gebhart/patrepeval huggingface dataset:
Masking of CD22 by cis ligands does not prevent redistribution of CD22 to sites of cell contact (2004)

CD22, a negative regulator of B cell signaling, is a member of the siglec family that binds to alpha2-6-linked sialic acids on glycoproteins. Previous reports demonstrated that binding of multivalent sialoside probes to CD22 is blocked, or "masked," by endogenous (cis) ligands, unless they are first destroyed by sialidase treatment. These results suggest that cis ligands on B cells make CD22 functionally unavailable for binding to ligands in trans. Through immunofluorescence microscopy, however, we observed that CD22 on resting B cells redistributes to the site of contact with other B or T lymphocytes. Redistribution is mediated by interaction with trans ligands on the opposing cell because it does not occur with ligand-deficient lymphocytes from ST6GalI-null mice. Surprisingly, CD45, proposed as both a cis and trans ligand of CD22, was not required for redistribution to sites of cell contact, given that redistribution of CD22 was independent of CD45 and was observed with lymphocytes from CD45-deficient mice. Furthermore, CD45 is not required for CD22 masking as similar levels of masking were observed in the WT and null mice. Comparison of the widely used sialoside-polyacrylamide probe with a sialoside-streptavidin probe revealed that the latter bound a subset of B cells without sialidase treatment, suggesting that cis ligands differentially impacted the binding of these two probes in trans. The combined results suggest that equilibrium binding to cis ligands does not preclude binding of CD22 to ligands in trans, and allows for its redistribution to sites of contact between lymphocytes.
Isolation and molecular structure of unusual oxochromium(V) cations for the catalytic epoxidation of alkenes (1983)

T. L. Siddall, N. Miyaura, J. C. Huffman and J. K. Kochi, J. Chem. Soc., Chem. Commun., 1983, 1185 DOI: 10.1039/C39830001185
Safety, tolerability and antiviral activity of the antisense oligonucleotide bepirovirsen in patients with chronic hepatitis B: a phase 2 randomized controlled trial (2021)

Chronic infection with hepatitis B virus (HBV) leads to an increased risk of death from cirrhosis and hepatocellular carcinoma. Functional cure rates are low with current treatment options (nucleos(t)ide analogs (NAs) and pegylated interferons). Bepirovirsen is an antisense oligonucleotide targeting all HBV messenger RNAs; in cell culture and animal models, bepirovirsen leads to reductions in HBV-derived RNAs, HBV DNA and viral proteins. This phase 2 double-blinded, randomized, placebo-controlled trial is the first evaluation of the safety and activity of an antisense oligonucleotide targeting HBV RNA in both treatment-naïve and virally suppressed individuals with chronic HBV infection. The primary objective was to assess the safety and tolerability of bepirovirsen in individuals with chronic hepatitis B (CHB) (NCT02981602). The secondary objective was to assess antiviral activity, including the change from baseline to day 29 in serum hepatitis B surface antigen (HBsAg) concentration. Participants with CHB infection ≥6 months and serum HBsAg ≥50 IU ml<sup>-1</sup> were enrolled from seven centers across Hong Kong and the Republic of Korea and randomized (3:1 within each dose cohort) to receive bepirovirsen or placebo via subcutaneous injection twice weekly during weeks 1 and 2 (days 1, 4, 8 and 11) and once weekly during weeks 3 and 4 (days 15 and 22). Participants were then followed for 26 weeks. Twenty-four participants were treatment-naïve and seven were receiving stable NA therapy. Treatment-emergent adverse events were mostly mild/moderate (most commonly injection site reactions). Eleven (61.1%) and three (50.0%) treatment-naïve participants experienced one or more treatment-emergent adverse event in the bepirovirsen and placebo groups, respectively. In participants receiving NA therapy, the corresponding numbers were three (60.0%) and one (50.0%). Transient, self-resolving alanine aminotransferase flares (≥2× upper limit of normal) were observed in eight treatment-naïve participants and three participants on stable NA regimens in the bepirovirsen treatment arms. HBsAg reductions were observed and were significant versus placebo for treatment-naïve participants receiving bepirovirsen 300 mg (P = 0.001), but not for the bepirovirsen 150 mg group (P = 0.245) or participants receiving stable NA therapy (P = 0.762). Two participants in each of the 300 mg dose groups achieved HBsAg levels below the lower limit of quantitation by day 29 (n = 3) or day 36 (n = 1). Bepirovirsen had a favorable safety profile. These preliminary observations warrant further investigation of the safety and activity of bepirovirsen in a larger CHB patient population.
Unconventional Magnetization below 25 K in Nitrogen-doped Diamond provides hints for the existence of Superconductivity and Superparamagnetism (2019)

