gebhart/patrepeval huggingface dataset:
Normal Cellular Prion Protein Protects against Manganese-Induced Oxidative Stress and Apoptotic Cell Death (2007)

The normal prion protein is abundantly expressed in the central nervous system, but its biological function remains unclear. The prion protein has octapeptide repeat regions that bind to several divalent metals, suggesting that the prion proteins may alter the toxic effect of environmental neurotoxic metals. In the present study, we systematically examined whether prion protein modifies the neurotoxicity of manganese (Mn) by comparing the effect of Mn on mouse neural cells expressing prion protein (PrP(C)-cells) and prion-knockout (PrP(KO)-cells). Exposure to Mn (10microM-10mM) for 24 h produced a dose-dependent cytotoxic response in both PrP(C)-cells and PrP(KO)-cells. Interestingly, PrP(C)-cells (EC(50) 117.6microM) were more resistant to Mn-induced cytotoxicity, as compared to PrP(KO)-cells (EC(50) 59.9microM), suggesting a protective role for PrP(C) against Mn neurotoxicity. Analysis of intracellular Mn levels showed less Mn accumulation in PrP(C)-cells as compared to PrP(KO)-cells, but no significant changes in the expression of the metal transporter proteins transferrin and DMT-1. Furthermore, Mn-induced mitochondrial depolarization and reactive oxygen species (ROS) generation were significantly attenuated in PrP(C)-cells as compared to PrP(KO)-cells. Measurement of antioxidant status revealed similar basal levels of glutathione (GSH) in PrP(C)-cells and PrP(KO)-cells; however, Mn treatment caused greater depletion of GSH in PrP(KO)-cells. Mn-induced mitochondrial depolarization and ROS production were followed by time- and dose-dependent activation of the apoptotic cell death cascade involving caspase-9 and -3. Notably, DNA fragmentation induced by both Mn treatment and the oxidative stress inducer hydrogen peroxide (100microM) was significantly suppressed in PrP(C)-cells as compared to PrP(KO)-cells. Together, these results demonstrate that prion protein interferes with divalent metal Mn uptake and protects against Mn-induced oxidative stress and apoptotic cell death.
Electrochemical Fuel Oxidation With a Novel Iron-Nickel Nanoparticle Catalyst (2013)

Abstract not Available.
Phase 1 study to access safety, tolerability, pharmacokinetics, and pharmacodynamics of kynurenine in healthy volunteers (2021)

The kynurenine pathway (KP) is the main path for tryptophan metabolism, and it represents a multitude of potential sites for drug discovery in neuroscience, including pain, stroke, and epilepsy. L-kynurenine (LKYN), the first active metabolite in the pathway, emerges to be a prodrug targeting glutamate receptors. The safety, tolerability, pharmacokinetics, and pharmacodynamics of LKYN in humans have not been previously investigated. In an open-label, single ascending dose study, six participants received an intravenous infusion of 50, 100, and 150 µg/kg LKYN and new six participants received an intravenous infusion of 0.3, 0.5, 1, and 5 mg/kg LKYN. To compare the pharmacological effects between species, we investigated in vivo the vascular effects of LKYN in rats. In humans, LKYN was safe and well-tolerated at all dose levels examined. After infusion, LKYN plasma concentration increased significantly over time 3.23 ± 1.12 µg/mL (after 50 µg/kg), 4.04 ± 1.1 µg/mL (after 100 µg/kg), and 5.25 ± 1.01 µg/mL (after 150 µg/kg) (p ≤ 0.001). We observed no vascular changes after infusion compared with baseline. In rats, LKYN had no effect on HR and MAP and caused no dilation of dural and pial arteries. This first-in-human study of LKYN showed that LKYN was safe and well-tolerated after intravenous infusion up to 5 mg/kg over 20 minutes. The lack of change in LKYN metabolites in plasma suggests a relatively slow metabolism of LKYN and no or little feed-back effect of LKYN on its synthesis. The therapeutic potential of LKYN in stroke and epilepsy should be explored in future studies in humans.
Faculty Opinions recommendation of G protein-coupled receptors sense fluid shear stress in endothelial cells. (2006)

