Sample records for suhtlustarkvarad skype msn

  1. Web conferencing systems: Skype and MSN in telepathology

    PubMed Central

    Klock, Clóvis; Gomes, Regina de Paula Xavier

    2008-01-01

    Virtual pathology is a very important tool that can be used in several ways, including interconsultations with specialists in many areas and for frozen sections. We considered in this work the use of Windows Live Messenger and Skype for image transmission. The conference was made through wide broad internet using Nikon E 200 microscope and Digital Samsung Colour SCC-131 camera. Internet speed for transmission varied from 400 Kb to 2.0 Mb. Both programs allow voice transmission concomitant to image, so the communication between the involved pathologists was possible using microphones and speakers. Alive image could be seen by the receptor pathologist who was able to ask for moving the field or increase/diminish the augmentation. No phone call or typing required. The programs MSN and Skype can be used in many ways and with different operational systems installed in the computer. The capture system is simple and relatively cheap, what proves the viability of the system to be used in developing countries and in cities where do not exist pathologists. With the improvement of software and the improvement of digital image quality, associated to the use of the high speed broad band Internet this will be able to become a new modality in surgical pathology. PMID:18673501

  2. Web conferencing systems: Skype and MSN in telepathology.

    PubMed

    Klock, Clóvis; Gomes, Regina de Paula Xavier

    2008-07-15

    Virtual pathology is a very important tool that can be used in several ways, including interconsultations with specialists in many areas and for frozen sections. We considered in this work the use of Windows Live Messenger and Skype for image transmission. The conference was made through wide broad internet using Nikon E 200 microscope and Digital Samsung Colour SCC-131 camera. Internet speed for transmission varied from 400 Kb to 2.0 Mb. Both programs allow voice transmission concomitant to image, so the communication between the involved pathologists was possible using microphones and speakers. A live image could be seen by the receptor pathologist who was able to ask for moving the field or increase/diminish the augmentation. No phone call or typing required. The programs MSN and Skype can be used in many ways and with different operational systems installed in the computer. The capture system is simple and relatively cheap, what proves the viability of the system to be used in developing countries and in cities where do not exist pathologists. With the improvement of software and the improvement of digital image quality, associated to the use of the high speed broad band Internet this will be able to become a new modality in surgical pathology.

  3. Comparing Six Video Chat Tools: A Critical Evaluation by Language Teachers

    ERIC Educational Resources Information Center

    Eroz-Tuga, Betil; Sadler, Randall

    2009-01-01

    This article presents a critical comparison of the usefulness and practicality of six CMC video chat tools (CUworld, ICQ, MSN Messenger, Paltalk, Skype, and Yahoo Messenger) from the perspective of language teaching professionals. This comparison is based on the results of a semester-long project between graduate students at an American university…

  4. Identifying hidden voice and video streams

    NASA Astrophysics Data System (ADS)

    Fan, Jieyan; Wu, Dapeng; Nucci, Antonio; Keralapura, Ram; Gao, Lixin

    2009-04-01

    Given the rising popularity of voice and video services over the Internet, accurately identifying voice and video traffic that traverse their networks has become a critical task for Internet service providers (ISPs). As the number of proprietary applications that deliver voice and video services to end users increases over time, the search for the one methodology that can accurately detect such services while being application independent still remains open. This problem becomes even more complicated when voice and video service providers like Skype, Microsoft, and Google bundle their voice and video services with other services like file transfer and chat. For example, a bundled Skype session can contain both voice stream and file transfer stream in the same layer-3/layer-4 flow. In this context, traditional techniques to identify voice and video streams do not work. In this paper, we propose a novel self-learning classifier, called VVS-I , that detects the presence of voice and video streams in flows with minimum manual intervention. Our classifier works in two phases: training phase and detection phase. In the training phase, VVS-I first extracts the relevant features, and subsequently constructs a fingerprint of a flow using the power spectral density (PSD) analysis. In the detection phase, it compares the fingerprint of a flow to the existing fingerprints learned during the training phase, and subsequently classifies the flow. Our classifier is not only capable of detecting voice and video streams that are hidden in different flows, but is also capable of detecting different applications (like Skype, MSN, etc.) that generate these voice/video streams. We show that our classifier can achieve close to 100% detection rate while keeping the false positive rate to less that 1%.

  5. Testing Skype as an interview method in epidemiologic research: response and feasibility.

    PubMed

    Weinmann, Tobias; Thomas, Silke; Brilmayer, Susanne; Heinrich, Sabine; Radon, Katja

    2012-12-01

    Despite its popularity, Skype has not been tested as a tool for epidemiologic research. We examined its feasibility in Germany. A population-based sample of young adults was randomly invited to a Skype (n = 150) or a phone interview (n = 150). Response and duration of interviews were analysed to evaluate the feasibility of Skype interviews. Response was low and, with 10 % (95 % CI 5-15 %), even worse among Skype candidates, compared to 22 % (15-28 %) in the phone group. A third of the Skype group asked for being interviewed by phone. Median duration was 34.0 minutes for Skype interviews and 37.0 minutes for phone interviews. Skype is not yet a feasible tool for data collection in Germany.

  6. Design and implementation of Skype USB user gateway software

    NASA Astrophysics Data System (ADS)

    Qi, Yang

    2017-08-01

    With the widespread application of VoIP, the client with private protocol becomes more and more popular. Skype is one of the representatives. How to connect Skype with PSTN just by Skype client has gradually become hot. This paper design and implement the software based on a kind of USB User Gateway. With the software Skype user can freely communicate with PSTN phone. FSM is designed as the core of the software, and Skype control is separated by the USB Gateway control. In this way, the communication becomes more flexible and efficient. In the actual user testing, the software obtains good results.

  7. Clinical use of Skype: a review of the evidence base.

    PubMed

    Armfield, Nigel R; Gray, Leonard C; Smith, Anthony C

    2012-04-01

    Skype is a popular and free software application that allows PCs and mobile devices to be used for video communication over the Internet. We reviewed the literature to determine whether the clinical use of Skype is supported by evidence. One small (n = 7) controlled clinical trial had assessed the effect of nursing communication using Skype on elderly patients with dementia and their carers. However, we were unable to identify any large, well-designed studies which had formally evaluated the safety, clinical effectiveness, security and privacy of Skype for the routine delivery of patient care. While there were many case reports and small studies, no firm evidence either in favour of, or against the use of Skype for clinical telehealth was found. The risks and benefits of using Skype for clinical purposes are not known.

  8. Skype and Podcasting: Disruptive Technologies for Language Learning

    ERIC Educational Resources Information Center

    Godwin-Jones, Robert

    2005-01-01

    This article describes two emerging technologies--Skype and podcasting. Both Skype and podcasting can be considered "disruptive technologies" in that they allow for new and different ways of doing familiar tasks, and in the process, may threaten traditional industries. Skype, the "people's telephone," is a free, Internet-based alternative to…

  9. The stress-regulatory transcription factors Msn2 and Msn4 regulate fatty acid oxidation in budding yeast.

    PubMed

    Rajvanshi, Praveen Kumar; Arya, Madhuri; Rajasekharan, Ram

    2017-11-10

    The transcription factors Msn2 and Msn4 (multicopy suppressor of SNF1 mutation proteins 2 and 4) bind the stress-response element in gene promoters in the yeast Saccharomyces cerevisiae However, the roles of Msn2/4 in primary metabolic pathways such as fatty acid β-oxidation are unclear. Here, in silico analysis revealed that the promoters of most genes involved in the biogenesis, function, and regulation of the peroxisome contain Msn2/4-binding sites. We also found that transcript levels of MSN2/MSN4 are increased in glucose-depletion conditions and that during growth in nonpreferred carbon sources, Msn2 is constantly localized to the nucleus in wild-type cells. Of note, the double mutant msn2 Δ msn4 Δ exhibited a severe growth defect when grown with oleic acid as the sole carbon source and had reduced transcript levels of major β-oxidation genes. ChIP indicated that Msn2 has increased occupancy on the promoters of β-oxidation genes in glucose-depleted conditions, and in vivo reporter gene analysis indicated reduced expression of these genes in msn2 Δ msn4 Δ cells. Moreover, mobility shift assays revealed that Msn4 binds β-oxidation gene promoters. Immunofluorescence microscopy with anti-peroxisome membrane protein antibodies disclosed that the msn2 Δ msn4 Δ strain had fewer peroxisomes than the wild type, and lipid analysis indicated that the msn2 Δ msn4 Δ strain had increased triacylglycerol and steryl ester levels. Collectively, our data suggest that Msn2/Msn4 transcription factors activate expression of the genes involved in fatty acid oxidation. Because glucose sensing, signaling, and fatty acid β-oxidation pathways are evolutionarily conserved throughout eukaryotes, the msn2 Δ msn4 Δ strain could therefore be a good model system for further study of these critical processes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Professors and Students Ask Colleges Not to Hang up on Skype

    ERIC Educational Resources Information Center

    Woo, Stu

    2006-01-01

    San Jose State University is planning to ban Skype, a popular Internet telephone service, from the campus network because of concerns about security and bandwidth. University administrators say that the technical aspects that make Skype effective also make it dangerous and potentially crippling to a university's network bandwidth. Skype has a…

  11. The Saccharomyces cerevisiae zinc finger proteins Msn2p and Msn4p are required for transcriptional induction through the stress response element (STRE).

    PubMed Central

    Martínez-Pastor, M T; Marchler, G; Schüller, C; Marchler-Bauer, A; Ruis, H; Estruch, F

    1996-01-01

    The MSN2 and MSN4 genes encode homologous and functionally redundant Cys2His2 zinc finger proteins. A disruption of both MSN2 and MSN4 genes results in a higher sensitivity to different stresses, including carbon source starvation, heat shock and severe osmotic and oxidative stresses. We show that MSN2 and MSN4 are required for activation of several yeast genes such as CTT1, DDR2 and HSP12, whose induction is mediated through stress-response elements (STREs). Msn2p and Msn4p are important factors for the stress-induced activation of STRE dependent promoters and bind specifically to STRE-containing oligonucleotides. Our results suggest that MSN2 and MSN4 encode a DNA-binding component of the stress responsive system and it is likely that they act as positive transcription factors. Images PMID:8641288

  12. See Me, Hear Me: Skype in the Classroom

    ERIC Educational Resources Information Center

    Foote, Carolyn

    2008-01-01

    In this article, the author describes how she was able to allow her students to talk with author Cynthia Leitich Smith through Skype, a free Internet telephony service. The author also describes how Skype can be used for recording podcasts and enhancing the reference services of libraries. Here, the author shares ideas on using Skype in libraries.

  13. The clinical use of Skype--For which patients, with which problems and in which settings? A snapshot review of the literature.

    PubMed

    Armfield, Nigel R; Bradford, Madeleine; Bradford, Natalie K

    2015-10-01

    Low-cost and no-cost software-based video tools may be a feasible and effective way to provide some telemedicine services, particularly in low-resource settings. One of the most popular tools is Skype; it is freely available, may be installed on many types of devices, and is easy to use by clinicians and patients. While a previous review found no evidence in favor of, or against the clinical use of Skype, anecdotally it is believed to be widely used in healthcare for providing clinical services. However, the range of clinical applications in which Skype has been used has not been described. We aimed to identify and summarize the clinical applications of Skype. We reviewed the literature to identify studies that reported the use of Skype in clinical care or clinical education. We searched three electronic databases using the single search term "Skype". We found 239 unique articles. Twenty seven of the articles met our criteria for further review. The use of Skype was most prevalent in the management of chronic diseases such as cardiovascular diseases and diabetes, followed by educational and speech and language pathology applications. Most reported uses were in developed countries. In all but one case, Skype was reported by the authors to be feasible and to have benefit. However, while Skype may be a pragmatic approach to providing telemedicine services, in the absence of formal studies, the clinical and economic benefits remain unclear. Copyright © 2015. Published by Elsevier Ireland Ltd.

  14. A qualitative study of the use of Skype for psychotherapy consultations in the Ukraine.

    PubMed

    Edirippulige, Sisira; Levandovskaya, Marina; Prishutova, Anna

    2013-10-01

    There has been rather limited use of Skype for health and medical purposes. We investigated the use of Skype for delivering psychotherapy services in the Ukraine. A provider questionnaire was distributed to all delegates (n = 50) at the Annual Symposium of Psychotherapists. One copy of a client questionnaire was also given to each service provider and they were instructed to request their next client to complete the survey. In total, 29 providers and 23 clients responded to the questionnaire. The majority of clients (61%) and providers (72%) had used Skype for a range of services. The services they provided were related to a wide range of paradigms including psycho-analysis, psycho-drama, Gestalt therapy, cognitive behavioural therapy and existential therapy. A key reason for using Skype was to allow practitioners to contact clients who were not easily accessible, e.g. those who lived in other countries. Most practitioners (n = 24) thought their clients considered the services received on Skype were good or excellent. All 26 practitioners charged for Skype consultations. The majority of clients and providers showed high satisfaction with the use of Skype for psychotherapy services.

  15. Use of Skype in interviews: the impact of the medium in a study of mental health nurses.

    PubMed

    Oates, Jennifer

    2015-03-01

    To discuss the use of Skype as a medium for undertaking semi-structured interviews. Internet-based research is becoming increasingly popular, as communication using the internet takes a bigger role in our working and personal lives. Technology such as Skype allows research encounters with people across geographical divides. The semi-structured interview is a social encounter with a set of norms and expectations for both parties ( Doody and Noonan 2012 ). Proceedings must take account of the social context of both semi-structured interviews per se, and that of internet mediated communication. The findings of the qualitative phase of a mixed-methods study are compared with other reports comparing the use of Skype with face-to-face and telephone interviews. This paper is a methodological discussion of the use of Skype as an online research methodology. Choosing Skype as a means of interviewing may affect the characteristics of participants and decisions about consent. Rapport, sensitivity and collaboration may be addressed differently in Skype interviews compared with face-to-face interviews. Skype offers researchers the opportunity to reach a geographical spread of participants more safely, cheaply and quickly than face-to-face meetings. Rapport, sensitivity and degrees of collaboration can be achieved using this medium. The use of Skype as a medium for semi-structured interview research is better understood. This paper contributes to the growing body of literature on the use of the internet as a medium for research by nurses.

  16. Mesoporous silica nanoparticles functionalized with hyaluronic acid. Effect of the biopolymer chain length on cell internalization.

    PubMed

    Nairi, Valentina; Magnolia, Silvia; Piludu, Marco; Nieddu, Mariella; Caria, Cristian Antonio; Sogos, Valeria; Vallet-Regì, Maria; Monduzzi, Maura; Salis, Andrea

    2018-02-12

    Mesoporous silica nanoparticles (MSNs) were functionalized with amino groups (MSN-NH 2 ) and then with hyaluronic acid, a biocompatible biopolymer which can be recognized by CD44 receptors in tumor cells, to obtain a targeting drug delivery system. To this purpose, three hyaluronic acid samples differing for the molecular weight, namely HA S (8-15 kDa), HA M (30-50 kDa) and HA L (90-130 kDa), were used. The MSN-HA S , MSN-HA M , and MSN-HA L materials were characterized through zeta potential and dynamic light scattering measurements at pH = 7.4 and T = 37 °C to simulate physiological conditions. While zeta potential showed an increasing negative value with the increase of the HA chain length, an anomalous value of the hydrodynamic diameter was observed for MSN-HA L , which was smaller than that of MSN-HA S and MSN-HA M samples. The cellular uptake of MSN-HA samples on HeLa cells at 37 °C was studied by optical and electron microscopy. HA chain length affected significantly the cellular uptake that occurred at a higher extent for MSN-NH 2 and MSN-HA S than for MSN-HA M and MSN-HA L samples. Cellular uptake experiments carried out at 4 °C showed that the internalization process was inhibited for MSN-HA samples but not for MSN-NH 2 . This suggests the occurrence of two different mechanisms of internalization. For MSN-NH 2 the uptake is mainly driven by the attractive electrostatic interaction with membrane phospholipids, while MSN-HA internalization involves CD44 receptors overexpressed in HeLa cells. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Mesoporous silica nanoparticles for efficient rivastigmine hydrogen tartrate delivery into SY5Y cells.

    PubMed

    Karimzadeh, Mahmonir; Rashidi, Ladan; Ganji, Fariba

    2017-04-01

    Rivastigmine hydrogen tartrate (RT) is a molecule with both hydrophilic and hydrophobic properties used for the treatment of the Alzheimer's disease. In this work, the larger pore size of mesoporous silica nanoparticles (P1-MSN) was synthesized and then, P1-MSN were functionalized by succinic anhydride (S-P1-MSN) and 3-aminopropyltriethoxysilane (APTES) (AP-CO-P1-MSN) using the grafting and co-condensation methods, respectively. A new method was used for the functionalization of P1-MSN by succinic anhydride at room temperature. Nanoparticles were characterized by special instrumental analysis and loaded by RT. Maximum entrapment efficiency and RT loading percentage into P1-MSN, AP-CO-P1-MSN and S-P1-MSN were respectively obtained as 21.26 and 25.5%, 41.5 and 49.8%, and 11.9 and 14.28% for 24 h. In the simulated gastric and body fluids, the release rate of RT-loaded AP-CO-P1-MSN (AP-CO-P1-MSN-RT) was lower than that of other RT-loaded nanoparticles. In oral pathway, the sustained release of RT was observed in AP-CO-P1-MSN-RT. Moreover, no cytotoxicity effect was observed for P1-MSN, but the cells treated by AP-CO-P1-MSN showed a reduction in SY5Y cell viability due to easy entrance of these nanoparticles and their accumulation in different parts of the cell as observed by TEM.

  18. The Ste20 kinase misshapen regulates both photoreceptor axon targeting and dorsal closure, acting downstream of distinct signals.

    PubMed

    Su, Y C; Maurel-Zaffran, C; Treisman, J E; Skolnik, E Y

    2000-07-01

    We have previously shown that the Ste20 kinase encoded by misshapen (msn) functions upstream of the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase module in Drosophila. msn is required to activate the Drosophila JNK, Basket (Bsk), to promote dorsal closure of the embryo. A mammalian homolog of Msn, Nck interacting kinase, interacts with the SH3 domains of the SH2-SH3 adapter protein Nck. We now show that Msn likewise interacts with Dreadlocks (Dock), the Drosophila homolog of Nck. dock is required for the correct targeting of photoreceptor axons. We have performed a structure-function analysis of Msn in vivo in Drosophila in order to elucidate the mechanism whereby Msn regulates JNK and to determine whether msn, like dock, is required for the correct targeting of photoreceptor axons. We show that Msn requires both a functional kinase and a C-terminal regulatory domain to activate JNK in vivo in Drosophila. A mutation in a PXXP motif on Msn that prevents it from binding to the SH3 domains of Dock does not affect its ability to rescue the dorsal closure defect in msn embryos, suggesting that Dock is not an upstream regulator of msn in dorsal closure. Larvae with only this mutated form of Msn show a marked disruption in photoreceptor axon targeting, implicating an SH3 domain protein in this process; however, an activated form of Msn is not sufficient to rescue the dock mutant phenotype. Mosaic analysis reveals that msn expression is required in photoreceptors in order for their axons to project correctly. The data presented here genetically link msn to two distinct biological events, dorsal closure and photoreceptor axon pathfinding, and thus provide the first evidence that Ste20 kinases of the germinal center kinase family play a role in axonal pathfinding. The ability of Msn to interact with distinct classes of adapter molecules in dorsal closure and photoreceptor axon pathfinding may provide the flexibility that allows it to link to distinct upstream signaling systems.

  19. The Ste20 Kinase Misshapen Regulates Both Photoreceptor Axon Targeting and Dorsal Closure, Acting Downstream of Distinct Signals

    PubMed Central

    Su, Yi-Chi; Maurel-Zaffran, Corinne; Treisman, Jessica E.; Skolnik, Edward Y.

    2000-01-01

    We have previously shown that the Ste20 kinase encoded by misshapen (msn) functions upstream of the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase module in Drosophila. msn is required to activate the Drosophila JNK, Basket (Bsk), to promote dorsal closure of the embryo. A mammalian homolog of Msn, Nck interacting kinase, interacts with the SH3 domains of the SH2-SH3 adapter protein Nck. We now show that Msn likewise interacts with Dreadlocks (Dock), the Drosophila homolog of Nck. dock is required for the correct targeting of photoreceptor axons. We have performed a structure-function analysis of Msn in vivo in Drosophila in order to elucidate the mechanism whereby Msn regulates JNK and to determine whether msn, like dock, is required for the correct targeting of photoreceptor axons. We show that Msn requires both a functional kinase and a C-terminal regulatory domain to activate JNK in vivo in Drosophila. A mutation in a PXXP motif on Msn that prevents it from binding to the SH3 domains of Dock does not affect its ability to rescue the dorsal closure defect in msn embryos, suggesting that Dock is not an upstream regulator of msn in dorsal closure. Larvae with only this mutated form of Msn show a marked disruption in photoreceptor axon targeting, implicating an SH3 domain protein in this process; however, an activated form of Msn is not sufficient to rescue the dock mutant phenotype. Mosaic analysis reveals that msn expression is required in photoreceptors in order for their axons to project correctly. The data presented here genetically link msn to two distinct biological events, dorsal closure and photoreceptor axon pathfinding, and thus provide the first evidence that Ste20 kinases of the germinal center kinase family play a role in axonal pathfinding. The ability of Msn to interact with distinct classes of adapter molecules in dorsal closure and photoreceptor axon pathfinding may provide the flexibility that allows it to link to distinct upstream signaling systems. PMID:10848599

  20. Skype: a tool for functional assessment in orthopaedic research.

    PubMed

    Good, Daniel W; Lui, Darren F; Leonard, Michael; Morris, Seamus; McElwain, John P

    2012-03-01

    Skype is a free program which enables PC users to make video calls to other users with Internet access. We carried out a prospective review of all acromioclavicular joint hook plates for lateral-third clavicle fractures over a five-year period. Functional assessment with Oxford and Constant shoulder scores were carried out using Skype and compared to outpatient review using the Bland-Altman method. Of 36 patients (mean age 36 years), 33 had a computer with a video camera, all 33 had Internet access and 22 were already users of Skype. In total 29 patients were happy to take part in Skype assessment (83%). In comparison with outpatient review, there was a mean difference in the Oxford score of -0.48 (95% confidence interval -0.84, -0.12); the mean difference for the Constant score was -0.68 (95% confidence interval -1.08, -0.29). These differences were not clinically significant, confirming that Skype can be used as an alternative to goniometry in this clinical setting. A survey showed that 93% of 29 patients surveyed preferred the use of Skype for follow-up, mainly due to the convenience and cost-saving involved. The study demonstrates the potential for this new technique in providing patients with more options for follow-up.

  1. The use of Skype in analysis and training: a research and literature review.

    PubMed

    Merchant, John

    2016-06-01

    Of recent years there has not only been an increasing use of Skype in analytic treatment, supervision and teaching, but also a number of writers have been endeavouring to assess its effectiveness. Whilst it is generally agreed that Skype can facilitate an analytic encounter where distance prohibits a face-to-face process, where continuity needs to be maintained and where analysands are in areas far from specialized centres, there is divergence in the literature as to whether analysis, as opposed to psychotherapy, can be successful using Skype. This paper reviews the literature and concludes that the essentials of a genuine analytic process are not necessarily precluded by Skype. One central reason is because there exists a cross-modal communication channel between the human senses (underpinned by audiovisual mirror neurons) in addition to the recently discovered instinct for communication and interpersonal understanding, and these can override the need for physical proximity of the participants. The essentials of an analytic frame can thus be maintained, and the continuity that Skype enables means that containment is also facilitated and this counters the negative aspects of shuttle analysis. The critical issues for the profession then become the professional development for practitioners in the use of Skype and suggestions are listed. © 2016, The Society of Analytical Psychology.

  2. Glycyrrhetinic acid-functionalized mesoporous silica nanoparticles as hepatocellular carcinoma-targeted drug carrier.

    PubMed

    Lv, Yongjiu; Li, Jingjing; Chen, Huali; Bai, Yan; Zhang, Liangke

    2017-01-01

    In this study, a glycyrrhetinic acid-functionalized mesoporous silica nanoparticle (MSN-GA) was prepared for active tumor targeting. MSN-GA exhibited satisfactory loading capacity for insoluble drugs, uniform size distribution, and specific tumor cell targeting. Glycyrrhetinic acid, a hepatocellular carcinoma-targeting group, was covalently decorated on the surface of MSN via an amido bond. The successful synthesis of MSN-GA was validated by the results of Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), and zeta potential measurement. TEM images revealed the spherical morphology and uniform size distribution of the naked MSN and MSN-GA. Curcumin (CUR), an insoluble model drug, was loaded into MSN-GA (denoted as MSN-GA-CUR) with a high-loading capacity (8.78%±1.24%). The results of the in vitro cellular experiment demonstrated that MSN-GA-CUR significantly enhanced cytotoxicity and cellular uptake toward hepatocellular carcinoma (HepG2) cells via a specific GA receptor-mediated endocytosis mechanism. The results of this study provide a promising nanoplatform for the targeting of hepatocellular carcinoma.

  3. Technology in the Classroom: Using Skype for Exciting Projects

    ERIC Educational Resources Information Center

    Morgan, Hani

    2013-01-01

    Many teachers are organizing interactive Skype sessions. By taking advantage of Skype to allow students to interact with guests outside the classroom, sometimes thousands of miles away, teachers from all over the world are creating new opportunities for students to make academic gains in a motivating way. In this article, the author discusses the…

  4. Modified mesoporous silica nanoparticles for enhancing oral bioavailability and antihypertensive activity of poorly water soluble valsartan.

    PubMed

    Biswas, Nikhil

    2017-03-01

    The aim was to improve the oral bioavailability and antihypertensive activity of poorly soluble drug valsartan (VAL) by modifying the design and delivery of mesoporous silica nanoparticles (MSNs). The synthesized MSNs were functionalized with aminopropyl groups (AP-MSN) through postsynthesis and coated with pH sensitive polymer Eudragit L100-55 (AP-MSN-L100-55) for pH dependant sustain release of anionic VAL. MSNs were characterized by Brauner-Emmett-Teller (BET) surface area analyzer, zeta sizer, Field Emission Scanning Electron Microscope (FESEM), Powder X-Ray Diffraction (PXRD) and Differential Scanning Calorimetry (DSC). Functionalized MSNs showed highest entrapment efficiency (59.77%) due to strong ionic interaction with VAL. In vitro dissolution of M-MSN [MSN-VAL and AP-MSN-VAL-L100-55 mixed equally] at physiological conditions demonstrated immediate release (MSN-VAL fraction) followed by sustained release (AP-MSN-VAL-L100-55 fraction) of 96% VAL in 960min. The dramatic improvement in dissolution was attributed to the amorphization of crystalline VAL by MSNs as evidenced by DSC and PXRD studies. No noticeable cytotoxicity was observed for MSN, AP-MSN and AP-MSN-L100-55 in MTT assay. Pharmacokinetic study of M-MSN confirmed 1.82 fold increases in bioavailability compared to commercial Diovan tablet in fasted male rabbits. Blood pressure monitoring in rats showed that the morning dosing of Diovan tablet efficiently controlled BP for just over 360min whereas the effect of M-MSN lasted for >840min. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity

    PubMed Central

    Görner, Wolfram; Durchschlag, Erich; Martinez-Pastor, Maria Teresa; Estruch, Francisco; Ammerer, Gustav; Hamilton, Barbara; Ruis, Helmut; Schüller, Christoph

    1998-01-01

    Msn2p and the partially redundant factor Msn4p are key regulators of stress-responsive gene expression in Saccharomyces cerevisiae. They are required for the transcription of a number of genes coding for proteins with stress-protective functions. Both Msn2p and Msn4p are Cys2His2 zinc finger proteins and bind to the stress response element (STRE). In vivo footprinting studies show that the occupation of STREs is enhanced in stressed cells and dependent on the presence of Msn2p and Msn4p. Both factors accumulate in the nucleus under stress conditions, such as heat shock, osmotic stress, carbon-source starvation, and in the presence of ethanol or sorbate. Stress-induced nuclear localization was found to be rapid, reversible, and independent of protein synthesis. Nuclear localization of Msn2p and Msn4p was shown to be correlated inversely to cAMP levels and protein kinase A (PKA) activity. A region with significant homologies shared between Msn2p and Msn4p is sufficient to confer stress-regulated localization to a SV40–NLS–GFP fusion protein. Serine to alanine or aspartate substitutions in a conserved PKA consensus site abolished cAMP-driven nuclear export and cytoplasmic localization in unstressed cells. We propose stress and cAMP-regulated intracellular localization of Msn2p to be a key step in STRE-dependent transcription and in the general stress response. PMID:9472026

  6. Induction of neutral trehalase Nth1 by heat and osmotic stress is controlled by STRE elements and Msn2/Msn4 transcription factors: variations of PKA effect during stress and growth.

    PubMed

    Zähringer, H; Thevelein, J M; Nwaka, S

    2000-01-01

    Saccharomyces cerevisiae neutral trehalase, encoded by NTH1, controls trehalose hydrolysis in response to multiple stress conditions, including nutrient limitation. The presence of three stress responsive elements (STREs, CCCCT) in the NTH1 promoter suggested that the transcriptional activator proteins Msn2 and Msn4, as well as the cAMP-dependent protein kinase (PKA), control the stress-induced expression of Nth1. Here, we give direct evidence that Msn2/Msn4 and the STREs control the heat-, osmotic stress- and diauxic shift-dependent induction of Nth1. Disruption of MSN2 and MSN4 abolishes or significantly reduces the heat- and NaCl-induced increases in Nth1 activity and transcription. Stress-induced increases in activity of a lacZ reporter gene put under control of the NTH1 promoter is nearly absent in the double mutant. In all instances, basal expression is also reduced by about 50%. The trehalose concentration in the msn2 msn4 double mutant increases less during heat stress and drops more slowly during recovery than in wild-type cells. This shows that Msn2/Msn4-controlled expression of enzymes of trehalose synthesis and hydrolysis help to maintain trehalose concentration during stress. However, the Msn2/Msn4-independent mechanism exists for heat control of trehalose metabolism. Site-directed mutagenesis of the three STREs (CCCCT changed to CATCT) in NTH1 promoter fused to a reporter gene indicates that the relative proximity of STREs to each other is important for the function of NTH1. Elimination of the three STREs abolishes the stress-induced responses and reduces basal expression by 30%. Contrary to most STRE-regulated genes, the PKA effect on the induction of NTH1 by heat and sodium chloride is variable. During diauxic growth, NTH1 promoter-controlled reporter activity strongly increases, as opposed to the previously observed decrease in Nth1 activity, suggesting a tight but opposite control of the enzyme at the transcriptional and post-translational levels. Apparently, inactive trehalase is accumulated concomitant with the accumulation of trehalose. These results might help to elucidate the general connection between control by STREs, Msn2/Msn4 and PKA and, in particular, how these components play a role in control of trehalose metabolism.

  7. Effect of amino groups of mesoporous silica nanoparticles on CpG oligodexynucleotide delivery

    NASA Astrophysics Data System (ADS)

    Xu, Yi; Claiden, Peter; Zhu, Yufang; Morita, Hiromi; Hanagata, Nobutaka

    2015-08-01

    In this study, we proposed to modify mesoporous silica nanoparticles (MSNs) with 3-aminopropyltriethoxysilane (NH2-TES), aminoethylaminopropyltriethoxysilane (2NH2-TES) and 3-[2-(2-aminoethylamino)ethylamino] propyl-trimethoxysilane (3NH2-TES) for binding of cytosine-phosphate-guanosine oligodexynucleotides (CpG ODN), and investigated the effect of different amino groups of MSNs on the CpG ODN delivery. Serum stability, in vitro cytotoxicity, and cytokine interleukin-6 (IL-6) induction by MSN-NH2/CpG, MSN-2NH2/CpG and MSN-3NH2/CpG complexes were investigated in detail. The results showed that three kinds of aminated-MSN-based CpG ODN delivery systems had no cytotoxicity to RAW264.7 cells, and binding of CpG ODN to MSN-NH2, MSN-2NH2 and MSN-3NH2 nanoparticles enhanced the serum stability of CpG ODN due to protection by the nanoparticles. However, three aminated MSN-based CpG ODN delivery systems exhibited different CpG ODN delivery efficiency, and MSN-NH2/CpG complexes had the highest ability to induce IL-6 secretion.

  8. Glycyrrhetinic acid-functionalized mesoporous silica nanoparticles as hepatocellular carcinoma-targeted drug carrier

    PubMed Central

    Lv, Yongjiu; Li, Jingjing; Chen, Huali; Bai, Yan; Zhang, Liangke

    2017-01-01

    In this study, a glycyrrhetinic acid-functionalized mesoporous silica nanoparticle (MSN-GA) was prepared for active tumor targeting. MSN-GA exhibited satisfactory loading capacity for insoluble drugs, uniform size distribution, and specific tumor cell targeting. Glycyrrhetinic acid, a hepatocellular carcinoma-targeting group, was covalently decorated on the surface of MSN via an amido bond. The successful synthesis of MSN-GA was validated by the results of Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), and zeta potential measurement. TEM images revealed the spherical morphology and uniform size distribution of the naked MSN and MSN-GA. Curcumin (CUR), an insoluble model drug, was loaded into MSN-GA (denoted as MSN-GA-CUR) with a high-loading capacity (8.78%±1.24%). The results of the in vitro cellular experiment demonstrated that MSN-GA-CUR significantly enhanced cytotoxicity and cellular uptake toward hepatocellular carcinoma (HepG2) cells via a specific GA receptor-mediated endocytosis mechanism. The results of this study provide a promising nanoplatform for the targeting of hepatocellular carcinoma. PMID:28652738

  9. A dynamic interplay of nucleosome and Msn2 binding regulates kinetics of gene activation and repression following stress

    PubMed Central

    Elfving, Nils; Chereji, Răzvan V.; Bharatula, Vasudha; Björklund, Stefan; Morozov, Alexandre V.; Broach, James R.

    2014-01-01

    The transcription factor Msn2 mediates a significant proportion of the environmental stress response, in which a common cohort of genes changes expression in a stereotypic fashion upon exposure to any of a wide variety of stresses. We have applied genome-wide chromatin immunoprecipitation and nucleosome profiling to determine where Msn2 binds under stressful conditions and how that binding affects, and is affected by, nucleosome positioning. We concurrently determined the effect of Msn2 activity on gene expression following stress and demonstrated that Msn2 stimulates both activation and repression. We found that some genes responded to both intermittent and continuous Msn2 nuclear occupancy while others responded only to continuous occupancy. Finally, these studies document a dynamic interplay between nucleosomes and Msn2 such that nucleosomes can restrict access of Msn2 to its canonical binding sites while Msn2 can promote reposition, expulsion and recruitment of nucleosomes to alter gene expression. This interplay may allow the cell to discriminate between different types of stress signaling. PMID:24598258

  10. Combining Skype with Blogging: A Chance to Stop Reinforcement of Stereotypes in Intercultural Exchanges?

    ERIC Educational Resources Information Center

    Kirschner, L. Lynette

    2015-01-01

    This papers looks into whether combining Skype, blogging and class discussions reinforces or refutes stereotypes. The hypothesis was that some students do not have an adequate chance to reflect on their skype experience and course content. To see if students have made improvements in reducing stereotypes, the Standards for Foreign Language…

  11. Enhancement of the Initial Rate of Ethanol Fermentation Due to Dysfunction of Yeast Stress Response Components Msn2p and/or Msn4p▿ †

    PubMed Central

    Watanabe, Daisuke; Wu, Hong; Noguchi, Chiemi; Zhou, Yan; Akao, Takeshi; Shimoi, Hitoshi

    2011-01-01

    Sake yeasts (strains of Saccharomyces cerevisiae) produce high concentrations of ethanol in sake fermentation. To investigate the molecular mechanisms underlying this brewing property, we compared gene expression of sake and laboratory yeasts in sake mash. DNA microarray and reporter gene analyses revealed defects of sake yeasts in environmental stress responses mediated by transcription factors Msn2p and/or Msn4p (Msn2/4p) and stress response elements (STRE). Furthermore, we found that dysfunction of MSN2 and/or MSN4 contributes to the higher initial rate of ethanol fermentation in both sake and laboratory yeasts. These results provide novel insights into yeast stress responses as major impediments of effective ethanol fermentation. PMID:21131516

  12. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kinoshita, Takashi; Nohata, Nijiro; Fuse, Miki

    Highlights: Black-Right-Pointing-Pointer Tumor suppressive microRNA-133a regulates moesin (MSN) expression in HNSCC. Black-Right-Pointing-Pointer Silencing of MSN in HNSCC cells suppressed proliferation, migration and invasion. Black-Right-Pointing-Pointer The expression level of MSN was significantly up-regulated in cancer tissues. -- Abstract: Recently, many studies suggest that microRNAs (miRNAs) contribute to the development, invasion and metastasis of various types of human cancers. Our recent study revealed that expression of microRNA-133a (miR-133a) was significantly reduced in head and neck squamous cell carcinoma (HNSCC) and that restoration of miR-133a inhibited cell proliferation, migration and invasion in HNSCC cell lines, suggesting that miR-133a function as a tumor suppressor.more » Genome-wide gene expression analysis of miR-133a transfectants and TargetScan database showed that moesin (MSN) was a promising candidate of miR-133a target gene. MSN is a member of the ERM (ezrin, radixin and moesin) protein family and ERM function as cross-linkers between plasma membrane and actin-based cytoskeleton. The functions of MSN in cancers are controversial in previous reports. In this study, we focused on MSN and investigated whether MSN was regulated by tumor suppressive miR-133a and contributed to HNSCC oncogenesis. Restoration of miR-133a in HNSCC cell lines (FaDu, HSC3, IMC-3 and SAS) suppressed the MSN expression both in mRNA and protein level. Silencing study of MSN in HNSCC cell lines demonstrated significant inhibitions of cell proliferation, migration and invasion activities in si-MSN transfectants. In clinical specimen with HNSCC, the expression level of MSN was significantly up-regulated in cancer tissues compared to adjacent non-cancerous tissues. These data suggest that MSN may function as oncogene and is regulated by tumor suppressive miR-133a. Our analysis data of novel tumor-suppressive miR-133a-mediated cancer pathways could provide new insights into the potential mechanisms of HNSCC oncogenesis.« less

  13. Experiences of SKYPE Communication in Education and Research--Data Collection Concerning Young Children with Long-Term Illness

    ERIC Educational Resources Information Center

    Svensson, Agneta Simeonsdotter; Samuelsson, Ingrid Pramling; Hellström, Anna-Lena; Nolbris, Margaretha Jenholt

    2014-01-01

    The purpose of this paper is to provide knowledge about communication using SKYPE with young children with chronic illness; advantages and barriers are investigated related to education and data issues collection. A qualitative exploratory research method was applied to interviews and notes via SKYPE between children and their web teachers. The…

  14. Skype-Based English Activities: A Case for Compelling Input? Correlational Changes before and after Skype Exchanges

    ERIC Educational Resources Information Center

    Ockert, David

    2015-01-01

    This paper reports the results of a small, longitudinal study involving a group of Japanese elementary school students (N = 29) involved in exploratory research using foreign language activities, including two Skype exchanges between these students and students in Australia. The purpose of the research was to test for the impact of a series of…

  15. How Does Skype, as an Online Communication Software Tool, Contribute to K-12 Administrators' Level of Self-Efficacy?

    ERIC Educational Resources Information Center

    Kiriakidis, Peter

    2012-01-01

    How does Skype, as an online communication tool, contribute to school and district administrators' reported level of self-efficacy? A sample of n = 39 participants of which 22 were school administrators and 17 were district administrators was purposefully selected to use Skype in their offices with a webcam and microphone to communicate with other…

  16. Stress-response transcription factors Msn2 and Msn4 couple TORC2-Ypk1 signaling and mitochondrial respiration to ATG8 gene expression and autophagy.

    PubMed

    Vlahakis, Ariadne; Lopez Muniozguren, Nerea; Powers, Ted

    2017-01-01

    Macroautophagy/autophagy is a starvation and stress-induced catabolic process critical for cellular homeostasis and adaptation. Several Atg proteins are involved in the formation of the autophagosome and subsequent degradation of cytoplasmic components, a process termed autophagy flux. Additionally, the expression of several Atg proteins, in particular Atg8, is modulated transcriptionally, yet the regulatory mechanisms involved remain poorly understood. Here we demonstrate that the AGC kinase Ypk1, target of the rapamycin-insensitive TORC2 signaling pathway, controls ATG8 expression by repressing the heterodimeric Zinc-finger transcription factors Msn2 and Msn4. We find that Msn2 and Msn4 promote ATG8 expression downstream of the histone deacetylase complex (HDAC) subunit Ume6, a previously identified negative regulator of ATG8 expression. Moreover, we demonstrate that TORC2-Ypk1 signaling is functionally linked to distinct mitochondrial respiratory complexes. Surprisingly, we find that autophagy flux during amino acid starvation is also dependent upon Msn2-Msn4 activity, revealing a broad role for these transcription factors in the autophagy response.

