Miracle-dz/UniFAR-FTUs huggingface dataset:
Die Rolle von mikroRNAs in der TRAIL induzierten Apoptose bei Pankreasadenokarzinomzellen

MikroRNAs sind kleine nicht kodierende RNAs die regulierend auf post-transkriptionaler Ebene in die Genexpression eingreifen. TRAIL gehort zur TNF Superfamilie und induziert Apoptose hauptsachlich in Tumorzellen. PDACs weisen oftmals eine TRAIL-induzierte Apoptoseresistenz auf. Um die mogliche Deregulation der mikroRNA-Genexpression nach TRAIL-Rezeptor Aktivierung zu untersuchen, wurden Colo357-Zellen mit TRAIL behandelt und die Genexpression der mikroRNAs mittels mikroRNA-Array Analyse und qRT-PCR analysiert. Die TRAIL-Behandlung induzierte die Genexpression der reifen mikroRNA-197 und reduzierte die Genexpression der reifen mikroRNA-432* in TRAIL-sensitiven Colo357-Zellen. Des Weiteren wirkte sich das experimentelle Aus- und Anschalten von mehreren mikroRNAs (miR-197, miR-432* und miR 452*) nach TRAIL-induzierter Apoptose in TRAIL sensitiven Colo357-Zellen und in TRAIL-resistenten Panc89-Zellen auf die Apoptoseinduktion aus. Das Ausschalten der mikroRNA-197 in Panc89-Zellen erhohte auserdem die Sensibilitat gegenuber FasL, aber nicht gegenuber TNFα. Die Inhibition der mikroRNA-197 fuhrte zu einer PARP-Spaltung in unbehandelten Panc89-Zellen. Wohingegen die Uberexpression der mikroRNA-432* in Panc89-Zellen zu einer verstarkten PARP Spaltung nach TRAIL-induzierter Apoptose fuhrte. Das Ausschalten der mikroRNA-197 und das gleichzeitige Anschalten der mikroRNA-432* resultierte in einer verstarkten Apoptose nach TRAIL-Behandlung. Die Ergebnisse zeigen, dass mikroRNA-197 und mikroRNA-432* vielversprechende Kandidaten sein konnten, um TRAIL-resistente PDACs in TRAIL-sensitive PDACs umzuwandeln. Weiterhin reduzierte das Ausschalten der mikroRNA-197 Genexpression signifikant die Proliferation von Colo357- und Panc89-Zellen durch die Aktivierung des p38 Signaltransduktionsweges und fuhrte auch zur Sezernierung von IL-6 und zu Caspase-abhangigen Zelltod. Ahnlich Effekte wurden auch bei HeLa-Zellen gemessen. Durch differentielle 2D-Gelelektrophorese und anschliesende Massenspektometrie wurde nach Ausschalten der mikroRNA-197 eine Hochregulation der Ran GTPase Genexpression gemessen. MikroRNA-mRNA-Bindesequenzvorhersageprogramme zeigen, dass mikroRNA-197 an die 3’-UTR der mRNA der Ran GTPase binden kann. Dies konnte experimentell verifiziert werden. Da das Gen der Ran GTPase in vielen unterschiedlichen Tumoren uberexprimiert wird und die Inhibition in Tumorzellen aber nicht in gesunden Zellen zu Apoptose fuhrt, zeigen diese Daten, dass mikroRNA-197 eine wichtige Rolle in der Malignitat von epithelialen Zellen, durch die Regulation der Ran GTPase-Genexpression, spielen konnte.
Comparative biochemical and genetic analysis of naphthalene degradation among Pseudomonas stutzeri strains

Of a 49-strain collection of Pseudomonas stutzeri species, 11 isolates were able to degrade naphthalene and 1 isolate was able to use m- and p-toluate as sole carbon and energy sources. Of these 12 strains, 10 shared a highly homologous set of naphthalene catabolic genes, even though they belong to four different genomovars. These genes differed from those present in plasmid NAH7. In only one of these degraders could a plasmid-encoded pathway be demonstrated, and a chromosome-encoded pathway is proposed for the remaining strains. meta cleavage of catechol was only observed in those strains able to metabolize alkyl derivatives of catechol.
Pharmacological characterization of A2-adenosine receptors in guinea-pig ventricular cardiomyocytes.

