gebhart/patrepeval huggingface dataset:
64 USE OF INTERMEDIATE TEMPERATURES TO REVERT ATRIAL FIBRILLATION (2005)

<h3></h3> Previous work has shown the ability of iced saline to revert acetylcholine-induced atrial fibrillation in the pig model. The present study investigated whether room temperature saline could also be effective for this purpose. The left atria of 3 Sus domesticus 25-30 kg were exposed by left thoracotomy, and atrial fibrillation induced by direct application of 1:100 acetylcholine solution accompanied by gentle stroking of the tissue. The time duration of the resultant arrhythmias was measured during no intervention and applications of room temperature (22°C) and iced saline (4°C) compresses to the exposed portion of the atria. A total of 16 episodes each for control, room, and iced interventions were randomly conducted. In control episodes, an average of 3 minutes was recorded. In room temperature, the average dropped to 1.6 minutes, and for the iced intervention was 1.2 minutes. The data were examined with GraphPad InStat version 3.05. Normality was checked using the Kolmogorov-Smirnov test and then analyzed by a one-way analysis of variance (ANOVA). There appeared to be a linear trend of efficacy with temperature. Although the difference between the iced saline and room temperature interventions was not statistically significant, there were significant differences between the control (37°C) and iced saline (4°C) times and between control and room temperature (22°C). We conclude that atrial chilling to revert atrial fibrillation is feasible even using temperatures more modest than iced saline. (Figure)
<title>Multisensor feature fusion methods and results</title> (2001)

Analysts responsible for supporting time dominated threat decisions are faced with a growing volume of sensor data. Most efforts to increase discrimination among targets using multiple types of sensors encounter the same problems: · Sensor data are received in large volumes. · Sensor data are highly variable. · Signature features are represented by many dimensions. · Feature values are inter-correlated, random, or not related to target differences. · Decision rules for classifying new target data are difficult to define. This paper describes a new methodology for solving several problems: selecting signature features, reducing variability, increasing discrimination accuracy, and developing decision rules for classifying new target signatures. The results from using a combination of exploratory and multi-variate statistical techniques show potential improvements over the traditional Dempster-Shafer approach. This project uses data from operational prototype sensors and vehicles of interest for threat analysis. Acoustic and seismic sensor data came from an unattended ground sensor and three military vehicles. Although the resulting algorithms are specific to the data set, the data screening and fusion methods tested in this project may be useful with other types of sensor and target data.
Identification of synaptotagmin effectors via acute inhibition of secretion from cracked PC12 cells (2003)

The synaptotagmins (syts) are a family of membrane proteins proposed to regulate membrane traffic in neuronal and nonneuronal cells. In neurons, the Ca2+-sensing ability of syt I is critical for fusion of docked synaptic vesicles with the plasma membrane in response to stimulation. Several putative Ca2+-syt effectors have been identified, but in most cases the functional significance of these interactions remains unknown. Here, we have used recombinant C2 domains derived from the cytoplasmic domains of syts I-XI to interfere with endogenous syt-effector interactions during Ca2+-triggered exocytosis from cracked PC12 cells. Inhibition was closely correlated with syntaxin-SNAP-25 and phosphatidylinositol 4,5-bisphosphate (PIP2)-binding activity. Moreover, we measured the expression levels of endogenous syts in PC12 cells; the major isoforms are I and IX, with trace levels of VII. As expected, if syts I and IX function as Ca2+ sensors, fragments from these isoforms blocked secretion. These data suggest that syts trigger fusion via their Ca2+-regulated interactions with t-SNAREs and PIP2, target molecules known to play critical roles in exocytosis.
ChemInform Abstract: C(15) CONFIGURATION OF ISOPIMARENE‐15,16‐DIOLS (1980)

Abstract Umlagerungsreaktionen an Pimaradien und verwandten Verbindungen u.a. zu den Derivaten (I) werden diskutiert.
Malonyl-CoA:ACP Transacylase from Streptomyces coelicolor Has Two Alternative Catalytically Active Nucleophiles (2001)

