gebhart/patrepeval huggingface dataset:
Data from LKB1-Dependent Regulation of TPI1 Creates a Divergent Metabolic Liability between Human and Mouse Lung Adenocarcinoma (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;i&gt;KRAS&lt;/i&gt; is the most frequently mutated oncogene in human lung adenocarcinomas (hLUAD), and activating mutations frequently co-occur with loss-of-function mutations in &lt;i&gt;TP53&lt;/i&gt; or &lt;i&gt;STK11/LKB1&lt;/i&gt;. However, mutation of all three genes is rarely observed in hLUAD, even though engineered comutation is highly aggressive in mouse lung adenocarcinoma (mLUAD). Here, we provide a mechanistic explanation for this difference by uncovering an evolutionary divergence in the regulation of triosephosphate isomerase (TPI1). In hLUAD, TPI1 activity is regulated via phosphorylation at Ser21 by the salt inducible kinases (SIK) in an LKB1-dependent manner, modulating flux between the completion of glycolysis and production of glycerol lipids. In mice, Ser21 of TPI1 is a Cys residue that can be oxidized to alter TPI1 activity without a need for SIKs or LKB1. Our findings suggest this metabolic flexibility is critical in rapidly growing cells with &lt;i&gt;KRAS&lt;/i&gt; and &lt;i&gt;TP53&lt;/i&gt; mutations, explaining why the loss of LKB1 creates a liability in these tumors.&lt;/p&gt;Significance:&lt;p&gt;Utilizing phosphoproteomics and metabolomics in genetically engineered human cell lines and genetically engineered mouse models (GEMM), we uncover an evolutionary divergence in metabolic regulation within a clinically relevant genotype of human LUAD with therapeutic implications. Our data provide a cautionary example of the limits of GEMMs as tools to study human diseases such as cancers.&lt;/p&gt;&lt;p&gt;&lt;a href="https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-13-4-ITI" target="_blank"&gt;This article is highlighted in the In This Issue feature, p. 799&lt;/a&gt;&lt;/p&gt;&lt;/div&gt;
Monolithically Integrated InGaN-Based Multicolor Light-Emitting Diodes Fabricated by Wide-Stripe Selective Area Metal–Organic Vapor Phase Epitaxy (2010)

We have demonstrated monolithic integration of multicolor light-emitting diodes (LEDs) by selective-area metalorganic vapor phase epitaxy (SA-MOVPE). The use of relatively wide (>30 µm) masks resulted in a large in-plane modulation of both InGaN layer thickness and composition, allowing us a wide range of wavelength modulation. A wider mask shifted the electroluminescence spectrum to longer wavelengths due to vapor-phase diffusion of precursors. LED elements were formed at the center of the 60-µm-wide growth area, the peak wavelength of which covered 454–545 nm around turn-on voltages and 454–485 nm under a high-injection condition.
Reaction Coordinate of Incipient Methane Clathrate Hydrate Nucleation (2014)

Nucleation from solution is a ubiquitous phenomenon with relevance to myriad scientific disciplines, including pharmaceuticals, biomineralization, and disease. One prominent example is the nucleation of clathrate hydrates, multicomponent crystalline inclusion compounds relevant to the energy industry where they block pipelines and also constitute a potential vast energy resource. Despite their importance, the molecular mechanism of incipient hydrate formation remains unknown. Herein, we employ advanced molecular simulation tools (pB histogram, equilibrium path sampling) to provide a statistical-mechanical basis for extracting physical insight into the molecular steps by which clathrates form. Through testing the Mutually Coordinated Guest (MCG) order parameter, we demonstrate that both guest (methane) and host (water) structuring are crucial to accurately describe the nucleation of hydrates and determine a critical nucleus size of MCG-1 = 16 at 255 K and 500 bar. Equipped with a validated (and novel) reaction coordinate, subsequent equilibrium path sampling simulations yield the free energy barrier and nucleation rate. The resulting quantitative nucleation process is described by the MCG clustering mechanism. This constitutes a significant advance in the field of hydrates research, as the fitness of a molecular descriptor has never been statistically verified. More broadly, this work has significance to a wide range of multicomponent nucleation contexts wherein the formation mechanism depends on contributions from both solute and solvent.
Heavy, ultrafast scintillator of Yb<sup>3+</sup>-doped transparent ceramic Lu<inf>2</inf>O<inf>3</inf> (2013)

