gebhart/patrepeval huggingface dataset:
Insulin resistance and neurodegeneration: roles of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis. (2009)

Recent studies have linked obesity, type 2 diabetes mellitus (T2DM) or non-alcoholic steatohepatitis (NASH) to insulin resistance in the brain, cognitive impairment and neurodegeneration. Insulin resistance compromises cell survival, metabolism and neuronal plasticity, and increases oxidative stress, cytokine activation and apoptosis. T2DM/NASH has been demonstrated to be associated with increased ceramide generation, suggesting a mechanistic link between peripheral insulin resistance and neurodegeneration because ceramides mediate insulin resistance and can cross the blood-brain barrier (BBB). Peripheral insulin resistance diseases may potentially cause brain insulin resistance via a liver-brain axis of neurodegeneration as a result of the trafficking of ceramides across the BBB. Therapy that includes insulin-sensitizing agents may help prevent brain insulin resistance-mediated cognitive impairment.
Vasculotide Reduces Pulmonary Permeability in Streptococcus pneumonia Infected and Mechanically Ventilated Mice (2019)

Introduction Community acquired pneumonia (CAP), commonly caused by Streptococcus pneumonia (S. pn.), is a significant cause of mortality worldwide. Despite adequate antibiotic treatment, pneumococcal pneumonia is able to provoke pulmonary endothelial hyperpermeability leading to potentially lethal lung edema and acute-respiratory distress syndrome (ARDS). This condition often requires mechanical ventilation (MV) causing additional damage to the lung (Ventilator-induced lung injury; VILI). Angiopoietin-1 mediated Tie2-receptor activation stabilizes the endothelial barrier and reduces vascular hyperpermeability. The PEGylated (polyethylene glycol) Tie2-agonist Vasculotide (VT) mimics Angiopietin-1 effects. Moreover, we have recently shown that VT reduces pulmonary hyperpermeability in murine pneumococcal pneumonia. The aim of our study was to investigate whether VT could ameliorate lung injury in S. pn. infected and mechanically ventilated mice. Methods Mice were infected intranasally with S. pn. or received an equal amount of phosphate buffered saline. After 22 h they were treated either with or without Ampicillin ± VT. At 24 h post infection the mice were subjected to six hours of MV with a second dose of VT at 28.5 h post infection. Afterwards pulmonary hyperpermeability, immune cell response and bacterial load were quantified. Additionally, histological analysis was performed to evaluate pathomorphological lung changes due to pneumonia and VILI. Results Ampicillin significantly reduced systemic cytokine levels and bacteremia without influencing endothelial permeability in ventilated and S. pn. infected mice. VT did not alter local or systemic immune responses or bacterial burden. Interestingly, combination treatment with Ampicillin and VT significantly reduced pulmonary hyperpermeability, histological lung damage and edema formation in S. pn. infected and mechanically ventilated mice compared to mere antibiotic therapy. Conclusion Our results suggest that adjunctive therapy with VT may reduce ventilator induced lung injury in severe pneumococcal pneumonia.
Abstract 1701: Improvement of tumor mutation burden measurement by removal of deaminated bases in FFPE DNA (2019)

Abstract Tumor mutation burden (TMB) is a positive predictive factor for response to immune-checkpoint inhibitors in certain types of cancer. The Oncomine™ Tumor Mutation Load Assay, a 1.7Mb targeted next generation sequencing (NGS) panel, measures TMB and detects mutations in 409 cancer genes. The TMB values obtained using targeted sequencing are positively correlated with TMB measured by whole exome sequencing in NSCLC, colorectal, endometrial and gastric cancers. TMB from these tumor samples are correlated with other phenotypes associated with genomic instability, specifically microsatellite instability (MSI) and mutations involved in mismatch repair and cancer related genes. Analysis of the Oncomine™ TML Assay results with Torrent Suite and Ion Reporter software uniquely measures the degree of deamination of cytosines to uracils in fixed tissues. FFPE preservation methods can lead to significant cytosine deamination of the isolated DNA, resulting in decreased sequencing quality. In these samples, uracils are propagated as thymines and result in false C&amp;gt;T substitutions. To minimize the influence that excess deamination has on TMB results, we have incorporated a UDG enzyme treatment to eliminate damaged targets and improve usable TMB values of DNA from damaged FFPE tumor tissue. The Oncomine™ TML assay for TMB on Ion GeneStudio™ S5 in conjunction with MSI detection is informative and potentially predictive for the use of checkpoint inhibitors in multiple cancer types. Citation Format: Warren Tom, Ruchi Chaudhary, Vinay Mittal, Dinesh Cyanam, Iris Casuga, Elaine Wong-Ho, Rob Bennett, Fiona Hyland, Seth Sadis, Janice Au-Young. Improvement of tumor mutation burden measurement by removal of deaminated bases in FFPE DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1701.
Second harmonic imaging and scoring of collagen in fibrotic tissues (2007)

