gebhart/patrepeval huggingface dataset:
Zur Kenntnis des Faktors F430 aus methanogenen Bakterien: Über die Natur der Isolierungsartefakte von F430, ein Beitrag zur Chemie von F430 und zur konformationellen Stereochemie der Ligandperipherie von hydroporphinoiden Nickel(II)‐Komplexen (1985)

Factor F430 from Methanogenic Bacteria: On the Nature of the Isolation Artefacts of F430, a Contribution to the Chemistry of F430 and the Conformational Stereochemistry of the Ligand Periphery of Hydroporphinoid Nickel(II) Complexes Factor F430 ( 1 ), a coenzyme from methanogenic bacteria, when heated in aqueous solution isomerizes to 12,13‐di‐epi‐F430 ( 5 ) via 13‐epi‐F430 ( 3 ). The equilibrium mixture of the three F430 isomers in aqueous phosphate buffer solution (pH 7, 100°) contains 88 % of 5 , 8 % of 3 , and 4 % of 1 (Scheme 1) . The structural assignment for the F430 isomers rests on FAB‐MS‐, UV/VIS‐, 1 H‐ and 13 C‐NMR spectra of their pentamethyl esters. Chemical proof for the double epimerization at the two chiral centers of F430's ring C was provided by ozonolytic degradation of the di‐epimer to give a ring‐C‐derived succinimide derivative that was shown to be the enantiomer of the one previously obtained by ozonolysis of F430M (see Scheme 2 ). The two F430 ring‐C epimers 3 and 5 are the isolation artefacts described in the earlier F430 literature. F430 is susceptible to autoxidation in air and the product, that absorbs at 560 nm, was shown to be the 12,13‐didehydro derivative 8 of F430 by spectroscopic characterization of its pentamethyl ester 9 . The dehydrogenation product 8 can be diastereoselectively reduced with Zn in AcOH to give natural F430 as the main product rather than the thermodynamically more stable F430‐di‐epimer ( Scheme 3 ). In the double epimerization of F430, the two ring‐C side chains change from a trans ‐quasi‐diaxial arrangement to the (locally) enantiomorphic position in which the same side chains are again in a trans ‐quasi‐diaxial arrangement. This equilibrium paradox as well as the kinetic diastereoselectivity of the reduction of 12,13‐didehydro‐F430 ( 8 ) are rationalized to be consequences of the general phenomenon documented earlier (see the preceding paper) according to which hydroporphinoid Ni(II) complexes all show a characteristic conformational ruffling of their ligand system due to the tendency of the (small) Ni(II) ion to contract the size of the ligand's central coordination hole (see Fig. 5 and 6 ).
Molecular analysis of NOZZLE , a gene involved in pattern formation and early sporogenesis during sex organ development in Arabidopsis thaliana (1999)

Sexual reproduction is a salient aspect of plants, and elaborate structures, such as the flowers of angiosperms, have evolved that aid in this process. Within the flower the corresponding sex organs, the anther and the ovule, form the male and female sporangia, the pollen sac and the nucellus, respectively. However, despite their central role for sexual reproduction little is known about the mechanisms that control the establishment of these important structures. Here we present the identification and molecular characterization of the NOZZLE (NZZ) gene in the flowering plant Arabidopsis thaliana. In several nzz mutants the nucellus and the pollen sac fail to form. It indicates that NZZ plays an early and central role in the development of both types of sporangia and that the mechanisms controlling these processes share a crucial factor. In addition, NZZ may have an early function during male and female sporogenesis as well. The evolutionary aspects of these findings are discussed. NZZ encodes a putative protein of unknown function. However, based on sequence analysis we speculate that NZZ is a nuclear protein and possibly a transcription factor.
A dose error evaluation study for 4D dose calculations (2014)

