gebhart/patrepeval huggingface dataset:
The Transcriptomic Response of the Murine Thyroid Gland to Iodide Overload and the Role of the Nrf2 Antioxidant System (2020)

Iodide overload induces the Nrf2 cytoprotective response and upregulates inflammatory, immune, and fibrosis pathways similar to autoimmune hyperthyroidism (Graves' disease) and PTC.
Awakening a latent carbon fixation cycle in Escherichia coli (2020)

Carbon fixation is one of the most important biochemical processes. Most natural carbon fixation pathways are thought to have emerged from enzymes that originally performed other metabolic tasks. Can we recreate the emergence of a carbon fixation pathway in a heterotrophic host by recruiting only endogenous enzymes? In this study, we address this question by systematically analyzing possible carbon fixation pathways composed only of Escherichia coli native enzymes. We identify the GED (Gnd-Entner-Doudoroff) cycle as the simplest pathway that can operate with high thermodynamic driving force. This autocatalytic route is based on reductive carboxylation of ribulose 5-phosphate (Ru5P) by 6-phosphogluconate dehydrogenase (Gnd), followed by reactions of the Entner-Doudoroff pathway, gluconeogenesis, and the pentose phosphate pathway. We demonstrate the in vivo feasibility of this new-to-nature pathway by constructing E. coli gene deletion strains whose growth on pentose sugars depends on the GED shunt, a linear variant of the GED cycle which does not require the regeneration of Ru5P. Several metabolic adaptations, most importantly the increased production of NADPH, assist in establishing sufficiently high flux to sustain this growth. Our study exemplifies a trajectory for the emergence of carbon fixation in a heterotrophic organism and demonstrates a synthetic pathway of biotechnological interest.
Applications of spherical aberration correction in STEM and TEM (2010)

Extended abstract of a paper presented at Microscopy and Microanalysis 2010 in Portland, Oregon, USA, August 1 – August 5, 2010.
<scp>BRAF</scp> and <scp>MEK</scp> inhibitor therapy eliminates Nestin‐expressing melanoma cells in human tumors (2018)

Little is known about the in vivo impacts of targeted therapy on melanoma cell abundance and protein expression. Here, 21 antibodies were added to an established melanoma mass cytometry panel to measure 32 cellular features, distinguish malignant cells, and characterize dabrafenib and trametinib responses in BRAF<sup>V600mut</sup> melanoma. Tumor cells were biopsied before neoadjuvant therapy and compared to cells surgically resected from the same site after 4 weeks of therapy. Approximately 50,000 cells per tumor were characterized by mass cytometry and computational tools t-SNE/viSNE, FlowSOM, and MEM. The resulting single-cell view of melanoma treatment response revealed initially heterogeneous melanoma tumors were consistently cleared of Nestin-expressing melanoma cells. Melanoma cell subsets that persisted to week 4 were heterogeneous but expressed SOX2 or SOX10 proteins and specifically lacked surface expression of MHC I proteins by MEM analysis. Traditional histology imaging of tissue microarrays from the same tumors confirmed mass cytometry results, including persistence of NES- SOX10+ S100β+ melanoma cells. This quantitative single-cell view of melanoma treatment response revealed protein features of malignant cells that are not eliminated by targeted therapy.
Cooperative Transition‐Metal and Chiral Brønsted Acid Catalysis: Enantioselective Hydrogenation of Imines To Form Amines (2011)

Control with an iron hand: A broad range of ketimines underwent enantioselective hydrogenation in the presence of a chiral Brønsted catalyst and a well-defined nonchiral iron catalyst (see scheme). This procedure constitutes an attractive and environmentally favorable alternative to well-established asymmetric hydrogenation reactions with precious-metal catalysts.
Interconversion of Molybdenum Imido and Amido Complexes by Proton‐Coupled Electron Transfer (2018)

