gebhart/patrepeval huggingface dataset:
ThiN as a Versatile Domain of Transcriptional Repressors and Catalytic Enzymes of Thiamine Biosynthesis (2017)

Thiamine biosynthesis is commonly regulated by a riboswitch mechanism; however, the enzymatic steps and regulation of this pathway in archaea are poorly understood. <i>Haloferax volcanii</i>, one of the representative archaea, uses a eukaryote-like Thi4 (thiamine thiazole synthase) for the production of the thiazole ring and condenses this ring with a pyrimidine moiety synthesized by an apparent bacterium-like ThiC (2-methyl-4-amino-5-hydroxymethylpyrimidine [HMP] phosphate synthase) branch. Here we found that archaeal Thi4 and ThiC were encoded by leaderless transcripts, ruling out a riboswitch mechanism. Instead, a novel ThiR transcription factor that harbored an N-terminal helix-turn-helix (HTH) DNA binding domain and C-terminal ThiN (TMP synthase) domain was identified. In the presence of thiamine, ThiR was found to repress the expression of <i>thi4</i> and <i>thiC</i> by a DNA operator sequence that was conserved across archaeal phyla. Despite having a ThiN domain, ThiR was found to be catalytically inactive in compensating for the loss of ThiE (TMP synthase) function. In contrast, bifunctional ThiDN, in which the ThiN domain is fused to an N-terminal ThiD (HMP/HMP phosphate [HMP-P] kinase) domain, was found to be interchangeable for ThiE function and, thus, active in thiamine biosynthesis. A conserved Met residue of an extended α-helix near the active-site His of the ThiN domain was found to be important for ThiDN catalytic activity, whereas the corresponding Met residue was absent and the α-helix was shorter in ThiR homologs. Thus, we provide new insight into residues that distinguish catalytic from noncatalytic ThiN domains and reveal that thiamine biosynthesis in archaea is regulated by a transcriptional repressor, ThiR, and not by a riboswitch.<b>IMPORTANCE</b> Thiamine pyrophosphate (TPP) is a cofactor needed for the enzymatic activity of many cellular processes, including central metabolism. In archaea, thiamine biosynthesis is an apparent chimera of eukaryote- and bacterium-type pathways that is not well defined at the level of enzymatic steps or regulatory mechanisms. Here we find that ThiN is a versatile domain of transcriptional repressors and catalytic enzymes of thiamine biosynthesis in archaea. Our study provides new insight into residues that distinguish catalytic from noncatalytic ThiN domains and reveals that archaeal thiamine biosynthesis is regulated by a ThiN domain transcriptional repressor, ThiR, and not by a riboswitch.
An oxadiazole-based compound potentiates anti-tuberculosis treatment by increasing host resistance via zinc poisoning (2023)

Abstract Anti-tuberculosis drugs, mostly developed over 60 years ago, combined with a poorly effective vaccine, have failed to eradicate tuberculosis. More worryingly, multi-resistant strains of Mycobacterium tuberculosis are constantly emerging. Innovative strategies are thus urgently needed to improve tuberculosis treatment. Recently, host-directed therapy has emerged as a promising strategy to be used in adjunct with existing or future antibiotics, by improving innate immunity or limiting immunopathology. Here, using high content imaging, we identified novel 1,2,4-oxadiazole-based compounds, that allow human macrophages to control MTB replication. Genome-wide gene expression analysis revealed that these molecules induced zinc remobilization inside cells, resulting in bacterial zinc intoxication. More importantly, we also demonstrated that, upon treatment with these novel compounds, M. tuberculosis became even more sensitive to anti-tuberculosis drugs, in vitro and in vivo , in a mouse model of tuberculosis. Manipulation of heavy metal homeostasis holds thus great promise to be exploited to develop host-directed therapeutic interventions.
Abstract 2697: Drug combinations for breast cancer based on synthetic lethality screens in yeast (2016)