Transparent ceramic Yb-doped Lu <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> were evaluate on scintillation properties. In X-ray excited radioluminescence, they exhibited Yb <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3+</sup> charge transfer luminescence around 350 nm. Scintillation decay time profiles were investigated and they showed ultrafast scintillation of around ~ 1ns. Light yields under <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">137</sup> Cs 662 keV γ-ray excitation were around 500 ph/MeV.
DOCA‐salt hypertension promotes leukocyte (but not platelet) adhesion in cerebral venules (2009)

Although hypertension is a major risk factor for the development of ischemic stroke, the mechanisms underlying the influence of increased blood pressure on stroke risk remain poorly understood. Since both platelets and inflammatory cells have been implicated in the pathogenesis of ischemic stroke, we examined whether DOCA‐salt induced hypertension alters the behavior of platelets and leukocytes in cerebral venules in male mice. A 50 mg DOCA pellet was implanted via s.c. in uninephrectomized C57Bl/6 mice placed on 1 % saline for a period of 3 weeks, which produced a significant increase in blood pressure (from 103±2 to 127±2 mmHg) as well as cardiac and renal hypertrophy (relative to controls). Platelets isolated from matched donor mice were labeled ex vivo with CSFE while rhodamine was administered i.v. for in vivo labeling of leukocytes. Intravital microscopic observation of blood cell trafficking in pial venules revealed a large increase in the number of adherent leukocytes in DOCA‐salt mice (558±58 per mm 2 vs 183±39 per mm 2 ). However, platelet adhesion within venules was unaffected by DOCA‐salt (12±7 per mm 2 vs 4±4 per mm 2 ). These findings indicate that DOCA‐salt induced hypertension induced a pro‐inflammatory, but not a pro‐thrombogenic, phenotype in the cerebral microvasculature. The accumulation of inflammatory cells in the brain during hypertension may predispose this tissue to ischemic tissue injury. (Supported by HL26441).
Cisplatin Selects for Multidrug-Resistant CD133+ Cells in Lung Adenocarcinoma by Activating Notch Signaling (2012)

Platinum-based chemotherapy is the first-line treatment for non-small cell lung cancer, but recurrence occurs in most patients. Recent evidence suggests that CD133(+) cells are the cause of drug resistance and tumor recurrence. However, the correlation between chemotherapy and regulation of CD133(+) cells has not been investigated methodically. In this study, we revealed that CD133(+) lung cancer cells labeled by a human CD133 promoter-driven GFP reporter exhibited drug resistance and stem cell characteristics. Treatment of H460 and H661 cell lines with low-dose cisplatin (IC(20)) was sufficient to enrich CD133(+) cells, to induce DNA damage responses, and to upregulate ABCG2 and ABCB1 expression, which therefore increased the cross-resistance to doxorubicin and paclitaxel. This cisplatin-induced enrichment of CD133(+) cells was mediated through Notch signaling as judged by increased levels of cleaved Notch1 (NICD1). Pretreatment with the γ-secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT), or Notch1 short hairpin RNAs (shRNA) remarkably reduced the cisplatin-induced enrichment of CD133(+) cells and increased the sensitivity to doxorubicin and paclitaxel. Ectopic expression of NICD1 reversed the action of DAPT on drug sensitivity. Immunohistochemistry showed that CD133(+) cells were significantly increased in the relapsed tumors in three of six patients with lung cancer who have received cisplatin treatment. A similar effect was observed in animal experiments as cisplatin treatment increased Notch1 cleavage and the ratio of CD133(+) cells in engrafted tumors. Intratumoral injection of DAPT with cisplatin treatment significantly reduced CD133(+) cell number. Together, our results showed that cisplatin induces the enrichment of CD133(+) cells, leading to multidrug resistance by the activation of Notch signaling.
Future Interconnect Materials and System Integration Strategies for Data-Intensive Applications (2018)