Hemodynamic shear stress stimulates a number of intracellular events that both regulate vessel structure and influence development of vascular pathologies. The precise molecular mechanisms by which endothelial cells transduce this mechanical stimulus into intracellular biochemical response have not been established. Here, we show that mechanical perturbation of the plasma membrane leads to ligand-independent conformational transitions in a G protein-coupled receptor (GPCR). By using time-resolved fluorescence microscopy and GPCR conformation-sensitive FRET we found that stimulation of endothelial cells with fluid shear stress, hypotonic stress, or membrane fluidizing agent leads to a significant increase in activity of bradykinin B2 GPCR in endothelial cells. The GPCR conformational dynamics was detected by monitoring redistribution of GPCRs between inactive and active conformations in a single endothelial cell under fluid shear stress in real time. We show that this response can be blocked by a B(2)-selective antagonist. Our data demonstrate that changes in cell membrane tension and membrane fluidity affect conformational dynamics of GPCRs. Therefore, we suggest that GPCRs are involved in mediating primary mechanochemical signal transduction in endothelial cells. We anticipate our experiments to be a starting point for more sophisticated studies of the effects of changes in lipid bilayer environment on GPCR conformational dynamics. Furthermore, because GPCRs are a major target of drug development, a detailed characterization of mechanochemical signaling via the GPCR pathway will be relevant for the development of new antiatherosclerosis drugs. PMID: 17030791 Funding information This work was supported by: NHLBI NIH HHS, United States Grant ID: HL40696 NHLBI NIH HHS, United States Grant ID: R37 HL040696 NHLBI NIH HHS, United States Grant ID: R01 HL040696
A High Power, Narrow Linewidth and Wavelength Tunable Semiconductor Laser Using a Photopolymer Bragg Grating as One of the Cavity Mirrors (2014)

A PQ-PMMA Bragg grating served as one of the cavity mirrors in an external V-shaped laser cavity using a tapered-amplifier as the gain medium. The laser achieves singe longitudinal mode with the output power exceed 600 mW, and has 30 nm tunable spectral range.
RECENT DEVELOPMENTS IN MEMBRANE-BASED SEPARATIONS IN BIOTECHNOLOGY PROCESSES: REVIEW (2011)

Membrane-based separations are the most ubiquitous unit operations in biotech processes. There are several key reasons for this. First, they can be used with a large variety of applications including clarification, concentration, buffer exchange, purification, and sterilization. Second, they are available in a variety of formats, such as depth filtration, ultrafiltration, diafiltration, nanofiltration, reverse osmosis, and microfiltration. Third, they are simple to operate and are generally robust toward normal variations in feed material and operating parameters. Fourth, membrane-based separations typically require lower capital cost when compared to other processing options. As a result of these advantages, a typical biotech process has anywhere from 10 to 20 membrane-based separation steps. In this article we review the major developments that have occurred on this topic with a focus on developments in the last 5 years.
ChemInform Abstract: Recent Advances in the Chemistry of Water‐Soluble Phosphines ‐ Catalytic and Biomedical Aspects (1996)

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.
Enteral nutrition decreases hospitalization rate in patients with Crohn's disease (2010)

The use of an elemental diet of 900 kcal/day may be effective in avoiding hospitalization in CD patients with ileal lesions. This diet may be useful in improving the long-term convalescence of these patients.
High-Density Lipoprotein Therapy in Stroke: Evaluation of Endothelial SR-BI-Dependent Neuroprotective Effects (2020)

High-density lipoproteins (HDLs) display endothelial protective effects. We tested the role of SR-BI, an HDL receptor expressed by endothelial cells, in the neuroprotective effects of HDLs using an experimental model of acute ischemic stroke. After transient intraluminal middle cerebral artery occlusion (tMCAO), control and endothelial SR-BI deficient mice were intravenously injected by HDLs or saline. Infarct volume and blood-brain barrier (BBB) breakdown were assessed 24 h post tMCAO. The potential of HDLs and the role of SR-BI to maintain the BBB integrity was assessed by using a human cellular model of BBB (hCMEC/D3 cell line) subjected to oxygen-glucose deprivation (OGD). HDL therapy limited the infarct volume and the BBB leakage in control mice relative to saline injection. Interestingly, these neuroprotective effects were thwarted by the deletion of SR-BI in endothelial cells and preserved in mice deficient for SR-BI in myeloid cells. In vitro studies revealed that HDLs can preserve the integrity of the BBB in OGD conditions, and that this effect was reduced by the SR-BI inhibitor, BLT-1. The protection of BBB integrity plays a pivotal role in HDL therapy of acute ischemic stroke. Our results show that this effect is partially mediated by the HDL receptor, SR-BI expressed by endothelial cells.
Drug Development in Solid Organ Transplantation and the Approval Process for Transplant Immunosuppressants (2014)