Fatty acids and polyketides are synthesized by mechanistically and evolutionarily related multienzyme systems. Their carbon chain backbones are synthesized via repeated decarboxylative condensations of alpha-carboxylated building blocks onto a growing acyl chain. These alpha-carboxylated building blocks are transferred from the corresponding coenzyme A thioesters onto the phosphopantetheine arm of an acyl carrier protein (ACP) by acyl transferases, which operate by a ping-pong mechanism involving an acyl-O-serine intermediate. In the course of our studies on the malonyl-CoA:ACP transacylase (MAT) from Streptomyces coelicolor, we observed that an active-site Ser (97) --> Ala mutant retains activity as well as the ability to be covalently labeled by (14)C malonyl-CoA. Here we demonstrate that an alternative, catalytically competent nucleophile exists in the active site of this enzyme. Next to the active-site serine is a histidine residue that is conserved in some, but not all acyl transferases. The H96A mutant is also active and can be labeled, but an H96A/S97A double mutant is inactive and cannot be labeled. The ability of H96 to form a malonyl-imidazole adduct was confirmed by proteolysis, followed by radio-HPLC and mass spectrometric analysis of the S97A mutant enzyme. Kinetic analysis revealed that the k(cat) of the S97A mutant was within 10-fold that of the wild-type enzyme, whereas the K(M)s of the two enzymes were comparable. Sequence comparison with the E. coli MAT (whose X-ray structure is known) led to the identification of H201 as the putative base in the serine-histidine catalytic dyad of the S. coelicolor enzyme. The absence of MAT activity in the H201A mutant and the detection of weak activity in the H201Q mutant was consistent with this proposal. The implications of this unexpected finding are discussed.
Laparoscopic urology: Past, present, and future (1993)

Laparoscopy has begun to have a significant impact on the management of urologic problems. Although initially limited to diagnostic pediatric problems, it has more recently been used to resolve myriad adult urologic conditions. Indeed, during the past year laparoscopic urology has moved well beyond the diagnosis of the undescended testicle and has been successfully used for pelvic lymphadenectomy, varicocelectomy, ureterolysis, drainage of a pelvic lymphocele, bladder suspension, and nephrectomy. Future applications of laparoscopy in urology may well include nephroureterectomy, cystectomy, and creation of an ileal conduit.
UPREGULATION OF CYTOKINES ASSOCIATED WITH MACROPHAGE ACTIVATION IN THE LEWIS-TO-F344 RAT TRANSPLANTATION MODEL OF CHRONIC CARDIAC REJECTION1,2 (1995)

Lewis-to-F344 rat cardiac allografts develop chronic rejection and arteriosclerotic lesions rich in mononuclear cells (especially macrophages). This study was performed to determine whether cytokine pathways associated with macrophage activation are upregulated in hearts undergoing chronic rejection. Gene transcript levels for IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IL-6 were measured with reverse-transcription PCR assays optimized for each gene. Gene products were confirmed by immunohistology. For all three genes, transcript levels in rat cardiac allografts increased significantly on day 7 and remained elevated on days 14 and 28 posttransplantation, as compared with naive hearts, paired host hearts, and syngrafts (P<0.006). For the inducible genes IFN-γ and MCP-1, high transcript levels in cardiac allografts were in contrast with low levels in host spleens. On the other hand, transcript levels for the basally expressed gene IL-6 were elevated in both organs. Immunostaining confirmed allograft-specific expression for all three cytokines and localized the gene products to infiltrating mononuclear cells in the interstitium and vasculature. The sustained expression of these cytokines in cardiac allografts undergoing chronic rejection supports the widely held hypothesis that the intimal changes associated with transplant arteriosclerosis are mediated by cellular activation and cytokine production.
Obstructive sleep apnea classification based on spectrogram patterns in the electrocardiogram (2002)

Describes the findings of an exploratory study of the effect of obstructive sleep apnea (OSA) on the electrocardiogram (ECG) signal. Episodes of sleep apnea are characterized by periodic cycles of breathing cessation find restoration. The authors' analysis was guided by the hypothesis that these cycles synchronously alter the ECG. They discovered several characteristic indicators of apnea in the ECG signal. Their study focused on data sets provided for the Computers in Cardiology (CINC) 2000 apnea classification competition. After careful QRS detection, artifact removal, and preprocessing, the authors found that they could recognize sleep apnea by visually inspecting spectrograms of various features of the ECG such as the heart rate (HR), S-pulse amplitude, and pulse energy. As part of this study the authors entered both CINC competitions. They were able to correctly classify 28 out of 30 subjects in their initial competition entry and 30 out of 30 in their third entry. Once each signal was classified as a whole, the authors were able to correctly classify each minute in 13,626 out of 17,268 cases in their initial entry and 15,994 cases in their fourth entry.
Facteurs de transcriptions, cytokines et atopie (2000)

