gebhart/patrepeval huggingface dataset:
Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: Synthesis and in vitro studies (2008)

Synthesis of cationic plastoquinone derivatives (SkQs) containing positively charged phosphonium or rhodamine moieties connected to plastoquinone by decane or pentane linkers is described. It is shown that SkQs (i) easily penetrate through planar, mitochondrial, and outer cell membranes, (ii) at low (nanomolar) concentrations, posses strong antioxidant activity in aqueous solution, BLM, lipid micelles, liposomes, isolated mitochondria, and cells, (iii) at higher (micromolar) concentrations, show pronounced prooxidant activity, the "window" between anti- and prooxidant concentrations being very much larger than for MitoQ, a cationic ubiquinone derivative showing very much lower antioxidant activity and higher prooxidant activity, (iv) are reduced by the respiratory chain to SkQH2, the rate of oxidation of SkQH2 being lower than the rate of SkQ reduction, and (v) prevent oxidation of mitochondrial cardiolipin by OH*. In HeLa cells and human fibroblasts, SkQs operate as powerful inhibitors of the ROS-induced apoptosis and necrosis. For the two most active SkQs, namely SkQ1 and SkQR1, C(1/2) values for inhibition of the H2O2-induced apoptosis in fibroblasts appear to be as low as 1x10(-11) and 8x10(-13) M, respectively. SkQR1, a fluorescent representative of the SkQ family, specifically stains a single type of organelles in the living cell, i.e. energized mitochondria. Such specificity is explained by the fact that it is the mitochondrial matrix that is the only negatively-charged compartment inside the cell. Assuming that the Deltapsi values on the outer cell and inner mitochondrial membranes are about 60 and 180 mV, respectively, and taking into account distribution coefficient of SkQ1 between lipid and water (about 13,000 : 1), the SkQ1 concentration in the inner leaflet of the inner mitochondrial membrane should be 1.3x10(8) times higher than in the extracellular space. This explains the very high efficiency of such compounds in experiments on cell cultures. It is concluded that SkQs are rechargeable, mitochondria-targeted antioxidants of very high efficiency and specificity. Therefore, they might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner mitochondrial membrane in vivo.
Novel Platform for Regulation of Extracellular Vesicles and Metabolites Secretion from Cells Using a Multi-Linkable Horizontal Co-Culture Plate (2021)

Microfluidics is applied in biotechnology research via the creation of microfluidic channels and reaction vessels. Filters are considered to be able to simulate microfluidics. A typical example is the cell culture insert, which comprises two vessels connected by a filter. Cell culture inserts have been used for years to study cell-to-cell communication. These systems generally have a bucket-in-bucket structure and are hereafter referred to as a vertical-type co-culture plate (VTCP). However, VTCPs have several disadvantages, such as the inability to simultaneously observe samples in both containers and the inability of cell-to-cell communication through the filters at high cell densities. In this study, we developed a novel horizontal-type co-culture plate (HTCP) to overcome these disadvantages and confirm its performance. In addition, we clarified the migration characteristics of substances secreted from cells in horizontal co-culture vessels. It is generally assumed that less material is exchanged between the horizontal vessels. However, the extracellular vesicle (EV) transfer was found to be twice as high when using HTCP. Other merits include control of the degree of co-culture via the placement of cells. We believe that this novel HTCP container will facilitate research on cell-to-cell communication in various fields.
DSP implementation in programmable logic (2002)

Recently, much press has been given to DSP implementations in programmable logic, often on the strength of a few simple benchmarks. This paper will examine more complicated DSP systems design in programmable logic, starting with an analysis of the support models required from the device vendors, and the new tools that will be needed. A set of examples, from simple to complex, that have been designed with initial versions of the tools called for in this paper will be presented. Finally, some methods for achieving high performance designs in programmable logic will be described.
Essential Role of Dopamine D2Receptor in the Maintenance of Wakefulness, But Not in Homeostatic Regulation of Sleep, in Mice (2010)

