gebhart/patrepeval huggingface dataset:
Eplerenone prevented obesity-induced inflammasome activation and glucose intolerance (2017)

Obesity-associated activation of the renin-angiotensin-aldosterone system is implicated in the pathogenesis of insulin resistance; however, influences of mineralocorticoid receptor (MR) inhibition remain unclear. Therefore, we aimed to clarify the anti-inflammatory mechanisms of MR inhibition using eplerenone, a selective MR antagonist, in C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks. Eplerenone prevented excessive body weight gain and fat accumulation, ameliorated glucose intolerance and insulin resistance and enhanced energy metabolism. In the epididymal white adipose tissue (eWAT), eplerenone prevented obesity-induced accumulation of F4/80<sup>+</sup>CD11c<sup>+</sup>CD206<sup>-</sup>-M1-adipose tissue macrophage (ATM) and reduction of F4/80<sup>+</sup>CD11c<sup>-</sup>CD206<sup>+</sup>-M2-ATM. Interestingly, M1-macrophage exhibited lower expression levels of MR, compared with M2-macrophage, in the ATM of eWAT and <i>in vitro</i>-polarized bone marrow-derived macrophages (BMDM). Importantly, eplerenone and MR knockdown attenuated the increase in the expression levels of <i>proIl1b, Il6</i> and <i>Tnfa,</i> in the eWAT and liver of HFD-fed mice and LPS-stimulated BMDM. Moreover, eplerenone suppressed IL1b secretion from eWAT of HFD-fed mice. To reveal the anti-inflammatory mechanism, we investigated the involvement of NLRP3-inflammasome activation, a key process of IL1b overproduction. Eplerenone suppressed the expression of the inflammasome components, <i>Nlrp3</i> and <i>Caspase1,</i> in the eWAT and liver. Concerning the second triggering factors, ROS production and ATP- and nigericin-induced IL1b secretion were suppressed by eplerenone in the LPS-primed BMDM. These results indicate that eplerenone inhibited both the priming and triggering signals that promote NLRP3-inflammasome activation. Therefore, we consider MR to be a crucial target to prevent metabolic disorders by suppressing inflammasome-mediated chronic inflammation in the adipose tissue and liver under obese conditions.
Evaluation and Implementation of a Commercially Available Mass-Guided SFC Purification Platform in a High Throughput Purification Laboratory in Drug Discovery (2009)

Abstract The evaluation and implementation of a commercially available, off the shelf, analytical SFC/MS and a mass directed, semi-preparative SFC-MS system for use in a high throughput purification laboratory is described. The advantages of the use of SFC to support high throughput purification includes rapid evaporation of the chromatographic mobile phase in isolated fractions, resulting in faster sample turnaround time. In addition, SFC provides a complimentary separation technique based on normal phase, adsorption chromatography mechanisms. The screening scheme employed on the associated analytical SFC-MS and the methodology developed for the mass directed, semi-prep SFC-MS are presented in detail. The utilization of standard FractionLynx/AutoPurify functionalities to enable rapid incorporation into high throughput environments is also emphasized.
Modeling and mechanistic approach for acid red 88 dye removal by hydrothermally synthesized magnetic chitosan-grafted with side chain salicylaldehyde (2023)

Abstract This research used the hydrothermal process to cross-link biopolymer magnetic chitosan (CS/Fe 3 O 4 ) with an aromatic aldehyde (salicylaldehyde, SA) for the adsorption of acidic azo dye (AR88) from an aqueous environment. Analyses of VSM, pH pzc , CHNS, XRD, SEM-EDX, FTIR, and BET were used to determine the properties of CS-SL/Fe 3 O 4 material. Using the Box-Behnken design (BBD), the effects of A: CS-SL/Fe 3 O 4 dose range from 0.02–0.1 g, B: [AR88] concentration (10–50 mg/L), C: pH (4–10), and D: duration (10–90 min) on the adsorption performance of CS-SL/Fe 3 O 4 toward AR88 dye were systematically investigated. In this research, the Freundlich isotherm and pseudo-second-order kinetic models were applicable to describe the adsorption rate of AR888 molecules. The maximum adsorption capacity ( q max ) of the hydrothermally cross-linked CS-SL/Fe 3 O 4 for AR88 dye was 137.3 mg/g. Multiple mechanisms, including electrostatic attraction, π-π stacking, n-π interaction, and H-bonding, are responsible for AR88 adsorption by CS-SL/Fe 3 O 4 . This study demonstrates that hydrothermal preparation of cross-linked CS-SL/Fe 3 O 4 offers an effective and promising adsorbent for removing acidic dyes from polluted water.
A Quantitative Approach to Characterizing Cell Lysis Caused by Mechanical Agitation of Streptomyces clavuligerus (2001)

