gebhart/patrepeval huggingface dataset:
Light‐Activation of DNA‐Methyltransferases (2021)

Abstract 5‐Methylcytosine (5mC), the central epigenetic mark of mammalian DNA, plays fundamental roles in chromatin regulation. 5mC is written onto genomes by DNA methyltransferases (DNMT), and perturbation of this process is an early event in carcinogenesis. However, studying 5mC functions is limited by the inability to control individual DNMTs with spatiotemporal resolution in vivo. We report light‐control of DNMT catalysis by genetically encoding a photocaged cysteine as a catalytic residue. This enables translation of inactive DNMTs, their rapid activation by light‐decaging, and subsequent monitoring of de novo DNA methylation. We provide insights into how cancer‐related DNMT mutations alter de novo methylation in vivo, and demonstrate local and tuneable cytosine methylation by light‐controlled DNMTs fused to a programmable transcription activator‐like effector domain targeting pericentromeric satellite‐3 DNA. We further study early events of transcriptome alterations upon DNMT‐catalyzed cytosine methylation. Our study sets a basis to dissect the order and kinetics of diverse chromatin‐associated events triggered by normal and aberrant DNA methylation.
Partial purification and characterization of the messenger RNA for cell fibronectin (1979)

Fibronectin mRNA has been partially purified by guanidine extraction, oligo-(dT)-cellulose chromatography and sucrose density gradient centrifugation. We obtain a fraction which programs a wheat germ in vitro translation system to synthesize a polypeptide species which co-electrophoreses with fibronectin in SDS-polyacrylamide gels and which is immunoprecipitated with affinity purified fibronectin-specific IgG. Analysis of this RNA fraction by methyl mercury hydroxide-agarose gel electrophoresis reveals the presence of a band accounting for 30 percent to 50 percent of the ethidium bromide-staining material in the fraction. The RNA of this band has an estimated molecular weight of about 3 million daltons and is greatly reduced in the corresponding RNA fraction from RSV transformed CEF. This RNA has been tentatively identified as fibronectin mRNA.
Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation (2018)

The human immunodeficiency virus type 1 (HIV-1) envelope (Env) trimer evades antibody recognition by adopting a closed prefusion conformation. Here, we show that two conserved tyrosines (Y173, Y177) within the second variable (V2) loop of the gp120 Env glycoprotein are key regulators of the closed, antibody-protected state of the trimer by establishing intramolecular interaction with the base of the third variable (V3) loop. Mutation of Y177 and/or Y173 to phenylalanine or alanine dramatically altered the susceptibility of diverse HIV-1 strains to neutralization, increasing sensitivity to weakly and nonneutralizing antibodies directed against diverse Env regions, consistent with the adoption of an open trimer configuration. Conversely, potent broadly neutralizing antibodies (bNAbs) against different supersites of HIV-1 vulnerability exhibited reduced potency against V2 loop tyrosine mutants, consistent with their preferential targeting of the closed trimer. Mutation of V3 loop residues predicted to interact with the V2 loop tyrosines yielded a similar neutralization phenotype. Sera from chronically HIV-1-infected patients contained very high titers of antibodies capable of neutralizing V2 loop tyrosine mutants but not wild-type viruses, indicating that the bulk of antibodies produced in infected hosts are unable to penetrate the protective shield of the closed trimer. These results identify the tyrosine-mediated V2-V3 loop complex at the trimer apex as a key structural constraint that facilitates HIV-1 evasion from the bulk of host antibodies.<b>IMPORTANCE</b> The extraordinary ability of human immunodeficiency virus type 1 (HIV-1) to evade host immunity represents a major obstacle to the development of a protective vaccine. Thus, elucidating the mechanisms whereby HIV-1 protects its external envelope (Env), which is the sole target of virus-neutralizing antibodies, is an essential step toward vaccine design. We identified a key structural element that maintains the HIV-1 Env trimer in a closed, antibody-resistant conformation. A major role is played by two conserved tyrosines at the apex of the Env spike, whose mutation causes a global opening of the trimer structure, exposing multiple concealed targets for neutralizing antibodies. We also found that HIV-infected individuals produce very large amounts of antibodies that neutralize the open Env form; however, the bulk of these antibodies are unable to penetrate the tight defensive shield of the native virus. This work may help to devise new strategies to overcome the viral defensive mechanisms and facilitate the development of an effective HIV-1 vaccine.
Graphene delamination using ‘electrochemical methods’: an ion intercalation effect (2018)