The aim of the present study was to elucidate the question of whether cardiomyocytes possess stimulatory adenylyl cyclase-coupled A2-adenosine receptors and whether these receptors modify contractility. In isolated electrically driven ventricular cardiomyocytes from guinea-pig hearts the effects of the A2-adenosine receptor agonist 2-[(p-2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamide-adenos ine (CGS 21680C) alone and in the presence of isoprenaline on cAMP content and contractile response were investigated. In addition, we characterized these effects with selective A1- and A2-adenosine receptor antagonists [1,3-dipropyl-8-cyclopentylxanthine, DPCPX and 9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo-(1,5-c)quinazolin++ +-5-imine, CGS 15943A, respectively]. To investigate the signal transduction pathway, the influence of pertussis toxin, known to inhibit signal transducing GTP-binding proteins (Gi/o-proteins), on these effects was studied. CGS 21680C alone and in the presence of isoprenaline increased cAMP content concentration-dependently (0.1 nmol/l-10 mumol/l) to maximally 154% of control and 137% of isoprenaline value, respectively. In the presence of the A1-adenosine receptor antagonist DPCPX (0.3 mumol/l) or after pertussis toxin-pretreatment (18 micrograms/kg i.v. 24-26 h) the cAMP increase was further elevated. The A2-adenosine receptor antagonist CGS 15943A (0.01 mumol/l) abolished these effects, indicating that these effects are mediated by A2-adenosine receptors. The elevation in cAMP content was not accompanied by an increase in contractile response. However, in the presence of isoprenaline CGS 21680C reduced contractile response to 62% of the isoprenaline value. The A1-adenosine receptor antagonist DPCPX abolished the decrease in contractility, whereas the A2-adenosine receptor antagonist CGS 15943A did not effect contractility. Thus the reduction in contractility is mediated via cAMP-decreasing A1-adenosine receptors. The results provide evidence for the coexistence of cAMP-reducing A1- and cAMP-elevating A2-adenosine receptors on ventricular cardiomyocytes. Only stimulation of A1-adenosine receptors leads to a subsequent reduction in contractile response, whereas A2-adenosine receptors do not affect contractility.
Tracing local energy markets: A literature review

Abstract We conduct a structured literature review on the concept of local energy markets (LEMs). LEMs have gained increasing attention in the last two decades. Yet, a holistic definition and clear demarcation of LEMs is still missing. The review shows current works to shift their focus from conceptual implementation and design to increasingly realistic applications of LEMs. Secure access to (near) real-time smart meter data is a prerequisite for LEMs. Current research gaps, e. g. the inclusion of network constraints, agent-centric LEM designs or a comparison of market mechanisms, are identified.
A Novel Congestion Control Algorithm for Large BDP Networks with Wireless Links

A new TCP protocol can succeed for large bandwidth delay product when it meets network bandwidth utilization efficiency and fair sharing. We introduce a novel congestion control algorithm which employs queueing delay information in order to calculate the amount of congestion window increment in increase phase, and reduces congestion window to optimal estimated bound as packet loss occurs. Combination of such methods guarantees that the proposal utilizes fully network bandwidth, recovers quickly from packet loss in wireless link, and preserves fairness for competing flows mixed short RTT and long RTT. Our simulations show that features of the proposed TCP meet the desired requirements.
Neuropsychological functioning in children and adolescents with restrictive-type anorexia nervosa: An in-depth investigation with NEPSY–II

Several studies have investigated the neuropsychological functioning of patients with anorexia nervosa restrictive type (AN-r), but results are conflicting. Here we compared the neuropsychological profile of 23 female children and adolescents with AN-r and of 46 typical controls (aged 9–16 years) using the second edition of the NEPSY (a Developmental Neuropsychology Assessment) neuropsychological battery. AN-r patients presented subtle cognitive flexibility impairments in audiomotor responses (p = .033). Conversely, superior performance in verbal fluency (p = .024) and memory (p = .034) was observed only in AN-r patients with an associated unipolar mood disorder. This profile of marginally impaired and enhanced performance was independent from illness duration and starvation degree, suggesting that it may preexist and represent a vulnerability factor for the disease onset.
Bridging to Cardiac Transplantation With the Thoratec Ventricular Assist Device

