Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of nuclear factor E2-related factor 2–mediated gene expression in mice liver and small intestine by cancer chemopreventive agent curcumin

Curcumin has been shown to prevent and inhibit carcinogen-induced tumorigenesis in different organs of rodent carcinogenesis models. Our objective is to study global gene expression profiles elicited by curcumin in mouse liver and small intestine as well as to identify curcumin-regulated nuclear factor E2-related factor 2 (Nrf2)–dependent genes. Wild-type C57BL/6J and Nrf2 knockout C57BL/6J/Nrf2(−/−) mice were given a single oral dose of curcumin at 1,000 mg/kg. Liver and small intestine were collected at 3 and 12 hours after treatments. Total RNA was extracted and analyzed using Affymetrix (Santa Clara, CA) mouse genome 430 array (45K) and GeneSpring 6.1 software (Silicon Genetics, Redwood City, CA). Genes that were induced or suppressed >2-fold by curcumin treatments compared with vehicle in wild-type mice but not in knockout mice were filtered using GeneSpring software and regarded as Nrf2-dependent genes. Among those well-defined genes, 822 (664 induced and 158 suppressed) and 222 (154 induced and 68 suppressed) were curcumin-regulated Nrf2-dependent genes identified in the liver and small intestine, respectively. Based on their biological functions, these genes can be classified into the category of ubiquitination and proteolysis, electron transport, detoxification, transport, apoptosis and cell cycle control, cell adhesion, kinase and phosphatase, and transcription factor. Many phase II detoxification/antioxidant enzyme genes, which are regulated by Nrf2, are among the identified genes. The identification of curcumin-regulated Nrf2-dependent genes not only provides potential novel insights into the biological effects of curcumin on global gene expression and chemoprevention but also points to the potential role of Nrf2 in these processes. [Mol Cancer Ther 2006;5(1):39–51]
Appropriate Models for the Management of Infectious Diseases

Background Mathematical models have become invaluable management tools for epidemiologists, both shedding light on the mechanisms underlying observed dynamics as well as making quantitative predictions on the effectiveness of different control measures. Here, we explain how substantial biases are introduced by two important, yet largely ignored, assumptions at the core of the vast majority of such models. Methods and Findings First, we use analytical methods to show that (i) ignoring the latent period or (ii) making the common assumption of exponentially distributed latent and infectious periods (when including the latent period) always results in underestimating the basic reproductive ratio of an infection from outbreak data. We then proceed to illustrate these points by fitting epidemic models to data from an influenza outbreak. Finally, we document how such unrealistic a priori assumptions concerning model structure give rise to systematically overoptimistic predictions on the outcome of potential management options. Conclusion This work aims to highlight that, when developing models for public health use, we need to pay careful attention to the intrinsic assumptions embedded within classical frameworks.
CD8+ T Cells Specific for Immunodominant Trans-Sialidase Epitopes Contribute to Control of Trypanosoma cruzi Infection but Are Not Required for Resistance

CD8+ T cells are essential for controlling Trypanosoma cruzi infection. During Brazil strain infection, C57BL/6 mice expand parasite-specific CD8+ T cells recognizing the dominant TSKB20 (ANYKFTLV) and subdominant TSKB74 (VNYDFTLV) trans-sialidase gene (TS)-encoded epitopes with up to 40% of all CD8+ T cells specific for these epitopes. Although this is one of the largest immunodominant T cell responses described for any infection, most mice fail to clear T. cruzi and subsequently develop chronic disease. To determine if immunodominant TS-specific CD8+ T cells are necessary for resistance to infection, we epitope-tolerized mice by high-dose i.v. injections of TSKB20 or TSKB74 peptides. Tolerance induction led to deletion of TS-specific CD8+ T cells but did not prevent the expansion of other effector CD8+ T cell populations. Mice tolerized against either TSKB20 or TSKB74, or both epitopes simultaneously, exhibited transient increases in parasite loads, although ultimately they controlled the acute infection. Furthermore, BALB/c mice tolerized against the TSKD14 peptide effectively controlled acute T. cruzi infection. These data are consistent with the hypothesis that development of high-frequency CD8+ T cell populations focused on TS-derived epitopes contributes to optimal control of acute infection but is not required for the development of immune resistance.
Aortic Pulse Wave Velocity Is Associated With the Presence and Quantity of Coronary Artery Calcium: A Community-Based Study

