gebhart/patrepeval huggingface dataset:
Ratchet Cellular Automata (2003)

In this work we propose a ratchet effect which provides a general means of performing clocked logic operations on discrete particles, such as single electrons or vortices. The states are propagated through the device by the use of an applied ac drive. We numerically demonstrate that a complete logic architecture is realizable using this ratchet. We consider specific nanostructured superconducting geometries using superconducting materials under an applied magnetic field, with the positions of the individual vortices in samples acting as the logic states. These devices can be used as the building blocks for an alternative microelectronic architecture.
Discovery of 1,3,4-oxidiazole scaffold compounds as inhibitors of superoxide dismutase expression (2014)

The treatment of neurodegenerative diseases is difficult because of multiple etiologies and the interplay of genetics and environment as precipitating factors. In the case of amyotrophic lateral sclerosis (ALS), we have knowledge of a handful of genes that cause disease when mutated. However, drugs to counteract the effect of genetic mutations have not yet been found. One of the causative genes, Cu, Zn-superoxide dismutase (SOD1) is responsible for about 10-15% of the genetically linked autosomal dominant disease. Our rationale was that compounds that reduce expression of the mutant protein would be beneficial to slow onset and/or disease progression. We screened candidate compounds using a cell-based in vitro assay for those that reduce mutant SOD1 (G93A) protein expression. This led to the discovery of 2-[3-iodophenyl)methylsulfanyl]-5pyridin-4-yl-1,3,4-oxadiazole, a known protein kinase inhibitor that decreases G93A-SOD1 expression in vitro and in the brain and spinal cord in vivo. However, this compound has a biphasic dose response curve and a likely toxophore which limit its therapeutic window for chronic disease such as ALS. Therefore, we designed and tested a focused library of analogs for their ability to decrease SOD1 expression in vitro. This exercise resulted in the identification of a lead compound with improved drug-like characteristics and activity. Development of small molecules that reduce the expression of etiologically relevant toxic proteins is a strategy that may also be extended to familial ALS linked to gain of function mutations in other genes.
Ceria/Polymer Hybrid Nanoparticles as Efficient Catalysts for the Hydration of Nitriles to Amides (2015)

We report the synthesis of ceria/polymer hybrid nanoparticles and their use as effective supported catalysts for the hydration of nitriles to amide, exemplified with the conversion of 2-cyanopiridine to 2-picolinamide. The polymeric cores, made of either polystyrene (PS) or poly(methyl methacrylate) (PMMA), are prepared by miniemulsion copolymerization in the presence of different functional comonomers that provide carboxylic or phosphate groups: acrylic acid, maleic acid, and ethylene glycol methacrylate phosphate. The functional groups of the comonomers generate a corona around the main polymer particle and serve as nucleating agents for the in situ crystallization of cerium(IV) oxide. The obtained hybrid nanoparticles can be easily redispersed in water or ethanol. The conversion of amides to nitriles was quantitative for most of the catalytic samples, with yields close to 100%. According to our experimental observations by high-performance liquid chromatography (HPLC), no work up is needed to separate the product from unreacted substrate. The substrate remains absorbed on the catalyst surface, whereas the product can be easily separated. The catalysts are shown to be recyclable and can be reused for a large number of cycles without loss in efficiency.
Mitochondrial DNA lesions and copy number are strain dependent in endurance‐trained mice (2020)

In this pilot work, we selected two inbred strains that respond well to endurance training (ET) (FVB/NJ, and SJL/J strains), and two strains that respond poorly (BALB/cByJ and NZW/LacJ), to determine the effect of a standardized ET treadmill program on mitochondrial and nuclear DNA (nucDNA) integrity, and mitochondrial DNA (mtDNA) copy number. DNA was isolated from plantaris muscles (n = 37) and a gene-specific quantitative PCR-based assay was used to measure DNA lesions and mtDNA copy number. Mean mtDNA lesions were not different within strains in the sedentary or exercise-trained states. However, mtDNA lesions were significantly higher in trained low-responding NZW/LacJ mice (0.24 ± 0.06 mtDNA lesions/10 Kb) compared to high-responding strains (mtDNA lesions/10 Kb: FVB/NJ = 0.11 ± 0.01, p = .049; SJL/J = 0.04 ± 0.02; p = .003). ET did not alter mean mtDNA copy numbers for any strain, although both sedentary and trained FVB/NJ mice had significantly higher mtDNA copies (99,890 ± 4,884 mtDNA copies) compared to low-responding strains (mtDNA copies: BALB/cByJ = 69,744 ± 4,675; NZW/LacJ = 65,687 ± 5,180; p < .001). ET did not change nucDNA lesions for any strain, however, SJL/J had the lowest mean nucDNA lesions (3.5 ± 0.14 nucDNA lesions/6.5 Kb) compared to all other strains (nucDNA lesions/6.5 Kb: FVB/NJ = 4.4 ± 0.11; BALB/cByJ = 4.7 ± 0.09; NZW/LacJ = 4.4 ± 0.11; p < .0001). Our results demonstrate strain differences in plantaris muscle mtDNA lesions in ET mice and, independent of condition, differences in mean mtDNA copy and nucDNA lesions between strains.
Deciphering the Glycosylome of Dystroglycanopathies Using Haploid Screens for Lassa Virus Entry (2013)