Abstract Synthetic lethality describes an interdependent relationship between two genes, where the loss of either one alone can be compensated, while the simultaneous loss of both genes causes a non-viable phenotype. In recent years, first therapeutics based on this concept entered the clinic, most notably the PARP inhibitors for BRCA1/2-mutated cancers. In the present study, we analyzed synthetic lethal interactions in yeast to identify new and potentially synergistic drug combinations for breast cancer therapy. We were able to confirm significantly enhanced cytotoxicity for predicted drug pairs in breast cancer cell lines in vitro. First, a predictor built from publicly available yeast genetic interactions in the Data Repository of Yeast Genetic INteraction (DRYGIN) was used to predict potential synthetic lethal genetic interactions in human. Independently, a data set containing all pharmacological approaches, targeted or cytostatic, in breast cancer therapy was created. These drug combinations and their respective targets were then analyzed regarding their coverage of predicted synthetic lethal interactions. New drug combinations, previously unused in breast cancer therapy, were identified in silico by combining drugs already in use for breast cancer therapy (individually or in other combinations) in such a manner that their combination covers one or more potential synthetic lethal gene pairs. From this set of new drug combination and their synthetic lethal gene pairs we further pursued the predicted interdependencies between farnesyl diphosphate synthase (FDPS) and tubulin, beta 1 (TUBB1) and between FDPS and phosphoinositide-dependent kinase-1 (PDPK1) as well as prostaglandin-endoperoxide synthase 2 (PTGS2). Drugs targeting these genes are celecoxib (PDPK1, PTGS2), an anti-inflammatory drug, and zoledronic acid (FDPS), a bone degradation inhibitor, as well as the cytotoxic agent paclitaxel (TUBB1). We performed cell viability and cytotoxicity assays to determine therapeutic effects of celecoxib, zoledronic acid and paclitaxel alone and in combination on selected breast cancer cell lines. Our results showed statistically significant decreases in cell viability for the combinational treatment with zoledronic acid and paclitaxel as well as with the per se non-cytotoxic combination of zoledronic acid and celecoxib when compared to single agent treatment. In conclusion, we present a bioinformatics approach to predict potentially synergistic gene interactions based on synthetic lethality found in yeast and a strategy for utilizing these interactions for identifying new potentially synergistic drug combinations. Citation Format: Michael Schwarz, Erwin Tomasich, Maximilian Marhold, Andreas Heinzel, Paul Perco, Peter Horak, Bernd Mayer, Michael Krainer. Drug combinations for breast cancer based on synthetic lethality screens in yeast. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2697.
Microwave-enhanced infrared thermography (1999)

Microwave heating of the ground can enhance IR signatures of buried objects. The extent of the enhancement depends upon many parameters including wavelength, polarization, angle of incidence, and properties of the solid and the object. We show that angle of incidence and dielectric properties of the object are important, with some analytical and experimental results.
GaSb-based VCSELs emitting in the mid-infrared wavelength range (2-3 µm) grown by molecular beam epitaxy (2008)

International audience
Origin of high electrical conductivity in alkaline-earth doped LaCoO3 (2012)

Alkaline-earth doped LaCoO3 has been found to be promising as conductive oxides instead of standard metals for use as electrodes. Electrical conductivity has a maximum, σ = 4.4 × 103 S cm−1, in La0.6Sr0.4CoO3. We believe that the increase in mobility was caused by the decrease in the Co–O bond length.
Herbicides, Inhibiting 4‐Hydroxyphenylpyruvate Dioxygenase (<scp>HPPD</scp>) (2002)

Abstract 4‐Hydroxyphenyl pyruvate dioxygenase (HPPD) is a recently identified herbicide target site. There are currently seven known herbicides that inhibit this target; five commercialized: sulcotrione, isoxaflutole, benzofenap, pyrazolynate, and pyrazoxyfen, and two in the process of being commercialized: mesotrione and benzobicyclon. These herbicides can be classed within three families of 4‐benzoyl‐cyclic aryl or heteroaryl compounds: the benzoyl‐isoxazoles, the benzoyl‐cyclohexanediones, and the benzoyl‐hydroxypyrazoles. As enzymes inhibitors, all share or can give rise to a diketone pharmacophore within their structure. All of these herbicides produce characteristic bleaching symptoms in susceptible species due to the consequences of HPPD inhibition. HPPD catalyzes a complex reaction in which the ketoacid of tyrosine, namely, hydroxyphenylpyruvate (HPPA) is oxidized, decarboxylated, and then rearranged to give 2,5‐dihydroxyphenylacetic acid, or homogentisic acid (HGA). HGA is the precursor of plastoquinone and tocopherols, and the former is a cofactor of phytoene desaturase. This enzyme is key in the biosynthesis of carotenoids, inhibition of which leads to the bleaching symptoms due to the reduction of photosynthetic pigment (chlorophylls and carotenoids) and chloroplast development. The structure and available physicochemical data, toxicology and ecotoxicology data, of these bleaching herbicides is presented, together with a more detailed review of each compound.
COVID-KOP: Integrating Emerging COVID-19 Data with the ROBOKOP Database (2020)

