gebhart/patrepeval huggingface dataset:
TheDrosophilaeffector caspase Dcp-1 regulates mitochondrial dynamics and autophagic flux via SesB (2014)

Increasing evidence reveals that a subset of proteins participates in both the autophagy and apoptosis pathways, and this intersection is important in normal physiological contexts and in pathological settings. In this paper, we show that the Drosophila effector caspase, Drosophila caspase 1 (Dcp-1), localizes within mitochondria and regulates mitochondrial morphology and autophagic flux. Loss of Dcp-1 led to mitochondrial elongation, increased levels of the mitochondrial adenine nucleotide translocase stress-sensitive B (SesB), increased adenosine triphosphate (ATP), and a reduction in autophagic flux. Moreover, we find that SesB suppresses autophagic flux during midoogenesis, identifying a novel negative regulator of autophagy. Reduced SesB activity or depletion of ATP by oligomycin A could rescue the autophagic defect in Dcp-1 loss-of-function flies, demonstrating that Dcp-1 promotes autophagy by negatively regulating SesB and ATP levels. Furthermore, we find that pro-Dcp-1 interacts with SesB in a nonproteolytic manner to regulate its stability. These data reveal a new mitochondrial-associated molecular link between nonapoptotic caspase function and autophagy regulation in vivo.
Advances in 3x150 mm Hot-Wall and 6x150 mm Warm-Wall SiC Epitaxy for 10kV-Class Power Devices (2016)

Initial results from a custom, 3x150 mm horizontal hot-wall, SiC Vapor-Phase epitaxial growth reactor (VPE), with full planetary motion are reported. Epitaxial layer properties are compared with those grown on previously reported 1x150 mm hot-wall and 6x150 mm warm-wall reactors for epitaxial wafers of up to 100 microns thickness. The median intra-wafer thickness and doping uniformity (σ/mean) for the 3x150 mm reactor are 0.9% and 6.10%, respectively. The intra-run thickness and doping variation are 0.18% and 1.01%. The projected 5x5 mm useable area for layers of nominal 5 to 30 μm thickness for all the reactor configurations (as measured by a Candela CS2 optical surface analyzer) are approximately 92%, corresponding to an effective defect density of about 0.35 cm -2 . Useable areas as high as 86.5% and 1-2 nm rms roughness have been observed for layers of over 100 μm thickness. Initial morphological results using a higher resolution, LaserTec SICA6X confocal differential interference contrast (CDIC) microscope, are also presented.
Electrochemical Activation of Single-Walled Carbon Nanotubes with Pseudo-Atomic-Scale Platinum for the Hydrogen Evolution Reaction (2017)

The development of effective and inexpensive hydrogen evolution reaction (HER) electrocatalysts for future renewable energy systems is highly desired. Platinum-based materials are the most active electrocatalysts for catalyzing HER, but reducing the use of Pt is required because of the high price and scarcity of Pt. Here, we achieve pseudo-atomic-scale dispersion of Pt, i.e. individual atoms or subnanometer clusters, on the sidewalls of single-walled carbon nanotubes (SWNTs) with a simple and readily upscalable electroplating deposition method. These SWNTs activated with an ultralow amount of Pt exhibit activity similar to that of commercial Pt/C with a notably higher (∼66–333-fold) Pt loading for catalyzing the HER under the acidic conditions required in proton exchange membrane technology. These catalysts resemble pseudo-atomic-scale Pt systems which are mainly composed of a few to tens of Pt atoms dispersed on the sidewalls of the SWNTs. The Pt loading is only 0.19–0.75 atom % at the electrode surface, and characteristic peaks for Pt cyclic voltammograms are undetectable. The atomic dispersion increases the portion of the surface active-atom sites, and therefore, notably lower Pt loading is needed to attain a high catalytic activity. Density functional theory (DFT) calculations suggest higher ability for SWNTs, in comparison to graphene, as a catalyst support for immobilizing Pt atoms, thus providing an atomic dispersion. Moreover, a high HER activity for the SWNTs activated with Pt atoms, similar to that of bulk Pt, is predicted.
Evaluation of JNJ-54717793 a Novel Brain Penetrant Selective Orexin 1 Receptor Antagonist in Two Rat Models of Panic Attack Provocation (2017)