Glycosylated α-dystroglycan (α-DG) serves as cellular entry receptor for multiple pathogens, and defects in its glycosylation cause hereditary Walker-Warburg syndrome (WWS). At least eight proteins are critical to glycosylate α-DG, but many genes mutated in WWS remain unknown. To identify modifiers of α-DG, we performed a haploid screen for Lassa virus entry, a hemorrhagic fever virus causing thousands of deaths annually that hijacks glycosylated α-DG to enter cells. In complementary screens, we profiled cells for absence of α-DG carbohydrate chains or biochemically related glycans. This revealed virus host factors and a suite of glycosylation units, including all known Walker-Warburg genes and five additional factors critical for the modification of α-DG. Our findings accentuate the complexity of this posttranslational feature and point out genes defective in dystroglycanopathies.
NtrBC Regulates Invasiveness and Virulence of Pseudomonas aeruginosa During High-Density Infection (2020)

<i>Pseudomonas aeruginosa</i> is an opportunistic pathogen that is a major cause of nosocomial and chronic infections contributing to morbidity and mortality in cystic fibrosis patients. One of the reasons for its success as a pathogen is its ability to adapt to a broad range of circumstances. Here, we show the involvement of the general nitrogen regulator NtrBC, which is structurally conserved but functionally diverse across species, in pathogenic and adaptive states of <i>P. aeruginosa</i>. The role of NtrB and NtrC was examined in progressive or chronic infections, which revealed that mutants (Δ<i>ntrB</i>, Δ<i>ntrC</i>, and Δ<i>ntrBC</i>) were reduced in their ability to invade and cause damage in a high-density abscess model <i>in vivo.</i> Progressive infections were established with mutants in the highly virulent PA14 genetic background, whereas chronic infections were established with mutants in the less virulent clinical isolate LESB58 genetic background. Characterization of adaptive lifestyles <i>in vitro</i> confirmed that the double Δ<i>ntrBC</i> mutant demonstrated >40% inhibition of biofilm formation, a nearly complete inhibition of swarming motility, and a modest decrease and altered surfing motility colony appearance; with the exception of swarming, single mutants generally had more subtle or no changes. Transcriptional profiles of deletion mutants under swarming conditions were defined using RNA-Seq and unveiled dysregulated expression of hundreds of genes implicated in virulence in PA14 and LESB58 chronic lung infections, as well as carbon and nitrogen metabolism. Thus, transcriptional profiles were validated by testing responsiveness of mutants to several key intermediates of central metabolic pathways. These results indicate that NtrBC is a global regulatory system involved in both pathological and physiological processes relevant to the success of <i>Pseudomonas</i> in high-density infection.
The critical role of histone H2A-deubiquitinase Mysm1 in hematopoiesis and lymphocyte differentiation (2011)

Stem cell differentiation and lineage specification depend on coordinated programs of gene expression, but our knowledge of the chromatin-modifying factors regulating these events remains incomplete. Ubiquitination of histone H2A (H2A-K119u) is a common chromatin modification associated with gene silencing, and controlled by the ubiquitin-ligase polycomb repressor complex 1 (PRC1) and H2A-deubiquitinating enzymes (H2A-DUBs). The roles of H2A-DUBs in mammalian development, stem cells, and hematopoiesis have not been addressed. Here we characterized an H2A-DUB targeted mouse line Mysm1(tm1a/tm1a) and demonstrated defects in BM hematopoiesis, resulting in lymphopenia, anemia, and thrombocytosis. Development of lymphocytes was impaired from the earliest stages of their differentiation, and there was also a depletion of erythroid cells and a defect in erythroid progenitor function. These phenotypes resulted from a cell-intrinsic requirement for Mysm1 in the BM. Importantly, Mysm1(tm1a/tm1a) HSCs were functionally impaired, and this was associated with elevated levels of reactive oxygen species, γH2AX DNA damage marker, and p53 protein in the hematopoietic progenitors. Overall, these data establish a role for Mysm1 in the maintenance of BM stem cell function, in the control of oxidative stress and genetic stability in hematopoietic progenitors, and in the development of lymphoid and erythroid lineages.
Cooperative Localization with Angular Measurements and Posterior Linearization (2020)