Interconversion of the molybdenum amido [(<sup>Ph</sup> Tpy)(PPh<sub>2</sub> Me)<sub>2</sub> Mo(NHtBuAr)][BArF<sup>24</sup> ] (<sup>Ph</sup> Tpy=4'-Ph-2,2',6',2"-terpyridine; tBuAr=4-tert-butyl-C<sub>6</sub> H<sub>4</sub> ; ArF<sup>24</sup> =(C<sub>6</sub> H<sub>3</sub> -3,5-(CF<sub>3</sub> )<sub>2</sub> )<sub>4</sub> ) and imido [(<sup>Ph</sup> Tpy)(PPh<sub>2</sub> Me)<sub>2</sub> Mo(NtBuAr)][BArF<sup>24</sup> ] complexes has been accomplished by proton-coupled electron transfer. The 2,4,6-tri-tert-butylphenoxyl radical was used as an oxidant and the non-classical ammine complex [(<sup>Ph</sup> Tpy)(PPh<sub>2</sub> Me)<sub>2</sub> Mo(NH<sub>3</sub> )][BArF<sup>24</sup> ] as the reductant. The N-H bond dissociation free energy (BDFE) of the amido N-H bond formed and cleaved in the sequence was experimentally bracketed between 45.8 and 52.3 kcal mol<sup>-1</sup> , in agreement with a DFT-computed value of 48 kcal mol<sup>-1</sup> . The N-H BDFE in combination with electrochemical data eliminate proton transfer as the first step in the N-H bond-forming sequence and favor initial electron transfer or concerted pathways.
The Isocyanide–Cyanide Rearrangement; Mechanism and Preparative Applications (1991)

Abstract Until recently the isocyanide–cyanide rearrangement was of interest almost solely as an example of a unimolecular gas‐phase reaction, and kinetic studies had been carried out in only a few simple cases. Kinetic measurements in solution were made possible only by the discovery and suppression of a parallel free‐radical chain process which leads to the same products. The rate of the isomerization is almost independent of the structure of the starting material and of the substituents present. An exception is provided by extreme steric hindrance in three dimensions which, as in tris‐α‐substituted triptycyl isocyanides, leads to a considerable increase in the activation energy. The results can be interpreted in terms of a purely sigmatropic mechanism, as predicted by ab initio calculations. The preparative application of this rearrangement reaction requires the suppression of side reactions and can best be carried out by flash pyrolysis; yields are then almost quantitative. Allyl isocyanides react without allyl isomerization, optically active isocyanides with complete retention of configuration. New, economically interesting syntheses for the known nonsteroidal anti‐inflammatory drugs ibuprofen and (S)‐naproxene are described. The application of the useful synthetic building blocks, the optically active β‐acyloxy cyanides, which are formed from optically active α‐amino acids, will be demonstrated.
Spirulina platensis as biosorbent of chromium and nickel from industrial effluents (2015)

The time-dependent biosorption capacity of the cyanobacterium Spirulina platensis was studied in regards to nickel and chromium removal from the industrial effluents of electroplating units. The elemental content of the S. platensis biomass and the metal concentrations of industrial effluents were traced through two analytical techniques, neutron activation analysis and atomic adsorption spectrometry, respectively. A rapid rate of chromium adsorption (initial concentration 9.4 mg/L) was observed within the first 15 min of the reaction. Furthermore, a high amount of iron (48%) and nickel (94%) was removed from the chromium containing industrial effluents by the spirulina biomass. During a 1 h period of the reaction, the biomass of cyanobacterium accumulated from the nickel containing industrial effluents 66% of the initial nickel content (14.1 mg/L), 52% of the initial iron, 30% of the initial zinc, and 50% of the intial barium content. Fourier transform infrared spectroscopy was used to identify functional groups responsible for metal binding.
What's new in electrosurgical instrumentation? (1978)

A 1976 report of the use of radiofrequency current to devitalize carcinomas in man stimulated this review of the historical background, the presently used techniques, and the problems associated with electrosurgery. Difficulties in electrosurgical techniques requiring further research are identified--i.e., the high heating and variable performance of dry dispersive electrodes, the hazards of tissue stimulation, high-frequency interference, and the potential impact of government regulation.
Simvastatin-dependent apoptosis in Hodgkin's lymphoma cells and growth impairment of human Hodgkin's tumors in vivo (2007)

Statins are used to treat hypercholesterolemia and seem to have a preventive effect against cancer through pleiotropic effects including prenylation-inhibition. So far nothing is known about the activity of statins or more specific prenylation-inhibitors in Hodgkin's lymphoma (HL). We, therefore, evaluated the anti-HL activity of simvastatin and specific prenylation-inhibitors. 2 microM Simvastatin induced caspase-related apoptosis via depletion of prenylation-substrates in several HL-cell lines. Furthermore, it effectively impaired tumor growth in a mouse model for HL. Since the prenylation-inhibitors FTI-277 and GGTI-298 were also effective against HL-cells, we conclude that statins and specific prenylation-inhibitors should be evaluated in HL patients.
Sensitivity in binding free energies due to protein reorganization (2016)