Before an immunosuppressant drug can be specifically indicated for use in transplantation, a time intensive process involving discovery, formulation, characterization and preclinical and clinical evaluation is required that ideally culminates in approval by regulatory authorities and acceptance by practitioners and patients. This chapter discusses the step-by-step process followed by pharmaceutical companies, as well as the criteria required of a drug candidate, before gaining regulatory approval. The approval process highlights the close interactions with regulatory agencies required, as well as the rigorous standards required.
Analysis and perception of spectral 1/f characteristics of amplitude and period fluctuations in normal sustained vowels (1999)

Two kinds of fluctuations are always observed in the steady parts of normal sustained vowels. One is amplitude fluctuation, defined as the cyclic changes of maximum peak amplitudes. The other is period fluctuation, defined as the cyclic changes of pitch periods. The primary purpose of this paper is to present quantitative descriptions of amplitude and period sequences obtained from normal sustained vowels. These fluctuation sequences consisted of maximum peak amplitudes or pitch periods extracted successively from 512 consecutive pitch periods in the steady part. Results of the frequency analysis indicated that their frequency characteristics seemed to be subject to the spectral 1/f power law. In order to investigate the possibility that the frequency characteristics of the fluctuation sequences influence the voice quality of sustained vowels, psychoacoustic experiments were conducted. Amplitude and period sequences evaluated in the experiments were spectral 1/f0 (white noise), 1/f, 1/f2, and 1/f3 sequences, respectively. The experimental results indicated that the subjective voice quality of synthesized sustained vowels could reflect the differences in the frequency characteristics of the fluctuation sequences.
Novel global effector mining from the transcriptome of early life stages of the soybean cyst nematode Heterodera glycines (2018)

Soybean cyst nematode (SCN) Heterodera glycines is an obligate parasite that relies on the secretion of effector proteins to manipulate host cellular processes that favor the formation of a feeding site within host roots to ensure its survival. The sequence complexity and co-evolutionary forces acting upon these effectors remain unknown. Here we generated a de novo transcriptome assembly representing the early life stages of SCN in both a compatible and an incompatible host interaction to facilitate global effector mining efforts in the absence of an available annotated SCN genome. We then employed a dual effector prediction strategy coupling a newly developed nematode effector prediction tool, N-Preffector, with a traditional secreted protein prediction pipeline to uncover a suite of novel effector candidates. Our analysis distinguished between effectors that co-evolve with the host genotype and those conserved by the pathogen to maintain a core function in parasitism and demonstrated that alternative splicing is one mechanism used to diversify the effector pool. In addition, we confirmed the presence of viral and microbial inhabitants with molecular sequence information. This transcriptome represents the most comprehensive whole-nematode sequence currently available for SCN and can be used as a tool for annotation of expected genome assemblies.
Abstract P1-08-09: EGFR expression is associated with decreased response from HER2 targeted therapeutics in the neo-adjuvant setting in the NeoALTTO trial (2013)