Les manifestations cliniques de l’atopie, extremement frequentes au sein de la population generale, associent l’asthme, les rhino-conjonctivites, l’eczema et sont generalement caracterisees par un taux eleve d’IgE. Dans les deux dernieres annees, plusieurs travaux ont apporte des donnees nouvelles concernant la physiopathologie de l’atopie [revue dans references 1-4, et voir l’excellente revue d’articles dans le supplement de Nature 1999 ; 402, n° 6760]. Les manifestations pathologiques de l’asthme associent l’inflammation des voies aeriennes superieures et une hypersecretion de mucus qui joue un role central dans la pathogenie de l’asthme. La muqueuse et la sous-muqueuse des voies aeriennes superieures des patients asthmatiques sont infiltrees par des cellules mononucleees, notamment des eosinophiles et des lymphocytes. Des lymphocytes T CD4, particuliers par leur synthese de cytokine de type TH2 (voir plus bas), jouent un role essentiel dans la generation de l’inflammation en reponse a differents stimuli (bacteriens ou allergenes).
Flow cytometric analysis of human epidermal cell ageing using two fluorescent mitochondrial probes. (1995)

Cardiolipin, mitochondrial transmembrane potential, cell refringence and cell diameter were examined in epidermal cells obtained from 42 women between 9- to 75-year-old. The study was carried out in situ by flow cytometry on cells having incorporated either Nonyl Acridine Orange or Rhodamine 123, 2 mitochondria-specific dyes. Cardiolipin levels, determined by the binding of the cardiolipin-specific probe Nonyl Acridine Orange, decreased significantly with age, especially in young individuals. This suggests 2 stages in the age-dependent transformation of mitochondria (organelle number and/or size): one during childhood development and to adulthood (9 to 27 years) in which cardiolipin levels decrease dramatically (slope: -3.742; p = 0.0243) and the other corresponding to senescence (35 to 75 years) in which this decrease is less pronounced (slope: -0.618; p = 0.0467). These changes have no effect on mitochondrial potential, measured by Rhodamine 123 incorporation, which remained constant with age. This function, controlling calcium partitioning within the cell, might allow keratinocytes to differentiate and maintain the skin barrier function of the epidermis. Like cardiolipin, intrinsic parameters such as cell size and refringence also significantly decreased in epidermal cells from elderly subjects. The methodology can be used to determine physiological ageing in various cell types and to analyse human ageing and related parameters.
Identifying critical elements in drinking water distribution networks using graph theory (2020)

Abstract Drinking water distribution networks (WDNs) are a crucial infrastructure for life in cities. Deterioration of this ageing, and partly hidden from view, infrastructure can result in losses due to leakage and an increased contamination risk. To counteract this, maintenance strategies are required to maintain the service level. Information on the most critical elements of a WDN, with respect to the functioning of the system as a whole, is essential for prioritising maintenance or rehabilitation activities. In this study a Graph theory based method is developed and applied for efficiently identifying the most critical elements. The main advantage of this method is that it avoids the need to perform elaborate hydrodynamic model calculations. Instead, the structure of the network is the main starting point. The results show that the structure of the network is more decisive than the hydraulics with respect to the criticality of the system’s performance as a whole. Results depict that the suggested approach is applicable not only to the main (primary) network, but also to the capillaries which are normally beyond the scope of the traditional methods applied so-far because of the complexity of the networks and the required calculation time.
Quinolinylmethanone-Based Thermally Activated Delayed Fluorescence Emitters and the Application in OLEDs: Effect of Intramolecular H-Bonding (2019)

