gebhart/patrepeval huggingface dataset:
Development of GSK's reagent guides – embedding sustainability into reagent selection (2013)

Reagent guides ranking commonly used reagents for 15 transformations have been developed to reduce the environmental impact of drug discovery and development. Reagents have been scored by a combination of health, safety and environmental risk phrases, life cycle analysis (where possible) and an assessment of the chemistry including considerations of atom efficiency, stoichiometry, work-up and other issues. Guides covering alkene reduction, amide formation, C–H bromination, C–H chlorination, deoxychlorination, epoxidation, ester formation, ether formation, fluorination, iodination, ketone reduction, nitro reduction, oxidation of alcohols to aldehydes and ketones, reductive amination and sulfur oxidation are shared, with an explanation of the methodology behind their generation.
Mixed Adenoneuroendocrine Carcinoma Is a Rare but Important Tumour Found in the Oesophagus (2016)

Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumour of the gastrointestinal tract that consists of a dual adenocarcinomatous and neuroendocrine differentiation, each component representing at least 30% of the tumour. We report a case of a 68-year-old man who presented with two-month history of postprandial pain and vomiting. Gastric endoscopy revealed a polypoid mass in the lower part of the oesophagus. In contrast to the majority of these tumours, this biopsy was immunohistochemically positive for chromogranin A, and synaptophysin and Ki-67 index was 50% and the tumour was diagnosed as poorly differentiated neuroendocrine carcinoma of the oesophagus. The patient underwent surgery and lower oesophagus resection was performed. Based on the histopathology and immunohistochemistry of the tumour in the oesophagogastrectomy specimen, a mixed adenoneuroendocrine carcinoma (MANEC) was diagnosed. The objective of this case report is to advocate for the focus on the MANEC diagnosis as such patients need to be referred to a centre of excellence with expertise in NET tumours, to have the correct diagnostic work-up, treatment, and secondary diagnostic procedures performed at progression, as this will have paramount influence of the choice of treatment.
A three-pulse model of DC side harmonic flow in HVDC systems (1989)

A model for analysis of DC side harmonics in HVDC systems is proposed. The model includes the stray capacitances of converter transformers and bushings and represents the 12-pulse converter as four three-pulse harmonic voltage sources. The appearance of ground-mode triplen harmonics of troublesome magnitude in pole and electrode lines, as noted in recent site measurements, is explained, as is the increase in magnitude of the characteristic 12-pulse harmonics. The consequences for DC design and the specification of telephone interference criteria are also discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A novel assay for drug-DNA binding mode, affinity, and exclusion number: scanning force microscopy. (1996)

Determining the mode-of-binding of a DNA ligand is not always straightforward. Here, we establish a scanning force microscopic assay for mode-of-binding that is (i) direct: lengths of individual DNA-ligand complexes are directly measured; (ii) rapid: there are no requirements for staining or elaborate sample preparation; and (iii) unambiguous: an observed increase in DNA length upon addition of a ligand is definitive evidence for an intercalative mode-of-binding. Mode-of-binding, binding affinity, and site-exclusion number are readily determined from scanning force microscopy measurements of the changes in length of individual drug-DNA complexes as a function of drug concentration. With this assay, we resolve the ambiguity surrounding the mode of binding of 2,5-bis(4-amidinophenyl) furan (APF) to DNA and show that it binds to DNA by nonintercalative modes. APF is a member of an important class of aromatic dicationic drugs that show significant activity in the treatment of Pneumocystis carinii pneumonia, an opportunistic infection that is the leading cause of death in AIDS patients.
Obtaining candidate words by polling in a large vocabulary speech recognition system (2003)

Considers the problem of rapidly obtaining a short list of candidate words for more detailed inspection in a large vocabulary, vector-quantizing speech recognition system. An approach called polling is advocated, in which each label produced by the vector quantizer casts a varying, real-valed vote for each word in the vocabulary. The words receiving the highest votes are placed on a short list to be matched in detail at a later stage of processing. Expressions are derived for these votes under the assumption that for any given word, the observed label frequencies have Poisson distributions. Although the method is more general, particular attention is paid to the implementation of polling in speech recognition systems which use hidden Markov models during the acoustic match computation. Results are presented of experiments with speaker-dependent and speaker-independent Markov models on two different isolated word recognition tasks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Extreme Optics: Inverse Design and Experimental Realizations of Ultra-Large-Area Complex Meta-Optics (2021)