We investigated the relationship of aortic pulse wave velocity (aPWV), a measure of central arterial stiffness, with the presence and quantity of coronary artery calcium (CAC) in a community-based sample of adults without prior history of heart attack or stroke (n=401, mean age 59.8 years, 53% men). ECG-gated waveforms of the right carotid and right femoral artery were obtained by applanation tonometry, and aPWV was calculated using established methods. CAC was measured noninvasively by electron beam computed tomography, and CAC score was calculated. aPWV was significantly correlated with log(CAC +1; r=0.41; P<0.0001) and pulse pressure (r=0.47; P<0.0001). Multivariable logistic and linear regression models were used to identify independent predictors of the presence and quantity of CAC, respectively. In multivariable logistic regression analyses, aPWV was associated with the presence of CAC (P=0.011) after adjustment for age, male sex, total cholesterol, high-density lipoprotein cholesterol, diabetes, history of smoking, systolic blood pressure, body mass index, and use of hypertension and statin medications. In multivariable linear regression analyses, aPWV was significantly associated with log(CAC +1) after adjustment for the covariates enumerated above (P<0.0001). aPWV remained significantly associated with both the presence and quantity of CAC even after the additional adjustment for diastolic blood pressure. We conclude that aPWV is related to subclinical coronary atherosclerosis independent of conventional risk factors (including indices of blood pressure) and may be a biomarker of cardiovascular risk in asymptomatic individuals.
A MAXIMAL-CORRELATION APPROACH USING ICA FOR TESTING FUNCTIONAL NETWORK CONNECTIVITY APPLIED TO SCHIZOPHRENIA

There has been a growing interest in analyzing brain activation differences between patients and controls by studying resting-state fMRI brain networks. Functional connectivity of the resting brain has been studied by analyzing correlation differences in time courses among seed voxels, regions, or volume of interest with other voxels of the brain in patients versus controls. Spatial differences have also been analyzed among component maps derived from independent component analysis (ICA) in patients with schizophrenia and in healthy controls. However, the relationship among ICA component time courses, (which we define as functional network connectivity), has not been studied. We propose a novel technique to determine FNC applied to schizophrenia which does not rely on the time series of specific brain voxels or regions of interest and instead focuses upon the connectivity between functional networks (components) estimated from ICA using maximal correlation between component time series.
Novel Nosocomial Infections by Stenotrophomonas maltophilia: First Reported Case from Lucknow, North India

ABSTRACT We describe a case of empyema with infected ascites caused by Stenotrophomonas maltophilia, which has rarely been reported as pathogenic. The source was determined to a disinfectant solution. The isolate was sensitive to a newer carbapenem-meropenem, and the patient was treated successfully. This case represents a novel dual presentation of a nosocomial infection by the isolate in question.
Analysis of the interfacial interactions in polypropylene/silica nanocomposites

Polypropylene-based composites were prepared by melt blending with nano-silica, which was pre-treated by grafting polymerization onto the surface. Tensile moduli and strengths of the composites were determined as a function of the nano-silica content and the amount of the grafting polymers chemically attached to the nanoparticles, ie percentage grafting. To analyse the relationships between the interfacial interactions in the composites and tensile performance, a number of models dealing with the static and dynamic mechanical behaviours of the particulate composites were applied. It was found that stronger interfacial interactions exist in the grafted nano-silica-filled polypropylene composites as compared to the composites with untreated nano-silica. Since the interfacial interactions occur only within a very short range, the greatest interaction between the modified nanoparticles and the matrix is achieved in the case of low silica concentration and low percentage grafting. An increase in the percentage grafting for various grafted nanoparticles definitely results in an increase of interphase thickness, but the interfacial interactions and the tensile performance of the composites are not necessarily improved because the agglomeration structure of the nanoparticles and the miscibility between the components play the leading role. Copyright © 2004 Society of Chemical Industry
Isoflurane Is a Potent Modulator of Extrasynaptic GABAA Receptors in the Thalamus