Orexin neurons originating in the perifornical and lateral hypothalamic area are highly reactive to anxiogenic stimuli and have strong projections to anxiety and panic-associated circuitry. Recent studies support a role for the orexin system and in particular the orexin 1 receptor (OX1R) in coordinating an integrative stress response. However, no selective OX1R antagonist has been systematically tested in two preclinical models of using panicogenic stimuli that induce panic attack in the majority of people with panic disorder, namely an acute hypercapnia-panic provocation model and a model involving chronic inhibition of GABA synthesis in the perifornical hypothalamic area followed by intravenous sodium lactate infusion. Here we report on a novel brain penetrant, selective and high affinity OX1R antagonist JNJ-54717793 (1S,2R,4R)-7-([(3-fluoro-2-pyrimidin-2-ylphenyl)carbonyl]-<i>N</i>-[5-(trifluoromethyl)pyrazin-2-yl]-7-azabicyclo[2.2.1]heptan-2-amine). JNJ-54717793 is a high affinity/potent OX1R antagonist and has an excellent selectivity profile including 50 fold versus the OX2R. <i>Ex vivo</i> receptor binding studies demonstrated that after oral administration JNJ-54717793 crossed the blood brain barrier and occupied OX1Rs in the rat brain. While JNJ-54717793 had minimal effect on spontaneous sleep in rats and in wild-type mice, its administration in OX2R knockout mice, selectively promoted rapid eye movement sleep, demonstrating target engagement and specific OX1R blockade. JNJ-54717793 attenuated CO<sub>2</sub> and sodium lactate induced panic-like behaviors and cardiovascular responses without altering baseline locomotor or autonomic activity. These data confirm that selective OX1R antagonism may represent a novel approach of treating anxiety disorders, with no apparent sedative effects.
Supplementary Materials and Methods. Immunohistochemical staining and automated analysis methods from Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium (2023)

&lt;p&gt;This file describes immunohistochemistry staining for ER, PR and HERs in tissue microarrays, in addition to automated quantification of staining.&lt;/p&gt;
Total internal reflection focal molography (TIR-M) (2021)

Focal molography ("molography" in short) is a sensitive implementation of a diffractometric biosensor and has emerged as a new platform technology to study biomolecular interactions label-free in complex fluids and living cells. In contrast to established refractometric biosensors, in particular surface plasmon resonance, molography is almost insensitive to environmental noise, i.e. temperature gradients and nonspecific binding. Molography achieves this by modulating the analyte binding at a high spatial frequency and reads it out in Fourier space via diffraction of light at the bound molecules, i.e. molography applies the spatial lock-in principle for discrimination of the binding signal from disturbing effects on the sensor surface. In previous implementations of focal molography, the sensor was illuminated by a waveguide mode. While this arrangements has an outstanding resolution, it suffers from several drawbacks such as wavefront instabilities of the guided mode, the relatively high refractive index contrast at the waveguide interfaces and the manufacturing cost of waveguide and grating couplers. In this paper, we propose a simpler and more robust configuration for focal molography. Instead of a waveguide mode, it is based on darkfield illumination by total internal reflection (TIR) of a free space mode. We derive the coherent binding pattern, describe the fabrication process, show that its intensity distribution is as expected, derive the quantitative readout formula and perform a background and noise analysis. Real-time binding curves of streptavidin in buffer and concentrated bovine serum albumin solution show that TIR molography exhibits excellent resolution and robustness.
4’-Fluorouridine mitigates lethal infection with pandemic human and highly pathogenic avian influenza viruses (2022)

