gebhart/patrepeval huggingface dataset:
Pre-existing astrocytes form functional perisynaptic processes on neurons generated in the adult hippocampus (2014)

The adult dentate gyrus produces new neurons that morphologically and functionally integrate into the hippocampal network. In the adult brain, most excitatory synapses are ensheathed by astrocytic perisynaptic processes that regulate synaptic structure and function. However, these processes are formed during embryonic or early postnatal development and it is unknown whether astrocytes can also ensheathe synapses of neurons born during adulthood and, if so, whether they play a role in their synaptic transmission. Here, we used a combination of serial-section immuno-electron microscopy, confocal microscopy, and electrophysiology to examine the formation of perisynaptic processes on adult-born neurons. We found that the afferent and efferent synapses of newborn neurons are ensheathed by astrocytic processes, irrespective of the age of the neurons or the size of their synapses. The quantification of gliogenesis and the distribution of astrocytic processes on synapses formed by adult-born neurons suggest that the majority of these processes are recruited from pre-existing astrocytes. Furthermore, the inhibition of astrocytic glutamate re-uptake significantly reduced postsynaptic currents and increased paired-pulse facilitation in adult-born neurons, suggesting that perisynaptic processes modulate synaptic transmission on these cells. Finally, some processes were found intercalated between newly formed dendritic spines and potential presynaptic partners, suggesting that they may also play a structural role in the connectivity of new spines. Together, these results indicate that pre-existing astrocytes remodel their processes to ensheathe synapses of adult-born neurons and participate to the functional and structural integration of these cells into the hippocampal network.
Microstructural characterization of YBa/sub 2/Cu/sub 3/O/sub 7-//sub x/ (1987)

A detailed characterization study on polycrystalline specimens of YBa/sub 2/Cu/sub 3/O/sub 7-//sub x/ that were prepared by solid-state reaction techniques has been carried out. In the samples studied, magnetization and resistivity measurements indicate superconductivity onset temperatures of up to 89 K. Transmission electron microscopy (TEM) techniques have been used to facilitate direct microstructural characterization. It is shown that the planar defects on (001) planes form during the ion milling of the samples and are not directly connected with superconductivity. Laser Raman spectroscopy has revealed that these materials are sensitive to environmental degradation.
2-Aminoethoxydiphenyl borate activates the mechanically gated human KCNK channels KCNK 2 (TREK-1), KCNK 4 (TRAAK), and KCNK 10 (TREK-2) (2013)

Two-pore domain K(+) (KCNK, K2P) channels underlie the "leak" (background) potassium conductance in many types of excitable cells. They oppose membrane depolarization and cell excitability. These channels have been reported to be modulated by several physical and chemical stimuli. The compound 2-aminoethoxydiphenyl borate (2-APB) was originally described as an inhibitor of IP3-induced Ca(2+) release but has been shown to act as either a blocker or an activator for several ion channels. Here, we report the effects of this compound on members of the TREK (TWIK related K(+) channels) subfamily of human KCNK channels. We injected Xenopus laevis oocytes with cRNAs (complementary RNAs) encoding several KCNK channels and measured their response using the two-electrode voltage clamp technique. 2-APB was found to be an effective activator for all members of the TREK subfamily (hKCNK2, hKCNK4, and hKCNK10), with the highest efficacy in hKCNK10. We also found that 2-APB was able to activate these channels in cell-excised patches of HEK293 (human embryonic kidney 293) cell transfected with hKCNK4 or hKCNK10, demonstrating direct activation. TREK channels are widely expressed in the central nervous system and peripheral tissues, where they play roles in several key processes. However, little is known regarding their pharmacology; therefore, the identification of a common, stable and inexpensive agonist should aid further investigations of these channels. Additionally, 2-APB has been used to study native receptors in cell systems that endogenously express members of the TREK subfamily (e.g., rat dorsal root ganglia); our results thus warn against the use of 2-APB at high concentrations in these systems.
ChemInform Abstract: Crystal Structures and Sodium/Silver Distributions within the Ionic Conductors Na5Ag2Fe3 (As2O7)4 and Na2Ag5Fe3 (P2O7)4. (2010)