Abstract Background: Epidermal Growth Factor Receptor (EGFR, HER1) is known to heterodimerize with HER2 and may modulate the effectiveness of trastuzumab or lapatinib. Historically, it has been difficult to measure, but recently we reported a new, standardized, quantitative immunofluorescence assay and a novel EGFR antibody which showed that high levels of EGFR were associated with decreased benefit in the concurrent arm of the North Central Cancer Treatment Group (NCCTG/Alliance) N9831 trial (Rimm et al, SABCS 2012). Here we assess its value in the neo-adjuvant setting in the NeoALTTO trial. Methods: NeoALTTO randomized 455 breast cancer patients to neoadjuvant trastuzumab, lapatinib or both and showed benefit in both single anti-HER2 therapy arms, and the combination therapy showing about twice as much benefit as either single drug arm. We used the previously described AQUA method of quantitative immunofluorescence to measure EGFR levels using the D38B1 antibody on between 4 and 140 fields of view per slide on 353 specimens. The averaged EGFR score was standardized to the absolute concentration using cell lines and western blots and the 13 ng/ug total protein established in the N9831 trial was tested to determine predictive value for pathological complete response (pCR) defined as ypT0/is. Results: In NeoALTTO, 19% of the patients had EGFR levels above 13 ng/ug, compared to 16% in NCCTG N9831. The pCR rate was 35.3% in the patients with low EGFR, compared with 29.8% for high EGFR but this difference was not statistically significant. However, when adjusted for treatment and hormone receptor (HR) status, high EGFR is statistically significantly associated with lower response rate(p = 0.038). Continuous analysis measures were not significant. The effect on overall response at 6 weeks was also weakly significant when adjusting for treatment and HR status (p = 0.06). Surprisingly, for HR negative patients in the lapatinib only arm, the pCR rate in the low EGFR group was 47.2% compared with 16.0% in the high group. While this difference is statistically significant (p = 0.014), it should be interpreted cautiously because of the small numbers of patients and the multiple tests performed. Conclusions: High expression of EGFR by the AQUA platform appears to be associated with decreased pCR rate from HER2 targeted therapy in the neoadjuvant setting. This observation is consistent with NCCTG N9831. Although underpowered, high EGFR levels predicted decreased pCR rate from lapatinib, the opposite of that anticipated for this small molecule dual EGFR/HER2 inhibitor. Further studies are required to determine the clinical utility of this assay and the biological mechanisms underlying these observations. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-09.
Understanding Structure Changes during Cycling of MoS<sub>2</sub>-based Mg Batteries (2019)

Aberration-corrected (scanning) transmission electron microscopy ((S)TEM) has been used as an important tool to characterize battery materials. However, the dis/charge processes often generate a large number of defects in the electrode materials strongly distorting their crystalline structure or even making them amorphous. At the same time, the solid electrolyte interface (SEI) is formed and they are electrolyte coated after cycling. This intrinsically limits application of atomically resolved imaging techniques and even conventional diffraction. Furthermore, the signal of analytical methods such as EDX and EELS spectral imaging is obscured as the nanosized electrode particles are mostly surrounded by carbonaceous additives, which are used for enhancing electron conductivity of the battery electrode in the realistic electrochemical environment [1] . The atomic pair distribution function (PDF) obtained from diffraction [2] , measuring the interatomic distances and coordination, directly probes the atomic configuration, also for strongly distorted or disordered materials. In contrast to X-ray and neutron diffraction, electron diffraction in TEM provides highly flexible spatial resolution from micro-to tens of nanometer [3] . The recently developed 4D STEM-PDF [4] analysis offers PDF mapping with sub-nanometer spatial resolution and, at the same time, samples a statistically meaningful area representing the global sample properties. The power to answer structural questions of complex materials has been demonstrated, e.g. analyzing the structure evolution of phase transformation [3, 5] and the structure of metallic nanoglasses [6] . In this talk, we demonstrate that PDF analysis of electron diffraction in TEM associated with multivariate statistical analysis (MSA) can overcome the above mentioned issues and provide detailed structural and bonding analysis for long-time cycled real batteries. We explore our approach using MoS2-based Mg batteries, as the rechargeable Mg batteries are one of the most promising candidates for the next generation battery technologies. However, the crystalline structure of the host material is significantly destroyed during cycling because of the strong interaction between double charged Mg 2+ and the intercalation host, which leads to a transition from a short-and medium range order similar to 1H MoS2 to 2T MoS2 during cycling. As shown in figure This proves that the high charge density of Mg 2+ may be mitigated through dimethoxyethane solvation, which avoids the sluggish desolvation process at the cathode electrolyte interfaces and reduces the trapping force of the cathode lattice to the cations, facilitating Mg 2+ diffusion. In addition, the 4DSTEM-PDF line scan in the charged sample (figure It explains the ambiguous correlation between the X-ray photo-emission spectroscopy (XPS) result and the electrochemistry [8] .
Latanoprost's effects on TIMP-1 and TIMP-2 expression in human ciliary muscle cells. (2002)