We compare second harmonic generation (SHG) to histological and immunohistochemical techniques for the visualization and scoring of collagen in biological tissues. We show that SHG microscopy is highly specific for fibrillar collagens and that combined SHG and two-photon excited fluorescence (2PEF) imaging can provide simultaneous three-dimensional visualization of collagen synthesis and assembly sites in transgenic animal models expressing GFP constructs. Finally, we propose several scores for characterizing collagen accumulation based on SHG images and appropriate for different types of collagen distributions. We illustrate the sensitivity of these scores in a murine model of renal fibrosis using a morphological segmentation of the tissue based on endogenous 2PEF signals.
Concordância entre os estadiamentos clínico e patológico em pacientes com câncer de pulmão não-pequenas células, estádios I e II, submetidos a tratamento cirúrgico (2007)

The concordance between clinical and pathological staging is low, and patients are frequently understaged (in the present study, only one case was overstaged). Strategies are necessary to improve clinical staging and, consequently, the treatment and prognosis of patients with non-small cell lung cancer.
A Survey of Modern HighPerformance Switching Techniques (2009)

The rapid evolution in the field of telecommunications has led to the emergence of new switching technologies to support a variety of communication services with a wide range of transmission rates in a common, unified integrated services network. At the same time, the progress in the field of VSLI technology has brought up new design principles of high-performance, high-capacity switching fabrics to be used in the integrated networks of the future. Most of the recent proposals for such high-performance switching fabrics have been based on a principle known as fast packet switching. This principle employs a high degree of parallelism, distributed control, and routing performed at the hardware level. In this paper, we present a survey of high-performance switch fabric architectures which incorporate fast packet switching as their underlying switching technique to handle various traffic types. Our intention is to give a descriptive overview of the major activities in this rapidly evolving field of telecommunications.
Alpha-ketoglutarate ameliorates abdominal aortic aneurysm via inhibiting PXDN/HOCL/ERK signaling pathways (2022)

Abdominal aortic aneurysm (AAA) represents the serious vascular degenerative disorder, which causes high incidence and mortality. Alpha-ketoglutarate (AKG), a crucial metabolite in the tricarboxylic acid (TCA) cycle, has been reported to exert significant actions on the oxidative stress and inflammation. However, its role in AAA still remains elusive. Herein, we examined the effects of AKG on the formation of AAA. The study established an elastase-induced mouse abdominal aortic aneurysms model as well as a TNF-α-mediated vascular smooth muscle cells (VSMCs) model, respectively. We displayed that AKG pre-treatment remarkably prevented aneurysmal dilation assessed by diameter and volume and reduced aortic rupture. In addition, it was also observed that AKG treatment suppressed the development of AAA by attenuating the macrophage infiltration, elastin degradation and collagen fibers remodeling. In vitro, AKG potently decreased TNF-α-induced inflammatory cytokines overproduction, more apoptotic cells and excessive superoxide. Mechanistically, we discovered that upregulation of vpo1 in AAA was significantly suppressed by AKG treatment. By exploring the RNA-seq data, we found that AKG ameliorates AAA mostly though inhibiting oxidative stress and the inflammatory response. PXDN overexpression neutralized the inhibitory effects of AKG on ROS generation and inflammatory reaction in MOVAS. Furthermore, AKG treatment suppressed the expression of p-ERK1/2, 3-Cl Tyr in vivo and in vitro. ERK activator disrupted the protective of AKG on TNF-α-induced VSMCs phenotypic switch. Conclusively, AKG can serve as a beneficial therapy for AAA through regulating PXDN/HOCL/ERK signaling pathways.
Murine embryonal carcinoma cells: Universal targets for mammalian nk cells? (1981)

