gebhart/patrepeval huggingface dataset:
No small surprise – small cell carcinoma of the ovary, hypercalcaemic type, is a malignant rhabdoid tumour (2014)

Whole-exome sequencing (WES) is revolutionizing medical diagnostics and taxonomy. In less than 5 years since its first use, WES has revealed unexpected molecular drivers of numerous cancers. Here, we describe our use of WES to uncover the true nature of an enigmatic pathological entity, small-cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), which has resisted definitive characterisation since it was first described in 1979. We conducted WES using three families with SCCOHT and identified deleterious mutations in the chromatin-remodelling gene SMARCA4 (encoding BRG1) in all cases. Follow-up of these findings, using both Sanger sequencing and WES of formalin-fixed paraffin-embedded tumours, showed that virtually all SCCOHTs we studied lacked functional SMARCA4/BRG1. Notably, this gene, and the related SMARCB1 gene, is mutated in most, if not all, atypical teratoid/rhabdoid tumours and malignant rhabdoid tumours. Other groups have similar findings. We review the relationship between these three neoplasms, discuss how they were distinguished from morphologically similar neoplasms, consider their similarities and show how WES has revealed that SCCOHTs are in fact rhabdoid tumours. We propose that SCCOHT be renamed 'malignant rhabdoid tumour of the ovary' (MRTO) to reflect these observations.
4-(Phenylsulfanyl)butan-2-One Suppresses Melanin Synthesis and Melanosome Maturation In Vitro and In Vivo (2015)

In this study, we screened compounds with skin whitening properties and favorable safety profiles from a series of marine related natural products, which were isolated from Formosan soft coral Cladiella australis. Our results indicated that 4-(phenylsulfanyl)butan-2-one could successfully inhibit pigment generation processes in mushroom tyrosinase platform assay, probably through the suppression of tyrosinase activity to be a non-competitive inhibitor of tyrosinase. In cell-based viability examinations, it demonstrated low cytotoxicity on melanoma cells and other normal human cells. It exhibited stronger inhibitions of melanin production and tyrosinase activity than arbutin or 1-phenyl-2-thiourea (PTU). Also, we discovered that 4-(phenylsulfanyl)butan-2-one reduces the protein expressions of melanin synthesis-related proteins, including the microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (Trp-1), dopachrome tautomerase (DCT, Trp-2), and glycoprotein 100 (GP100). In an in vivo zebrafish model, it presented a remarkable suppression in melanogenesis after 48 h. In summary, our in vitro and in vivo biological assays showed that 4-(phenylsulfanyl)butan-2-one possesses anti-melanogenic properties that are significant in medical cosmetology.
Salt Restriction Leads to Activation of Adult Renal Mesenchymal Stromal Cell–Like Cells via Prostaglandin E2 and E-Prostanoid Receptor 4 (2015)

Despite the importance of juxtaglomerular cell recruitment in the pathophysiology of cardiovascular diseases, the mechanisms that underlie renin production under conditions of chronic stimulation remain elusive. We have previously shown that CD44+ mesenchymal-like cells (CD44+ cells) exist in the adult kidney. Under chronic sodium deprivation, these cells are recruited to the juxtaglomerular area and differentiate to new renin-expressing cells. Given the proximity of macula densa to the juxtaglomerular area and the importance of macula densa released prostanoids in renin synthesis and release, we hypothesized that chronic sodium deprivation induces macula densa release of prostanoids, stimulating renal CD44+ cell activation and differentiation. CD44+ cells were isolated from adult kidneys and cocultured with the macula densa cell line, MMDD1, in normal or low-sodium medium. Low sodium stimulated prostaglandin E2 production by MMDD1 and induced migration of CD44+ cells. These effects were inhibited by addition of a cyclooxygenase 2 inhibitor (NS398) or an E-prostanoid receptor 4 antagonist (AH23848) to MMDD1 or CD44+ cells, respectively. Addition of prostaglandin E2 to CD44+ cells increased cell migration and induced renin expression. In vivo activation of renal CD44+ cells during juxtaglomerular recruitment was attenuated in wild-type mice subjected to salt restriction in the presence of cyclooxygenase 2 inhibitor rofecoxib. Similar results were observed in E-prostanoid receptor 4 knockout mice subjected to salt restriction. These results show that the prostaglandin E2/E-prostanoid receptor 4 pathway plays a key role in the activation of renal CD44+ mesenchymal stromal cell-like cells during conditions of juxtaglomerular recruitment; highlighting the importance of this pathway as a key regulatory mechanism of juxtaglomerular recruitment.
Noninvasive Drug Delivery Using Ultrasound: Targeting Melanoma Using siRNA Against Mutant (V600E) B-Raf (2009)