The microelectronics industry today faces multiple inflections: increasing technology complexity, emerging data-intensive market drivers like the Internet of Things (IoT) and Artificial Intelligence (AI), and an increasing focus on system-level integration & optimization. These inflections challenge the industry to build innovative collaboration models that cut across traditional silos. SEMI has built a collaborative platform specifically to address this challenge by providing early and comprehensive assessment of future technologies (5-8 years out). The first project focused on interconnect materials and integration strategies, which are critical to most computing systems. Specific elements studied here include the increase in resistivity with narrowing wire-widths, supply-chain issues with proposed solutions, and the impact on latency for simple circuit systems. In addition, we also compared a two-dimensional (2D) system with an interposer-based system (2.5D) to quantify the impact of the latter on the energy-delay product for various applications.
Lipid A mimetics BECC438 and BECC470 potentiate durable and balanced immune responses using an ovalbumin murine vaccine model (2021)

Abstract The need for effective infectious disease vaccines has become an inescapable topic over the past year. Continued development of next-generation vaccines that provide robust protective immunity is imperative. Such vaccines will likely include an adjuvant that avoids excessive adverse reactions and allows for dose and antigen sparing. Bacterial lipid A mimetics BECC438 and BECC470 have recently emerged as lead adjuvant candidates across several experimental models of infectious disease including Yersinia pestis (plague), human papilloma virus (HPV), and influenza-A (flu). To further define BECC438 and BECC470 as immuno-adjuvants, even without antigen from an infectious pathogen, studies presented here use ovalbumin (Ova) as a model antigen in a murine prime-boost vaccine model. Higher magnitude and more balanced production of antibody isotypes IgG1 and IgG2 are observed when BECC adjuvants are compared to classic adjuvants alum and PHAD. This optimal antibody response is durable and maintained for at least 12 weeks post-vaccination. Initial experiments use C57BL6 mice and are expanded to include BALBc and CD-1 (outbred) mice. Observed immune metrics maintained similar trends across male and females, and genetic backgrounds tested. Biacore immunogenicity analysis of C57BL6 serum found an increased half-life of Ova-specific antibodies in BECC438-adjuvanted animals potentially indicative of a higher antigen binding affinity. Toxicity studies conducted in New Zealand White rabbits report that BECC438 was well tolerated with no significant reactogenicity after 50μg and 100μg intra-muscular adjuvant injection. These studies provide continued evidence supporting development of BECC adjuvants in vaccines for human use.
650 V, 7 mΩ 4H-SiC DMOSFETs for Dual-Side Sintered Power Modules (2018)

In this paper, we present our latest results on 650 V 4H-SiC DMOSFET developments for dual-side sintered power modules in electric drive vehicles. A low specific on-resistance (R sp , on ) of 1.8 mΩ⋅cm 2 has been achieved on 650 V, 7 mΩ 4H-SiC DMOSFETs at 25°C, which increases to 2.4 mΩ⋅cm 2 at 150°C. For the first time, the DMOSFET chip is designed specifically for use in dual-side soldering and sintering processes, and a 650 V, 1.7 mΩ SiC DMOSFET multichip half bridge power module has been built using the wirebond-free assembly. Compared to a similarly rated Si IGBT module, the conduction and switching losses were reduced by 80% and ~50%, respectively.
Electric characteristics of normally-off type 5 kV class 4H-SiC JFET, "SEJEET" (2005)

A normally-off type 5.3kV 4H-SiC JFET with low specific on-resistance, called SEJFET (Static Expansion channel JFET), has been fabricated. Its normally-off operation was realized by a thin regrown epitaxial channel layer and using the buried p+ regions as a gate in addition to the top p+ regions. The achieved blocking voltage is the highest class BV among the reported SiC JFET. In a 5.3kV 4H-SiC SEJFET, the lowest specific on resistance of 69mΩcm2. Furthermore, the highest current capability among SiC JFET of 3.3A is achieved. In all reported FETs, the SEJFET has the best trade-off between RonS and blocking voltage (BV), which is about 1/230th lower than theoretical limit of a Si FET. Furthermore, the figure of merit (BV2/RonS) is 407MW/cm2, and this value is the highest among reported normally off SiC FETs.
Quantifying photovoltaic fluctuation with 5 kHz data: Implications for energy loss via maximum power point trackers (2016)