We present a design framework for metasurface that uses a hybrid approximate solver for Maxwell&#x2019;s equations, which separates the computation for the metasurface&#x2019;s nanoscale and macro-scale, and thus makes large-diameter inverse design tractable on a laptop. We further demonstrate experimental realizations of ultra-large-area metasurfaces designed using this framework: (1) a lens with extended depth of field with a millimeter diameter, and (2) polychromatic lenses with diameters of up to 1 cm.
The hydrolysis mechanism of a GH45 cellulase and its potential relation to lytic transglycosylase and expansin function (2020)

Family 45 glycoside hydrolases (GH45) are endoglucanases that are integral to cellulolytic secretomes, and their ability to break down cellulose has been successfully exploited in textile and detergent industries. In addition to their industrial relevance, understanding the molecular mechanism of GH45-catalyzed hydrolysis is of fundamental importance because of their structural similarity to cell wall-modifying enzymes such as bacterial lytic transglycosylases (LTs) and expansins present in bacteria, plants, and fungi. Our understanding of the catalytic itinerary of GH45s has been incomplete because a crystal structure with substrate spanning the -1 to +1 subsites is currently lacking. Here we constructed and validated a putative Michaelis complex <i>in silico</i> and used it to elucidate the hydrolytic mechanism in a GH45, Cel45A from the fungus <i>Humicola insolens</i>, via unbiased simulation approaches. These molecular simulations revealed that the solvent-exposed active-site architecture results in lack of coordination for the hydroxymethyl group of the substrate at the -1 subsite. This lack of coordination imparted mobility to the hydroxymethyl group and enabled a crucial hydrogen bond with the catalytic acid during and after the reaction. This suggests the possibility of a nonhydrolytic reaction mechanism when the catalytic base aspartic acid is missing, as is the case in some LTs (murein transglycosylase A) and expansins. We calculated reaction free energies and demonstrate the thermodynamic feasibility of the hydrolytic and nonhydrolytic reaction mechanisms. Our results provide molecular insights into the hydrolysis mechanism in <i>Hi</i>Cel45A, with possible implications for elucidating the elusive catalytic mechanism in LTs and expansins.
Radioluminescence pumping (2004)

Studies of some optical materials, like fluored glass, crystals or polymers, show an important luminescence in the visible spectrum, near UV, due to high energy radiation (&#945;, &#946;, n, X-rays or &gamma;). This phenomenon, known as radioluminescence or scintillation, is especially used for medical physics and dosimetry. Those materials can be doped by heavy metal ions, like rare-earth elements. Recent studies show that the irradiation of such rare-earth doped scintillators, can emit visible spectral rays. Those are corresponding to rare-earth transitions, in addition to the normal radioluminescence of the undoped material. Those peaks cannot correspond to the propagation of the self-trapped exciton in the inorganic scintillator. We actually believe the rare-earth ions are just excited by the light (blue) emitted by the scintillator, and that finally this phenomenon is not electronic but photonic, thus a kind of radioluminofluorescence.
Modeling heat transfers across a silicone-based intumescent coating (2018)

International audience
Quantitative analysis of Triton X-100 in plasmid pUDKH by high performance liquid chromatography (2004)

PurposeIn the process of plasmid pUDKH production, Triton X-100 was used as a virus inactivated solvent. The residual Triton X-100 concentration must be determined in final products.MethodsA high performance liquid chromatography was used. The system included a Hypersil silica column, eluted with acetonitrile -H 2O(70∶30). The flow rate was 1.0 ml/min. ResultsThe detection limit was low (1.0 μg/ml) with detection at 223nm. The calibration linear range was between 1.25 μg/ml and 20 μg/ml.ConclusionThe method was rapid. It did not need sample pretreatment. The residual Triton X-100 in our final pUDKH products was determined at 2.27～3.00 μg/ml level.
Percutaneous posterior cervical fusion with the DTRAX Facet System for single-level radiculopathy: results in 60 patients (2013)

Results indicate that the DTRAX Facet System is safe and effective for treatment of cervical radiculopathy.
Single mode optofluidic distributed feedback dye laser (2006)