Mechanical circulatory support has become an established procedure for bridging patients to cardiac transplantation. One of the devices available is the Thoratec VAD, which can be applied for univentricular or biventricular support. Between March 1992 and June 1997, 74 patients were bridged with Thoratec VAD to cardiac transplantation. In 67 patients the system was applied exclusively (26 LVAD, 38 BVAD, 3 TAH), in 7 patients subsequently or in combination with another MCS device. 71.6% with exclusive Thoratec application underwent transplantation with a post-transplant survival rate of 90%, 4 patients are still waiting. Transplant rate in LVAD and BVAD patients was 84% and 71.4%, respectively, posttransplant survival 95.2% and 88%, respectively. 28.6% with a combined application of Thoratec and another MCS device survived to be discharged from hospital. Main complications were bleeding, liver failure, multiple organ failure, and infections. In terms of reliability and efficacy the Thoratec VAD is the system of choice for mid-term application in patients bridged to cardiac transplantation.
Rethinking the value of high wood density

Summary 1. Current thinking holds that wood density mediates a tradeoff between strength and economy of construction, with higher wood density providing higher strength but at higher cost. 2. Yet the further away wood fibres are from the central axis of the trunk, the more they increase the strength of the trunk; thus, a fat trunk of low-density wood can achieve greater strength at lower construction cost than a thin trunk of high-density wood. 3. What then are the countervailing advantages of high wood density? 4. We hypothesize that high wood density is associated with lower maintenance costs due to lower trunk surface area, as surface area correlates with maintenance respiration. 5. This advantage would be particularly important to long-lived trees and could in part explain why they tend to have high wood density. 6. High wood density has also been associated with lower risk of trunk breakage, xylem implosion and pathogen invasion, but we argue that these relationships are not causal and instead reflect correlated selection on other traits of value to long-lived trees. 7. This revaluation of the costs and benefits of high wood density has important implications for understanding tree life-history evolution, functional diversity, forest carbon stocks and the impacts of global change.
A VapBC Toxin-Antitoxin Module Is a Posttranscriptional Regulator of Metabolic Flux in Mycobacteria

ABSTRACT The largest family of toxin-antitoxin (TA) modules are encoded by the vapBC operons, but their roles in bacterial physiology remain enigmatic. Microarray analysis in Mycobacterium smegmatis overexpressing VapC/VapBC revealed a high percentage of downregulated genes with annotated roles in carbon transport and metabolism, suggesting that VapC was targeting specific metabolic mRNA transcripts. To validate this hypothesis, purified VapC was used to identify the RNA cleavage site in vitro. VapC had RNase activity that was sequence specific, cleaving single-stranded RNA substrates at AUAU and AUAA in vitro and in vivo (viz., MSMEG_2121 to MSMEG_2124). A bioinformatic analysis of these regions suggested that an RNA hairpin 3′ of the AUA(U/A) motif is also required for efficient cleavage. VapC-mediated regulation in vivo was demonstrated by showing that MSMEG_2124 (dhaF) and MSMEG_2121 (dhaM) were upregulated in a ΔvapBC mutant growing on glycerol. The ΔvapBC mutant had a specific rate of glycerol consumption that was 2.4-fold higher than that of the wild type during exponential growth. This increased rate of glycerol consumption was not used for generating bacterial biomass, suggesting that metabolism by the ΔvapBC mutant was uncoupled from growth. These data suggest a model in which VapC regulates the rate of glycerol utilization to match the anabolic demands of the cell, allowing for fine-tuning of the catabolic rate at a posttranscriptional level.
Mechanism of drug-induced lupus. I. Cloned Th2 cells modified with DNA methylation inhibitors in vitro cause autoimmunity in vivo.