Abstract Tremendous recent improvements in computer hardware, coupled with advances in sampling techniques and force fields, are now allowing protein-ligand binding free energy calculations to be routinely used to aid pharmaceutical drug discovery projects. However, despite these recent innovations, there are still needs for further improvement in sampling algorithms to more adequately sample protein motion relevant to protein-ligand binding. Here, we report our work identifying and studying such clear and remaining needs in the apolar cavity of T4 Lysozyme L99A. In this study, we model recent experimental results that show the progressive opening of the binding pocket in response to a series of homologous ligands. 1 Even while using enhanced sampling techniques, we demonstrate that the predicted relative binding free energies (RBFE) are sensitive to the initial protein conformational state. Particularly, we highlight the importance of sufficient sampling of protein conformational changes and demonstrate how inclusion of three key protein residues in the ‘hot’ region of the FEP/REST simulation improves the sampling and resolves this sensitivity.
Airspace Restriction Planner for Sector Congestion Management (2005)

In today's operations, managing sector congestion problems is inherently a manual process. This paper describes a capability, called the Airspace Restriction Planner (ARP), which is designed to predict and manage sector congestion problems. The capability allows the Traffic Management Coordinators (TMCs) to identify the sectors that are going to be over-congested, identify the detailed characteristics of incoming traffic, and plan traffic flow management restrictions such as altitude capping, rerouting, departure delays, and time-based metering or miles-in-trail restrictions. The capability also provides immediate feedback on the effectiveness of the planned restrictions prior to their execution. This capability was prototyped using the NASA's Future Air Traffic Management Concepts Evaluation Tool. Using Cleveland Air Route Traffic Control Center's (ARTCC's) Ravenna sector airspace, human-in-the-loop simulations were conducted to examine the effectiveness and usability of the ARP. The results indicated that the TMCs were able to plan more accurate traffic flow management restrictions with the ARP. All eight participants indicated that this capability is valuable and needed for more precise ARTCC-level sector congestion management operations.
Development of Fluorescent Substrates and Assays for the Key Autophagy-Related Cysteine Protease Enzyme, ATG4B (2014)

The cysteine protease ATG4B plays a role in key steps of the autophagy process and is of interest as a potential therapeutic target. At an early step, ATG4B cleaves proLC3 isoforms to form LC3-I for subsequent lipidation to form LC3-II and autophagosome membrane insertion. ATG4B also cleaves phosphatidylethanolamine (PE) from LC3-II to regenerate LC3-I, enabling its recycling for further membrane biogenesis. Here, we report several novel assays for monitoring the enzymatic activity of ATG4B. An assay based on mass spectrometric analysis and quantification of cleavage of the substrate protein LC3-B was developed and, while useful for mechanistic studies, was not suitable for high throughput screening (HTS). A doubly fluorescent fluorescence resonance energy transfer (FRET) ligand YFP-LC3B-EmGFP (FRET-LC3) was constructed and shown to be an excellent substrate for ATG4B with rates of cleavage similar to that for LC3B itself. A HTS assay to identify candidate inhibitors of ATG4B utilizing FRET-LC3 as a substrate was developed and validated with a satisfactory Z′ factor and high signal-to-noise ratio suitable for screening small molecule libraries. Pilot screens of the 1,280-member library of pharmacologically active compounds (LOPAC™) and a 3,481-member library of known drugs (KD2) gave hit rates of 0.6% and 0.5% respectively, and subsequent titrations confirmed ATG4B inhibitory activity for three compounds, both in the FRET and mass spectrometry assays. The FRET- and mass spectrometry–based assays we have developed will allow for both HTS for inhibitors of ATG4B and mechanistic approaches to study inhibition of a major component of the autophagy pathway.
Paul K Strudler: The Oracle of RAD (2022)

Paul Strudler who facilitated the support of photodynamic therapy by an NIH study section.
Crowdsourcing-based evaluation of privacy in HDR images (2014)