Single frequency lasing from organic dye solutions on a monolithic poly(dimethylsiloxane) (PDMS) elastomer chip is demonstrated. The laser cavity consists of a single mode liquid core/PDMS cladding channel waveguide and a phase shifted 15th order distributed feedback (DFB) structure. A 1mM solution of Rhodamine 6G in a methanol and ethylene glycol mixture was used as the gain medium. Using 6 nanosecond 532nm Nd:YAG laser pulses as the pump light, we achieved threshold pump fluence of ~0.8mJ/cm(2) and single-mode operation at pump levels up to ten times the threshold. This microfabricated dye laser provides a compact and inexpensive coherent light source for microfluidics and integrated optics covering from near UV to near IR spectral region.
Novel Electrophilic and Photoaffinity Covalent Probes for Mapping the Cannabinoid 1 Receptor Allosteric Site(s) (2015)

Undesirable side effects associated with orthosteric agonists/antagonists of cannabinoid 1 receptor (CB1R), a tractable target for treating several pathologies affecting humans, have greatly limited their translational potential. Recent discovery of CB1R negative allosteric modulators (NAMs) has renewed interest in CB1R by offering a potentially safer therapeutic avenue. To elucidate the CB1R allosteric binding motif and thereby facilitate rational drug discovery, we report the synthesis and biochemical characterization of first covalent ligands designed to bind irreversibly to the CB1R allosteric site. Either an electrophilic or a photoactivatable group was introduced at key positions of two classical CB1R NAMs: Org27569 (1) and PSNCBAM-1 (2). Among these, 20 (GAT100) emerged as the most potent NAM in functional assays, did not exhibit inverse agonism, and behaved as a robust positive allosteric modulator of binding of orthosteric agonist CP55,940. This novel covalent probe can serve as a useful tool for characterizing CB1R allosteric ligand-binding motifs.
Cloning and Mapping of the MEIS1 Gene, the Human Homolog of a Murine Leukemogenic Gene (1997)

The mammalian homeobox genes encode a family of transcription factors that are important in a wide range of cellular processes, including hematopoiesis. Aberrant expression of some homeobox genes is known to be oncogenic. We report the cloning and initial characterization of a human homeobox gene, MEIS1, identified in a survey of homeobox genes expressed in the human fetal liver. The complete cDNA sequence shows that MEIS1 is likely to be the human homolog of Meis1, a mouse gene that is known to be activated in myeloid leukemia by retroviral insertion. We found that the MEIS1 gene is expressed at low levels in normal immunohematopoietic tissues, including the fetal liver. However, consistent with its possible role in myeloid leukemogenesis, MEIS1 was expressed in a subset of myeloid leukemia cell lines, with the highest expression seen in those with a megakaryocytic-erythroid phenotype. The gene is also expressed at high levels in the cerebellum. The gene is located on human chromosome region 2p13-p14 and contains the previously identified anonymous markers D2S134 and NIB1519. Whether this gene, which is leukemogenic in mice, also plays a leukemogenic role in humans will require further study.
Experimental validation of crosstalk simulations for on-chip interconnects at high frequencies using S-parameters (2003)

Since advanced microprocessors are designed based on simulation tools, accurate assessments of the amount of crosstalk noise are of paramount importance to avoid logic failures and less-than-optimal designs. With increasing clock frequencies, inductive effects become more important, and the validity of assumptions commonly used in simulation tools and approaches is unclear. We compared accurate experimental S-parameters with results derived from both magneto-quasi-static and fullwave simulation tools, for simple crosstalk structures with various capacitive and inductive couplings, in the presence of parallel and orthogonal conductors. Our validation approach made possible the identification of the strengths and weaknesses of both tools as a function of frequency, which provides useful guidance to designers who have to balance the trade-offs between accuracy and computation expenses for a large variety of cases.
Author Correction: Mapping the Dynamic Functions and Structural Features of AcrB Efflux Pump Transporter Using Accelerated Molecular Dynamics Simulations (2019)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Resonance-enhanced optical annealing of silicon nanowires (2005)

We consider the visible-light absorption by Si nanowires. Because of the cylindrical geometry of the nanowire, there is an $S$-wave resonance mode with $m=0$, which greatly enhances the visible-light absorption of Si nanowire with diameters of about $20\phantom{\rule{0.3em}{0ex}}\mathrm{nm}$. The energy dissipations by thermal radiation and heat convection are also discussed. Our results give a quantitative explanation using electromagnetic theory of recent experimental phenomena that Si nanowires can ignite in air after a photographic flash.
Tethered capsule endomicroscopy: from bench to bedside at a primary care practice (2016)