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.
Impact of Prior Prostate Radiation on Complications After Radical Prostatectomy (2010)

Medical and surgical complications of prostatectomy are significantly increased in the setting of prior radiotherapy. Understanding the magnitude of this increased risk is important for patient counseling.
Tissue Engineering Applications of Therapeutic Cloning (2004)

Few treatment options are available for patients suffering from diseased and injured organs because of a severe shortage of donor organs available for transplantation. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for replacement therapy. Scientists in the field of tissue engineering apply the principles of cell transplantation, material science, and engineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. The present chapter reviews recent advances that have occurred in therapeutic cloning and tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.
Development of an E. coli strain for cell-free ADC manufacturing (2021)

Recent advances in cell-free protein synthesis have enabled the folding and assembly of full-length antibodies at high titers with extracts from prokaryotic cells. Coupled with the facile engineering of the E. coli translation machinery, E. coli based in vitro protein synthesis reactions have emerged as a leading source of IgG molecules with non-natural amino acids incorporated at specific locations for producing homogeneous antibody drug conjugates. While this has been demonstrated with extract produced in batch fermentation mode, continuous extract fermentation would facilitate supplying material for large-scale manufacturing of protein therapeutics. To accomplish this, the IgG-folding chaperones DsbC and FkpA, and orthogonal tRNA for non-natural amino acid production were integrated onto the chromosome with high strength constitutive promoters. This enabled co-expression of all three factors at a consistently high level in the extract strain for the duration of a five-day continuous fermentation. Cell-free protein synthesis reactions with extract produced from cells grown continuously yielded titers of IgG containing non-natural amino acids above those from extract produced in batch fermentations. In addition, the quality of the synthesized IgGs and the potency of ADC produced with continuously fermented extract were indistinguishable from those produced with batch extract. These experiments demonstrate that continuous fermentation of E. coli to produce extract for cell-free protein synthesis is feasible and helps unlock the potential for cell-free protein synthesis as a platform for biopharmaceutical production.
A study of GTBT characteristics driven by pulse current (2002)

This paper describes a novel technique to reduce the size and cost of a current source used in the gate drive circuit of a GTBT. A compact current source, capable of supplying gate current of up to 100 A and occupying the same area as that of a 600 V/600 A-class GTBT chip, and a drive circuit have been designed using the proposed technique, for possible implementation in an inverter module. Characteristics of the transistor driven by the newly developed circuit have been studied and found to agree well with estimations made with a charge-control model.
A pathogenic trace of Tannerella forsythia – shedding of soluble fully active tumor necrosis factor α from the macrophage surface by karilysin (2014)

Tannerella forsythia is implicated as a pathogen causing chronic and aggressive periodontitis. However, its virulence factors, including numerous putative proteases, are mostly uncharacterized. Karilysin is a newly described matrix metalloprotease-like enzyme of T. forsythia. Since pathogen-derived proteases may affect the host defense system via modulation of the cytokine network, the aim of this study was to determine the influence of karilysin on tumor necrosis factor-α (TNF-α). The results showed that karilysin cleaved the membrane form of TNF-α on the surface of macrophages, and that this led to an increased concentration of soluble TNF-α in the conditioned medium. Importantly, despite partial degradation of soluble TNF-α by karilysin, the released cytokine retained its biological activity, inducing apoptosis and stimulating autocrine pathway of pro-inflammatory gene expression. Notably, the observed effect required proteolytic activity by karilysin, since a catalytically inactive mutant of the enzyme did not affect TNF-α secretion. The shedding was independent of the activity of ADAM17, a major endogenous TNF-α converting enzyme. Karilysin-dependent TNF-α release from the cell surface is likely to occur in vivo because human plasma, the main constituent of gingival crevicular fluid, only slightly affected the sheddase activity of karilysin. Taken together, these results indicate that karilysin modulates the host immune response through regulation of TNF-α secretion, and should therefore be considered as a new virulence factor of T. forsythia.
A Tick-Borne Langat Virus Mutant That Is Temperature Sensitive and Host Range Restricted in Neuroblastoma Cells and Lacks Neuroinvasiveness for Immunodeficient Mice (2006)