  17. Control-release microcapsule of famotidine loaded biomimetic synthesized mesoporous silica nanoparticles: Controlled release effect and enhanced stomach adhesion in vitro.

    PubMed

    Li, Jing; Wang, Hongyu; Yang, Baixue; Xu, Lu; Zheng, Nan; Chen, Hongtao; Li, Sanming

    2016-01-01

    In the present work, control-release microcapsule of famotidine (FMT) loaded biomimetic synthesized mesoporous silica nanoparticles (B-MSNs) was developed, and controlled release effect and stomach adhesion of this formulation in vitro were mainly investigated. B-MSN was previously synthesized and it was amorphous mesoporous nanoparticles with helical channels. Cytotoxicity of B-MSN was studied using human breast cancer cells (MCF-7) and the result indicated that cytotoxicity of B-MSN can be neglected. After loading FMT into B-MSN, specific surface area, pore volume and pore diameter of B-MSN were obviously reduced. In vitro dissolution test showed that B-MSN had the ability to slow down FMT release for 15 min. In order to prolong controlled release effect and remained the advantage of B-MSN (improve drug stability due to its rigid silica framework), the combined application of control-release microcapsule (using cellulose and hydroxypropyl methylcellulose K15M as excipients) with B-MSN was designed. It was obvious that newly designed formulation significantly controlled FMT release with Fickian diffusion mechanism and showed enhanced stomach adhesion in vitro, which has significant value in widening the application of B-MSN in formulation design. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Applicability of avidin protein coated mesoporous silica nanoparticles as drug carriers in the lung

    NASA Astrophysics Data System (ADS)

    van Rijt, S. H.; Bölükbas, D. A.; Argyo, C.; Wipplinger, K.; Naureen, M.; Datz, S.; Eickelberg, O.; Meiners, S.; Bein, T.; Schmid, O.; Stoeger, T.

    2016-04-01

    Mesoporous silica nanoparticles (MSNs) exhibit unique drug delivery properties and are thus considered as promising candidates for next generation nano-medicines. In particular, inhalation into the lungs represents a direct, non-invasive delivery route for treating lung disease. To assess MSN biocompatibility in the lung, we investigated the bioresponse of avidin-coated MSNs (MSN-AVI), as well as aminated (uncoated) MSNs, after direct application into the lungs of mice. We quantified MSN distribution, clearance rate, cell-specific uptake, and inflammatory responses to MSNs within one week after instillation. We show that amine-functionalized (MSN-NH2) particles are not taken up by lung epithelial cells, but induced a prolonged inflammatory response in the lung and macrophage cell death. In contrast, MSN-AVI co-localized with alveolar epithelial type 1 and type 2 cells in the lung in the absence of sustained inflammatory responses or cell death, and showed preferential epithelial cell uptake in in vitro co-cultures. Further, MSN-AVI particles demonstrated uniform particle distribution in mouse lungs and slow clearance rates. Thus, we provide evidence that avidin functionalized MSNs (MSN-AVI) have the potential to serve as versatile biocompatible drug carriers for lung-specific drug delivery.Mesoporous silica nanoparticles (MSNs) exhibit unique drug delivery properties and are thus considered as promising candidates for next generation nano-medicines. In particular, inhalation into the lungs represents a direct, non-invasive delivery route for treating lung disease. To assess MSN biocompatibility in the lung, we investigated the bioresponse of avidin-coated MSNs (MSN-AVI), as well as aminated (uncoated) MSNs, after direct application into the lungs of mice. We quantified MSN distribution, clearance rate, cell-specific uptake, and inflammatory responses to MSNs within one week after instillation. We show that amine-functionalized (MSN-NH2) particles are not taken up by lung epithelial cells, but induced a prolonged inflammatory response in the lung and macrophage cell death. In contrast, MSN-AVI co-localized with alveolar epithelial type 1 and type 2 cells in the lung in the absence of sustained inflammatory responses or cell death, and showed preferential epithelial cell uptake in in vitro co-cultures. Further, MSN-AVI particles demonstrated uniform particle distribution in mouse lungs and slow clearance rates. Thus, we provide evidence that avidin functionalized MSNs (MSN-AVI) have the potential to serve as versatile biocompatible drug carriers for lung-specific drug delivery. Electronic supplementary information (ESI) available: Synthesis of MSN particles. Characterisation of MSN particles (Fig. S1 and S2), DLS measurements of MSNs over time, lymphocyte and PMN cell count after MSN exposure (Fig. S3). Toxicity in BAL cytospins controls, phalloidin staining on BAL cytospins of MSN-NH2 exposed mice (Fig. S4), nanoparticle distribution in lung cryo-slices of Balb/c mice exposed to 100 μg MSNs (Fig. S5). Balb/c mice cryo-slices exposed to MSN-AVI for 1 or 7 days, co-stained with alveolar epithelial cell type 1 marker or with alveolar epithelial cell type 2 marker (Fig. S6), DiD selective labeling in a co-culture set-up (Fig. S7). See DOI: 10.1039/c5nr04119h

  19. Case management for frail older adults through tablet computers and Skype.

    PubMed

    Berner, Jessica; Anderberg, Peter; Rennemark, Mikael; Berglund, Johan

    2016-12-01

    Frail older adults are high consumers of medical care due to their age and multiple chronic conditions. Regular contact with a case manager has been proven to increase well-being of frail older adults and reduce their number of health-care visits. Skype calls through tablet PCs can offer easier communication. This paper examines frail older adults' use of tablet computers and Skype, with their case managers. Interviews were conducted on 15 frail older adults. A content analysis was used to structure and analyze the data. The results indicate that tablet computers were experienced in a positive way for most frail older adults. Conflicting feelings did emerge, however, as to whether the frail elderly would adopt this in the long run. Skype needs to be tested further as to whether this is a good solution for communication with their case managers. Strong technical support and well-functioning technology are important elements to facilitate use. Using Skype and tablet PCs do have potential for frail older adults, but need to be tested further.

  20. An Author in Every Classroom: Kids Connecting with Authors via Skype. It's the next Best Thing to Being There

    ERIC Educational Resources Information Center

    Messner, Kate

    2010-01-01

    This article discusses how Skype and other video-conferencing software have become a staple for teachers, librarians, and authors who want to get kids excited about reading. The past year has brought a huge increase in the number of schools and libraries using Skype to connect classrooms and bring in experts to talk with kids. And with cuts in…

  1. Dynamic nonrobotic telemicroscopy via skype: A cost effective solution to teleconsultation.

    PubMed

    Sirintrapun, Sahussapont J; Cimic, Adela

    2012-01-01

    Skype is a peer to peer software application that has been historically used for voice and video calls, instant messaging, and file transfer over the Internet. Few studies are available using Skype specifically for telepathology. Our aim is to show that dynamic nonrobotic teleconsultation is possible and even effective via means of a standard microscope camera capable of live acquisition, Skype, an established broad band internet connection, and experienced pathologists. Both the consulting "sending" pathologist and consultant "receiving" pathologist are reasonably experienced general surgical pathologists at junior attending level with several years of experience in sign out. Forty-five cases were chosen encompassing a broad range of surgical pathology specimens. The cases were prospectively evaluated with the consultant diagnosis used as a preliminary pathologic impression with the final diagnosis being confirmation. Versions of Skype 5.0 and above were used along with established broadband internet connections, usually between academic medical institutions. Forty of forty-five cases (89%) were essentially concordant. In four of forty-five cases (9%), the consulting impression gave a differential, but favored an entity which did not match the final diagnosis. Only one case (2%) did the consulting impression not match the final diagnosis; a discordant opinion. The image quality via Skype screen sharing option is excellent. Essentially no lag time was seen. We have shown in our small pilot study that Skype is an effective cost-efficient means for teleconsultation, particularly in the setting of entity-related differential diagnoses in surgical pathology and when both the consulting and consultant pathologists are reasonably experienced.

  2. Acute glucose starvation activates the nuclear localization signal of a stress-specific yeast transcription factor

    PubMed Central

    Görner, Wolfram; Durchschlag, Erich; Wolf, Julia; Brown, Elizabeth L.; Ammerer, Gustav; Ruis, Helmut; Schüller, Christoph

    2002-01-01

    In yeast, environmental conditions control the transcription factor Msn2, the nuclear accumulation and function of which serve as a sensitive indicator of nutrient availablity and environmental stress load. We show here that the nuclear localization signal (NLS) of Msn2 is a direct target of cAMP-dependent protein kinase (cAPK). Genetic analysis suggests that Msn2-NLS function is inhibited by phosphorylation and activated by dephosphorylation. Msn2-NLS function is unaffected by many stress conditions that normally induce nuclear accumulation of full-length Msn2. The Msn2-NLS phosphorylation status is, however, highly sensitive to carbohydrate fluctuations during fermentative growth. Dephosphorylation occurs in >2 min after glucose withdrawal but the effect is reversed rapidly by refeeding with glucose. This response to glucose depletion is due to changes in cAPK activity rather than an increase in protein phosphatase activity. Surprisingly, the classical glucose-sensing systems are not connected to this rapid response system. Our results further imply that generic stress signals do not cause short-term depressions in cAPK activity. They operate on Msn2 by affecting an Msn5-dependent nuclear export and/or retention mechanism. PMID:11782433

  3. Web GIS in practice III: creating a simple interactive map of England's Strategic Health Authorities using Google Maps API, Google Earth KML, and MSN Virtual Earth Map Control

    PubMed Central

    Boulos, Maged N Kamel

    2005-01-01

    This eye-opener article aims at introducing the health GIS community to the emerging online consumer geoinformatics services from Google and Microsoft (MSN), and their potential utility in creating custom online interactive health maps. Using the programmable interfaces provided by Google and MSN, we created three interactive demonstrator maps of England's Strategic Health Authorities. These can be browsed online at – Google Maps API (Application Programming Interface) version, – Google Earth KML (Keyhole Markup Language) version, and – MSN Virtual Earth Map Control version. Google and MSN's worldwide distribution of "free" geospatial tools, imagery, and maps is to be commended as a significant step towards the ultimate "wikification" of maps and GIS. A discussion is provided of these emerging online mapping trends, their expected future implications and development directions, and associated individual privacy, national security and copyrights issues. Although ESRI have announced their planned response to Google (and MSN), it remains to be seen how their envisaged plans will materialize and compare to the offerings from Google and MSN, and also how Google and MSN mapping tools will further evolve in the near future. PMID:16176577

  4. The combined use of Skype and the STORZ CMAC video laryngoscope in field intubation training with the Nebraska National Air Guard.

    PubMed

    Boedeker, Ben H; Bernhagen, Mary; Miller, David J; Miljkovic, Nikola; Kuper, Gail M; Murray, W Bosseau

    2011-01-01

    This study examined the feasibility of using Skype technology in basic manikin intubation instruction of Nebraska National Air Guard personnel at a Casualty Training Exercise. Results show that the Skype monitor provided clear sound and visualization of the airway view to the trainees and the combination of VoIP technology and videolaryngoscopy for intubation training was highly valued by study participants.

  5. Msn2p and Msn4p Control a Large Number of Genes Induced at the Diauxic Transition Which Are Repressed by Cyclic AMP in Saccharomyces cerevisiae

    PubMed Central

    Boy-Marcotte, Emmanuelle; Perrot, Michel; Bussereau, Françoise; Boucherie, Hélian; Jacquet, Michel

    1998-01-01

    The multicopy suppressors of the snf1 defect, Msn2p and Msn4p transcription factors (Msn2/4p), activate genes through the stress-responsive cis element (CCCCT) in response to various stresses. This cis element is also the target for repression by the cyclic AMP (cAMP)-signaling pathway. We analyzed the two-dimensional gel electrophoresis pattern of protein synthesis of the msn2 msn4 double mutant and compared it with that of the wild-type strain during exponential growth phase and at the diauxic transition. Thirty-nine gene products (including those of ALD3, GDH3, GLK1, GPP2, HSP104, HXK1, PGM2, SOD2, SSA3, SSA4, TKL2, TPS1, and YBR149W) are dependent upon Msn2/4p for their induction at the diauxic transition. The expression of all these genes is repressed by cAMP. Thirty other genes identified during this study are still inducible in the mutant. A subset of these genes were found to be superinduced at the diauxic transition, and others were subject to cAMP repression (including ACH1, ADH2, ALD6, ATP2, GPD1, ICL1, and KGD2). We conclude from this analysis that Msn2/4p control a large number of genes induced at the diauxic transition but that other, as-yet-uncharacterized regulators, also contribute to this response. In addition, we show here that cAMP repression applies to both Msn2/4p-dependent and -independent control of gene expression at the diauxic shift. Furthermore, the fact that all the Msn2/4p gene targets are subject to cAMP repression suggests that these regulators could be targets for the cAMP-signaling pathway. PMID:9495741

  6. Dynamic nonrobotic telemicroscopy via skype: A cost effective solution to teleconsultation

    PubMed Central

    Sirintrapun, Sahussapont J.; Cimic, Adela

    2012-01-01

    Context: Skype is a peer to peer software application that has been historically used for voice and video calls, instant messaging, and file transfer over the Internet. Few studies are available using Skype specifically for telepathology. Aims: Our aim is to show that dynamic nonrobotic teleconsultation is possible and even effective via means of a standard microscope camera capable of live acquisition, Skype, an established broad band internet connection, and experienced pathologists. Settings and Design: Both the consulting “sending” pathologist and consultant “receiving” pathologist are reasonably experienced general surgical pathologists at junior attending level with several years of experience in sign out. Forty-five cases were chosen encompassing a broad range of surgical pathology specimens. The cases were prospectively evaluated with the consultant diagnosis used as a preliminary pathologic impression with the final diagnosis being confirmation. Materials and Methods: Versions of Skype 5.0 and above were used along with established broadband internet connections, usually between academic medical institutions. Results: Forty of forty-five cases (89%) were essentially concordant. In four of forty-five cases (9%), the consulting impression gave a differential, but favored an entity which did not match the final diagnosis. Only one case (2%) did the consulting impression not match the final diagnosis; a discordant opinion. Conclusions: The image quality via Skype screen sharing option is excellent. Essentially no lag time was seen. We have shown in our small pilot study that Skype is an effective cost-efficient means for teleconsultation, particularly in the setting of entity-related differential diagnoses in surgical pathology and when both the consulting and consultant pathologists are reasonably experienced. PMID:23024887

  7. Using Skype to support palliative care surveillance.

    PubMed

    Jones, Jacqueline

    2014-02-01

    The aim of this article is to demonstrate how a novel yet important tool can facilitate family involvement in person-centred care, despite geographical distance. The author presents a case study as an in-depth example of the use of Skype in the context of palliative care at home. Skype enhanced family surveillance and symptom management, augmented shared decision making, provided a space for virtual bedside vigil, and ultimately provided the rapport necessary for optimal end of life care.

  8. Mesoporous silica nanoparticle supported PdIr bimetal catalyst for selective hydrogenation, and the significant promotional effect of Ir

    NASA Astrophysics Data System (ADS)

    Yang, Hui; Huang, Chao; Yang, Fan; Yang, Xu; Du, Li; Liao, Shijun

    2015-12-01

    A mesoporous silica nanoparticle (MSN) supported bimetal catalyst, PdIr/MSN, was prepared by a facile impregnation and hydrogen reduction method. The strong promotional effect of Ir was observed and thoroughly investigated. At the optimal molar ratio of Ir to Pd (NIr/NPd = 0.1), the activity of PdIr0.1/MSN was up to eight times and 28 times higher than that of monometallic Pd/MSN and Ir/MSN, respectively. The catalysts were characterized comprehensively by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, and hydrogen temperature programmed reduction, which revealed that the promotional effect of Ir may be due to the enhanced dispersion of active components on the MSN, and to the intensified Pd-Ir electronic interaction caused by the addition of Ir.

  9. Amine functionalized cubic mesoporous silica nanoparticles as an oral delivery system for curcumin bioavailability enhancement

    NASA Astrophysics Data System (ADS)

    Budi Hartono, Sandy; Hadisoewignyo, Lannie; Yang, Yanan; Meka, Anand Kumar; Antaresti; Yu, Chengzhong

    2016-12-01

    In the present work, a simple method was used to develop composite curcumin-amine functionalized mesoporous silica nanoparticles (MSN). The nanoparticles were used to improve the bioavailability of curcumin in mice through oral administration. We investigated the effect of particle size on the release profile, solubility and oral bioavailability of curcumin in mice, including amine functionalized mesoporous silica micron-sized-particles (MSM) and MSN (100-200 nm). Curcumin loaded within amine functionalized MSN (MSN-A-Cur) had a better release profile and a higher solubility compared to amine MSM (MSM-A-Cur). The bioavailability of MSN-A-Cur and MSM-A-Cur was considerably higher than that of ‘free curcumin’. These results indicate promising features of amine functionalized MSN as a carrier to deliver low solubility drugs with improved bioavailability via the oral route.

  10. Untangling Basal Ganglia Network Dynamics and Function: Role of Dopamine Depletion and Inhibition Investigated in a Spiking Network Model.

    PubMed

    Lindahl, Mikael; Hellgren Kotaleski, Jeanette

    2016-01-01

    The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson's disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model. Simulation experiments predict that both local inhibition in striatum and the existence of an indirect pathway are important for basal ganglia to function properly over a large range of cortical drives. The dopamine depletion-induced increase of AMPA efficacy in corticostriatal synapses to medium spiny neurons (MSNs) with dopamine receptor D2 synapses (CTX-MSN D2) and the reduction of MSN lateral connectivity (MSN-MSN) were found to contribute significantly to the enhanced synchrony and oscillations seen in PD. Additionally, reversing the dopamine depletion-induced changes to CTX-MSN D1, CTX-MSN D2, TA-MSN, and MSN-MSN couplings could improve or restore basal ganglia action selection ability. In summary, we found multiple changes of parameters for synaptic efficacy and neural excitability that could improve action selection ability and at the same time reduce oscillations. Identification of such targets could potentially generate ideas for treatments of PD and increase our understanding of the relation between network dynamics and network function.

  11. Digital exploration via Skype: connecting your classroom with the experts

    NASA Astrophysics Data System (ADS)

    Hay, Rachel

    2014-05-01

    This presentation describes experiences of using Skype in the classroom to connect learners with scientists and explorers all over the world in order to deepen learners' knowledge and understanding of course material, develop their enquiry skills, and broaden their perspectives on life beyond the classroom walls. In a session organised by the Royal Scottish Geographical Society (RSGS) in partnership with Digital Explorer, twenty-five Perth High School students who were studying coral reefs took part in an exciting live Skype chat with researchers on Australia's Great Barrier Reef. Students spoke to a marine biologist and a geographer who were on-board their research vessel some 15,000km away. They learned about the Catlin Survey's cutting-edge research, which was set up to study conditions on the reef, take 50,000 images, and create a baseline for future comparisons. In addition, the scientists aimed to develop an underwater equivalent of Google Streetview, called Seaview, which will allow people everywhere to engage with this incredible ecosystem. We heard about the divers' encounter with Tiger sharks earlier that same day, and had a tour of the research vessel, as well as asking the experts questions about their research findings and career paths. Feedback from the students was extremely positive, and it was clear that the experience had greatly enhanced their studies. For myself and the other teachers involved, it was an exciting (and surreal!) experience, and helped to update our knowledge of our subjects. Between July and December 2013 I volunteered as Community Manager for Digital Explorer in their partnership with Skype in the classroom. Digital Explorer is an educational social enterprise dedicated to engaging young people in global issues, and preparing them to tackle environmental and technological changes in the 21st century. We offered seventeen lessons as part of Skype in the classroom's Exploring Oceans event in October and November, which aimed to educate and enthuse young people about the world's oceans. It was fascinating to connect with other teachers and with the guest speakers, and there is huge potential for future events on different themes. This presentation will outline what I think are the main benefits of, and challenges to, embedding the use of Skype in more classrooms, and offer some tips for successful Skype lessons. Value is added when Skype lessons are incorporated into a well-planned scheme of work that utilises high-quality, innovative resources, such as those produced by Digital Explorer. The use of this technology in schools increases student engagement in course material, as well as in local and global issues, thus facilitating the development of successful learners and informed global citizens. In addition, it provides opportunities for learners to take responsibility for, and direct, their own learning and skill development. I hope that more teachers will develop their confidence in using Skype with their students, as it offers exciting opportunities for creating interactive lessons and bringing the world into your classroom. Acknowledgements: Jamie Buchanan-Dunlop - Director, Digital Explorer http://digitalexplorer.com @de_updates Charlotte Moore - Made By Many/Skype in the Classroom https://education.skype.com/ @SkypeClassroom Dr Joyce Gilbert - Education Officer, Royal Scottish Geographical Society http://www.rsgs.org/ @RoyalScotGeoSoc

  12. Overexpression of the transcription activator Msn2 enhances the fermentation ability of industrial baker's yeast in frozen dough.

    PubMed

    Sasano, Yu; Haitani, Yutaka; Hashida, Keisuke; Ohtsu, Iwao; Shima, Jun; Takagi, Hiroshi

    2012-01-01

    We constructed a self-cloning diploid baker's yeast strain that overexpressed the transcription activator Msn2. It showed higher tolerance to freeze-thaw stress and higher intracellular trehalose level than observed in the wild-type strain. Overexpression of Msn2 also enhanced the fermentation ability of baker's yeast cells in frozen dough. Hence, Msn2-overexpressing baker's yeast should be useful in frozen-dough baking.

  13. Monitoring the Stimulated Uncapping Process of Gold-Capped Mesoporous Silica Nanoparticles

    DOE PAGES

    Augspurger, Ashley E.; Sun, Xiaoxing; Trewyn, Brian G.; ...

    2018-02-05

    To establish a new method for tracking the interaction of nanoparticles with chemical cleaving agents, we exploited the optical effects caused by attaching 5-10 nm gold nanoparticles with molecular linkers to large mesoporous silica nanoparticles (MSN). At low levels of gold loading onto MSN, the optical spectra resemble colloidal suspensions of gold. As the gold is removed, by cleaving agents, the MSN revert to the optical spectra typical of bare silica. Time-lapse images of gold-capped MSN stationed in microchannels reveal that the rate of gold release is dependent on the concentration of the cleaving agent. Finally, the uncapping process wasmore » also monitored successfully for MSN endocytosed by A549 cancer cells, which produce the cleaving agent glutathione. These experiments demonstrate that the optical properties of MSN can be used to directly monitor cleaving kinetics, even in complex cellular settings.« less

  14. Monitoring the Stimulated Uncapping Process of Gold-Capped Mesoporous Silica Nanoparticles.

    PubMed

    Augspurger, Ashley E; Sun, Xiaoxing; Trewyn, Brian G; Fang, Ning; Stender, Anthony S

    2018-03-06

    To establish a new method for tracking the interaction of nanoparticles with chemical cleaving agents, we exploited the optical effects caused by attaching 5-10 nm gold nanoparticles with molecular linkers to large mesoporous silica nanoparticles (MSN). At low levels of gold loading onto MSN, the optical spectra resemble colloidal suspensions of gold. As the gold is removed, by cleaving agents, the MSN revert to the optical spectra typical of bare silica. Time-lapse images of gold-capped MSN stationed in microchannels reveal that the rate of gold release is dependent on the concentration of the cleaving agent. The uncapping process was also monitored successfully for MSN endocytosed by A549 cancer cells, which produce the cleaving agent glutathione. These experiments demonstrate that the optical properties of MSN can be used to directly monitor cleaving kinetics, even in complex cellular settings.

  15. The SH2/SH3 adaptor protein dock interacts with the Ste20-like kinase misshapen in controlling growth cone motility.

    PubMed

    Ruan, W; Pang, P; Rao, Y

    1999-11-01

    Recent studies suggest that the SH2/SH3 adaptor Dock/Nck transduces tyrosine phosphorylation signals to the actin cytoskeleton in regulating growth cone motility. The signaling cascade linking the action of Dock/Nck to the reorganization of cytoskeleton is poorly understood. We now demonstrate that Dock interacts with the Ste20-like kinase Misshapen (Msn) in the Drosophila photoreceptor (R cell) growth cones. Loss of msn causes a failure of growth cones to stop at the target, a phenotype similar to loss of dock, whereas overexpression of msn induces pretarget growth cone termination. Physical and genetic interactions between Msn and Dock indicate a role for Msn in the Dock signaling pathway. We propose that Msn functions as a key controller of growth cone cytoskeleton in response to Dock-mediated signals.

  16. Monitoring the Stimulated Uncapping Process of Gold-Capped Mesoporous Silica Nanoparticles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Augspurger, Ashley E.; Sun, Xiaoxing; Trewyn, Brian G.

    To establish a new method for tracking the interaction of nanoparticles with chemical cleaving agents, we exploited the optical effects caused by attaching 5-10 nm gold nanoparticles with molecular linkers to large mesoporous silica nanoparticles (MSN). At low levels of gold loading onto MSN, the optical spectra resemble colloidal suspensions of gold. As the gold is removed, by cleaving agents, the MSN revert to the optical spectra typical of bare silica. Time-lapse images of gold-capped MSN stationed in microchannels reveal that the rate of gold release is dependent on the concentration of the cleaving agent. Finally, the uncapping process wasmore » also monitored successfully for MSN endocytosed by A549 cancer cells, which produce the cleaving agent glutathione. These experiments demonstrate that the optical properties of MSN can be used to directly monitor cleaving kinetics, even in complex cellular settings.« less

  17. Self-assembled Multilayers of Silica Nanospheres for Defect Reduction in Non- and Semipolar Gallium Nitride Epitaxial Layers

    PubMed Central

    2015-01-01

    Non- and semipolar GaN have great potential to improve the efficiency of light emitting devices due to much reduced internal electric fields. However, heteroepitaxial GaN growth in these crystal orientations suffers from very high dislocation and stacking faults densities. Here, we report a facile method to obtain low defect density non- and semipolar heteroepitaxial GaN via selective area epitaxy using self-assembled multilayers of silica nanospheres (MSN). Nonpolar (11–20) and semipolar (11–22) GaN layers with high crystal quality have been achieved by epitaxial integration of the MSN and a simple one-step overgrowth process, by which both dislocation and basal plane stacking fault densities can be significantly reduced. The underlying defect reduction mechanisms include epitaxial growth through the MSN covered template, island nucleation via nanogaps in the MSN, and lateral overgrowth and coalescence above the MSN. InGaN/GaN multiple quantum wells structures grown on a nonpolar GaN/MSN template show more than 30-fold increase in the luminescence intensity compared to a control sample without the MSN. This self-assembled MSN technique provides a new platform for epitaxial growth of nitride semiconductors and offers unique opportunities for improving the material quality of GaN grown on other orientations and foreign substrates or heteroepitaxial growth of other lattice-mismatched materials. PMID:27065755

  18. Fluorescent carbon dot-gated multifunctional mesoporous silica nanocarriers for redox/enzyme dual-responsive targeted and controlled drug delivery and real-time bioimaging.

    PubMed

    Wang, Ying; Cui, Yu; Zhao, Yating; He, Bing; Shi, Xiaoli; Di, Donghua; Zhang, Qiang; Wang, Siling

    2017-08-01

    A distinctive and personalized nanocarrier is described here for controlled and targeted antitumor drug delivery and real-time bioimaging by combining a redox/enzyme dual-responsive disulfide-conjugated carbon dot with mesoporous silica nanoparticles (MSN-SS-CD HA ). The carbon dot with controlling and targeting abilities was prepared through a polymerizing reaction by applying citric acid and HA as starting materials (named CD HA ). The as-prepared MSN-SS-CD HA exhibited not only superior photostability and excellent biocompatibility, but also the ability to target A549 cells with overexpression of CD44 receptors. Upon loading the antitumor drug, doxorubicin (DOX), into the mesoporous channels of MSN nanoparticles, CD HA with a diameter size of 3nm completely blocked the pore entrance of DOX-encapsulated MSN nanoparticles with a pore size of about 3nm, thus preventing the premature leakage of DOX and increasing the antitumor activity until being triggered by specific stimuli in the tumor environment. The results of the cell imaging and cytotoxicity studies demonstrated that the redox/enzyme dual-responsive DOX-encapsulated MSN-SS-CD HA nanoparticles can selectively deliver and control the release of DOX into tumor cells. Ex vivo fluorescence images showed a much stronger fluorescence of MSN-SS-CD HA -DOX in the tumor site than in normal tissues, greatly facilitating the accumulation of DOX in the target tissue. However, its counterpart, MSN-SH-DOX exhibited no or much lower tumor cytotoxicity and drug accumulation in tumor tissue. In addition, MSN-SS-CD was also used as a control to investigate the ability of MSN-SS-CD HA to target A549 cells. The results obtained indicated that MSN-SS-CD HA possessed a higher cellular uptake through the CD44 receptor-mediated endocytosis compared with MSN-SS-CD in the A549 cells. Such specific redox/enzyme dual-responsive targeted nanocarriers are a useful strategy achieving selective controlled and targeted delivery of therapeutic reagents with real-time bioimaging, and may also facilitate the development of drug delivery systems for a number of clinical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Miniscalpel-Needle versus Steroid Injection for Plantar Fasciitis: A Randomized Controlled Trial with a 12-Month Follow-Up

    PubMed Central

    Li, Shuming; Shen, Tong; Liang, Yongshan; Zhang, Ying; Bai, Bo

    2014-01-01

    Plantar fasciitis is the most common cause of heel pain in adults. A novel alternative medical instrument, the miniscalpel-needle (MSN), which is based on an acupuncture needle, has been recently developed in China. The objective of this study was to evaluate the effectiveness of the MSN release treatment versus that of traditional steroid injection for plantar fasciitis. Patients with plantar fasciitis were randomly assigned to 2 groups and followed up for 12 months, with 29 receiving MSN treatment and 25 receiving steroid injection treatment. The results showed that visual analog scale scores for morning pain, active pain, and overall heel pain all were decreased significantly in the MSN group from 1 to 12 months after treatment. In contrast, treatment with steroid injection showed a significant effect only at the 1-month follow-up but not at 6 or 12 months after treatment. Moreover, the MSN group achieved more rapid and sustained improvements than the steroid group throughout the duration of this study. No severe side effects were observed with MSN treatment. Our data suggest that the MSN release treatment is safe and has a significant benefit for plantar fasciitis compared to steroid injection. PMID:25114704

  20. Synthesis of mesoporous silica nanoparticles and nanorods: Application to doxorubicin delivery

    NASA Astrophysics Data System (ADS)

    Rahmani, Saher; Durand, Jean-Olivier; Charnay, Clarence; Lichon, Laure; Férid, Mokhtar; Garcia, Marcel; Gary-Bobo, Magali

    2017-06-01

    The synthesis and application of mesoporous silica nanoparticles (MSN) and mesoporous silica nanorods (MSNR) for drug delivery were described. MSN or MSNR were obtained by adjusting the amount of added cosolvent to the sol-gel solution. Therefore, the addition of ethanol (EtOH) has contributed to the control of the particle shape and to the structure of the mesoporosity. MSN and MSNR particles were then loaded with doxorubicin and incubated with MCF-7 breast cancer cells. MSN and MSNR particles were efficient in killing cancer cells but their behavior in drug delivery was altered on account of the difference in their morphology. MSN showed a burst release of doxorubicin in cells whereas MSNR showed a sustained delivery of the anti-cancer drug.

  1. Trivalent galactosyl-functionalized mesoporous silica nanoparticles as a target-specific delivery system for boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Lai, Chian-Hui; Lai, Nien-Chu; Chuang, Yung-Jen; Chou, Fong-In; Yang, Chia-Min; Lin, Chun-Cheng

    2013-09-01

    A multi-functional mesoporous silica nanoparticle (MSN)-based boron neutron capture therapy (BNCT) agent, designated as T-Gal-B-Cy3@MSN, was synthesized with hydrophobic mesopores for incorporating a large amount of o-carborane (almost 60% (w/w) boron atoms per MSN), and the amines on the external surface were conjugated with trivalent galactosyl ligands and fluorescent dyes for cell targeting and imaging, respectively. The polar and hydrophilic galactosyl ligands enhance the water dispersibility of the BNCT agent and inhibit the possible leakage of o-carborane loaded in the MSN. Confocal microscopic images showed that T-Gal-B-Cy3@MSNs were endocytosed by cells and were then released from lysosomes into the cytoplasm of cells. Moreover, in comparison with the commonly used clinical BNCT agent, sodium borocaptate (BSH), T-Gal-B-Cy3@MSN provides a higher delivery efficiency (over 40-50 fold) of boron atoms and a better effect of BNCT in neutron irradiation experiments. MTT assays show a very low cytotoxicity for T-Gal-B-Cy3@MSN over a 2 h incubation time. The results are promising for the design of multifunctional MSNs as potential BNCT agents for clinical use.A multi-functional mesoporous silica nanoparticle (MSN)-based boron neutron capture therapy (BNCT) agent, designated as T-Gal-B-Cy3@MSN, was synthesized with hydrophobic mesopores for incorporating a large amount of o-carborane (almost 60% (w/w) boron atoms per MSN), and the amines on the external surface were conjugated with trivalent galactosyl ligands and fluorescent dyes for cell targeting and imaging, respectively. The polar and hydrophilic galactosyl ligands enhance the water dispersibility of the BNCT agent and inhibit the possible leakage of o-carborane loaded in the MSN. Confocal microscopic images showed that T-Gal-B-Cy3@MSNs were endocytosed by cells and were then released from lysosomes into the cytoplasm of cells. Moreover, in comparison with the commonly used clinical BNCT agent, sodium borocaptate (BSH), T-Gal-B-Cy3@MSN provides a higher delivery efficiency (over 40-50 fold) of boron atoms and a better effect of BNCT in neutron irradiation experiments. MTT assays show a very low cytotoxicity for T-Gal-B-Cy3@MSN over a 2 h incubation time. The results are promising for the design of multifunctional MSNs as potential BNCT agents for clinical use. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr02594b

  2. Skype interviewing: The new generation of online synchronous interview in qualitative research

    PubMed Central

    Roudsari, Robab Latifnejad; Taghipour, Ali

    2014-01-01

    The most commonly used method for data collection in qualitative research is interviewing. With technology changes over the last few decades, the online interview has overcome time and financial constraints, geographical dispersion, and physical mobility boundaries, which have adversely affected onsite interviews. Skype as a synchronous online service offers researchers the possibility of conducting individual interviews as well as small focus groups, comparable to onsite types. This commentary presents the characteristics of the Skype interview as an alternative or supplemental choice to investigators who want to change their conventional approach of interviewing. PMID:24746247

  3. Skype interviewing: the new generation of online synchronous interview in qualitative research.

    PubMed

    Janghorban, Roksana; Latifnejad Roudsari, Robab; Taghipour, Ali

    2014-01-01

    The most commonly used method for data collection in qualitative research is interviewing. With technology changes over the last few decades, the online interview has overcome time and financial constraints, geographical dispersion, and physical mobility boundaries, which have adversely affected onsite interviews. Skype as a synchronous online service offers researchers the possibility of conducting individual interviews as well as small focus groups, comparable to onsite types. This commentary presents the characteristics of the Skype interview as an alternative or supplemental choice to investigators who want to change their conventional approach of interviewing.

  4. Utp9p facilitates Msn5p-mediated nuclear reexport of retrograded tRNAs in Saccharomyces cerevisiae.

    PubMed

    Eswara, Manoja B K; McGuire, Andrew T; Pierce, Jacqueline B; Mangroo, Dev

    2009-12-01

    Utp9p is a nucleolar protein that is part of a subcomplex containing several U3 snoRNA-associated proteins including Utp8p, which is a protein that shuttles aminoacyl-tRNAs from the nucleolus to the nuclear tRNA export receptors Los1p and Msn5p in Saccharomyces cerevisiae. Here we show that Utp9p is also an intranuclear component of the Msn5p-mediated nuclear tRNA export pathway. Depletion of Utp9p caused nuclear accumulation of mature tRNAs derived from intron-containing precursors, but not tRNAs made from intronless pre-tRNAs. Utp9p binds tRNA directly and saturably, and copurifies with Utp8p, Gsp1p, and Msn5p, but not with Los1p or aminoacyl-tRNA synthetases. Utp9p interacts directly with Utp8p, Gsp1p, and Msn5p in vitro. Furthermore, Gsp1p forms a complex with Msn5p and Utp9p in a tRNA-dependent manner. However, Utp9p does not shuttle between the nucleus and the cytoplasm. Because tRNA splicing occurs in the cytoplasm and the spliced tRNAs are retrograded back to the nucleus, we propose that Utp9p facilitates nuclear reexport of retrograded tRNAs. Moreover, the data suggest that Utp9p together with Utp8p translocate aminoacyl-tRNAs from the nucleolus to Msn5p and assist with formation of the Msn5p-tRNA-Gsp1p-GTP export complex.

  5. Nanoengineered mesoporous silica nanoparticles for smart delivery of doxorubicin

    NASA Astrophysics Data System (ADS)

    Mishra, Akhilesh Kumar; Pandey, Himanshu; Agarwal, Vishnu; Ramteke, Pramod W.; Pandey, Avinash C.

    2014-08-01

    The motive of the at hand exploration was to contrive a proficient innovative pH-responsive nanocarrier designed for an anti-neoplastic agent that not only owns competent loading capacity but also talented to liberate the drug at the specific site. pH sensitive hollow mesoporous silica nanoparticles ( MSN) have been synthesized by sequence of chemical reconstruction with an average particle size of 120 nm. MSN reveal noteworthy biocompatibility and efficient drug loading magnitude. Active molecules such as Doxorubicin (DOX) can be stocked and set free from the pore vacuities of MSN by tuning the pH of the medium. The loading extent of MSN was found up to 81.4 wt% at pH 7.8. At mild acidic pH, DOX is steadily released from the pores of MSN. Both, the nitrogen adsorption-desorption isotherms and X-ray diffraction patterns reflects that this system holds remarkable stable mesostructure. Additionally, the outcomes of cytotoxicity assessment further establish the potential of MSN as a relevant drug transporter which can be thought over an appealing choice to a polymeric delivery system.

  6. Researching the acceptability of using Skype to provide Speech and Language Therapy

    PubMed Central

    Matthews, Rebecca Alison; Woll, Bencie; Clarke, Mike

    2012-01-01

    In the current economic climate, whilst the demand for health services, including Speech and Language Therapy (SLT) continues to rise, there is pressure to reduce health service budgets, Tele-technology—the use of tele-communication technology to link patient and clinician remotely—could potentially provide a solution to meeting the demand for SLT with reduced resources. However, only a few SLT services in the United Kingdom (UK) have reported on using tele-technology to provide their service (Howell, Tripoliti and Pring, 2009; Styles, 2008; McCullough, 2001; Katsavarus, 2001). In 2002 the American Speech and Hearing Association (ASHA) surveyed its members on their experience and views of using tele-technology and specifically video-conferencing to provide an SLT service. The analysis of the responses identified five areas of concern—lack of professional guidelines, limited evidence of clinical efficacy, disruption and problems managing the technology, change in the interaction and loss of rapport as well as anticipated, additional costs to provide the service. The study reported here set up an SLT service using the desktop videoconferencing system, Skype, in an independent SLT practice based in the UK. Data were collected to evaluate the acceptability of the clinical sessions, the technology, the quality of interaction and costs of an SLT service using Skype. Eleven participants aged between 7 and 14 years with varying therapy needs took part. Each received a mix of face-to-face (F2F) and Skype SLT over the ten session trial period. Data were collected for every session using a report card; adults supporting the children were asked for their views using a questionnaire at the beginning and end of the trial; the child participants were interviewed after the trial period was over; one F2F and one Skype session was video recorded for each participant; work activity was recorded along with identifiable costs of F2F and Skype SLT sessions. A total of 110 session report cards, 24 questionnaires, 10 interviews and 16 hours of video recording were analysed. The responses from interviews and questionnaires were compared with the discourse analysis of the session video recordings and session report cards. A greater percentage of goals were completed in the Skype sessions. Whilst there were breaks in internet connection, this did not reduce the number of goals achieved. The ratio of turn moves and utterance functions were the same for therapist and child in both session formats; the only difference identified was the increased use of requests for objects/action in the F2F session. The discourse analysis supported the participant observations that the children worked harder and focused better in the Skype sessions. The presence of clarifications and the reduced numbers of interruptions were in line with other research observations that the speakers were able to judge the mood of the conversation partner in remote interaction. Costs of Skype SLT were lower than equivalent F2F sessions. The combination of positive findings suggests that Skype SLT sessions are potentially acceptable and are likely to have a useful role to play in service provision.