Abstract Influenza outbreaks are associated with substantial morbidity, mortality and economic burden. Next generation antivirals are needed to treat seasonal infections and prepare against zoonotic spillover of avian influenza viruses with pandemic potential. Having previously identified oral efficacy of the nucleoside analog 4’-Fluorouridine (4’-FlU, EIDD-2749) against SARS-CoV-2 and respiratory syncytial virus, we explored activity of the compound against seasonal and highly pathogenic influenza (HPAI) viruses in cell culture, human airway epithelium organoids, and/or two animal models, ferrets and mice, that assess IAV transmission and lethal viral pneumonia, respectively. 4’-FlU inhibited a panel of relevant influenza A and B viruses with nanomolar potency in organoids. In vitro polymerase assays revealed immediate chain termination of IAV polymerase after 4’-FlU incorporation, in contrast to delayed chain termination of SARS-CoV-2 and RSV polymerase. Once-daily oral treatment of ferrets with 2 mg/kg 4’-FlU initiated 12 hours after infection rapidly stopped virus shedding and prevented direct-contact transmission to untreated sentinels. Treatment of mice infected with a lethal inoculum of pandemic A/CA/07/2009 (H1N1)pdm09 (Ca09) with 2 mg/kg 4’-FlU alleviated pneumonia. Three doses mediated complete survival when treatment was initiated up to 60 hours after infection, indicating an unusually broad window for effective intervention. Therapeutic oral 4’-FlU ensured survival of animals infected with HPAI A/VN/12/2003 (H5N1) and of immunocompromised mice infected with pandemic Ca09. Recoverees were fully protected against homologous reinfection. This study defines the mechanistic foundation for high sensitivity of influenza viruses to 4’-FlU and supports 4’-FlU as developmental candidate for the treatment of seasonal and pandemic influenza. Author Summary Next-generation antiviral therapeutics are needed to better mitigate seasonal influenza and prepare against zoonotic virus spillover from animal reservoirs. At greatest risk are the immunocompromised and patients infected with highly pathogenic influenza viruses. In this study, we have demonstrated efficacy of a broad-spectrum nucleoside analog, 4’-fluorouridine, against a representative panel of influenza viruses in cell culture, human organoids, and two animal models, ferrets and mice. Acting as an immediate chain terminator of the influenza virus polymerase, once-daily oral treatment protected against lethal infection with seasonal and highly pathogenic avian influenza viruses, prevented direct-contact transmission to untreated sentinels, and mitigated lethal infection of immunocompromised hosts. These results support the developmental potential of 4’-fluorouridine for treatment of vulnerable patient groups and mitigation of pandemic influenza, providing a much-needed additional therapeutic option for improved disease management.
Partial Articular-sided Rotator Cuff Tears: In Situ Repair Versus Tear Completion Prior to Repair (2013)

Uncertainty exists over the ideal surgical treatment method for partial articular-sided rotator cuff tears, with options ranging from debridement to in situ repair to tear completion prior to repair. The purpose of this study was to determine whether in situ repair was a viable biomechanical treatment option compared with tear completion prior to repair of partial articular-sided rotator cuff tears. Fourteen fresh-frozen cadaveric shoulders were dissected. Partial articular-sided tears were created and repaired using in situ repair or tear completion prior to the repair. Strain and displacement were measured at 45°, 60°, and 90° of glenohumeral abduction. Testing was performed with a load of 100 N applied for 30 cycles. Data from the biomechanical testing displayed 4 conditions that showed improved characteristics of in situ repair over completion and repair: bursal-sided strain anteriorly at 45°, bursal-sided strain anteriorly at 90°, bursal-sided displacement anteriorly at 45°, and bursal-sided displacement anteriorly at 90°. The data indicate that in situ repair is a viable biomechanical treatment option compared with tear completion prior to repair of partial articular-sided rotator cuff tears. When clinically appropriate, the in situ repair may offer some biomechanical advantages, with lower strain and displacement observed on the bursal side compared with tear completion prior to repair.
Automated co-alignment of coherent fiber laser arrays via active phase-locking (2012)

We demonstrate a novel closed-loop approach for high-precision co-alignment of laser beams in an actively phase-locked, coherently combined fiber laser array. The approach ensures interferometric precision by optically transducing beam-to-beam pointing errors into phase errors on a single detector, which are subsequently nulled by duplication of closed-loop phasing controls. Using this approach, beams from five coherent fiber tips were simultaneously phase-locked and position-locked with sub-micron accuracy. Spatial filtering of the sensed light is shown to extend the control range over multiple beam diameters by recovering spatial coherence despite the lack of far-field beam overlap.
Monoclonal antibodies (MAb) in clinical oncology. (1986)

The clinical role of MAbs in the serum and immunohistochemical diagnostics is already established. Their potential usefulness for immunoscintigraphy is in the progress of evaluation and will probably be introduced in nuclear medical routine very soon. First clinical trials with special untagged or radiolabelled MAbs indicate their potency for the therapy of certain tumors. Clinical investigations with drug MAb conjugates have been started and will hopefully reveal significant therapeutic effects.
Effects of hypertonic saline and dextran 70 resuscitation on microvascular permeability after burn (1992)