Three new quinoline TADF emitters, 2QPM-mDC, 2QPM-mDTC, and 4QPM-mDTC, were designed and synthesized and the emitters show Δ E<sub>ST</sub> as low as 0.07 eV and high PL quantum yield (PLQY) up to 98%. An electroluminescence device based on 2QPM-mDTC can reach high EQE over 24%. Compared with the reported TADF devices, the device shows narrow emission bandwidth and high color purity. The excellent device performance is likely ascribed to the molecular design of 2QPM-mDTC containing an intramolecular H-bonding in the molecule.
Figure S1 from Cabozantinib Reverses Renal Cell Carcinoma–mediated Osteoblast Inhibition in Three-dimensional Coculture <i>In Vitro</i> and Reduces Bone Osteolysis <i>In Vivo</i> (2023)

&lt;p&gt;Differentiation of pre-osteoblast MC3T3-E1 cells in 3D hydrogel&lt;/p&gt;
IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms (2012)

Parasitic helminths are a major cause of chronic human disease, affecting more than 3 billion people worldwide. Host protection against most parasitic helminths relies upon Type 2 cytokine production, but the mechanisms that regulate interleukin (IL) 4 and 13 production from CD4(+) T helper 2 cells (T(H)2) and innate lymphoid type 2 cells (ILC2s) remain incompletely understood. The epithelial cell-derived cytokines IL-25 and IL-33 promote Type 2 responses, but the extent of functional redundancy between these cytokines is unclear and whether Type 2 memory relies upon either IL-25 or IL-33 is unknown. Herein, we demonstrate a pivotal role for IL-33 in driving primary and anamnestic immunity against the rodent hookworm Nippostrongylus brasiliensis. IL-33-deficient mice have a selective defect in ILC2-derived IL-13 during both primary and secondary challenge infections but generate stronger canonical CD4(+) T helper 2 cells responses (IL-4, IgE, mast cells, and basophils) than WT controls. Lack of IL-13 production in IL-33-deficient mice impairs resistin-like molecule beta (RELMβ) expression and eosinophil recruitment, which are two mechanisms that eliminate N. brasiliensis parasites from infected hosts. Thus, IL-33 is requisite for IL-13 but not IL-4-driven Type 2 responses during hookworm infection.
Unified model for coordinated control of permanent magnet synchronous wind generator system (2011)

The design of PI controller plays a significance role in the realization of wind generator system. Recognizing the state-of-art of the control strategy the permanent magnet synchronous generator (PMSG) for wind power generation is designed with different subsystems with different reference, and neglecting the mutual influence between the grid and machine sides PWM control and coordinated with PI parameter coordinated with field test. This paper provides a unified model, which present a systematic viewpoint to the different PI controllers with the same reference. The mathematical description for the grid side converter with PI controller (GCC) and the machine side converter with PI controller (MCC) in the same reference is involved in the proposed model. The model describes the general PMSG system with PI controllers as a differential algebraic equation. Based on the proposed model, the method to determine the coordinated parameter is presented. The RTDS simulation results show the effectiveness of the proposed model and method.
Retuning mortality risk prediction in paediatric cardiac surgery: the additional role of early postoperative metabolic and respiratory profile (2016)

Early postoperative respiratory and metabolic parameters increased the accuracy and discrimination of the ABC Score. An external validation is needed to confirm our results.
Mesenchymal stem cell behavior on bioactive crystalline titanium dioxide/hydroxyapatite surfaces functionalized with bone morphogenetic protein 2 (2009)

Mesenchymal stem cell behavior on bioactive crystalline titanium dioxide/hydroxyapatite surfaces functionalized with bone morphogenetic protein 2
Artificial Organ Treatment for Multiple Organ Failure, Acute Renal Failure, and Sepsis: Recent New Trends (2003)

Sepsis remains the major cause of mortality worldwide, claiming millions of lives each year. The past decade has seen major advances in the understanding of the biological mechanisms involved in this complex process. Unfortunately, no definitive therapy yet exists that can successfully treat sepsis and its complications. At variance with targeting single mediators, therapeutic intervention aimed at the nonselective removal of pro- and anti-inflammatory mediators seems a rational concept and a possible key to successful extracorporeal therapies. A further advantage may lie in the continuous nature of such therapy. With such continuous therapy, sequentially appearing peaks of systemic mediator overflow may be attenuated and persistently high plasma levels reduced. This theoretical framework is proposed as the underlying biological rationale for a series of innovative modalities in sepsis. In this editorial, we will review recent animal and human trials that lend support to this concept. We will also review the importance of treatment dose during continuous renal replacement therapy as a major factor affecting survival in critically ill patients with acute renal failure. Additionally, we will review novel information related to other blood purification techniques using large pore membranes or plasma filtration with adsorbent perfusion. Although these approaches are still in the early stages of clinical testing, they are conceptually promising and might represent an important advance.
Author response: Two locus inheritance of non-syndromic midline craniosynostosis via rare SMAD6 and common BMP2 alleles (2016)