The magnetization of nitrogen-doped single crystalline diamond bulk samples shows unconventional field and temperature hysteresis loops at T [Formula: see text] 25 K. The results suggest the existence of superparamagnetic and superconducting regions in samples with nitrogen concentration <200 ppm. Both phases vanish at temperatures above 25 K where the samples show diamagnetic behavior similar to undoped diamond. The observation of superparamagnetism and superconductivity is attributed to the nitrogen doping and to the existence of defective regions. From particle-induced X-ray emission with ppm resolution we rule out that the main observations below 25 K are due to magnetic impurities. We investigated also the magnetic properties of ferromagnetic/high-temperature superconducting oxide bilayers. The magnetization results obtained from those bilayers show remarkable similarities to the ones in nitrogen-doped diamond.
Dihydroartemisinin is potential therapeutics for treating late-stage CRC by targeting the elevated c-Myc level (2021)

Currently, no frontline treatment is effective for the late-stage colorectal cancer (CRC). Understanding the molecular differences in different stages of CRC can help us to identify the critical therapeutic targets for designing therapeutic strategy. Our data show that c-Myc protein is highly expressed in late-stage CRC when compared with early-stage CRC in both clinical samples and in cell lines representing different cancer stages. Given that c-Myc is a well-known oncogenic driver in CRC, its high expression in the late-stage CRC may represent a critical therapeutic target for treating the cancer. Dihydroartemisinin treatment significantly increases c-Myc protein degradation and hence reduces its expression in CRC. The treatment also reduces CRC cell viability. Interestingly, dihydroartemisinin exhibits a more potent growth-inhibitory effect in late-stage CRC than the early-stage CRC. The treatment also possesses potent growth-inhibitory effects in mouse models bearing c-Myc-overexpressed CRC. The reduced c-Myc level and its reduced transcriptional activity reduce the expressions of acetyl-CoA carboxylase, fatty acid synthase, carnitine-palmitoyltransferase-1, and medium-chain acyl-CoA dehydrogenase in the cancer cells. Lipidomics study also shows that dihydroartemisinin treatment changes the metabolic phenotypes in CRC, reduces oxygen consumption, respiration, and ATP production, hence reduces the cell proliferation and induces apoptosis. Our study provides strong pharmacological evidence to support the translation of dihydroartemisinin for the treatment of late-stage CRC by targeting c-Myc.
Influence of Laser‐Induced Topography Changes on the Activity of Catalyst Coatings as Examined by Infrared Thermography (2008)

Abstract A mixed metal oxide catalyst coating is subjected to laser irradiation by a Nd:YAG laser operating at 266 nm to induce local changes in surface topography. The coating is exposed to laser interference patterns as well as to direct laser irradiation without interference. Samples are characterized by means of White Light Interferometry and Scanning Electron Microscopy. Irradiation with interference patterns causes the formation of wave‐like surface patterns in micrometer scale whereas direct laser irradiation generates porosity with pore sizes in the range of 100nm. Emissivity‐corrected infrared thermography (ecIRT) is applied to analyze the effect of surface topography changes on the catalytic activity of coatings in parallel. The catalytic combustion of iso‐octane with different contents of oxygen in nitrogen is used as a test reaction for catalytic activity. Local temperature increase on the substrate is chosen as a measure for catalytic activity. For laser interference structured coating, the catalytic activity improves with increase in geometric surface area caused by the wave‐like pattern. For direct laser irradiation, the porosity created by the laser enhances catalytic activity with respect to the unstructured coating.
Attenuation of Ultrasonic Surface Waves by Phonon Viscosity and Heat Conduction (1969)