  7. Influence of Telecommunication Modality, Internet Transmission Quality, and Accessories on Speech Perception in Cochlear Implant Users

    PubMed Central

    Koller, Roger; Guignard, Jérémie; Caversaccio, Marco; Kompis, Martin; Senn, Pascal

    2017-01-01

    Background Telecommunication is limited or even impossible for more than one-thirds of all cochlear implant (CI) users. Objective We sought therefore to study the impact of voice quality on speech perception with voice over Internet protocol (VoIP) under real and adverse network conditions. Methods Telephone speech perception was assessed in 19 CI users (15-69 years, average 42 years), using the German HSM (Hochmair-Schulz-Moser) sentence test comparing Skype and conventional telephone (public switched telephone networks, PSTN) transmission using a personal computer (PC) and a digital enhanced cordless telecommunications (DECT) telephone dual device. Five different Internet transmission quality modes and four accessories (PC speakers, headphones, 3.5 mm jack audio cable, and induction loop) were compared. As a secondary outcome, the subjective perceived voice quality was assessed using the mean opinion score (MOS). Results Speech telephone perception was significantly better (median 91.6%, P<.001) with Skype compared with PSTN (median 42.5%) under optimal conditions. Skype calls under adverse network conditions (data packet loss > 15%) were not superior to conventional telephony. In addition, there were no significant differences between the tested accessories (P>.05) using a PC. Coupling a Skype DECT phone device with an audio cable to the CI, however, resulted in higher speech perception (median 65%) and subjective MOS scores (3.2) than using PSTN (median 7.5%, P<.001). Conclusions Skype calls significantly improve speech perception for CI users compared with conventional telephony under real network conditions. Listening accessories do not further improve listening experience. Current Skype DECT telephone devices do not fully offer technical advantages in voice quality. PMID:28438727

  8. Influence of Telecommunication Modality, Internet Transmission Quality, and Accessories on Speech Perception in Cochlear Implant Users.

    PubMed

    Mantokoudis, Georgios; Koller, Roger; Guignard, Jérémie; Caversaccio, Marco; Kompis, Martin; Senn, Pascal

    2017-04-24

    Telecommunication is limited or even impossible for more than one-thirds of all cochlear implant (CI) users. We sought therefore to study the impact of voice quality on speech perception with voice over Internet protocol (VoIP) under real and adverse network conditions. Telephone speech perception was assessed in 19 CI users (15-69 years, average 42 years), using the German HSM (Hochmair-Schulz-Moser) sentence test comparing Skype and conventional telephone (public switched telephone networks, PSTN) transmission using a personal computer (PC) and a digital enhanced cordless telecommunications (DECT) telephone dual device. Five different Internet transmission quality modes and four accessories (PC speakers, headphones, 3.5 mm jack audio cable, and induction loop) were compared. As a secondary outcome, the subjective perceived voice quality was assessed using the mean opinion score (MOS). Speech telephone perception was significantly better (median 91.6%, P<.001) with Skype compared with PSTN (median 42.5%) under optimal conditions. Skype calls under adverse network conditions (data packet loss > 15%) were not superior to conventional telephony. In addition, there were no significant differences between the tested accessories (P>.05) using a PC. Coupling a Skype DECT phone device with an audio cable to the CI, however, resulted in higher speech perception (median 65%) and subjective MOS scores (3.2) than using PSTN (median 7.5%, P<.001). Skype calls significantly improve speech perception for CI users compared with conventional telephony under real network conditions. Listening accessories do not further improve listening experience. Current Skype DECT telephone devices do not fully offer technical advantages in voice quality. ©Georgios Mantokoudis, Roger Koller, Jérémie Guignard, Marco Caversaccio, Martin Kompis, Pascal Senn. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.04.2017.

  9. Activation cross sections of alpha-induced reactions on natIn for 117mSn production

    NASA Astrophysics Data System (ADS)

    Aikawa, M.; Saito, M.; Ukon, N.; Komori, Y.; Haba, H.

    2018-07-01

    The production of 117mSn by charged-particle induced reactions is an interesting topic for medical application. Production cross sections of α-induced reactions on natIn for 117mSn up to 50 MeV were measured using the stacked foil technique and activation method. The integral yield of 117mSn was estimated using the measured cross sections. The results were compared with experimental data investigated earlier and theoretical calculation. Measured cross sections for 113Sn and 116m,117,118mSb isotopes were also presented.

  10. Lateral and feedforward inhibition suppress asynchronous activity in a large, biophysically-detailed computational model of the striatal network

    PubMed Central

    Moyer, Jason T.; Halterman, Benjamin L.; Finkel, Leif H.; Wolf, John A.

    2014-01-01

    Striatal medium spiny neurons (MSNs) receive lateral inhibitory projections from other MSNs and feedforward inhibitory projections from fast-spiking, parvalbumin-containing striatal interneurons (FSIs). The functional roles of these connections are unknown, and difficult to study in an experimental preparation. We therefore investigated the functionality of both lateral (MSN-MSN) and feedforward (FSI-MSN) inhibition using a large-scale computational model of the striatal network. The model consists of 2744 MSNs comprised of 189 compartments each and 121 FSIs comprised of 148 compartments each, with dendrites explicitly represented and almost all known ionic currents included and strictly constrained by biological data as appropriate. Our analysis of the model indicates that both lateral inhibition and feedforward inhibition function at the population level to limit non-ensemble MSN spiking while preserving ensemble MSN spiking. Specifically, lateral inhibition enables large ensembles of MSNs firing synchronously to strongly suppress non-ensemble MSNs over a short time-scale (10–30 ms). Feedforward inhibition enables FSIs to strongly inhibit weakly activated, non-ensemble MSNs while moderately inhibiting activated ensemble MSNs. Importantly, FSIs appear to more effectively inhibit MSNs when FSIs fire asynchronously. Both types of inhibition would increase the signal-to-noise ratio of responding MSN ensembles and contribute to the formation and dissolution of MSN ensembles in the striatal network. PMID:25505406

  11. Dynamic Changes in Nucleosome Occupancy Are Not Predictive of Gene Expression Dynamics but Are Linked to Transcription and Chromatin Regulators

    PubMed Central

    Huebert, Dana J.; Kuan, Pei-Fen; Keleş, Sündüz

    2012-01-01

    The response to stressful stimuli requires rapid, precise, and dynamic gene expression changes that must be coordinated across the genome. To gain insight into the temporal ordering of genome reorganization, we investigated dynamic relationships between changing nucleosome occupancy, transcription factor binding, and gene expression in Saccharomyces cerevisiae yeast responding to oxidative stress. We applied deep sequencing to nucleosomal DNA at six time points before and after hydrogen peroxide treatment and revealed many distinct dynamic patterns of nucleosome gain and loss. The timing of nucleosome repositioning was not predictive of the dynamics of downstream gene expression change but instead was linked to nucleosome position relative to transcription start sites and specific cis-regulatory elements. We measured genome-wide binding of the stress-activated transcription factor Msn2p over time and found that Msn2p binds different loci with different dynamics. Nucleosome eviction from Msn2p binding sites was common across the genome; however, we show that, contrary to expectation, nucleosome loss occurred after Msn2p binding and in fact required Msn2p. This negates the prevailing model that nucleosomes obscuring Msn2p sites regulate DNA access and must be lost before Msn2p can bind DNA. Together, these results highlight the complexities of stress-dependent chromatin changes and their effects on gene expression. PMID:22354995

  12. Using Skype to support remote clinical supervision for health professionals delivering a sustained maternal early childhood programme: a phenomenographical study.

    PubMed

    Bruce, Tracey; Byrne, Fiona; Kemp, Lynn

    2018-02-01

    Skype technology was implemented by the Australian Maternal Early Childhood Sustained Home-visiting (MECSH) Support Service as a tool for the remote provision of clinical supervision for clinicians working in the MECSH program in Seoul, South Korea. To gain a better understanding of the processes underpinning sustainable delivery of remote clinical supervision using digital technologies. A phenomenographical study. Recorded notes and reflections on each supervision session, noting exemplars and characteristics of the experience were read and re-read to derive the characterizations of the experience. The experience has provided learnings in three domains: (1) the processes in using Skype; (2) supervisory processes; and (3) language translation, including managing clarity of, and time for translation. Skype has potential for use in remote provision of clinical supervision, including where translation is required. Further research evaluating the benefit of telesupervision from supervisor and supervisee perspectives is necessary to determine if it is a sustainable process.

  13. Skype Me! Astronomers, Students, and Cutting-Edge Research

    NASA Astrophysics Data System (ADS)

    Hickox, Ryan C.; Gauthier, Adrienne J.

    2014-06-01

    A primary goal of many university science courses is to promote understanding of the process of contemporary scientific inquiry. One powerful way to achieve this is for students to explore current research and then interact directly with the leading scientist, the feasibility of which has recently increased dramatically due to free online video communication tools. We report on a program implemented at Dartmouth College in which students connect with a guest astronomer through Skype (video chat). The Skype session is wrapped in a larger activity where students explore current research articles, interact with the astronomer, and then reflect on the experience. The in-class Skype discussions require a small time commitment from scientists (20-30 minutes, with little or no need for preparation) while providing students direct access to researchers at the cutting edge of modern astronomy. We outline the procedures used to implement these discussions, and present qualitative assessments of student's understanding of the process of research, as well as feedback from the guest astronomers.

  14. Continuous light exposure causes cumulative stress that affects the localization oscillation dynamics of the transcription factor Msn2p.

    PubMed

    Bodvard, Kristofer; Wrangborg, David; Tapani, Sofia; Logg, Katarina; Sliwa, Piotr; Blomberg, Anders; Kvarnström, Mats; Käll, Mikael

    2011-02-01

    Light exposure is a potentially powerful stress factor during in vivo optical microscopy studies. In yeast, the general transcription factor Msn2p translocates from the cytoplasm to the nucleus in response to illumination. However, previous time-lapse fluorescence microscopy studies of Msn2p have utilized a variety of discrete exposure settings, which makes it difficult to correlate stress levels and illumination parameters. We here investigate how continuous illumination with blue light, corresponding to GFP excitation wavelengths, affects the localization pattern of Msn2p-GFP in budding yeast. The localization pattern was analyzed using a novel approach that combines wavelet decomposition and change point analysis. It was found that the Msn2p nucleocytoplasmic localization trajectories for individual cells exhibit up to three distinct and successive states; i) Msn2p localizes to the cytoplasm; ii) Msn2p rapidly shuttles between the cytoplasm and the nucleus; iii) Msn2p localizes to the nucleus. Many cells pass through all states consecutively at high light intensities, while at lower light intensities most cells only reach states i) or ii). This behaviour strongly indicates that continuous light exposure gradually increases the stress level over time, presumably through continuous accumulation of toxic photoproducts, thereby forcing the cell through a bistable region corresponding to nucleocytoplasmic oscillations. We also show that the localization patterns are dependent on protein kinase A (PKA) activity, i.e. yeast cells with constantly low PKA activity showed a stronger stress response. In particular, the nucleocytoplasmic oscillation frequency was found to be significantly higher for cells with low PKA activity for all light intensities. 2010 Elsevier B.V. All rights reserved.

  15. The glucose sensor Snf1 and the transcription factors Msn2 and Msn4 regulate transcription of the vacuolar iron importer gene CCC1 and iron resistance in yeast.

    PubMed

    Li, Liangtao; Kaplan, Jerry; Ward, Diane M

    2017-09-15

    The budding yeast Saccharomyces cerevisiae stores iron in the vacuole, which is a major resistance mechanism against iron toxicity. One key protein involved in vacuolar iron storage is the iron importer Ccc1, which facilitates iron entry into the vacuole. Transcription of the CCC1 gene is largely regulated by the binding of iron-sulfur clusters to the activator domain of the transcriptional activator Yap5. Additional evidence, however, suggests that Yap5-independent transcriptional activation of CCC1 also contributes to iron resistance. Here, we demonstrate that components of the signaling pathway involving the low-glucose sensor Snf1 regulate CCC1 transcription and iron resistance. We found that SNF1 deletion acts synergistically with YAP5 deletion to regulate CCC1 transcription and iron resistance. A kinase-dead mutation of Snf1 lowered iron resistance as did deletion of SNF4 , which encodes a partner protein of Snf1. Deletion of all three alternative partners of Snf1 encoded by SIT1 , SIT2 , and GAL83 decreased both CCC1 transcription and iron resistance. The Snf1 complex is known to activate the general stress transcription factors Msn2 and Msn4. We show that Msn2 and Msn4 contribute to Snf1-mediated CCC1 transcription. Of note, SNF1 deletion in combination with MSN2 and MSN4 deletion resulted in additive effects on CCC1 transcription, suggesting that other activators contribute to the regulation of CCC1 transcription. In conclusion, we show that yeast have developed multiple transcriptional mechanisms to regulate Ccc1 expression and to protect against high cytosolic iron toxicity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Using Blackboard and Skype for Mentoring Beginning Teachers

    ERIC Educational Resources Information Center

    Suk Hwang, Young; Vrongistinos, Konstantinos

    2012-01-01

    The purpose of this article is to examine the nature of the Blackboard and Skype-based electronic mentoring system for beginning teachers. The Quality Teachers for Quality Students project developed an electronic mentoring system between beginning teachers and experienced teachers to support beginning teachers' instructional and classroom…

  17. Skype clinics after intestinal transplantation - follow-up beyond post codes.

    PubMed

    Gerlach, Undine A; Vrakas, Georgios; Holdaway, Lydia; O'Connor, Marion; Macedo, Rubens; Reddy, Srikanth; Friend, Peter J; Giele, Henk; Vaidya, Anil

    2016-07-01

    The follow-up after intestinal transplantation (ITX) is complex and limited to specialized centers. ITX recipients often travel all over the country to be seen in the outpatient clinic of specialized centers which is costly and time-consuming. Videoconferences through Skype have been implemented to eliminate travel time, costs, and to improve patient compliance without jeopardizing safety. Eighteen of 19 patients followed up after ITX or modified multivisceral transplantation (MMVTX) in conventional outpatient clinics in Oxford agreed to attend additional Skype clinics. All patients who were followed up through Skype clinics after ITX/MMVTX received a questionnaire to measure their satisfaction with methods and technical aspects of videoconferencing as well as time/mode of traveling, travel expenses/costs, waiting time in outpatient clinic and patients' satisfaction. Mean travel distance to Oxford was 236 ± 168 miles, mean travel time was 277 ± 175 min, and mean travel cost was 200 ± 56 Great Britain Pounds. A total of 56% had to take time off work and/or find child/family care for the time spent in travel. These patients reported a satisfaction score of 4.38 ± 0.77 of 5 points as opposed to 2.88 ± 0.90 for attending the conventional outpatient clinic. Skype clinics have been proven successful and feasible in highly specialized fields like ITX in eligible patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Loss of msnA, a putative stress regulatory gene, in Aspergillus parasiticus and Aspergillus flavus increased production of conidia, aflatoxins and kojic acid

    USDA-ARS?s Scientific Manuscript database

    Production of the harmful carcinogenic aflatoxins by Aspergillus parasiticus and Aspergillus flavus has been postulated to be a mechanism to relieve oxidative stress. The msnA gene, the ortholog of Saccharomyces cerevisiae MSN2 associated with multi-stress response, of the two species was disrupted....

  19. The Bermuda Triangle of Cocaine-Induced Neuroadaptations

    PubMed Central

    Wolf, Marina E.

    2010-01-01

    Activation of medium spiny neurons (MSN) of the nucleus accumbens is critical for goal-directed behaviors including cocaine seeking. Studies in cocaine-experienced rodents have revealed three major categories of neuroadaptations that influence the ability of glutamate inputs to activate MSN: changes in synaptic AMPA receptor levels, changes in extracellular non-synaptic glutamate levels, and changes in MSN intrinsic membrane excitability. Most studies have focused on one of these adaptations. Here, we consider the possibility that they are causally related and speculate about how time-dependent changes in their interactions may regulate MSN output during early and late withdrawal from repeated cocaine exposure. PMID:20655604

  20. pH responsive cylindrical MSN for oral delivery of insulin-design, fabrication and evaluation.

    PubMed

    Guha, Arijit; Biswas, Nikhil; Bhattacharjee, Kaustav; Sahoo, Nityananda; Kuotsu, Ketousetuo

    2016-11-01

    The objective of the present study was to develop novel PMV [poly (methacrylic acid-co-vinyl triethoxylsilane)]-coated mesoporous silica nanoparticles (MSN) with improved hypoglycemic effect for oral insulin (INS) delivery. MSN was synthesized under acidic condition using Pluronic® P 123 and Tetra ethoxy orthosilane. Surfactant was removed by calcination. Calcined MSN was coated with pH sensitive polymer PMV. Cytotoxicity of this coated MSN was evaluated by MTT assay using CHO-K1 cell line. Different MSN samples were characterized with BET surface area analyzer, FESEM, TEM, FT-IR, XRD, TG-DTA. In vivo study was performed using male rats. Pharmacokinetic study was conducted using HPLC. Highest surface area (304.3921 m 2 /g) was observed in case of calcined sample. Adsorption pore width of final coated sample was highest (64.7844 nm) compared with others. No noticeable cytotoxicity was observed for this coated support. The entrapment efficiency of insulin was found to be 39.39%. In vitro studies were done at different pH using Franz-diffusion cell. Results showed significant release at pH 7.4. Cumulative drug release over a period of 6 h was more than 48% at this systemic pH. Effect of this MSN-PMV-INS on blood glucose level was retained for 16 h. This novel formulation has shown 73.10% relative bioavailability of insulin. A novel-coated mesoporous silica support was successfully developed for delivery of insulin through oral route.

  1. Using Skype in the Second and Foreign Language Classroom

    ERIC Educational Resources Information Center

    Eaton, Sarah Elaine

    2010-01-01

    This presentation introduced Skype and how it can be used to: (1) connect teachers with other professionals - and save on long distance charges - even internationally (2) empower language teachers and tutors (3) give presentations and workshops (4) be a stepping stone to using more sophisticated technology in the classroom. It was noted that for…

  2. Skype Videoconferencing for Less Commonly Taught Languages: Examining the Effects on Students' Foreign Language Anxiety

    ERIC Educational Resources Information Center

    Terantino, Joe

    2014-01-01

    This study compared students' foreign language anxiety levels while completing oral assessments administered face-to-face (F2F) and via Skype videoconferencing for university courses delivered under the self-instructional language program (SILP) model (Dunkel, Brill, & Kohl, 2002). Data were gathered by administering a modified Foreign…

  3. Chinese-French Case Study of English Language Learning via Wikispaces, Animoto and Skype

    ERIC Educational Resources Information Center

    Hartwell, Laura M.; Zou, Bin

    2013-01-01

    This paper reports on the learning experience of Chinese and French students participating in a computer mediated communication (CMC) collaboration conducted in English and supported by Wikispaces, Animoto, and Skype. Several studies have investigated CMC contexts in which at least some participants were native speakers. Here, we address the…

  4. Golgi study of medium spiny neurons from dorsolateral striatum of the turtle Trachemys scripta elegans.

    PubMed

    González, Carolina; Mendoza, Janeth; Avila-Costa, María Rosa; Arias, Juan M; Barral, Jaime

    2013-11-27

    Comparative anatomy has shown similarities between reptilian and mammalian basal ganglia. Here the morphological characteristics of the medium spiny neurons (MSN) in the dorsolateral striatum (DLS) of the turtle are described after staining them with the Golgi technique. The soma of MSN in DLS showed three main forms: spherical, ovoid, and fusiform. The number of primary dendritic branches (3-4 den-drites/cell) was less than observed in mammals. The MSN axon originates mainly from the soma, and randomly it emerges at the beginning of the primary dendrite. The main differences between turtle and mammalian MSN were detected on dendritic spines. Short, thin, bifurcated and fungiform types of den-dritic spines were observed in the turtle's MSN, according to their shape. In most of the analyzed spines,it was found that its length considerably exceeded that reported in mammals, with dendritic spines upto 8 μm in length. These differences could play an important role in the modulation of motor networks preserved along the vertebrate evolution.

  5. MiR-200c Inhibits the Tumor Progression of Glioma via Targeting Moesin

    PubMed Central

    Qin, Yuanyuan; Chen, Weilong; Liu, Bingjie; Zhou, Lei; Deng, Lu; Niu, Wanxiang; Bao, Dejun; Cheng, Chuandong; Li, Dongxue; Liu, Suling; Niu, Chaoshi

    2017-01-01

    We attempt to demonstrate the regulatory role of miR-200c in glioma progression and its mechanisms behind. Here, we show that miR-200c expression was significantly reduced in the glioma tissues compared to paratumor tissues, especially in malignant glioma. Exogenous overexpression of miR-200c inhibited the proliferation and invasion of glioma cells. In addition, the in vivo mouse xenograft model showed that miR-200c inhibited glioma growth and liver metastasis, which is mainly regulated by targeting moesin (MSN). We demonstrated that the expression of MSN in glioma specimens were negatively correlated with miR-200c expression, and MSN overexpression rescued the phenotype about cell proliferation and invasion induced by miR-200c. Moreover, knockdown of MSN was able to mimic the effects induced by miR-200c in glioma cells. These results indicate that miR-200c plays an important role in the regulation of glioma through targeting MSN. PMID:28529643

  6. Redox and pH dual-responsive mesoporous silica nanoparticles for site-specific drug delivery

    NASA Astrophysics Data System (ADS)

    Wang, Ying; Cui, Yu; Huang, Jiahao; Di, Donghua; Dong, Yanyan; Zhang, Xiaojing; Zhao, Qinfu; Han, Ning; Gao, Yikun; Jiang, Tongying; Wang, Siling

    2015-11-01

    In this paper, a mesoporous silica nanoparticles (MSN)-based redox and pH dual-responsive delivery system (MSN-SS-PAA) was developed for site-specific drug delivery, in which poly(acrylic acid) (PAA), a polyanion polymer, was grafted on the outlets of MSN via the cleavable disulfide bonds. PAA was chosen as a gatekeeper to block drugs within the mesopores of MSN mainly because PAA possesses many favorable features, such as appropriate molecular weight to block the entrances of MSNs, good biocompatibility, and ability to prolong the blood circulation time and improve the dispersing stability of MSN in physiological conditions. RhB, a fluorescent dye, was used as a model drug. In vitro release profiles indicated that RhB was markedly blocked within the mesopores in the absence of GSH or in pH 7.4 PBS; however, the release of RhB was dramatically increased after the addition of GSH or in pH 5.0 PBS. Moreover, the release of RhB was further improved in the simultaneous presence of GSH and pH 5.0 PBS. This paper provided an exploration of stimuli-responsive delivery system and the results demonstrated that MSN-SS-PAA exhibiting dual-responsive drug release property can be further considered as a promising candidate for cancer therapy.

  7. Multifunctional nanoparticles for real-time evaluation of toxicity during fetal development

    PubMed Central

    Adamcakova-Dodd, Andrea; Thorne, Peter S.; Assouline, Jose G.

    2018-01-01

    Increasing production of nanomaterials in industrial quantities has led to public health concerns regarding exposure, particularly among pregnant women and developing fetuses. Information regarding the barrier capacity of the placenta for various nanomaterials is limited due to challenges working with ex vivo human placentas or in vivo animal models. To facilitate real-time in vivo imaging of placental transport, we have developed a novel, multifunctional nanoparticle, based on a core of mesoporous silica nanoparticles (MSN), and functionalized for magnetic resonance imaging (MRI), ultrasound, and fluorescent microscopy. Our MSN particles were tested as a tracking method for harmful and toxic nanomaterials. In gravid mice, intravenous injections of MSN were administered in the maternal circulation in early gestation (day 9) and late gestation (day 14). MRI and ultrasound were used to track the MSN following the injections. Changes in contrast relative to control mice indicated that MSN were observed in the embryos of mice following early gestation injections, while MSN were excluded from the embryo by the placenta following late gestation injections. The timing of transplacental barrier porosity is consistent with the notion that in mice there is a progressive increasing segregation by the placenta in later gestation. In addition, built-in physico-chemical properties of our MSN may present options for the therapeutic treatment of embryonic exposure. For example, if preventive measures such as detoxification of harmful compounds are implemented, the particle size and exposure timing can be tailored to selectively distribute to the maternal side of the trophoblast or delivered to the fetus. PMID:29420606

  8. Untangling Basal Ganglia Network Dynamics and Function: Role of Dopamine Depletion and Inhibition Investigated in a Spiking Network Model

    PubMed Central

    2016-01-01

    Abstract The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson’s disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model. Simulation experiments predict that both local inhibition in striatum and the existence of an indirect pathway are important for basal ganglia to function properly over a large range of cortical drives. The dopamine depletion–induced increase of AMPA efficacy in corticostriatal synapses to medium spiny neurons (MSNs) with dopamine receptor D2 synapses (CTX-MSN D2) and the reduction of MSN lateral connectivity (MSN–MSN) were found to contribute significantly to the enhanced synchrony and oscillations seen in PD. Additionally, reversing the dopamine depletion–induced changes to CTX–MSN D1, CTX–MSN D2, TA–MSN, and MSN–MSN couplings could improve or restore basal ganglia action selection ability. In summary, we found multiple changes of parameters for synaptic efficacy and neural excitability that could improve action selection ability and at the same time reduce oscillations. Identification of such targets could potentially generate ideas for treatments of PD and increase our understanding of the relation between network dynamics and network function. PMID:28101525

  9. Multifunctional nanoparticles for real-time evaluation of toxicity during fetal development.

    PubMed

    Sweeney, Sean; Adamcakova-Dodd, Andrea; Thorne, Peter S; Assouline, Jose G

    2018-01-01

    Increasing production of nanomaterials in industrial quantities has led to public health concerns regarding exposure, particularly among pregnant women and developing fetuses. Information regarding the barrier capacity of the placenta for various nanomaterials is limited due to challenges working with ex vivo human placentas or in vivo animal models. To facilitate real-time in vivo imaging of placental transport, we have developed a novel, multifunctional nanoparticle, based on a core of mesoporous silica nanoparticles (MSN), and functionalized for magnetic resonance imaging (MRI), ultrasound, and fluorescent microscopy. Our MSN particles were tested as a tracking method for harmful and toxic nanomaterials. In gravid mice, intravenous injections of MSN were administered in the maternal circulation in early gestation (day 9) and late gestation (day 14). MRI and ultrasound were used to track the MSN following the injections. Changes in contrast relative to control mice indicated that MSN were observed in the embryos of mice following early gestation injections, while MSN were excluded from the embryo by the placenta following late gestation injections. The timing of transplacental barrier porosity is consistent with the notion that in mice there is a progressive increasing segregation by the placenta in later gestation. In addition, built-in physico-chemical properties of our MSN may present options for the therapeutic treatment of embryonic exposure. For example, if preventive measures such as detoxification of harmful compounds are implemented, the particle size and exposure timing can be tailored to selectively distribute to the maternal side of the trophoblast or delivered to the fetus.

  10. Language Learning Going Global: Linking Teachers and Learners via Commercial Skype-Based CMC

    ERIC Educational Resources Information Center

    Terhune, N. M.

    2016-01-01

    This paper reports on students' use of face-to-face synchronous computer-mediated communication (CMC) for oral language learning. It describes a university English language class designed to prepare students for overseas study in which a Skype-based English conversation school was piloted. The study offers analysis of how students used the CMC…

  11. The Skype-Buddy Model in an Online Environment: Patterns and Perceptions of Language Teachers in a Professional Development Program

    ERIC Educational Resources Information Center

    Macharaschwili, Carmen E.

    2013-01-01

    Patterns and perceptions of language teachers in a professional development program were examined through various forms of classroom discourse & multimodal products. Research questions include: What kinds of learning patterns emerge with the use of Skype in an online environment? What phases of cognitive engagement are evident in Skype…

  12. Student Perceptions and Experiences Using Jing and Skype in an Accounting Information Systems Class

    ERIC Educational Resources Information Center

    Charron, Kimberly; Raschke, Robyn

    2014-01-01

    The authors examine the use of technology to support students in their learning of practical accounting software applications while taking a traditional on-campus class. Specifically, they look at how Jing and Skype are used to facilitate successful completion of a series of simulations using Netsuite (NetSuite, Inc., San Mateo, CA) accounting…

  13. Using Virtual Environments as Professional Development Tools for Pre-Service Teachers Seeking ESOL Endorsement

    ERIC Educational Resources Information Center

    Blankenship, Rebecca J.

    2010-01-01

    The purpose of this study was to investigate the potential use of Second Life (Linden Labs, 2004) and Skype (Skype Limited, 2009) as simulated virtual professional development tools for pre-service teachers seeking endorsement in teaching English as a Second Official Language (ESOL). Second Life is an avatar-based Internet program that allows…

  14. Sustained delivery of siRNA/mesoporous silica nanoparticle (siRNA/MSN) complexes from nanofiber scaffolds for long-term gene silencing.

    PubMed

    Pinese, Coline; Lin, Junquan; Milbreta, Ulla; Li, Mingqiang; Wang, Yucai; Leong, Kam W; Chew, Sing Yian

    2018-06-08

    A low toxicity and efficient delivery system is needed to deliver small interfering RNAs (siRNA) in vitro and in vivo. The use of mesoporous silica nanoparticles (MSN) is becoming increasingly common due to its biocompatibility, tunable pore size and customizable properties. However, bolus delivery of siRNA/MSN complexes remains suboptimal, especially when a sustained and long-term administration is required. Here, we utilized electrospun scaffolds for sustained delivery of siRNA/MSN-PEI through surface adsorption and nanofiber encapsulation. As a proof-of-concept, we targeted collagen type I expression to modulate fibrous capsule formation. Surface adsorption of siRNA/MSN-PEI provided sustained availability of siRNA for at least 30 days in vitro. As compared to conventional bolus delivery, such scaffold-mediated transfection provided more effective gene silencing (p < 0.05). On the contrary, a longer sustained release was attained (at least 5 months) when siRNA/MSN-PEI complexes were encapsulated within the electrospun fibers. In vivo subcutaneous implantation and biodistribution analysis of these scaffolds revealed that siRNA remained localized up to ∼290 μm from the implants. Finally, a fibrous capsule reduction of ∼45.8 % was observed after 4 weeks in vivo as compared to negative scrambled siRNA treatment. Taken together, these results demonstrate the efficacy of scaffold-mediated sustained delivery of siRNA/MSN-PEI for long-term non-viral gene silencing applications. The bolus delivery of siRNA/ Mesoporous Silica Nanoparticles (MSN) complexes shows high efficiency to silence protein agonists of tumoral processes as cancer treatments. However, in tissue engineering area, scaffold mediated delivery is desired to achieve a local and sustained release of therapeutics. We showed the feasibility and the efficacy of siRNA/MSN delivered from electrospun scaffolds through surface adsorption and nanofiber encapsulation. We showed that this method enhances siRNA transfection efficiency and sustained targeted proteins silencing in vitro and in vivo. As a proof of concept, in this study, we targeted collagen type I expression to modulate fibrous capsule formation. However this platform can be applied to the release and transfection of siRNA or miRNA in cancer and tissue engineering applications. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  15. A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide.

    PubMed

    Setnik, Beatrice; Roland, Carl L; Sommerville, Kenneth W; Pixton, Glenn C; Berke, Robert; Calkins, Anne; Goli, Veeraindar

    2015-01-01

    To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone hydrochloride (MSN) using a standardized conversion guide. This open-label, single-arm study was conducted in 157 primary care centers in the United States. A total of 684 opioid-experienced adults with chronic moderate-to-severe pain were converted to oral administration of MSN from transdermal fentanyl and oral formulations of hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and other morphine products using a standardized conversion guide. The primary endpoint was the percentage of patients achieving a stable MSN dose within a 6-week titration phase. Secondary endpoints included duration of time to stable dose, number of titration steps, safety and efficacy measures, and investigator assessment of conversion guide utility. Of the 684 patients, 51.3% were converted to a stable dose of MSN (95% confidence interval: 47.5%, 55.1%). The mean (standard deviation) number of days to stable dose was 20 (8.94), and number of titration steps to stable dose was 2.4 (1.37). The majority of adverse events were mild/moderate and consistent with opioid therapy. Mean pain scores at stable dose decreased from baseline. Investigators were generally satisfied with the conversion guide and, in 94% of cases, reported they would use it again. Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of opioid-experienced patients with chronic moderate-to-severe pain. Investigators found the guide to be a useful tool to assist conversion of opioid-experienced patients to MSN.

  16. Fine-tuning the release of molecular guests from mesoporous silicas by controlling the orientation and mobility of surface phenyl substituents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Manzano, J. Sebastian; Singappuli-Arachchige, Dilini; Parikh, Bosky L.

    Phenyl-functionalized mesoporous silica materials were used to explore the effect of non-covalent interactions on the release of Ibuprofen into simulated body fluid. Variations in orientation and conformational mobility of the surface phenyl groups were introduced by selecting different structural precursors: a rigid upright orientation was obtained using phenyl groups directly bound to surface Si atoms (Ph-MSN), mobile groups were produced by using ethylene linkers to connect phenyl groups to the surface (PhEt-MSN), and groups co-planar to the surface were obtained by synthesizing a phenylene-bridged periodic mesoporous organosilica (Ph-PMO). The Ibuprofen release profiles from these materials and non-functionalized mesoporous silica nanoparticlesmore » (MSN) were analyzed using an adsorption-diffusion model. The model provided kinetic and thermodynamic parameters that evidenced fundamental differences in drug-surface interactions between the materials. All phenyl-bearing materials show lower Ibuprofen initial release rates than bare MSN. The conformationally locked Ph-MSN and Ph-PMO have stronger interactions with the drug (negative ΔG of adsorption) than the flexible PhEt-MSN and bare MSN (positive ΔG of adsorption). These differences in strength of adsorption are consistent with differences between interaction geometries obtained from DFT calculations. B3LYP-D3-optimized models show that π-π interactions contribute more to drug adsorption than H-bonding with silanol groups. Here, the results suggest that the type and geometry of interactions control the kinetics and extent of drug release, and should therefore serve as a guide to design new drug delivery systems with precise release behaviors customized to any desired target.« less

  17. Fine-tuning the release of molecular guests from mesoporous silicas by controlling the orientation and mobility of surface phenyl substituents

    DOE PAGES

    Manzano, J. Sebastian; Singappuli-Arachchige, Dilini; Parikh, Bosky L.; ...

    2017-12-05

    Phenyl-functionalized mesoporous silica materials were used to explore the effect of non-covalent interactions on the release of Ibuprofen into simulated body fluid. Variations in orientation and conformational mobility of the surface phenyl groups were introduced by selecting different structural precursors: a rigid upright orientation was obtained using phenyl groups directly bound to surface Si atoms (Ph-MSN), mobile groups were produced by using ethylene linkers to connect phenyl groups to the surface (PhEt-MSN), and groups co-planar to the surface were obtained by synthesizing a phenylene-bridged periodic mesoporous organosilica (Ph-PMO). The Ibuprofen release profiles from these materials and non-functionalized mesoporous silica nanoparticlesmore » (MSN) were analyzed using an adsorption-diffusion model. The model provided kinetic and thermodynamic parameters that evidenced fundamental differences in drug-surface interactions between the materials. All phenyl-bearing materials show lower Ibuprofen initial release rates than bare MSN. The conformationally locked Ph-MSN and Ph-PMO have stronger interactions with the drug (negative ΔG of adsorption) than the flexible PhEt-MSN and bare MSN (positive ΔG of adsorption). These differences in strength of adsorption are consistent with differences between interaction geometries obtained from DFT calculations. B3LYP-D3-optimized models show that π-π interactions contribute more to drug adsorption than H-bonding with silanol groups. Here, the results suggest that the type and geometry of interactions control the kinetics and extent of drug release, and should therefore serve as a guide to design new drug delivery systems with precise release behaviors customized to any desired target.« less

  18. Mesoporous Silica-Supported Amidozirconium-Catalyzed Carbonyl Hydroboration

    DOE PAGES

    Eedugurala, Naresh; Wang, Zhuoran; Chaudhary, Umesh; ...

    2015-11-04

    The hydroboration of aldehydes and ketones using a silica-supported zirconium catalyst is reported. Reaction of Zr(NMe 2) 4 and mesoporous silica nanoparticles (MSN) provides the catalytic material Zr(NMe 2) n@MSN. Exhaustive characterization of Zr(NMe 2) n@MSN with solid-state (SS)NMR and infrared spectroscopy, as well as through reactivity studies, suggests its surface structure is primarily ≡SiOZr(NMe 2) 3. The presence of these nitrogen-containing zirconium sites is supported by 15N NMR spectroscopy, including natural abundance 15N NMR measurements using dynamic nuclear polarization (DNP) SSNMR. The Zr(NMe 2) n@MSN material reacts with pinacolborane (HBpin) to provide Me 2NBpin and the material ZrH/Bpin@MSN thatmore » is composed of interacting surface-bonded zirconium hydride and surface-bonded borane ≡SiOBpin moieties in an approximately 1:1 ratio, as well as zirconium sites coordinated by dimethylamine. The ZrH/Bpin@MSN is characterized by 1H/ 2H and 11B SSNMR and infrared spectroscopy and through its reactivity with D 2. The zirconium hydride material or the zirconium amide precursor Zr(NMe 2) n@MSN catalyzes the selective hydroboration of aldehydes and ketones with HBpin in the presence of functional groups that are often reduced under hydroboration conditions or are sensitive to metal hydrides, including olefins, alkynes, nitro groups, halides, and ethers. Remarkably, this catalytic material may be recycled without loss of activity at least eight times, and air-exposed materials are catalytically active. These supported zirconium centers are robust catalytic sites for carbonyl reduction and that surface-supported, catalytically reactive zirconium hydride may be generated from zirconium-amide or zirconium alkoxide sites.« less

  19. Mesoporous Silica-Supported Amidozirconium-Catalyzed Carbonyl Hydroboration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Eedugurala, Naresh; Wang, Zhuoran; Chaudhary, Umesh

    The hydroboration of aldehydes and ketones using a silica-supported zirconium catalyst is reported. Reaction of Zr(NMe 2) 4 and mesoporous silica nanoparticles (MSN) provides the catalytic material Zr(NMe 2) n@MSN. Exhaustive characterization of Zr(NMe 2) n@MSN with solid-state (SS)NMR and infrared spectroscopy, as well as through reactivity studies, suggests its surface structure is primarily ≡SiOZr(NMe 2) 3. The presence of these nitrogen-containing zirconium sites is supported by 15N NMR spectroscopy, including natural abundance 15N NMR measurements using dynamic nuclear polarization (DNP) SSNMR. The Zr(NMe 2) n@MSN material reacts with pinacolborane (HBpin) to provide Me 2NBpin and the material ZrH/Bpin@MSN thatmore » is composed of interacting surface-bonded zirconium hydride and surface-bonded borane ≡SiOBpin moieties in an approximately 1:1 ratio, as well as zirconium sites coordinated by dimethylamine. The ZrH/Bpin@MSN is characterized by 1H/ 2H and 11B SSNMR and infrared spectroscopy and through its reactivity with D 2. The zirconium hydride material or the zirconium amide precursor Zr(NMe 2) n@MSN catalyzes the selective hydroboration of aldehydes and ketones with HBpin in the presence of functional groups that are often reduced under hydroboration conditions or are sensitive to metal hydrides, including olefins, alkynes, nitro groups, halides, and ethers. Remarkably, this catalytic material may be recycled without loss of activity at least eight times, and air-exposed materials are catalytically active. These supported zirconium centers are robust catalytic sites for carbonyl reduction and that surface-supported, catalytically reactive zirconium hydride may be generated from zirconium-amide or zirconium alkoxide sites.« less

  20. Mesoporous silica for drug delivery: Interactions with model fluorescent lipid vesicles and live cells.

    PubMed

    Bardhan, Munmun; Majumdar, Anupa; Jana, Sayantan; Ghosh, Tapas; Pal, Uttam; Swarnakar, Snehasikta; Senapati, Dulal

    2018-01-01

    Formulated mesoporous silica nanoparticle (MSN) systems offer the best possible drug delivery system through the release of drug molecules from the accessible pores. In the present investigation, steady state and time resolved fluorescence techniques along with the fluorescence imaging were applied to investigate the interactions of dye loaded MSN with fluorescent unilamellar vesicles and live cells. Here 1,2-dimyristoyl-sn-glycero-3-phospocholine (DMPC) was used to prepare Small Unilamellar Vesicles (SUVs) as the model membrane with fluorescent 1,6-diphenyl-1,3,5-hexatriene (DPH) molecule incorporated inside the lipid bilayer. The interaction of DPH incorporated DMPC membrane with Fluorescein loaded MSN lead to the release of Fluorescein (Fl) dye from the interior pores of MSN systems. The extent of release of Fl and spatial distribution of the DPH molecule has been explored by monitoring steady-state fluorescence intensity and fluorescence lifetime at physiological condition. To investigate the fate of drug molecule released from MSN, fluorescence anisotropy has been used. The drug delivery efficiency of the MSN as a carrier for doxorubicin (DOX), a fluorescent chemotherapeutic drug, has also been investigated at physiological conditions. The study gives a definite confirmation for high uptake and steady release of DOX in primary oral mucosal non-keratinized squamous cells in comparison to naked DOX treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Polydopamine-like Coatings as Payload Gatekeepers for Mesoporous Silica Nanoparticles.