The mechanism of graphene delamination from a Pt catalyst growth surface with electrochemical methods is studied. After a water intercalation step, an electrochemical graphene delamination process is done with a variety of different electrolytes. It is shown that (hydrogen or oxygen) bubble formation is not the main driving force to decouple graphene from its catalyst growth substrate. Ion intercalation is identified as the primary component for a fast graphene delamination process from its catalytic growth substrate. When the Pt/graphene sample is negatively charged, cations will intercalate, assuming they do not reduce within the electrochemical window of the solvent. This cation intercalation does result in graphene delamination. In the same way, anions intercalate in positively charged Pt/graphene samples when they do not react within the electrochemical window of the solvent. Furthermore, it is shown that applying a potential is sufficient (current is not needed) to induce ion intercalation and, as a result, graphene delamination. These findings open the door to avoid Na<sup>+</sup> or K<sup>+</sup> contamination introduced during currently described electrochemical graphene delamination. Alternative electrolytes (i.e. ammonium hydroxide and tetraethylammonium hydroxide) are proposed, due to the absence of alkali contaminants and rapid cation intercalation to delaminate graphene.
The ratio of CD8+/FOXP3 T lymphocytes infiltrating breast tissues predicts the relapse of ductal carcinoma in situ (2016)

In a series of 248 tumor samples obtained from image-guided biopsies from patients diagnosed with ductal carcinoma <i>in situ</i> of the breast, we attempted to identify biomarkers that predict microinfiltration at definitive surgery or relapse during follow-up. For this, we used immunohistochemical methods, followed by automated image analyses, to measure the mean diameter of nuclei (which correlates with ploidy), the phosphorylation of eukaryotic initiation factor 2α (eIF2α, which reflects endoplasmic reticulum stress) as well as the density and ratio of CD8<sup>+</sup> cytotoxic T lymphocytes and FOXP3<sup>+</sup> regulatory T cells. The median nuclear diameter of malignant cells correlated with eIF2α phosphorylation (in cancerous tissue), which in turn correlated with the density of the CD8<sup>+</sup> infiltrate and the CD8<sup>+</sup>/FOXP3 ratio (both in cancerous and the adjacent non-cancerous parenchyma). Neither microinfiltration nor lymph node involvement was associated with the probability of relapse. Both correlated positively with the CD8<sup>+</sup>/FOXP3 ratio in the malignant area. In contrast, relapse was associated with a paucity of the CD8<sup>+</sup> infiltrate as well as an unfavorable CD8<sup>+</sup>/FOXP3 ratio, both in malignant and non-malignant parenchyma. The combined analysis of the CD8<sup>+</sup>/FOXP3 ratio in cancerous and non-cancerous tissues revealed a significant impact of their interaction on the probability of relapse, but not on the presence of microinfiltration or lymph node metastasis. Altogether, these results support the idea of an immunosurveillance system that determines the risk of relapse in ductal carcinoma <i>in situ</i> of the breast.
Author Correction: Newcastle disease virus-based H5 influenza vaccine protects chickens from lethal challenge with a highly pathogenic H5N2 avian influenza virus (2018)

[This corrects the article DOI: 10.1038/s41541-017-0034-4.].
IL-38 Gene Deletion Worsens Murine Colitis (2022)