Natural killer (NK) cells from mice lyse murine teratocarcinoma stem cells in accordance with their appropriate cellular, genetic and interferon inducible features. In addition, rat and human putative NK cells were found to exhibit cytotoxicity of these embryonal carcinoma stem cells. By contrast, endodermal cells derived from such stem cells, either as cell lines or by recent induction with retinoic acid, were relatively resistant to effectors from all three mammalian species tested. Attempts to elicit a murine T-cell response to embryonal carcinoma by secondary in vitro stimulation failed. As previously shown, T killers directed to H-2 determinants were unable to lyse the MHC lacking embryonal carcinoma cells. The use of lectin "glues", a procedure supposedly capable of revealing the total cytotoxic. T-cell potential regardless of specificity, also failed to elicit lysis of these target cells. We have therefore failed to find evidence for T-cell recognition or lysis of embryonal carcinoma while NK cells from different species seemingly regard these latter cells as "universal" targets.
MEMS inductor fabrication and emerging applications in power electronics and neurotechnologies (2021)

MEMS inductors are used in a wide range of applications in micro- and nanotechnology, including RF MEMS, sensors, power electronics, and Bio-MEMS. Fabrication technologies set the boundary conditions for inductor design and their electrical and mechanical performance. This review provides a comprehensive overview of state-of-the-art MEMS technologies for inductor fabrication, presents recent advances in 3D additive fabrication technologies, and discusses the challenges and opportunities of MEMS inductors for two emerging applications, namely, integrated power electronics and neurotechnologies. Among the four top-down MEMS fabrication approaches, 3D surface micromachining and through-substrate-via (TSV) fabrication technology have been intensively studied to fabricate 3D inductors such as solenoid and toroid in-substrate TSV inductors. While 3D inductors are preferred for their high-quality factor, high power density, and low parasitic capacitance, in-substrate TSV inductors offer an additional unique advantage for 3D system integration and efficient thermal dissipation. These features make in-substrate TSV inductors promising to achieve the ultimate goal of monolithically integrated power converters. From another perspective, 3D bottom-up additive techniques such as ice lithography have great potential for fabricating inductors with geometries and specifications that are very challenging to achieve with established MEMS technologies. Finally, we discuss inspiring and emerging research opportunities for MEMS inductors.
Trading-off on-die observability for cache minimum supply voltage reduction in system-on-chip (SoC) processors (2014)

Circuit techniques for reducing the minimum supply voltage (V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">MIN</inf> ) of last-level and intermediate static random-access memory (SRAM) caches enhance processor energy efficiency. For the first time at a 16nm technology node, projections of a high-density 6-transistor SRAM bit cell indicate that the VMIN of a 4Mb or larger cache exceeds the maximum supply voltage (V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">MAX</inf> ) for reliability. Thus, circuit techniques for cache VMIN reduction are transitioning from an energy-efficient solution to a requirement for cache functionality. Traditionally, error-correcting codes (ECC) such as single-error correction, double-error detection (SECDED) aim to protect the cache operation from radiation-induced soft errors. Moreover, during the qualification of a system-on-chip (SoC) processor, test engineers monitor the rate of correctable cache errors from SECDED for observing the on-die interactions between integrated components (e.g., CPU, GPU, DSP, etc.). This presentation highlights the opportunity to exploit ECC for reducing the cache V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">MIN</inf> while simultaneously providing coverage for radiation-induced soft errors. Silicon test-chip measurements from a 7Mb data cache in a 20nm technology demonstrate a V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">MIN</inf> reduction of 19% from SECDED. In addition, silicon measurements provide a salient insight in that only 0.12% of the cache words contain an error when operating at the cache V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">MIN</inf> with SECDED. Therefore, SECDED improves V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">MIN</inf> by 19% while maintaining 99.88% coverage for radiation-induced soft errors. In applying SECDED for a lower cache VMIN, the rate of correctable errors exponentially increases, thus eliminating a useful metric for on-die observability. The presentation concludes by offering alternative solutions for on-die observability.
Assembly Algorithms for Deep Sequencing Data: Basics and Pitfalls (2013)