Melanoma is the most deadly form of skin cancer. Currently early surgical removal is the best treatment option for melanoma patients with little hope of successful treatment of late stage melanoma. Clearly new treatment options must be explored. Topical administration of drugs provides the advantage of being able to apply large quantities of drug in close proximity to the tumor without the issue of systemic side effects. However, the natural barrier formed by the skin must first be overcome for topical treatment to become a viable option. With this in mind we have sought to use low‐frequency ultrasound to transiently permeabilize the stratum corneum and successfully deliver liposomal siRNA to melanoma cells residing at the basement membrane. B‐Raf is one of the most frequently activated genes in melanoma, making it an ideal candidate for targeting via siRNA. The novel liposomes used in this study load siRNA, protect if from the outside environment and lead to knockdown of target message. Combining ultrasound with liposomal siRNA we show that siRNA can be delivered into melanoma cells. Additionally, we show that siRNA to mutant B‐Raf can effectively inhibit melanoma growth in reconstructs and in mice by 60% and 30% respectively. Therefore, ultrasound with liposomal siRNA is a potentially valuable treatment option for melanoma patients.
Revisiting the mechanism of macrolide-antibiotic resistance mediated by ribosomal protein L22 (2008)

Bacterial antibiotic resistance can occur by many mechanisms. An intriguing class of mutants is resistant to macrolide antibiotics even though these drugs still bind to their targets. For example, a 3-residue deletion (DeltaMKR) in ribosomal protein L22 distorts a loop that forms a constriction in the ribosome exit tunnel, apparently allowing nascent-chain egress and translation in the presence of bound macrolides. Here, however, we demonstrate that DeltaMKR and wild-type ribosomes show comparable macrolide sensitivity in vitro. In Escherichia coli, we find that this mutation reduces antibiotic occupancy of the target site on ribosomes in a manner largely dependent on the AcrAB-TolC efflux system. We propose a model for antibiotic resistance in which DeltaMKR ribosomes alter the translation of specific proteins, possibly via changes in programmed stalling, and modify the cell envelope in a manner that lowers steady-state macrolide levels.
Effects of seductive details evidenced by gaze duration (2014)

According to a meta-analysis of empirical studies, seductive details such as emotionally interesting text segments and attention-grabbing pictures have significant negative effects on the reader's recall, reading comprehension, and learning of important textual information. This study investigates the negative effects of seductive details on recall of main ideas and reading comprehension by using an eye-tracking technique. In the experiment, a total of 56 undergraduate students read a block of expository text with seductive details, and the spatial and temporal distribution of attention was measured by gaze duration and recorded by an eye tracker. Then recall and reading comprehension tests were employed. Two multiple regression analyses were conducted to investigate the relationship between attention allocation and reading performance. The results indicate that increased attention to seductive sentences, not to seductive pictures, was a major determinant of poor performance in terms of both recall and reading comprehension, suggesting that increased attentional allocation to seductive sentences may hinder information retrieval and produce a less coherent mental representation of given text.
Comparison of recombinant cell bioassays for the detection of Ah receptor agonists (2004)