IL-38 is a recently discovered cytokine and member of the IL-1 Family. In the IL-1 Family, IL-38 is unique because the cytokine is primarily a B lymphocyte product and functions to suppress inflammation. Studies in humans with inflammatory bowel disease (IBD) suggest that IL-38 may be protective for ulcerative colitis or Crohn's disease, and that IL-38 acts to maintain homeostasis in the intestinal tract. Here we investigated the role of endogenous IL-38 in experimental colitis in mice deficient in IL-38 by deletion of exons 1-4 in C57 BL/6 mice. Compared to WT mice, IL-38 deficient mice subjected to dextran sulfate sodium (DSS) showed greater severity of disease, more weight loss, increased intestinal permeability, and a worse histological phenotype including increased neutrophil influx in the colon. Mice lacking IL-38 exhibited elevated colonic <i>Nlrp3</i> mRNA and protein levels, increased caspase-1 activation, and the concomitant increased processing of IL-1β precursor into active IL-1β. Expression of IL-1α, an exacerbator of IBD, was also upregulated. Colonic myleloperoxidase protein and <i>Il17a</i>, and <i>Il17f</i> mRNA levels were higher in the IL-38 deficient mice. Daily treatment of IL-38 deficient mice with an NLRP3 inhibitor attenuated diarrhea and weight loss during the recovery phase. These data implicate endogenous IL-38 as an anti-inflammatory cytokine that reduces DSS colitis severity. We propose that a relative deficiency of IL-38 contributes to IBD by disinhibition of the NLRP3 inflammasome.
Miniaturized Bioaffinity Assessment Coupled to Mass Spectrometry for Guided Purification of Bioactives from Toad and Cone Snail (2014)

A nano-flow high-resolution screening platform, featuring a parallel chip-based microfluidic bioassay and mass spectrometry coupled to nano-liquid chromatography, was applied to screen animal venoms for nicotinic acetylcholine receptor like (nAChR) affinity by using the acetylcholine binding protein, a mimic of the nAChR. The potential of this microfluidic platform is demonstrated by profiling the Conus textile venom proteome, consisting of over 1,000 peptides. Within one analysis (<90 min, 500 ng venom injected), ligands are detected and identified. To show applicability for non-peptides, small molecular ligands such as steroidal ligands were identified in skin secretions from two toad species (Bufo alvarius and Bufo marinus). Bioactives from the toad samples were subsequently isolated by MS-guided fractionation. The fractions analyzed by NMR and a radioligand binding assay with α7-nAChR confirmed the identity and bioactivity of several new ligands.
TAK1-mediated autophagy and fatty acid oxidation prevent hepatosteatosis and tumorigenesis (2014)

The MAP kinase kinase kinase TGFβ-activated kinase 1 (TAK1) is activated by TLRs, IL-1, TNF, and TGFβ and in turn activates IKK-NF-κB and JNK, which regulate cell survival, growth, tumorigenesis, and metabolism. TAK1 signaling also upregulates AMPK activity and autophagy. Here, we investigated TAK1-dependent regulation of autophagy, lipid metabolism, and tumorigenesis in the liver. Fasted mice with hepatocyte-specific deletion of Tak1 exhibited severe hepatosteatosis with increased mTORC1 activity and suppression of autophagy compared with their WT counterparts. TAK1-deficient hepatocytes exhibited suppressed AMPK activity and autophagy in response to starvation or metformin treatment; however, ectopic activation of AMPK restored autophagy in these cells. Peroxisome proliferator-activated receptor α (PPARα) target genes and β-oxidation, which regulate hepatic lipid degradation, were also suppressed in hepatocytes lacking TAK1. Due to suppression of autophagy and β-oxidation, a high-fat diet challenge aggravated steatohepatitis in mice with hepatocyte-specific deletion of Tak1. Notably, inhibition of mTORC1 restored autophagy and PPARα target gene expression in TAK1-deficient livers, indicating that TAK1 acts upstream of mTORC1. mTORC1 inhibition also suppressed spontaneous liver fibrosis and hepatocarcinogenesis in animals with hepatocyte-specific deletion of Tak1. These data indicate that TAK1 regulates hepatic lipid metabolism and tumorigenesis via the AMPK/mTORC1 axis, affecting both autophagy and PPARα activity.
Accurate Measurement of the Switching Losses of Ultra High Switching Speed CoolMOS Power Transistor / SiC Diode Combination Employed in Unity Power Factor PWM Rectifier Systems (2002)

The topic of this paper is a detailed analysis of the switching behavior of a CoolMOS / SiC diode combination applied in a 3.5kW single-phase unity power PWM rectifier system. The focus is on the development of guidelines to accurate measure the switching behavior and the turn-on and turn-off power losses at high switching speeds. Further subjects are the improved design of the power circuit, and the comparison of two high bandwidth current measurement methods applied in the power circuit.
Analysis and Correction of Inappropriate Image Duplication: The Molecular and Cellular Biology Experience (2018)