    PubMed

    Moreno-Villaécija, Miguel-Ángel; Sedó-Vegara, Josep; Guisasola, Eduardo; Baeza, Alejandro; Regí, María Vallet; Nador, Fabiana; Ruiz-Molina, Daniel

    2018-03-07

    We report the use of bis-catecholic polymers as candidates for obtaining effective, tunable gatekeeping coatings for mesoporous silica nanoparticles (MSNs) intended for drug release applications. In monomers, catechol rings act as adhesive moieties and reactive sites for polymerization, together with middle linkers which may be chosen to tune the physicochemical properties of the resulting coating. Stable and low-toxicity coatings (pNDGA and pBHZ) were prepared from two bis-catechols of different polarity (NDGA and BHZ) on MSN carriers previously loaded with rhodamine B (RhB) as a model payload, by means of a previously reported synthetic methodology and without any previous surface modification. Coating robustness and payload content were shown to depend significantly on the workup protocol. The release profiles in a model physiological PBS buffer of coated systems (RhB@MSN@pNDGA and RhB@MSN@pBHZ) showed marked differences in the "gatekeeping" behavior of each coating, which correlated qualitatively with the chemical nature of their respective linker moieties. While the uncoated system (RhB@MSN) lost its payload almost completely after 2 days, release from RhB@MSN@pNDGA was virtually negligible, likely due to the low polarity of the parent bis-catechol (NDGA). As opposed to these extremes, RhB@MSN@pBHZ presented the most promising behavior, showing an intermediate release of 50% of the payload in the same period of time.

  2. The quality of internet information relating to oral leukoplakia.

    PubMed

    López-Jornet, Pía; Camacho-Alonso, Fabio

    2010-09-01

    The Internet provides great opportunities for patient healthcare education, but poses risks that inaccurate, outdated or harmful information will be disseminated. Our objective was determine the quality of the information available on the internet in relation to oral leukoplakia. Sites were identified using 3 search engines (Google, Yahoo and MSN), and the search term oral leukoplakia. The first 100 consecutive sites in each search were visited and classified. The websites were evaluated for quality of content by using the validated DISCERN rating instrument and the JAMA benchmarks; the existence of the Health on the Net (HON) seal was also registered. The Google search yielded 54.300 sites for oral leukoplakia, while Yahoo yielded 243.000 and MSN 103.000. We reviewed 21 Google websites, 20 Yahoo websites and 19 MSN. Based on the JAMA benchmarks, only 4 sites (19.1%) met the four criteria in the Google search, versus 2 sites (10%) in the Yahoo and 5 (26.3%) in MSN. With the DISCERN instrument, no site obtained the maximum score, with Google 13 sites presented serious deficiencies (61.9%), in the Yahoo search 14 (70%), and in MSN 15 (78.9%). Lastly, 4 of the Google sites (19.1%), four of the Yahoo sites (20%) and 2 (10.5%) MSN sites presented the HON seal. The quality of the health care information related to oral leukoplakia on the internet is poor.

  3. Enhanced Gene and siRNA Delivery by Polycation-Modified Mesoporous Silica Nanoparticles Loaded with Chloroquine

    PubMed Central

    Bhattarai, Shanta Raj; Muthuswamy, Elayaraja; Wani, Amit; Brichacek, Michal; Castañeda, Antonio L.; Brock, Stephanie L.

    2014-01-01

    Purpose To prepare mesoporous silica-based delivery systems capable of simultaneous delivery of drugs and nucleic acids. Methods The surface of mesoporous silica nanoparticles (MSN) was modified with poly(ethylene glycol) (PEG) and poly(2-(dimethylamino)ethylmethacrylate) (PDMAEMA) or poly (2-(diethylamino)ethylmethacrylate) (PDEAEMA). The particles were then loaded with a lysosomotropic agent chloroquine (CQ) and complexed with plasmid DNA or siRNA. The ability of the synthesized particles to deliver combinations of CQ and nucleic acids was evaluated using luciferase plasmid DNA and siRNA targeting luciferase and GAPDH. Results The results show a slow partial MSN dissolution to form hollow silica nanoparticles in aqueous solution. The biological studies show that polycation-modified MSN are able to simultaneously deliver CQ with DNA and siRNA. The co-delivery of CQ and the nucleic acids leads to a significantly increased transfection and silencing activity of the complexes compared with MSN not loaded with CQ. Conclusion PEGylated MSN modified with polycations are promising delivery vectors for combination drug/nucleic acid therapies. PMID:20730557

  4. Golgi Study of Medium Spiny Neurons from Dorsolateral Striatum of the Turtle Trachemys scripta elegans.

    PubMed

    González, Carolina; Mendoza, Janeth; Avila-Costa, María Rosa; Arias, Juan M; Barral, Jaime

    2013-10-25

    Comparative anatomy has shown similarities between reptilian and mammalian basal ganglia. Here the morphological characteristics of the medium spiny neurons (MSN) in the dorsolateral striatum (DLS) of the turtle are described after staining them with the Golgi technique. The soma of MSN in DLS showed three main forms: spherical, ovoid, and fusiform. The number of primary dendritic branches (3-4 dendrites/cell) was less than observed in mammals. The MSN axon originates mainly from the soma, and randomly it emerges at the beginning of the primary dendrite. The main differences between turtle and mammalian MSN were detected on dendritic spines. Short, thin, bifurcated and fungiform types of dendritic spines were observed in the turtle's MSN, according to their shape. In most of the analyzed spines, it was found that its length considerably exceeded that reported in mammals, with dendritic spines up to 8μm in length. These differences could play an important role in the modulation of motor networks preserved along the vertebrate evolution. Copyright © 2013. Published by Elsevier Ireland Ltd.

  5. Contributory Role of Virtual Courses via Skype to Control Embarrassment of Iranian EFL Learners' Performance

    ERIC Educational Resources Information Center

    Jahanbakhsh, Elham; Chalak, Azizeh

    2018-01-01

    In recent years, there has been an increasing interest in integration of technology for pedagogical purposes. The present study aimed at finding out how presentation in the frame of virtual courses can control embarrassment and shyness of Iranian EFL learners. The practical part concentrated on using Skype for the purpose of presentation in…

  6. Teaching a Student to Read through a Screen: Using SKYPE to Facilitate a Field Experience

    ERIC Educational Resources Information Center

    Gunther, Jeanne

    2016-01-01

    The Distance Clinical Connecting Candidates and Children (DC4) is an innovative new model for providing a clinical experience in a reading methods course. Pre-service teachers used this model to implement assessments and lessons via SKYPE with local elementary students. I designed this model to provide a clinical experience when faced with…

  7. Oral Proficiency Teaching with WebCERF and Skype: Scenarios for Online Production and Interaction Tasks

    ERIC Educational Resources Information Center

    Jager, Sake; Meima, Estelle; Oggel, Gerdientje

    2013-01-01

    This article reports our findings on using WebCEF as a CEFR familiarization and self-assessment tool for oral proficiency. Furthermore, we outline how we have implemented Skype as a tool for telecollaboration in our language programmes. The primary purpose of our study was to explore how students and teachers would perceive the potential benefits…

  8. YouTube and Skype Modes of Virtual Learning Performance in Relations to Cognitive Styles of Students

    ERIC Educational Resources Information Center

    Jena, Ananta Kumar; Deka, Monisha; Barman, Munmi

    2017-01-01

    The study aimed to find out the relationship between cognitive styles, YouTube learning and Skype learning performance of secondary school students. For that purpose, the researchers randomly selected 20 students from two 9th standards of two English medium secondary schools of Silchar Town, Assam, India to conduct the experiment. Quasi…

  9. Overcoming Geographical Obstacles: The Use of Skype in a Graduate-Level Social Media and Marketing Course

    ERIC Educational Resources Information Center

    Faulds, David J.

    2015-01-01

    This paper presents the results of a three-year research and teaching effort that focused on measuring the perceived effectiveness of Skype as a delivery platform for presentations made to students enrolled in a Professional MBA program by nationally acclaimed authors working in the area of social media. The research also investigated the authors'…

  10. Immune response to functionalized mesoporous silica nanoparticles for targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Heidegger, Simon; Gößl, Dorothée; Schmidt, Alexandra; Niedermayer, Stefan; Argyo, Christian; Endres, Stefan; Bein, Thomas; Bourquin, Carole

    2015-12-01

    Multifunctional mesoporous silica nanoparticles (MSN) have attracted substantial attention with regard to their high potential for targeted drug delivery. For future clinical applications it is crucial to address safety concerns and understand the potential immunotoxicity of these nanoparticles. In this study, we assess the biocompatibility and functionality of multifunctional MSN in freshly isolated, primary murine immune cells. We show that the functionalized silica nanoparticles are rapidly and efficiently taken up into the endosomal compartment by specialized antigen-presenting cells such as dendritic cells. The silica nanoparticles showed a favorable toxicity profile and did not affect the viability of primary immune cells from the spleen in relevant concentrations. Cargo-free MSN induced only very low immune responses in primary cells as determined by surface expression of activation markers and release of pro-inflammatory cytokines such as Interleukin-6, -12 and -1β. In contrast, when surface-functionalized MSN with a pH-responsive polymer capping were loaded with an immune-activating drug, the synthetic Toll-like receptor 7 agonist R848, a strong immune response was provoked. We thus demonstrate that MSN represent an efficient drug delivery vehicle to primary immune cells that is both non-toxic and non-inflammagenic, which is a prerequisite for the use of these particles in biomedical applications.Multifunctional mesoporous silica nanoparticles (MSN) have attracted substantial attention with regard to their high potential for targeted drug delivery. For future clinical applications it is crucial to address safety concerns and understand the potential immunotoxicity of these nanoparticles. In this study, we assess the biocompatibility and functionality of multifunctional MSN in freshly isolated, primary murine immune cells. We show that the functionalized silica nanoparticles are rapidly and efficiently taken up into the endosomal compartment by specialized antigen-presenting cells such as dendritic cells. The silica nanoparticles showed a favorable toxicity profile and did not affect the viability of primary immune cells from the spleen in relevant concentrations. Cargo-free MSN induced only very low immune responses in primary cells as determined by surface expression of activation markers and release of pro-inflammatory cytokines such as Interleukin-6, -12 and -1β. In contrast, when surface-functionalized MSN with a pH-responsive polymer capping were loaded with an immune-activating drug, the synthetic Toll-like receptor 7 agonist R848, a strong immune response was provoked. We thus demonstrate that MSN represent an efficient drug delivery vehicle to primary immune cells that is both non-toxic and non-inflammagenic, which is a prerequisite for the use of these particles in biomedical applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06122a

  11. Msn2p/Msn4p act as a key transcriptional activator of yeast cytoplasmic thiol peroxidase II.

    PubMed

    Hong, Seung-Keun; Cha, Mee-Kyung; Choi, Yong-Soo; Kim, Won-Cheol; Kim, Il-Han

    2002-04-05

    We observed that the transcription of Saccharomyces cerevisiae cytoplasmic thiol peroxidase type II (cTPx II) (YDR453C) is regulated in response to various stresses (e.g. oxidative stress, carbon starvation, and heat-shock). It has been suggested that both transcription-activating proteins, Yap1p and Skn7p, regulate the transcription of cTPx II upon exposure to oxidative stress. However, a dramatic loss of transcriptional response to various stresses in yeast mutant strains lacking both Msn2p and Msn4p suggests that the transcription factors act as a principal transcriptional activator. In addition to two Yap1p response elements (YREs), TTACTAA and TTAGTAA, the presence of two stress response elements (STREs) (CCCCT) in the upstream sequence of cTPx II also suggests that Msn2p/Msn4p could control stress-induced expression of cTPx II. Analysis of the transcriptional activity of site-directed mutagenesis of the putative STREs (STRE1 and STRE2) and YREs (TRE1 and YRE2) in terms of the activity of a lacZ reporter gene under control of the cTPx II promoter indicates that STRE2 acts as a principal binding element essential for transactivation of the cTPx II promoter. The transcriptional activity of the cTPx II promoter was exponentially increased after postdiauxic growth. The transcriptional activity of the cTPx II promoter is greatly increased by rapamycin. Deletion of Tor1, Tor2, Ras1, and Ras2 resulted in a considerable induction when compared with their parent strains, suggesting that the transcription of cTPx II is under negative control of the Ras/cAMP and target of rapamycin signaling pathways. Taken together, these results suggest that cTPx II is a target of Msn2p/Msn4p transcription factors under negative control of the Ras-protein kinase A and target of rapamycin signaling pathways. Furthermore, the accumulation of cTPx II upon exposure to oxidative stress and during the postdiauxic shift suggests an important antioxidant role in stationary phase yeast cells.

  12. Client-side Skype forensics: an overview

    NASA Astrophysics Data System (ADS)

    Meißner, Tina; Kröger, Knut; Creutzburg, Reiner

    2013-03-01

    IT security and computer forensics are important components in the information technology. In the present study, a client-side Skype forensics is performed. It is designed to explain which kind of user data are stored on a computer and which tools allow the extraction of those data for a forensic investigation. There are described both methods - a manual analysis and an analysis with (mainly) open source tools, respectively.

  13. The Use of Skype as a Synchronous Communication Tool between Foreign Language College Students and Native Speakers

    ERIC Educational Resources Information Center

    Guerrero, Mario

    2012-01-01

    The rapid growth and interest of college students in Computer Mediated Communication and social media have impacted the second language learning and teaching process. This article reports on a pilot project that attempts to analyze the use of Skype as a synchronous communication tool in regard to the attitudes of students in learning a foreign…

  14. Hsf1p and Msn2/4p cooperate in the expression of Saccharomyces cerevisiae genes HSP26 and HSP104 in a gene- and stress type-dependent manner.

    PubMed

    Amorós, M; Estruch, F

    2001-03-01

    Saccharomyces cerevisiae possesses several transcription factors involved in the transcriptional activation of stress-induced genes. Among them, the heat shock factor (Hsf1p) and the zinc finger proteins of the general stress response (Msn2p and Msn4p) have been shown to play a major role in stress protection. Some heat shock protein (HSP) genes contain both heat shock elements (HSEs) and stress response elements (STREs), suggesting the involvement of both transcription factors in their regulation. Analysis of the stress-induced expression of two of these genes, HSP26 and HSP104, reveals that the contribution of Hsf1p and Msn2/4p is different depending on the gene and the stress condition.

  15. X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene.

    PubMed

    Lagresle-Peyrou, Chantal; Luce, Sonia; Ouchani, Farid; Soheili, Tayebeh Shabi; Sadek, Hanem; Chouteau, Myriam; Durand, Amandine; Pic, Isabelle; Majewski, Jacek; Brouzes, Chantal; Lambert, Nathalie; Bohineust, Armelle; Verhoeyen, Els; Cosset, François-Loïc; Magerus-Chatinet, Aude; Rieux-Laucat, Frédéric; Gandemer, Virginie; Monnier, Delphine; Heijmans, Catherine; van Gijn, Marielle; Dalm, Virgil A; Mahlaoui, Nizar; Stephan, Jean-Louis; Picard, Capucine; Durandy, Anne; Kracker, Sven; Hivroz, Claire; Jabado, Nada; de Saint Basile, Geneviève; Fischer, Alain; Cavazzana, Marina; André-Schmutz, Isabelle

    2016-12-01

    We investigated 7 male patients (from 5 different families) presenting with profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, a poor immune response to vaccine antigens, and increased susceptibility to bacterial and varicella zoster virus infections. We sought to characterize the genetic defect involved in a new form of X-linked immunodeficiency. We performed genetic analyses and an exhaustive phenotypic and functional characterization of the lymphocyte compartment. We observed hemizygous mutations in the moesin (MSN) gene (located on the X chromosome and coding for MSN) in all 7 patients. Six of the latter had the same missense mutation, which led to an amino acid substitution (R171W) in the MSN four-point-one, ezrin, radixin, moesin domain. The seventh patient had a nonsense mutation leading to a premature stop codon mutation (R533X). The naive T-cell counts were particularly low for age, and most CD8 + T cells expressed the senescence marker CD57. This phenotype was associated with impaired T-cell proliferation, which was rescued by expression of wild-type MSN. MSN-deficient T cells also displayed poor chemokine receptor expression, increased adhesion molecule expression, and altered migration and adhesion capacities. Our observations establish a causal link between an ezrin-radixin-moesin protein mutation and a primary immunodeficiency that could be referred to as X-linked moesin-associated immunodeficiency. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Msn2 Coordinates a Stoichiometric Gene Expression Program

    PubMed Central

    Stewart-Ornstein, Jacob; Nelson, Christopher; DeRisi, Joe; Weissman, Jonathan S.; El-Samad, Hana

    2014-01-01

    Summary Background Many cellular processes operate in an “analog” regime in which the magnitude of the response is precisely tailored to the intensity of the stimulus. In order to maintain the coherence of such responses, the cell must provide for proportional expression of multiple target genes across a wide dynamic range of induction states. Our understanding of the strategies used to achieve graded gene regulation is limited. Results In this work, we document a relationship between stress responsive gene expression and the transcription factor Msn2 that is graded over a large range of Msn2 cocnentrations. We use computational modeling, in vivo, and in vitro analysis to dissect the roots of this relationship. Our studies reveal a simple and general strategy based on non-cooperative low-affinity interactions between Msn2 and its cognate binding sites, as well as competition over a large number of Msn2 binding sites in the genome relative to the number of Msn2 molecules. Conclusions In addition to enabling precise tuning of gene expression to the state of the environment, this strategy ensures co-linear activation of target genes, allowing for stoichiometric expression of large groups of genes without extensive promoter tuning. Furthermore, such a strategy enables precise modulation of the activity of any given promoter by addition of binding sites without altering the qualitative relationship between different genes in a regulon. This feature renders a given regulon highly ‘evolvable’. PMID:24210615

  17. "Sounds a Bit Crazy, But It Was Almost More Personal:" A Qualitative Study of Patient and Clinician Experiences of Physical Therapist-Prescribed Exercise For Knee Osteoarthritis Via Skype.

    PubMed

    Hinman, R S; Nelligan, R K; Bennell, K L; Delany, C

    2017-12-01

    To explore the experience of patients and physical therapists with Skype for exercise management of knee osteoarthritis (OA). This was a qualitative study. The Donabedian model for quality assessment in health care (structure, process, and outcomes) informed semistructured individual interview questions. The study involved 12 purposively sampled patients with knee OA who received physical therapist-prescribed exercise over Skype, and all therapists (n = 8) who delivered the intervention in a clinical trial were interviewed about their experiences. Interviews were audio recorded and transcribed. Two investigators undertook coding and analysis using a thematic approach. Six themes arose from both patients and therapists. The themes were Structure: technology (easy to use, variable quality, set-up assistance helpful) and patient convenience (time efficient, flexible, increased access); Process: empowerment to self-manage (facilitated by home environment and therapists focusing on effective treatment) and positive therapeutic relationships (personal undivided attention from therapists, supportive friendly interactions); and Outcomes: satisfaction with care (satisfying, enjoyable, patients would recommend, therapists felt Skype more useful as adjunct to usual practice) and patient benefits (reduced pain, improved function, improved confidence and self-efficacy). A seventh theme arose from therapists regarding process: adjusting routine treatment (need to modify habits, discomfort without hands-on, supported by research environment). Patients and physical therapists described mostly positive experiences using Skype as a service delivery model for physical therapist-supervised exercise management of moderate knee OA. Such a model is feasible and acceptable and has the potential to increase access to supervised exercise management for people with knee OA, either individually or in combination with traditional in-clinic visits. © 2017, American College of Rheumatology.

  18. Intrinsic radiolabeling of Titanium-45 using mesoporous silica nanoparticles.

    PubMed

    Chen, Feng; Valdovinos, Hector F; Hernandez, Reinier; Goel, Shreya; Barnhart, Todd E; Cai, Weibo

    2017-06-01

    Titanium-45 ( 45 Ti) with a three-hour half-life (t 1/2 =3.08 h), low maximum positron energy and high positron emission branching ratio, is a suitable positron emission tomography (PET) isotope whose potential has not yet been fully explored. Complicated radiochemistry and rapid hydrolysis continue to be major challenges to the development of 45 Ti compounds based on a traditional chelator-based radiolabeling strategy. In this study we introduced an intrinsic (or chelator-free) radiolabeling technique for the successful labeling of 45 Ti using mesoporous silica nanoparticle (MSN). We synthesized uniform MSN with an average particle size of ∼150 nm in diameter. The intrinsic 45 Ti-labeling was accomplished through strong interactions between 45 Ti (hard Lewis acid) and hard oxygen donors (hard Lewis bases), the deprotonated silanol groups (-Si-O-) from the outer surface and inner meso-channels of MSN. In vivo tumor-targeted PET imaging of as-developed PEGylated [ 45 Ti]MSN was further demonstrated in the 4T1 murine breast tumor-bearing mice. This MSN-based intrinsic radiolabeling strategy could open up new possibilities and speed up the biomedical applications of 45 Ti in the future.

  19. The use of Skype in a community hospital inpatient palliative medicine consultation service.

    PubMed

    Brecher, David B

    2013-01-01

    Skype™, an Internet-based communication tool, has enhanced communication under numerous circumstances. As telemedicine continues to be an increasing part of medical practice, there will be more opportunities to use Skype and similar tools. Numerous scenarios in the lay literature have helped to highlight the potential uses. Although most commonly used to enhance physician-to-patient communication, there has been limited reported use of Skype for patient-to-family communication, especially in end of life and palliative care. Our inpatient Palliative Medicine Consultation Service has offered and used this technology to enhance our patients' quality of life. The objective was to provide another tool for our patients to use to communicate with family and/or friends, especially under circumstances in which clinical symptoms, functional status, financial concerns, or geographic limitations preclude in-person face-to face communication.

  20. A subset of FG-nucleoporins is necessary for efficient Msn5-mediated nuclear protein export

    PubMed Central

    Finn, Erin M.; DeRoo, Elise P.; Clement, George W.; Rao, Sheila; Kruse, Sarah E.; Kokanovich, Kate M.; Belanger, Kenneth D.

    2013-01-01

    The transport of proteins between the cytoplasm and nucleus requires interactions between soluble transport receptors (karyopherins) and phenylalanine-glycine (FG) repeat domains on nuclear pore complex proteins (nucleoporins). However, the role of specific FG repeat-containing nucleoporins in nuclear protein export has not been carefully investigated. We have developed a novel kinetic assay to investigate the relative export kinetics mediated by the karyopherin Msn5/Kap142 in yeast containing specific FG-Nup mutations. Using the Msn5 substrate Crz1 as a marker for Msn5-mediated protein export, we observe that deletions of NUP100 or NUP2 result in decreased rates of Crz1 export, while nup60Δ and nup42Δ mutants do not vary significantly from wild type. The decreased Msn5 export rate in nup100Δ was confirmed using Mig1-GFP as a transport substrate. A nup100ΔGLFG mutant shows defects in nuclear export kinetics similar to a nup100Δ deletion. Removal of FG-repeats from Nsp1 also decreases export kinetics, while a loss of Nup1 FXFGs does not. To confirm that our export data reflected functional differences in protein localization, we performed Crz1 transcription activation assays using a CDRE::LacZ reporter gene that is upregulated upon increased transcription activation by Crz1 in vivo. We observe that expression from this reporter increases in nup100ΔGLFG and nsp1ΔFGΔFXFG strains that exhibit decreased Crz1 export kinetics but resembles wild-type levels in nup1ΔFXFG strains that do not exhibit export defects. These data provide evidence that the export of Msn5 is likely mediated by a specific subset of FG-Nups and that the GLFG repeat domain of Nup100 is important for Msn5-mediated nuclear protein export. PMID:23295456

  1. Using skype as an alternative for residency selection interviews.

    PubMed

    Edje, Louito; Miller, Christine; Kiefer, Jacklyn; Oram, David

    2013-09-01

    Residency interviews can place significant time and financial burdens on applicants. To determine whether the use of Skype as a screening tool during interview season in a family medicine residency is cost-effective and time-efficient for the applicant and the residency program. We surveyed 2 groups of medical students during interviews for our family medicine program. Thirty-two students were interviewed via our face-to-face, traditional interview (TI) process, and 10 students, the second group, who did not meet the program's standard interview selection criteria for TI, underwent our Skype interview (SI) process. Using an unpaired t test, we found that the applicants' costs of an SI were significantly less than a TI, $566 (95% confidence interval [CI] $784-$349, P < .001). Direct cash savings plus indirect salary savings to the program were $5,864, with a time savings of 7 interview days. Three of the applicants who were participants in the SI limb of the study were in our final rank order list. For interviewing in family medicine residencies, use of Skype may be a cost-effective and time-efficient screening tool for both the applicant and the program. Alternate uses of SI may include the time-sensitive, postmatch Supplemental Offer and Acceptance Program.

  2. Using Skype as an Alternative for Residency Selection Interviews

    PubMed Central

    Edje, Louito; Miller, Christine; Kiefer, Jacklyn; Oram, David

    2013-01-01

    Background Residency interviews can place significant time and financial burdens on applicants. Objective To determine whether the use of Skype as a screening tool during interview season in a family medicine residency is cost-effective and time-efficient for the applicant and the residency program. Methods We surveyed 2 groups of medical students during interviews for our family medicine program. Thirty-two students were interviewed via our face-to-face, traditional interview (TI) process, and 10 students, the second group, who did not meet the program's standard interview selection criteria for TI, underwent our Skype interview (SI) process. Results Using an unpaired t test, we found that the applicants' costs of an SI were significantly less than a TI, $566 (95% confidence interval [CI] $784–$349, P < .001). Direct cash savings plus indirect salary savings to the program were $5,864, with a time savings of 7 interview days. Three of the applicants who were participants in the SI limb of the study were in our final rank order list. Conclusions For interviewing in family medicine residencies, use of Skype may be a cost-effective and time-efficient screening tool for both the applicant and the program. Alternate uses of SI may include the time-sensitive, postmatch Supplemental Offer and Acceptance Program. PMID:24404318

  3. Web-based objective structured clinical examination with remote standardized patients and Skype: resident experience.

    PubMed

    Langenau, Erik; Kachur, Elizabeth; Horber, Dot

    2014-07-01

    Using Skype and remote standardized patients (RSPs), investigators sought to evaluate user acceptance of a web-based objective structured clinical examination (OSCE) among resident physicians. After participating in four web-based clinical encounters addressing pain with RSPs, 59 residents from different training programs, disciplines and geographic locations completed a 52-item questionnaire regarding their experience with Skype and RSPs. Open-ended responses were solicited as well. The majority of participants (97%) agreed or strongly agreed the web-based format was convenient and a practical learning exercise, and 90% agreed or strongly agreed the format was effective in teaching communication skills. Although 93% agreed or strongly agreed they could communicate easily with RSPs using Skype, 80% preferred traditional face-to-face clinical encounters, and 58% reported technical difficulties during the encounters. Open-ended written responses supported survey results. Findings from this study expose challenges with technology and human factors, but positive experiences support the continued investigation of web-based OSCEs as a synchronous e-learning initiative for teaching and assessing doctor-patient communication. Such educational programs are valuable but unlikely to replace face-to-face encounters with patients. This web-based OSCE program provides physician learners with additional opportunity to improve doctor-patient communication. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington's disease model mice.

    PubMed

    Tong, Xiaoping; Ao, Yan; Faas, Guido C; Nwaobi, Sinifunanya E; Xu, Ji; Haustein, Martin D; Anderson, Mark A; Mody, Istvan; Olsen, Michelle L; Sofroniew, Michael V; Khakh, Baljit S

    2014-05-01

    Huntington's disease (HD) is characterized by striatal medium spiny neuron (MSN) dysfunction, but the underlying mechanisms remain unclear. We explored roles for astrocytes, in which mutant huntingtin is expressed in HD patients and mouse models. We found that symptom onset in R6/2 and Q175 HD mouse models was not associated with classical astrogliosis, but was associated with decreased Kir4.1 K(+) channel functional expression, leading to elevated in vivo striatal extracellular K(+), which increased MSN excitability in vitro. Viral delivery of Kir4.1 channels to striatal astrocytes restored Kir4.1 function, normalized extracellular K(+), ameliorated aspects of MSN dysfunction, prolonged survival and attenuated some motor phenotypes in R6/2 mice. These findings indicate that components of altered MSN excitability in HD may be caused by heretofore unknown disturbances of astrocyte-mediated K(+) homeostasis, revealing astrocytes and Kir4.1 channels as therapeutic targets.

  5. Bromelain Surface Modification Increases the Diffusion of Silica Nanoparticles in the Tumor Extracellular Matrix

    PubMed Central

    2015-01-01

    Tumor extracellular matrix (ECM) represents a major obstacle to the diffusion of therapeutics and drug delivery systems in cancer parenchyma. This biological barrier limits the efficacy of promising therapeutic approaches including the delivery of siRNA or agents intended for thermoablation. After extravasation due to the enhanced penetration and retention effect of tumor vasculature, typical nanotherapeutics are unable to reach the nonvascularized and anoxic regions deep within cancer parenchyma. Here, we developed a simple method to provide mesoporous silica nanoparticles (MSN) with a proteolytic surface. To this extent, we chose to conjugate MSN to Bromelain (Br–MSN), a crude enzymatic complex, purified from pineapple stems, that belongs to the peptidase papain family. This surface modification increased particle uptake in endothelial, macrophage, and cancer cell lines with minimal impact on cellular viability. Most importantly Br–MSN showed an increased ability to digest and diffuse in tumor ECM in vitro and in vivo. PMID:25119793

  6. Bromelain surface modification increases the diffusion of silica nanoparticles in the tumor extracellular matrix.

    PubMed

    Parodi, Alessandro; Haddix, Seth G; Taghipour, Nima; Scaria, Shilpa; Taraballi, Francesca; Cevenini, Armando; Yazdi, Iman K; Corbo, Claudia; Palomba, Roberto; Khaled, Sm Z; Martinez, Jonathan O; Brown, Brandon S; Isenhart, Lucas; Tasciotti, Ennio

    2014-10-28

    Tumor extracellular matrix (ECM) represents a major obstacle to the diffusion of therapeutics and drug delivery systems in cancer parenchyma. This biological barrier limits the efficacy of promising therapeutic approaches including the delivery of siRNA or agents intended for thermoablation. After extravasation due to the enhanced penetration and retention effect of tumor vasculature, typical nanotherapeutics are unable to reach the nonvascularized and anoxic regions deep within cancer parenchyma. Here, we developed a simple method to provide mesoporous silica nanoparticles (MSN) with a proteolytic surface. To this extent, we chose to conjugate MSN to Bromelain (Br-MSN), a crude enzymatic complex, purified from pineapple stems, that belongs to the peptidase papain family. This surface modification increased particle uptake in endothelial, macrophage, and cancer cell lines with minimal impact on cellular viability. Most importantly Br-MSN showed an increased ability to digest and diffuse in tumor ECM in vitro and in vivo.

  7. Glycogen function in adult central and peripheral nerves.

    PubMed

    Evans, Richard D; Brown, Angus M; Ransom, Bruce R

    2013-08-01

    We studied the roles of glycogen in axonal pathways of the central nervous system (CNS) and peripheral nervous system (PNS). By using electrophysiological recordings, in combination with biochemical glycogen assay, it was possible to determine whether glycogen was crucial to axon function under different conditions. Glycogen was present both in mouse optic nerve (MON) and in mouse sciatic nerve (MSN). Aglycemia caused loss of the compound action potential (CAP) in both pathways after a latency of 15 min (MON) and 120 min for myelinated axons (A fibers) in the MSN. With the exception of unmyelinated axons (C fibers) in the MSN, CAP decline began when usable glycogen was exhausted. Glycogen was located in astrocytes in the MON and in myelinating Schwann cells in the MSN; it was absent from the Schwann cells surrounding unmyelinated C fibers. In MON, astrocytic glycogen is metabolized to lactate and "shuttled" to axons to support metabolism. The ability of lactate to support A fiber conduction in the absence of glucose suggests a common pathway in both the CNS and the PNS. Lactate is released from MON and MSN in substantial quantities. That lactate levels fall in MSN in the presence of diaminobenzidine, which inhibits glycogen phosphorylase, strongly suggests that glycogen metabolism contributes to lactate release under resting conditions. Glycogen is a "backup" energy substrate in both the CNS and the PNS and, beyond sustaining excitability during glucose deprivation, has the capacity to subsidize the axonal energy demands during times of intense activity in the presence of glucose. Copyright © 2013 Wiley Periodicals, Inc.

  8. Assignment of the Stereochemistry and Anomeric Configuration of Sugars within Oligosaccharides Via Overlapping Disaccharide Ladders Using MSn

    NASA Astrophysics Data System (ADS)

    Konda, Chiharu; Londry, Frank A.; Bendiak, Brad; Xia, Yu

    2014-08-01

    A systematic approach is described that can pinpoint the stereo-structures (sugar identity, anomeric configuration, and location) of individual sugar units within linear oligosaccharides. Using a highly modified mass spectrometer, dissociation of linear oligosaccharides in the gas phase was optimized along multiple-stage tandem dissociation pathways (MSn, n = 4 or 5). The instrument was a hybrid triple quadrupole/linear ion trap mass spectrometer capable of high-efficiency bidirectional ion transfer between quadrupole arrays. Different types of collision-induced dissociation (CID), either on-resonance ion trap or beam-type CID could be utilized at any given stage of dissociation, enabling either glycosidic bond cleavages or cross-ring cleavages to be maximized when wanted. The approach first involves optimizing the isolation of disaccharide units as an ordered set of overlapping substructures via glycosidic bond cleavages during early stages of MSn, with explicit intent to minimize cross-ring cleavages. Subsequently, cross-ring cleavages were optimized for individual disaccharides to yield key diagnostic product ions ( m/ z 221). Finally, fingerprint patterns that establish stereochemistry and anomeric configuration were obtained from the diagnostic ions via CID. Model linear oligosaccharides were derivatized at the reducing end, allowing overlapping ladders of disaccharides to be isolated from MSn. High confidence stereo-structural determination was achieved by matching MSn CID of the diagnostic ions to synthetic standards via a spectral matching algorithm. Using this MSn ( n = 4 or 5) approach, the stereo-structures, anomeric configurations, and locations of three individual sugar units within two pentasaccharides were successfully determined.

  9. Medical teleconference about thoracic surgery using free Internet software.

    PubMed

    Obuchi, Toshiro; Shiono, Hiroyuki; Shimada, Junichi; Kaga, Kichizo; Kurihara, Masatoshi; Iwasaki, Akinori

    2011-11-01

    Surgical teleconferences using advanced academic networks are becoming common; however, reports regarding Internet teleconferencing using free software packages such as Skype, USTREAM, and Dropbox are very rare. Teleconferences concerning mainly surgical techniques were held five times between Fukuoka University Hospital and other institutions from April to September 2010. These teleconferences used Skype and USTREAM as videophones to establish communication. Both PowerPoint presentations and surgical videos were made. These presentation files were previously sent to all stations via mail, e-mail, or Dropbox, and shared. A slide-show was simultaneously performed following the presenter's cue in each station. All teleconferences were successfully completed, even though there were minor instances of the Skype link being broken for unknown reasons during the telecommunication. Internet surgical teleconferences using ordinary software are therefore considered to be sufficiently feasible. This method will become more convenient and common as the Internet environments advance.

  10. From Cork to Budapest by Skype: living and dying.

    PubMed

    Battley, Jodie E; Balding, Lucy; Gilligan, Oonagh; O'Connell, Catherine; O'Brien, Tony

    2012-06-01

    Effective communication is a prerequisite to the delivery of good palliative care. The increasing use of web-based technologies and social media challenges us to reassess traditional communication styles and to define appropriate applications of evolving technologies. The use of Skype, blogging and webcams by patients in our hospitals and hospices is increasing. As illustrated in this case, the availability of such technology enables patients and families to communicate across wide geographical boundaries. This has particular advantages in situations where family members cannot routinely attend at the hospital because of other commitments or distance. The authors report on the varying use of Skype video-telephony over the course of a cancer patient's illness from the initial treatment phase through to the final days and hours of life. The benefits and challenges of using such technologies in a hospital setting and particularly in end-of-life circumstances are discussed.

  11. LC-MSn Analysis of Isomeric Chondroitin Sulfate Oligosaccharides Using a Chemical Derivatization Strategy

    PubMed Central

    Huang, Rongrong; Pomin, Vitor H.; Sharp, Joshua S.

    2011-01-01

    Improved methods for structural analyses of glycosaminoglycans (GAGs) are required to understand their functional roles in various biological processes. Major challenges in structural characterization of complex GAG oligosaccharides using liquid chromatography-mass spectrometry (LC-MS) include the accurate determination of the patterns of sulfation due to gas-phase losses of the sulfate groups upon collisional activation and inefficient on-line separation of positional sulfation isomers prior to MS/MS analyses. Here, a sequential chemical derivatization procedure including permethylation, desulfation, and acetylation was demonstrated to enable both on-line LC separation of isomeric mixtures of chondroitin sulfate (CS) oligosaccharides and accurate determination of sites of sulfation by MSn. The derivatized oligosaccharides have sulfate groups replaced with acetyl groups, which are sufficiently stable to survive MSn fragmentation and reflect the original sulfation patterns. A standard reversed-phase LC-MS system with a capillary C18 column was used for separation, and MSn experiments using collision-induced dissociation (CID) were performed. Our results indicate that the combination of this derivatization strategy and MSn methodology enables accurate identification of the sulfation isomers of CS hexasaccharides with either saturated or unsaturated nonreducing ends. Moreover, derivatized CS hexasaccharide isomer mixtures become separable by LC-MS method due to different positions of acetyl modifications. PMID:21953261

  12. Controlled release and intracellular protein delivery from mesoporous silica nanoparticles.

    PubMed

    Deodhar, Gauri V; Adams, Marisa L; Trewyn, Brian G

    2017-01-01

    Protein therapeutics are promising candidates for disease treatment due to their high specificity and minimal adverse side effects; however, targeted protein delivery to specific sites has proven challenging. Mesoporous silica nanoparticles (MSN) have demonstrated to be ideal candidates for this application, given their high loading capacity, biocompatibility, and ability to protect host molecules from degradation. These materials exhibit tunable pore sizes, shapes and volumes, and surfaces which can be easily functionalized. This serves to control the movement of molecules in and out of the pores, thus entrapping guest molecules until a specific stimulus triggers release. In this review, we will cover the benefits of using MSN as protein therapeutic carriers, demonstrating that there is great diversity in the ways MSN can be used to service proteins. Methods for controlling the physical dimensions of pores via synthetic conditions, applications of therapeutic protein loaded MSN materials in cancer therapies, delivering protein loaded MSN materials to plant cells using biolistic methods, and common stimuli-responsive functionalities will be discussed. New and exciting strategies for controlled release and manipulation of proteins are also covered in this review. While research in this area has advanced substantially, we conclude this review with future challenges to be tackled by the scientific community. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Concentration-Dependent Effects of Rhodiola Rosea on Long-Term Survival and Stress Resistance of Yeast Saccharomyces Cerevisiae: The Involvement of YAP 1 and MSN2/4 Regulatory Proteins

    PubMed Central

    Bayliak, Maria M.; Burdyliuk, Nadia I.; Izers’ka, Lilia I.; Lushchak, Volodymyr I.

