gebhart/patrepeval huggingface dataset:
Abstract 1808: HM-032, a novel PI3K/mTOR dual inhibitor, is active on K-Ras/Raf mutation tumors through up-regulation of Bim (2012)

Abstract PIK3CA gene amplification and mutations have been identified in many types of tumors, suggesting the deregulation of PI3K/AKT/mTOR axis plays pivotal roles in tumorigenesis and development. K-Ras/Raf mutation is recognized as one of the key drug resistant factors for tumors against TKIs. HM-032 was reported here as a potent, selective and reversible ATP-competitive PI3K/mTOR dual inhibitor with special apoptotic activity in tumor cells harboring K-Ras mutations. HM-032 showed potent kinase inhibition with IC50 of 0.0008, 0.002, 0.001, 0.002 and 0.001 µM on PI3Kα, β, δ, ≤ and mTOR, respectively. In human prostate PC3 cells, it inhibited p-AKTS473, p-S6 and p-4EPB1 with IC50s of 0.002, 0.015 and 0.056 μM. Of the 89 tumor cell lines from lung, colon, breast, ovarian, and other tumor types, it was found that tumor cells with HER2 gene amplification, or PIK3CA mutation were relatively more sensitive to HM-032. Attractively, HM-032 showed apoptotic induction activity in the tumor cells harboring Ras/Raf mutations through inhibiting p-Erk and increasing gene expression of pro-apoptotic protein Bim. This result suggested that HM-032 might bring benefits to patients carrying K-Ras/Raf mutations in the clinic. Consistent with in vitro studies, HM-032 exhibited significant tumor growth inhibition in a dose dependent manner on multiple human xenograft models, including breast tumor MDA-MB-361(PIK3CAE545K, Her2 amplification), lung tumors H460 (PIK3CAE545K, K-RasQ61H) and A549 (LKB1 del, K-RasG12S), and glioblastoma U87MG (PTEN del) after 3 weeks oral dosing. Correspondingly, decrease of p-AKT and p-S6 was observed in the tumor xenograft tissues upon treatment with HM-032. In addition, HM-032 exhibited unique in vivo PK properties characterized by low clearance and long t1/2, which supported the intermittent dosing schedule in xenograft models. Based on the pre-clinical study results, HM-032 is anticipated to be a promising agent against solid tumors including carrying Ras/Raf mutations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1808. doi:1538-7445.AM2012-1808
180° walls structures in exchange-coupled multilayers with in-plane uniaxial anisotropy (1997)

First, the number of irreducible wall configurations is derived, both for an odd and an even number of magnetic layers. Second, the comparison of simulated wall structures in stacks made of three and four magnetic layers serves as an illustration of the interplay between flux–closure mechanisms and interlayer exchange interactions. Flux closure is shown either to compete or accommodate with ferromagnetic-type interlayer exchange interactions owing to its short- or long-range character. Last, an equivalent single layer behavior is shown to develop with an increasing number of magnetic layers, magnetic layer thickness, and interlayer (ferromagnetic-type) exchange parameter.
Daisy quorum drives for the genetic restoration of wild populations (2017)