The application of cooperative localization in vehicular networks is attractive to improve accuracy and coverage of the positioning. Conventional distance measurements between vehicles are limited by the need for synchronization and provide no heading information of the vehicle. To address this, we present a cooperative localization algorithm using posterior linearization belief propagation (PLBP) utilizing angle-of-arrival (AoA)-only measurements. Simulation results show that both directional and positional root mean squared error (RMSE) of vehicles can be decreased significantly and converge to a low value in a few iterations. Furthermore, the influence of parameters for the vehicular network, such as vehicle density, communication radius, prior uncertainty, and AoA measurements noise, is analyzed.
Modelling dynamic and static recrystallization using mean field and finite element methods (2011)

International audience
Homogeneity of Cell Envelope Protein Subtypes, Lipopolysaccharide Serotypes, and Biotypes among Haemophilus influenzae Type b from Patients with Meningitis in The Netherlands (1983)

Eighty strains of &lt;it&gt;Haemophilus influenzae&lt;/it&gt; type b were randomly selected from 531 strains collected between 1975 and 1982 from patients with meningitis in The Netherlands. Subtyping by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that 67 of 80 isolates had identical major outer membrane protein patterns (subtype 1). Among the 13 other isolates four different polyacrylamide gel electrophoresis patterns were observed, two of which closely resembled subtype 1. Lipopolysaccharides were characterized immunologically by immunoprecipitation (Ouchterlony technique) and the gel-immune-radio-assay. Four serotypes were found among the 80 selected strains, leaving one strain not typable. Seventy-four strains (93%) belonged to the same lipopolysaccharide serotype; 77 (97%) of 80 of the strains belonged to biotype I. Sixty strains (75%) had identical major outer membrane protein patterns (subtype 1), lipopolysaccharide serotypes (serotype 1), and biotypes (I).
Ferrofluid Microdroplet Splitting for Population‐Based Microfluidics and Interfacial Tensiometry (2020)

Ferrofluids exhibit a unique combination of liquid properties and strong magnetic response, which leads to a rich variety of interesting functional properties. Here, the magnetic-field-induced splitting of ferrofluid droplets immersed in an immiscible liquid is presented, and related fascinating dynamics and applications are discussed. A magnetic field created by a permanent magnet induces instability on a mother droplet, which divides into two daughter droplets in less than 0.1 s. During the splitting process, the droplet undergoes a Plateau-Rayleigh-like instability, which is investigated using high-speed imaging. The dynamics of the resulting satellite droplet formation is shown to depend on the roughness of the supporting surface. Further increasing the field results in additional splitting events and self-assembly of microdroplet populations, which can be magnetically actuated. The effects of magnetization and interfacial tension are systematically investigated by varying magnetic nanoparticles and surfactant concentrations, and a variety of outcomes from labyrinthine patterns to discrete droplets are observed. As the splitting process depends on interfacial tension, the droplet splitting can be used as a measure for interfacial tension as low as 0.1 mN m<sup>-1</sup>. Finally, a population-based digital microfluidics concept based on the self-assembled microdroplets is presented.
Multiplicative multiscale image decompositions: analysis and modeling (2000)

Multiscale processing, in particular using the wavelet transform, has emerged as an incredibly effective paradigm for signal processing and analysis. In this paper, we discuss a close relative of the Haar wavelet transform, the multiscale multiplicative decomposition. While the Haar transform captures the differences between signal approximations at different scales, the multiplicative decomposition captures their ratio. The multiplicative decomposition has many of the properties that have made wavelets so successful. Most notably, the multipliers are a sparse representative for smooth signals, they have a dependency structure similar to wavelet coefficients, and they can be calculated efficiently. The multiplicative decomposition is also a more natural signal representation than the wavelet transform for some problems. For example, it is extremely easy to incorporate positivity constraints into multiplier domain processing. In addition, there is a close relationship between the multiplicative decomposition and the Poisson process; a fact that has been exploited in the field of photon-limited imaging. In this paper, we will show that the multiplicative decomposition is also closely tied with the Kullback-Leibler distance between two signals. This allows us to derive an n-term KL approximation scheme using the multiplicative decomposition.
Efficient Linear Millimeter-Wave Distributed Transceivers in CMOS SOI (2018)