    2014-01-01

    Concentration-dependent effects of aqueous extract from R. rosea root on long-term survival and stress resistance of budding yeast Saccharomyces cerevisiae were studied. At low concentrations, R. rosea aqueous extract extended yeast chronological lifespan, enhanced oxidative stress resistance of stationary-phase cells and resistance to number stressors in exponentially growing cultures. At high concentrations, R. rosea extract sensitized yeast cells to stresses and shortened yeast lifespan. These biphasic concentration-responses describe a common hormetic phenomenon characterized by a low-dose stimulation and a high-dose inhibition. Yeast pretreatment with low doses of R. rosea extract enhanced yeast survival and prevented protein oxidation under H2O2-induced oxidative stress. Positive effect of R. rosea extract on yeast survival under heat shock exposure was not accompanied with changes in antioxidant enzyme activities and levels of oxidized proteins. The deficiency in transcriptional regulators, Msn2/Msn4 and Yap1, abolished the positive effect of low doses of R. rosea extract on yeast viability under stress challenges. Potential involvement of Msn2/Msn4 and Yap1 regulatory proteins in realization of R. rosea beneficial effects is discussed. PMID:24659935

  14. YSA-conjugated mesoporous silica nanoparticles effectively target EphA2-overexpressing breast cancer cells.

    PubMed

    Liu, Zhi; Tao, Zijian; Zhang, Qing; Wan, Song; Zhang, Fenglin; Zhang, Yan; Wu, Guanyu; Wang, Jiandong

    2018-04-01

    Neoadjuvant chemotherapy is commonly used to treat patients with locally advanced breast cancer and a common option for primary operable disease. However, systemic toxicity including cardiotoxicity and inefficient delivery are significant challenges form any chemotherapeutics. The development of targeted treatments that lower the risk of toxicity has, therefore, become an active area of research in the field of novel cancer therapeutics. Mesoporous silica nanoparticles (MSNs) have attracted significant attention as efficient drug delivery carriers, due to their high surface area and tailorable mesoporous structures. Eph receptors are the largest receptor tyrosine kinase family, which are divided into the A- and the B-type. Eph receptors play critical roles in embryonic development and human diseases including cancer. EphA2 is expressed in breast cancer cells and has roles in carcinogenesis, progression and prognosis of breast cancer. A homing peptide with the sequence YSAYPDSVPMMSK (YSA) that binds specifically to EphA2 was used to functionalize MSN. We focus on a novel EphA2-targeted delivery MSN system for breast cancer cells. We show that the EphA2 receptor is differentially expressed in breast cancer cells and highly expressed in the HER2-negative breast cancer cell line MCF7. Our results suggest that EphA2-targeted MSN for doxorubicin delivery (MSN-YSA-DOX) are more effective than MSN-DOX in treating breast cancer cell lines in vitro. Our preliminary observations suggest that the EphA2-targeted MSN delivery system may provide a strategy for enhancing delivery of therapeutic agents to breast cancer cells expressing EphA2, and potentially reduce toxicity while enhancing therapeutic efficacy.

  15. Nucleus accumbens medium spiny neuron subtypes mediate depression-related outcomes to social defeat stress.

    PubMed

    Francis, T Chase; Chandra, Ramesh; Friend, Danielle M; Finkel, Eric; Dayrit, Genesis; Miranda, Jorge; Brooks, Julie M; Iñiguez, Sergio D; O'Donnell, Patricio; Kravitz, Alexxai; Lobo, Mary Kay

    2015-02-01

    The nucleus accumbens is a critical mediator of depression-related outcomes to social defeat stress. Previous studies demonstrate distinct neuroplasticity adaptations in the two medium spiny neuron (MSN) subtypes, those enriched in dopamine receptor D1 versus dopamine receptor D2, in reward and reinforcement leading to opposing roles for these MSNs in these behaviors. However, the distinct roles of nucleus accumbens MSN subtypes, in depression, remain poorly understood. Using whole-cell patch clamp electrophysiology, we examined excitatory input to MSN subtypes and intrinsic excitability measures in D1-green fluorescent protein and D2-green fluorescent protein bacterial artificial chromosome transgenic mice that underwent chronic social defeat stress (CSDS). Optogenetic and pharmacogenetic approaches were used to bidirectionally alter firing of D1-MSNs or D2-MSNs after CSDS or before a subthreshold social defeat stress in D1-Cre or D2-Cre bacterial artificial chromosome transgenic mice. We demonstrate that the frequency of excitatory synaptic input is decreased in D1-MSNs and increased in D2-MSNs in mice displaying depression-like behaviors after CSDS. Enhancing activity in D1-MSNs results in resilient behavioral outcomes, while inhibition of these MSNs induces depression-like outcomes after CSDS. Bidirectional modulation of D2-MSNs does not alter behavioral responses to CSDS; however, repeated activation of D2-MSNs in stress naïve mice induces social avoidance following subthreshold social defeat stress. Our studies uncover novel functions of MSN subtypes in depression-like outcomes. Notably, bidirectional alteration of D1-MSN activity promotes opposite behavioral outcomes to chronic social stress. Therefore, targeting D1-MSN activity may provide novel treatment strategies for depression or other affective disorders. Copyright © 2015 Society of Biological Psychiatry. All rights reserved.

  16. Systems and Methods for Decoy Routing and Convert Channel Bonding

    DTIC Science & Technology

    2013-11-26

    34 Proc. R. Soc. A, vol. 463, Jan. 12, 2007, pp. 1-16. " Stupid censorship Web Proxy," http://www.stupidcensorship.com/, retrieved from the internet on...services such as those offered by Google or Skype, web or microblogs such as Twitter, various social media services such as Face- book, and file...device (e.g., Skype, Google , Jabber, Firefox) to be directed to the proprietary software for processing. For instance, the proprietary software of

  17. Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington's disease model mice

    PubMed Central

    Tong, Xiaoping; Ao, Yan; Faas, Guido C.; Nwaobi, Sinifunanya E.; Xu, Ji; Haustein, Martin D.; Anderson, Mark A.; Mody, Istvan; Olsen, Michelle L.; Sofroniew, Michael V.; Khakh, Baljit S.

    2014-01-01

    Huntington's disease (HD) is characterized by striatal medium spiny neuron (MSN) dysfunction, but the underlying mechanisms remain unclear. We explored roles for astrocytes, which display mutant huntingtin in HD patients and mouse models. We found that symptom onset in R6/2 and Q175 HD mouse models is not associated with classical astrogliosis, but is associated with decreased Kir4.1 K+ channel functional expression, leading to elevated in vivo levels of striatal extracellular K+, which increased MSN excitability in vitro. Viral delivery of Kir4.1 channels to striatal astrocytes restored Kir4.1 function, normalized extracellular K+, recovered aspects of MSN dysfunction, prolonged survival and attenuated some motor phenotypes in R6/2 mice. These findings indicate that components of altered MSN excitability in HD may be caused by heretofore unknown disturbances of astrocyte–mediated K+ homeostasis, revealing astrocytes and Kir4.1 channels as novel therapeutic targets. PMID:24686787

  18. Assessment of pollutant mean concentrations in the Yangtze estuary based on MSN theory.

    PubMed

    Ren, Jing; Gao, Bing-Bo; Fan, Hai-Mei; Zhang, Zhi-Hong; Zhang, Yao; Wang, Jin-Feng

    2016-12-15

    Reliable assessment of water quality is a critical issue for estuaries. Nutrient concentrations show significant spatial distinctions between areas under the influence of fresh-sea water interaction and anthropogenic effects. For this situation, given the limitations of general mean estimation approaches, a new method for surfaces with non-homogeneity (MSN) was applied to obtain optimized linear unbiased estimations of the mean nutrient concentrations in the study area in the Yangtze estuary from 2011 to 2013. Other mean estimation methods, including block Kriging (BK), simple random sampling (SS) and stratified sampling (ST) inference, were applied simultaneously for comparison. Their performance was evaluated by estimation error. The results show that MSN had the highest accuracy, while SS had the highest estimation error. ST and BK were intermediate in terms of their performance. Thus, MSN is an appropriate method that can be adopted to reduce the uncertainty of mean pollutant estimation in estuaries. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Mesoporous Silica Nanomaterials for Applications in Catalysis, Sensing, Drug Delivery and Gene Transfection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Radu, Daniela Rodica

    2004-01-01

    The central theme of this dissertation is represented by the versatility of mesoporous silica nanomaterials in various applications such as catalysis and bio-applications, with main focus on biological applications of Mesoporous Silica Nanospheres (MSN). The metamorphosis that we impose to these materials from catalysis to sensing and to drug and gene delivery is detailed in this dissertation. First, we developed a synthetic method that can fine tune the amount of chemically accessible organic functional groups on the pores surface of MSN by exploiting electrostatic and size matching between the cationic alkylammonium head group of the cetyltrimethylammonium bromide (CTAB) surfactant andmore » various anionic organoalkoxysilane precursors at the micelle-water interface in a base-catalyzed condensation reaction of silicate. Aiming nature imitation, we demonstrated the catalytic abilities of the MSNs, We utilized an ethylenediamine functional group for chelating Cu 2+ as a catalytic functional group anchored inside the mesopores. Thus, a polyalkynylene-based conducting polymer (molecular wire) was synthesized within the Cu-functionalized MSNs silica catalyst. For sensing applications, we have synthesized a poly(lactic acid) coated mesoporous silica nanosphere (PLA-MSN) material that serves as a fluorescence sensor system for detection of amino-containing neurotransmitters in neutral aqueous buffer. We exploited the mesoporosity of MSNs for encapsulating pharmaceutical drugs. We examined bio-friendly capping molecules such as polyamidoamine dendrimers of generations G2 to G4, to prevent the drug leaching. Next, the drug delivery system employed MSNs loaded with Doxorubicin, an anticancer drug. The results demonstrated that these nano-Trojan horses have ability to deliver Doxorubicin to cancer cells and induce their death. Finally, to demonstrate the potential of MSN as an universal cellular transmembrane nanovehicle, we anchored positively charged dendrimers on the surface of MSN and utilize them to complex cationic DNA. The p-EGFP-CI gene-coated MSN nanocomposite was able to transfect cancer cell lines, such as human HeLa and CHO cancer cell lines. The gene carrier ability of MSNs was further proved by transfecting primary cells and cotransfecting of two different genes in cancer cell lines. In sum, MSN are versatile partners in several types of applications.« less

  20. Hydrophobic interaction mediated coating of Pluronics on mesoporous silica nanoparticle with stimuli responsiveness for cancer therapy.

    PubMed

    Sha, Luping; Wang, Da; Mao, Yuling; Shi, Wei; Gao, Tianbin; Zhao, Qinfu; Wang, Si-Ling

    2018-05-22

    In this research, a novel method was used to successfully make Pluronic P123 stably coated on mesoporous silica nanoparticles (MSN). That P123 and MSN co-constructed a drug delivery system (DDS) had not been reported. In this DDS, the coating of P123 was realized through hydrophobic interaction with octadecyl chain modified MSN. Experiments found only Pluronic with an appropriate ratio of hydrophilic and lipophilic segment could keep the nanoassemblies stable. For comparison, nanoassemblies consisted of P123 and octadecyl chain modified MSN with or without disulfide bond were prepared, which were denoted as PSMSN and PMSN respectively. Disulfide bond was expected to endow the system with redox-responsiveness to enhance the therapeutic effect meanwhile decrease toxicity. A series of experiments including characterization of the nanoparticles, in vitro drug release, cell uptake and cellular drug release, in vitro cytotoxicity, cell migration and biodistribution of the nanoparticles were carried out. Compared with PMSN, PSMSN displayed redox-responsive drug release property not only in in vitro release text, but also on the cellular level. In addition, cell migration experiments proved that the coating of P123 endowed the system with the ability of anti-metastasis. The accumulation of P123 in tumor was enhanced after coating on MSN by virtue of the "EPR" effect of nanoparticles compared with the solution form. . © 2018 IOP Publishing Ltd.

  1. Heritable stress response dynamics revealed by single-cell genealogy

    PubMed Central

    2018-01-01

    Cells often respond to environmental stimuli by activating specific transcription factors. Upon exposure to glucose limitation stress, it is known that yeast Saccharomyces cerevisiae cells dephosphorylate the general stress response factor Msn2, leading to its nuclear localization, which in turn activates the expression of many genes. However, the precise dynamics of Msn2 nucleocytoplasmic translocations and whether they are inherited over multiple generations in a stress-dependent manner are not well understood. Tracking Msn2 localization events in yeast lineages grown on a microfluidic chip, here we report how cells modulate the amplitude, duration, frequency, and dynamic pattern of the localization events in response to glucose limitation stress. Single yeast cells were found to modulate the amplitude and frequency of Msn2 nuclear localization, but not its duration. Moreover, the Msn2 localization frequency was epigenetically inherited in descendants of mother cells, leading to a decrease in cell-to-cell variation in localization frequency. An analysis of the time dynamic patterns of nuclear localizations between genealogically related cell pairs using an information theory approach found that the magnitude of pattern similarity increased with stress intensity and was strongly inherited by the descendant cells at the highest stress level. By dissecting how general stress response dynamics is contributed by different modulation schemes over long time scales, our work provides insight into which scheme evolution might have acted on to optimize fitness in stressful environments. PMID:29675464

  2. Phototherapeutic spectrum expansion through synergistic effect of mesoporous silica trio-nanohybrids against antibiotic-resistant gram-negative bacterium.

    PubMed

    Kuthati, Yaswanth; Kankala, Ranjith Kumar; Busa, Prabhakar; Lin, Shi-Xiang; Deng, Jin-Pei; Mou, Chung-Yuan; Lee, Chia-Hung

    2017-04-01

    The extensive impact of antibiotic resistance has led to the exploration of new anti-bacterial modalities. We designed copper impregnated mesoporous silica nanoparticles (Cu-MSN) with immobilizing silver nanoparticles (SNPs) to apply photodynamic inactivation (PDI) of antibiotic-resistant E. coli. SNPs were decorated over the Cu-MSN surfaces by coordination of silver ions on diamine-functionalized Cu-MSN and further reduced to silver nanoparticles with formalin. We demonstrate that silver is capable of sensitizing the gram-negative bacteria E. coli to a gram-positive specific phototherapeutic agent in vitro; thereby expanding curcumin's phototherapeutic spectrum. The mesoporous structure of Cu-MSN remains intact after the exterior decoration with silver nanoparticles and subsequent curcumin loading through an enhanced effect from copper metal-curcumin affinity interaction. The synthesis, as well as successful assembly of the functional nanomaterials, was confirmed by various physical characterization techniques. Curcumin is capable of producing high amounts of reactive oxygen species (ROS) under light irradiation, which can further improve the silver ion release kinetics for antibacterial activity. In addition, the positive charged modified surfaces of Cu-MSN facilitate antimicrobial response through electrostatic attractions towards negatively charged bacterial cell membranes. The antibacterial action of the synthesized nanocomposites can be activated through a synergistic mechanism of energy transfer of the absorbed light from SNP to curcumin. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Highly efficient siRNA delivery from core-shell mesoporous silica nanoparticles with multifunctional polymer caps

    NASA Astrophysics Data System (ADS)

    Möller, Karin; Müller, Katharina; Engelke, Hanna; Bräuchle, Christoph; Wagner, Ernst; Bein, Thomas

    2016-02-01

    A new general route for siRNA delivery is presented combining porous core-shell silica nanocarriers with a modularly designed multifunctional block copolymer. Specifically, the internal storage and release of siRNA from mesoporous silica nanoparticles (MSN) with orthogonal core-shell surface chemistry was investigated as a function of pore-size, pore morphology, surface properties and pH. Very high siRNA loading capacities of up to 380 μg per mg MSN were obtained with charge-matched amino-functionalized mesoporous cores, and release profiles show up to 80% siRNA elution after 24 h. We demonstrate that adsorption and desorption of siRNA is mainly driven by electrostatic interactions, which allow for high loading capacities even in medium-sized mesopores with pore diameters down to 4 nm in a stellate pore morphology. The negatively charged MSN shell enabled the association with a block copolymer containing positively charged artificial amino acids and oleic acid blocks, which acts simultaneously as capping and endosomal release agent. The potential of this multifunctional delivery platform is demonstrated by highly effective cell transfection and siRNA delivery into KB-cells. A luciferase reporter gene knock-down of up to 80-90% was possible using extremely low cell exposures with only 2.5 μg MSN containing 0.5 μg siRNA per 100 μL well.A new general route for siRNA delivery is presented combining porous core-shell silica nanocarriers with a modularly designed multifunctional block copolymer. Specifically, the internal storage and release of siRNA from mesoporous silica nanoparticles (MSN) with orthogonal core-shell surface chemistry was investigated as a function of pore-size, pore morphology, surface properties and pH. Very high siRNA loading capacities of up to 380 μg per mg MSN were obtained with charge-matched amino-functionalized mesoporous cores, and release profiles show up to 80% siRNA elution after 24 h. We demonstrate that adsorption and desorption of siRNA is mainly driven by electrostatic interactions, which allow for high loading capacities even in medium-sized mesopores with pore diameters down to 4 nm in a stellate pore morphology. The negatively charged MSN shell enabled the association with a block copolymer containing positively charged artificial amino acids and oleic acid blocks, which acts simultaneously as capping and endosomal release agent. The potential of this multifunctional delivery platform is demonstrated by highly effective cell transfection and siRNA delivery into KB-cells. A luciferase reporter gene knock-down of up to 80-90% was possible using extremely low cell exposures with only 2.5 μg MSN containing 0.5 μg siRNA per 100 μL well. Electronic supplementary information (ESI) available: MSN synthesis and analysis, sample preparation for cell transfections as well as additional studies including experiments with a second cell line and a toxicity assay. See DOI: 10.1039/c5nr06246b

  4. Using MSN Money to Perform Financial Ratio Analysis

    ERIC Educational Resources Information Center

    Hsu, H. Christine

    2010-01-01

    In today's information technology world, real time financial data is readily available via many financial websites, such as MSN Money, Google Finance, Yahoo Finance, etc. The incorporation of computer technology in finance classes has become more popular than ever in this information technology rich environment. Mediated classrooms have rapidly…

  5. Application of solid state NMR for the study of surface bound species and fossil fuels

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Althaus, Stacey

    2014-01-01

    In this study, stimulated echo with pulsed field gradients was used to measure the diffusion of two different solvents, water and hexane, in AP-MSN-2.7 and AP-MSN-3.7. The resulting data were then fit using two different methods. Based on these fits, the diffusion of hexane in AP-MSN-2.7 was shown to be slower than in the larger pores. This agrees well with our studies of catalytic activity, which show an increase in the reaction rate with the increase in pore size. Thus, both substrate inhibition and diffusion played a role in the decreased efficiency of the APMSN with small pore sizes.

  6. Real-time video streaming of sonographic clips using domestic internet networks and free videoconferencing software.

    PubMed

    Liteplo, Andrew S; Noble, Vicki E; Attwood, Ben H C

    2011-11-01

    As the use of point-of-care sonography spreads, so too does the need for remote expert over-reading via telesonogrpahy. We sought to assess the feasibility of using familiar, widespread, and cost-effective existent technology to allow remote over-reading of sonograms in real time and to compare 4 different methods of transmission and communication for both the feasibility of transmission and image quality. Sonographic video clips were transmitted using 2 different connections (WiFi and 3G) and via 2 different videoconferencing modalities (iChat [Apple Inc, Cupertino, CA] and Skype [Skype Software Sàrl, Luxembourg]), for a total of 4 different permutations. The clips were received at a remote location and recorded and then scored by expert reviewers for image quality, resolution, and detail. Wireless transmission of sonographic clips was feasible in all cases when WiFi was used and when Skype was used over a 3G connection. Images transmitted via a WiFi connection were statistically superior to those transmitted via 3G in all parameters of quality (average P = .031), and those sent by iChat were superior to those sent by Skype but not statistically so (average P = .057). Wireless transmission of sonographic video clips using inexpensive hardware, free videoconferencing software, and domestic Internet networks is feasible with retention of image quality sufficient for interpretation. WiFi transmission results in greater image quality than transmission by a 3G network.

  7. Testing the Feasibility of Skype and FaceTime Updates With Parents in the Neonatal Intensive Care Unit.

    PubMed

    Epstein, Elizabeth Gingell; Sherman, Jessica; Blackman, Amy; Sinkin, Robert A

    2015-07-01

    Effective provider-parent relationships are essential during critical illness when treatment decisions are complex, the environment is crowded and unfamiliar, and outcomes are uncertain. To evaluate the feasibility of daily Skype or FaceTime updates with parents of patients in the neonatal intensive care unit (NICU) and to assess the intervention's potential for improving parent-provider relationships. A pre/post mixed-methods approach was used. NICU parent participants received daily Skype or FaceTime updates for 5 days and completed demographic and feasibility surveys. Parents also completed Penticuff's Parents' Understanding survey before and after the intervention. Nurses and physicians completed feasibility surveys after each update. Twenty-six parents were enrolled and 15 completed the study. More than 90% of providers and parents perceived the intervention to be reliable and easy to use, and about 80% of parents and providers rated video and audio quality as either excellent or good. Frozen screens and missed updates due to scheduling problems were challenges. Two of the 4 subscores on the Parents' Understanding survey improved significantly. Qualitative data favor the intervention as meaningful for parents. Real-time videoconferencing via Skype or FaceTime is feasible for providing updates for parents when they cannot be present in the NICU and can be used to include parents in bedside rounds. Videoconferencing updates may improve relationships between parents and the health care team. ©2015 American Association of Critical-Care Nurses.

  8. The use of telehealth (text messaging and video communications) in patients with cystic fibrosis: A pilot study.

    PubMed

    Gur, Michal; Nir, Vered; Teleshov, Anna; Bar-Yoseph, Ronen; Manor, Eynav; Diab, Gizelle; Bentur, Lea

    2017-05-01

    Background Poor communications between cystic fibrosis (CF) patients and health-care providers may result in gaps in knowledge and misconceptions about medication usage, and can lead to poor adherence. We aimed to assess the feasibility of using WhatsApp and Skype to improve communications. Methods This single-centre pilot study included CF patients who were older than eight years of age assigned to two groups: one without intervention (control group), and one with intervention. Each patient from the intervention group received Skype-based online video chats and WhatsApp messages from members of the multidisciplinary CF team. CF questionnaires, revised (CFQ-R) scores, knowledge and adherence based on CF My Way and patients satisfaction were evaluated before and after three months. Feasibility was assessed by session attendance, acceptability and satisfaction survey. Descriptive analysis and paired and non-paired t-tests were used as applicable. Results Eighteen patients were recruited to this feasibility study (nine in each group). Each intervention group participant had between four and six Skype video chats and received 22-45 WhatsApp messages. In this small study, CFQ-R scores, knowledge, adherence and patient satisfaction were similar in both groups before and after the three-month intervention. Conclusions A telehealth-based approach, using Skype video chats and WhatsApp messages, was feasible and acceptable in this pilot study. A larger and longer multi-centre study is warranted to examine the efficacy of these interventions to improve knowledge, adherence and communication.

  9. Audience and Witnessing: Research into Dramatherapy using Vignettes and aMSN Messenger

    ERIC Educational Resources Information Center

    Jones, Phil

    2008-01-01

    This article describes the process of research undertaken to examine therapists' responses to the concept of the core processes of change in dramatherapy. The research uses a combination of vignette description and analysis using aMSN messenger. The article describes the theoretical underpinning and rationale to the approach, and the…

  10. In Vivo Integrity and Biological Fate of Chelator-Free Zirconium-89-Labeled Mesoporous Silica Nanoparticles

    PubMed Central

    2015-01-01

    Traditional chelator-based radio-labeled nanoparticles and positron emission tomography (PET) imaging are playing vital roles in the field of nano-oncology. However, their long-term in vivo integrity and potential mismatch of the biodistribution patterns between nanoparticles and radio-isotopes are two major concerns for this approach. Here, we present a chelator-free zirconium-89 (89Zr, t1/2 = 78.4 h) labeling of mesoporous silica nanoparticle (MSN) with significantly enhanced in vivo long-term (>20 days) stability. Successful radio-labeling and in vivo stability are demonstrated to be highly dependent on both the concentration and location of deprotonated silanol groups (−Si–O–) from two types of silica nanoparticles investigated. This work reports 89Zr-labeled MSN with a detailed labeling mechanism investigation and long-term stability study. With its attractive radio-stability and the simplicity of chelator-free radio-labeling, 89Zr-MSN offers a novel, simple, and accurate way for studying the in vivo long-term fate and PET image-guided drug delivery of MSN in the near future. PMID:26213260

  11. In Vivo Integrity and Biological Fate of Chelator-Free Zirconium-89-Labeled Mesoporous Silica Nanoparticles.

    PubMed

    Chen, Feng; Goel, Shreya; Valdovinos, Hector F; Luo, Haiming; Hernandez, Reinier; Barnhart, Todd E; Cai, Weibo

    2015-08-25

    Traditional chelator-based radio-labeled nanoparticles and positron emission tomography (PET) imaging are playing vital roles in the field of nano-oncology. However, their long-term in vivo integrity and potential mismatch of the biodistribution patterns between nanoparticles and radio-isotopes are two major concerns for this approach. Here, we present a chelator-free zirconium-89 ((89)Zr, t1/2 = 78.4 h) labeling of mesoporous silica nanoparticle (MSN) with significantly enhanced in vivo long-term (>20 days) stability. Successful radio-labeling and in vivo stability are demonstrated to be highly dependent on both the concentration and location of deprotonated silanol groups (-Si-O(-)) from two types of silica nanoparticles investigated. This work reports (89)Zr-labeled MSN with a detailed labeling mechanism investigation and long-term stability study. With its attractive radio-stability and the simplicity of chelator-free radio-labeling, (89)Zr-MSN offers a novel, simple, and accurate way for studying the in vivo long-term fate and PET image-guided drug delivery of MSN in the near future.

  12. Mucin1 antibody-conjugated dye-doped mesoporous silica nanoparticles for breast cancer detection in vivo

    NASA Astrophysics Data System (ADS)

    Vivero-Escoto, Juan L.; Moore Jeffords, Laura; Dréau, Didier; Alvarez-Berrios, Merlis; Mukherjee, Pinku

    2017-02-01

    The development of novel methods for tumor detection is a burgeoning area of research. In particular, the use of silica nanoparticles for optical imaging in the near infrared (NIR) represents a valuable tool because their chemical inertness, biocompatibility, and transparency in the ultraviolet-visible and NIR regions of the electromagnetic spectrum. Moreover, silica nanoparticles can be modified with a wide variety of functional groups such as aptamers, small molecules, antibodies and polymers. Here, we report the development of a mucin 1(MUC1)-specific dye-doped NIR emitting mesoporous silica nanoparticles (MUC1-NIR-MSN) platform for the optical detection of breast cancer tissue overexpressing human tumor-associated MUC1. We have characterized the structural properties and the in vitro performance of this system. The MSN-based optical imaging probe is non-cytotoxic and targets efficiently murine mammary epithelial cancer cells overexpressing human MUC1. Finally, the ability of MUC1-NIR-MSN contrast imaging agent to selectively detect breast cancer tumors overexpressing human tumor-associated MUC1 was successfully demonstrated in a transgenic murine mouse model. The NIR imaging experiments on tumor-bearing animals showed specific accumulation of the MSN-based probe in human MUC1-positive tumors and small signal in control tumors. We envision that this MUC1-specific MSN-based optical probe has the potential to greatly aid in screening prospective patients for early breast cancer detection and in monitoring the efficacy of drug therapy.

  13. Kinetics of oxidation of an organic amine with a Cr(V) salen complex in homogeneous aqueous solution and on the surface of mesoporous silica

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Szajna-Fuller, Ewa; Huang, Yulin; Rapp, Jennifer L.

    2009-03-09

    A comparative study of catalytic activity under homogeneous and heterogeneous conditions was carried out using the (salen)Cr{sup III}-catalyzed oxidation of tetramethylbenzidine (TMB) with iodosobenzene as a model reaction. Amine-functionalized mesoporous silica nanoparticles (MSN) were synthesized in a co-condensation reaction and functionalized with salen via a covalent Si-C bond. A Cr(III) complex of this supported ligand, MSN-(salen)Cr{sup III}, was prepared and characterized. Data from powder XRD, BET isotherms and BJH pore size distribution all showed that MSN-(salen)Cr{sup III} still had the typical MSN high surface area, narrow pore size distribution, and ordered hexagonal pore structure, which were further confirmed by transmissionmore » electron microscopy (TEM) images. {sup 13}C and {sup 29}Si solid-state NMR data provided structural information about the catalyst and verified successful functionalization of the salen ligand and coordination to Cr(III). No unreacted salen or Cr(III) were observed. The loadings of salen and salen-Cr{sup III} complex were determined via TGA and EDX, respectively. Both measurements indicated that approximately 0.5 mmol/g of catalyst was loaded on the surface of MSN. The oxidation of TMB with iodosobenzene using MSN-(salen)Cr{sup III} as a heterogeneous catalyst exhibited both similarities and differences with the analogous homogeneous reaction using (salen)Cr{sup III}(H{sub 2}O){sup +} as a catalyst in aqueous acetonitrile. In the presence of 0.10 M HClO{sub 4}, the two catalytic reactions proceeded at similar rates and generated the doubly oxidized product TMB{sup 2+}. In the absence of acid, the radical cation TMB{sup +} was produced. The kinetics of the heterogeneous reaction in the absence of added acid responded to concentrations of all three reagents, i.e. (salen)Cr{sup III}, TMB, and PhIO.« less

  14. Alizarin Complexone Functionalized Mesoporous Silica Nanoparticles: A Smart System Integrating Glucose-Responsive Double-Drugs Release and Real-Time Monitoring Capabilities.

    PubMed

    Zou, Zhen; He, Dinggeng; Cai, Linli; He, Xiaoxiao; Wang, Kemin; Yang, Xue; Li, Liling; Li, Siqi; Su, Xiaoya

    2016-04-06

    The outstanding progress of nanoparticles-based delivery systems capable of releasing hypoglycemic drugs in response to glucose has dramatically changed the outlook of diabetes management. However, the developed glucose-responsive systems have not offered real-time monitoring capabilities for accurate quantifying hypoglycemic drugs released. In this study, we present a multifunctional delivery system that integrates both delivery and monitoring issues using glucose-triggered competitive binding scheme on alizarin complexone (ALC) functionalized mesoporous silica nanoparticles (MSN). In this system, ALC is modified on the surface of MSN as the signal reporter. Gluconated insulin (G-Ins) is then introduced onto MSN-ALC via benzene-1,4-diboronic acid (BA) mediated esterification reaction, where G-Ins not only blocks drugs inside the mesopores but also works as a hypoglycemic drug. In the absence of glucose, the sandwich-type boronate ester structure formed by BA binding to the diols of ALC and G-Ins remains intact, resulting in an fluorescence emission peak at 570 nm and blockage of pores. Following a competitive binding, the presence of glucose cause the dissociation of boronate ester between ALC and BA, which lead to the pores opening and disappearance of fluorescence. As proof of concept, rosiglitazone maleate (RSM), an insulin-sensitizing agent, was doped into the MSN to form a multifunctional MSN (RSM@MSN-ALC-BA-Ins), integrating with double-drugs loading, glucose-responsive performance, and real-time monitoring capability. It has been demonstrated that the glucose-responsive release behaviors of insulin and RSM in buffer or in human serum can be quantified in real-time through evaluating the changes of fluorescence signal. We believe that this developed multifunctional system can shed light on the invention of a new generation of smart nanoformulations for optical diagnosis, individualized treatment, and noninvasive monitoring of diabetes management.

  15. In Vivo Lighted Fluorescence via Fenton Reaction: Approach for Imaging of Hydrogen Peroxide in Living Systems.

    PubMed

    Liu, Changhui; Chen, Weiju; Qing, Zhihe; Zheng, Jing; Xiao, Yue; Yang, Sheng; Wang, Lili; Li, Yinhui; Yang, Ronghua

    2016-04-05

    By virtue of its high sensitivity and rapidity, Fenton reaction has been demonstrated as a powerful tool for in vitro biochemical analysis; however, in vivo applications of Fenton reaction still remain to be exploited. Herein, we report, for the first time, the design, formation and testing of Fenton reaction for in vivo fluorescence imaging of hydrogen peroxide (H2O2). To realize in vivo fluorescence imaging of H2O2 via Fenton reaction, a functional nanosphere, Fc@MSN-FDNA/PTAD, is fabricated from mesoporous silica nanoparticle (MSN), a Fenton reagent of ferrocene (Fc), ROX-labeled DNA (FDNA), and a cationic perylene derivative (PTAD). The ferrocene molecules are locked in the pore entrances of MSN, and exterior of MSN is covalently immobilized with FDNA. As a key part, PTAD acts as not only the gatekeeper of MSN but also the efficient quencher of ROX. H2O2 can permeate into the nanosphere and react with ferrocene to product hydroxyl radical (·OH) via Fenton reaction, which cleaves FDNA to detach ROX from PTAD, thus in turn, lights the ROX fluorescence. Under physiological condition, H2O2 can be determined from 5.0 nM to 1.0 μM with a detection limit of 2.4 nM. Because of the rapid kinetics of Fenton reaction and high specificity for H2O2, the proposed method meets the requirement for real applications. The feasibility of Fc@MSN-FDNA/PTAD for in vivo applications is demonstrated for fluorescence imaging of exogenous and endogenous H2O2 in cells and mice. We expect that this work will not only contribute to the H2O2-releated studies but also open up a new way to exploit in vivo Fenton reaction for biochemical research.

  16. Prehospital high-dose sublingual nitroglycerin rarely causes hypotension.

    PubMed

    Clemency, Brian M; Thompson, Jeffrey J; Tundo, Gina N; Lindstrom, Heather A

    2013-10-01

    High-dose intravenous nitroglycerin is a common in-hospital treatment for respiratory distress due to congestive heart failure (CHF) with hypertension. Intravenous (IV) nitroglycerin administration is impractical in the prehospital setting. In 2011, a new regional Emergency Medical Services (EMS) protocol was introduced allowing advanced providers to treat CHF with high-dose oral nitroglycerin. The protocol calls for patients to be treated with two sublingual tabs (0.8 mg) when systolic blood pressure (SBP) was >160 mm Hg, or three sublingual tabs (1.2 mg) when SBP was >200 mm Hg, every five minutes as needed. Hypothesis/Problem To assess the protocol's safety, the incidence of hypotension following prehospital administration of multiple simultaneous nitroglycerin (MSN) tabs by EMS providers was studied. This study was a retrospective cohort study of patients from a single commercial EMS agency over a 6-month period. Records from patients with at least one administration of MSN were reviewed. For each administration, the first documented vital signs pre- and post-administration were compared. Administrations were excluded if pre- or post-administration vital signs were missing. One hundred case-patients had at least one MSN administration by an advanced provider during the study period. Twenty-five case-patients were excluded due to incomplete vital signs. Seventy-five case-patients with 95 individual MSN administrations were included for analysis. There were 65 administrations of two tabs, 29 administrations of three tabs, and one administration of four tabs. The mean change in SBP following MSN was -14.7 mm Hg (SD = 30.7; range, +59 to -132). Three administrations had documented systolic hypotension in the post-administration vital signs (97/71, 78/50 and 66/47). All three patients were over 65 years old, were administered two tabs, had documented improved respiratory status, and had repeat SBP of at least 100. The incidence of hypotension following MSN administration was 3.2%. Discussion High-dose oral nitroglycerin administration is a practical alternative to IV nitroglycerin in the prehospital setting when administered by advanced providers. The prehospital protocol for high dose oral nitroglycerin was demonstrated to be safe in the cohort of patients studied. Limitations of the study include the relatively small sample size and the inability to identify hypotension that may have occurred following the cessation of data collection in the field. Hypotension was rare and self-limited in prehospital patients receiving MSN.

  17. Loss of Plasticity in the D2-Accumbens Pallidal Pathway Promotes Cocaine Seeking.

    PubMed

    Heinsbroek, Jasper A; Neuhofer, Daniela N; Griffin, William C; Siegel, Griffin S; Bobadilla, Ana-Clara; Kupchik, Yonatan M; Kalivas, Peter W

    2017-01-25

    Distinct populations of D1- and D2-dopamine receptor-expressing medium spiny neurons (D1-/D2-MSNs) comprise the nucleus accumbens, and activity in D1-MSNs promotes, whereas activity in D2-MSNs inhibits, motivated behaviors. We used chemogenetics to extend D1-/D2-MSN cell specific regulation to cue-reinstated cocaine seeking in a mouse model of self-administration and relapse, and found that either increasing activity in D1-MSNs or decreasing activity in D2-MSNs augmented cue-induced reinstatement. Both D1- and D2-MSNs provide substantial GABAergic innervation to the ventral pallidum, and chemogenetic inhibition of ventral pallidal neurons blocked the augmented reinstatement elicited by chemogenetic regulation of either D1- or D2-MSNs. Because D1- and D2-MSNs innervate overlapping populations of ventral pallidal neurons, we next used optogenetics to examine whether changes in synaptic plasticity in D1- versus D2-MSN GABAergic synapses in the ventral pallidum could explain the differential regulation of VP activity. In mice trained to self-administer cocaine, GABAergic LTD was abolished in D2-, but not in D1-MSN synapses. A μ opioid receptor antagonist restored GABA currents in D2-, but not D1-MSN synapses of cocaine-trained mice, indicating that increased enkephalin tone on presynaptic μ opioid receptors was responsible for occluding the LTD. These results identify a behavioral function for D1-MSN innervation of the ventral pallidum, and suggest that losing LTD GABA in D2-MSN, but not D1-MSN input to ventral pallidum may promote cue-induced reinstatement of cocaine-seeking. More than 90% of ventral striatum is composed of two cell types, those expressing dopamine D1 or D2 receptors, which exert opposing roles on motivated behavior. Both cell types send GABAergic projections to the ventral pallidum and were found to differentially promote cue-induced reinstatement of cocaine seeking via the ventral pallidum. Furthermore, after cocaine self-administration, synaptic plasticity was selectively lost in D2, but not D1 inputs to the ventral pallidum. The selective impairment in D2 afferents may promote the influence of D1 inputs to drive relapse to cocaine seeking. Copyright © 2017 the authors 0270-6474/17/370757-11$15.00/0.

  18. Loss of Plasticity in the D2-Accumbens Pallidal Pathway Promotes Cocaine Seeking

    PubMed Central

    Neuhofer, Daniela N.; Griffin, William C.; Siegel, Griffin S.; Bobadilla, Ana-Clara; Kupchik, Yonatan M.

    2017-01-01

    Distinct populations of D1- and D2-dopamine receptor-expressing medium spiny neurons (D1-/D2-MSNs) comprise the nucleus accumbens, and activity in D1-MSNs promotes, whereas activity in D2-MSNs inhibits, motivated behaviors. We used chemogenetics to extend D1-/D2-MSN cell specific regulation to cue-reinstated cocaine seeking in a mouse model of self-administration and relapse, and found that either increasing activity in D1-MSNs or decreasing activity in D2-MSNs augmented cue-induced reinstatement. Both D1- and D2-MSNs provide substantial GABAergic innervation to the ventral pallidum, and chemogenetic inhibition of ventral pallidal neurons blocked the augmented reinstatement elicited by chemogenetic regulation of either D1- or D2-MSNs. Because D1- and D2-MSNs innervate overlapping populations of ventral pallidal neurons, we next used optogenetics to examine whether changes in synaptic plasticity in D1- versus D2-MSN GABAergic synapses in the ventral pallidum could explain the differential regulation of VP activity. In mice trained to self-administer cocaine, GABAergic LTD was abolished in D2-, but not in D1-MSN synapses. A μ opioid receptor antagonist restored GABA currents in D2-, but not D1-MSN synapses of cocaine-trained mice, indicating that increased enkephalin tone on presynaptic μ opioid receptors was responsible for occluding the LTD. These results identify a behavioral function for D1-MSN innervation of the ventral pallidum, and suggest that losing LTDGABA in D2-MSN, but not D1-MSN input to ventral pallidum may promote cue-induced reinstatement of cocaine-seeking. SIGNIFICANCE STATEMENT More than 90% of ventral striatum is composed of two cell types, those expressing dopamine D1 or D2 receptors, which exert opposing roles on motivated behavior. Both cell types send GABAergic projections to the ventral pallidum and were found to differentially promote cue-induced reinstatement of cocaine seeking via the ventral pallidum. Furthermore, after cocaine self-administration, synaptic plasticity was selectively lost in D2, but not D1 inputs to the ventral pallidum. The selective impairment in D2 afferents may promote the influence of D1 inputs to drive relapse to cocaine seeking. PMID:28123013

  19. Effects of Cognitive Styles on an MSN Virtual Learning Companion System as an Adjunct to Classroom Instructions

    ERIC Educational Resources Information Center

    Hsieh, Sheng-Wen

    2011-01-01

    This study designed a chatbot system, Confucius, as a MSN virtual learning companion to examine how specific application design variables within educational software affect the learning process of subjects as defined by the cognitive continuum of field-dependent and field-independent learners. 104 college students participated in a 12 week…

  20. UHPLC-PDA-ESI/HRMS/MSn analysis of anthocyanins, flavonol glycosides, and hydroxycinnamic acid derivatives in red mustard green (Brassica juncea (L) Coss variety)

    USDA-ARS?s Scientific Manuscript database

    An UHPLC-PDA-ESI/HRMS/MSn profiling method was used for a comprehensive study of the polyphenols in red mustard greens and identified 209 phenolic compounds: 67 anthocyanin, 102 flavonol glycosides, and 40 hydroxycinnamic acid derivatives. The glycosylation patterns of the flavonoids were assigned ...