Dopamine (DA) and its D(2) receptor (R) are involved in cognition, reward processing, and drug addiction. However, their roles in sleep-wake regulation remain unclear. Herein we investigated the role of D(2)R in sleep-wake regulation by using D(2)R knock-out (KO) mice and pharmacological manipulation. Compared with WT mice, D(2)R KO mice exhibited a significant decrease in wakefulness, with a concomitant increase in non-rapid eye movement (non-REM, NREM) and REM sleep and a drastic decrease in the low-frequency (0.75-2 Hz) electroencephalogram delta power of NREM sleep, especially during the first 4 h after lights off. The KO mice had decreased mean episode duration and increased episode numbers of wake and NREM sleep, many stage transitions between wakefulness and NREM sleep during the dark period, suggesting the instability of the wake stage in these D(2)R KO mice. When the KO mice were subjected to a cage change or an intraperitoneal saline injection, the latency to sleep in the KO mice decreased to half of the level for WT mice. The D(2)R antagonist raclopride mimicked these effects in WT mice. When GBR12909, a dopamine transport inhibitor, was administered intraperitoneally, it induced wakefulness in WT mice in a dose-dependent manner, but its arousal effect was attenuated to one-third in the D(2)R KO mice. However, these 2 genotypes showed an identical response in terms of sleep rebound after 2, 4, and 6 h of sleep deprivation. These results indicate that D(2)R plays an essential role in the maintenance of wakefulness, but not in homeostatic regulation of NREM sleep.
NMR-Based Screening with Competition Water−Ligand Observed via Gradient Spectroscopy Experiments:  Detection of High-Affinity Ligands (2002)

Water-ligand observed via gradient spectroscopy (WaterLOGSY) represents a powerful method for primary NMR screening in the identification of compounds interacting with macromolecules, including proteins and DNA or RNA fragments. The method is useful for the detection of compounds binding to a receptor with binding affinity in the micromolar range. The Achille's heel of the method, as with all the techniques that detect the ligand resonances, is its inability to identify strong ligands with slow dissociation rates. We show here that the use of a reference compound with a known K(D) in the micromolar range together with properly designed competition binding experiments (c-WaterLOGSY) permits the detection of strong binders. A derived mathematical expression is used for the selection of the appropriate setup NMR experimental conditions and for an approximate determination of the binding constant. The experiment requires low ligand concentration, therefore allowing its application in the identification of potential strong inhibitors that are only marginally soluble. The technique is particularly suitable for rapid screening of chemical mixtures and plant or fungi extracts.
FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases (FAST-01): Protocol for the First Prospective Feasibility Study (Preprint) (2022)

<sec> <title>BACKGROUND</title> In preclinical studies, FLASH therapy (radiation delivered at ultra-high dose rates ≥40 Gy/second) has been shown to cause less injury to normal tissues than radiotherapy delivered at conventional dose rates. This first-in-human clinical investigation is designed to assess the workflow feasibility of proton FLASH therapy treatment in a clinical setting for the treatment of painful bone metastases in the extremities. A single dose of 8 Gy will be administered, as this dose is well established for palliative therapy from prior investigations using conventional dose-rate photon radiotherapy. Use of this dose regimen will permit an assessment of FLASH treatment efficacy and toxicity relative to the historical comparators. </sec> <sec> <title>OBJECTIVE</title> The FAST-01 study is a prospective, single-center study. Primary endpoints include assessing the workflow feasibility as well as the toxicities of FLASH treatment. The secondary endpoint is pain response at the treated site(s) as measured by patient reported pain scores, use of pain medication, and any flare in bone pain after treatment. </sec> <sec> <title>METHODS</title> Following informed consent, 10 subjects ≥18 years old with up to 3 painful bone metastases in the extremities (excluding feet, hands, wrists) will be enrolled. A treatment field selected from a pre-defined library of plans with fixed field sizes (from 7.5 cm x 7.5 cm up to 7.5 cm x 20 cm) will be used for treatment, and subjects will receive 8 Gy in a single fraction. A FLASH-enabled Varian ProBeam™ Proton Therapy unit will be used to deliver treatment to the target volume at a dose rate of ≥40 Gy/sec using the plateau (transmission) portion of the proton beam. After treatment, patients will be assessed for pain response as well as any side-effects of FLASH radiation. </sec> <sec> <title>RESULTS</title> Results will be compared to historically reported results with conventional dose-rate photon radiotherapy using the same radiation dose and fractionation. </sec> <sec> <title>CONCLUSIONS</title> The results of this investigation will contribute to further developing and optimizing the FLASH- enabled ProBeam™ Proton Therapy System workflow. The pain response and toxicity data acquired on this study will provide greater understanding of FLASH treatment effects on tumor response and normal tissue toxicities, and they will inform future FLASH trial design. </sec> <sec> <title>CLINICALTRIAL</title> ClinicalTrials.gov NCT04592887 </sec>
Intratumoral INF-γ triggers an antiviral state in GL261 tumor cells: a major hurdle to overcome for oncolytic vaccinia virus therapy of cancer (2015)