In this study, we have compared the time and dose response curves for TCDD using the pGudLuc1.1-chemically activated luciferase expression (CALUX) cell bioassay and two new recombinant cell lines that contain a stably transfected mutated form of firefly luciferase reporter gene (pGudLuc6.1) or enhanced green fluorescent protein (EGFP) reporter gene (pGreen1.1). The time course of induction with pGudLuc1.1-containing H1L1.1c2 cells is transient, with maximal activity observed at 4 hours after treatment with 1 nM TCDD. In contrast, expression of luciferase from the pGudLuc6.1-containing H1L6.1c2 cells and the pGreen1.1-containing H1G1.1c3 cells progressively increases with time, with luciferase activity increasing at a significant faster rate than that of EGFP. Dose response analysis with each cell line at optimal analysis times reveal similar relative dose response curves and EC50s for H1L6.1c2 and H1G1.1c3 cells, while the EC50 for TCDD in the H1L1.1c2 cells was about 7-fold lower. In addition, these bioassay systems respond to halogenated and/or polycyclic aromatic hydrocarbons in a dose-specific manner. Given the above differences between cell lines and reporters, the choice of which cell line to use will certainly be dependent on the specific questions and issues being examined.
PRIME—toward process-integrated modeling environments (1999)

Research in process-centered environments (PCEs) has focused on project management support and has neglected method guidance for the engineers performing the (software) engineering process. It has been dominated by the search for suitable process-modeling languages and enactment mechanisms. The consequences of process orientation on the computer-based engineering environments, i.e., the interactive tools used during process performance, have been studied much less. In this article, we present the PRIME (Process Integrated Modeling Environments) framework which empowers method guidance through process-integrated tools. In contrast to the tools of PCEs, the process-integrated tools of PRIME adjust their behavior according to the current process situation and the method definitions. Process integration of PRIME tools is achieved through (1) the definition of tool models; (2) the integration of the tool models and the method definitions; (3) the interpretation of the integrated environment model by the tools, the process-aware control integration mechanism, and the enactment mechanism; and (4) the synchronization of the tools and the enactment mechanism based on a comprehensive interaction protocol. We sketch the implementation of PRIME as a reusable implementation framework which facilitates the realization of process-integrated tools as well as the process integration of external tools. We define a six-step procedure for building a PRIME-based process-integrated environment (PIE) and illustrate how PRIME facilitates change integration on an easy-to-adapt modeling level.
Dual-Polarization, Tunable Breaking Window in the Polarization Conversion Pass Band in a Terahertz Dirac Semimetal-Based Metamaterial (2019)

We propose a planar THz hybrid bulk Dirac semimetal (BDS)-metal metamaterial which consists of a hybrid BDS-metal array on a dielectric layer and a back metallic mirror. The simulation results show that a spectral window that possesses high reflectance with no polarization conversion effect arises in the polarization conversion pass band due to the existence of the BDS rods. Interestingly, though the proposed structure possesses no symmetry property, the effects are nearly the same for x- and y-polarization incidences. We analyze the electric field distributions at the breaking frequency and attribute the phenomena to plasmonic analogue of electromagnetically induced reflectance (EIR-like) effect for x-polarization incidence and direct back scattering for y-polarization incidence. The dependence of the breaking window on the BDS rod length shows that, for both x- and y-polarization incidences, the breaking characteristic is mainly determined by the dipole resonance on the BDS rod. Moreover, the breaking window can be independently and dynamically manipulated by changing the Fermi energy of the BDS rods. Our results may provide potential applications in designing new polarization control devices.
Level set based brain aneurysm capturing in 3D (2010)

Brain aneurysm rupture has been reported to be closely related toaneurysm size. The current method used to determine aneurysm sizeis to measure the dimension of the aneurysm dome and the width ofthe aneurysm neck. Since aneurysms usually have complicatedshapes, using just the size of the aneurysm dome and neck may notbe accurate and may overlook important geometrical information. Inthis paper we present a level set based surface capturingalgorithm to first capture the aneurysms from the vascular tree.Since aneurysms are described by level set functions, volumes,curvatures and other geometric quantities of the aneurysm surfacecan easily be computed for medical studies. Experiments andcomparisons with models used for capturing illusory contours in 2Dimages are performed. Applications to medical images are alsopresented to show the accuracy, consistency and robustness of ourmethod in capturing brain aneurysms and volume quantification.
Mechanosensitive fibroblasts in the sino‐atrial node region of rat heart: interaction with cardiomyocytes and possible role (1994)