Abstract An ideal gene drive system to alter wild populations would 1) exclusively affect organisms within the political boundaries of consenting communities, and 2) be capable of restoring any engineered population to its original genetic state. Here we describe ‘daisy quorum’ drive systems that meet these criteria by combining daisy drive with underdominance. A daisy quorum drive system is predicted to spread through a population until all of its daisy elements have been lost, at which point its fitness becomes frequency-dependent: mostly altered populations become fixed for the desired change, while engineered genes at low frequency are swiftly eliminated by natural selection. The result is an engineered population surrounded by wild-type organisms with limited mixing at the boundary. Releasing large numbers of wild-type organisms or a few bearing a population suppression element can reduce the engineered population below the quorum, triggering elimination of all engineered sequences. In principle, the technology can restore any drive-amenable population carrying engineered genes to wild-type genetics. Daisy quorum systems may enable efficient, community-supported, and genetically reversible ecological engineering. Summary Local communities should be able to control their own environments without forcing those choices on others. Ideally, each community could reversibly alter local wild organisms in ways that cannot spread beyond their own boundaries, and any engineered population could be restored to its original genetic state. We've invented a 'daisy quorum' drive system that appears to meet these criteria. “Daisy” refers to a daisy drive, which typically uses a daisy-chain of linked genes to spread a change through a local population while losing links every generation until it stops spreading. “Quorum” reflects the system's ability to “vote” on whether a local population should be altered or not: once all daisy elements are lost, it favors replication by the altered version or the original depending on which is more abundant in the local area. Put together, they result in a change that first spreads through a local population, then either becomes locally prevalent is eliminating, inhibiting mixing at the boundary. All organisms in the target population are altered, but changes are unable to spread much beyond that area due to being greatly outnumbered by wild-type organisms and consequently less able to replicate. We haven't yet performed any experiments involving daisy quorum systems. Rather, we’re describing what we intend to do, including the safeguards we will use and our assessment of risks, in the hope that others will evaluate our plans and tell us if there's anything wrong that we missed. We hope that all researchers working on gene drive systems - and other technologies that could impact the shared environment - will similarly pre-register their plans. Sharing plans can reduce needless duplication, accelerate progress, and make the proposed work safer for everyone.
Induction of apoptosis by ethanol extract of <i>Citrus unshiu</i> Markovich peel in human bladder cancer T24 cells through ROS-mediated inactivation of the PI3K/Akt pathway (2017)

Citrus unshiu peel has been used to prevent and treat various diseases in traditional East-Asian medicine including in Korea. Extracts of C. unshiu peel are known to have various pharmacological effects including antioxidant, anti-inflammatory, and antibacterial properties. Although the possibility of their anti-cancer activity has recently been reported, the exact mechanisms in human cancer cells have not been sufficiently studied. In this study, the inhibitory effect of ethanol extract of C. unshiu peel (EECU) on the growth of human bladder cancer T24 cells was evaluated and the underlying mechanism was investigated. The present study demonstrated that the suppression of T24 cell viability by EECU is associated with apoptosis induction. EECU-induced apoptosis was found to correlate with an activation of caspase-8, -9, and -3 in concomitance with a decrease in the expression of the inhibitor of apoptosis family of proteins and an increase in the Bax:Bcl-2 ratio accompanied by the proteolytic degradation of poly(ADP-ribose) polymerase. EECU also increased the generation of reactive oxygen species (ROS), collapse of mitochondrial membrane potential, and cytochrome c release to the cytosol, along with a truncation of Bid. In addition, EECU inactivated phosphatidylinositol 3-kinase (PI3K) as well as Akt, a downstream molecular target of PI3K, and LY294002, a specific PI3K inhibitor significantly enhanced EECU-induced apoptosis and cell viability reduction. However, N-acetyl cysteine, a general ROS scavenger, completely reversed the EECU-induced dephosphorylation of PI3K and Akt, as well as cell apoptosis. Taken together, these findings suggest that EECU inhibits T24 cell proliferation by activating intrinsic and extrinsic apoptosis pathways through a ROS-mediated inactivation of the PI3K/Akt pathway.
Fluorine‐Enabled Cationic Gold Catalysis: Functionalized Hydration of Alkynes (2010)

Fluor macht's möglich: Eine kationische Fluor-Gold-Spezies, die durch Fluorierung eines niedervalenten Goldkomplexes hergestellt wurde, vermittelt die „funktionalisierende Hydratation“ von Alkinen. Eine Dreifachbindung wird hierbei genutzt, um in einem Eintopfprozess unter milden Bedingungen eine Carbonylgruppe und zwei neue Bindungen am α-Kohlenstoffatom einzuführen (siehe Schema). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Effects of Hizikia fusiforme Extracts on Adipocyte Differentiation and Adipogenesis in 3T3-L1 Preadipocytes (2012)