Oncolytic vaccinia virus (VACV) therapy is an alternative treatment option for glioblastoma multiforme. Here, we used a comparison of different tumor locations and different immunologic and genetic backgrounds to determine the replication efficacy and oncolytic potential of the VACV LIVP 1.1.1, an attenuated wild-type isolate of the Lister strain, in murine GL261 glioma models. With this approach, we expected to identify microenvironmental factors, which may be decisive for failure or success of oncolytic VACV therapy. We found that GL261 glioma cells implanted subcutaneously or orthotopically into Balb/c athymic, C57BL/6 athymic, or C57BL/6 wild-type mice formed individual tumors that respond to oncolytic VACV therapy with different outcomes. Surprisingly, only Balb/c athymic mice with subcutaneous tumors supported viral replication. We identified intratumoral IFN-γ expression levels that upregulate MHCII expression on GL261 cells in C57BL/6 wild-type mice associated with a non-permissive status of the tumor cells. Moreover, this IFN-γ-induced tumor cell phenotype was reversible.
The Revolution of Silicon Photonics (2019)

We are now experiencing a revolution in optical technologies, where one can print and control massive optical circuits, on a microelectronic chip. This revolution is enabling a whole range of applications that are in need for scalable optical technologies and its opening the door to areas that only a decade ago were unimaginable.
A CMOS embedded RF-MEMS tunable capacitor for multi-band/multi-mode smartphones (2012)

This paper reports on 1-chip RF-MEMS tunable capacitor that equips CMOS driver circuit in the underlying layer. A Wafer Level Chip Scale Package (WLCSP) optimized for RF-MEMS is employed to minimize the module size. The MEMS actuation voltage is generated by an Actuation Voltage Generator (AVG). The boost mechanism employed in the AVG enables instant high voltage generation and reduction of the dielectric charging. The measured noise at RF frequencies is less than -120dbm, thanks to a shield metal layer formed between MEMS and CMOS layers. To achieve high power handing and high creep immunity, we employ the previously reported techniques, the Quadruple Series Capacitor (QSC) [1] and the SiN springs [2]. The quality factor measured in the WLCSP is larger than 100 at 1GHz. The capacitance can be changed from 1.4pF to 5pF by a step of 0.45pF.
SH2 domain-containing phosphatase-SHP-2 is a novel anti-fibrotic regulator in pulmonary fibrosis (2016)

<b>Rationale:</b> Idiopathic Pulmonary Fibrosis (IPF) is a chronic fatal lung disease with dismal prognosis and ineffective treatment. The potential role of the ubiquitously expressed SH2 domain-containing-tyrosine phosphatase (SHP2) as a therapeutic target has not been studied in IPF <b>Objectives:</b> To determine the role of SHP2 in Pulmonary Fibrosis. <b>Methods:</b> The effects of SHP2 overexpression and inhibition on fibroblast response to pro-fibrotic stimuli were analyzed <i>in-vitro</i> in primary human and mouse lung fibroblasts and <i>in-vivo</i> in the bleomycin-model of lung fibrosis. <b>Results:</b> SHP2 was downregulated in lungs derived from patients with IPF at the mRNA and protein level and immunolocalization studies revealed that SHP2 expression was absent within fibroblastic foci. Loss of SHP2 expression or activity was sufficient to induce fibroblast to myofibroblast differentiation in primary human lung fibroblasts. Overexpression of constitutively active SHP2 reduced the responsiveness of fibroblasts to pro-fibrotic stimuli, including significant reductions in cell survival and myofibroblast differentiation. SHP2 effects were mediated through deactivation of fibrosis-relevant tyrosine-kinase and serine/threonine-kinase signaling pathways. Mice carrying the Noonan-syndrome-associated gain-of-function SHP2 mutation (<i>SHP2<sup>D61G/+</sup>)</i> were resistant to bleomycin-induced pulmonary fibrosis. Restoration of SHP2 levels <i>in-vivo</i> through lentiviral delivery blunted bleomycin-induced pulmonary fibrosis. <b>Conclusions:</b> Our data suggest that SHP2 is an important regulator of fibroblast homeostasis. Augmentation of SHP2 activity or expression should be investigated as a novel therapeutic strategy for IPF.
Novel Alignment Mechanism of Liquid Crystal on a Hydrogenated Amorphous Silicon Oxide (2005)