Streptomyces clavuligerus is a commercially important actinomycete that is used to produce clavulanic acid, a beta-lactamase inhibitor. Observations during 10 batch cultivations with S. clavuligerus on defined media have led to the finding that the organism is very sensitive to shear when grown in batch cultures with increasing stirrer speed. The stirrer speed was increased to keep the dissolved oxygen level above 50% air saturation. A quantitative approach based on the calculation of elemental balances and a simple mathematical model is proposed to characterize the biomass lysis. Finally, a linear relation between biomass yield and observed specific growth rate is determined. Results show that cell lysis occurs at a high degradation rate, e.g., mu(max) = 0.16 h(-1) and k(d) = 0.07 h(-1), when the gassed power input increases above 1.1, 1.7, or 2.0 kW/m(3), respectively, depending on the medium composition. The overall biomass yield on substrate is dramatically reduced in all experiments (>30%).
Weighted Cumulative Sum Technique (1989)

A class of weighted control schemes that generalizes the basic cumulative sum (CUSUM) technique is introduced. The schemes of the first type, in which the weights represent information concomitant with the data, prove to be especially useful when handling charts corresponding to samples of varying sizes. The schemes of the second type are based on giving greater weight to more recent information. Representatives of this class are shown to have better run length characteristics with respect to drift in the level of a controlled process than does the classical CUSUM, while maintaining good sensitivity with respect to shifts. Analogous to the classical CUSUM scheme, they admit a dual graphical representation; that is, the scheme can be applied by means of a one- or two-sided decision interval or via a V mask. A special case of this type of scheme, designated the geometric CUSUM, is considered in detail. It can be viewed as a CUSUM-type counterpart of the exponentially weighted moving average.
Multiprobe Study of the Solid Electrolyte Interphase on Silicon-Based Electrodes in Full-Cell Configuration (2016)

The failure mechanism of silicon-based electrodes has been studied only in a half-cell configuration so far. Here, a combination of <sup>7</sup>Li, <sup>19</sup>F MAS NMR, XPS, TOF-SIMS, and STEM-EELS, provides an in-depth characterization of the solid electrolyte interphase (SEI) formation on the surface of silicon and its evolution upon aging and cycling with LiNi<sub>1/3</sub>Mn<sub>1/3</sub>Co<sub>1/3</sub>O<sub>2</sub> as the positive electrode in a full Li-ion cell configuration. This multiprobe approach indicates that the electrolyte degradation process observed in the case of full Li-ion cells exhibits many similarities to what has been observed in the case of half-cells in previous works, in particular during the early stages of the cycling. Like in the case of Si/Li half-cells, the development of the inorganic part of the SEI mostly occurs during the early stage of cycling while an incessant degradation of the organic solvents of the electrolyte occurs upon cycling. However, for extended cycling, all the lithium available for cycling is consumed because of parasitic reactions and is either trapped in an intermediate part of the SEI or in the electrolyte. This nevertheless does not prevent the further degradation of the organic electrolyte solvents, leading to the formation of lithium-free organic degradation products at the extreme surface of the SEI. At this point, without any available lithium left, the cell cannot function properly anymore. Cycled positive and negative electrodes do not show any sign of particles disconnection or clogging of their porosity by electrolyte degradation products and can still function in half-cell configuration. The failure mechanism for full Li-ion cells appears then very different from that known for half-cells and is clearly due to a lack of cyclable lithium because of parasitic reactions occurring before the accumulation of electrolyte degradation products clogs the porosity of the composite electrode or disconnects the active material particles.
2D curtailed harmonic memory polynomial for reduced complexity in concurrent dual‐band modelling and digital predistortion with the second band at harmonic frequency (2018)