본 연구에서는 톳 분획물의 항비만 효과 및 그에 따른 생화학적 기전의 해석을 위하여 톳 분획물이 비만유도인자에 의하여 인위적으로 유발된 adipogenesis 과정에 있어서 어떠한 영향을 미치는 지를 조사하였고, 이때 <TEX>$PPAR{\gamma}$</TEX>, C/<TEX>$EBP{\alpha}$</TEX> 및 C/<TEX>$EBP{\beta}$</TEX> 등과 같은 adipogenic transcription factor들의 발현에 어떠한 변화가 유발되었는지를 조사하였다. 각각의 톳 분획물들이 성숙한 지방세포에서 나타나는 lipid droplet 및 TG 생성에 어떠한 영향을 미치는 지를 확인한 결과, 모든 분획물에서 lipid droplet 및 TG 생성억제가 나타났지만 특히 WFHF 처리군에서 이러한 현상이 가장 강하게 나타났다. 또한 lipid droplet 및 TG 생성에 중요한 역할을 하는 것으로 알려진 adipogenic transcription factor들의발현에각각의분획물들이 어떠한영향을미치는지를확인한결과,WFHF 처리군에서 <TEX>$PPAR{\gamma}$</TEX>, C/<TEX>$EBP{\alpha}$</TEX> 및 C/<TEX>$EBP{\beta}$</TEX>의 발현이 현저하게 감소하였음을 확인하였다. 이상의 결과를 종합해 보면 다섯 종류의 톳 분획물 모두 비만억제 효과가 있는 것으로 나타났고 특히 WFHF의 비만억제 효과가 강하게 나타났음을 알 수 있었다. 본 연구 결과는 톳의 비만억제 가능성을 제시하는 것으로서 항비만 기전에 대한 생화학적 해석 및 이를 활용한 향후 지속적인 연구를 위한 자료로서 그 가치가 매우 높을 것으로 생각된다. The present study was conducted to evaluate the effects of various extracts of Hizikia fusiforme on the anti-obesity effects in 3T3-L1 preadipocytes. We used H. fusiforme extracts from ethanol (EEHF), dichloromethane (CFHF), ethyl acetate (EAFHF), butanol (BFHF), and water (WFHF). Treatment with these extracts significantly suppressed terminal differentiation of 3T3-L1 preadipocytes in a dose-dependent manner as confirmed by a decrease in lipid droplet content through Oil Red O staining; this effect was higher in WFHF than in other extracts. The concentrations of cellular triglyceride were also reduced in 3T3-L1 cells by exposure with these extracts, especially when compared with the controls. Treatment with 200 <TEX>${\mu}g/ml$</TEX> of WFHF and CFHF caused approximately 42.6% and 23.7% reduction, respectively. In addition, the extracts of H. fusiforme significantly reduced the expression levels of key pro-adipogenic transcription factors, including peroxisome proliferator-activated receptor <TEX>${\gamma}$</TEX> (<TEX>$PPAR{\gamma}$</TEX>) and CCAAT/enhancer binding proteins <TEX>${\alpha}$</TEX> (C/<TEX>$EBP{\alpha}$</TEX>) and C/<TEX>$EBP{\beta}$</TEX> as compared with controls. Accordingly, our data indicated that WFHF has a preeminent effect on inhibition of adipocyte differentiation among various extracts, and H. fusiforme extracts may be an ideal candidate for obesity relief.
Multiple access options for cellular based personal communications (2002)

The possible evolution of time division multiple access (TDMA) by, e.g., introducing frequency hopping and/or adaptive channel allocation, is described. The possibilities of direct sequence (DS) code division multiple access (CDMA) are considered. The different multiple access methods are examined. In particular, the concept of hierarchical cell structures is emphasized. The capacity depends on both the cell capacity and the ability to support hierarchical cell structures.
Comparison of discrete fracture and effective media representation of fractures on azimuthal AVO (2005)

In fractured reservoir development, azimuthal AVO (AVOaz) properties of reflected PP waves from reservoir tops are often used to infer fracture properties. The fracture parameter inversion is based on either effective media model (EMM) or discrete fracture model (DFM). We address the differences in fracture properties that may be inferred by AVOaz based on the two models. We focus on fractures whose length and spacing are comparable to the seismic wavelength. First, we compute the elastic parameters describing the fractured reservoir. Then we synthesize seismic data using a finite‐difference program for both sets of elastic parameters. By performing AVOaz analysis, we find that EMM and DFM predict different optimal offsets for maximal magnitudes of AVOaz. The DFM results show larger AVOaz magnitude with farther offsets. Phase changes at offsets larger than 35 degrees may indicate compliant fractures in a reservoir. Fracture strike determined using AVOaz based on EMM may be normal to the true strike. DFM may be better suited for modeling wavelength‐scale fractures.
Measuring and Modifying Interface Properties of PVA Fibers in ECC Matrix (2001)

