainly in the form of a sodium dodecyl sulfate-stable 125I-t-PA.PAI-1 complex. When availability of matrix-associated PAI-1 was blocked by preincubation with anti-PAI-1 antibody or removed by elastase treatment, specific 125I-t-PA binding to MH1C1 cells was unaffected, whereas most of the specific 125I-t-PA binding to HepG2 cells was abolished. Furthermore, when the active site of t-PA was inactivated with diisopropyl fluorophosphate, the diisopropyl fluorophosphate-t-PA specifically competed for binding of 125I-t-PA to MH1C1 cells, but failed to block specific 125I-t-PA binding to HepG2 cells. At 37 degrees C, PAI-1-independent t-PA binding to MH1C1 cells was followed by ligand uptake and degradation with kinetics similar to that seen in HepG2 cells. Chemical cross-linking of t-PA to MH1C1 cells revealed a specific t-PA binding protein with a molecular mass of about 500,000 daltons. Ligand-receptor complexes generated by chemical cross-linking were immunoprecipitable by anti-t-PA antibody but not by anti-PAI-1 antibody, further supporting the finding that binding of t-PA to MH1C1 cells is PAI-1-independent.
ChemInform Abstract: 1,2,5‐THIADIAZOLE‐1‐OXIDES. II. THE CHEMISTRY OF THE AMINES (1982)

Abstract Einige Alkylierungs‐ und Acylierungsreaktionen des Aminothiadiazoloxids (I) werden beschrieben.
Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: <i>in vitro</i> studies (2002)

Endothelins (ETs), 21-amino-acid peptides involved in the pathogenesis of various diseases, bind to ET(A) and ET(B) receptors to initiate their effects. Based on the same core structure, we have developed four small-molecule ET receptor antagonists, ABT-627, ABT-546, A-182086 and A-192621, which exhibit difference in selectivity for ET(A) and ET(B) receptors. In this report, we compare the potency and selectivity of these four antagonists in inhibiting (125)I-labelled ET-1 binding to cloned human ET(A) and ET(B) receptors, and in blocking ET-1-induced functional responses (arachidonic acid release and phosphatidylinositol hydrolysis).
Laser writing of colour centres in diamond (2019)

Laser writing of colour centres in diamond offers a new method for the engineering of quantum materials and devices. Here we will describe our latest progress in the writing of highly coherent nitrogen-vacancy centres and in the deterministic writing of NV centres using laser annealing.
Design of nanoparticulate group 2 influenza hemagglutinin stem antigens that activate unmutated ancestor B cell receptors of broadly neutralizing antibody lineages (2018)

Influenza vaccines targeting the highly-conserved stem of the hemagglutinin (HA) surface glycoprotein have the potential to protect against pandemic and drifted seasonal influenza viruses not covered by current vaccines. While HA stem-based immunogens derived from group 1 influenza A have been shown to induce intra-group heterosubtypic protection, HA stem-specific antibody lineages originating from group 2 may be more likely to possess broad cross-group reactivity. We report the structure-guided development of mammalian cell-expressed candidate vaccine immunogens based on influenza A group 2 H3 and H7 HA stem trimers displayed on self-assembling ferritin nanoparticles using an iterative, multipronged approach involving helix stabilization, loop optimization, disulfide bond addition, and side chain repacking. These immunogens were thermostable, formed uniform and symmetric nanoparticles, were recognized by cross-group-reactive broadly neutralizing antibodies (bNAbs) with nanomolar affinity, and elicited protective, homosubtypic antibodies in mice. Importantly, several immunogens were able to activate B cells expressing inferred unmutated common ancestor (UCA) versions of cross-group-reactive human bNAbs from two multi-donor classes, suggesting they could initiate elicitation of these bNAbs in humans.
High-stiffness-driven micromechanical resonator oscillator with enhanced phase noise performance (2012)

A two-port micromechanical beam resonator driven by its high stiffness locations has been used to enable a series-resonant resonator oscillator, for the first time, with enhanced power handling and phase noise performance as compared with the same resonator design but using low-stiffness driving configuration. The key to attaining better power handling capability relies on driving electrode arrangement where critical handling power becomes much larger by driving the resonator at its high-stiffness locations than low-stiffness areas since power handling of a resonator is proportional to its effective stiffness. With 16.9X improvement on power handling capability for a 9.7-MHz beam resonator via the proposed high-stiffness driving concept, a MEMS-based oscillator referenced to it greatly benefit from power handling enhancement, therefore leading to 26.5 dB reduction in far-from-carrier phase noise as compared to its low-stiffness driving counterpart.
Small-molecule activation of SERCA2a SUMOylation for the treatment of heart failure (2015)

Decreased activity and expression of the cardiac sarcoplasmic reticulum calcium ATPase (SERCA2a), a critical pump regulating calcium cycling in cardiomyocyte, are hallmarks of heart failure. We have previously described a role for the small ubiquitin-like modifier type 1 (SUMO-1) as a regulator of SERCA2a and have shown that gene transfer of SUMO-1 in rodents and large animal models of heart failure restores cardiac function. Here, we identify and characterize a small molecule, N106, which increases SUMOylation of SERCA2a. This compound directly activates the SUMO-activating enzyme, E1 ligase, and triggers intrinsic SUMOylation of SERCA2a. We identify a pocket on SUMO E1 likely to be responsible for N106's effect. N106 treatment increases contractile properties of cultured rat cardiomyocytes and significantly improves ventricular function in mice with heart failure. This first-in-class small-molecule activator targeting SERCA2a SUMOylation may serve as a potential therapeutic strategy for treatment of heart failure.
Immersion heat treatments for inactivation of <i>Salmonella enteritidis</i> with intact eggs (1997)

The effects of water-bath immersion heat treatments on the inactivation of Salmonella enteritidis within intact shell eggs were evaluated. Six pooled strains of Salm. enteritidis (ca 3 x 10(8) cfu, inoculated near the centre of the yolk) were completely inactivated within 50-57.5 min at a bath temperature of 58 degrees C and within 65-75 min at 57 degrees C (an 8.4 to 8.5-D process per egg). Following the initial 24 to 35-min come-up period, semilogarithmic survivor curves obtained at 58 and 57 degrees C yielded apparent decimal reduction times (D-values) of 4.5 and 6.0 min, respectively. Haugh unit values increased during heating, while yolk index and albumen pH values were unaffected. Albumen clarity and functionality were affected by the thermal treatments; therefore, extended whip times would be required for meringue preparation using immersion-heated egg whites. Immersion-heated shell eggs could provide Salmonella-free ingredients for the preparation of a variety of minimally-cooked foods of interest to consumers and foodservice operators.