Multi‐band transmitter systems are evolving to support the smooth transition from 4G to 5G communication systems. Moreover, recent developments of multi‐band and ultra‐wideband power amplifiers have led to a possible scenario where the second carrier signal is transmitted at the harmonic frequency of the first carrier signal. This results in harmonic interference from the first carrier signal as well as additional cross‐modulation and intermodulation distortion (IMD) components, which cannot be filtered out. The computational and memory requirements for digital predistortion (DPD) in such scenario increase drastically to include all interference terms. This study presents a novel two‐dimensional curtailed harmonic memory polynomial (2D‐CHMP) model to capture harmonic interferences, cross‐modulation and IMDs. The model complexity and memory requirement of 2D‐CHMP are very less as compared to the state‐of‐the‐art two‐dimensional harmonic memory polynomial (2D‐HMP) model. For proof‐of‐concept, it is shown with two different measurement setups that the proposed 2D‐CHMP DPD provides similar linearisation performances as compared to the 2D‐HMP DPD with less number of coefficients and computational complexity. As a study, it is shown that the proposed model can be further adapted to a low‐precision (low‐bit) environment by utilising principal component analysis.
A UK NEQAS ISH Multicenter Ring Study Using the Ventana HER2 Dual-Color ISH Assay (2010)

We performed a multicenter assessment of a new HER2 dual-color chromogenic in situ hybridization (CISH) test and herein report on concordance of CISH data with fluorescence in situ hybridization (FISH) data and intraobserver and interlaboratory scoring consistency. HER2 results were evaluated using duplicate cores from 30 breast cancers in 5 laboratories using the Ventana HER2 dual-color ISH assay (Ventana Medical Systems, Cambridgeshire, England) and in 1 central laboratory using a standard FISH assay. Overall 93.3% of cases were successfully analyzed by CISH across the 5 participating laboratories. There was excellent concordance (98.0% overall) for diagnosis of HER2 amplification by CISH compared with FISH. Intraobserver variability (7.7%) and intersite variability (9.1%) of absolute HER2/chromosome enumeration probe 17 ratios were tightly controlled across all participating laboratories. The Ventana HER2 dual-color ISH assay is robust and reproducible, shows good concordance with a standard FISH assay, and complies with requirements in national and international guidelines for performance of ISH-based diagnostic tests.
Source decomposition of acoustic variability in a modular connectionist network (1991)

A modular connectionist network model for capturing invariant relationships between the acoustic signal and phonetic categories is developed. The model addresses variations in the acoustic manifestation of phonemes as a function of loudness, speaker identity, speaking rate, and phonetic context. These sources of variation are referred to separate specialized network modules. Each module transforms the representation of its input signal in order to normalize the effect of different source variables. Components of the model have been tested on isolated words for speaker-adaptive vowel recognition (97%) and context-dependent vowel recognition (99.7%). A model integrating amplitude-normalization, speaker-normalization, and context-modulation for continuous speech recognition is under development.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
RNA Interference-Based Pesticides and Antiviral Agents: Microbial Overproduction Systems for Double-Stranded RNA for Applications in Agriculture and Aquaculture (2022)

RNA interference (RNAi)-based pesticides are pest control agents that use RNAi mechanisms as the basis of their action. They are regarded as environmentally friendly and are a promising alternative to conventional chemical pesticides. The effective substance in RNAi-based pesticides is double-stranded RNA (dsRNA) designed to match the nucleotide sequence of a target essential gene of the pest of concern. When taken up by the pest, this exerts an RNAi effect and inhibits some vital biochemical/biological process in the pest. dsRNA products are also expected to be applied for the control of viral diseases in aquaculture by RNAi, especially in shrimp farming. A critical issue in the practical application of RNAi agents is that production of the dsRNA must be low-cost. Here, we review recent methods for microbial production of dsRNAs using representative microorganisms (Escherichia coli, Pseudomonas syringae, Corynebacterium glutamicum, Chlamydomonas reinhardtii, and others) as host strains. The characteristics of each dsRNA production system are discussed.
Multiplexed proteomics of autophagy deficient macrophages reveals enhanced anti-microbial immunity via the oxidative stress response (2021)