We aim to systematically quantify photovoltaic (PV) variability contained within different frequency bands, primarily for applications in PV maximum power point tracking (MPPT) design. We first discuss the usefulness in quantifying energy capture for various maximum power point (MPP) update rates from nearly 500 days of 5 kHz photovoltaic recordings. Next, we justify the methods used to convert MPP sweep data to single-point, usable, current, voltage, and power values. We discuss fitting methods that yield the MPP under calm irradiance dynamics and explore the approach used during periods of more stochastic changes. This is followed by analysis of raw, high-frequency content and a proposed method to calculate associated energy capture reduction. The conclusion finds an absolute upper bound on solar data variability for a given MPP update rate in terms of energy capture. Finally, we use the previous results and demonstrate an economic analysis that can aid in designing future MPP tracker specifications.
Creating a Simulation Environment to Analyze Benefits of Real-time Taxi Flow Optimization Using Actual Data (2011)

To make optimal use of the available runway and taxiway infrastructure and to prevent the workload of the controllers becoming a limitation, a route-planning function that generates routes automatically is needed. The uncertainty in the taxi process is an important disturbance in today’s surface operations. To allow for deconfliction in the planning domain, the routes need to include time information. The route-planning function will need to use time-margins to provide a certain level of robustness against disturbances. A determining factor in the selection of the size of the margins is the tradeoff between the (maximum) capacity that can theoretically be achieved in the absence of disturbances and the robustness against disturbances. A key challenge is the identification of the relation needed to specify time margins as a function of traffic density and disturbance statistics. An important uncertainty of the taxi processes is the taxi speed. This paper will describe a method to obtain and quantify taxi traffic flow performance and taxi speed distribution using real world data from Amsterdam airport. Furthermore the development of a simulation environment to evaluate the performance of various route-planning functions for selectable time-margins and disturbance statistics is described. In addition a method is described to extract surface traffic scenarios from real world data. The scenarios are used to verify the fidelity of the surface traffic simulation.
Fas Ligand Overexpression on Allograft Endothelium Inhibits Inflammatory Cell Infiltration and Transplant-Associated Intimal Hyperplasia (2001)

Despite recent advances in immunosuppressive therapy, accelerated coronary atherosclerosis remains a major problem in the long-term survival of transplant recipients. Chronic graft vasculopathy is believed to result from recipient inflammatory responses, and it is characterized by early mononuclear cell infiltration of the transplanted vessel. Here we show that endothelial cells can be genetically modified to overexpress functional, cell-surface Fas ligand (FasL) by adenovirus-mediated gene transfer without undergoing self-destruction. In a rodent model of transplant graft vasculopathy, endothelial overexpression of FasL attenuated T cell and macrophage infiltration at 1 wk posttransplantation. These vessels also displayed reduced neointima formation at one and 2 mo posttransplantation. These results indicate that inhibition of the early inflammatory response to allografted vessels by endothelial cell-specific overexpression of FasL may have utility in the treatment of transplant arteriosclerosis.
Bio-Bar-Code-Based DNA Detection with PCR-like Sensitivity (2004)

Novel two-component oligonucleotide-modified nanoparticle probes have been designed and used in a bio-bar-code assay with a 500 zeptomolar target DNA sensitivity limit.
Synthesis of an Anionically Chargeable, High-Molar-Mass, Second-Generation Dendronized Polymer and the Observation of Branching by Scanning Force Microscopy (2006)

An efficient synthesis of a methacrylate-based, second-generation (G2) dendronized macromonomer and its free radical polymerization to the corresponding high-molar-mass G2 dendronized polymer are described. The molar mass is determined by gel permeation chromatography (GPC), light-scattering, and analytical ultracentrifugation and compared with values estimated from a scanning force microscopy (SFM) contour lengths analysis of individualized polymer strands on mica. The polymer carries terminal tert-butyl-protected carboxyl groups, the degree of deprotection of which with trifluoroacetic acid is quantified by NMR spectroscopy using the highest molar mass sample. SFM imaging of both protected (noncharged) and unprotected (charged) dendronized polymers on solid substrates reveals mostly linear chains but also some with main-chain branches. The nature of these branches is investigated and the degree roughly estimated to which they are formed. Finally, a synthetic model experiment is described which sheds some light on the aspect of whether chain transfer, a process that could lead to covalent branching, is of importance in the synthesis of the present dendronized polymers.
A Fluid-Structure Interaction Model for 3D Heart Valve Dynamics (2008)