Previous studies have shown that respiration induced motion is not negligible for Stereotactic Body Radiation Therapy. The intrafractional breathing induced motion influences the delivered dose distribution on the underlying patient geometry such as the lung or the abdomen. If a static geometry is used, a planning process for these indications does not represent the entire dynamic process. The quality of a full 4D dose calculation approach depends on the dose coordinate transformation process between deformable geometries. This article provides an evaluation study that introduces an advanced method to verify the quality of numerical dose transformation generated by four different algorithms.The used transformation metric value is based on the deviation of the dose mass histogram (DMH) and the mean dose throughout dose transformation. The study compares the results of four algorithms. In general, two elementary approaches are used: dose mapping and energy transformation. Dose interpolation (DIM) and an advanced concept, so called divergent dose mapping model (dDMM), are used for dose mapping. The algorithms are compared to the basic energy transformation model (bETM) and the energy mass congruent mapping (EMCM). For evaluation 900 small sample regions of interest (ROI) are generated inside an exemplary lung geometry (4DCT). A homogeneous fluence distribution is assumed for dose calculation inside the ROIs. The dose transformations are performed with the four different algorithms.The study investigates the DMH-metric and the mean dose metric for different scenarios (voxel sizes: 8 mm, 4 mm, 2 mm, 1 mm; 9 different breathing phases). dDMM achieves the best transformation accuracy in all measured test cases with 3-5% lower errors than the other models. The results of dDMM are reasonable and most efficient in this study, although the model is simple and easy to implement. The EMCM model also achieved suitable results, but the approach requires a more complex programming structure. The study discloses disadvantages for the bETM and for the DIM. DIM yielded insufficient results for large voxel sizes, while bETM is prone to errors for small voxel sizes.
The role of pro‐resolution lipid mediators in infectious disease (2013)

Inflammation is an essential host defence against infection, but can be damaging when excessive. Resolution of inflammation is an active process, and the pro-resolution effects of lipoxins, resolvins and protectins have received significant interest. Here, we review emerging data on the role of these lipid mediators in infectious disease. Lipoxins influence host control of Mycobacterium tuberculosis, Toxoplasma gondii, Trypanosoma cruzi and Plasmodium berghei cerebral malaria in mice. Their effects are protective in toxoplasmosis, T. cruzi infection and cerebral malaria but detrimental in tuberculosis; related to the balance between pathogen-control and excessive immune response. Topical lipoxin abrogates the tissue damage seen in a rabbit model of Porphyromonas gingivalis periodontitis. The increased virulence of H5N1 influenza A virus in mice correlates with reduced expression of SOCS2, required to mediate the effects of lipoxin. Mice unable to synthesize lipoxin suffer increased lung pathology during respiratory syncytial virus infection. Protectin suppresses influenza A virus replication in vitro and increases survival in a mouse model of severe influenza infection. Resolvins were investigated in a number of animal models of systemic bacterial infection, and were found to enhance phagocytic clearance of bacteria, reduce inflammation severity, promote neutrophil apoptosis, modulate neutrophil chemotaxis and importantly, reduce mortality. Interestingly, resolvin also enhances the antibacterial effect of ciprofloxacin and vancomycin. Topical resolvin application reduces the severity of herpes simplex virus ocular infection in mice. If the effects of these mediators translate from pre-clinical studies into successful clinical trials, they represent promising new strategies in managing infectious disease.
Cell cycle control in Plasmodium falciparum: a genomics perspective (2004)

The molecular mechanisms regulating cell proliferation and development in malaria parasites are still largely unknown. Phenomenological observations, pertaining to the organisation of the cell cycle during schizogony or to the signal transduction pathways whose activation is responsible for the developmental stage transitions, can now be complemented with information gathered from genomic databases. The PlasmoDB database has been used extensively to identify putative homologues of a number of eukaryotic cell cycle regulators such as cyclins, cyclin-dependent kinases, factors involved in the control of DNA synthesis, and components of signal transduction pathways. However, gene identification based on sequence homology is limited by the fact that any Plasmodium-specific functional homologue will be missed by this approach. Furthermore, experimental data indicate that the structure of some regulatory pathways (unlike that of metabolic pathways) cannot be deducted directly from database mining. Because of these limitations in the direct exploitation of genomic database, elucidation of the organisation of the signal transduction and cell cycle machineries requires experimental, proteomics-based approaches such as the characterisation of protein complexes containing cell cycle regulators and the establishment of a map of protein-protein interactions involving these elements
ChemInform Abstract: Chemistry, Nutrition, and Health‐Promoting Properties of Hericium Erinaceus (Lion′s Mane) Mushroom Fruiting Bodies and Mycelia and Their Bioactive Compounds (2015)