The ability of High Dynamic Range imaging (HDRi) to capture details in high-contrast environments, making both dark and bright regions clearly visible, has a strong implication on privacy. However, the extent to which HDRi affects privacy when it is used instead of typical Standard Dynamic Range imaging (SDRi) is not yet clear. In this paper, we investigate the effect of HDRi on privacy via crowdsourcing evaluation using the Microworkers platform. Due to the lack of HDRi standard privacy evaluation dataset, we have created such dataset containing people of varying gender, race, and age, shot indoor and outdoor and under large range of lighting conditions. We evaluate the tone-mapped versions of these images, obtained by several representative tone-mapping algorithms, using subjective privacy evaluation methodology. Evaluation was performed using crowdsourcing-based framework, because it is a popular and effective alternative to traditional lab-based assessment. The results of the experiments demonstrate a significant loss of privacy when even tone-mapped versions of HDR images are used compared to typical SDR images shot with a standard exposure.
Isolates from Colonic Spirochetosis in Humans Show High Genomic Divergence and Potential Pathogenic Features but Are Not Detected Using Standard Primers for the Human Microbiota (2019)

Colonic spirochetosis, diagnosed based on the striking appearance in histological sections, still has an obscure clinical relevance, and only a few bacterial isolates from this condition have been characterized to date. In a randomized, population-based study in Stockholm, Sweden, 745 healthy individuals underwent colonoscopy with biopsy sampling. Of these individuals, 17 (2.3%) had colonic spirochetosis, which was associated with eosinophilic infiltration and a 3-fold-increased risk for irritable bowel syndrome (IBS). We aimed to culture the bacteria and perform whole-genome sequencing of the isolates from this unique representative population sample. From 14 out of 17 individuals with spirochetosis we successfully isolated, cultured, and performed whole-genome sequencing of in total 17 isolates, including the <i>Brachyspira aalborgi</i> type strain, 513A. Also, 16S analysis of the mucosa-associated microbiota was performed in the cases and nonspirochetosis controls. We found one isolate to be of the species <i>Brachyspira pilosicoli</i>; all remaining isolates were of the species <i>Brachyspira aalborgi</i> Besides displaying extensive genetic heterogeneity, the isolates harbored several mucin-degrading enzymes and other virulence-associated genes that could confer a pathogenic potential in the human colon. We also showed that 16S amplicon sequencing using standard primers for human microbiota studies failed to detect <i>Brachyspira</i> due to primer incompatibility.<b>IMPORTANCE</b> This is the first report of whole-genome analysis of clinical isolates from individuals with colonic spirochetosis. This characterization provides new opportunities in understanding the physiology and potentials of these bacteria that densely colonize the gut in the individuals infected. The observation that standard 16S amplicon primers fail to detect colonic spirochetosis may have major implications for studies searching for associations between members of the microbiota and clinical conditions such as irritable bowel syndrome (IBS) and should be taken into consideration in project design and interpretation of gastrointestinal tract microbiota in population-based and clinical settings.
Quinone Moieties Link the Microbial Respiration of Natural Organic Matter to the Chemical Reduction of Diverse Nitroaromatic Compounds (2022)

Insensitive munitions compounds (IMCs) are emerging nitroaromatic contaminants developed by the military as safer-to-handle alternatives to conventional explosives. Biotransformation of nitroaromatics via microbial respiration has only been reported for a limited number of substrates. Important soil microorganisms can respire natural organic matter (NOM) by reducing its quinone moieties to hydroquinones. Thus, we investigated the NOM respiration combined with the abiotic reduction of nitroaromatics by the hydroquinones formed. First, we established nitroaromatic concentration ranges that were nontoxic to the quinone respiration. Then, an enrichment culture dominated by <i>Geobacter anodireducens</i> could indirectly reduce a broad array of nitroaromatics by first respiring NOM components or the NOM surrogate anthraquinone-2,6-disulfonate (AQDS). Without quinones, no nitroaromatic tested was reduced except for the IMC 3-nitro-1,2,4-triazol-5-one (NTO). Thus, the quinone respiration expanded the spectrum of nitroaromatics susceptible to transformation. The system functioned with very low quinone concentrations because NOM was recycled by the nitroaromatic reduction. A metatranscriptomic analysis demonstrated that the microorganisms obtained energy from quinone or NTO reduction since respiratory genes were upregulated when AQDS or NTO was the electron acceptor. The results indicated microbial NOM respiration sustained by the nitroaromatic-dependent cycling of quinones. This process can be applied as a nitroaromatic remediation strategy, provided that a quinone pool is available for microorganisms.
MUSIC: Cardiac Imaging, Modelling and Visualisation Software for Diagnosis and Therapy (2022)