Volatile anesthetics are used clinically to produce analgesia, amnesia, unconsciousness, blunted autonomic responsiveness, and immobility. Previous work has shown that the volatile anesthetic isoflurane, at concentrations that produce unconsciousness (250–500 μM), enhances fast synaptic inhibition in the brain mediated by GABAA receptors (GABAA-Rs). In addition, isoflurane causes sedation at concentrations lower than those required to produce unconsciousness or analgesia. In this study, we found that isoflurane, at low concentrations (25–85 μM) associated with its sedative actions, elicits a sustained current associated with a conductance increase in thalamocortical neurons in the mouse ventrobasal (VB) nucleus. These isoflurane-evoked currents reversed polarity close to the Cl– equilibrium potential and were totally blocked by the GABAA-R antagonist gabazine. Isoflurane (25–250 μM) produced no sustained current in VB neurons from GABAA-R α4-subunit knockout (Gabra4–/–) mice, although 250 μM isoflurane enhanced synaptic inhibition in VB neurons from both wild-type and Gabra4–/– mice. These data indicate an obligatory requirement for α4-subunit expression in the generation of the isoflurane-activated current. In addition, isoflurane directly activated α4β2δ GABAA-Rs expressed in human embryonic kidney 293 cells, and it was more potent at α4β2δ than at α1β2γ2 receptors (the presumptive extrasynaptic and synaptic GABAA-R subtypes in VB neurons). We conclude that the extrasynaptic GABAA-Rs of thalamocortical neurons are sensitive to low concentrations of isoflurane. In view of the crucial role of the thalamus in sensory processing, sleep, and cognition, the modulation of these extrasynaptic GABAA-Rs by isoflurane may contribute to the sedation and hypnosis associated with low doses of this anesthetic agent.
Radiation characteristics of extreme UV and soft X-ray sources

Electromagnetic radiation in the extreme UV and soft x-ray spectral range is of steadily increasing importance in fundamental research and industrial applications. For instance, the molecular structure of certain proteins and viruses has become accessible by coherent imaging techniques and already today, lithographic processes for the microchip production are being adapted to that wavelength range. For both examples, a comprehensive beam characterization is an essential condition for an ideal use of the available photons. Following that goal, this work addresses the pathway of extreme UV and soft x-ray radiation from its generation, through the beam transport by the beamline to the probe position. Experimentally, those aspects are optimized at a laser-produced plasma source and at an arrangement for the generation of high-harmonics. Additionally, the coherence of laser beams is analyzed by measurements of the Wigner distribution function. This method is applied to the photon beam of the free-electron laser FLASH, resulting in the entire characterization of its propagation properties. Z U S A M M E N FA S S U N G Elektromagnetische Strahlung im extremen UV und weichen Röntgenspektralbereich ist von stetig wachsender Bedeutung, sowohl im Bereich der Forschung als auch in industriellen Anwendungen. So konnte beispielsweise erstmals die Molekülstruktur bestimmter Proteine und Viren entschlüsselt werden und bereits heute werden die lithographischen Prozesse zur Herstellung von Mikrochips auf diesen Wellenlängenbereich adaptiert. Dabei ist eine umfassende Strahlcharakterisierung die Grundlage für eine ideale Nutzung der Photonen. Unter dieser Zielsetzung behandelt die vorliegende Arbeit den gesamten Weg der extremen UV und weichen Röntgenstrahlung, von ihrer Erzeugung, über die Strahlführung bis hin zur Probenposition. Experimentell werden diese Aspekte an einer Laser-produzierten Plasmaquelle beziehungsweise an einer Anordnung zur Erzeugung Hoher Harmonischen optimiert. Weiterhin wird die Kohärenz von Laserstrahlen anhand der Wigner Verteilungsfunktion analysiert. Die Methode wird auf den Photonenstrahl des Freie-Elektronen Lasers FLASH angewendet und liefert eine vollständige Beschreibung seiner Propagationseigenschaften.
CLEAVAGE FURROW FORMATION IN A TELOLECITHAL EGG (LOLIGO PEALII)