Due to the relatively high cost and inconvenience of upper endoscopic biopsy and the rising incidence of esophageal adenocarcinoma, there is currently a need for an improved method for screening for Barrett’s esophagus. Ideally, such a test would be applied in the primary care setting and patients referred to endoscopy if the result is suspicious for Barrett’s. Tethered capsule endomicroscopy (TCE) is a recently developed technology that rapidly acquires microscopic images of the entire esophagus in unsedated subjects. Here, we present our first experience with clinical translation and feasibility of TCE in a primary care practice. The acceptance of the TCE device by the primary care clinical staff and patients shows the potential of this device to be useful as a screening tool for a broader population.
Mitotic MELK-eIF4B signaling controls protein synthesis and tumor cell survival (2016)

The protein kinase maternal and embryonic leucine zipper kinase (MELK) is critical for mitotic progression of cancer cells; however, its mechanisms of action remain largely unknown. By combined approaches of immunoprecipitation/mass spectrometry and peptide library profiling, we identified the eukaryotic translation initiation factor 4B (eIF4B) as a MELK-interacting protein during mitosis and a bona fide substrate of MELK. MELK phosphorylates eIF4B at Ser406, a modification found to be most robust in the mitotic phase of the cell cycle. We further show that the MELK-eIF4B signaling axis regulates protein synthesis during mitosis. Specifically, synthesis of myeloid cell leukemia 1 (MCL1), an antiapoptotic protein known to play a role in cancer cell survival during cell division, depends on the function of MELK-elF4B. Inactivation of MELK or eIF4B results in reduced protein synthesis of MCL1, which, in turn, induces apoptotic cell death of cancer cells. Our study thus defines a MELK-eIF4B signaling axis that regulates protein synthesis during mitosis, and consequently influences cancer cell survival.
Drug target identification and quantitative proteomics (2006)

The emerging technologies in proteomic analysis provide great opportunity for the discovery of novel therapeutic drug targets for unmet medical needs through delivering of key information on protein expression, post-translational modifications and protein-protein interactions. This review presents a summary of current quantitative proteomic concepts and mass spectrometric technologies, which enable the acceleration of target discovery. Examples of the strategies and current technologies in the target identification/validation process are provided to illustrate the successful application of proteomics in target identification, in particular for monoclonal antibody therapies. Current bottlenecks and future directions of proteomic studies for target and biomarker identification are also discussed to better facilitate the application of this technology.
CO/sub 2/ gas-dynamic laser with a high hydrogen content in the working mixture (1982)

Population inversion and relaxation time were studied for CO/sub 2/ lasers with a large proportion of Hz. Temperature and pressure dependence measurements were performed. (AIP)
An Intervention for Enhancing Compliance With Screening Recommendations for Diabetic Retinopathy: A bicoastal experience (1997)

This study and the prior study demonstrate that such a "reminder" intervention can improve compliance with diabetic retinal screening recommendations. A generalizable intervention, such as this, may be applicable on a national level. For these programs to be successful, however, HMOs and physicians must have a collaborative relationship.
Intramuscular and Liver Triglycerides Are Increased in the Elderly (2004)

Magnetic resonance spectroscopy studies have shown that intramyocellular lipids (IMCL) and liver fat (LFAT) levels vary with insulin sensitivity and obesity, which are common in the elderly. Thus, magnetic resonance spectroscopy was used to investigate the hypothesis that IMCL and LFAT are increased in the elderly. IMCL and LFAT in young (aged 20-32 yr) and elderly (aged 65-74 yr) were measured fasted, and glucose, insulin, total free fatty acids levels, and free fatty acids profiles were measured during a 2-h oral glucose tolerance test. Body fat percentage was determined with dual x-ray absorptiometry. The elderly had significantly greater IMCL (0.12 +/- 0.01 vs. 0.08 +/- 0.01, mean +/- sem; P = 0.01) and LFAT (0.28 +/- 0.06 vs. 0.08 +/- 0.01; P = 0.004; expressed as ratios to Intralipid standard) than the young. The elderly had increased insulin resistance as calculated by the Matsuda model compared with the young (5.1 +/- 0.9 vs. 9.9 +/- 1.4; P = 0.02). Regression analysis of all subjects indicated that the increases in IMCL and LFAT were correlated with insulin sensitivity, glycosylated hemoglobin, plasma lipids, and body fat. Furthermore, the correlation between insulin sensitivity and IMCL and LFAT remained significant, after accounting for the effect of body fat. Increases of IMCL and LFAT occur in elderly individuals and may be related to insulin resistance.
SEPARATION OF COPPER FROM A LEACHING SOLUTION OF PRINTED CIRCUIT BOARDS BY USING SOLVENT EXTRACTION WITH D2EHPA (2018)