The mechanism of liquid crystal (LC) alignment has been investigated during the last few decades for inorganic materials as well as for organic materials; however, it has not been clearly confirmed for some alignment materials. Inorganic alignment materials such as amorphous silicon oxide (a-SiOx) and hydrogenated amorphous silicon oxide (a-SiOx:H) are deposited on indium tin oxide (ITO) films on glass by reactive sputtering deposition. After deposition, the inorganic alignment materials are irradiated using an Ar+ ion beam (IB) for LC alignment. On the basis of the experimental results, a-SiOx films deposited by the sputtering do not align the LC, but a-SiOx:H films treated with varying IB energies, IB incident angles, IB doses, and IB irradiation times have excellent alignment properties and electrooptical properties, identical to those of polyimide (PI). These results imply that inorganic alignment layers irradiated by IB can be adopted as an LC alignment layer instead of rubbed PI. Additionally, hydrogen plays an important role in LC alignment because of the difference in alignment properties between a-SiOx films and a-SiOx:H films. We investigate the mechanism of IB-treated inorganic alignment layers and suggest that LCs are aligned by chemical effects, such as van der Waals interaction, more than by physical effects, such as morphology effects, in the inorganic alignment layer irradiated by IB.
An investigation of structure and properties in a model set of diblock copolymer-homopolymer blends (1982)

Thesis (Sc.D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1982.
Thermal Stability of Phosphonic Acid Self-Assembled Monolayers on Alumina Substrates (2020)

Thermal stability of several representative self-assembled monolayers (SAMs) with phosphonic acid (PA) anchoring group on Al2O3 substrates was studied by in situ high resolution X-ray photoelectron spectroscopy, complemented by thermogravimetric analysis of the relevant bulk materials and theoretical simulations. The range of thermal stability and the degradation pathways were found to be dependent on the chemical composition of the SAM forming molecules, with backbone-specific “weak links”. Whereas the anchoring groups were hardly affected by annealing up to 773 K (highest temperature applied for most of the samples), temperature-induced breakup of the bond between the backbone and anchoring group or a specific bond within the backbone was observed. The former is the case for nonsubstituted alkyl backbone, which is cleaved at temperatures above 673–773 K (depending on the backbone length), with the subsequent desorption of the released fragments. The latter is the case for the substituted (pentafluorophenoxy) or partly fluorinated alkyl backbone, with the bond cleavage occurring at temperatures above 523 K, either between the substitution and alkyl linker or between the fluorinated and nonfluorinated segments of the backbone. The above results suggest a higher robustness and better thermal stability of PA monolayers as compared to other types of SAMs, such as thiolates on coinage metal substrates. It is however advisible to test thermal stability of a specifically designed, functional PA SAM in context of possible “weak links” as far as this is important for a particular application.
VREUD -- An End-User Development Tool to Simplify the Creation of\n Interactive VR Scenes (2021)