Langat virus (LGT), the naturally attenuated member of the tick-borne encephalitis virus (TBEV) complex, was tested extensively in clinical trials as a live TBEV vaccine and was found to induce a protective, durable immune response; however, it retained a low residual neuroinvasiveness in mice and humans. In order to ablate or reduce this property, LGT mutants that produced a small plaque size or temperature-sensitive (ts) phenotype in Vero cells were generated using 5-fluorouracil. One of these ts mutants, clone E5-104, exhibited a more than 10(3)-fold reduction in replication at the permissive temperature in both mouse and human neuroblastoma cells and lacked detectable neuroinvasiveness for highly sensitive immunodeficient mice. The E5-104 mutant possessed five amino acid substitutions in the structural protein E and one change in each of the nonstructural proteins NS3 and NS5. Using reverse genetics, we demonstrated that a Lys(46)-->Glu substitution in NS3 as well as a single Lys(315)-->Glu change in E significantly impaired the growth of LGT in neuroblastoma cells and reduced its peripheral neurovirulence for SCID mice. This study and our previous experience with chimeric flaviviruses indicated that a decrease in viral replication in neuroblastoma cells might serve as a predictor of in vivo attenuation of the neurotropic flaviviruses. The combination of seven mutations identified in the nonneuroinvasive E5-104 mutant provided a useful foundation for further development of a live attenuated TBEV vaccine. An evaluation of the complete sequence of virus recovered from brain of SCID mice inoculated with LGT mutants identified sites in the LGT genome that promoted neurovirulence/neuroinvasiveness.
PoseRBPF: A Rao-Blackwellized Particle Filter for 6D Object Pose Tracking (2019)

Tracking 6D poses of objects from videos provides rich information to a robot in performing different tasks such as manipulation and navigation. In this work, we formulate the 6D object pose tracking problem in the Rao-Blackwellized particle filtering framework, where the 3D rotation and the 3D translation of an object are decoupled. This factorization allows our approach, called PoseRBPF, to efficiently estimate the 3D translation of an object along with the full distribution over the 3D rotation. This is achieved by discretizing the rotation space in a fine-grained manner, and training an auto-encoder network to construct a codebook of feature embeddings for the discretized rotations. As a result, PoseRBPF can track objects with arbitrary symmetries while still maintaining adequate posterior distributions. Our approach achieves state-of-the-art results on two 6D pose estimation benchmarks. A video showing the experiments can be found at https://youtu.be/lE5gjzRKWuA
FILM COOLING: BREAKING THE LIMITS OF DIFFUSION SHAPED HOLES (2009)

The study of gas turbine film cooling encompasses several thousands of technical papers since the 1960's. Yet today virtually all applications use only two types of film hole geometries, round holes and diffuser shaped holes. There has been no substantive improvement upon diffuser shaped film hole adiabatic effectiveness that has made its way into production turbine components. The present study is an examination of why this apparent limitation has not been overcome. Thirty examples of proposed discrete hole film cooling geometries, including the standard bearer of diffuser shaped holes, are viewed to discern what is possible, what the typical detractors to implementation are, and how the community might go forward to entitlement. Eight key factors are used to judge the application potential for each of the film hole geometries. In the end, while the diffuser shaped film hole is still the best option today, a few other geometries are identified as candidates for significant improvement in film effectiveness. Three examples of film cooling with increasing levels of improvement over diffuser shaped holes are presented for consideration.
PCR-Based Tandem Epitope Tagging System for Escherichia Coli Genome Engineering (2006)