Abstract The present study analyzed 960 papers published in Molecular and Cellular Biology (MCB) from 2009-2016 and found 59 (6.1%) to contain inappropriately duplicated images. The 59 instances of inappropriate image duplication led to 42 corrections, 5 retractions and 12 instances in which no action was taken. Our experience suggests that the majority of inappropriate image duplications result from errors during figure preparation that can be remedied by correction. Nevertheless, ~10% of papers with inappropriate image duplications in MCB were retracted. If this proportion is representative, then as many as 35,000 papers in the literature are candidates for retraction due to image duplication. The resolution of inappropriate image duplication concerns after publication required an average of 6 h of journal staff time per published paper. MCB instituted a pilot program to screen images of accepted papers prior to publication that identified 12 manuscripts (14.5% out of 83) with image concerns in two months. The screening and correction of papers before publication required an average of 30 min of staff time per problematic paper. Image screening can identify papers with problematic images prior to publication, reduces post-publication problems and requires significantly less staff time than the correction of problems after publication.
Field trial results for high-speed wireless indoor data communications (2000)

This paper reports on the development of a flexible 5-MBd equalized M-QAM testbed for high-speed wireless data communications. The unit operates in real time and was field tested in typical indoor environments. A total of 3600 independent experiments were conducted using the testbed where one of 4-, 16-, 64-QAM constellations were transmitted, and the performance as a function of adaptive equalization and antenna selection diversity was studied. The experimental results presented here help put previous simulation and analytical results into perspective and demonstrate some of the performance bounds associated with a practical implementation. The field trial results show that with only 10-mW of transmit power, reliable 10-Mbit/s data communication can take place in between rooms with a coverage radius of 17 m, and better than 15% outage at an uncoded bit error rate (BER) of 10/sup -3/. The addition of two-branch antenna selection diversity to the system would allow 10-Mbit/s transmission at better than 3% outage and 20-Mbit/s transmission at 10% outage in the same environment. Moreover, 30-Mbit/s data transmission is feasible when both the transmitter and receiver are located within the same room, albeit at higher outage levels. In general, the results demonstrate the tremendous impact that adaptive equalization can have on the achievable performance of indoor links. Average SNR was improved anywhere from 8 dB to 12 dB depending on the particular environment and data rate. The impact on the outage performance, however, was much more dramatic.
Development of diagnostic method for bone and soft tissue sarcomas of various histological subtypes using serum microRNA profiles. (2018)

12019 Background: Diagnosis of sarcomas is considered to be quite difficult because of the rarity and diversity of the disease. The development of a novel diagnostic test for sarcoma is eagerly awaited. The aim of this study is to address whether serum miRNA profiles can be used to detect only malignant cases (sarcomas) of bone and soft tissue tumors regardless of histological subtypes. Methods: The case-control study included 1,002 patients with bone and soft tissue tumors representing more than 43 histological subtypes, including sarcomas, intermediate, and benign tumors. As controls, 275 healthy and 240 patients with other cancers were enrolled. MiRNA levels were measured using microarray. Patients were divided into three cohorts: a discovery to identify differentially expressed miRNAs; a training to establish a diagnostic index; and a validation to validate the utility of the index. An exploratory cohort was used to evaluate the index in recurrent sarcomas, intermediate tumors, and other cancers. Results: Circulating serum miRNA profiles, determined by microarray analysis, in malignant cases of bone and sarcomas, were clearly distinct from those in benign and healthy controls. A promising molecular detector, diagnostic index II, was developed using the serum levels of three miRNAs. Diagnostic index II also clearly separated sarcomas from benign and healthy controls with remarkable high sensitivity (94%), specificity (90%), and accuracy (91%). Conclusions: Comprehensive analysis of serum miRNA profiles in approximately 1000 cases of bone and soft tissue tumors identified a promising classifier, diagnostic index II, calculated using the serum levels of three miRNAs with remarkable performance for the detection of sarcoma. The present data overcome a serious problem associated with sarcoma diagnosis and provide the basis for the development and implementation of miRNA-based strategies for diagnostic purposes in the clinic.
Fabrication and Electrical and Thermal Properties of Ti2InC, Hf2InC and (Ti,Hf)2InC. (2002)