Administration of hyperosmolar fluids to burn patients has been proposed as a means of decreasing resuscitative fluid volume and, subsequently, wound edema accumulation. To test this hypothesis, canine hindpaw lymph flow (QL) and lymph (CL) and plasma (CP) total protein concentrations were measured, and capillary filtration coefficient (Kf) was calculated before and for 6 h after a 5-s 100 degrees C footpaw scald. Scald was followed 30 min later by bolus infusion (4 ml/kg) of 7% saline or 6% Dextran 70 or the two in combination. Before scald, venous pressure was elevated until a minimal CL/CP was reached. The reflection coefficient (sigma d) was calculated by the formula: 1-minimal CL/CP. Scald increased QL, CL/CP, and Kf, but sigma d was decreased (P less than 0.05). Compared with burn alone, 7% saline exacerbated burn-induced increases in QL and Kf. In contrast, infusion of Dextran 70 did not exacerbate these changes in QL or Kf. Perhaps more importantly, Dextran 70 may have attenuated the increase in CL/CP and reduced edema formation in the burned hindpaw. However, the addition of 7% saline to the dextran eliminated these beneficial effects.
Conductive layer for charge dissipation during electron-beam exposures (2012)

Electron beam resists develop a surface potential during exposure that can lead to image placement errors of up to several nanometers [1] and cause poor CD uniformity and image quality. To address this problem, we have formulated a conductive polymer that can be coated onto the resist. Our conductive discharge layer (CDL) is water soluble and it is easily removed during subsequent processing steps. We have established that our material has low enough resistance for full charge dissipation during e-beam exposure and have carried out extensive tests to evaluate the impact of the layer on lithographic performance. We will report these findings, which include measurements of the effect of the CDL application on resist resolution, contrast, speed, and roughness on both wafer and on mask.
A functional promoter polymorphism in monocyte chemoattractant protein–1 is associated with increased susceptibility to pulmonary tuberculosis (2005)

We examined the distribution of single nucleotide polymorphisms (SNPs) in nitric oxide synthase 2A, monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein-1alpha genes in tuberculosis patients and healthy controls from Mexico. The odds of developing tuberculosis were 2.3- and 5.4-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Cases of homozygous GG had the highest plasma levels of MCP-1 and the lowest plasma levels of IL-12p40, and these values were negatively correlated. Furthermore, stimulation of monocytes from healthy carriers of the genotype GG with Mycobacterium tuberculosis antigens yielded higher MCP-1 and lower IL-12p40 concentrations than parallel experiments with monocytes from homozygous AA. Addition of anti-MCP-1 increased IL-12p40 levels in cultures of M. tuberculosis-stimulated monocytes from homozygous GG, and addition of exogenous MCP-1 reduced IL-12p40 production by M. tuberculosis-stimulated monocytes from homozygous AA. Furthermore, we could replicate our results in Korean subjects, in whom the odds of developing tuberculosis were 2.8- and 6.9-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Our findings suggest that persons bearing the MCP-1 genotype GG produce high concentrations of MCP-1, which inhibits production of IL-12p40 in response to M. tuberculosis and increases the likelihood that M. tuberculosis infection will progress to active pulmonary tuberculosis.
Technique for estimating the angle of incidence and depth of focus of an electron beam (2005)

In order to cope with the problems with scanning electron microscopes for semiconductor manufacturing, the ability to measure the focal depth and incident angle of an electron beam is required. A technique for estimating the angle of incidence and the depth of focus has been devised. The main feature of the technique is to employ the specimen with a special pit, which is formed from sidewalls with an accurate tilt angle and a surface structure. In this work, the pit was formed on a (100) silicon-crystal substrate and from four (111) sidewalls with an accurate tilt angle of 54.74° and a step-like surface. The incident angle and focal depth of an electron beam was estimated by using the pit. The estimation result agreed approximately with the expected.
Yeast sphingolipids do not need to contain very long chain fatty acids (2006)