  1. Comparison of stratified and non-stratified most similar neighbour imputation for estimating stand tables

    Treesearch

    Bianca N. I. Eskelson; Hailemariam Temesgen; Tara M. Barrett

    2008-01-01

    Many growth and yield simulators require a stand table or tree-list to set the initial condition for projections in time. Most similar neighbour (MSN) approaches can be used for estimating stand tables from information commonly available on forest cover maps (e.g. height, volume, canopy cover, and species composition). Simulations were used to compare MSN (using an...

  2. Controlled release of silyl ether camptothecin from thiol-ene click chemistry-functionalized mesoporous silica nanoparticles.

    PubMed

    Yan, Yue; Fu, Jie; Wang, Tianfu; Lu, Xiuyang

    2017-03-15

    As efficient drug carriers, stimuli-responsive mesoporous silica nanoparticles are at the forefront of research on drug delivery systems. An acid-responsive system based on silyl ether has been applied to deliver a hybrid prodrug. Thiol-ene click chemistry has been successfully utilized for tethering this prodrug to mesoporous silica nanoparticles. Here, by altering the steric bulk of the substituent on the silicon atom, the release rate of a model drug, camptothecin, was controlled. The synthesized drug delivery system was investigated by analytical methods to confirm the functionalization and conjugation of the mesoporous silica nanoparticles. Herein, trimethyl silyl ether and triethyl silyl ether were selected to regulate the release rate. Under normal plasma conditions (pH 7.4), both types of camptothecin-loaded mesoporous silica nanoparticles (i.e., MSN-Me-CPT and MSN-Et-CPT) did not release the model drug. However, under in vitro acidic conditions (pH 4.0), based on a comparison of the release rates, camptothecin was released from MSN-Me-CPT more rapidly than from MSN-Et-CPT. To determine the biocompatibility of the modified mesoporous silica nanoparticles and the in vivo camptothecin uptake behavior, MTT assays with cancer cells and confocal microscopy observations were conducted, with positive results. These functionalized nanoparticles could be useful in clinical treatments requiring controlled drug release. As the release rate of drug from drug-carrier plays important role in therapy effects, trimethyl silyl ether (TMS) and triethyl silyl ether (TES) were selected as acid-sensitive silanes to control the release rates of model drugs conjugated from MSNs by thiol-ene click chemistry. The kinetic profiles of TMS and TES materials have been studied. At pH 4.0, the release of camptothecin from MSN-Et-CPT occurred after 2h, whereas MSN-Me-CPT showed immediate drug release. The results showed that silyl ether could be used to control release rates of drugs from MSNs under acid environment, which could be useful in clinical treatments requiring controlled drug release. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. Low-cost and highly sensitive immunosensing platform for aflatoxins using one-step competitive displacement reaction mode and portable glucometer-based detection.

    PubMed

    Tang, Dianping; Lin, Youxiu; Zhou, Qian; Lin, Yuping; Li, Peiwu; Niessner, Reinhard; Knopp, Dietmar

    2014-11-18

    Aflatoxins are highly toxic secondary metabolites produced by a number of different fungi and present in a wide range of food and feed commodities. Herein, we designed a simple and low-cost immunosensing platform for highly sensitive detection of mycotoxins (aflatoxin B1, AFB1, used as a model) on polyethylenimine (PEI)-coated mesoporous silica nanocontainers (PEI-MSN). The assay was carried out by using a portable personal glucometer (PGM) as the readout based on a competitive displacement reaction mode between target AFB1 and its pseudo-hapten (PEI-MSN) for monoclonal anti-AFB1 antibody (mAb). To construct such an assay protocol, two nanostructures including mAb-labeled gold nanoparticle (mAb-AuNP) and PEI-MSN were initially synthesized, and then numerous glucose molecules were gated into the pores based on the interaction between negatively charged mAb-AuNP and positively charged PEI-MSN. In the presence of target AFB1, a competitive-type displacement reaction was implemented between mAb-AuNP and PEI-MSN by target AFB1 through the specific antigen-antibody reaction. Accompanying the reaction, target AFB1 could displace the mAb-AuNP from the surface of PEI-MSN, resulting in the release of the loading glucose from the pores due to the gate opened. The released glucose molecules could be quantitatively determined by using a portable PGM. Under optimal conditions, the PGM signal increased with the increment of AFB1 concentration in the range from 0.01 to 15 μg/kg (ppb) with a detection limit (LOD) of 5 ng/kg (5 ppt) at the 3sblank criterion. The selectivity and precision were acceptable. Importantly, the methodology was further validated for assaying naturally contaminated or spiked blank peanut samples, and consistent results between the PGM-based immunoassay and the referenced enzyme-linked immunosorbent assay (ELISA) were obtained. Therefore, the developed immunoassay provides a promising approach for rapid screening of organic pollutants because it is simple, low-cost, sensitive, specific, and without the need of multiple separation and washing steps.

  4. Adaptation of Saccharomyces cerevisiae to the Herbicide 2,4-Dichlorophenoxyacetic Acid, Mediated by Msn2p- and Msn4p-Regulated Genes: Important Role of SPI1

    PubMed Central

    Simões, T.; Teixeira, M. C.; Fernandes, A. R.; Sá-Correia, Isabel

    2003-01-01

    The possible roles of 13 Msn2p- and Msn4p-regulated genes in the adaptation of Saccharomyces cerevisiae to the herbicide 2,4-d-dichlorophenoxyacetic acid (2,4-D) were examined. Single deletion of genes involved in defense against oxidizing agents (CTT1, GRX1, and GRX2/TTR1) or encoding chaperones of the HSP70 family (SSA1, SSA4, and SSE2) showed a slight effect. A more significant role was observed for the heat shock genes HSP78, HSP26, HSP104, HSP12, and HSP42, most of which encode molecular chaperones. However, the SPI1 gene, encoding a member of the glycosylphosphatidylinositol-anchored cell wall protein family, emerged as the major determinant of 2,4-D resistance. SPI1 expression reduced the loss of viability of an unadapted yeast population suddenly exposed to the herbicide, allowing earlier growth resumption. Significantly, yeast adaptation to 2,4-D involves the rapid and transient Msn2p- and Msn4p-mediated activation (fivefold) of SPI1 transcription. SPI1 mRNA levels were reduced to values slightly above those in unstressed cells when the adapted population started duplication in the presence of 2,4-D. Since SPI1 deletion leads to the higher β-1,3-glucanase sensitivity of 2,4-D-stressed cells, it was hypothesized that adaptation may involve an Spi1p-mediated increase in the diffusional restriction of the liposoluble acid form of the herbicide across the cell envelope. Such a cell response would avoid a futile cycle due to acid reentry into the cell counteracting the active export of the anionic form, presumably through an inducible plasma membrane transporter(s). Consistent with this concept, the concentration of 14C-labeled 2,4-D in 2,4-D-energized adapted Δspi1 mutant cells and the consequent intracellular acidification are higher than in wild-type cells. PMID:12839777

  5. Novel electrochemical immunoassay for quantitative monitoring of biotoxin using target-responsive cargo release from mesoporous silica nanocontainers.

    PubMed

    Zhang, Bing; Liu, Bingqian; Liao, Jiayao; Chen, Guonan; Tang, Dianping

    2013-10-01

    A novel homogeneous immunoassay protocol was designed for quantitative monitoring of small molecular biotoxin (brevetoxin B, PbTx-2, as a model) by using target-responsive cargo release from polystyrene microsphere-gated mesoporous silica nanocontainer (MSN). Initially, monoclonal mouse anti-PbTx-2 capture antibody was covalently conjugated onto the surface of MSN (mAb-MSN), and the electroactive cargo (methylene blue, MB) was then trapped in the pores of mAb-MSN by using aminated polystyrene microspheres (APSM) based on the electrostatic interaction. Upon addition of target PbTx-2, the positively charged APSM was displaced from the negatively charged mAb-MSN because of the specific antigen-antibody reaction. Thereafter, the molecular gate was opened, and the trapped methylene blue was released from the pores. The released methylene blue could be monitored by using a square wave voltammetry (SWV) in a homemade microelectrochemical detection cell. Under optimal conditions, the SWV peak current increased with the increasing of PbTx-2 concentration in the range from 0.01 to 3.5 ng mL(-1) with a detection limit (LOD) of 6 pg mL(-1) PbTx-2 at the 3Sblank criterion. Intra- and interassay coefficients of variation with identical batches were ≤6% and 9.5%, respectively. The specificity and sample matrix interfering effects were acceptable. The analysis in 12 spiked seafood samples showed good accordance between results obtained by the developed immunoassay and a commercialized enzyme-linked immunosorbent assay (ELISA) method. Importantly, the target-responsive controlled release system-based electrochemical immunoassay (CRECIA) offers a promising scheme for the development of advanced homogeneous immunoassay without the sample separation and washing procedure.

  6. Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles-A Platform for Drug Development.

    PubMed

    Wickström, Henrika; Hilgert, Ellen; Nyman, Johan O; Desai, Diti; Şen Karaman, Didem; de Beer, Thomas; Sandler, Niklas; Rosenholm, Jessica M

    2017-11-21

    Mesoporous silica nanoparticles (MSNs) have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV) and poorly permeable (BCS class III, IV) drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN) ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D) for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI) surface functionalized MSNs, as well as drug-free and drug-loaded MSN-PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.

  7. Pore size and concentration effect of mesoporous silica nanoparticles on the coefficient of thermal expansion and optical transparency of poly(ether sulfone) films.

    PubMed

    Vo, Nhat Tri; Patra, Astam K; Kim, Dukjoon

    2017-01-18

    Mesoporous silica nanoparticles (MSNs) with uniform size (<50 nm) yet with different pore diameters were synthesized, and used as fillers in poly(ether sulfone) (PES) films in order to decrease their coefficient of thermal expansion (CTE) without sacrificing optical transparency. Here, both CTE and optical transparency of the MSN/PES nanocomposite films gradually decreased with increasing MSN concentration. The PES films containing MSNs with larger pores showed the best performance in CTE and optical transparency. While the CTE decreased by 32.3% with increasing MSN content up to 0.5 wt%, the optical transparency decreased by only less than 6.9% because of the small and uniform particle size of less than 50 nm, which minimizes light scattering. This pore size effect is more clearly observed via an annealing process, which enables the polymer chains to slowly move and fill in the free volume in the pores of the MSN, and thus restricts the thermal motion. The effect of the silica nanoparticles was investigated not only on the thermal stability but also on the mechanical stability. We expect the MSNs synthesized in this study to be used as a promising filler to enhance the thermal and mechanical stability of the PES substrate without sacrificing its optical transparency.

  8. Cortical Regulation of Striatal Medium Spiny Neuron Dendritic Remodeling in Parkinsonism: Modulation of Glutamate Release Reverses Dopamine Depletion–Induced Dendritic Spine Loss

    PubMed Central

    Garcia, Bonnie G.; Neely, M. Diana

    2010-01-01

    Striatal medium spiny neurons (MSNs) receive glutamatergic afferents from the cerebral cortex and dopaminergic inputs from the substantia nigra (SN). Striatal dopamine loss decreases the number of MSN dendritic spines. This loss of spines has been suggested to reflect the removal of tonic dopamine inhibitory control over corticostriatal glutamatergic drive, with increased glutamate release culminating in MSN spine loss. We tested this hypothesis in two ways. We first determined in vivo if decortication reverses or prevents dopamine depletion–induced spine loss by placing motor cortex lesions 4 weeks after, or at the time of, 6-hydroxydopamine lesions of the SN. Animals were sacrificed 4 weeks after cortical lesions. Motor cortex lesions significantly reversed the loss of MSN spines elicited by dopamine denervation; a similar effect was observed in the prevention experiment. We then determined if modulating glutamate release in organotypic cocultures prevented spine loss. Treatment of the cultures with the mGluR2/3 agonist LY379268 to suppress corticostriatal glutamate release completely blocked spine loss in dopamine-denervated cultures. These studies provide the first evidence to show that MSN spine loss associated with parkinsonism can be reversed and point to suppression of corticostriatal glutamate release as a means of slowing progression in Parkinson's disease. PMID:20118184

  9. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chung, Po-Wen

    The dissertation begins with Chapter 1, which is a general introduction of the fundamental synthesis of mesoporous silica materials, the selective functionlization of mesoporous silica materials, and the synthesis of nanostructured porous materials via nanocasting. In Chapter 2, the thermo-responsive polymer coated mesoporous silica nanoparticles (MSN) was synthesized via surface-initated polymerization and exhibited unique partition activities in a biphasic solution with the thermally induced change. In Chapter 3, the monodispersed spherical MSN with different mesoporous structure (MCM-48) was developed and employed as a template for the synthesis of mesoporous carbon nanoparticles (MCN) via nanocasting. MCN was demonstrated for the deliverymore » of membrane impermeable chemical agents inside the cells. The cellular uptake efficiency and biocompabtibility of MCN with human cervical cancer cells were also investigated. In addition to the biocompabtibility of MCN, MCN was demonstrated to support Rh-Mn nanoparticles for catalytic reaction in Chapter 4. Owing to the unique mesoporosity, Rh-Mn nanoparticles can be well distributed inside the mesoporous structure and exhibited interesting catalytic performance on CO hydrogenation. In Chapter 5, the synthesis route of the aforementioned MCM-48 MSN was discussed and investigated in details and other metal oxide nanoparticles were also developed via nanocasting by using MCM-48 MSN as a template. At last, there is a general conclusion summarized in Chapter 6.« less

  10. Implementing an MSN nursing program at a distance through an urban-rural partnership.

    PubMed

    Zukowsky, Ksenia; Swan, Beth Ann; Powell, Mary; Frisby, Tony; Lauver, Lori; West, Margaret Mary; Marsella, Alexis

    2011-04-01

    Recruiting, retaining, and educating advanced practice nurses is essential to meet the growing need for advanced practice nurses in rural and urban communities. Through the support of Health Resources and Services Administration funding, the urban school of nursing expanded its MSN program and implemented the graduate curriculum on its rural campus by utilizing emerging online and distance education technologies. The purpose of this manuscript is to provide an overview of expanding an existing MSN program offered in an urban, traditional classroom setting to rural graduate nursing students via an online synchronous format. In addition, the article will describe the rural growth of the existing neonatal nurse practitioner program as an exemplar and the different methodologies that are being used in each program to engage the rural nurse practitioner students in clinical courses. In addition, strategies to address barriers related to rural nurse practitioner student recruitment and retention will be discussed.

  11. Facile synthesis of blue-emitting carbon dots@mesoporous silica composite spheres

    NASA Astrophysics Data System (ADS)

    Guo, Ziying; Zhu, Zhenpeng; Zhang, Xinguo; Chen, Yibo

    2018-02-01

    This paper reported a facile and effective approach towards high-efficient composite luminophores by embedding blue-emitting N-doped carbon dots into spherical SiO2 matrix (CDs@SiO2). Mesoporous silica microspheres (r-CDs@MSN) with strong luminescence were synthesized by removing CTAB templates in CDs@SiO2 using reflux with acetone. The r-CDs@MSN possess a spherical morphology with smooth surface and a diameter of 130 nm, while it exhibits an excitation-independent blue emission peak at 440 nm with an internal quantum yield of 21.5%. BET result shows that the corresponding surface area and adsorption total pore volume are 156.27 m2/g and 0.682 cm3/g, which is suitable for the drugs loading and release. The results indicate that r-CDs@MSN might act as a potential fluorescent drug carrier.

  12. Mesoporous silica nanoparticles as smart and safe devices for regulating blood biomolecule levels

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhao, Yan

    2011-01-01

    Stimuli-responsive end-capped MSN materials are promising drug carriers that securely deliver a large payload of drug molecules without degradation or premature release. A general review of the recent progress in this field is presented, including a summary of a series of hard and soft caps for drug encapsulation and a variety of internal and external stimuli for controlled release of different therapeutics, a discussion of the biocompatibility of MSN both in vitro and in vivo, and a description of the sophisticated stimuli-responsive systems with novel capping agents and controlled release mechanism. The unique internal and external surfaces of MSN weremore » utilized for the development of a glucose-responsive double delivery system end-capped with insulin. This unique system consists of functionalized MSNs capable of releasing insulin when the concentration of sugar in blood exceeds healthy levels. The insulin-free nanoparticles are then up taken by pancreatic cells, and release inside of them another biomolecule that stimulates the production of more insulin. The in vivo application of this system for the treatment of diabetes requires further understanding on the biological behaviors of these nanoparticles in blood vessels. The research presented in this dissertation demonstrated the size and surface effects on the interaction of MSNs with red blood cell membranes, and discovered how the surface of the nanoparticles can be modified to improve their compatibility with red blood cells and avoid their dangerous side effects. In order to optimize the properties of MSN for applying them as efficient intracellular drug carriers it is necessary to understand the factors that can regulate their internalization into and exocytosis out of the cells. The correlation between the particle morphology and aggregation of MSNs to the effectiveness of cellular uptake is discussed and compared with different cell lines. The differences in the degree of exocytosis of MSNs between healthy and cancer cells is reported and found to be responsible for the asymmetric transfer of the particles between both cell types. The fundamental studies on the hemocompatibility, endo- and exocytosis of MSN along with its ability to sequentially release multiple therapeutics in response to different stimuli, allow us to propose MSN as an intravascular vehicle with a great potential for various biomedical applications.« less

  13. Identification of triacylglycerol using automated annotation of high resolution multistage mass spectral trees.

    PubMed

    Wang, Xiupin; Peng, Qingzhi; Li, Peiwu; Zhang, Qi; Ding, Xiaoxia; Zhang, Wen; Zhang, Liangxiao

    2016-10-12

    High complexity of identification for non-target triacylglycerols (TAGs) is a major challenge in lipidomics analysis. To identify non-target TAGs, a powerful tool named accurate MS(n) spectrometry generating so-called ion trees is used. In this paper, we presented a technique for efficient structural elucidation of TAGs on MS(n) spectral trees produced by LTQ Orbitrap MS(n), which was implemented as an open source software package, or TIT. The TIT software was used to support automatic annotation of non-target TAGs on MS(n) ion trees from a self-built fragment ion database. This database includes 19108 simulate TAG molecules from a random combination of fatty acids and corresponding 500582 self-built multistage fragment ions (MS ≤ 3). Our software can identify TAGs using a "stage-by-stage elimination" strategy. By utilizing the MS(1) accurate mass and referenced RKMD, the TIT software can discriminate unique elemental composition candidates. The regiospecific isomers of fatty acyl chains will be distinguished using MS(2) and MS(3) fragment spectra. We applied the algorithm to the selection of 45 TAG standards and demonstrated that the molecular ions could be 100% correctly assigned. Therefore, the TIT software could be applied to TAG identification in complex biological samples such as mouse plasma extracts. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. In vivo biochemical analyses reveal distinct roles of β-importins and eEF1A in tRNA subcellular traffic

    PubMed Central

    Huang, Hsiao-Yun

    2015-01-01

    Bidirectional tRNA movement between the nucleus and the cytoplasm serves multiple biological functions. To gain a biochemical understanding of the mechanisms for tRNA subcellular dynamics, we developed in vivo β-importin complex coimmunoprecipitation (co-IP) assays using budding yeast. Our studies provide the first in vivo biochemical evidence that two β-importin family members, Los1 (exportin-t) and Msn5 (exportin-5), serve overlapping but distinct roles in tRNA nuclear export. Los1 assembles complexes with RanGTP and tRNA. Both intron-containing pre-tRNAs and spliced tRNAs, regardless of whether they are aminoacylated, assemble into Los1–RanGTP complexes, documenting that Los1 participates in both primary nuclear export and re-export of tRNAs to the cytoplasm. In contrast, β-importin Msn5 preferentially assembles with RanGTP and spliced, aminoacylated tRNAs, documenting its role in tRNA nuclear re-export. Tef1/2 (the yeast form of translation elongation factor 1α [eEF1A]) aids the specificity of Msn5 for aminoacylated tRNAs to form a quaternary complex consisting of Msn5, RanGTP, aminoacylated tRNA, and Tef1/2. Assembly and/or stability of this quaternary complex requires Tef1/2, thereby facilitating efficient re-export of aminoacylated tRNAs to the cytoplasm. PMID:25838545

  15. Anion photoelectron spectroscopy of germanium and tin clusters containing a transition- or lanthanide-metal atom; MGe(n)- (n = 8-20) and MSn(n)- (n = 15-17) (M = Sc-V, Y-Nb, and Lu-Ta).

    PubMed

    Atobe, Junko; Koyasu, Kiichirou; Furuse, Shunsuke; Nakajima, Atsushi

    2012-07-14

    The electronic properties of germanium and tin clusters containing a transition- or lanthanide-metal atom from group 3, 4, or 5, MGe(n) (M = Sc, Ti, V, Y, Zr, Nb, Lu, Hf, and Ta) and MSn(n) (M = Sc, Ti, Y. Zr, and Hf), were investigated by anion photoelectron spectroscopy at 213 nm. In the case of the group 3 elements Sc, Y, and Lu, the threshold energy of electron detachment of MGe(n)(-) exhibits local maxima at n = 10 and 16, while in the case of the group 4 elements Ti, Zr, and Hf, it exhibits a local minimum only at n = 16, associated with the presence of a small bump in the spectrum. A similar behavior is observed for MSn(n)(-) around n = 16, and these electronic characteristics of MGe(n) and MSn(n) are closely related to those of MSi(n). Compared to MSi(n), however, the larger cavity size of a Ge(n) cage allows metal atom encapsulation at a smaller size n. A cooperative effect between the electronic and geometric structures of clusters with a large cavity of Ge(16) or Sn(16) is discussed together with the results of experiments that probe their geometric stability via their reactivity to H(2)O adsorption.

  16. Enhanced antibacterial activity of silver-decorated sandwich-like mesoporous silica/reduced graphene oxide nanosheets through photothermal effect

    NASA Astrophysics Data System (ADS)

    Liu, Rong; Wang, Xuandong; Ye, Jun; Xue, Ximei; Zhang, Fangrong; Zhang, Huicong; Hou, Xuemei; Liu, Xiaolong; Zhang, Yun

    2018-03-01

    Drug resistance of bacteria has become a global health problem, as it makes conventional antibiotics less efficient. It is urgently needed to explore novel antibacterial materials and develop effective treatment strategies to overcome the drug resistance of antibiotics. Herein, we successfully synthesized silver decorated sandwich-like mesoporous silica/reduced graphene oxide nanosheets (rGO/MSN/Ag) as a novel antibacterial material through facile method. The rGO and Ag nanoparticles can be reduced in the reaction system without adding any other reductants. In addition, the rGO/MSN/Ag showed higher photothermal conversion capacity due to the modification of silver nanoparticles and exhibited excellent antibacterial activities against Pseudomonas putida, Escherichia coli and Rhodococcus at relatively low dosages, which was confirmed by the minimum inhibitory concentration (MIC) test. Meanwhile, the E. coli with a high concentration was selected for exposure using an 808 nm laser, and the antibacterial effect was obviously enhanced by the near-infrared irradiation induced photothermal effect. Moreover, the hepatocyte LO2 were used for the cytotoxicity evaluation, and the rGO/MSN/Ag showed low toxicity and were without detectable cytotoxicity at the antimicrobial dose. As the prepared rGO/MSN/Ag nanosheets have the advantages of low-cost and high antibacterial activity, they might be of promising and useful antibacterial agents for different applications.

  17. Optimal balance of the striatal medium spiny neuron network.

    PubMed

    Ponzi, Adam; Wickens, Jeffery R

    2013-04-01

    Slowly varying activity in the striatum, the main Basal Ganglia input structure, is important for the learning and execution of movement sequences. Striatal medium spiny neurons (MSNs) form cell assemblies whose population firing rates vary coherently on slow behaviourally relevant timescales. It has been shown that such activity emerges in a model of a local MSN network but only at realistic connectivities of 10 ~ 20% and only when MSN generated inhibitory post-synaptic potentials (IPSPs) are realistically sized. Here we suggest a reason for this. We investigate how MSN network generated population activity interacts with temporally varying cortical driving activity, as would occur in a behavioural task. We find that at unrealistically high connectivity a stable winners-take-all type regime is found where network activity separates into fixed stimulus dependent regularly firing and quiescent components. In this regime only a small number of population firing rate components interact with cortical stimulus variations. Around 15% connectivity a transition to a more dynamically active regime occurs where all cells constantly switch between activity and quiescence. In this low connectivity regime, MSN population components wander randomly and here too are independent of variations in cortical driving. Only in the transition regime do weak changes in cortical driving interact with many population components so that sequential cell assemblies are reproducibly activated for many hundreds of milliseconds after stimulus onset and peri-stimulus time histograms display strong stimulus and temporal specificity. We show that, remarkably, this activity is maximized at striatally realistic connectivities and IPSP sizes. Thus, we suggest the local MSN network has optimal characteristics - it is neither too stable to respond in a dynamically complex temporally extended way to cortical variations, nor is it too unstable to respond in a consistent repeatable way. Rather, it is optimized to generate stimulus dependent activity patterns for long periods after variations in cortical excitation.

  18. Optimal Balance of the Striatal Medium Spiny Neuron Network

    PubMed Central

    Ponzi, Adam; Wickens, Jeffery R.

    2013-01-01

    Slowly varying activity in the striatum, the main Basal Ganglia input structure, is important for the learning and execution of movement sequences. Striatal medium spiny neurons (MSNs) form cell assemblies whose population firing rates vary coherently on slow behaviourally relevant timescales. It has been shown that such activity emerges in a model of a local MSN network but only at realistic connectivities of and only when MSN generated inhibitory post-synaptic potentials (IPSPs) are realistically sized. Here we suggest a reason for this. We investigate how MSN network generated population activity interacts with temporally varying cortical driving activity, as would occur in a behavioural task. We find that at unrealistically high connectivity a stable winners-take-all type regime is found where network activity separates into fixed stimulus dependent regularly firing and quiescent components. In this regime only a small number of population firing rate components interact with cortical stimulus variations. Around connectivity a transition to a more dynamically active regime occurs where all cells constantly switch between activity and quiescence. In this low connectivity regime, MSN population components wander randomly and here too are independent of variations in cortical driving. Only in the transition regime do weak changes in cortical driving interact with many population components so that sequential cell assemblies are reproducibly activated for many hundreds of milliseconds after stimulus onset and peri-stimulus time histograms display strong stimulus and temporal specificity. We show that, remarkably, this activity is maximized at striatally realistic connectivities and IPSP sizes. Thus, we suggest the local MSN network has optimal characteristics – it is neither too stable to respond in a dynamically complex temporally extended way to cortical variations, nor is it too unstable to respond in a consistent repeatable way. Rather, it is optimized to generate stimulus dependent activity patterns for long periods after variations in cortical excitation. PMID:23592954

  19. Web-based depression screening and psychiatric consultation for college students: a feasibility and acceptability study.

    PubMed

    Williams, Aya; Larocca, Rachel; Chang, Trina; Trinh, Nhi-Ha; Fava, Maurizio; Kvedar, Joseph; Yeung, Albert

    2014-01-01

    Background. A steady rise in the prevalence of depression among college students has negatively affected student quality of life. This study investigates the feasibility and acceptability of a Web-based model, including Skype, to screen and provide psychiatric consultation to depressed college students. Methods. Students completed the 9-item Patient Health Questionnaire (PHQ-9) online; those who screened positive (PHQ-9 ≥ 10) or endorsed any level of suicidal ideation were offered Web-based psychiatric consultation using Skype. After the consultation, students filled out a 7-item satisfaction questionnaire to report on the acceptability of this Web-based method. Results. A total of 972 students consented to the online depression screening and 285 screened positive. Of those, 69 students consented and 17 students successfully completed the psychiatric consultation via Skype. Thirteen (76.4%) students found the interview useful in helping them understand their depression. Fifteen (88.2%) students thought that psychologists and psychiatrists could successfully see patients via videoconferencing. Conclusions. Current online technologies can provide depression screening and psychiatric consultation to college students; those who participated reported a positive experience. Future studies will need to address the low levels of participation among college students and attract students who are underserved, as well as use a videoconferencing platform that adequately protects data confidentiality.

  20. Web-Based Depression Screening and Psychiatric Consultation for College Students: A Feasibility and Acceptability Study

    PubMed Central

    Williams, Aya; LaRocca, Rachel; Chang, Trina; Trinh, Nhi-Ha; Fava, Maurizio

    2014-01-01

    Background. A steady rise in the prevalence of depression among college students has negatively affected student quality of life. This study investigates the feasibility and acceptability of a Web-based model, including Skype, to screen and provide psychiatric consultation to depressed college students. Methods. Students completed the 9-item Patient Health Questionnaire (PHQ-9) online; those who screened positive (PHQ-9 ≥ 10) or endorsed any level of suicidal ideation were offered Web-based psychiatric consultation using Skype. After the consultation, students filled out a 7-item satisfaction questionnaire to report on the acceptability of this Web-based method. Results. A total of 972 students consented to the online depression screening and 285 screened positive. Of those, 69 students consented and 17 students successfully completed the psychiatric consultation via Skype. Thirteen (76.4%) students found the interview useful in helping them understand their depression. Fifteen (88.2%) students thought that psychologists and psychiatrists could successfully see patients via videoconferencing. Conclusions. Current online technologies can provide depression screening and psychiatric consultation to college students; those who participated reported a positive experience. Future studies will need to address the low levels of participation among college students and attract students who are underserved, as well as use a videoconferencing platform that adequately protects data confidentiality. PMID:24799895

  1. Multi-Timescale Complex Adaptation

    DTIC Science & Technology

    2006-03-01

    Hucka et al., 2001), Cluster/TreeView (Eisen et al., 1998), Pajek ( Batagelj & Mrvar , 1998) and Cytoscape (Ideker et al., 2002). These can be used in the...targets of MCM1 or FKH2 individually or the product of MCM1 and FKH2. STRE is bound by MSN2 and/or MSN4 (Schmitt and McEntee, 1996 ) and for this...Ghosh, Scale based clustering using a radial basis function network. IEEE Transactions on Neural Networks, 2(5):1250-1261, 1996 . Chen, K.C., Csikasz

  2. Mucin-1-Antibody-Conjugated Mesoporous Silica Nanoparticles for Selective Breast Cancer Detection in a Mucin-1 Transgenic Murine Mouse Model.

    PubMed

    Dréau, Didier; Moore, Laura Jeffords; Alvarez-Berrios, Merlis P; Tarannum, Mubin; Mukherjee, Pinku; Vivero-Escoto, Juan L

    2016-12-01

    Mucin-1 (MUC1), a transmembrane glycoprotein is aberrantly expressed on ~90% of breast cancer and is an excellent target for nanoparticulate targeted imaging. In this study, the development of a dye-doped NIR emitting mesoporous silica nanoparticles platform conjugated to tumor-specific MUC1 antibody (ab-tMUC1-NIR-MSN) for in vivo optical detection of breast adenocarcinoma tissue is reported. The structural properties, the in vitro and in vivo performance of this nanoparticle-based probe were evaluated. In vitro studies showed that the MSN-based optical imaging nanoprobe is non-cytotoxic and targets efficiently mammary cancer cells overexpressing human tMUC1 protein. In vivo experiments with female C57BL/6 mice indicated that this platform accumulates mainly in the liver and did not induce short-term toxicity. In addition, we demonstrated that the ab-tMUC1-NIR-MSN nanoprobe specifically detects mammary gland tumors overexpressing human tMUC1 in a human MUC1 transgenic mouse model.

  3. Study on the Alkaloids in Tibetan Medicine Aconitum pendulum Busch by HPLC–MSn Combined with Column Chromatography

    PubMed Central

    Wang, Beibei; Dong, Jie; Ji, Jiaojiao; Yuan, Jiang; Wang, Jiali; Wu, Jiarui; Tan, Peng; Liu, Yonggang

    2016-01-01

    A rapid, convenient and effective identification method of alkaloids was established and an attempt on isolating and analyzing the alkaloids in Aconitum pendulum Busch was conducted successfully. In this article, four high-content components including deoxyaconitine, benzoylaconine, aconine and neoline were isolated by using column chromatography. HPLC–MSn was employed to deduce the regulations of fragmentation of diterpenoid alkaloids which displayed a characteristic behavior of loss of CO(28u), CH3COOH(60u), CH3OH(32u), H2O(18u) and C6H5COOH(122u). Then, according to fragmentation regulation of mass spectrometry, 42 alkaloids were found in A. pendulum. Among them, 38 compounds were identified and 29 alkaloids were reported for the first time for this herb. Therefore, this means that HPLC–MSn combined with column chromatography could work as an effective and reliable tool for rapid identification of the chemical components of herbal medicine. PMID:26896350

  4. Pathway and Cell-Specific Kappa-Opioid Receptor Modulation of Excitatory-Inhibitory Balance Differentially Gates D1 and D2 Accumbens Neuron Activity

    PubMed Central

    Tejeda, Hugo A.; Wu, Jocelyn; Kornspun, Alana R.; Pignatelli, Marco; Kashtelyan, Vadim; Krashes, Michael J.; Lowell, Brad B.; Carlezon, William A.; Bonci, Antonello

    2018-01-01

    Endogenous dynorphin signaling via the kappa-opioid receptor (KOR) in the nucleus accumbens (NAcc) powerfully mediates negative affective states and stress reactivity. Excitatory inputs from the hippocampus and amygdala play a fundamental role in shaping the activity of both NAcc D1 and D2 MSNs, which encode positive and negative motivational valences, respectively. However, a circuit-based mechanism by which KOR modulation of excitation-inhibition balance modifies D1 and D2 MSN activity is lacking. Here, we provide a comprehensive synaptic framework wherein presynaptic KOR inhibition decreases excitatory drive of D1 MSN activity by the amygdala, but not hippocampus. Conversely, presynaptic inhibition by KORs of inhibitory synapses on D2 MSNs enhances integration of excitatory drive by the amygdala and hippocampus. In conclusion, we describe a circuit-based mechanism showing differential gating of afferent control of D1 and D2 MSN activity by KORs in a pathway specific manner. PMID:28056342

  5. Double-scattering/reflection in a Single Nanoparticle for Intensified Ultrasound Imaging

    PubMed Central

    Zhang, Kun; Chen, Hangrong; Guo, Xiasheng; Zhang, Dong; Zheng, Yuanyi; Zheng, Hairong; Shi, Jianlin

    2015-01-01

    Ultrasound contrast agents (UCAs) designed by the conventional composition-based strategy, often suffer from relatively low ultrasound utilization efficiency. In this report, a structure-based design concept of double-scattering/reflection in a single nanoparticle for enhancing ultrasound imaging has been proposed. To exemplify this concept, a rattle-type mesoporous silica nanostructure (MSN) with two contributing interfaces has been employed as the ideal model. Contributed by double-scattering/reflection interfaces, the rattle-type MSN, as expected, performs much better in in vitro and in vivo ultrasound imaging than the other two nanostructures (solid and hollow) containing only one scattering/reflection interface. More convincingly, related acoustic measurements and simulation calculations also confirm this design concept. Noticeably, the rattle-type MSN has also been demonstrated capable of improving intracellular ultrasound molecular imaging. As a universal method, the structure-design concept can extend to guide the design of new generation UCAs with many other compositions and similar structures (e.g., heterogeneous rattle-type, double-shelled). PMID:25739832

  6. Double-scattering/reflection in a single nanoparticle for intensified ultrasound imaging.

    PubMed

    Zhang, Kun; Chen, Hangrong; Guo, Xiasheng; Zhang, Dong; Zheng, Yuanyi; Zheng, Hairong; Shi, Jianlin

    2015-03-05

    Ultrasound contrast agents (UCAs) designed by the conventional composition-based strategy, often suffer from relatively low ultrasound utilization efficiency. In this report, a structure-based design concept of double-scattering/reflection in a single nanoparticle for enhancing ultrasound imaging has been proposed. To exemplify this concept, a rattle-type mesoporous silica nanostructure (MSN) with two contributing interfaces has been employed as the ideal model. Contributed by double-scattering/reflection interfaces, the rattle-type MSN, as expected, performs much better in in vitro and in vivo ultrasound imaging than the other two nanostructures (solid and hollow) containing only one scattering/reflection interface. More convincingly, related acoustic measurements and simulation calculations also confirm this design concept. Noticeably, the rattle-type MSN has also been demonstrated capable of improving intracellular ultrasound molecular imaging. As a universal method, the structure-design concept can extend to guide the design of new generation UCAs with many other compositions and similar structures (e.g., heterogeneous rattle-type, double-shelled).

  7. Gold Functionalized Mesoporous Silica Nanoparticle Mediated Protein and DNA Codelivery to Plant Cells Via the Biolistic Method

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Martin-Ortigosa, Susana; Valenstein, Justin S.; Lin, Victor S.-Y.

    2012-09-11

    The synthesis and characterization of a gold nanoparticle functionalized mesoporous silica nanoparticle (Au-MSN) platform for codelivery of proteins and plasmid DNA to plant tissues using a biolistic particle delivery system is reported. The in vitro uptake and release profiles of fluorescently labeled bovine serum albumin (BSA) and enhanced green fluorescent protein (eGFP) are investigated. As a proof-of-concept demonstration, Au-MSN with large average pore diameters (10 nm) are shown to deliver and subsequently release proteins and plasmid DNA to the same cell after passing through the plant cell wall upon bombardment. Release of fluorescent eGFP indicates the delivery of active, non-denaturedmore » proteins to plant cells. This advance represents the first example of biolistic-mediated codelivery of proteins and plasmid DNA to plant cells via gold-functionalized MSN and provides a powerful tool for both fundamental and applied research of plant sciences.« less

  8. Simultaneous separation and identification of oligomeric procyanidins and anthocyanin-derived pigments in raw red wine by HPLC-UV-ESI-MSn.

    PubMed

    Pati, S; Losito, I; Gambacorta, G; La Notte, E; Palmisano, F; Zambonin, P G

    2006-07-01

    Samples of raw red wine (Primitivo di Manduria, Apulia, Southern Italy) were analysed without any pre-treatment (except 1:2 dilution with water) using HPLC with detection based on UV absorbance and Electrospray Ionisation Sequential Mass Spectrometry (ESI-MSn, with n = 1-3) in a series configuration. In particular, absorbance at 520 nm was monitored for UV detection in order to identify pigments responsible for wine colour. On the other hand, two subsequent stages of MS detection based on positive ions were adopted. The first consisted of an explorative MS acquisition, aimed at the individuation of the m/z ratios for positively charged compounds; the second was based on fragmentation of the detected ions within an ion trap analyser, followed by MS/MS and, if required, MS3 acquisitions. The synergy between UV detection and MSn analysis led to the identification of 41 pigments, which can be classified into five groups: grape anthocyanins, pyranoanthocyanins, vinyl-linked anthocyanin-flavanol pigments, ethyl-bridged anthocyanin-flavanol pigments and flavanol-anthocyanin compounds. Many isomeric and oligomeric structures were found within each group. A further class of compounds, not absorbing in the visible spectrum, could be also characterised by ESI-MSn and corresponded to B-type procyanidins, i.e. proanthocyanidins arising from C4-->C8/C4-->C6 couplings between catechin or epicatechin units. In particular, oligomeric structures (from dimers to pentamers), often present with several isomers, were identified and their fragmentation patterns clarified.

  9. In vivo biochemical analyses reveal distinct roles of β-importins and eEF1A in tRNA subcellular traffic.

    PubMed

    Huang, Hsiao-Yun; Hopper, Anita K

    2015-04-01

    Bidirectional tRNA movement between the nucleus and the cytoplasm serves multiple biological functions. To gain a biochemical understanding of the mechanisms for tRNA subcellular dynamics, we developed in vivo β-importin complex coimmunoprecipitation (co-IP) assays using budding yeast. Our studies provide the first in vivo biochemical evidence that two β-importin family members, Los1 (exportin-t) and Msn5 (exportin-5), serve overlapping but distinct roles in tRNA nuclear export. Los1 assembles complexes with RanGTP and tRNA. Both intron-containing pre-tRNAs and spliced tRNAs, regardless of whether they are aminoacylated, assemble into Los1-RanGTP complexes, documenting that Los1 participates in both primary nuclear export and re-export of tRNAs to the cytoplasm. In contrast, β-importin Msn5 preferentially assembles with RanGTP and spliced, aminoacylated tRNAs, documenting its role in tRNA nuclear re-export. Tef1/2 (the yeast form of translation elongation factor 1α [eEF1A]) aids the specificity of Msn5 for aminoacylated tRNAs to form a quaternary complex consisting of Msn5, RanGTP, aminoacylated tRNA, and Tef1/2. Assembly and/or stability of this quaternary complex requires Tef1/2, thereby facilitating efficient re-export of aminoacylated tRNAs to the cytoplasm. © 2015 Huang and Hopper; Published by Cold Spring Harbor Laboratory Press.