Treating activated CD4+ T cells with DNA methyltransferase inhibitors modifies gene expression and induces autoreactivity. Adoptive transfer of viable polyclonal autoreactive cells causes a lupus-like disease, most likely because of one or more effector functions expressed by the autoreactive cells. However, the number of potential effector mechanisms expressed by polyclonal cells is large. To more readily identify responsible mechanisms, we asked if autoimmunity can be induced by using the conalbumin-reactive, cloned Th2 cell line D10.G4. 1, treated with 5-azacytidine (5-azaC) or procainamide (Pca). Treated, but not untreated, cells responded to syngeneic APCs without Ag, overexpressed LFA-1, spontaneously lysed syngeneic macrophages, and secreted relatively large amounts of IL-6, small amounts of IL-4, and no detectable IL-2 nor IFN-gamma. Adoptive transfer of treated, but not untreated, cells induced a severe immune complex glomerulonephritis, pulmonary alveolitis, central nervous system abnormalities including fibrinoid necrosis, karyorrhexis, and meningitis, and bile duct proliferation with periportal inflammatory cell infiltration resembling primary biliary cirrhosis. Anti-ssDNA, anti-dsDNA, and anti-histone Abs were also found. These experiments demonstrate that modification of this cloned T cell line with DNA methyltransferase inhibitors is sufficient to cause an autoimmune disease, with features of lupus as well as autoimmune liver disease. The results also raise the possibility that macrophage lysis, IL-6 secretion, and LFA-1 overexpression could contribute to the disease process. This system may be useful in testing the role of these and other pathologic mechanisms in the development of specific autoimmune lesions.
Influence of TOF information in OpenPET image reconstruction

We have proposed an “OpenPET” geometry, which consists of two axially separated detector rings. The central point of the field of view, where the highest sensitivity is obtained, is opened. The OpenPET mainly has three applications, namely, simultaneous PET/CT, extension of the axial FOV, and in-beam PET. In our previous report, we showed that axial spatial resolution, which is degraded with the extended gap due to the parallax error, can be recovered by use of depth-of-interaction (DOI) detectors. On the other hand, image reconstruction of the OpenPET is an incomplete problem because projection data do not satisfy Orlov's condition. Low-frequency components are missing in oblique LORs, i.e., LORs with large ring differences. The gap would suffer from loss of low-frequency components because the gap, where direct LORs (i.e., LORs in the same ring) do not exist, is imaged only from the oblique LORs. In this paper, we focused on time-of-flight (TOF) information, which is expected to compensate for the loss of low-frequency components in the gap. We investigated influence of TOF information in the OpenPET image reconstruction through numerical simulations. Simulated OpenPET scanner had dual detector rings (827.0 mm in diameter and axial length of 153.6 mm each) separated by a gap of 153.6 mm. We supposed that the detectors had a DOI capability of 8 layers and had a TOF capability of 400 ps FWHM resolution. For the non-TOF case, hot-spot objects, which are commonly seen in cancer diagnosis with use of FDG, were imaged without any artifacts, but objects containing more low-frequency components suffered from strong distortion. However, these artifacts were effectively reduced by using TOF information. These results showed that TOF information can compensate for low-frequency components missing in the gap.
Etudes physiologiques et comportemenales de la fertilité mâle chez un hyménoptère parasitoïdique, nasonia vitripennis

La plupart des etudes sur l’influence de la temperature sur la production des spermatozoides portent en grande partie sur les vertebres. Neanmoins, les invertebres constituent la majorite de la biodiversite terrestre animale, sont egalement plus sensibles a ces variations de temperature. Les travaux realises au cours de cette these ont porte sur la comprehension des capacites de reproduction, et sur l’influence d’une augmentation de temperature sur les fonctions mâles chez Nasonia vitripennis, un hymenoptere parasitoide. Ce travail de these m’a permis de confirmer que chez cette espece, la spermatogenese etait synchronisee et de decrire pour la premiere fois, un systeme de stockage intermediaire des spermatozoides entre les testicules et les vesicules seminales. De plus, j’ai pu mettre en evidence que la spermatogenese etait sensible a une augmentation de temperature pendant le developpement, alterant le sexe ratio de la descendance par des modifications d’allocations des sexes par les femelles. Ces resultats apportent de nouvelles connaissances sur la fertilite mâle chez cette espece et demontrent la sensibilite de la spermatogenese a la temperature.
Drug‐induced Apoptotic Neurodegeneration in the Developing Brain