For the most part, TIMP-1, and not TIMP-2, contributes to regulation of MMP within the uveoscleral outflow pathway after exposure to latanoprost. Moreover, this induction appears to be meditated by activation of PKC.
Self-tuning cooperative control of manipulators with position/orientation uncertainties in the closed-kinematic loop (2011)

Bilateral teleoperation systems have been extensively utilized for implementing tasks in remote or hazardous environments. However, due to the cognitive limitations of the human operator, efficient teleoperation of complex robotic system operating in cluttered environments has been difficult to achieve. In this paper, we study the control problem of a semi-autonomous teleoperation system, where the redundant slave robot can autonomously satisfy several constraints while tracking the position of the master robot in the task space. Considering heterogeneous master and slave robots, we first develop a control algorithm to ensure task space position and velocity tracking between the master and slave robots in the presence of dynamic uncertainties and communication delays. The redundancy of the slave robot is then utilized for achieving sub-task control, such as singularity avoidance, joint limits, and collision avoidance. The control algorithms for the proposed semi-autonomous teleoperation system are validated using numerical simulations on a non-redundant master and a redundant slave robot.
Jean-Jacques Rousseau on the Fear of Death and the Happiness of Life (2021)

This chapter considers Jean-Jacques Rousseau's two-fold “correction” of Thomas Hobbes: that the fear of death is unnatural, and that a complete happiness is available to people in the sentiment of existence. It examines Rousseau’s reasons for denying that man naturally fears death, and then considers whether a way exists for l’homme present to recover, on the plane of humanity rather than animality, the tranquility and happiness Rousseau attributes to l’homme naturel. Rousseau emphasizes that the faculties natural man possessed in potentiality which, once activated, destroyed his physical and psychic self-sufficiency, developed only by chance; thus he might have remained “eternally” in his primitive condition. In his autobiographical writings, Rousseau offers himself as a new model of the man of nature, “enlightened by reason,” bearing “the yoke of necessity,” and enjoying his existence &quot;without much worry about what men think of it and without much concern for the future&quot;.
Personal Vehicles Evaluated against Climate Change Mitigation Targets (2016)

Meeting global climate change mitigation goals will likely require that transportation-related greenhouse gas emissions begin to decline within the next two decades and then continue to fall. A variety of vehicle technologies and fuels are commercially available to consumers today that can reduce the emissions of the transportation sector. Yet what are the best options, and do any suffice to meet climate policy targets? Here, we examine the costs and carbon intensities of 125 light-duty vehicle models on the U.S. market today and evaluate these models against U.S. emission-reduction targets for 2030, 2040, and 2050 that are compatible with the goal of limiting mean global temperature rise to 2 °C above preindustrial levels. Our results show that consumers are not required to pay more for a low-carbon-emitting vehicle. Across the diverse set of vehicle models and powertrain technologies examined, a clean vehicle is usually a low-cost vehicle. Although the average carbon intensity of vehicles sold in 2014 exceeds the climate target for 2030 by more than 50%, we find that most hybrid and battery electric vehicles available today meet this target. By 2050, only electric vehicles supplied with almost completely carbon-free electric power are expected to meet climate-policy targets.
Study on Advanced Humid Air Turbine System : (2) Humidification Methods and System Performance (2004)

The characteristic of a saturator (a humidification tower), which is used as a humidifier of the AHAT( Advanced Humid Air Turbine) system, were studied. For various pressure ratios (from 8 to 24) of a gas turbine, the required packing height and the exit water temperature from the saturator were analyzed. Thermal efficiency of the system was compared with the simple cycle and the recuperated cycle. The highest thermal efficiency of the system was 54.7% LHV when the pressure ratio was 20. The efficiency can be raised further by cooling blades with humid air. When the packing height of the saturator was changed, the required size of three heat exchangers around the saturator (a recuperator, an economizer and an air cooler) varied. The packing height with which the sum total of the size of the saturator and these heat exchangers become the minimum was 1m when the pressure ratio was 8, and 6m when the pressure ratio was 24.