Abstract Review: 139 refs.
Anticoagulation for Extracorporeal Life Support (2015)

Since its introduction to bedside clinical practice over 40 years ago, extracorporeal life support (ECLS) has been continually changing and improving as a life-saving technology. Extracorporeal life support disrupts the normal finely maintained balance of coagulation and fibrinolysis by exposing large amounts of blood to nonendothelial surfaces. This leads to an inflammatory response with activation of the coagulation cascade and the need for systemic anticoagulation. Unfractionated heparin (UNFH) is currently the standard anticoagulant in ECLS. Alternative anticoagulants have been recently developed with improved safety profiles and reliable monitoring. Within this group of agents are the direct thrombin inhibitors (DTIs) bivalirudin and argatroban. The purpose of this article is to compare these DTIs to the current standard of UNFH anticoagulation during ECLS, to evaluate the current literature surrounding the use of these drugs in ECLS, and finally to propose therapeutic guidelines for their use in ECLS.
Intraocular Biodistribution of Mono-L-aspartyl Chlorin e6 in a Primate Choroidal Neovascularization Model (2007)

This study demonstrated the selective accumulation of NPe6 photosensitizer and ICG dye within experimental CNV and rapid clearance from the circulation and retinochoroidal tissue.
Design and performance of compensated reluctance synchronous machine drive with extended constant power speed range (2012)

Reluctance synchronous machine drives are known to be efficient, however are also known to have a poor constant power speed range. Interior permanent magnets are normally used in the reluctance synchronous machine to improve the constant power speed range. In this paper an alternative reluctance synchronous machine drive that extends the constant power speed range without using permanent magnets is proposed and investigated. In the proposed drive the DC-link current is used through a compensating or assisting field winding on the rotor. The analysis and design aspects of such a reluctance machine are presented in the paper. The results show, amongst others, that the proposed drive can generate constant power up to 3.5 per unit speed and improve the power factor of the machine in certain cases by more than 20%.
Base Flipping within the α-Hemolysin Latch Allows Single-Molecule Identification of Mismatches in DNA (2015)

A method for identifying and differentiating DNA duplexes containing the mismatched base pairs CC and CA at single molecule resolution with the protein pore α-hemolysin (αHL) is presented. Unique modulating current signatures are observed for duplexes containing the CC and CA mismatches when the mismatch site in the duplex is situated in proximity to the latch constriction of αHL during DNA residence inside the pore. The frequency and current amplitude of the modulation states are dependent on the mismatch type (CC or CA) permitting easy discrimination of these mismatches from one another, and from a fully complementary duplex that exhibits no modulation. We attribute the modulating current signatures to base flipping and subsequent interaction with positively charged lysine residues at the latch constriction of αHL. Our hypothesis is supported by the extended residence times of DNA duplexes within the pore when a mismatch is in proximity to the latch constriction, and by the loss of the two-state current signature in low pH buffers (<6.3), where the protonation of one of the cytosine bases increases the stability of the intrahelical state.
Quantifying the absolute benefit of neoadjuvant chemotherapy followed by definitive therapy in patients with muscle-invasive bladder cancer: A systematic review and meta-analysis. (2022)