  10. Protein Kinase A Regulates Constitutive Expression of Small Heat-Shock Genes in an Msn2/4p-Independent and Hsf1p-Dependent Manner in Saccharomyces cerevisiae

    PubMed Central

    Ferguson, Scott B.; Anderson, Erik S.; Harshaw, Robyn B.; Thate, Tim; Craig, Nancy L.; Nelson, Hillary C. M.

    2005-01-01

    Hsf1p, the heat-shock transcription factor from Saccharomyces cerevisiae, has a low level of constitutive transcriptional activity and is kept in this state through negative regulation. In an effort to understand this negative regulation, we developed a novel genetic selection that detects altered expression from the HSP26 promoter. Using this reporter strain, we identified mutations and dosage compensators in the Ras/cAMP signaling pathway that decrease cAMP levels and increase expression from the HSP26 promoter. In yeast, low cAMP levels reduce the catalytic activity of the cAMP-dependent kinase PKA. Previous studies had proposed that the stress response transcription factors Msn2p/4p, but not Hsf1p, are repressed by PKA. However, we found that reduction or elimination of PKA activity strongly derepresses transcription of the small heat-shock genes HSP26 and HSP12, even in the absence of MSN2/4. In a strain deleted for MSN2/4 and the PKA catalytic subunits, expression of HSP12 and HSP26 depends on HSF1 expression. Our findings indicate that Hsf1p functions downstream of PKA and suggest that PKA might be involved in negative regulation of Hsf1p activity. These results represent a major change in our understanding of how PKA signaling influences the heat-shock response and heat-shock protein expression. PMID:15545649

  11. Different correlation patterns of cholinergic and GABAergic interneurons with striatal projection neurons

    PubMed Central

    Adler, Avital; Katabi, Shiran; Finkes, Inna; Prut, Yifat; Bergman, Hagai

    2013-01-01

    The striatum is populated by a single projection neuron group, the medium spiny neurons (MSNs), and several groups of interneurons. Two of the electrophysiologically well-characterized striatal interneuron groups are the tonically active neurons (TANs), which are presumably cholinergic interneurons, and the fast spiking interneurons (FSIs), presumably parvalbumin (PV) expressing GABAergic interneurons. To better understand striatal processing it is thus crucial to define the functional relationship between MSNs and these interneurons in the awake and behaving animal. We used multiple electrodes and standard physiological methods to simultaneously record MSN spiking activity and the activity of TANs or FSIs from monkeys engaged in a classical conditioning paradigm. All three cell populations were highly responsive to the behavioral task. However, they displayed different average response profiles and a different degree of response synchronization (signal correlation). TANs displayed the most transient and synchronized response, MSNs the most diverse and sustained response and FSIs were in between on both parameters. We did not find evidence for direct monosynaptic connectivity between the MSNs and either the TANs or the FSIs. However, while the cross correlation histograms of TAN to MSN pairs were flat, those of FSI to MSN displayed positive asymmetrical broad peaks. The FSI-MSN correlogram profile implies that the spikes of MSNs follow those of FSIs and both are driven by a common, most likely cortical, input. Thus, the two populations of striatal interneurons are probably driven by different afferents and play complementary functional roles in the physiology of the striatal microcircuit. PMID:24027501

  12. A novel mesoporous silica nanosphere matrix for the immobilization of proteins and their applications as electrochemical biosensor.

    PubMed

    Li, Juan; Qin, Xingzhang; Yang, Zhanjun; Qi, Huamei; Xu, Qin; Diao, Guowang

    2013-01-30

    A mesoporous silica nanoshpere (MSN) was proposed to modify glassy carbon electrode (GCE) for the immobilization of protein. Using glucose oxidase (GOD) as a model, direct electrochemistry of protein and biosensing at the MSN modified GCE was studied for the first time. The MNS had large surface area and offered a favorable microenvironment for facilitating the direct electron transfer between enzyme and electrode surface. Scanning electron microscopy, transmission electron microscopy, UV-vis spectroscopy and cyclic voltammetry were used to examine the interaction between GOD and the MSN matrix. The results demonstrated that the immobilized enzyme on the MSN retained its native structure and bioactivity. In addition, the electrochemical reaction showed a surface controlled, reversible two-proton and two-electron transfer process with the apparent electron transfer rate constant of 3.96 s(-1). The MNS-based glucose biosensor exhibited the two linear ranges of 0.04-2.0 mM and 2.0-4.8 mM, a high sensitivity of 14.5 mA M(-1) cm(-2) and a low detection limit of 0.02 mM at signal-to-noise of 3. The proposed biosensor showed excellent selectivity, good reproducibility, acceptable stability and could be successfully applied in the reagentless detection of glucose in real samples at -0.45 V. The work displayed that mesoporous silica nanosphere provided a promising approach for immobilizing proteins and fabrication of excellent biosensors. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Novel Sfp1 Transcriptional Regulation of Saccharomyces cerevisiae Gene Expression Changes During Spaceflight

    NASA Astrophysics Data System (ADS)

    Coleman, Chasity B.; Allen, Patricia L.; Rupert, Mark; Goulart, Carla; Hoehn, Alexander; Stodieck, Louis S.; Hammond, Timothy G.

    2008-12-01

    This study identifies transcriptional regulation of stress response element (STRE) genes in space in the model eukaryotic organism, Saccharomyces cerevisiae. To determine transcription-factor dependence, gene expression changes in space were examined in strains bearing green fluorescent protein tagged (GFP-tagged) reporters for YIL052C (Sfp1 dependent with stress), YST-2 (Sfp1/Rap1 dependent with stress), or SSA4 (Msn4 dependent with stress), along with strains of SSA4-GFP and YIL052C-GFP with individual deletions of the Msn4 or Sfp1. When compared to parallel ground controls, spaceflight induces significant gene expression changes in SSA4 (35% decrease) and YIL052C (45% decrease), while expression of YST-2 (0.08% decrease) did not change. In space, deletion of Sfp1 reversed the SSA4 gene expression effect (0.00% change), but Msn4 deletion yielded a similar decrease in SSA4 expression (34% change), which indicates that SSA4 gene expression is dependent on the Sfp1 transcription factor in space, unlike other stresses. For YIL052C, deletion of Sfp1 reversed the effect (0.01% change), and the Msn4 deletion maintained the decrease in expression (30% change), which indicates that expression of YIL052C is also dependent on Sfp1 in space. Spaceflight has selective and specific effects on SSA4 and YIL052C gene expression, indicated by novel dependence on Sfp1.

  14. S36. DIFFERENTIAL ENCODING OF SENSITIZATION AND CROSS SENSITIZATION TO PSYCHOSTIMULANTS AND ANTIPSYCHOTICS IN NUCLEUS ACCUMBENS D1- AND D2- RECEPTOR EXPRESSING MEDIUM SPINY NEURONS

    PubMed Central

    Amato, Davide; Heinsbroek, Jasper; Kalivas, Peter W

    2018-01-01

    Abstract Background Nearly half of all individuals diagnosed with schizophrenia abuse addictive substances such as cocaine. Currently, the neurobiological mechanisms in patients with schizophrenia that lead to cocaine abuse are unknown. A possible explanation for the co-morbidity between schizophrenia and addiction is that the rewarding properties of cocaine reverse the diminished motivational drive caused by chronic antipsychotic regimen. Moreover, chronic antipsychotic treatment can sensitize and amplify cocaine rewarding effects and exacerbate psychoses. Methods The rewarding properties of cocaine are attributed to the differential effects of dopamine on D1 and D2 receptor-expressing medium spiny neurons (MSNs) in the nucleus accumbens (NAc). Using in vivo Ca2+ miniature microscopic imaging, we characterize the role of D1 and D2 MSN in mono- and a cross- sensitization paradigms. D1- and D2-Cre mice were injected with a Cre dependent calcium indicator (gCaMP6f) and implanted with a gradient index (GRIN) lens above the nucleus accumbens and calcium activity was recorded using a head mounted miniature microscope. Cocaine sensitization was measured after a classic repeated cocaine regiment and antipsychotic and psychostimulant cross-sensitization was measured by a single cocaine injection after chronic pre-treatment with haloperidol. Results We found that both D1-MSN and D2-MSN populations are modulated by initial cocaine experience and further modulated during the expression of cocaine sensitization. A subpopulation of D1-MSN displayed initial activation, but reduced activity during the expression of sensitization. By contrast, the majority of D2-MSNs were suppressed by initial cocaine experience, but became active during the expression of sensitization. Furthermore, activity of D1- and D2-MSNs bidirectionally related with the observed behavioral responses to cocaine. Cross-sensitization following haloperidol treatment led to increased behavioral responses to psychostimulants. Current experiments are set out to investigate the neuronal responses of D1 and D2-MSN during cross sensitization between haloperidol and cocaine. Discussion Cocaine sensitization leads to differential neuronal responses in D1- and D2-MSN and these responses are differentially correlated with the magnitude of the sensitized behavioral response. These results reveal important new insights in the neurobiological processes in the nucleus accumbens that underlie psychostimulant sensitization and provide an important new model for studying the pharmacology of antipsychotic effects on striatal function and its potential role in increasing the susceptibility of schizophrenic patients to developing drug addiction.

  15. Remote Teaching of Histopathology Using Scanned Slides via Skype Between the United Kingdom and Nigeria.

    PubMed

    Rotimi, Olorunda; Orah, Nnamdi; Shaaban, Abeer; Daramola, Adetola O; Abdulkareem, Fatimah B

    2017-02-01

    -Web-based learning is a major component of distance education. -To explore Web-based applications for pathology teaching in resource-limited sub-Saharan Africa. -The participants were consultant pathologists and trainees drawn from tertiary institutions in Nigeria. They viewed the digital slides via the Leeds virtual pathology Web site, after which, interactive lectures were given via Skype (Skype Communications, Luxembourg City, Luxembourg). Questionnaires were administered via SurveyMonkey (Palo Alto, California) to all participants of 12 sessions between 2014 and 2015. -Nine consultant pathologists and 33 trainees participated in this survey. Of all respondents, 29 (69%) thought it was fairly easy to navigate the system, 11 (26.2%) thought it was easy, whereas 2 (4.8%) felt it was difficult. In addition, 26 respondents (61.9%) found it fairly easy to make a make a diagnosis, 13 (31%) thought it was easy, and 3 (7.1%) noted that it was difficult. Twenty-four respondents (57.1%) had a fairly smooth user experience, 12 (28.6%) experienced occasional crashes, whereas 6 (14.3%) reported a smooth experience. Almost all (41 of 42; 97.6%) respondents felt the pathology teaching was beneficial to their local pathology practice, and all (100%) indicated the need for additional, similar sessions. -The beneficial applications of Internet-based lectures make them a viable, cheaper, and cost-effective alternative to face-to-face lectures in our environment.

  16. FoxP1 marks medium spiny neurons from precursors to maturity and is required for their differentiation.

    PubMed

    Precious, S V; Kelly, C M; Reddington, A E; Vinh, N N; Stickland, R C; Pekarik, V; Scherf, C; Jeyasingham, R; Glasbey, J; Holeiter, M; Jones, L; Taylor, M V; Rosser, A E

    2016-08-01

    Identifying the steps involved in striatal development is important both for understanding the striatum in health and disease, and for generating protocols to differentiate striatal neurons for regenerative medicine. The most prominent neuronal subtype in the adult striatum is the medium spiny projection neuron (MSN), which constitutes more than 85% of all striatal neurons and classically expresses DARPP-32. Through a microarray study of genes expressed in the whole ganglionic eminence (WGE: the developing striatum) in the mouse, we identified the gene encoding the transcription factor Forkhead box protein P1 (FoxP1) as the most highly up-regulated gene, thus providing unbiased evidence for the association of FoxP1 with MSN development. We also describe the expression of FoxP1 in the human fetal brain over equivalent gestational stages. FoxP1 expression persisted through into adulthood in the mouse brain, where it co-localised with all striatal DARPP-32 positive projection neurons and a small population of DARPP-32 negative cells. There was no co-localisation of FoxP1 with any interneuron markers. FoxP1 was detectable in primary fetal striatal cells following dissection, culture, and transplantation into the adult lesioned striatum, demonstrating its utility as an MSN marker for transplantation studies. Furthermore, DARPP-32 expression was absent from FoxP1 knock-out mouse WGE differentiated in vitro, suggesting that FoxP1 is important for the development of DARPP-32-positive MSNs. In summary, we show that FoxP1 labels MSN precursors prior to the expression of DARPP-32 during normal development, and in addition suggest that FoxP1 labels a sub-population of MSNs that are not co-labelled by DARPP-32. We demonstrate the utility of FoxP1 to label MSNs in vitro and following neural transplantation, and show that FoxP1 is required for DARPP-32 positive MSN differentiation in vitro. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  17. A theranostic nrGO@MSN-ION nanocarrier developed to enhance the combination effect of sonodynamic therapy and ultrasound hyperthermia for treating tumor

    NASA Astrophysics Data System (ADS)

    Chen, Yu-Wei; Liu, Tse-Ying; Chang, Po-Hsueh; Hsu, Po-Hung; Liu, Hao-Li; Lin, Hong-Cheu; Chen, San-Yuan

    2016-06-01

    Sonodynamic therapy (SDT), which induces activation of sonosensitizers in cancer cells through ultrasound irradiation, has emerged as an alternative and promising noninvasive therapeutic approach to kill both superficial and deep parts of tumors. In this study, mesoporous silica (MSN) grown on reduced graphene oxide nanosheet (nrGO) capped with Rose Bengal (RB)-PEG-conjugated iron-oxide nanoparticles (IONs), nrGO@MSN-ION-PEG-RB, was strategically designed to have targeted functionality and therapeutic efficacy under magnetic guiding and focused ultrasound (FUS) irradiation, respectively. The singlet oxygen produced by ultrasound-activated RB and the ultrasound-induced heating effect was enhanced by rGO and IONs, which improved the cytotoxic effect in cancer cells. In an animal experiment, we demonstrated that the combination of sonodynamic/hyperthermia therapy with magnetic guidance using this nanocomposite therapeutic agent can produce remarkable efficacious therapy in tumor growth inhibition. Furthermore, the combination effect induced by FUS irradiation produces significant damage to both superficial and deep parts of the targeted tumor.Sonodynamic therapy (SDT), which induces activation of sonosensitizers in cancer cells through ultrasound irradiation, has emerged as an alternative and promising noninvasive therapeutic approach to kill both superficial and deep parts of tumors. In this study, mesoporous silica (MSN) grown on reduced graphene oxide nanosheet (nrGO) capped with Rose Bengal (RB)-PEG-conjugated iron-oxide nanoparticles (IONs), nrGO@MSN-ION-PEG-RB, was strategically designed to have targeted functionality and therapeutic efficacy under magnetic guiding and focused ultrasound (FUS) irradiation, respectively. The singlet oxygen produced by ultrasound-activated RB and the ultrasound-induced heating effect was enhanced by rGO and IONs, which improved the cytotoxic effect in cancer cells. In an animal experiment, we demonstrated that the combination of sonodynamic/hyperthermia therapy with magnetic guidance using this nanocomposite therapeutic agent can produce remarkable efficacious therapy in tumor growth inhibition. Furthermore, the combination effect induced by FUS irradiation produces significant damage to both superficial and deep parts of the targeted tumor. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07782f

  18. Genomic variants in an inbred mouse model predict mania-like behaviors.

    PubMed

    Saul, Michael C; Stevenson, Sharon A; Zhao, Changjiu; Driessen, Terri M; Eisinger, Brian E; Gammie, Stephen C

    2018-01-01

    Contemporary rodent models for bipolar disorders split the bipolar spectrum into complimentary behavioral endophenotypes representing mania and depression. Widely accepted mania models typically utilize single gene transgenics or pharmacological manipulations, but inbred rodent strains show great potential as mania models. Their acceptance is often limited by the lack of genotypic data needed to establish construct validity. In this study, we used a unique strategy to inexpensively explore and confirm population allele differences in naturally occurring candidate variants in a manic rodent strain, the Madison (MSN) mouse strain. Variants were identified using whole exome resequencing on a small population of animals. Interesting candidate variants were confirmed in a larger population with genotyping. We enriched these results with observations of locomotor behavior from a previous study. Resequencing identified 447 structural variants that are mostly fixed in the MSN strain relative to control strains. After filtering and annotation, we found 11 non-synonymous MSN variants that we believe alter protein function. The allele frequencies for 6 of these variants were consistent with explanatory variants for the Madison strain's phenotype. The variants are in the Npas2, Cp, Polr3c, Smarca4, Trpv1, and Slc5a7 genes, and many of these genes' products are in pathways implicated in human bipolar disorders. Variants in Smarca4 and Polr3c together explained over 40% of the variance in locomotor behavior in the Hsd:ICR founder strain. These results enhance the MSN strain's construct validity and implicate altered nucleosome structure and transcriptional regulation as a chief molecular system underpinning behavior.

  19. A socialization intervention in remote health coaching for older adults in the home.

    PubMed

    Jimison, Holly B; Klein, Krystal A; Marcoe, Jennifer L

    2013-01-01

    Previous studies have shown that social ties enhance both physical and mental health, and that social isolation has been linked to increased cognitive decline. As part of our cognitive training platform, we created a socialization intervention to address these issues. The intervention is designed to improve social contact time of older adults with remote family members and friends using a variety of technologies, including Web cameras, Skype software, email and phone. We used usability testing, surveys, interviews and system usage monitoring to develop design guidance for socialization protocols that were appropriate for older adults living independently in their homes. Our early results with this intervention show increased number of social contacts, total communication time (we measure email, phone, and Skype usage) and significant participant satisfaction with the intervention.

  20. A Socialization Intervention in Remote Health Coaching for Older Adults in the Home*

    PubMed Central

    Jimison, Holly B.; Klein, Krystal A.; Marcoe, Jennifer L.

    2014-01-01

    Previous studies have shown that social ties enhance both physical and mental health, and that social isolation has been linked to increased cognitive decline. As part of our cognitive training platform, we created a socialization intervention to address these issues. The intervention is designed to improve social contact time of older adults with remote family members and friends using a variety of technologies, including Web cameras, Skype software, email and phone. We used usability testing, surveys, interviews and system usage monitoring to develop design guidance for socialization protocols that were appropriate for older adults living independently in their homes. Our early results with this intervention show increased number of social contacts, total communication time (we measure email, phone, and Skype usage) and significant participant satisfaction with the intervention. PMID:24111362

  1. Formation of medical radioisotopes {sup 111}In, {sup 117m}Sn, {sup 124}Sb, and {sup 177}Lu in photonuclear reactions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Danagulyan, A. S.; Hovhannisyan, G. H., E-mail: hov-gohar@ysu.am; Bakhshiyan, T. M.

    2015-06-15

    The possibility of the photonuclear production of radioisotopes {sup 111}In, {sup 117m}Sn, {sup 124}Sb, and {sup 177}Lu is discussed. Reaction yields were measured by the gamma-activation method. The enriched tin isotopes {sup 112,} {sup 118}Sn and Te and HfO{sub 2} of natural isotopic composition were used as targets. The targets were irradiated at the linear electron accelerator of Alikhanian National Science Laboratory (Yerevan) at the energy of 40 MeV. The experimental results obtained in this way reveal that the yield and purity of radioisotopes {sup 111}In and {sup 117}mSn are acceptable for their production via photonuclear reactions. Reactions proceeding onmore » targets from Te and HfO{sub 2} of natural isotopic composition and leading to the formation of {sup 124}Sb and {sup 177}Lu have small yields and are hardly appropriate for the photoproduction of these radioisotopes even in the case of enriched targets.« less

  2. Ion Mobility Separation of Isomeric Carbohydrate Precursor Ions and Acquisition of their Independent Tandem Mass Spectra

    PubMed Central

    Zhu, Maolei; Bendiak, Brad; Clowers, Brian; Hill, Herbert H.

    2010-01-01

    The rapid separation of isomeric precursor ions of oligosaccharides prior to their analysis by MSn was demonstrated using an ambient pressure ion mobility spectrometer (IMS) interfaced with a quadrupole ion trap. Separations were not limited to specific types of isomers; representative isomers differing solely in the stereochemistry of sugars, in their anomeric configurations, and in their overall branching patterns and linkage positions could be resolved in the millisecond time frame. Physical separation of precursor ions permitted independent mass spectra of individual oligosaccharide isomers to be acquired to at least MS3, the number of stages of dissociation limited only practically by the abundance of specific product ions. IMS-MSn analysis was particularly valuable in the evaluation of isomeric oligosaccharides that yielded identical sets of product ions in MS/MS experiments, revealing pairs of isomers that would otherwise not be known to be present in a mixture if evaluated solely by MS dissociation methods alone. A practical example of IMS-MSn analysis of a set of isomers included within a single HPLC fraction of oligosaccharides released from bovine submaxillary mucin is described. PMID:19562326

  3. Mucin-1-Antibody-Conjugated Mesoporous Silica Nanoparticles for Selective Breast Cancer Detection in a Mucin-1 Transgenic Murine Mouse Model

    PubMed Central

    Dréau, Didier; Moore, Laura Jeffords; Alvarez-Berrios, Merlis P.; Tarannum, Mubin; Mukherjee, Pinku; Vivero-Escoto, Juan L.

    2017-01-01

    Mucin-1 (MUC1), a transmembrane glycoprotein is aberrantly expressed on ~90% of breast cancer and is an excellent target for nanoparticulate targeted imaging. In this study, the development of a dye-doped NIR emitting mesoporous silica nanoparticles platform conjugated to tumor-specific MUC1 antibody (ab-tMUC1-NIR-MSN) for in vivo optical detection of breast adenocarcinoma tissue is reported. The structural properties, the in vitro and in vivo performance of this nanoparticle-based probe were evaluated. In vitro studies showed that the MSN-based optical imaging nanoprobe is non-cytotoxic and targets efficiently mammary cancer cells overexpressing human tMUC1 protein. In vivo experiments with female C57BL/6 mice indicated that this platform accumulates mainly in the liver and did not induce short-term toxicity. In addition, we demonstrated that the ab-tMUC1-NIR-MSN nanoprobe specifically detects mammary gland tumors overexpressing human tMUC1 in a human MUC1 transgenic mouse model. PMID:28522938

  4. Methionine sulfone-containing orbitides, good indicators to evaluate oxidation process of flaxseed oil.

    PubMed

    Zou, Xian-Guo; Hu, Jiang-Ning; Zhu, Xue-Mei; Wang, Yu-Fu; Deng, Ze-Yuan

    2018-06-01

    This study aimed to explore the possibility of using methionine sulfone (Msn)-containing orbitides as indicators to evaluate the oxidation process of flaxseed oils. Results showed that after 4 days' heating, oxidation values slightly increased (p > .05) with significant decrease in methionine (Met)-containing peptides (p < .05) instead of γ-tocopherol (p > .05). However, as oxidation time continues increasing, oxidation values significantly increased (p < .05) with significant reduction of γ-tocopherol (p < .05). It demonstrated that Met-containing peptides were more readily oxidized compared with γ-tocopherol and showed certain antioxidant activity. Besides, high logarithmic correlations were found between oxidation values and Msn-containing orbitides (0.94-1.00), such as between total carbonyl compounds and orbitide [1-8-NαC],[1-MetO 2 ]-CLE (64.95 lnx - 52.14, R 2  = 0.99, Dingya23 oil). Therefore, in comparison with common oxidation indices, Msn-containing orbitides may be better indicators for evaluating the oxidation process of flaxseed oil with superior separation efficiency, specific information and high stability. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Porcine, murine and human sialoadhesin (Sn/Siglec-1/CD169): portals for porcine reproductive and respiratory syndrome virus entry into target cells.

    PubMed

    Van Breedam, Wander; Verbeeck, Mieke; Christiaens, Isaura; Van Gorp, Hanne; Nauwynck, Hans J

    2013-09-01

    Porcine sialoadhesin (pSn; a sialic acid-binding lectin) and porcine CD163 (pCD163) are molecules that facilitate infectious entry of porcine reproductive and respiratory syndrome virus (PRRSV) into alveolar macrophages. In this study, it was shown that murine Sn (mSn) and human Sn (hSn), like pSn, can promote PRRSV infection of pCD163-expressing cells. Intact sialic acid-binding domains are crucial, since non-sialic acid-binding mutants of pSn, mSn and hSn did not promote infection. Endodomain-deletion mutants of pSn, mSn and hSn promoted PRRSV infection less efficiently, but also showed markedly reduced expression levels, making further research into the potential role of the Sn endodomain in PRRSV receptor activity necessary. These data further complement our knowledge on Sn as an important PRRSV receptor, and suggest - in combination with other published data - that species differences in the main PRRSV entry mediators Sn and CD163 do not account for the strict host species specificity displayed by the virus.

  6. [Identification of chemical constituents in Sinopodophylli Fructus by HPLC-DAD-ESI-IT-TOF-MSn].

    PubMed

    Wang, Ai-Hua; Ma, Li-Man; Fan, Shan-Shan; Liu, Guang-Xue; Xu, Feng; Shang, Ming-Ying; Cai, Shao-Qing

    2018-01-01

    This experiment was performed to analyze and identify the chemical constituents of Sinopodophylli Fructus by HPLC-DAD-ESI-IT-TOF-MSn. The analysis was performed on an Agilent Zorbax SB-C₁₈ (4.6 mm×250 mm, 5 μm) column.The mobile phase consisted of 0.1% formic acid was used for gradient at a flow rate of 1.0 mL·min⁻¹. Electrospray ionization ion trap time-of-flight multistage mass spectrometry was applied for qualitative analysis under positive and negative ion modes. The results indicated that 54 compounds consisted of 18 lignans and 36 flavonoids from Xiaoyelian had been detected by their HRMS data, the information of literature and reference substance. Among them, 27 compounds were reported in Sinopodophylli Fructus for the first time. In conclusion, an HPLC-DAD-ESI-IT-TOF-MSn method was established to qualitative analysis of Xiaoyelian in this study, which will provide the evidence for evaluating the quality of Xiaoyelian herbs, clarifying the mechanism, and guiding the development of pharmacological active ingredients. Copyright© by the Chinese Pharmaceutical Association.

  7. Silanol-assisted carbinolamine formation in an amine-functionalized mesoporous silica surface: Theoretical investigation by fragmentation methods

    DOE PAGES

    de Lima Batista, Ana P.; Zahariev, Federico; Slowing, Igor I.; ...

    2015-12-15

    The aldol reaction catalyzed by an amine-substituted mesoporous silica nanoparticle (amine-MSN) surface was investigated using a large molecular cluster model (Si 392O 958C 6NH 361) combined with the surface integrated molecular orbital/molecular mechanics (SIMOMM) and fragment molecular orbital (FMO) methods. Three distinct pathways for the carbinolamine formation, the first step of the amine-catalyzed aldol reaction, are proposed and investigated in order to elucidate the role of the silanol environment on the catalytic capability of the amine-MSN material. Here the computational study reveals that the most likely mechanism involves the silanol groups actively participating in the reaction, forming and breaking covalentmore » bonds in the carbinolamine step. Furthermore, the active participation of MSN silanol groups in the reaction mechanism leads to a significant reduction in the overall energy barrier for the carbinolamine formation. In addition, a comparison between the findings using a minimal cluster model and the Si 392O 958C 6NH 361 cluster suggests that the use of larger models is important when heterogeneous catalysis problems are the target.« less

  8. UHPLC-PDA-ESI/HRMS/MSn Analysis of Anthocyanins, Flavonol Glycosides, and Hydroxycinnamic Acid Derivatives in Red Mustard Greens (Brassica juncea Coss Variety)

    PubMed Central

    Lin, Long-Ze; Sun, Jianghao; Chen, Pei; Harnly, James

    2013-01-01

    An UHPLC-PDA-ESI/HRMS/MSn profiling method was used for a comprehensive study of the phenolic components of red mustard greens (Brassica juncea Coss variety) and identified 67 anthocyanins, 102 flavonol glycosides, and 40 hydroxycinnamic acid derivatives. The glycosylation patterns of the flavonoids were assigned on the basis of direct comparison of the parent flavonoid glycosides with reference compounds. The putative identifications were obtained from tandem mass data analysis and confirmed by the retention time, elution order, and UV–vis and high-resolution mass spectra. Further identifications were made by comparing the UHPLC-PDA-ESI/HRMS/MSn data with those of reference compounds in the polyphenol database and in the literature. Twenty-seven acylated cyanidin 3-sophoroside-5-diglucosides, 24 acylated cyanidin 3-sophoroside-5- glucosides, 3 acylated cyanidin triglucoside-5-glucosides, 37 flavonol glycosides, and 10 hydroxycinnamic acid derivatives were detected for the first time in brassica vegetables. At least 50 of them are reported for the first time in any plant materials. PMID:21970730

  9. Learning Skills Profiles of master's students in nursing administration: assessing the impact of problem-based learning.

    PubMed

    Baker, Constance M; McDaniel, Anna M; Pesut, Daniel J; Fisher, Mary L

    2007-01-01

    Attempts to compare graduate student performances before and after introducing new curricula are rare; yet faculties need outcome measures to justify program costs and demonstrate effectiveness. Boyatzis and Kolb's Learning Skills Profile is used to assess the outcomes of a problem-based learning MSN program. Increases were demonstrated among all 12 learning skills; statistically significant increases were found in eight of the personal learning skills and six of the job skill demands. Comparisons are made between scores of students in the MSN program and scores of master's students in business administration.

  10. Seeing Is Believing: Using Skype to Improve Diabetes Outcomes in Youth.

    PubMed

    Harris, Michael A; Freeman, Kurt A; Duke, Danny C

    2015-08-01

    The objective of this study was to compare the relative effectiveness of two modes of delivering Behavioral Family Systems Therapy for Diabetes (BFST-D) to improve adherence and glycemic control among adolescents with type 1 diabetes with suboptimal glycemic control (HbA(1c) ≥9.0% [≥74.9 mmol/mol]): face to face in clinic (Clinic) and Internet videoconferencing (Skype) conditions. Adolescents aged 12 to 18 years and at least one adult caregiver were randomized to receive BFST-D via the Clinic or Skype condition. Participants completed up to 10 therapy sessions within a 12-week period. Changes in youth- and parent-reported adherence and glycemic control were compared before and after the intervention and at follow-up assessment. Using an intent-to-treat analytic approach, no significant between-group differences were identified between the before, after, and follow-up assessments. Groups were collapsed to examine the overall effects of BFST-D on adherence and glycemic control. Results identified that statistically significant improvements in adherence and glycemic control occurred from before to after the intervention; improvements were maintained at 3-month follow-up. Delivery of BFST-D via Internet-based videoconferencing is viable for addressing nonadherence and suboptimal glycemic control in adolescents with type 1 diabetes, potentially reducing important barriers to care for youth and families. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  11. Prolonged and continuous antibacterial and anti-biofilm activities of thin films embedded with gentamicin-loaded mesoporous silica nanoparticles

    NASA Astrophysics Data System (ADS)

    Tamanna, Tasnuva; Landersdorfer, Cornelia B.; Ng, Hooi Jun; Bulitta, Jürgen B.; Wood, Peter; Yu, Aimin

    2018-05-01

    The application of mesoporous silica nanoparticles (MSNs) in drug delivery systems has become highly attractive since the early 2000s. In this study, thin-film coatings embedded with gentamicin-loaded mesoporous silica nanoparticles (MSN-G) were prepared to provide antibacterial and anti-biofilm activity over a prolonged period of time. The prolonged and continuous activity of MSN-G films against Staphylococcus aureus throughout the release period was studied via two methods, namely, (1) disc diffusion of released gentamicin and (2) by shifting the MSN-G thin film to a new agar plate at certain time intervals. The expansion of the inhibition zone from 4.6 ± 0.5 to 9.7 ± 0.5 mm as caused by the released fraction of gentamicin from the first week to the eighth week indicated the controlled and slow release behaviour of loaded antibiotic and prolonged antibacterial efficacy of these films. In addition, the appearance of an inhibition zone after each shifting of the film to a new agar plate was persistent up to 103 days which confirmed that thin films successively prevented bacterial growth over a long period of time. In addition, the anti-biofilm activity of MSN-G films was evaluated by imaging bacterial cells attachment via confocal laser scanning microscopy and scanning electron microscopy. Remarkably, the anti-biofilm performance remained active for more than 2 months. To the best of our knowledge, such a slow and controlled release of antibiotic from nanoparticle embedded thin films with uninterrupted, continuous, and prolonged antibacterial effect for more than 2 months has not been reported yet.

  12. Structural rearrangement of mesostructured silica nanoparticles incorporated with ZnO catalyst and its photoactivity: Effect of alkaline aqueous electrolyte concentration

    NASA Astrophysics Data System (ADS)

    Jusoh, N. W. C.; Jalil, A. A.; Triwahyono, S.; Karim, A. H.; Salleh, N. F.; Annuar, N. H. R.; Jaafar, N. F.; Firmansyah, M. L.; Mukti, R. R.; Ali, M. W.

    2015-03-01

    ZnO-incorporated mesostructured silica nanoparticles (MSN) catalysts (ZM) were prepared by the introduction of Zn ions into the framework of MSN via a simple electrochemical system in the presence of various concentrations of NH4OH aqueous solution. The physicochemical properties of the catalysts were studied by XRD, 29Si MAS NMR, nitrogen adsorption-desorption, FE-SEM, TEM, FTIR, and photoluminescence spectroscopy. Characterization results demonstrated that the alkaline aqueous electrolyte simply generated abundant silanol groups on the surface of the catalysts as a consequence of desilication to form the hierarchical-like structure of the MSN. Subsequent restructuring of the silica network by the creation of oxygen vacancies and formation of Si-O-Zn during the electrolysis, as well as formation of new Si-O-Si bonds during calcination seemed to be the main factors that enhanced the catalytic performance of photodecolorization of methyl orange. A ZM prepared in the presence of 1.0 M NH4OH (ZM-1.0) was determined to be the most effective catalyst. The catalyst displays a higher first-order kinetics rate of 3.87 × 10-1 h-1 than unsupported ZnO (1.13 × 10-1 h-1) that prepared under the same conditions in the absence of MSN. The experiment on effect of scavengers showed that hydroxyl radicals generated from the three main sources; reduced O2 at the conduction band, decomposed water at the valence band and irradiated H2O2 in the solution, are key factors that influenced the reaction. It is also noted that the recycled ZM-1.0 catalyst maintained its activity up to five runs without serious catalyst deactivation.

  13. Neuromodulation targets intrinsic cardiac neurons to attenuate neuronally mediated atrial arrhythmias.

    PubMed

    Gibbons, David D; Southerland, E Marie; Hoover, Donald B; Beaumont, Eric; Armour, J Andrew; Ardell, Jeffrey L

    2012-02-01

    Our objective was to determine whether atrial fibrillation (AF) results from excessive activation of intrinsic cardiac neurons (ICNs) and, if so, whether select subpopulations of neurons therein represent therapeutic targets for suppression of this arrhythmogenic potential. Trains of five electrical stimuli (0.3-1.2 mA, 1 ms) were delivered during the atrial refractory period to mediastinal nerves (MSN) on the superior vena cava to evoke AF. Neuroanatomical studies were performed by injecting the neuronal tracer DiI into MSN sites that induced AF. Functional studies involved recording of neuronal activity in situ from the right atrial ganglionated plexus (RAGP) in response to MSN stimulation (MSNS) prior to and following neuromodulation involving either preemptive spinal cord stimulation (SCS; T(1)-T(3), 50 Hz, 200-ms duration) or ganglionic blockade (hexamethonium, 5 mg/kg). The tetramethylindocarbocyanine perchlorate (DiI) neuronal tracer labeled a subset (13.2%) of RAGP neurons, which also colocalized with cholinergic or adrenergic markers. A subset of DiI-labeled RAGP neurons were noncholinergic/nonadrenergic. MSNS evoked an ∼4-fold increase in RAGP neuronal activity from baseline, which SCS reduced by 43%. Hexamethonium blocked MSNS-evoked increases in neuronal activity. MSNS evoked AF in 78% of right-sided MSN sites, which SCS reduced to 33% and hexamethonium reduced to 7%. MSNS-induced bradycardia was maintained with SCS but was mitigated by hexamethonium. We conclude that MSNS activates subpopulations of intrinsic cardiac neurons, thereby resulting in the formation of atrial arrhythmias leading to atrial fibrillation. Stabilization of ICN local circuit neurons by SCS or the local circuit and autonomic efferent neurons with hexamethonium reduces the arrhythmogenic potential.

  14. Nuclear medicine technology progress report for quarter ending December 31, 1979

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Knapp, F.F. Jr.

    1980-04-01

    Platinum-195m-labeled cis-dichloro-trans-dihydroxy-bis-(isopropylamine)-platinum(IV) (CHIP) was prepared for the first time. This second-generation platinum antitumor agent appears superior to the widely used cis-dichloro-diammineplatinum(II) (cis-DDP) since the dose-limiting nephrotoxicity associated with cis-DDP therapy is not encountered. Platinum-195m-labeled CHIP is being used to determine the tissue-distribution, excretion, and other pharmacological properties of this new drug. Studies of the heart uptake in rats of /sup 75/Se and /sup 123m/Te-labeled long-chain fatty acids have continued. The greater heart uptake of /sup 123m/Te-9-telluraheptadecanoic acid compared with the selenium analog, /sup 75/Se-9-selenaheptadecanoic acid, was confirmed. Radiation dose estimates for a new adrenal imaging agent, /sup 117m/Sn-23-(trimethylstanna)-24-nor-5..cap alpha..-cholan-3..beta..-ol (23-TSC)more » have been completed. Tissue distribution and excretion data for /sup 117m/Sn-23-TSC were used to extrapolate the radiation dose values to humans. The calculated radiation dose values for /sup 117m/Sn-23-TSC are: adrenals, 83 rads/mCi; total body, 0.77 rad/mCi/; and ovaries, 4.4 rads/mCi. These values are considerably lower than similar estimates for a variety of other radiolabeled steroids and suggest that /sup 117m/Sn-23-TSC may be an attractive new agent for adrenal visualization in humans. The diffusion chamber assay system has been further assessed as a technique to determine the toxicity of As/sub 2/O/sub 3/ administration on the proliferation of cells within chambers implanted in the peritoneal cavities of rats and hamsters. Both human embryonic lung cells and human nasopharyngeal carcinoma cells were used in the studies.« less

  15. Nucleus accumbens core medium spiny neuron electrophysiological properties and partner preference behavior in the adult male prairie vole, Microtus ochrogaster.

    PubMed

    Willett, Jaime A; Johnson, Ashlyn G; Vogel, Andrea R; Patisaul, Heather B; McGraw, Lisa A; Meitzen, John

    2018-04-01

    Medium spiny neurons (MSNs) in the nucleus accumbens have long been implicated in the neurobiological mechanisms that underlie numerous social and motivated behaviors as studied in rodents such as rats. Recently, the prairie vole has emerged as an important model animal for studying social behaviors, particularly regarding monogamy because of its ability to form pair bonds. However, to our knowledge, no study has assessed intrinsic vole MSN electrophysiological properties or tested how these properties vary with the strength of the pair bond between partnered voles. Here we performed whole cell patch-clamp recordings of MSNs in acute brain slices of the nucleus accumbens core (NAc) of adult male voles exhibiting strong and weak preferences for their respective partnered females. We first document vole MSN electrophysiological properties and provide comparison to rat MSNs. Vole MSNs demonstrated many canonical electrophysiological attributes shared across species but exhibited notable differences in excitability compared with rat MSNs. Second, we assessed male vole partner preference behavior and tested whether MSN electrophysiological properties varied with partner preference strength. Male vole partner preference showed extensive variability. We found that decreases in miniature excitatory postsynaptic current amplitude and the slope of the evoked action potential firing rate to depolarizing current injection weakly associated with increased preference for the partnered female. This suggests that excitatory synaptic strength and neuronal excitability may be decreased in MSNs in males exhibiting stronger preference for a partnered female. Overall, these data provide extensive documentation of MSN electrophysiological characteristics and their relationship to social behavior in the prairie vole. NEW & NOTEWORTHY This research represents the first assessment of prairie vole nucleus accumbens core medium spiny neuron intrinsic electrophysiological properties and probes the relationship between cellular excitability and social behavior.