Formation of the first cleavage furrow in the telolecithal egg of Loligo was studied with the electron microscope. Before the actual furrow forms, a dense filamentous band develops below the plasma membrane from membrane-bounded dense bodies which appear to be Golgi-derived. The egg surface is thrown into a number of longitudinal folds which parallel the furrow and eventually become incorporated into it. These longitudinal folds contain a network of tubules and vesicles. Frequently, multivesiculate bodies are associated with the furrow and possibly give rise to the network of tubules and vesicles. Apparently part of the membrane between the two new blastomeres is derived from the surface of the longitudinal folds. The theory of furrow formation by contraction is discussed in light of the filamentous band.
Demography of Immigrant Youth: Past, Present, and Future

Jeffrey Passel surveys demographic trends and projections in the U.S. youth population, with an emphasis on trends among immigrant youth. He traces shifts in the youth population over the past hundred years, examines population projections through 2050, and offers some observations about the likely impact of the immigrant youth population on American society.Passel provides data on the legal status of immigrant youth and their families and on their geographic distribution and concentration across the United States. He emphasizes two demographic shifts. First, immigrant youth—defined as those children under age eighteen who are either foreign-born or U.S.-born to immigrant parents—now account for one-fourth of the nation's 75 million children. By 2050 they are projected to make up one-third of more than 100 million U.S. children. Second, the wave of immigration under way since the mid-1960s has made children the most racially and ethnically diverse age group in the United States. In 1960 Hispanic, Asian, and mixed-race youth made up about 6 percent of all U.S. children; today that share is almost 30 percent. During that same period the share of non-Hispanic white children steadily dropped from about 81 percent to 56 percent, while the share of black children climbed very slightly to 14 percent. By 2050 the share of non-Hispanic white children is projected to drop to 40 percent, while that of Hispanic children will increase to about one-third. This changing demographic structure in U.S. youth is likely to present policy makers with several challenges in coming decades, including higher rates of poverty among youth, particularly among foreign-born children and children of undocumented parents; high concentrations of immigrants in a handful of states; and a lack of political voice. A related challenge may be intergenerational competition between youth and the elderly for governmental support such as education funding, Social Security, and government health benefits. In conclusion, Passel notes that today's immigrants and their children will shape many aspects of American society and will provide virtually all the growth in the U.S. labor force over the next forty years. Their integration into American society and their accumulation of human capital thus require continued attention from researchers and policy makers.
PEITC-mediated inhibition of mRNA translation is associated with both inhibition of mTORC1 and increased eIF2α phosphorylation in established cell lines and primary human leukemia cells

Increased mRNA translation drives carcinogenesis and is an attractive target for the development of new anti-cancer drugs. In this work, we investigated effects of phenethylisothiocyanate (PEITC), a phytochemical with chemopreventive and anti-cancer activity, on mRNA translation. PEITC rapidly inhibited global mRNA translation in human breast cancer-derived MCF7 cells and mouse embryonic fibroblasts (MEFs). In addition to the known inhibitory effects of PEITC on mTORC1 activity, we demonstrate that PEITC increased eIF2α phosphorylation. PEITC also increased formation of stress granules which are typically associated with eIF2α phosphorylation and accumulation of translationally stalled mRNAs. Analysis of genetically modified MEFs demonstrated that optimal inhibition of global mRNA translation by PEITC was dependent on eIF2α phosphorylation, but not mTORC1 inhibition. We extended this study into primary leukemic B cells derived from patients with chronic lymphocytic leukaemia (CLL). CLL cells were stimulated in vitro with anti-IgM to mimic binding of antigen, a major driver of this leukemia. In CLL cells, PEITC increased eIF2α phosphorylation, inhibited anti-IgM-induced mTORC1 activation and decreased both basal and anti-IgM-induced global mRNA translation. PEITC also inhibited transcription and translation of MYC mRNA and accumulation of the MYC oncoprotein, in anti-IgM-stimulated cells. Moreover, treatment of CLL cells with PEITC and the BTK kinase inhibitor ibrutinib decreased anti-IgM-induced translation and induced cell death to a greater extent than either agent alone. Therefore, PEITC can inhibit both global and mRNA specific translation (including MYC) via effects on multiple regulatory pathways. Inhibition of mRNA translation may contribute to the chemopreventive and anti-cancer effects of PEITC.
Tomorrow's In-Car Interconnect? A Competitive Evaluation of IEEE 802.1 AVB and Time-Triggered Ethernet (AS6802)