4594 Background: Cisplatin based neoadjuvant chemotherapy (NAC) followed by definitive therapy improves survival in patients with muscle invasive bladder cancer (MIBC). However, the clinical benefit of NAC might vary with the choice of definitive therapy. Therefore, we assessed the absolute benefit of NAC followed by radical cystectomy or radical radiotherapy separately using the totality of evidence. Methods: MEDLINE and EMBASE were systematically searched to identify randomized trials assessing cisplatin based neoadjuvant chemotherapy followed by either radical cystectomy or definitive radiotherapy in patients with MIBC. Outcomes of interest included overall survival (OS) and disease-free survival (DFS). Treatment effects were expressed as hazard ratios (HR) with 95% confidence interval (CI). Incidence rate ratios were calculated to estimate time to event outcomes for trials not reporting HR. A random-effects DerSimonian-Laird meta-analysis was conducted. Absolute effects were then obtained using baseline risks from the control arm of RCTs. Results: Of 4887 studies identified, 13 trials with 2529 patients were included in this meta-analysis. Most trials included patients with T2-4 and N0 patients and only 3 trials included patients with node positive disease. Total of 180 (47%) DFS events were observed with NAC+RC compared to 213 (56%) events in RC alone (HR: 0.72; 95% CI: 0.59-0.89) and 346 (58%) OS events were observed with NAC+ RC compared to 385 (52%) events in RC alone (HR: 0.80; 95% CI: 0.69-0.92). Total of 186 (70%) DFS events were observed with NAC + radiotherapy compared to 205 (71%) events in radiotherapy alone (HR: 0.91; 95% CI: 0.74-1.12) and 263 (58%) OS events were observed with NAC+ radiotherapy compared to 294 (61%) events in radiotherapy alone (HR:0.93; 95% CI: 0.79-1.08). Conclusions: The choice of definitive therapy after cisplatin-based NAC impacts survival in patients with MIBC. RC after NAC improved DFS (114 fewer events per 1000 events) and OS (76 fewer per 1000 events) whereas radiotherapy after NAC showed no survival benefit. [Table: see text]
Application of Chemiluminescent Probe to Monitoring Superoxide Radicals and Hydrogen Peroxide in TiO2 Photocatalysis (1997)

A chemiluminescent probe, luminol, was successfully applied to monitoring superoxide ions (O2•-) and hydrogen peroxide (H2O2) produced on photocatalytic reaction in aqueous TiO2 suspension. Two chemiluminescent reactions were distinguished from the decay profile after the end of the irradiation, and the reaction mechanism was analyzed. The fast decay component gives information about O2•- and the slow one provides the amount of H2O2. The rate constant for the reaction of O2•- with luminol was found to be 1 × 104 M-1 s-1. The amount of O2•- during the irradiation on TiO2 in alkaline solution could be estimated to be on the order of 10-13 M. Detection of H2O2 in concentrations as small as 10-9 M was demonstrated in the photocatalytic water oxidation.
Compressed sensing subtracted rotational angiography with multiple sparse penalty (2012)

Digital Subtraction Rotational Angiography (DSRA) is a clinical protocol that allows three-dimensional (3D) visualization of vasculature during minimally invasive procedures. C-arm systems that are used to generate 3D reconstructions in interventional radiology have limited sampling rate and thus, contrast resolution. To address this particular subsampling problem, we propose a novel iterative reconstruction algorithm based on compressed sensing. To this purpose, we exploit both spatial and temporal sparsity of DSRA. For computational efficiency, we use a proximal implementation that accommodates multiple ℓ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> -penalties. Experiments on both simulated and clinical data confirm the relevance of our strategy for reducing subsampling streak artifacts.
Loss of the exocyst complex component EXOC3 promotes hemostasis and accelerates arterial thrombosis (2021)

The exocyst is an octameric complex comprising 8 distinct protein subunits, exocyst complex components (EXOC) 1 to 8. It has an established role in tethering secretory vesicles to the plasma membrane, but its relevance to platelet granule secretion and function remains to be determined. Here, EXOC3 conditional knockout (KO) mice in the megakaryocyte/platelet lineage were generated to assess exocyst function in platelets. Significant defects in platelet aggregation, integrin activation, α-granule (P-selectin and platelet factor 4), dense granule, and lysosomal granule secretion were detected in EXOC3 KO platelets after treatment with a glycoprotein VI (GPVI)-selective agonist, collagen-related peptide (CRP). Except for P-selectin exposure, these defects were completely recovered by maximal CRP concentrations. GPVI surface levels were also significantly decreased by 14.5% in KO platelets, whereas defects in proximal GPVI signaling responses, Syk and LAT phosphorylation, and calcium mobilization were also detected, implying an indirect mechanism for these recoverable defects due to decreased surface GPVI. Paradoxically, dense granule secretion, integrin activation, and changes in surface expression of integrin αIIb (CD41) were significantly increased in KO platelets after protease-activated receptor 4 activation, but calcium responses were unaltered. Elevated integrin activation responses were completely suppressed with a P2Y12 receptor antagonist, suggesting enhanced dense granule secretion of adenosine 5'-diphosphate as a critical mediator of these responses. Finally, arterial thrombosis was significantly accelerated in KO mice, which also displayed improved hemostasis determined by reduced tail bleeding times. These findings reveal a regulatory role for the exocyst in controlling critical aspects of platelet function pertinent to thrombosis and hemostasis.
Manufacture of Solid Oxide Fuel Cells Using Electroless Co-Deposition: A Review of Work Carried out at Edinburgh Napier University (2015)