Recent advances in Virtual Reality (VR) technology and the increased\navailability of VR-equipped devices enable a wide range of consumer-oriented\napplications. For novice developers, however, creating interactive scenes for\nVR applications is a complex and cumbersome task that requires high technical\nknowledge which is often missing. This hinders the potential of enabling\nnovices to create, modify, and execute their own interactive VR scenes.\nAlthough recent authoring tools for interactive VR scenes are promising, most\nof them focus on expert professionals as the target group and neglect the\nnovices with low programming knowledge. To lower the entry barrier, we provide\nan open-source web-based End-User Development (EUD) tool, called VREUD, that\nsupports the rapid construction and execution of interactive VR scenes.\nConcerning construction, VREUD enables the specification of the VR scene\nincluding interactions and tasks. Furthermore, VREUD supports the execution and\nimmersive experience of the created interactive VR scenes on VR head-mounted\ndisplays. Based on a user study, we have analyzed the effectiveness,\nefficiency, and user satisfaction of VREUD which shows promising results to\nempower novices in creating their interactive VR scenes.\n
Malleus-to-Footplate versus Malleus-to-Stapes-Head Ossicular Reconstruction Prostheses: Temporal Bone Pressure Gain Measurements and Clinical Audiological Data (2005)

The MFP ORP showed better average pressure gain compared with the MSH ORP across the speech frequencies. Surgeons performing ossiculoplasty with designs similar to Project HEAR HA ORPs, where there is direct columella-like connection between the malleus and stapes, should consider using the MFP ORP design to achieve a better postoperative audiologic result, even when the stapes superstructure is intact.
γ-Cyclodextrin Cuprate Sandwich-Type Complexes (2013)

Three structures, based on γ-cyclodextrin (γ-CD) and metal ions (Cu(2+), Li(+), Na(+), and Rb(+)), have been prepared in aqueous and alkaline media and characterized structurally by single-crystal X-ray diffraction. Their dimeric assemblies adopt cylindrical channels along the c axes in the crystals. Coordinative and hydrogen bonding between the cylinders and the solvent molecules lead to the formation of two-dimensional sheets, with the identity of the alkali-metal ion strongly influencing the precise nature of the solid-state structures. In the case of the Rb(+) complex, coordinative bonding involving the Rb(+) ions leads to the formation of an extended two-dimensional structure. Nonbound solvent molecules can be removed, and gas isotherm analyses confirm the permanent porosity of these new complexes. Carbon dioxide (CO2) adsorption studies show that the extended structure, obtained upon crystallization of the Rb(+)-based sandwich-type dimers, has the highest CO2 sequestration ability of the three γ-CD complexes reported.
Uncertainty in Peat Volume and Soil Carbon Estimated Using Ground‐Penetrating Radar and Probing (2012)

Estimating soil C stock in a peatland is highly dependent on accurate measurement of the peat volume. In this study, we evaluated the uncertainty in calculations of peat volume using high-resolution data to resolve the three-dimensional structure of a peat basin based on both direct (push probes) and indirect geophysical (ground-penetrating radar) measurements. We compared volumetric estimates from both approaches, accounting for potential sources of error, with values from the literature. Approximate uncertainty of 14 to 23% was observed in the basin volume, and the total uncertainty roughly doubled when incorporating peat properties to derive the estimated C pool. Uncertainties in final C stock values are based on the uncertainty of the basin volumes and the variability in the peat properties and range between 31 and 38%. The results indicate that the well-established ground-penetrating radar technique that is scalable to larger peatlands can be used to obtain estimates of peat basin volumes at uncertainty levels similar to those for invasive direct probe surveys. This investigation demonstrated that ground-penetrating radar can quantify peat basin volumes at uniquely high spatial resolution without the need for extensive and invasive direct probing.
Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings (2012)

APBD with GBE deficiency, with occasional exceptions, is a clinically homogenous disorder that should be suspected in patients with adult onset leukodystrophy or spastic paraplegia with early onset of urinary symptoms and spinal atrophy.
A Database for Peer-Reviewed Microscopy Images and Their Unpublished Brethren (2011)

With the advent of the computer age and in particular, the Internet, information sources have multiplied. However, the need for information verification has never been greater. In a day when anyone can easily produce a website, blog, or tweet, you can't believe what you read or see just because it's “published.” Scientific data and analysis require peer review, and peer-reviewed data need a home. Equally important, for every piece of data in a peer-reviewed publication, there are usually many pieces that provided essential support for the conclusions of the study but could not be included due to space limitations. This is especially true of image data, which are necessarily gigabyte-hungry.