Global generation of waste electrical and electronic equipment (WEEE) is increasing quickly. Metals from WEEE can be recovered by using unit operations of chemical engineering. This paper describes a combined hydrometallurgical route (sulfuric oxidant leaching + solvent extraction) to recover copper from printed circuit boards (PCBs). A non-magnetic fraction from comminuted PCBs was used to perform leaching tests at 75ºC for 6 hours in an oxidizing media (sulfuric acid + hydrogen peroxide). In order to separate zinc, aluminum, and copper from the leaching liquor, solvent extraction tests were carried out using D2EHPA. Parameters that influence the process, such as pH, extractant concentration, and the aqueous/organic (A/O) ratio were investigated. Solvent extraction experiments were carried out in two stages: i) separation of zinc, aluminum, and residual iron, and ii) copper separation. The results showed that the leaching obtained around 60% aluminum, 94% copper, 76% zinc, 50% nickel and residual iron from the non-magnetic fraction of PCBs. With the solvent experiments, in the first stage, 100 wt.% zinc, iron and aluminum were extracted at pH 3.5, 2:1 A/O, 10 % (v/v) D2EHPA, while, in the second stage 100% of the copper was extracted at pH 3.5, 1:1 A/O, 20 % (v/v) D2EHPA.
Mehrfachbindungen zwischen Hauptgruppenelementen und übergangsmetallen, CII. Flüchtige MN4‐Metallkomplexe von Niob und Tantal mit Dimethylsilyl‐Substituenten (1992)

Multiple Bonds between Main‐Group Elements and Transition Metals, CII [1] . — Volatile MN 4 Metal Complexes of Niobium and Tantalum Containing Dimethylsilyl Substituents Niobium and tantalum complexes 4a and 4b of formula (Me 2 SiH)N=M[N(SiHMe 2 ) 2 ] 3 ( a : M=Nb; b : M=Ta) are formed from lithium bis(dimethylsilyl)amide and either MOCl 3 ( 2a , b ) or MCl 5 ( 3a , b ). No β‐hydrogen decomposition of these compounds occurs under normal conditions.
A Mechanistic Investigation of Acid-Catalyzed Cleavage of Aryl-Ether Linkages: Implications for Lignin Depolymerization in Acidic Environments (2013)

Acid catalysis has long been used to depolymerize plant cell wall polysaccharides, and the mechanisms by which acid affects carbohydrates have been extensively studied. Lignin depolymerization, however, is not as well understood, primarily due to the heterogeneity and reactivity of lignin. We present an experimental and theoretical study of acid-catalyzed cleavage of two non-phenolic and two phenolic dimers that exhibit the β-O-4 ether linkage, the most common intermonomer bond in lignin. This work demonstrates that the rate of acid-catalyzed β-O-4 cleavage in dimers exhibiting a phenolic hydroxyl group is 2 orders of magnitude faster than in non-phenolic dimers. The experiments suggest that the major product distribution is similar for all model compounds, but a stable phenyl-dihydrobenzofuran species is observed in the acidolysis of two of the γ-carbinol containing model compounds. The presence of a methoxy substituent, commonly found in native lignin, prevents the formation of this intermediate. Reaction pathways were examined with quantum mechanical calculations, which aid in explaining the substantial differences in reactivity. Moreover, we use a radical scavenger to show that the commonly proposed homolytic cleavage pathway of phenolic β-O-4 linkages is unlikely in acidolysis conditions. Overall, this study explains the disparity between rates of β-O-4 cleavage seen in model compound experiments and acid pretreatment of biomass, and implies that depolymerization of lignin during acid-catalyzed pretreatment or fractionation will proceed via a heterolytic, unzipping mechanism wherein β-O-4 linkages are cleaved from the phenolic ends of branched, polymer chains inward toward the core of the polymer.