Synthesis of VLCFAs (very long chain fatty acids) and biosynthesis of DHS (dihydrosphingosine) both are of vital importance for Saccharomyces cerevisiae. The bulk of VLCFAs and DHS are used for ceramide synthesis by the Lag1p (longevity-assurance gene 1)/Lac1p (longevity-assurance gene cognate 1)/Lip1p (Lag1p/Lac1p interacting protein) ceramide synthase. LAG1 and LAC1 are redundant but LIP1 is essential. Here we show that 4Delta (lag1Deltalac1Deltaypc1Deltaydc1Delta) cells devoid of all known endogenous ceramide synthesis pathways are unviable but can be rescued by the expression of Lass5, a mouse LAG1 homologue. Ceramide synthase activity of 4Delta.Lass5 cells only utilizes C16 and C18 fatty acids and does not require the help of Lip1p, an essential cofactor of Lag1p/Lac1p. HPLC-electrospray ionization-MS/MS analysis demonstrated that in IPCs (inositolphosphorylceramides) of 4Delta.Lass5, the very long chain fatty acids (C26 and C24) account for <1% instead of the normal >97%. Notwithstanding, IPCs incorporated into glycosylphosphatidylinositol anchors of 4Delta.Lass5 show normal mobility on TLC and the ceramide- and raft-dependent traffic of Gas1p (glycophospholipid-anchored surface protein) from endoplasmic reticulum to Golgi remains almost normal. Moreover, the biosynthesis of C24:0 fatty acids remains essential. Thus, C(24:0) and dihydrosphingosine are both necessary for survival of yeast cells even if they utilize C16 and C18 fatty acids for sphingolipid biosynthesis.
SPICE Modeling of polysilicon thermal actuators (1997)

This paper reports on modeling the behavior of micromachined polysilicon thermal actuators. The thermal actuators used in this research were fabricated using the DARPA-sponsored multi-user MEMS processes. Data collected in both air and vacuum demonstrates that thermal actuators can be controlled and positioned using a pulsed input with a period much less than the thermal time constant of the device. Both pulse width and pulse amplitude modulation have been successfully employed to position lateral actuators, lateral actuator arrays, and piston micro-mirrors. In order to better exploit the power averaging characteristics of thermal actuators, SPICE models for polysilicon thermal actuators were developed using relationships between resistance, deflection, and average power. These models incorporate the polysilicon thermal actuators electrical load and transient characteristics necessary for predicting actuator performance and developing CMOS drive circuits. The SPICE models exhibit good agreement with theory and measured performance of the polysilicon thermal actuators.
GiLAN Roaming: Roam Like at Home in a Multi-Provider NFV Environment (2018)

`Roam Like at Home' is a slogan used to express the new roaming regulation applied to the countries within the European Union. Since June 15th, 2017, mobile network subscribers of the network operators within the European Union can use mobile services in other European countries without having extra charges for it. Although almost all mobile subscribers within countries of the European Union benefits from the new roaming rule, many mobile service providers are yet to be adapted to this change. Therefore, those providers bear the burden of the cost for the inter-provider traffic. Moreover, the latency between subscribers and their operator specific content must be reduced in order to provide a roaming service `like at home'. An emerging virtualization technology such as a Network Function Virtualization (NFV) sheds light on these challenges. This paper describes the concept of the mobile roaming service and our on-going implementation work as a part of 5G-PPP 5GEx project which aims at localizing inter-provider mobile traffic within the virtualized network infrastructure.
High-surface-area corundum nanoparticles by resistive hotspot-induced phase transformation (2022)

High-surface-area α-Al<sub>2</sub>O<sub>3</sub> nanoparticles are used in high-strength ceramics and stable catalyst supports. The production of α-Al<sub>2</sub>O<sub>3</sub> by phase transformation from γ-Al<sub>2</sub>O<sub>3</sub> is hampered by a high activation energy barrier, which usually requires extended high-temperature annealing (~1500 K, > 10 h) and suffers from aggregation. Here, we report the synthesis of dehydrated α-Al<sub>2</sub>O<sub>3</sub> nanoparticles (phase purity ~100%, particle size ~23 nm, surface area ~65 m<sup>2</sup> g<sup>-1</sup>) by a pulsed direct current Joule heating of γ-Al<sub>2</sub>O<sub>3</sub>. The phase transformation is completed at a reduced bulk temperature and duration (~573 K, < 1 s) via an intermediate δ'-Al<sub>2</sub>O<sub>3</sub> phase. Numerical simulations reveal the resistive hotspot-induced local heating in the pulsed current process enables the rapid transformation. Theoretical calculations show the topotactic transition (from γ- to δ'- to α-Al<sub>2</sub>O<sub>3</sub>) is driven by their surface energy differences. The α-Al<sub>2</sub>O<sub>3</sub> nanoparticles are sintered to nanograined ceramics with hardness superior to commercial alumina and approaching that of sapphire.