The positive chronotropic response of the heart to stretch of the right atrium is one of the major mechanisms adjusting the heart rate to variations in venous return on a beat-by-beat basis. The precise pathway of this mechano-electric feedback and its cellular basis are uncertain. In this study, a possible contribution of mechanosensitive fibroblasts, abundant in the sino-atrial node region, was investigated using a mathematical model of the electrical interaction of a mechanosensitive fibroblast and a sino-atrial pacemaker cell. Electrophysiological evidence for a bio-electrical interaction of mechanosensitive fibroblasts with surrounding cardiomyocytes has been studied in (i) the isolated spontaneously beating atrium of rat hearts, and (ii) cell cultures of the neonatal rat heart. These investigations were performed using (i) double-barrelled floating microelectrodes for intracellular potential registrations, and (ii) the double whole cell patch-clamp technique. It was shown that cardiac fibroblasts and surrounding cardiomyocytes can be either electrically well isolated from each other, or coupled both capacitively and electrotonically. The electrophysiological data obtained were incorporated into the OXSOFT HEART program. Assuming that equivalent coupling may occur between mechanosensitive fibroblasts and sino-atrial pacemaker cells, a heterologous cell pair consisting of one fibroblast and one sino-atrial node myocyte connected by ten to thirty single gap junctional channels with a conductance of 30 pS was modelled. The model of the electrotonic interaction of these cells showed that stretch of the fibroblast during atrial diastole, simulating increased atrial wall tension during atrial filling, can raise the spontaneous depolarization rate of the pacemaker cell in a stretch-dependent manner by up to 24%. These results show that cardiac mechanosensitive fibroblasts could form a cellular basis for the positive chronotropic response of the heart to stretch of the right atrium.
Complete exchange on a circuit switched mesh (2003)

The complete exchange ('all-to-all personalized') communication pattern is at the heart of numerous important multicomputer algorithms. Recent research has shown how this pattern can efficiently be performed on circuit-switched hypercubes. However, on circuit-switched meshes, this pattern is difficult to perform efficiently because the sparsity of the mesh interconnect leads to severe link contention. The authors develop a family of algorithms that proceed by recursively carrying out a series of contention-free exchanges on subdivisions of the mesh. Each member of this family is useful for some range of the parameters: mesh size, message size, startup time, and data transmission and permutation rates. The authors describe the performance of their algorithms on the Touchstone Delta mesh.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Radio Telephone Service for a Mobile Society (1982)

Telecom Australia has recently entered the field of automatic mobile telephone service with the establishment of Mobile Telephone Service MTS in Melbourne and Sydney. This service which provides a full facility telephone in a mobile environment adds to the long established telephone radio paging service Telefinder. This paper describes the operation and some of the technology and techniques of these two services with particular reference to their common use of a stored program switching and control exchange. Both systems were designed by Nippon Electric Co. of Japan and supplied by NEC Australia.
Proposed Mechanism of CO Mitigation in PEMFCs by Using Dilute H2O2 in the Anode Humidifier (1998)

CO poisoning in proton exchange membrane fuel cells (PEMFCs) can be mitigated by using dilute H2O2 in the anode humidifier. However, mitigation appears to be provided by an "unintended" O2 bleed produced by decomposition of H2O2 in the humidifier, rather than by H2O2 vapors transported from the humidifier to the anode. CO mitigation was effective when significant levels of O2 were present in the anode feed. The effectiveness of CO mitigation disappeared when non-catalytic materials were used to suppress H2O2 decomposition in the humidifier. (Safety Note: H2O2 decomposition in the anode humidifier may produce flammable compositions in the anode feed.)
Annexin A2 and A5 Serve as New Ligands for C1q on Apoptotic Cells (2012)

C1q is the initiator of the classical complement pathway and opsonizes apoptotic cells to facilitate phagocytosis. Deficiency of C1q is the strongest known risk factor for development of systemic lupus erythematosus (SLE), which appears to be related to ensuing impaired clearance of apoptotic material. The objective of the current study was to investigate new ligands for C1q on the surface of apoptotic cells. We revealed that the two phospholipid-binding proteins annexin A2 and A5 are, beside DNA, significant C1q ligands. We furthermore, demonstrated that C1q binds directly to histones exposed on the surface of dying cells but we did not detect significant interaction with phosphatidylserine. The complement inhibitors C4b-binding protein and factor H also interact with dying cells, most likely to decrease complement activation beyond the level of C3 to allow noninflammatory clearance. Despite the fact that C4b-binding protein, factor H, and C1q share some ligands on dying cells, we showed that these three proteins did not compete with one another for binding to apoptotic cells. We additionally demonstrated that the way in which apoptosis is induced influenced both the degree of apoptosis and the binding of C1q. The knowledge, that annexin A2 and A5 act as ligands for C1q on apoptotic cells, sheds new light on the pathophysiology of autoimmune diseases.
Development of a novel GLUT4 translocation assay for identifying potential novel therapeutic targets for insulin sensitization (2008)