Our ability to sequence the genomic data at our disposal is limited. At each experiment we can sequence reliably only a short fraction of even the smallest genome. We are then faced with the challenge of assembly—combining the short patches we have into a correct reconstruction of as large as possible a fragment of the original sample. The problem has been thoroughly researched and many commercial and academic tools exist to carry it out. However due to basic features of the problem the results of even our best efforts will be sometimes disappointing for the researcher. In this chapter we will try to explain why the assembly problem is so hard, what future directions may alleviate it in the near future, and what can be realistically expected from a current assembly experiment.
Abstract 669: Apabetalone (rvx-208) Decreases Risk of Major Adverse Cardiovascular Events in Diabetes Mellitus Patients With Cvd by Attenuating Monocyte Adhesion to Endothelial Cells (2018)

Apabetalone (RVX-208, 200 mg/d) given orally to patients with diabetes mellitus (DM) and CVD leads to a 57% relative risk reduction in major adverse cardiovascular events (MACE). Potential actions of RVX-208, an inhibitor (BETi) of bromodomain extra-terminal (BET) proteins that are epigenetic readers of acetylated lysine residues within histones, in lowering MACE is explored by testing its effect on genes mediating monocyte adhesion to endothelial cells in response to high glucose (HG) and the dietary metabolite trimethyl-amine oxide (TMAO). Cultured THP-1 monocytes, HUVEC endothelial cells and primary human hepatocytes (PHH) were exposed to varying concentrations of glucose and TMAO. Results showed that HG (25.6 mM) induced Very Late Antigen-4 (VLA-4) mRNA, a gene mediating THP-1 adhesion by 1.3-fold and RVX-208 suppressed it &gt;50%. Similarly, BETi blocked TMAO induction of VLA-4 mRNA by &gt;50% in THP-1. In HUVECs RVX-208 abrogated HG induction of E-selectin and MYD88 mRNA by 2- and 1.3-fold, respectively and lowered TMAO induction of these mRNAs by &gt;50%. Microbiome processing of dietary phospholipids followed by hepatic flavin mono-oxygenase-3 (FMO3) metabolism yields TMAO. In PHH exposed for 24 hrs to RVX-208, FMO3 mRNA was lower by 40% but it also suppressed a transcriptional regulator of FMO3, farnesoid X receptor (FXR). BETi suppressed both FXR mRNA and protein within 6 hrs by &gt;80% suggesting a direct effect of BETi on the gene encoding FXR. Furthermore, ChiP data showed that BRD4, a BET protein, dissociated immediately from FXR gene upon exposure to RVX-208. Since BRD4 guides a complex containing RNA pol II along actively transcribed genes containing histones that are highly acetylated, the dissociation of BRD4 from FXR DNA would halt transcription of this gene. In summary, Apabetalone inhibits HG and TMAO enhanced adhesion of THP-1 to HUVECs a process that mimics a step in the pathogenesis of CVD. RVX-208 suppresses genes underlying cellular adhesion; VLA-4 in THP-1 and both E-selectin plus MYD88 in HUVECs. BETi blocks not only activity of TMAO but also its production by inhibiting FXR expression, a regulator of FMO3 gene transcription. The rapid actions of BETi in dissociating BRD4 from FXR DNA suggests a direct effect of RVX-208 on transcription of this gene.
Coexistence of Low Damping and Strong Magnetoelastic Coupling in Epitaxial Spinel Ferrite Thin Films (2017)

Low-loss magnetization dynamics and strong magnetoelastic coupling are generally mutually exclusive properties due to opposing dependencies on spin-orbit interactions. So far, the lack of low-damping, magnetostrictive ferrite films has hindered the development of power-efficient magnetoelectric and acoustic spintronic devices. Here, magnetically soft epitaxial spinel NiZnAl-ferrite thin films with an unusually low Gilbert damping parameter (<3 × 10<sup>-3</sup> ), as well as strong magnetoelastic coupling evidenced by a giant strain-induced anisotropy field (≈1 T) and a sizable magnetostriction coefficient (≈10 ppm), are reported. This exceptional combination of low intrinsic damping and substantial magnetostriction arises from the cation chemistry of NiZnAl-ferrite. At the same time, the coherently strained film structure suppresses extrinsic damping, enables soft magnetic behavior, and generates large easy-plane magnetoelastic anisotropy. These findings provide a foundation for a new class of low-loss, magnetoelastic thin film materials that are promising for spin-mechanical devices.
Leadership Education: Advancing a Community of Practice (2019)