In response to the COVID-19 pandemic, we established COVID-KOP, a new knowledgebase integrating the existing ROBOKOP biomedical knowledge graph with information from recent biomedical literature on COVID-19 annotated in the CORD-19 collection. COVID-KOP can be used effectively to test new hypotheses concerning repurposing of known drugs and clinical drug candidates against COVID-19. COVID-KOP is freely accessible at <a href="https://covidkop.renci.org/">https://covidkop.renci.org/</a>. For code and instructions for the original ROBOKOP, see: https://github.com/NCATS-Gamma/robokop.
Global loss minimization control of PMSM considering cross-coupling and saturation (2015)

A global permanent magnet synchronous machine (PMSM) loss minimization control method is proposed based on nonlinear optimization in this paper. A look-up table based PMSM flux-linkage model is introduced to account for the saturation and cross-coupling effect, and the iron loss model is also numerically developed to account for the harmonic effect. The loss minimization problem can be programmed as a convex nonlinear optimization problem, which can be solved by an optimizer efficiently and effectively. The accuracy of the torque and iron loss is verified by FEA simulations, which confirm the effectiveness of the proposed method.
Carbo-loading in Coccidioides spp.: a quantitative analysis of CAZyme abundance and resulting glycan populations (2019)

Coccidioides spp. are important pneumonia-causing pathogens of the American southwest, but little is known about their glycobiology and how their glycosylations differ from other pneumonia-causing fungi. There is mounting preliminary evidence to suggest genus or even species-specific glycosylations in the fungal kingdom due to the presence of unique carbohydrate-active enzymes (CAZymes) in fungal genomes (Deshpande et al. 2008, Glycobiology, 18(8), 626-637; Karkowska-Kuleta and Kozik 2015, Acta Biochim Pol., 62(3), 339-351). If Coccidioides spp.-specific glycans can be identified, it may be possible to exploit these differences to develop more specific diagnostic approaches and more effective therapeutics. Herein, we i) mined Coccidioides spp. and other pathogenic fungal genomes to identify CAZymes specific for Coccidioides spp., ii) proteomically determined the Coccidioides spp. "CAZome" produced in vivo and in vitro, and iii) utilized glycomics to differentiate Coccidioides genus-specific N-glycans from other pathogenic fungi. As far as we are aware, this is the first proteomic and glycomic comparison of the N-glycomes and CAZomes of different fungal genera during infection in human hosts.
In-Plane Distribution of Phase Transition Temperature of KTa<sub>1-<i>x</i></sub>Nb<sub><i>x</i></sub>O<sub>3</sub>Measured with Single Temperature Sweep (2008)

We demonstrate that the paraelectric to ferroelectric phase transition temperature TC distribution of KTa1-xNbxO3 (KTN) crystal can be measured with a single temperature sweep by using scanning nonlinear dielectric microscopy (SNDM) in a chamber. We achieve this using our newly developed probe, which we designed to maintain a constant contact force during the temperature sweep. The TC measurement precision (standard deviation) is estimated to be 0.05 °C, where the standard deviation is defined as [∑i = 120∑j = 14(TCij-TCi)2/(4×20-1)]1/2, in which TCij is the TC value at point i measured in the jth trial, and TCi is the trial average of TC at point i.
Enhanced bioavailability of zeaxanthin in a milk-based formulation of wolfberry (Gou Qi Zi;<i>Fructus barbarum</i> L.) (2006)