A single fiber pullout test was used in this study to measure the bond properties of polyvinyl alcohol fibers that are available at various diameters in a mortar matrix. Despite short fiber embedment lengths, the small diameter fibers ruptured during the pullout tests. However, it is shown that even if full fiber pullout is not achieved, it is still possible to determine a chemical debonding energy, Gd, and an initial interfacial frictional bond strength, τ0. Despite high Gd values, the fibers did not rupture during the fiber chemical debonding process, but during fiber pull-out, a strong slip-hardening effect, characterized by the high values of the slip-hardening coefficient, β, induced severe abrasion damage visible under scanning electron microscope on the fiber surface. As a consequence, when the fiber apparent tensile strength was exceeded, fibers ruptured by delamination. Finally, an attempt was made to lower the values of the bond properties to minimize fiber rupture during pullout. This goal was partially achieved by applying an oil coating on the hydrophilic polyvinyl alcohol fiber surface to reduce any strong fiber/mortar interaction.
Functional involvement of Pax‐1 in somite development: Somite dysmorphogenesis in chick embryos treated with Pax‐1 paired‐box antisense oligodeoxynucleotide (1995)

The metameric pattern of the vertebrate axial skeleton, defined by structures such as the vertebral bodies and ribs, is a result of segmentation events that occur during embryogenesis. The key event in axial segmentation is somite formation. This study examines the role of Pax-1, a member of the paired-box containing Pax gene family, in chick somite development. To investigate whether misexpression of Pax-1 during somite development is functionally related to abnormal axial patterning, antisense methodologies were used to perturb Pax-1 expression. An antisense, phosphorothioate-modified oligodeoxynucleotide (ODN) was designed based on the mouse Pax-1 paired-box sequence, and was either injected into or directly applied topically to early, somitic stage chick embryos. Abnormalities in somite structure and pattern were subsequently observed and scored, including loss of somites (18% of injected embryos, 35% of embryos treated by topical application), fusion of somites (25% of injected, 6% with topical application), and shortened body axis (0% of injected, 11% with topical application). Control embryos receiving sense ODN or non-sense ODN (a scrambled sequence with base composition identical to the antisense ODN) showed substantially fewer somite anomalies, indicating that the effects were sequence-specific. These developmental abnormalities were analyzed using standard histological methods. Whole mount in situ hybridization was carried out to analyze the three-dimensional pattern of Pax-1 expression in whole embryos. In control, untreated embryos, the expression was localized to the entire epithelial somite, and as the somite matured, the expression was limited to its ventromedial region. With Pax-1 antisense ODN treatment, embryos with fused somites retained expression over the entire fused somite, and embryos that had complete loss of somites had greatly reduced expression of Pax-1 transcript. The results presented here provide strong evidence that Pax-1 is functionally important during somitogenesis and morphogenesis of the vertebral column. The spatial pattern of gene expression appears to delineate different populations of cells in the developing embryo (i.e., somite from somite, sclerotome from dermomyotome), and is consistent with the hypothesis that Pax-1 is involved in forming or maintaining boundaries at specific times and locations during development.
Scattering by thin shells in fluids: Fast solver and experimental validation (2021)

A numerical model facilitating fast analysis of acoustic scattering by thin shells immersed in fluids is presented. The shell is simulated by an effective boundary condition, in which the inertial properties of the shell are taken into account while the elastic ones are neglected. The problem reduces to a hypersingular surface integral equation, which is solved using the boundary element method accelerated by the multilevel nonuniform grid approach. The validity of the numerical method and the adopted physical approximations were tested by comparison with a water tank experiment on acoustic scattering from cylindrical metallic shells filled with water.
Longitudinal comparison of medial and lateral meniscal T2* values within elite basketball players and swimmers (2023)

Basketball players represent a population with an inherently high risk of sustaining meniscal injuries. Evaluation of quantitative MRI (qMRI) metrics of the meniscus within these athletes may improve clinical insight. To date, no studies have longitudinally evaluated meniscal T2* values in high performance athletes. Therefore, the purpose of this study was to utilize ultra-short TE (UTE) MRI to longitudinally evaluate medial and lateral meniscal T2* values within elite weight-bearing (basketball) and non-weight bearing (swimmers) athletes. Significant differences of T2* values were found between the medial and lateral menisci. No significant difference of meniscal T2* values were found between basketball players and swimmers.
Paper 87: What is the Stabilizing Mechanism of the Latarjet Procedure? (2012)