This paper reviews work carried out at Edinburgh Napier University on the manufacture of anodes and cathodes for solid oxide fuel cells (SOFCs) using electroless co-deposition of nickel and ceramic powders. Most of the work has been focused on anodes where the co-deposition of nickel and yttria stabilised zirconia (YSZ) negates the need for traditional manufacturing methods such as screen printing and removes the need for expensive and time consuming high temperature consolidation of the ceramic part of the composite. Work has also been carried out manufacturing cathodes by electroless co-deposition replacing YSZ with lanthanum strontium manganite and lanthanum nickel ferrite. Anodes and cathodes of both planar and tubular designs of SOFCs have been successfully manufactured using this technique and process variables have included ceramic particle size, bath pH, ceramic loading, the inclusion of pore-formers and tubular orientation in the electroless bath. Testing of the electrodes included impedance analysis, long term degradation testing at 850 o C for 500 and 1000-hours, high temperature electrical conductivity measurements, scanning electron microscopy and energy dispersive X-ray analysis. The cost benefits of the electroless co-deposition process compared with other conventional processes are also discussed.
Targeting Cullin–RING E3 ubiquitin ligases for drug discovery: structure, assembly and small-molecule modulation (2015)

In the last decade, the ubiquitin-proteasome system has emerged as a valid target for the development of novel therapeutics. E3 ubiquitin ligases are particularly attractive targets because they confer substrate specificity on the ubiquitin system. CRLs [Cullin-RING (really interesting new gene) E3 ubiquitin ligases] draw particular attention, being the largest family of E3s. The CRLs assemble into functional multisubunit complexes using a repertoire of substrate receptors, adaptors, Cullin scaffolds and RING-box proteins. Drug discovery targeting CRLs is growing in importance due to mounting evidence pointing to significant roles of these enzymes in diverse biological processes and human diseases, including cancer, where CRLs and their substrates often function as tumour suppressors or oncogenes. In the present review, we provide an account of the assembly and structure of CRL complexes, and outline the current state of the field in terms of available knowledge of small-molecule inhibitors and modulators of CRL activity. A comprehensive overview of the reported crystal structures of CRL subunits, components and full-size complexes, alone or with bound small molecules and substrate peptides, is included. This information is providing increasing opportunities to aid the rational structure-based design of chemical probes and potential small-molecule therapeutics targeting CRLs.
G-Induced Loss of Consciousness and Its Prevention (1988)

The current capabilities of trained individuals to maintain clear vision during sustained exposures to 9 Gz, an increase in protected G tolerance of about 4 G over World War II fighter pilots, is a result of combined use of a G suit and very effective self-protective straining maneuvers such as the M-1, L-1 and pressure breathing, all of which are variants of the Valsalva maneuver developed in the 1940s. However, more than ten fatal crashes attributed to acceleration-induced loss of consciousness have occurred in recent years. The most plausible causes are: (1) increased capability of jet-powered fighters to sustain, with minimal pilot effort, accelerations in the 7-10 Gz range for periods longer than the symptom-free 3-8 second cerebral ischemic anoxic period which precedes GLOC, (2) an improperly performed Valsalva-type straining maneuver, and (3) development of a hypotensive vasovagal type reaction. A foolproof GLOC warning system such as detection of zero arterial pulsations at ear level to activate an automatic plane control takeover system could avoid most GLOC crashes. However, an omni-directional surveillance fighter plane cockpit for a fully horizontal position, preferable prone, is the only physically and physiologically certain and safest way to eliminate GLOC and to achieve the probable tactical advantages of sustained combat maneuvering in the 9-15 Gz range. Keywords: Acceleration, G stress, Anti-G suit, Anti-G straining maneuver, Acceleration tolerance. (aw)