The carotenoid zeaxanthin is concentrated within the macula. Increased macular zeaxanthin is suggested to lower the risk of age-related macular degeneration. The small red berry, wolfberry ( Fructus barbarum L.; Gou Qi Zi and Kei Tze), is one of the richest natural sources of zeaxanthin. However, carotenoid bioavailability is low, and food-based products with enhanced bioavailability are of interest. The present study investigated zeaxanthin bioavailability from three wolfberry formulations. Berries were homogenised in hot (80°C) water, warm (40°C) skimmed milk and hot (80°C) skimmed milk, with freeze drying of each preparation into a powdered form. A zeaxanthin-standardised dose (15mg) of each was consumed, in randomised order, together with a standardised breakfast by twelve healthy, consenting subjects in a cross-over trial, with a 3–5-week washout period between treatments. Blood samples were taken via a venous cannula immediately before (fasting) and 2, 4, 6, 7, 8 and 10h post-ingestion. Zeaxanthin concentration in the triacylglycerol-rich lipoprotein fraction of plasma was measured by HPLC. Results showed that triacylglycerol-rich lipoprotein zeaxanthin peaked at 6h post-ingestion for all formulations. Zeaxanthin bioavailability from the hot milk formulation was significantly higher ( p &lt;0·001) than from the others. Mean area under the curve ( n 12) results were 9·73 (sem 2·45), 3·24 (sem 0·72) and 3·14 (sem 1·09) nmol×h/l for the hot milk, warm milk and hot water formulations, respectively. Results showed clearly that homogenisation of wolfberry in hot skimmed milk results in a formulation that has a 3-fold enhanced bioavailability of zeaxanthin compared with both the ‘classical’ hot water and warm skimmed milk treatment of the berries.
Development of expressive robotic head for bipedal humanoid robot (2012)

This paper describes the development of a new expressive robotic head for the bipedal humanoid robot. Facial expressions of our old robotic head have low facial expression recognition rate and in order to improve it we asked amateur cartoonists to create computer graphics (CG) images. To realize such expressions found in the CGs, the new head was provided with 24-DoFs and facial color. We designed compact mechanisms that fit into the head, which dimensions are based on average adult Japanese female size. We conducted a survey with pictures and videos to evaluate the expression ability. Results showed that facial expression recognition rates for the 6 basic emotions are increased compared to the old KOBIAN's head.
New approach for solving electrocardiography imaging inverse problem with missing data on the body surface (2017)

In this work, we provide a new mathematical formulation for the inverse problem in electrocardiography imaging. The novelty of this approach is that we take into account the missing measurements on the body surface. The electrocardiography imaging is formulated as a data completion problem for the Laplace equation. The Neumann boundary condition is given at the whole body surface. The difficulty comes from the fact that the Dirichlet boundary condition is only given on a part of the body surface. In order to construct the electrical potential on the heart surface, we use an optimal control approach where the unknown potential at the external boundary is also part of the control variables. We use the method of factorization of elliptic boundary value problems combined with the finite difference method. We illustrate the theoretical results by some numerical simulations in a cylindrical domain. We numerically study the effect of the size of the missing data zone on the accuracy of the inverse solution.
Photobiocatalysis by a Lytic Polysaccharide Monooxygenase Using Intermittent Illumination (2020)

Photobiocatalysis holds great promise toward the development of sustainable and environmentally friendly processes, harnessing light to drive biocatalytic reactions. However, photobiocatalysis at the interface of insoluble substrates, such as cellulose, has not been studied in much detail. In this context, the catalytic enhancement of lytic polysaccharide monooxygenases (LPMOs) by light is of great interest to the biorefinery field due to their capacity to oxidatively cleave such recalcitrant polysaccharides which can facilitate the degradation of lignocellulose. It has previously been reported that light-driven LPMO reactions have a huge catalytic potential, but effective continuous illumination in reactors may be challenging. Therefore, we investigated the impact of intermittent illumination. We show that illumination intervals as short as 1 s/min enable LPMO catalysis on phosphoric acid-swollen cellulose (PASC) to the same level as continuous illumination. Additionally, time-resolved measurements indicate that reductant depletion, and not enzyme inactivation, limits light-driven LPMO reactions. This study shows that a 60-fold reduction in illumination time enhances LPMO catalysis while protecting reaction elements, e.g., the reductant. Most importantly, the significant enhancement of LPMO catalysis with minimal and intermittent illumination is promising toward an application of photobiocatalytic depolymerization of lignocellulose where shading and light scattering minimize light availability and continuity.
Detecting Mild Phonotrauma in Daily Life (2023)

Level 4, case-control study Laryngoscope, 133:3094-3099, 2023.
Biomarkers of essential fatty acid consumption and risk of prostatic carcinoma. (1996)