The attenuation of elastic surface waves propagating on an arbitrarily oriented surface of a dielectric crystal has been calculated. Contributions to the attenuation from heat conduction and viscosity are considered. The result is valid when the sound wavelength is much greater than the thermal-phonon mean free path. Comparison is made with the experimental measurements of Salzmann et al. in quartz, and good agreement is obtained.
Development of Current Detecting Circuit with Wiring Inductance of Power Semiconductor Module (2018)

A high voltage and large capacity power semiconductor module has a sense-emitter terminal and emitter terminal for the gate drive. There exists a parasitic wiring inductance between the sense-emitter terminal and emitter terminal. When current flows through a module, induction voltage (differential value of module current) is generated. In this study, we develop a circuit that detects the current flowing through the module by integrating the induction voltage. The integrator has the problem of integral error. It was confirmed that this problem can be solved by adopting a method of reducing the output of the integrator during energization. Further, resistance exists in the wiring inductance. It was shown that this can be solved by using the metal-oxide-semiconductor field-effect-transistor (MOSFET). Finally, experiments were conducted using a 3300V/450A IGBT module. Through the results of the experiments, it was confirmed that the proposed circuit can detect the current and abnormal current, such as the short circuit current through a power semiconductor module.
Lessons learnt from large-scale exon re-sequencing of the X chromosome (2009)

A candidate gene approach to identifying novel causes of disease is concept-limiting and in the new era of high throughput sequencing there is now no need to restrict the experiment to a few interesting genes. We have recently completed a large-scale exon re-sequencing project using Sanger sequencing technology to analyse approximately 1 Mb of coding sequence of the X chromosome in probands from >200 families with various forms of intellectual disability. We review the lessons learnt from this experience. Comparing large data sets will certainly reveal pathogenic mutations in genes that were not possible to identify previously. However, the task of distinguishing pathogenic mutations from rare sequence variants is not easy and is the most substantial challenge to the next decade. High-throughput technology has the attraction of being cheap, fast and comprehensive but for projects that require detailed coverage of a genomic region at an exhaustive level they may require a combination of large-scale with a small-scale follow-up of difficult regions to sequence. The number of rare truncating variants present in coding regions of the X chromosome that are not pathogenic was 1%. The importance of the quality of the starting material both clinically and molecularly and the number of sequence variants both rare and common that any one individual has across their coding sequence is discussed.
tBDFS: Temporal Graph Neural Network Leveraging DFS (2022)

Temporal graph neural networks (temporal GNNs) have been widely researched, reaching state-of-the-art results on multiple prediction tasks. A common approach employed by most previous works is to apply a layer that aggregates information from the historical neighbors of a node. Taking a different research direction, in this work, we propose tBDFS -- a novel temporal GNN architecture. tBDFS applies a layer that efficiently aggregates information from temporal paths to a given (target) node in the graph. For each given node, the aggregation is applied in two stages: (1) A single representation is learned for each temporal path ending in that node, and (2) all path representations are aggregated into a final node representation. Overall, our goal is not to add new information to a node, but rather observe the same exact information in a new perspective. This allows our model to directly observe patterns that are path-oriented rather than neighborhood-oriented. This can be thought as a Depth-First Search (DFS) traversal over the temporal graph, compared to the popular Breath-First Search (BFS) traversal that is applied in previous works. We evaluate tBDFS over multiple link prediction tasks and show its favorable performance compared to state-of-the-art baselines. To the best of our knowledge, we are the first to apply a temporal-DFS neural network.
Bi-level Optimal Edge Computing Model for On-ramp Merging in Connected Vehicle Environment (2019)