Biological discovery in the postgenomic era requires a systematic and high-throughput experimental approach. To this end, a versatile PCR-based tandem epitope tagging system is described, which inserts a tandem epitope coding sequence into any desired position of the Escherichia coli chromosome. Template plasmids were constructed that carry tandem copies of the epitope encoding sequence, Flp recombinase target (FRT) sites, and antibiotic resistance genes. The linear DNA fragment, amplified from the template plasmid with extensions homologous to the end of the target gene and part of its downstream region, was transformed into E. coli K-12 MG1655 harboring the bacteriophage gamma Red recombination system. The antibiotic resistance gene was then removed from the inserted heterologous PCR fragment using Flp recombinase. This epitope tagging system was applied to global transcription factors of E. coli to obtain proteins fused with tandem c-myc epitope tags. The tandem myc epitope-fused transcription factors were successfully detected by Western blot analysis and chromatin immunoprecipitation with increased detection sensitivity and higher yield. Higher copy numbers of the epitope molecule allowed the use of more stringent experimental conditions to increase the signal-to-noise ratio in subsequent experimental applications. Furthermore, judging from the measurement of gene expression using reverse transcription PCR (RT-PCR), the epitope-fused transcription factors retained their normal function for gene regulation in vivo.
High Temperature Performance of Coiled Glass Capacitors (2012)

Alkali-free flat panel display glass is produced in large quantity and has excellent electrical insulating properties at high temperature. Aluminum borosilicate glass with alkaline-earth modifier has low sodium content and low dielectric loss (tan δ &amp;lt;0.1 at 250°C), high dielectric breakdown strength (109 V/m) and excellent high temperature stability. In addition, roll-to-roll processing of thin glass sheet has been demonstrated and glass capacitors that are configured in a coil. Excellent high power capability of these glasses was confirmed by analytical, finite element, and finite difference modeling. The modeling work indicates that a combination of hybrid electrode design and effective heat loss at the interface can further extend power capability of glass capacitors. Alkali-free glass is an ideal candidate material for high temperature capacitors.
IL-6 Receptor Inhibition by Tocilizumab Attenuated Expression of C5a Receptor 1 and 2 in Non-ST-Elevation Myocardial Infarction (2018)

<b>Background:</b> Elevated interleukin-6 (IL-6) and complement activation are associated with detrimental effects of inflammation in coronary artery disease (CAD). The complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the IL-6 receptor (IL-6R)-antagonist tocilizumab on the expression of the anaphylatoxin receptors in whole blood from non-ST-elevation myocardial infarction (NSTEMI) patients. Separately, anaphylatoxin receptor expression in peripheral blood mononuclear cells (PBMC) from patients with different entities of CAD was investigated. <b>Materials and Methods:</b> NSTEMI patients were randomized to one dose of tocilizumab (<i>n</i> = 28) or placebo (<i>n</i> = 32) and observed for 6 months. Whole blood samples drawn at inclusion, at day 2, 3 and after 6 months were used for mRNA isolation. Plasma was prepared for analysis of complement activation measured as sC5b-9 by ELISA. Furthermore, patients with different CAD entities comprising stable angina pectoris (SAP, <i>n</i> = 22), non-ST-elevation acute coronary syndrome (NSTE-ACS, <i>n</i> = 21) and ST-elevation myocardial infarction (STEMI, <i>n</i> = 20) were included. PBMC was isolated from blood samples obtained at admission to hospital and mRNA isolated. Anaphylatoxin-receptor-expression was analyzed with qPCR using mRNA from whole blood and PBMC, respectively. <b>Results:</b> Our main findings were (i) Tocilizumab decreased C5aR1 and C5aR2 mRNA expression significantly (<i>p</i> < 0.001) and substantially (>50%) at day 2 and 3, whereas C3aR expression was unaffected. (ii) Tocilizumab did not affect complement activation. (iii) In analyzes of different CAD entities, C5aR1 expression was significantly increased in all CAD subgroups compared to controls with the highest level in the STEMI patients (<i>p</i> < 0.001). For C5aR2 and C3aR the expression compared to controls were more moderate with increased expression of C5aR2 in the STEMI group (<i>p</i> < 0.05) and C3aR in the NSTE-ACS group (<i>p</i> < 0.05). <b>Conclusion:</b> Expression of C5aR1 and C5aR2 in whole blood was significantly attenuated by IL-6R-inhibition in NSTEMI patients. These receptors were significantly upregulated in PBMC CAD patients with particularly high levels of C5aR1 in STEMI patients.
Recent advances in columnar CsI(Tl) scintillator screens (2005)