The Latarjet procedure is one of common ones for patients with anterior instability of the shoulder and its excellent clinical results have been reported. It has also been used as a bone-grafting procedure in patients with a large glenoid defect. “Sling effect of the subscapularis muscle” or “bone block effect of the coracoid process” has been believed as a main stabilizing mechanism of this procedure. However, the true mechanism is still unknown and there have been no biomechanical studies in the literature.
Multi-objective parameter optimization of a series hybrid electric vehicle using evolutionary algorithms (2009)

Hybrid powertrain control strategy and component sizing significantly affect vehicle performance, fuel economy and emissions in hybrid vehicles. Recent research activities in this field show that component sizing and the control strategy are quite intertwined in such a way that concurrent optimization of component sizing and control strategy is warranted. In this paper, we study the total optimization problem in a series HEV and apply evolutionary algorithms to the optimization problem. We will show through experiments that the proposed optimization method has the capability of providing a set of trade-off optimal solutions among the fuel economy and various emissions.
Analysis of Transglucosylation Products of <i>Aspergillus niger</i> α-Glucosidase that Catalyzes the Formation of α-1,2- and α-1,3-Linked Oligosaccharides (2020)

According to whole-genome sequencing, Aspergillus niger produces multiple enzymes of glycoside hydrolases (GH) 31. Here we focus on a GH31 α-glucosidase, AgdB, from A. niger. AgdB has also previously been reported as being expressed in the yeast species, Pichia pastoris; while the recombinant enzyme (rAgdB) has been shown to catalyze tranglycosylation via a complex mechanism. We constructed an expression system for A. niger AgdB using Aspergillus nidulans. To better elucidate the complicated mechanism employed by AgdB for transglucosylation, we also established a method to quantify glucosidic linkages in the transglucosylation products using 2D NMR spectroscopy. Results from the enzyme activity analysis indicated that the optimum temperature was 65 °C and optimum pH range was 6.0–7.0. Further, the NMR results showed that when maltose or maltopentaose served as the substrate, α-1,2-, α-1,3-, and small amount of α-1,1-β-linked oligosaccharides are present throughout the transglucosylation products of AgdB. These results suggest that AgdB is an α-glucosidase that serves as a transglucosylase capable of effectively producing oligosaccharides with α-1,2-, α-1,3-glucosidic linkages.
In-situ chemical imager (2000)

A variety of in-situ planetary exploration tasks such as particulate analysis or life detection require a tool with a capability for combined imaging and chemical analysis with sub-micron spatial resolution.
The search for responsive clinical endpoints in primary progressive multiple sclerosis (2009)

T25FW has the highest event rate as a single scale, independent of baseline disability level. A term of 2 years turned out to be more meaningful to observe than 1 year. "Worsening on either T25FW or EDSS" is the most appropriate composite endpoint in this patient group.
An adaptive block management scheme using on-line detection of block reference patterns (2002)

Recent research has shown that near-optimal performance can be achieved by adaptive block replacement policies that use user-level hints regarding the block reference pattern. However, obtaining user-level hints requires considerable effort from users, making it difficult to apply adaptive replacement policies to diverse kinds of applications. We propose a new adaptive block management scheme that we call DEAR (DEtection-based Adaptive Replacement) which makes online detections of block reference patterns of applications using decision trees without user intervention. Based on the detected reference pattern, DEAR applies an appropriate replacement policy to each application. This scheme is suitable for buffer management in systems such as multimedia servers where data reference patterns of applications may be diverse. Results from trace-driven simulations show that the DEAR scheme can detect the reference patterns of applications and reduce the miss ratio by up to 15% compared to the LRU (least recently used) policy.
State-of-the-art flexible 2D nanoelectronics based on graphene and MoS<inf>2</inf> (2013)

The authors report a flexible transistors based on 2D atomic sheets such as graphene and MoS <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> that features record electrical-mechanical properties and offer the highest prospects for realizing Si-CMOS like performance on arbitrary plastic substrates. Graphene is ideal for analog RF devices while MoS <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> is ideal for digital low-power FETs.