Bioprosthetic heart valves are valve replacements constructed from animal tissue. Although they are geometrically similar to native aortic valves and offer comparable hemodynamic characteristics in their function, they have limited operational life, often requiring replacement 10–15 years after implantation. Though much is still unknown about bioprosthetic heart valve failure, it is generally accepted that this failure is to some extent due to structural decomposition. Although the mechanism for degradation is not clearly understood, it has been observed that these regions of failure are typically in locations where the leaflet undergoes large flexion and high compressive and tensile stresses [1]. An understanding of bioprosthetic heart valve failure necessitates detailed quantitative information on the complex motion of and the stresses on the leaflets particularly during the opening and closing phases and their relationship to structural failure.
ChemInform Abstract: Organocatalytic Asymmetric Transfer Hydrogenation of Imines (2011)

Abstract Review: 93 refs.
A Unique Mdm2-Binding Mode of the 3-Pyrrolin-2-one- and 2-Furanone-Based Antagonists of the p53-Mdm2 Interaction (2016)

The p53 pathway is inactivated in almost all types of cancer by mutations in the p53 encoding gene or overexpression of the p53 negative regulators, Mdm2 and/or Mdmx. Restoration of the p53 function by inhibition of the p53-Mdm2/Mdmx interaction opens up a prospect for a nongenotoxic anticancer therapy. Here, we present the syntheses, activities, and crystal structures of two novel classes of Mdm2-p53 inhibitors that are based on the 3-pyrrolin-2-one and 2-furanone scaffolds. The structures of the complexes formed by these inhibitors and Mdm2 reveal the dimeric protein molecular organization that has not been observed in the small-molecule/Mdm2 complexes described until now. In particular, the 6-chloroindole group does not occupy the usual Trp-23 pocket of Mdm2 but instead is engaged in dimerization. This entirely unique binding mode of the compounds opens new possibilities for optimization of the Mdm2-p53 interaction inhibitors.
Core Body Temperature Responses Immediately After Cutaneous Thermal Injury in Rats (1992)

Internal temperatures were continuously measured in rats that received 20% or 40% body surface area cutaneous scald injuries in 25 degrees C and 38.5 degrees C environments. In animals that received thermal injuries in the 25 degrees C environment, intraperitoneal, intraesophageal, and intrarectal temperatures rapidly rose to 40 degrees C within 5 minutes but returned to normal values within 15 minutes after injury. When 20% body surface area injuries were induced in a 25 degrees C environment, all of the animals survived. In the 25 degrees C environment, neither acute core body temperature elevations nor use of fluid resuscitation predicted survival. In contrast, in a 38.5 degrees C environment core body temperatures rapidly exceeded 41 degrees C with the 20% injury, and all of the animals died within minutes in spite of fluid resuscitation. These studies suggest that the ambient environmental temperature may significantly influence a thermally injured animal's ability to rapidly eliminate absorbed heat of injury and result in an elevated core body temperature, which may contribute to the immediate lethality of the injury.
Kansuinine A and Kansuinine B fromEuphorbia kansuiL. Inhibit IL-6-induced Stat3 Activation (2010)

The current study was performed to examine the mechanisms underlying the potential effects of E. KANSUI on IL-6-induced cellular signaling in human hepatoma cells. We found that two diterpenoids, kansuinine A and B, from E. KANSUI have an inhibitory effect on IL-6-induced Stat3 activation by activating ERK1/2. Inhibition of MEK significantly blocked the effects of kansuinine A and B on IL-6-induced Stat3 activation and tyrosine phosphorylation. These results suggest that blocking of IL-6-induced signal transduction is partially due to the sustained activation of ERK1/2 by kansuinine A and B, which in turn results in an increase of Stat3 serine phosphorylation and SOCS-3 expression. Treatment with kansuinine A and B represents a novel method to block these IL-6-induced effects.
Enhanced chlorhexidine skin penetration with 1,8-cineole (2017)

Enhanced delivery of CHG can be achieved in the presence of 1,8-cineole, which is the major component of eucalyptus oil. This may reduce the numbers of microorganisms located in the deeper layers of the skin which potentially could decrease the risk of surgical site infection.