Columnar CsI(Tl) screens are now routinely used in indirect digital x ray imaging detectors. The CsI(Tl) scintillator provides high density, high atomic number, and high scintillation efficiency. These properties, coupled with the fact that CsI(Tl) can be grown in columnar form, provide excellent spatial resolution, high x-ray absorption, and low noise resulting in detectors with high overall detective quantum efficiency (DQE(f)). While such screens are now commercially available, developments leading to further improvements in scintillator performance are ongoing at RMD. Here we report on the recent progress in developing very thin (10 &#956;m) to very thick (~3 mm) columnar screens and discuss their application potential in digital radiology and nuclear medicine.
Supplementary Methods from Folate Receptor Beta Designates Immunosuppressive Tumor-Associated Myeloid Cells That Can Be Reprogrammed with Folate-Targeted Drugs (2023)

&lt;p&gt;Supplemental Methods&lt;/p&gt;
The Chemistry of Phenol-Formaldehyde Resin Vulcanization of EPDM: Part I. Evidence for Methylene Crosslinks (1995)

Abstract The application of phenol-formaldehyde resins as crosslinking agents is increasing in importance due to the good high temperature properties of the corresponding vulcanizate and the use in thermoplastic vulcanizates. With respect to the chemistry of phenol-formaldehyde cure (reaction mechanism and structure of crosslink) there are still problems that have to be resolved. The reaction products of the phenol-formaldehyde resin curing of EPDM, contain 2-ethylidene norbornene (ENB) as the third monomer, have been studied. Since such an investigation is rather difficult to perform for the polymer system, a low molecular weight model for EPDM was used: 2-ethylidene norbornane (ENBH). Reaction of ENBH and a resole results in scission of the dimethylene ether bridges, i.e. in degradation of the resole into mono-, bis - and terisooctylphenol units. These are consequently converted into products, consisting of two ENBH molecules linked by mono-, bis - and terisooctylphenol units. The solid resole seems to be a technological solution for storing phenol in combination with formaldehyde. These results support the use of 2-hydroxymethylphenol (HMP) as a low molecular weight model for the resole. At low temperatures and/or short reaction times HMP oligomers (= resoles) and HMP oligomers linked to one ENBH molecule are formed, which are converted into ENBH/HMP (1:1) condensation products. The reaction products of ENBH with both the resole and HMP are shown to contain methylene linked structures, as demonstrated by the formation of monisooctylphenol crosslinks and the presence of residual unsaturation and hydroxyl groups, besides chroman linked structures. This is the first experimental evidence that during phenol-formaldehyde resin cure of rubber, formation of methylene bridges occurs.
A covalent strategy to target intrinsically disordered proteins: Discovery of novel tau aggregation inhibitors (2022)

Intrinsically disordered proteins (IDPs) play important roles in disease pathologies; however, their lack of defined stable 3D structures make traditional drug design strategies typically less effective against these targets. Based on promising results of targeted covalent inhibitors (TCIs) on challenging targets, we have developed a covalent design strategy targeting IDPs. As a model system we chose tau, an endogenous IDP of the central nervous system that is associated with severe neurodegenerative diseases via its aggregation. First, we mapped the tractability of available cysteines in tau and prioritized suitable warheads. Next, we introduced the selected vinylsulfone warhead to the non-covalent scaffolds of potential tau aggregation inhibitors. The designed covalent tau binders were synthesized and tested in aggregation models, and inhibited tau aggregation effectively. Our results revealed the usefulness of the covalent design strategy against therapeutically relevant IDP targets and provided promising candidates for the treatment of tauopathies.