Two Kuto V-band distributed amplifiers (DAs) based on nMOS and nMOS/pMOS gain stages and a distributed transceiver front end (DTFE) are presented for ultra-wideband power and low-noise amplification in a 45-nm RF CMOS silicon-on-insulator (SOI) technology. Supply scaling of gain stages through high-pass filter sections achieves high efficiency while maintaining a broadband 50-Ω match. The nMOS DA has a gain of 13 dB over a 3-dB bandwidth of 10-82 GHz and a minimum noise figure (NF) of 5.3 dB. The measured peak output power is 17.2 dBm with a peak power-added efficiency (PAE) of 17.4% at 50 GHz. The hybrid DA allows higher operating voltage and distortion cancelation of scaled pMOS devices to an achieve output power of 17.5 dBm with PAE of 20.2% and low third-order intermodulation and amplitude-phase nonlinearities. The DTFE utilizes time-domain duplexing to drive a shared antenna port for transmit (TX) and receive (RX) modes. It achieves TX gain of 11.7 dB from 12-76 GHz with peak output power of 17 dBm and PAE of 14.2%. RX gain is 9 dB from 11-77 GHz with a minimum NF of 6.2 dB. The 5-GHz wideband 16-QAM is demonstrated in the amplifier circuits for data rates exceeding 20 Gb/s.
ChemInform Abstract: Natural Kaolinitic Clay: A Mild and Efficient Catalyst for the Tetrahydropyranylation and Trimethylsilylation of Alcohols. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Structure—Activity Relationships of Novel anti‐Malarial Agents. Part 4. N‐(3‐Benzoyl‐4‐tolylacetylaminophenyl)‐3‐(5‐aryl‐2‐furyl)acrylic Acid Amides. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
The Structure of Lipoprotein(a) and Ligand-Induced Conformational Changes (2001)

Lipoprotein(a) is composed of low-density lipoprotein linked both covalently and noncovalently to apolipoprotein(a). The structure of lipoprotein(a) and the interactions between low-density lipoprotein and apolipoprotein(a) were investigated by electron microscopy and correlated with analytical ultracentrifugation. Electron microscopy of rotary-shadowed and unidirectionally shadowed lipoprotein(a) prepared without glycerol revealed that it is a nearly spherical particle with no large projections. After extraction of both lipoprotein(a) and low-density lipoprotein with glycerol prior to rotary shadowing, the protein components were observed to consist of a ring of density made up of nodules of different sizes, with apolipoprotein(a) and apolipoprotein B-100 closely associated with each other. However, when lipoprotein(a) was treated with a lysine analogue, 6-aminohexanoic acid, much of the apolipoprotein(a) separated from the apolipoprotein B-100. In 6-aminohexanoic acid-treated preparations without glycerol extraction, lipoprotein(a) particles had an irregular mass of density around the core. In contrast, lipoprotein(a) particles treated with 6-aminohexanoic acid in the presence of glycerol had a long tail, in which individual kringles could be distinguished, extending from the ring of apolipoprotein B-100. The length of the tail was dependent on the particular isoform of apolipoprotein(a). Dissociation of the noncovalent interactions between apolipoprotein(a) and low-density lipoprotein as a result of shear forces or changes in the microenvironment may contribute to selective retention of lipoprotein(a) in the vasculature.
Can We Prevent Antimicrobial Resistance by Using Antimicrobials Better? (2013)