Abstract This chapter offers reflection and recommendations for advancing leadership education as a community of practice through the lenses of identity, agency, and responsibility.
Spider dragline silk (2007)

Spider dragline silk possesses several desirable features of a biomaterial; it has extraordinary mechanical properties, is biocompatible and biodegradable. It consists of large proteins, major ampullate spidroins (MaSp:s), that contain alternating polyalanine- and glycine-rich blocks between non-repetitive C- and N-terminal domains. No full length MaSp gene has been cloned, hence the knowledge of their constitution is limited. The spider stores the silk in a liquid form, which is converted into a fibre by a poorly understood mechanism. Even truncated spidroins are difficult to produce recombinantly in soluble form. Most previous attempts to produce artificial spider silk fibres have included solubilization steps in non-physiological solvents and the use of spinning devises for fibre formation. This thesis presents a novel method for production of macroscopic fibres under physiological conditions, without using denaturing agents. A miniature spidroin is identified that can be produced recombinantly in E. coli when fused to a soluble fusion tag. Upon enzymatic release of the fusion tag, the miniature spidroins spontaneously form macroscopic fibres in physiological solution. These fibres resemble native silk and their strength equals that of fibres spun from regenerated silk. Initial studies suggest that the fibres are biocompatible. This represents a major breakthrough for future biomaterial development. Molecular studies of cDNA and genetic sequences encoding the dragline silk revealed an unexpectedly high level of heterogeneity and the presence of at least two MaSp1 genes. Furthermore, the E. australis MaSp2 was characterised for the first time, as well as a new MaSp-like spidroin. Sequence analysis of previously published spidroin N-terminal domains compared with that of E. australis MaSp1, enabled identification of signal peptides and a ∼130 residue non-repetitive domain common to dragline, flagelliform and cylindriform spidroins. Moreover, this highly conserved N-terminal domain was concluded to consist of five positionally conserved α-helices. Structural studies using circular dichroism spectroscopy on recombinantly produced MaSp1 N- and C-terminal domains showed that these are folded, stable and soluble and that salts or pH has no major effect on their secondary structures.
Construction of super-resolution microscope based on cw laser light source (2006)

We constructed a super-resolution microscope system based on a cw laser light source. Electro-optical modulators convert the cw laser light into a light pulse with a width of 15ns and provide a repetition rate of 100kHz. The performance of the microscope was evaluated using 100nmϕ fluorescence microbeads. The fluorescence signal from the beads can be detected with very low statistical fluctuation. The super-resolution image was obtained with better signal to noise ratio compared with that given by a pulse laser light source with a repetition rate of several tens of hertz. The fluorescent size of the beads was 150nm, which is 2.3 times smaller than the diffraction limit. Experimental results confirmed that the two-point resolution also overcomes the diffraction limit. The constructed system is expected to become a commercial microscope.
The kinetics and mechanism of the acid-catalysed detritylation of nucleotides in non-aqueous solution (2008)

The kinetics and mechanism of the deprotection (detritylation) of 5'-O-(4,4'-dimethoxytrityl)-2'-deoxythymidine nucleoside catalysed by dichloroacetic acid to give a 4,4'-dimethoxytrityl carbocation have been studied in toluene, dichloromethane and acetonitrile. There is little or no effect of solvent polarity on the equilibrium and rate constants. Entropies of activation are highly negative approximately -105 J K(-1) mol(-1) and similarly show little variation with solvent. Addition of small amounts of water to the reaction medium reduces the detritylation rate, presumably through its effect on the solution acidity. All observations are compatible with detritylation occurring through a concerted general acid-catalysed mechanism rather than a stepwise A1 process.