Ethernet-based in-car communication is currently a hot topic in the automotive industry. Soon Ethernet will start to oust MOST bus in its domain of info- and entertainment applications. However, the full benefit of a technologically integrated in-car network will only become rewarding with the deployment of an Ethernet-based backbone that integrates all automotive domains on a single layer at increased bandwidth, reduced complexity and cost, while opening car intelligence for future innovations. Such backbone must transport critical control data in real-time. Standard Ethernet requires extensions to comply with the strict timing requirements of driver assistance and safety applications while simultaneously supporting broadband multimedia traffic. In this paper, we compare IEEE 802.1 AVB and Time-triggered Ethernet, two competing real-time approaches. While the first fosters over- provisioning and prioritisation, the second is based on a coordinated time-division-multiple-access (TDMA) policy for media access. By simulating a realistic in-car backbone design and traffic model, we reveal the strengths and weaknesses of both protocols and point to the diverging characteristics of event- and time-triggered policies. Our results show that in this in-car network scenario both protocols are able to meet the rigid timing requirements, while each has its unique benefits and disadvantages.
The Effect of Central Loops in miRNA:MRE Duplexes on the Efficiency of miRNA-Mediated Gene Regulation

MicroRNAs (miRNAs) guide posttranscriptional repression of mRNAs. Hundreds of miRNAs have been identified but the target identification of mammalian mRNAs is still a difficult task due to a poor understanding of the interaction between miRNAs and the miRNA recognizing element (MRE). In recent research, the importance of the 5′ end of the miRNA:MRE duplex has been emphasized and the effect of the tail region addressed, but the role of the central loop has largely remained unexplored. Here we examined the effect of the loop region in miRNA:MRE duplexes and found that the location of the central loop is one of the important factors affecting the efficiency of gene regulation mediated by miRNAs. It was further determined that the addition of a loop score combining both location and size as a new criterion for predicting MREs and their cognate miRNAs significantly decreased the false positive rates and increased the specificity of MRE prediction.
Use of an electronic nose for the early detection and differentiation between spoilage fungi

Six spoilage fungi (four Eurotium species, a Penicillium sp. and Wallemia sebi) were grown as spore lawn surface cultures at 0·95 water activity and 25 °C. Prior to and during visible growth (24 and 48, and 72 h), single cultures were enclosed in polyethylene bags, the head space was sampled with an electronic nose unit, consisting of 14 polymer sensors, and the data analysed. There was good replication between volatile patterns of the same species and using principal component, discriminant function and cluster analyses it was possible to differentiate between the agar blanks, three Eurotium spp. , the Penicillium sp. and W. sebi during microscopic growth for the first time. This suggests that there is potential for the early detection of the activity of spoilage fungi in general, as well as possible differentiation between related xerophilic spoilage fungi, by detection of the patterns of volatile odours produced using an electronic nose system.
Self-motion signals in vestibular nuclei neurons projecting to the thalamus in the alert squirrel monkey.

Sixty vestibular nuclei neurons antidromically activated by electrical stimulation of the ventroposterior thalamus were recorded in two alert squirrel monkeys. The majority of these neurons were monosynaptically activated by vestibular nerve electrical stimulation. Forty-seven neurons responded to animal rotations around the earth-vertical axis; 16 of them also responded to translations in the horizontal plane. The mean sensitivity to 0.5-Hz rotations of 80 degrees /s velocity was 0.40 +/- 0.31 spikes.s(-1). deg(-1). s(-1). Rotational responses were in phase with stimulus velocity. Sensitivities to 0.5-Hz translations of 0.1 g acceleration varied from 92.2 to 359 spikes.s(-1). g(-1) and response phases varied from 10.1 degrees lead to -98 degrees lag. The firing behavior in 28 neurons was studied during rotation of the whole animal, of the trunk, and voluntary and involuntary rotations of the head. Two classes of vestibulothalamic neurons were distinguished. One class of neurons generated signals related to movement of the head that were similar either when the head and trunk move together or when the head moves on the stationary trunk. A fraction of these neurons fired during involuntary head movements only. A second class of neurons generated signals related to movement of the trunk. They responded when the trunk moved alone or simultaneously with the head, but did not respond to head rotations while the trunk was stationary.