Since their development over 60 years ago, antimicrobials have become an integral part of healthcare practice worldwide. Recently, this has been put in jeopardy by the emergence of widespread antimicrobial resistance, which is one of the major problems facing modern medicine. In the past, the development of new antimicrobials kept us one step ahead of the problem of resistance, but only three new classes of antimicrobials have reached the market in the last thirty years. A time is therefore approaching when we may not have effective treatment against bacterial infections, particularly for those that are caused by Gram-negative organisms. An important strategy to reduce the development of antimicrobial resistance is to use antimicrobials more appropriately, in ways that will prevent resistance. This involves a consideration of the pharmacokinetic and pharmacodynamics properties of antimicrobials, the possible use of combinations, and more appropriate choice of antimicrobials, which may include rapid diagnostic testing and antimicrobial cycling. Examples given in this review include Mycobacterium tuberculosis, Gram-negative and Gram-positive organisms. We shall summarise the current evidence for these strategies and outline areas for future development.
Mechanism of Bcl-2 and Bcl-X L inhibition of NLRP1 inflammasome: Loop domain-dependent suppression of ATP binding and oligomerization (2009)

NLRP1 (NLR family, pyrin domain-containing 1) is a contributor to innate immunity involved in intracellular sensing of pathogens, as well as danger signals related to cell injury. NLRP1 is one of the core components of caspase-1-activating platforms termed "inflammasomes," which are involved in proteolytic processing of interleukin-1beta (IL-1beta) and in cell death. We previously discovered that anti-apoptotic proteins Bcl-2 and Bcl-X(L) bind to and inhibit NLRP1 in cells. Using an in vitro reconstituted system employing purified recombinant proteins, we studied the mechanism by which Bcl-2 and Bcl-X(L) inhibit NLRP1. Bcl-2 and Bcl-X(L) inhibited caspase-1 activation induced by NLRP1 in a concentration-dependent manner, with K(i) approximately 10 nM. Bcl-2 and Bcl-X(L) were also determined to inhibit ATP binding to NLRP1, which is required for oligomerization of NLRP1, and Bcl-X(L) was demonstrated to interfere with NLRP1 oligomerization. Deletion of the flexible loop regions of Bcl-2 and Bcl-X(L), which are located between the first and second alpha-helices of these anti-apoptotic proteins and which were previously shown to be required for binding NLRP1, abrogated ability to inhibit caspase-1 activation, ATP binding and oligomerization of NLRP1. Conversely, synthetic peptides corresponding to the loop region of Bcl-2 were sufficient to potently inhibit NLRP1. These findings thus demonstrate that the loop domain is necessary and sufficient to inhibit NLRP1, providing insights into the mechanism by which anti-apoptotic proteins Bcl-2 and Bcl-X(L) inhibit NLRP1.
Inherited disorders of sulfur amino acid metabolism: recent advances in therapy (2020)

Complex regulation of pathways involved in SAA metabolism and cellular consequences of genetic defects in SAA metabolism are only partially understood. There is a pressing need to increase substantially our knowledge of the disease mechanisms to develop more effective therapies for patients suffering from these rare disorders.
SIRT1 Regulates Hepatocyte Lipid Metabolism through Activating AMP-activated Protein Kinase (2008)

Resveratrol may protect against metabolic disease through activating SIRT1 deacetylase. Because we have recently defined AMPK activation as a key mechanism for the beneficial effects of polyphenols on hepatic lipid accumulation, hyperlipidemia, and atherosclerosis in type 1 diabetic mice, we hypothesize that polyphenol-activated SIRT1 acts upstream of AMPK signaling and hepatocellular lipid metabolism. Here we show that polyphenols, including resveratrol and the synthetic polyphenol S17834, increase SIRT1 deacetylase activity, LKB1 phosphorylation at Ser(428), and AMPK activity. Polyphenols substantially prevent the impairment in phosphorylation of AMPK and its downstream target, ACC (acetyl-CoA carboxylase), elevation in expression of FAS (fatty acid synthase), and lipid accumulation in human HepG2 hepatocytes exposed to high glucose. These effects of polyphenols are largely abolished by pharmacological and genetic inhibition of SIRT1, suggesting that the stimulation of AMPK and lipid-lowering effect of polyphenols depend on SIRT1 activity. Furthermore, adenoviral overexpression of SIRT1 stimulates the basal AMPK signaling in HepG2 cells and in the mouse liver. AMPK activation by SIRT1 also protects against FAS induction and lipid accumulation caused by high glucose. Moreover, LKB1, but not CaMKKbeta, is required for activation of AMPK by polyphenols and SIRT1. These findings suggest that SIRT1 functions as a novel upstream regulator for LKB1/AMPK signaling and plays an essential role in the regulation of hepatocyte lipid metabolism. Targeting SIRT1/LKB1/AMPK signaling by polyphenols may have potential therapeutic implications for dyslipidemia and accelerated atherosclerosis in diabetes and age-related diseases.