The coordinated on-ramp merging is one of the most common but critical vehicular applications that require complex data transmission and low-latency communication in the Connected and Automated Vehicles (CAVs) environment.An effective way to address on-ramp merging is to leverage the edge computing to optimize the coordination among vehicles to achieve overall minimum vehicle travel time and energy consumption.In this study, we propose an Bi-level Optimal Edge Computing (BOEC) model for on-ramp merging in the CAVs environment to optimize both merge time and vehicle trajectory.The simulation results show that the proposed BOEC model achieves great benefits in vehicle mobility, energy saving and air pollutant emission reduction by providing an energy-efficient trajectory following the optimal merge time without compromising safety.
Effects of electron irradiation and coulombic interactions on the structure and mobility of small particles and amorphous phases (1991)

Abstract The question of structural instability during charging under electron irradiation in small particles and amorphous phases is semi-quantitatively explained. Experimental observations in electron microscopes during irradiation have reported that when the particle radius is less than ∼ 10 Å complete random diffusion of atoms is seen over the whole particle volume, whereas for larger sizes, only local areas fluctuate. In amorphous structures similar local fluctuations are seen during high flux electron irradiation. Using thermodynamic arguments an empirical criterion is used to define the critical size scale for instability when the coulombic stresses set up inside a particle enhance the point defect concentration such that the flux of atoms inside the particle reaches some critical value. Agreement is seen between the predicted size ranges and experimental results. Enhanced diffusion due to charging may also account for anisotropic growth in materials when irradiation is localized or formation of heterogeneous interfaces creates anisotropy.
Programmed death 1 (PD‐1) and ligand (PD‐L1) inhibitors in head and neck squamous cell carcinoma: A meta‐analysis (2022)

Meta-analysis shows the efficacy of PD-1 and PD-L1 inhibitors in HNSCC and suggests a possible difference in certain RECIST criterion between PD-1 and PD-L1 inhibitors. Future work to investigate the clinical significance of these findings is warranted.
DNA methylation repels binding of hypoxia-inducible transcription factors to maintain tumor immunotolerance (2020)

Our data elucidate the mechanism underlying cell-type-specific responses to hypoxia and suggest DNA methylation and hypoxia to underlie tumor immunotolerance.
Identification of CNS-Penetrant Aryl Sulfonamides as Isoform-Selective NaV1.6 Inhibitors with Efficacy in Mouse Models of Epilepsy (2019)

Nonselective antagonists of voltage-gated sodium (Na<sub>V</sub>) channels have been long used for the treatment of epilepsies. The efficacy of these drugs is thought to be due to the block of sodium channels on excitatory neurons, primarily Na<sub>V</sub>1.6 and Na<sub>V</sub>1.2. However, these currently marketed drugs require high drug exposure and suffer from narrow therapeutic indices. Selective inhibition of Na<sub>V</sub>1.6, while sparing Na<sub>V</sub>1.1, is anticipated to provide a more effective and better tolerated treatment for epilepsies. In addition, block of Na<sub>V</sub>1.2 may complement the anticonvulsant activity of Na<sub>V</sub>1.6 inhibition. We discovered a novel series of aryl sulfonamides as CNS-penetrant, isoform-selective Na<sub>V</sub>1.6 inhibitors, which also displayed potent block of Na<sub>V</sub>1.2. Optimization focused on increasing selectivity over Na<sub>V</sub>1.1, improving metabolic stability, reducing active efflux, and addressing a pregnane X-receptor liability. We obtained compounds <b>30-32</b>, which produced potent anticonvulsant activity in mouse seizure models, including a direct current maximal electroshock seizure assay.
Increased Neuronal Proliferation in the Dentate Gyrus of Aged Rats Following Neural Stem Cell Implantation (2009)