Abstract Macrophages play a critical role in clearance of cytosolic pathogens. Autophagy functions at the intersection of antimicrobial innate immunity, metabolism and protein quality control; however, the impacts of infection and autophagy on shaping the macrophage proteome are poorly understood. Here, we describe a deep multi-dimensional proteomic analysis of primary murine macrophages infected with Shigella flexneri (S. flexneri). Tandem mass tagging (TMT) revealed dynamic genotype- and infection-dependent differences in host and pathogen proteins, phosphorylation and ubiquitination. These data catalogue the complex circuitry connecting autophagy, inflammatory signaling and the oxidative stress response. Loss of the autophagy gene Atg16l1 induced basal oxidative stress, activated the compensatory glutathione biosynthetic machinery, and surprisingly, enhanced clearance of S. flexneri. Pathogen clearance was similarly enhanced in wild type macrophages upon pharmacological inhibition of cysteine import. Our study provides a resource for innate immunity research and unexpectedly reveals that ATG16L1 dampens antimicrobial immunity by regulating oxidative stress.
The Immunological Evolution of Catalysis (1996)

The germline genes used by the mouse to generate the esterolytic antibody 48G7 were cloned and expressed in an effort to increase our understanding of the detailed molecular mechanisms by which the immune system evolves catalytic function. The nine replacement mutations that were fixed during affinity maturation increased affinity for the transition state analogue by a factor of 10(4), primarily the result of a decrease in the dissociation rate of the hapten-antibody complex. There was a corresponding increase in the rate of reaction of antibody with substrate, k(cat)/k(m), from 1.7 x 10(2)M(-1) min(-1) to 1.4 x 10(4)M(-1) min(-1). The three-dimensional crystal structure of the 48G7-transition state analogue complex at 2.0 angstroms resolution indicates that one of the nine residues in which somatic mutations have been fixed directly contact the hapten. Thus, in the case of 48G7, affinity maturation appears to play a conformational role, either in reorganizing the active site geometry of limiting side-chain and backbone flexibility of the germline antibody. The crystal structure and analysis of somatic and directed active site mutants underscore the role of transition state stabilization in the evolution of this catalytic antibody.
Polygenic background modifies penetrance of monogenic variants conferring risk for coronary artery disease, breast cancer, or colorectal cancer (2019)

ABSTRACT Background Genetic variation can predispose to disease both through (i) monogenic risk variants in specific genes that disrupt a specific physiologic pathway and have a large effect on disease risk and (ii) polygenic risk that involves large numbers of variants of small effect that affect many different pathways. Few studies have explored the interaction between monogenic risk variants and polygenic risk. Methods We identified monogenic risk variants and calculated polygenic scores for three diseases, coronary artery disease, breast cancer, and colorectal cancer, in three study populations — case-control cohorts for coronary artery disease (UK Biobank; N=12,879) and breast cancer (Color Genomics; N=19,264), and an independent cohort of 49,738 additional UK Biobank participants. Results In the coronary artery disease case-control cohort, increased risk for carriers of a monogenic variant ranged from 1.3-fold for those in the lowest polygenic score quintile to 12.6-fold for those in the highest. For breast cancer, increased risk ranged from 2.4 to 6.9-fold across polygenic score quintiles. Among the 49,738 UK Biobank participants who carried a monogenic risk variant, the probability of disease at age 75 years was strongly modified by polygenic risk. Across individuals in the lowest to highest percentiles of polygenic risk, the probability of disease ranged from 17% to 78% for coronary artery disease; 13% to 76% for breast cancer; and 11% to 80% for colon cancer. Conclusions For three important genomic conditions, polygenic risk powerfully modifies the risk conferred by monogenic risk variants.
(Invited) Enabling Global Impact of Amperometric Gas Sensors (2017)