Abstract For Abstract see ChemInform Abstract in Full Text.
A High Throughput Beamforming Architecture for MIMO Systems (2006)

Quantized feedback in multiple antenna systems has potential to increase throughput or reduce probability of outage. In this paper, we present a method to generate quantization codebooks tailored for efficient implementation of beamforming- based MIMO transmissions. The proposed codebooks can reduce computational requirements significantly, making feasible an efficient architecture for a real-time transmit beamforming and receive combining MIMO orthogonal frequency division multiplexing (OFDM) system. Simulation results are used to validate the proposed codebook construction method and architecture.
Single‐walled carbon nanotubes as a template for coronene stack formation (2014)

Single‐walled carbon nanotubes can serve as a template for formation of various structures inside. Depending on conditions, the nanotube filling with coronene molecules may lead to creation of coronene stacks, graphene nanoribbons, or inner tubes. In this work, the formation of coronene stacks inside single‐walled carbon nanotubes was studied using photoluminescence (PL) spectroscopy. We demonstrate the difference in the excitation PL maps between the spectral features of coronene stacks inside the nanotubes and products formed outside the nanotube interior. The optical investigation was supported by calculations of adsorption energy of coronene molecules inside and outside nanotubes. The theoretical calculations predict the most energetically favorable configurations of coronene molecules with respect to the diameter of the outer nanotubes. Orientation of coronene stacks depends on the nanotube diameter. Models of ten coronene molecules placed inside (10,10) and (11,11) nanotubes (upper and lower image part, respectively).
2 W Semiconductor laser with diffraction-limited output beam at 1620 nm wavelength (2003)

With the broad-area waveguide aligned at an angle to the cleaved facet, the semiconductor laser is able to emit diffraction-limited beam. The divergence angle is only 0.7/spl deg/ and the output power could exceed 2 W.
Lithography simulation of sub-0.30-μm resist features for photomask fabrication using i-line optical pattern generators (1999)

The inorganic antireflection coating (AR3-chromium oxide) commonly used on photomask blanks was designed to minimize flare in h-line (405 nm) lithography steppers. The reflection of light (flare) off this coating (air-photomask) increases with shorter exposure wavelengths. High levels of flare occur in 248 nm and 193 nm IC steppers due to reflections off of the photomask surface. The reflections (standing waves) in photomask resists also increase during exposure using lower wavelengths of light. Lithography simulations and photomask manufacturing trials have led to resist processes that can generate sub-0.30 micron resist features on photomasks with I- line optical pattern generators (ALTA 3500). Lower developer concentration, higher exposure doses and the minimization of standing waves by incorporating a post-exposure bake and/or organic antireflection coatings (ARC) maximizes resolution. High resolution photoresists show standing waves on photomasks fabricated with optical pattern generators. Low contrast resist processes show only small standing waves or in certain cases resist 'footing.' The use of organic antireflection coatings can minimize standing waves and allow the use of high contrast resist processes. ARCs reduce the swing ratio, which improves linewidth uniformity. ARCs also improve the adhesion of the resist to the photomask surface. Simulations reveal that the optimal ARC coating thickness is around 46 nm for typical I-line systems and around 50 nm for 257 nm non- chemically amplified photomask resists. Preliminary I-line photomask manufacturing trials have been done with bottom antireflection coatings at the DPI Reticle Technology Center. The first process trials reveal that the standing waves in high resolution resists were reduced but not removed. Very precise control of the ARC thickness must be exercised to completely extinguish standing waves and careful film thickness optimization appears to be necessary to minimize these reflections.
Optical properties and carrier dynamics in m ‐plane InGaN quantum wells (2014)

Abstract Scanning near‐field and time‐resolved photoluminescence spectroscopy have been applied to characterize single m‐plane InGaN QW structures. The PL spectra were found to be formed by emission from the extended and the localized states. Lateral dimensions of uniform potential regions were placed around a few tens of nm. It was shown that optimization of the template for the QW growth results in a more uniform emission spectrum and a reduced effect of carrier localization. The radiative recombination time at low temperatures was found to be short, about 0.5 ns. At room temperature, nonradiative recombination via efficient recombination centres was prevailing. Complexes of Ga vacancies with O were suggested to play this role. (© 2014 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)