Physiological cell death (PCD), a process by which redundant or unsuccessful neurons are deleted by apoptosis (cell suicide) from the developing central nervous system, has been recognized as a natural phenomenon for many years. Whether environmental factors can interact with PCD mechanisms to increase the number of neurons undergoing PCD, thereby converting this natural phenomenon into a pathological process, is an interesting question for which new answers are just now becoming available. In a series of recent studies we have shown that 2 major classes of drugs (those that block NMDA glutamate receptors and those that promote GABAA receptor activation), when administered to immature rodents during the period of synaptogenesis, trigger widespread apoptotic neurodegeneration throughout the developing brain. In addition, we have found that ethanol, which has both NMDA antagonist and GABAmimetic properties, triggers a robust pattern of apoptotic neurodegeneration, thereby deleting large numbers of neurons from many different regions of the developing brain. These findings provide a more likely explanation than has heretofore been available for the reduced brain mass and lifelong neurobehavioral disturbances associated with the human fetal alcohol syndrome (FAS). The period of synaptogenesis, also known as the brain growth spurt period, occurs in different species at different times relative to birth. In rats and mice it is a postnatal event, but in humans it extends from the sixth month of gestation to several years after birth. Thus, there is a period in pre‐ and postnatal human development, lasting for several years, during which immature CNS neurons are prone to commit suicide if exposed to intoxicating concentrations of drugs with NMDA antagonist or GABAmimetic properties. These findings are important, not only because of their relevance to the FAS, but because there are many agents in the human environment, other than ethanol, that have NMDA antagonist or GABAmimetic properties. Such agents include drugs that may be abused by pregnant mothers (ethanol, phencyclidine [angel dust], ketamine [Special K], nitrous oxide [laughing gas], barbiturates, benzodiazepines), and many medicinals used in obstetric and pediatric neurology (anticonvulsants), and anesthesiology (all general anesthetics are either NMDA antagonists or GABAmimetics).
Supporting structured, semi-structured and unstructured data in digital libraries

This work presents an approach to the design of digital libraries by raising and addressing issues involved in supporting services for collections of structured, semi-structured and unstructured objects. We present a system architecture for a digital library that includes provisions for storing and retrieving data with differing structure levels (ranging from highly unstructured to highly structured). We have successfully instantiated this architecture via a practical implementation that integrates technologies such as relational and novel XML databases as well as indexing and information retrieval techniques. A number of digital library applications are using these facilities for handling differing structure levels in an integrated fashion.
A Multicenter Study of Bispectral Electroencephalogram Analysis for Monitoring Anesthetic Effect

Bispectral analysis (BIS) of the electroencephalogram (EEG) has been shown in retrospective studies to predict whether patients will move in response to skin incision.This prospective multicenter study was designed to evaluate the real-time utility of BIS in predicting movement response to skin incision using a variety of general anesthetic techniques. Three hundred patients from seven study sites received an anesthetic regimen expected to give an approximately 50% movement response at skin incision. EEG was continuously recorded via an Aspect B-500 monitor and BIS was calculated in real time from bilateral frontocentral channels displayed on the monitor. Half of the patients were randomized to a treatment group in which anesthetic drug doses were increased to produce a lower BIS. In the control group, BIS was recorded, but no action taken on the data displayed. A determination of movement in response to skin incision was made in the 2 min succeeding incision. Retrospective pharmacodynamic modeling was performed using STANPUMP to estimate effect-site concentrations of intravenously administered anesthetics. BIS values were significantly higher in the control group (66 +/- 19) versus the BIS-guided group, in which additional anesthesia was administered to produce a lower BIS (51 +/- 19). The movement response rate was significantly higher in the control group at 43% compared with 13% in the BIS-guided group, but response rates were low at sites which used larger doses of opioids. Logistic regression analysis showed that BIS, estimated opioid effect-site concentrations, and heart rate (in that order) were the best predictors of movement at skin incision. This study demonstrates that dosing anesthetic drugs to lower BIS values achieves a lower probability of movement in response to surgical stimulation. BIS is a significant predictor of patient response to incision, but the utility of the BIS depends on the anesthetic technique being used. When drugs such as propofol or isoflurane are used as the primary anesthetic, changes in BIS correlate with the probability of response to skin incision. When opioid analgesics are used, the correlation to patient movement becomes much less significant, so that patients with apparently "light" EEG profiles may not move or otherwise respond to incision. Therefore, the adjunctive use of opioid analgesics confounds the use of BIS as a measure of anesthetic adequacy when movement response to skin incision is used as the primary end point. (Anesth Analg 1997;84:891-99)