It is now well accepted that the brain is able to generate newborn neurons from a population of resident multipotential neural stem cells (NSCs) located in two discrete regions of the brain. The capacity for neurogenesis appears to diminish over the lifespan of an organism. Methods to potentiate the proliferation of new neuronal or glial cells within the central nervous system from resident NSCs could have therapeutic potential following an insult, such as stroke, or to replace lost cells as a result of a neurodegenerative disease. We implanted cells from a human NSC cell line, CTX0E03, originally derived from fetal cortical tissue directly into the ventricles of aged rats. CTX0E03 cells have angiogenic properties via secretion of growth factors, so we investigated if the implanted cells would stimulate proliferation of NSCs within the subgranular zone (SGZ) of the dentate gyrus. Bromodeoxyuridine staining demonstrated significantly increased proliferation in the SGZ. Absence of double labeling for human nuclear antigen suggested that the increased proliferation was from endogenous neural progenitor cells. The acute treatment also led to an increased number of immature neurons as demonstrated by immunohistochemical staining for the immature neuronal marker doublecortin. The data suggest that implants of exogenous NSCs may promote regeneration in aging organisms through stimulation of endogenous neurogenesis.
Irradiation microcell‐mediated chromosome transfer (XMMCT): The generation of specific chromosomal arm deletions (1990)

Abstract The microcell‐mediated chromosome transfer technique has been used to introduce whole chromosomes into malignant cells and revert the tumorigenic phenotype. However, in most instances the limited availability of selectable chromosomes has hindered the ability to reduce the region containing the tumor suppressive information. The work presented here describes a new method to enrich for specific chromosomal arm deletions of selectable chromosomes and thereby more finely focus upon the genetic region of interest. The irradiation‐microcell mediated chromosome transfer (XMMCT) technique involves the irradiation of microcells containing single human chromosomes followed by fusion to a nonirradiated host and cytogenetic characterization. The XMMCT procedure was performed on a microcell hybrid containing a der(11) as the only human chromosome. The resultant irradiated microcell hybrids were found to have deletions that ranged from simple interstitial deletions to complex deletions/rearrangements involving only the human der(11) chromosome. The XMMCT procedure has broad applications in generating chromosomal reagents for mapping genetic loci and for use in functional analyses such as tumor suppression studies.
Activation of ATP-Sensitive K+ Channels in the Ventromedial Hypothalamus Amplifies Counterregulatory Hormone Responses to Hypoglycemia in Normal and Recurrently Hypoglycemic Rats (2005)

The mechanism(s) by which glucosensing neurons detect fluctuations in glucose remains largely unknown. In the pancreatic beta-cell, ATP-sensitive K+ channels (K ATP channels) play a key role in glucosensing by providing a link between neuronal metabolism and membrane potential. The present study was designed to determine in vivo whether the pharmacological opening of ventromedial hypothalamic K ATP channels during systemic hypoglycemia would amplify hormonal counterregulatory responses in normal rats and those with defective counterregulation arising from prior recurrent hypoglycemia. Controlled hypoglycemia (approximately 2.8 mmol/l) was induced in vivo using a hyperinsulinemic (20 mU x kg(-1) x min(-1)) glucose clamp technique in unrestrained, overnight-fasted, chronically catheterized Sprague-Dawley rats. Immediately before the induction of hypoglycemia, the rats received bilateral ventromedial hypothalamic microinjections of either the potassium channel openers (KCOs) diazoxide and NN414 or their respective controls. In normal rats, both KCOs amplified epinephrine and glucagon counterregulatory responses to hypoglycemia. Moreover, diazoxide also amplified the counterregulatory responses in a rat model of defective hormonal counterregulation. Taken together, our data suggest that the K ATP channel plays a key role in vivo within glucosensing neurons in the ventromedial hypothalamus in the detection of incipient hypoglycemia and the initiation of protective counterregulatory responses. We also conclude that KCOs may offer a future potential therapeutic option for individuals with insulin-treated diabetes who develop defective counterregulation.
Dorsomorphin Promotes Human Embryonic Stem Cell Self‐Renewal (2011)

Selbsterneuerung: Ein Assay mit Hochdurchsatz-Screening identifizierte Dorsomorphin (siehe Schema) als niedermolekularen positiven Regulator der Selbsterneuerung menschlicher embryonaler Stammzellen (hESC). Dorsomorphin erreicht dieses Ziel, indem es den autokrinen BMP-Signalweg behindert. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.