The tremendous advancement of cardiac imaging methods, the substantial progress in predictive modelling, along with the amount of new investigative multimodalities, challenge the current technologies in the cardiology field. Innovative, robust and multimodal tools need to be created in order to fuse imaging data (e.g., MR, CT) with mapped electrical activity and to integrate those into 3D biophysical models. In the past years, several cross-platform toolkits have been developed to provide image analysis tools to help build such software. The aim of this study is to introduce a novel multimodality software platform dedicated to cardiovascular diagnosis and therapy guidance: MUSIC. This platform was created to improve the image-guided cardiovascular interventional procedures and is a robust platform for AI/Deep Learning, image analysis and modelling in a newly created consortium with international hospitals. It also helps our researchers develop new techniques and have a better understanding of the cardiac tissue properties and physiological signals. Thus, this extraction of quantitative information from medical data leads to more repeatable and reliable medical diagnoses.
What next for Fukushima? (2018)

Nearly seven years after a powerful tsunami caused catastrophic damage to Japan's Fukushima Daiichi nuclear-power plant, the clean-up and recovery is still ongoing. Bruce Drinkwater and Rob Malkin recently visited the disaster site and the undamaged Tsuruga plant to see if they can pinpoint the true extent of the damage in the dangerously radioactive reactors
Impact of recurrent disease and chronic allograft nephropathy on the long-term allograft outcome in patients with IgA nephropathy (2009)

Although recurrent IgA nephropathy (IgAN) may lead to graft dysfunction after transplantation, donation from living related donor (LRD), with whom the risk of recurrence may be higher, is not a contraindication. Herein, we evaluated the natural history of allograft in recipients with IgAN and the risk factors influencing long-term allograft outcome. Recurrence rate and graft survival were assessed retrospectively in 221 IgAN patients, including transplants from 139 LRDs (62.9%). Ten-year cumulative rate for recurrent IgAN was 30.8%. The operation at younger age and donation from LRD were significant for the recurrence by multivariate analysis. Ten-year graft survival was affected by recurrent IgAN (61.0% in recurrent IgAN group vs. 85.1% in nonrecurrent, P < 0.01). However, transplants from LRDs did not show poor graft survival when compared with those from other types of donors. In transplants from LRDs, the incidence of chronic allograft nephropathy (CAN) was lower than those in grafts from deceased donors (10.8% vs. 19.5%, P < 0.05). When CAN was considered in addition to recurrence, the variance of graft survival was affected significantly by the development of CAN than by the recurrence. These results suggest that the detection and adequate management of CAN could improve graft outcome in transplant recipients with IgAN.
Prenatal diagnosis of medium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency in a family with a previous fatal case of sudden unexpected death in childhood (1995)

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a potentially fatal inherited disease with a carrier frequency of approximately 1:100 in most Caucasian populations. The disease is implicated in sudden unexpected death in childhood. A prevalent disease-causing point mutation (A985G) in the MCAD gene has been characterized, thus rendering diagnosis easy in the majority of cases. Since the clinical spectrum of MCAD deficiency ranges from death in the first days of life to an asymptomatic life, there are probably other genetic factors--in addition to MCAD mutations--involved in the expression of the disease. Thus, families who have experienced the death of a child from MCAD deficiency might have an increased risk of a seriously affected subsequent child. In such a family we have therefore performed a prenatal diagnosis on a chorionic villus sample by a highly specific and sensitive polymerase chain reaction (PCR) assay for the G985 mutation. The analysis was positive and resulted in abortion. We verified the diagnosis by direct analysis on blood spots and other tissue material from the aborted fetus and from family members.
Optical Parametric Oscillator with intra cavity sum frequency mixing of alternating signal and idler radiation for generating tunable UV ns impulses (2019)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text P. Mahnke, "Optical Parametric Oscillator with intra cavity sum frequency mixing of alternating signal and idler radiation for generating tunable UV ns impulses," in Laser Congress 2019 (ASSL, LAC, LS&C), OSA Technical Digest (Optica Publishing Group, 2019), paper JW2A.16. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article