Animal studies have suggested that omega-6 fatty acids found in vegetable oils may promote prostate cancer. Our goal was to use erythrocyte membrane and adipose tissue fatty acid composition as biomarkers to investigate whether essential fatty acids modulated prostate cancer risk. An outpatient clinic-based study of 89 cases and 38 controls was conducted in North Carolina between July 1989 and December 1991. Cases were recruited from a university-based urology outpatient clinic. Eligible cases were more than 45 years of age and had histological confirmation of a prostate cancer diagnosis within 1 year of entry into the study. Controls were histologically confirmed free of prostate cancer. Erythrocyte membranes from venous blood and adipose tissue fatty acids from s.c. fat samples were analyzed in batches using capillary gas chromatography. Unconditional logistic regression analysis was used to calculate odds ratios for the association of each fatty acid with prostate cancer while controlling for potential confounders. Linoleic acid consumption was positively associated with prostate cancer risk. The odds ratios comparing the first and fourth quartiles of linoleic acid consumption were 3.54 (95% confidence interval, 1.0-12.53) with P trend < 0.04 for erythrocyte membranes, and 2.47 (95% confidence interval, 0.66-9.26) with P trend < 0.08 for adipose tissue. These data suggest that linoleic acid consumption may increase prostate cancer risk, which is consistent with results from animal experiments. Linoleic acid is found in vegetable oils used in cooking and in cereals, snack foods, and baked goods. Our data failed to demonstrate consistently a protective effect of marine omega-3 fatty acids on prostate cancer.
Energy-level engineering of self-assembled quantum dots by using AlGaAs alloy cladding layers (2000)

The ground-state energy level of an InAs quantum dot (QD) system can be changed from 1070 to 700 nm by changing the aluminum composition in the AlxGa1−xAs matrix. For all the QDs, the lattice-mismatched strains are the same as that of InAs/GaAs QDs, so that QDs are easily formed. Photoluminescence signals from the structures were strong at low temperature and stayed relatively high at room temperature. The results suggest that these highly strained QDs in the alloy matrices could be an excellent choice for the energy-level engineering of QDs.
Radiation‐Responsive Benzothiazolines as Potential Cleavable Fluorogenic Linkers for Drug Delivery (2023)

Radiosensitive compounds can be useful for the detection of radiations and also as prodrugs that can be activated during a radiotherapy. Herein we describe the use of benzothiazolines, which upon treatment with <sup>137</sup> Cs produced γ-irradiation in water give rise to fluorescent benzothiazoles and concomitant release of amines or carboxylic acids. In a proof of concept study, we showed that benzothiazolines may be used as new cleavable linkers that can be triggered upon irradiation.
Tridentate Aryloxy‐Based Titanium Catalysts towards Ethylene Oligomerization and Polymerization (2015)

Abstract A series of tridentate aryloxy‐based ligands were synthesized and characterized for their coordination behaviour towards Ti IV . Coordination studies revealed that the nature of the central atom (amine vs. ether) and the type of bridging spacer (aromatic vs. aliphatic) are important aryloxy ligand parameters and influence the ligand coordination mode and the formation of stable titanium complexes. This series of titanium complexes were evaluated in ethylene oligomerization and polymerization after activation with methylaluminoxane (MAO) and showed the preferential formation of polyethylene. In some cases, the formation of a small amount of 1‐hexene suggests the existence of several catalytic centres in the reaction mixture.
Editor’s Letter (2017)

1. Stanley J. Kon 1. Editor Hedging techniques are essential for risk management of fixed income portfolios. Great care must be taken, however, when the asset being hedged is illiquid. We begin this issue of The Journal of Fixed Income with an article by Arik Ben Dor and Jingling Guan that
lntron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain (1998)

At least 34 complex I subunits of the electron transport chain are encoded by the nuclear genome, but only 14 of these have been mapped in the human. To rapidly map additional subunits, we have performed a combination of database mining and direct "wet" experimentation to identify intron and/or 5' upstream genomic DNA regions for 16 complex I genes. Wet experimentation was applied to 5 genes, and involved direct PCR amplification of introns by inter-exon PCR or splinkerette based PCR walking. Database mining was applied to 11 genes, and entailed the identification of incompletely spliced mRNAs and genomic CpG island clone sequences. This data was in files that carried no documentary description of the non-exon regions. Non-exon sequences were thus derived for 15 complex I genes and used to design functional gene specific PCR assays. Radiation hybrid mapping of these PCRs located 15 complex I genes to chromosomes l, 4, 5 (2 genes), 7 (2 genes), 8, 9 (2 genes), 11, 14, 16 (2 genes), 18, and 19.