The bones in the front, back and sides of the human skull are not fused to one another at birth in order to allow the brain to double in size during the first year of life and continue growing into adulthood. However, one in 2,000 infants is born with a condition called craniosynostosis in which some of these bones have already fused. This fusion prevents the skull from growing properly, and can lead to the brain becoming compressed. As such, surgeons routinely undo the fusion in these infants to allow the brain and skull to grow normally. Eighty-five percent of craniosynostosis cases occur in infants with no other abnormalities, (called non-syndromic cases) and most have no other affected family member. It has therefore been unclear whether these infants have craniosynostosis due to a genetic or non-genetic cause. If the cause is genetic, it is also not clear whether a mutation in a single gene, the combined effects of many genes, or something in between is responsible. Now, by focusing on a group of 191 infants with premature fusion of bones joined at the midline of the skull, Timberlake et al. asked if any of the approximately 20,000 genes in the human genome were altered more frequently in these infants than would be expected by chance. This search revealed that rare mutations that disable one copy of a gene called SMAD6 in combination with a common DNA variant near another gene called BMP2 account for about 7% of infants with midline forms of craniosynostosis. These genes are both known to regulate how bones form, which explains how the mutation of these genes could lead to craniosynostosis. In all cases, the parents of these children were unaffected. This was typically because one parent had only the SMAD6 mutation while the other had only the common BMP2 variant; the transmission of both to their offspring resulted in craniosynostosis. The finding that a rare mutation’s effect is strongly modified by a common variant from another site in the genome is unprecedented. These findings will allow doctors to counsel families about the risk of having additional children with craniosynostosis. Timberlake et al. next plan to study more patients with craniosynostosis to identify additional genes that contribute to this disease. They will also look at other diseases to see whether the combination of rare mutation and common DNA variant could be behind other unexplained disorders.
Epidermal growth factor receptor expression as a molecular determinant of glioblastoma response to the dopamine receptor D2 antagonist, ONC201. (2020)

e14552 Background: Durable response in glioblastoma patients have been reported in phase I/II clinical trials for the blood-brain penetrant dopamine receptor D2 (DRD2) antagonist, ONC201. Here we examine potential molecular determinants of response to DRD2 inhibition. Methods: The Cancer Genome Atlas (TCGA) glioblastoma database and other published mRNA profiles were used to analyze the DRD2 expression pattern. In vitro and in vivo responses to ONC201 were determined using patient derived xenograft glioblastoma models. Immunohistochemical studies were performed on clinically annotated glioblastoma samples derived from phase I/II clinical trials involving ONC201. Results: For the majority of clinical glioblastoma specimens in both the TCGA and non-TCGA dataset, epidermal growth factor receptor (EGFR) expression was inversely correlated with DRD2. This observation was recapitulated in a panel of patient-derived glioblastoma lines. In this panel of DRD2 expressing lines, high EGFR expression was associated with poor response to ONC201 in vitro and in vivo. Moreover, ectopic expression of EGFR reduced DRD2 expression and ONC201 sensitivity, suggesting functional redundancy between DRD2 and EGFR. In cell lines and clinical glioblastoma samples, DRD2 expression closely associated with the expression of rate-limiting enzymes for dopamine synthesis, suggesting dependency of a subset of glioblastomas on autocrine DRD2 signaling. Analysis of specimens from patients treated with ONC201 (n = 15) showed an inverse correlation between the intensity of EGFR staining and clinical response. The median overall survival for patients with high and low EGFR staining was 162 and 373 days, respectively (p = 0.037). All patients who exhibited progression free survival beyond 200 days showed low to no EGFR expression. Conclusions: Our results suggest EGFR expression as a determinant of response to ONC201 in glioblastoma patients and should inform the design of future clinical trials.