The enabling technology needed to catch the integrated “sensing-computing-communicating” economic engine of the early 21 st century is that of environmental sensing. Human exposure to the environment [air, water, food, biologicals] is responsible for a major part of the disease burden of global populations and WHO predicts at least 6M premature deaths this year. A major route of exposure is inhalation and we all breathe the same air, and air pollution sensors that target the EPA priority pollutants of CO, NO 2 , Ozone, and SO 2 are of increasing importance. One must measure something in order to understand and mitigate its effects and gas sensors do this job. Disruptive technologies, i.e. those that bridge the cost-performance gap, are required to field measurement capability globally. The amperometric gas sensor 1,2 is an important contributor to environmental measurement capability. Recent advances have used printed electronics and semiconductor fabrication approaches to enable new commercialization opportunities. The ability to develop new sensor designs and to use advanced materials is key to setting up supply chain capability that has led to ever larger deployments of these sensors for breath/health measurements, environmental measurements, and safety. These new sensors exemplify a path to commercialization for high volume low-cost sensing with potential for high global societal impacts. 1] M. T. Carter, J. R. Stetter , M. W. Findlay and V. Patel, “Printed Amperometric Gas Sensors,” ECS Transactions , 50(12), 211-220 (2012). DOI 10.1149/0512.0211ecst. 2] Joseph R. Stetter and Jing Li, in Modern Topics in Chemical Sensing: Chapter 4, “Amperometric Gas Sensors – A Review,” Chemical Reviews, 108 (2), 2008, pp352-366.
Far-field optical nanoscopy with reduced number of state transition cycles (2011)

We report on a method to reduce the number of state transition cycles that a molecule undergoes in far-field optical nanoscopy of the RESOLFT type, i.e. concepts relying on saturable (fluorescence) state transitions induced by a spatially modulated light pattern. The method is exemplified for stimulated emission depletion (STED) microscopy which uses stimulated emission to transiently switch off the capability of fluorophores to fluoresce. By switching fluorophores off only if there is an adjacent fluorescent feature to be recorded, the method reduces the number of state transitions as well as the average time a dye is forced to reside in an off-state. Thus, the photobleaching of the sample is reduced, while resolution and recording speed are preserved. The power of the method is exemplified by imaging immunolabeled glial cells with up to 8-fold reduced photobleaching.
Tachykinin receptor antagonists and potential clinical applications at peripheral level (1991)

Conference Article| November 01 1991 Tachykinin receptor antagonists and potential clinical applications at peripheral level C. A. Maggi; C. A. Maggi 1Department of Pharmacology and Chemistry, A. Menarini Pharmaceuticals, Via Sette Santi 3, 50131, Florence, Italy Search for other works by this author on: This Site PubMed Google Scholar R. Patacchini; R. Patacchini 1Department of Pharmacology and Chemistry, A. Menarini Pharmaceuticals, Via Sette Santi 3, 50131, Florence, Italy Search for other works by this author on: This Site PubMed Google Scholar P. Rovero; P. Rovero 1Department of Pharmacology and Chemistry, A. Menarini Pharmaceuticals, Via Sette Santi 3, 50131, Florence, Italy Search for other works by this author on: This Site PubMed Google Scholar S. Giuliani; S. Giuliani 1Department of Pharmacology and Chemistry, A. Menarini Pharmaceuticals, Via Sette Santi 3, 50131, Florence, Italy Search for other works by this author on: This Site PubMed Google Scholar A. Giachetti A. Giachetti 1Department of Pharmacology and Chemistry, A. Menarini Pharmaceuticals, Via Sette Santi 3, 50131, Florence, Italy Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1991) 19 (4): 909–912. https://doi.org/10.1042/bst0190909 Article history Received: July 01 1991 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation C. A. Maggi, R. Patacchini, P. Rovero, S. Giuliani, A. Giachetti; Tachykinin receptor antagonists and potential clinical applications at peripheral level. Biochem Soc Trans 1 November 1991; 19 (4): 909–912. doi: https://doi.org/10.1042/bst0190909 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: TK, tachykinin, SP, substance P, NKA, neurokinin A, NKB, neurokinin B This content is only available as a PDF. © 1991 Biochemical Society1991 Article PDF first page preview Close Modal You do not currently have access to this content.
Elucidating the patterning mechanism of zirconium-based hybrid photoresists (2017)

We report a series of studies aimed at shedding more light on the development mechanism of zirconium (Zr)-based extreme-UV hybrid photoresists. In earlier works, our group demonstrated that Zr-based hybrid resists are capable of resolving 30-nm half-pitch features with a very high sensitivity in the range of 1 to 20 mJ/cm2, which renders these materials potential candidates in the area of nonchemically amplified inorganic resists. While attractive because of its high sensitivity, Zr-methacrylic acid suffers from scumming problems. In an effort to better understand what controls sensitivity and scumming phenomena, we employed a combination of analytical techniques (electrospray ionization mass spectrometry, x-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy) to study the patterning mechanism in detail, to be able to optimize the development process and develop systems with optimal features.