GLUT4 (glucose transporter 4) plays important roles in glucose homoeostasis in vivo. GLUT4 expression and function are diminished in diabetic human and animal subjects. The goal of the present study is to develop a cell-based assay for identifying negative regulators of GLUT4 translocation as potential targets for the treatment of Type 2 diabetes. Traditional GLUT4 translocation assays performed in differentiated myocytes or adipocytes are difficult to perform, particularly in HTS (high-throughput screening) mode. In the present study, we stably co-expressed c-Myc and eGFP [enhanced GFP (green fluorescent protein)] dual-tagged recombinant GLUT4 with recombinant IRS1 (insulin receptor substrate 1) in HEK-293 cells (human embryonic kidney cells) (HEK-293.IRS1.GLUT4 cells). Insulin treatment stimulated both glucose uptake and GLUT4 translocation in these cells. GLUT4 translocation is quantified by a TRF (time-resolved fluorescence) assay in a 96-well HTS format. TRF assays confirmed insulin-stimulated GLUT4 translocation, which can be inhibited by PI3K (phosphoinositide 3-kinase) or Akt [also called PKB (protein kinase B)] inhibitors. Treatment with palmitate increased IRS1 serine phosphorylation and reduced insulin-stimulated Akt phosphorylation and GLUT4 translocation, indicating insulin resistance. Knockdown of PTEN (phosphatase and tensin homologue deleted on chromosome 10) and PTP1B (protein tyrosine phosphatase 1B) gene expression by siRNA (small interfering RNA) treatment significantly increased GLUT4 translocation only in cells treated with palmitate but not in untreated cells. Similar results were obtained on treatment with siRNA of JNK1 (c-Jun N-terminal kinase 1), S6K1 (ribosomal protein S6 kinase, 70 kDa, polypeptide 1) and PKC(theta) (protein kinase C theta). In summary, we have established and validated a novel GLUT4 translocation assay that is optimal for identifying negative regulators of GLUT4 translocation. In combination with more physiologically relevant secondary assays in myotubes and adipocytes, this assay system can be used to identify potential novel therapeutic targets for the treatment of Type 2 diabetes.
Auditor switching for opinion shopping, and subsequnt audit quality and audit fee: Evidence from post-SOX period (2014)

Published in Auditing, May 2019, 38 (2), 101-123. https://doi.org/10.2308/ajpt-52154.
Real-Time, in Situ Monitoring of Bioactive Zone Dynamics in Heterogeneous Systems (2005)

Successful implementation of in situ bioremediation is contingent upon understanding how physicochemical and microbial factors affect the formation and dynamics of microbially active regions known as bioactive zones (BAZs). This study demonstrates how a novel fiber optic detection system can be used to test hypotheses concerning real-time, in situ BAZ formation and dynamics. This study focuses on naphthalene transport in saturated porous media containing defined physicochemical and microbial heterogeneities. Biological activity was measured using a lux reporter bacterium, Pseudomonas putida RB1353, that bioluminesces during naphthalene catabolism. Results show that the presence of defined heterogeneities drives the development of BAZs at material-property interfaces where the confluence of naphthalene, dissolved oxygen, and sufficient microbial density is optimal. Thus, despite successful transport of P. putida RB1353 into a sterile low-permeability region containing substrate, BAZ formation in this region was limited by local physicochemical conditions (e.g., naphthalene and dissolved oxygen bioavailability). In another instance, transport of P. putida RB1353 occurred against advective flow, resulting in BAZ formation upgradient of inoculated regions. Defined systems such as this can be used as a basis for predicting localization of activity in complex subsurface systems.