  16. Association Between ACE Gene Polymorphism and QT Dispersion in Patients with Acute Myocardial Infarction.

    PubMed

    Karahan, Zulkuf; Ugurlu, Murat; Ucaman, Berzal; Veysel Ulug, Ali; Kaya, Ilyas; Cevik, Kemal; Sahin Adiyaman, Mehmet; Oztürk, Onder; Iyem, Hikmet; Ozdemir, Ferit

    2016-01-01

    Angiotensin converting enzyme (ACE) gene polymorphism is associated with high renin-angiotensin system causing myocardial fibrosis and ventricular repolarization abnormality. Based on these findings, this study was designed to determine the association between ACE gene insertion/deletion (I/D) polymorphism and QT dispersion after acute myocardial infarction (MI). The study included 108 patients with acute MI. Blood samples were obtained from all the patients for genomic DNA analysis. ECGs were recorded at baseline and at the end of a 6-month follow up. The OT dispersion was manually calculated. The mean age of the patients was 57.5 ±9.9 years (ranging from 36 to 70). The patients with DD genotype showed longer QT dispersion than patients with II or DI genotype at the baseline, while at the end of the six-month follow up the patients with DI genotype showed longer QT dispersion than patients with DD or II genotypes. However, the magnitude of the QT dispersion prolongation was higher in patients carrying the ACE D allele than patients who were not carrying it, at baseline and at the end of six-month follow up (52.5 ±2.6 msn vs. 47.5±2.1 msn at baseline, 57±3.2 msn vs. 53±2.6 msn in months, P: 0.428 and P: 0.613, respectively). Carriers of the D allele of ACE gene I/D polymorphism may be associated with QT dispersion prolongation in patients with MI.An interaction of QT dispersion and ACE gene polymorphism may be associated with an elevation of serum type I-C terminal pro-collagen concentration, possibly leading to myocardial fibrosis, and increased action potential duration.

  17. The Evaluation of Anatomic and Functional Changes in Unilateral Moderate Amblyopic Eyes Using Optical Coherence Tomography and Pupil Cycle Time.

    PubMed

    Kusbeci, Tuncay; Karti, Omer; Karahan, Eyyup; Oguztoreli, Mustafa

    2017-12-01

    To investigate whether macular anatomic structure and afferent visual system function differ among amblyopic eyes, non-amblyopic fellow eyes, and controls, using spectral-domain optical coherence tomography (SD-OCT), and pupil cycle time (PCT). This observational, cross-sectional study included 30 patients with unilateral amblyopia and 30 healthy subjects. Optical coherence tomography (OCT) and pupil cycle time (PCT) were used to evaluate patients with unilateral amblyopia and were compared with their non-amblyopic fellow eyes and age- and gender-matched healthy eyes (30 participants). The amblyopic eyes were separated into two groups: anisometropic amblyopia (n = 16) and strabismic amblyopia (n = 14). OCT maps were used to calculate central macular thickness (CMT), retinal nerve fiber layer thickness (RNFLT), and ganglion cell-inner plexiform layer (GC-IPL) thickness. The average RNFLT, GC-IPL thickness, and CMT did not show any significant differences among the amblyopic eyes, non-amblyopic fellow eyes and controls (p > 0.05, Kruskal-Wallis test). Mean PCT was 773.57 ± 64 msn in strabismic eyes, 771.25 ± 58 msn in anisometropic eyes, 778.00 ± 72 msn in non-amblyopic fellow eyes, and 774.75 ± 69 msn in control eyes. The differences among the amblyopic eyes, its fellow and control eyes were not statistically significant (p > 0.05, Kruskal-Wallis test). In this study, we investigated morphological and functional differences among amblyopic eyes, non-amblyopic fellow eyes and controls by using SD-OCT and PCT. We did not find anatomical or functional changes in amblyopic eyes.

  18. Stimulus-response mesoporous silica nanoparticle-based chemiluminescence biosensor for cocaine determination.

    PubMed

    Chen, Zhonghui; Tan, Yue; Xu, Kefeng; Zhang, Lan; Qiu, Bin; Guo, Longhua; Lin, Zhenyu; Chen, Guonan

    2016-01-15

    Mesoporous silica nanoparticles (MSN) based controlled release system had been coupled with diverse detection technologies to establish biosensors for different targets. Chemiluminescence (CL) system of luminol/H2O2 owns the characters of simplicity, low cost and high sensitivity, but the targets of which are mostly focused on some oxidants or which can participate in a chemical reaction that yields a product with a role in the CL reaction. In this study, chemiluminescent detection technique had been coupled with mesoporous silica-based controlled released system for the first time to develop a sensitive biosensor for the target which does not cause effect to the CL system itself. Cocaine had been chosen a model target, the MSN support was firstly loaded with glucose, then the positively charged MSN interacted with negatively charged oligonucleotides (the aptamer cocaine) to close the mesopores of MSN. At the present of target, cocaine binds with its aptamer with high affinity; the flexible linear aptamer structured will become stems structured through currently well-defined non-Waston-Crick interactions and causes the releasing of entrapped glucose into the solution. With the assistant of glucose oxidase (GOx), the released glucose can react with the dissolved oxgen to produce gluconic acid and H2O2, the latter can enhance the CL of luminol in the NaOH solution. The enhanced CL intensity has a relationship with the cocaine concentration in the range of 5.0-60μM with the detection limit of 1.43μM. The proposed method had been successfully applied to detect cocaine in serum samples with high selectivity. The same strategy can be applied to develop biosensors for different targets. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Skyping Class: Using Videoconferencing in Organizational Communication Classes

    ERIC Educational Resources Information Center

    Garner, Johny T.; Buckner, Marjorie M.

    2013-01-01

    Organizations use this technology to connect employees and stakeholders because of reduced cost and greater participation among global stakeholders (Hertel, Geister, & Konradt, 2005). Scholars have examined videoconferencing in groups (Zornoza, Prieto, Marti, & Piero, 1993),…

  20. The Bermuda Triangle of cocaine-induced neuroadaptations.

    PubMed

    Wolf, Marina E

    2010-09-01

    Activation of medium spiny neurons (MSNs) of the nucleus accumbens is critical for goal-directed behaviors including cocaine seeking. Studies in cocaine-experienced rodents have revealed three major categories of neuroadaptations that influence the ability of glutamate inputs to activate MSNs: changes in synaptic AMPA receptor levels, changes in extracellular non-synaptic glutamate levels and changes in MSN intrinsic membrane excitability. Most studies have focused on one of these adaptations. This review will consider the possibility that they are causally related and speculate about how time-dependent changes in their interactions may regulate MSN output during early and late withdrawal from repeated cocaine exposure. Copyright 2010 Elsevier Ltd. All rights reserved.

  1. Luminescent GdVO4:Eu3+ functionalized mesoporous silica nanoparticles for magnetic resonance imaging and drug delivery.

    PubMed

    Huang, Shanshan; Cheng, Ziyong; Ma, Ping'an; Kang, Xiaojiao; Dai, Yunlu; Lin, Jun

    2013-05-14

    Luminescent GdVO4:Eu(3+) nanophosphor functionalized mesoporous silica nanoparticles (MSN) were prepared (denoted as GdVO4:Eu(3+)@MSN). The in vitro cytotoxicity tests show that the sample has good biocompatibility, which indicates that the nanocomposite could be a promising candidate for drug delivery. Flow cytometry and confocal laser scanning microscopy (CLSM) confirm that the sample can be effectively taken up by SKOV3 ovarian cancer cells and A549 lung adenocarcinoma cells. It was also shown that the GdVO4:Eu(3+)@MSN brightened the T1-weighted images and enhanced the r1 relaxivity of water protons, which suggested that they could act as T1 contrast agents for magnetic resonance (MR) imaging. It was found that the carriers present a pH-dependent drug release behavior for doxorubicin (DOX). The composites show a red emission under UV irradiation due to the GdVO4:Eu(3+) nanophosphors. Furthermore, the PL intensity of the composite shows correlation with the cumulative release of DOX. These results suggest that the composite can potentially act as a multifunctional drug carrier system with luminescent tagging, MR imaging and pH-controlled release property for DOX.

  2. Yeast adapt to near-freezing temperatures by STRE/Msn2,4-dependent induction of trehalose synthesis and certain molecular chaperones.

    PubMed

    Kandror, Olga; Bretschneider, Nancy; Kreydin, Evgeniy; Cavalieri, Duccio; Goldberg, Alfred L

    2004-03-26

    Virtually nothing is known about the biochemical adaptations in eukaryotic cells that may enhance survival at low temperatures or upon freezing. Here we demonstrate an adaptive response in yeast that is activated below 10 degrees C and increases tolerance to low temperatures and freezing. This response involves a dramatic accumulation of the chemical chaperone trehalose and induction of trehalose-synthesizing enzymes (Tps1, Tps2) and certain heat shock proteins (Hsp104, Hsp42, Hsp12, Ssa4). mRNAs for these proteins increase dramatically below 10 degrees C and even at 0 degrees C. Their expression requires Msn2,4 transcription factors but also involves marked mRNA stabilization. Upon return to 30 degrees C, TPS1, TPS2, and HSP104 mRNAs, trehalose levels and tolerance to freezing fall dramatically within minutes. Mutants lacking trehalose or Msn2,4 die more rapidly at 0 degrees C and upon freezing. Thus, below 10 degrees C, yeast show an adaptive response that sustains viability at low or freezing temperatures, which are commonly encountered in natural environments and laboratory refrigerators.

  3. Characterization of Anthocyanins in Perilla frutescens var. acuta Extract by Advanced UPLC-ESI-IT-TOF-MSn Method and Their Anticancer Bioactivity.

    PubMed

    He, Yan-Kang; Yao, You-Yuan; Chang, Ya-Ning

    2015-05-19

    The anthocyanin extract from a domestic Perilla cultivar (Perilla frutescens var. acuta) were isolated and characterized with high mass accuracy and multi-dimensional fragmentation by means of ultra-performance liquid chromatography (UPLC) and electrospray ionization-ion trap-time of flight mass spectrometry analysis (ESI-IT-TOF-MSn). The new developed and applied LC-MS method focused on in-depth screening of anthocyanin compounds with similar structures which also provided a new approach of anthocyanin characterization without the use of external standards. Selective detection of interested anthocyanins was achieved utilizing extracted ion chromatogram (EIC) analysis, while MSn spectra were recorded to allow identification of the anthocyanin based on characteristic fragmentation patterns. Seven anthocyanins including one feruloyl (Cyanidin 3-O-feruloylglucoside-5-O-glucoside), two caffeoyl (Cyanidin 3-O-caffeoylglucoside-5-O-glucoside, Cyanidin 3-O-caffeoylglucoside-5-O-malonylglucoside) and four coumaroyl substituted anthocyanins (Cis-shisonin, Malonyl-cis-shisonin, Shisonin, and Malonyl-shisonin) were identified. Annexin-V FITC/PI flow cytometric assay was performed to analyze the influence of anthocyanin extract of P. frutescens var. acuta on cell apoptosis. The results suggested that Perilla anthocyanins can induce Hela cell apoptosis by a dose dependent manner.

  4. Chemical profile analysis and comparison of two versions of the classic TCM formula Danggui Buxue Tang by HPLC-DAD-ESI-IT-TOF-MSn.

    PubMed

    Zhang, Ya-Zhou; Xu, Feng; Yi, Tao; Zhang, Jian-Ye; Xu, Jun; Tang, Yi-Na; He, Xi-Chen; Liu, Jing; Chen, Hu-Biao

    2014-04-30

    Danggui Buxue Tang (DBT) is a Traditional Chinese Medicine (TCM) formula primarily used to treat symptoms associated with menopause in women. Usually, DBT is composed of one portion of Radix Angelicae Sinensis (RAS) and five portions of Radix Astragali (RA). Clinically, Radix Hedysari (RH) is sometimes used by TCM physicians to replace RA in DBT. In order to verity whether the chemical constituents of the DBT1 (RA:RAS = 5:1, w/w) and DBT2 (RH:RAS = 5:1, w/w) share similarities the chemical profiles of the two DBTs crude extracts and urine samples were analyzed and compared with the aid of HPLC-DAD-ESI-IT-TOF-MSn, which determines the total ion chromatogram (TIC) and multi-stage mass spectra (MSn). Then, the DBT1 and DBT2 were identified and compared on the basis of the TIC and the MSn. In the first experiment (with crude extracts), 69 compounds (C1-C69) were identified from the DBT1; 46 compounds (c1-c46) were identified from the DBT2. In the second experiment(with urine samples), 44 compounds (M1-M44) were identified from the urine samples of rats that had been administered DBT1, and 34 compounds (m1-m34) were identified from the urine samples of rats that had been administered DBT2. Identification and comparison of the chemical compositions were carried out between the DBT1 and DBT2 of the crude extracts and urine samples respectively. Our results showed that the two crude extracts of the DBTs have quite different chemical profiles. The reasons for their differences were that the special astragalosides in DBT1 and the isoflavonoid glycosides formed the malonic acid esters undergo single esterification and acetyl esters undergo acetylation in DBT1. In contrast, the urine from DBT1-treated rats strongly resembled that of DBT2-treated rats. These metabolites originate mainly from formononetin, calycosin and their related glycosides, and they were formed mainly by the metabolic process of reduction, deglycosylation, demethylation, hydrogenation and sulfation. The HPLC-DAD-ESI-IT-TOF-MSn method was successfully applied for the rapid chemical profiles evaluation of two DBTs and their related urine samples.

  5. Evidence for a Role for the Plasma Membrane in the Nanomechanical Properties of the Cell Wall as Revealed by an Atomic Force Microscopy Study of the Response of Saccharomyces cerevisiae to Ethanol Stress

    PubMed Central

    Schiavone, Marion; Formosa-Dague, Cécile; Elsztein, Carolina; Teste, Marie-Ange; Martin-Yken, Helene; De Morais, Marcos A.; Dague, Etienne

    2016-01-01

    ABSTRACT A wealth of biochemical and molecular data have been reported regarding ethanol toxicity in the yeast Saccharomyces cerevisiae. However, direct physical data on the effects of ethanol stress on yeast cells are almost nonexistent. This lack of information can now be addressed by using atomic force microscopy (AFM) technology. In this report, we show that the stiffness of glucose-grown yeast cells challenged with 9% (vol/vol) ethanol for 5 h was dramatically reduced, as shown by a 5-fold drop of Young's modulus. Quite unexpectedly, a mutant deficient in the Msn2/Msn4 transcription factor, which is known to mediate the ethanol stress response, exhibited a low level of stiffness similar to that of ethanol-treated wild-type cells. Reciprocally, the stiffness of yeast cells overexpressing MSN2 was about 35% higher than that of the wild type but was nevertheless reduced 3- to 4-fold upon exposure to ethanol. Based on these and other data presented herein, we postulated that the effect of ethanol on cell stiffness may not be mediated through Msn2/Msn4, even though this transcription factor appears to be a determinant in the nanomechanical properties of the cell wall. On the other hand, we found that as with ethanol, the treatment of yeast with the antifungal amphotericin B caused a significant reduction of cell wall stiffness. Since both this drug and ethanol are known to alter, albeit by different means, the fluidity and structure of the plasma membrane, these data led to the proposition that the cell membrane contributes to the biophysical properties of yeast cells. IMPORTANCE Ethanol is the main product of yeast fermentation but is also a toxic compound for this process. Understanding the mechanism of this toxicity is of great importance for industrial applications. While most research has focused on genomic studies of ethanol tolerance, we investigated the effects of ethanol at the biophysical level and found that ethanol causes a strong reduction of the cell wall rigidity (or stiffness). We ascribed this effect to the action of ethanol perturbing the cell membrane integrity and hence proposed that the cell membrane contributes to the cell wall nanomechanical properties. PMID:27235439

  6. Evidence for a Role for the Plasma Membrane in the Nanomechanical Properties of the Cell Wall as Revealed by an Atomic Force Microscopy Study of the Response of Saccharomyces cerevisiae to Ethanol Stress.

    PubMed

    Schiavone, Marion; Formosa-Dague, Cécile; Elsztein, Carolina; Teste, Marie-Ange; Martin-Yken, Helene; De Morais, Marcos A; Dague, Etienne; François, Jean M

    2016-08-01

    A wealth of biochemical and molecular data have been reported regarding ethanol toxicity in the yeast Saccharomyces cerevisiae However, direct physical data on the effects of ethanol stress on yeast cells are almost nonexistent. This lack of information can now be addressed by using atomic force microscopy (AFM) technology. In this report, we show that the stiffness of glucose-grown yeast cells challenged with 9% (vol/vol) ethanol for 5 h was dramatically reduced, as shown by a 5-fold drop of Young's modulus. Quite unexpectedly, a mutant deficient in the Msn2/Msn4 transcription factor, which is known to mediate the ethanol stress response, exhibited a low level of stiffness similar to that of ethanol-treated wild-type cells. Reciprocally, the stiffness of yeast cells overexpressing MSN2 was about 35% higher than that of the wild type but was nevertheless reduced 3- to 4-fold upon exposure to ethanol. Based on these and other data presented herein, we postulated that the effect of ethanol on cell stiffness may not be mediated through Msn2/Msn4, even though this transcription factor appears to be a determinant in the nanomechanical properties of the cell wall. On the other hand, we found that as with ethanol, the treatment of yeast with the antifungal amphotericin B caused a significant reduction of cell wall stiffness. Since both this drug and ethanol are known to alter, albeit by different means, the fluidity and structure of the plasma membrane, these data led to the proposition that the cell membrane contributes to the biophysical properties of yeast cells. Ethanol is the main product of yeast fermentation but is also a toxic compound for this process. Understanding the mechanism of this toxicity is of great importance for industrial applications. While most research has focused on genomic studies of ethanol tolerance, we investigated the effects of ethanol at the biophysical level and found that ethanol causes a strong reduction of the cell wall rigidity (or stiffness). We ascribed this effect to the action of ethanol perturbing the cell membrane integrity and hence proposed that the cell membrane contributes to the cell wall nanomechanical properties. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  7. Rational assembly of a biointerfaced core@shell nanocomplex towards selective and highly efficient synergistic photothermal/photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Qin, Chenchen; Fei, Jinbo; Wang, Anhe; Yang, Yang; Li, Junbai

    2015-11-01

    To optimize synergistic cancer therapy, we rationally assemble an inorganic-organic nanocomplex using a folate-modified lipid bilayer spread on photosensitizer-entrapped mesoporous silica nanoparticle (MSN) coated gold nanorods (AuNRs). In this hybrid bioconjugate, the large specific surface area and pore size of AuNR@MSN guarantee a high loading capacity of small photosensitive molecules. The modification with selective mixed liposomes on the surface of AuNR@MSN enables faster cellular internalization and enhancement of endocytosis. Under one-time NIR two-photon illumination, AuNR-mediated hyperthermia can kill cancer cells directly. Meanwhile, the loaded photosensitizer, hypocrellin B, generates two kinds of reactive oxygen species (ROS) to induce cell apoptosis. Remarkably, hyperthermia can improve the yield of ROS. After intravenous injection of this bioconjugate into female BALB/c nude mice followed by laser irradiation (808 nm, 1.3 W cm-2, 6 min), the tumor growth is suppressed completely. The tumors are not recurrent within the observation time (19 days), and the normal or main organs are not obviously pathological. Thus, such a simplified and selective cancer treatment, combining photothermal and photodynamic therapy in a synergistic manner, provides outstanding efficiency in vivo. This nanocomplex with well-defined core@shell nanostructures integrated with a two-photon technique holds great promise to improve cancer phototherapy with a high efficiency in the clinic.To optimize synergistic cancer therapy, we rationally assemble an inorganic-organic nanocomplex using a folate-modified lipid bilayer spread on photosensitizer-entrapped mesoporous silica nanoparticle (MSN) coated gold nanorods (AuNRs). In this hybrid bioconjugate, the large specific surface area and pore size of AuNR@MSN guarantee a high loading capacity of small photosensitive molecules. The modification with selective mixed liposomes on the surface of AuNR@MSN enables faster cellular internalization and enhancement of endocytosis. Under one-time NIR two-photon illumination, AuNR-mediated hyperthermia can kill cancer cells directly. Meanwhile, the loaded photosensitizer, hypocrellin B, generates two kinds of reactive oxygen species (ROS) to induce cell apoptosis. Remarkably, hyperthermia can improve the yield of ROS. After intravenous injection of this bioconjugate into female BALB/c nude mice followed by laser irradiation (808 nm, 1.3 W cm-2, 6 min), the tumor growth is suppressed completely. The tumors are not recurrent within the observation time (19 days), and the normal or main organs are not obviously pathological. Thus, such a simplified and selective cancer treatment, combining photothermal and photodynamic therapy in a synergistic manner, provides outstanding efficiency in vivo. This nanocomplex with well-defined core@shell nanostructures integrated with a two-photon technique holds great promise to improve cancer phototherapy with a high efficiency in the clinic. Electronic supplementary information (ESI) available: The relevant TEM, DLS, UV spectra, photographs and chemical structures. See DOI: 10.1039/c5nr06501a

  8. Delivery of Chemically Glycosylated Cytochrome c Immobilized in Mesoporous Silica Nanoparticles Induces Apoptosis in HeLa Cancer Cells

    PubMed Central

    Méndez, Jessica; Cruz, Moraima Morales; Reyes, Yamixa Delgado; Figueroa, Cindy M.; Orellano, Elsie A.; Morales, Myraida; Monteagudo, Alina; Griebenow, Kai

    2014-01-01

    Cytochrome c (Cyt c) is a small mitochondrial heme protein involved in the intrinsic apoptotic pathway. Once Cyt c is released into the cytosol, the caspase mediated apoptosis cascade is activated resulting in programmed cell death. Herein, we explore the covalent immobilization of Cyt c into mesoporous silica nanoparticles (MSN) to generate a smart delivery system for intracellular drug delivery to cancer cells aiming at affording subsequent cell death. Cyt c was modified with sulfosuccinimidyl-6-[3′-(2-pyridyldithio)-propionamido] hexanoate (SPDP) and incorporated into SH-functionalized MSN by thiol-disulfide interchange. Unfortunately, delivery of Cyt c from the MSN was not efficient in inducing apoptosis in human cervical cancer HeLa cells. We tested whether chemical Cyt c glycosylation could be useful in overcoming the efficacy problems by potentially improving Cyt c thermodynamic stability and reducing proteolytic degradation. Cyt c lysine residues were modified with lactose at a lactose-to-protein molar ratio of 3.7±0.9 using mono-(lactosylamido)-mono-(succinimidyl) suberate linker chemistry. Circular dichroism (CD) spectra demonstrated that part of the activity loss of Cyt c was due to conformational changes upon its modification with the SPDP linker. These conformational changes were prevented in the glycoconjugate. In agreement with the unfolding of Cyt c by the linker, a proteolytic assay demonstrated that the Cyt c-SPDP conjugate was more susceptible to proteolysis than Cyt c. Attachment of the four lactose molecules reversed this increased susceptibility and protected Cyt c from proteolytic degradation. Furthermore, a cell-free caspase-3 assay revealed 47% and 87% of relative caspase activation by Cyt c-SPDP and the Cyt c-lactose bioconjugate, respectively, when compared to Cyt c. This again demonstrates the efficiency of the glycosylation to improve maintaining Cyt c structure and thus function. To test for cytotoxicity, HeLa cells were incubated with Cyt c loaded MSN at different Cyt c concentrations (12.5, 25.0, and 37.5 μg/mL) for 24 to 72 h and cellular metabolic activity determined by a cell proliferation assay. While MSN-SPDP-Cyt c did not induced cell death, the Cyt c-lactose bioconjugate induced significant cell death after 72 h, reducing HeLa cell viability to 67% and 45% at the 25 μg/mL and 37.5 μg/mL concentrations, respectively. Confocal microscopy confirmed that the MSN immobilized Cyt c-lactose bioconjugate was internalized by HeLa cells and that the bioconjugate was capable of endosomal escape. The results clearly demonstrate that chemical glycosylation stabilized Cyt c upon formulation of a smart drug delivery system and upon delivery into cancer cells and highlight the general potential of chemical protein glycosylation to improve the stability of protein drugs. PMID:24294910

  9. Real-time attended home-polysomnography with telematic data transmission.

    PubMed

    Bruyneel, Marie; Van den Broecke, Sandra; Libert, Walter; Ninane, Vincent

    2013-08-01

    Home-polysomnography (HPSG) has been proposed as a cost-effective alternative for obstructive sleep apnea (OSA) diagnosis. We assessed, in a feasibility study, whether telematic transmission using the Dream® and Sleepbox® technologies was associated with low HPSG failure rate. Patients referred by chest physicians for clinical suspicion of OSA underwent one HPSG, using Dream® and Sleepbox® (Medatec, Belgium), which is a wireless system able to communicate with Dream®, and with Internet through a wi-fi/3G interface. It is equipped with a digital infrared camera, and with a speaker/microphone system for bidirectional audio/video communication via Skype®. The Sleep Lab nurse performed a remote discontinuous monitoring of the PSG. In case of sensor loss, she called the patient who had been previously educated to replace the sensors. Twenty-one patients have been studied. 90% of the recordings were of excellent quality. We observed a 10% PSG failure rate: one failure of the Dream®, and one recording of poor quality. There were 2 successful Skype® interventions resulting in readjustment of the defective probes (nasal cannula and EEG). PSG signal visualization was possible in 90% of cases but Skype® connection was problematic in 19% of cases. However, patients could be reached by phone to solve the problem. Real-time attended HPSG through telematic data transmission is feasible and could be an interesting perspective to decrease the failure rate of home sleep studies, even if some technical aspects need to be improved. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Internet-based treatment for Romanian adults with panic disorder: protocol of a randomized controlled trial comparing a Skype-guided with an unguided self-help intervention (the PAXPD study).

    PubMed

    Ciuca, Amalia Maria; Berger, Thomas; Crişan, Liviu George; Miclea, Mircea

    2016-01-14

    Efficacy of self-help internet-based cognitive behavior therapy (ICBT) for anxiety disorders has been confirmed in several randomized controlled trials. However, the amount and type of therapist guidance needed in ICBT are still under debate. Previous studies have shown divergent results regarding the role of therapist guidance and its impact on treatment outcome. This issue is central to the development of ICBT programs and needs to be addressed directly. The present study aims to compare the benefits of regular therapist guidance via online real-time audio-video communication (i.e. Skype) to no therapist guidance during a 12-week Romanian self-help ICBT program for Panic Disorder. Both treatments are compared to a waiting-list control group. A parallel group randomized controlled trial is proposed. The participants, 192 Romanian adults fulfilling diagnostic criteria for panic disorder according to a diagnostic interview, conducted via secured Skype or telephone, are randomly assigned to one of the three conditions: independent use of the internet-based self-help program PAXonline, the same self-help treatment with regular therapist support via secured Skype, and waiting-list control group. The primary outcomes are severity of self-report panic symptoms (PDSS-SR) and diagnostic status (assessors are blind to group assignment), at the end of the intervention (12 weeks) and at follow-up (months 3 and 6). The secondary measures address symptoms of comorbid anxiety disorders, depression, quality of life, adherence and satisfaction with ICBT. Additional measures of socio-demographic characteristics, personality traits, treatment expectancies, catastrophic cognitions, body vigilance and working alliance are considered as potential moderators and/ or mediators of treatment outcome. To the best of our knowledge, the present study is the first effort to investigate the efficacy of a self-help internet-based intervention with therapist guidance via real-time video communication. A direct comparison between therapist guided versus unguided self-directed intervention for panic disorder will also be addressed for the first time. Findings from this study will inform researchers and practitioners about the added value of online video-therapy guidance sessions and the type of patients who may benefit the most from guided and unguided ICBT for Panic disorder. ACTRN12614000547640 (Australian New Zealand Clinical Trials Registry). Registered 22/05/2014.

  11. Porous, S-bearing silica in metal-sulfide nodules and in the interchondrule clastic matrix in two EH3 chondrites

    NASA Astrophysics Data System (ADS)

    Lehner, S. W.; Németh, P.; Petaev, M. I.; Buseck, P. R.

    2017-11-01

    Two new occurrences of porous, S-bearing, amorphous silica are described within metal-sulfide nodules (MSN) and as interchondrule patches in EH3 chondrites SAH 97072 and ALH 84170. This porous amorphous material, which was first reported from sulfide-bearing chondrules, consists of sinewy SiO2-rich areas containing S with minor Na or Ca as well as Fe, Mg, and Al. Some pores contain minerals including pyrite, pyrrhotite, and anhydrite. Most pores appear vacant or contain unidentified material that is unstable under analytical conditions. Niningerite, olivine, enstatite, albite, and kumdykolite occur enclosed within porous silica patches. Porous silica is commonly interfingered with cristobalite suggesting its amorphous structure resulted from high-temperature quenching. We interpret the S-bearing porous silica to be a product of silicate sulfidation, and the Na, Ca, Fe, Mg, and Al detectable within this material are chemical residues of sulfidized silicates and metal. The occurrence of porous silica in the cores of MSN, which are considered to be pre-accretionary objects, suggests the sulfidizing conditions occurred prior to final parent-body solidification. Ubiquitous S-bearing porous silica among sulfide-bearing chondrules, MSN, and in the interchondrule clastic matrix, suggests that similar sulfidizing conditions affected all the constituents of these EH3 chondrites.

  12. Regulation of tRNA Bidirectional Nuclear-Cytoplasmic Trafficking in Saccharomyces cerevisiae

    PubMed Central

    Murthi, Athulaprabha; Shaheen, Hussam H.; Huang, Hsiao-Yun; Preston, Melanie A.; Lai, Tsung-Po; Phizicky, Eric M.

    2010-01-01

    tRNAs in yeast and vertebrate cells move bidirectionally and reversibly between the nucleus and the cytoplasm. We investigated roles of members of the β-importin family in tRNA subcellular dynamics. Retrograde import of tRNA into the nucleus is dependent, directly or indirectly, upon Mtr10. tRNA nuclear export utilizes at least two members of the β-importin family. The β-importins involved in nuclear export have shared and exclusive functions. Los1 functions in both the tRNA primary export and the tRNA reexport processes. Msn5 is unable to export tRNAs in the primary round of export if the tRNAs are encoded by intron-containing genes, and for these tRNAs Msn5 functions primarily in their reexport to the cytoplasm. The data support a model in which tRNA retrograde import to the nucleus is a constitutive process; in contrast, reexport of the imported tRNAs back to the cytoplasm is regulated by the availability of nutrients to cells and by tRNA aminoacylation in the nucleus. Finally, we implicate Tef1, the yeast orthologue of translation elongation factor eEF1A, in the tRNA reexport process and show that its subcellular distribution between the nucleus and cytoplasm is dependent upon Mtr10 and Msn5. PMID:20032305

  13. Regulation of tRNA bidirectional nuclear-cytoplasmic trafficking in Saccharomyces cerevisiae.

    PubMed

    Murthi, Athulaprabha; Shaheen, Hussam H; Huang, Hsiao-Yun; Preston, Melanie A; Lai, Tsung-Po; Phizicky, Eric M; Hopper, Anita K

    2010-02-15

    tRNAs in yeast and vertebrate cells move bidirectionally and reversibly between the nucleus and the cytoplasm. We investigated roles of members of the beta-importin family in tRNA subcellular dynamics. Retrograde import of tRNA into the nucleus is dependent, directly or indirectly, upon Mtr10. tRNA nuclear export utilizes at least two members of the beta-importin family. The beta-importins involved in nuclear export have shared and exclusive functions. Los1 functions in both the tRNA primary export and the tRNA reexport processes. Msn5 is unable to export tRNAs in the primary round of export if the tRNAs are encoded by intron-containing genes, and for these tRNAs Msn5 functions primarily in their reexport to the cytoplasm. The data support a model in which tRNA retrograde import to the nucleus is a constitutive process; in contrast, reexport of the imported tRNAs back to the cytoplasm is regulated by the availability of nutrients to cells and by tRNA aminoacylation in the nucleus. Finally, we implicate Tef1, the yeast orthologue of translation elongation factor eEF1A, in the tRNA reexport process and show that its subcellular distribution between the nucleus and cytoplasm is dependent upon Mtr10 and Msn5.

  14. Developing nanotechnology for biofuel and plant science applications

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Valenstein, Justin

    2012-01-01

    This dissertation presents the research on the development of mesoporous silica based nanotechnology for applications in biofuels and plant science. Mesoporous silica nanoparticles (MSNs) have been the subject of great interest in the last two decades due to their unique properties of high surface area, tunable pore size and particle morphology. The robust nature of the silica framework is easily functionalized to make the MSNs a promising option for selective separations. Also, the independent channels that form the pores of MSN have been exploited in the use of particles as platforms for molecular delivery. Pore size and organic functionality aremore » varied to identify the ideal adsorbent material for free fatty acids (FFAs). The resulting material is able to sequester FFAs with a high degree of selectivity from a simulated solution and microalgal oil. The recyclability and industrial implications are also explored. A continuation of the previous material, further tuning of MSN pore size was investigated. Particles with a smaller diameter selectively sequester polyunsaturated free fatty acids (PUFAs) over monounsaturated FFAs and saturated FFAs. The experimental results were verified with molecular modeling. Mesoporous silica nanoparticle materials with a pore diameter of 10 nm (MSN-10) were decorated with small gold nanoparticles. The resulting materials were shown to deliver proteins and DNA into plant cells using the biolistic method.« less

  15. Development of high-resolution multi-scale modelling system for simulation of coastal-fluvial urban flooding

    NASA Astrophysics Data System (ADS)

    Comer, Joanne; Indiana Olbert, Agnieszka; Nash, Stephen; Hartnett, Michael

    2017-02-01

    Urban developments in coastal zones are often exposed to natural hazards such as flooding. In this research, a state-of-the-art, multi-scale nested flood (MSN_Flood) model is applied to simulate complex coastal-fluvial urban flooding due to combined effects of tides, surges and river discharges. Cork city on Ireland's southwest coast is a study case. The flood modelling system comprises a cascade of four dynamically linked models that resolve the hydrodynamics of Cork Harbour and/or its sub-region at four scales: 90, 30, 6 and 2 m. Results demonstrate that the internalization of the nested boundary through the use of ghost cells combined with a tailored adaptive interpolation technique creates a highly dynamic moving boundary that permits flooding and drying of the nested boundary. This novel feature of MSN_Flood provides a high degree of choice regarding the location of the boundaries to the nested domain and therefore flexibility in model application. The nested MSN_Flood model through dynamic downscaling facilitates significant improvements in accuracy of model output without incurring the computational expense of high spatial resolution over the entire model domain. The urban flood model provides full characteristics of water levels and flow regimes necessary for flood hazard identification and flood risk assessment.

  16. A co-delivery nanosystem of chemotherapeutics and DNAzyme overcomes cancer drug resistance and metastasis

    NASA Astrophysics Data System (ADS)

    Sun, Shu-Pin; Liu, Ching-Ping; Huang, I.-Ping; Chu, Chia-Hui; Chung, Ming-Fang; Cheng, Shih-Hsun; Lin, Shu-Yi; Lo, Leu-Wei

    2017-12-01

    Multidrug resistance (MDR) constitutes a major problem in the management of cancer and cancer metastasized from primary-source tumor causes cancer-related deaths. Our new approach is the co-delivery of chemotherapy drugs with a transcription-factor-targeting genetic agent to simultaneously inhibit the growth and metastasis of cancer cells. C-Jun is a transcription factor that regulates multidrug resistance-associated protein 1 (MRP1) pump efflux transcription and tumor metastasis. In this work, we reported that mesoporous silica nanoparticles (MSNs) can be functionalized to co-deliver doxorubicin (Dox) and DNAzyme (Dz) to increase cancer cell killing in an additive fashion. The MSNs were sequentially conjugated with Dox into the MSNs’ nanochannels and Dz onto the MSNs’ outermost surface to target c-Jun as the Dox@MSN-Dz co-delivery system. The Dox-resistant PC-3 cells treated with Dox@MSN-Dz efficiently enhanced the intracellular Dox concentration due to the abrogation of Dox-induced MRP1 expression through the downregulation of c-Jun expression by Dz. Additionally, significant reductions in invasion and migration related to metastasis were also observed in cells treated with Dox@MSN-Dz. Therefore, our results contribute new insight to the treatment of MDR combined metastatic cancer cells, worthwhile for studying its potential for development in clinical translation.

  17. Mesoporous silica nanoparticles as a promising skin delivery system for methotrexate.

    PubMed

    Sapino, Simona; Oliaro-Bosso, Simonetta; Zonari, Daniele; Zattoni, Andrea; Ugazio, Elena

    2017-09-15

    The systemic administration of methotrexate (MTX), a commonly used, antineoplastic drug which is also used in cutaneous disorders, is primarily associated with prolonged retention in the body and consequently with side effects. Innovative drug delivery techniques and alternative administration routes would therefore contribute to its safe and effective use. The general objective of this study is thus the development of MTX-based preparations for the topical treatment of skin disorders. MCM-41-like nanoparticles (MSN), are herein proposed as carriers which can improve the cutaneous absorption and hence the bioavailability and efficacy of MTX. The MTX/MSN complex, prepared via the impregnation procedure, has been physico-chemically characterized, while its cell cultures have had their biocompatibility and bioactivity tested. Furthermore, a series of stable MTX-based dermal formulations has been developed, some containing shea butter, a natural fat. Ex-vivo porcine skin absorption and the transepidermal permeation of MTX have also been monitored in a variety of media using Franz diffusion cells. Interestingly, the epidermal accumulation of the active molecule was increased by its inclusion into MSN, regardless of the surrounding medium. Furthermore, the presence of shea butter enhanced the skin uptake of the drug both in the free and in the loaded form. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Biomonitoring of Aristolactam-DNA Adducts in Human Tissues using Ultra-Performance Liquid Chromatography/Ion-Trap Mass Spectrometry

    PubMed Central

    Yun, Byeong Hwa; Rosenquist, Thomas; Sidorenko, Viktoriya; Iden, Charles; Chung-Hsin, Chen; Pu, Yeong-Shiau; Bonala, Radha; Johnson, Francis; Dickman, Kathleen G.; Grollman, Arthur P.; Turesky, Robert J.

    2012-01-01

    Aristolochic acids (AAs) are a structurally-related family of nephrotoxic and carcinogenic nitrophenanthrene compounds found in Aristolochia herbaceous plants, many of which have been used worldwide for medicinal purposes. AAs have been implicated in the etiology of so-called Chinese herbs nephropathy and of Balkan endemic nephropathy. Both of these disease syndromes are associated with carcinomas of the upper urinary tract (UUC). 8-Methoxy-6-nitrophenanthro-[3,4-d]-1,3-dioxolo-5-carboxylic acid (AA-I) is a principal component of Aristolochia herbs. Following metabolic activation, AA-I reacts with DNA to form aristolactam (AL-I)-DNA adducts. We have developed a sensitive analytical method, using ultra-performance liquid chromatography-electrospray ionization/multistage mass spectrometry (UPLC-ESI/MSn) with a linear quadrupole ion-trap mass spectrometer, to measure 7-(deoxyadenosin-N6-yl) aristolactam I (dA-AL-I) and 7-(deoxyguanosin-N2-yl) aristolactam I (dG-AL-I) adducts. Using 10 μg of DNA for measurements, the lower limits of quantitation of dA-AL-I and dG-AL-I are, respectively, 0.3 and 1.0 adducts per 108 DNA bases. We have used UPLC-ESI/MSn to quantify AL-DNA adducts in tissues of rodents exposed to AA, and in the renal cortex of patients with UUC who reside in Taiwan, where the incidence of this uncommon cancer is the highest reported for any country in the world. In human tissues, dA-AL-I was detected at levels ranging from 9 to 338 adducts per 108 DNA bases, whereas dG-AL-I was not found. We conclude that UPLC-ESI/MSn is a highly sensitive, specific and robust analytical method, positioned to supplant 32P-postlabeling techniques currently used for biomonitoring of DNA adducts in human tissues. Importantly, UPLC-ESI/MSn could be used to document exposure to AA, the toxicant responsible for AA nephropathy and its associated UUC. PMID:22515372

  19. An EGFR inhibitor enhances the efficacy of SN38, an active metabolite of irinotecan, in SN38-refractory gastric carcinoma cells

    PubMed Central

    Yashiro, M; Qiu, H; Hasegawa, T; Zhang, X; Matsuzaki, T; Hirakawa, K

    2011-01-01

    Background: Acquired drug resistance to irinotecan is one of the significant obstacles in the treatment of advanced gastric cancer. This study was performed to clarify the effect of epidermal growth factor receptor (EGFR) inhibitors in combination with SN38, an active metabolite of irinotecan, on the proliferation of irinotecan-refractory gastric cancer. Methods: Two irinotecan-resistant gastric cancer cell lines, OCUM-2M/SN38 and OCUM-8/SN38 were, respectively, established by stepwise exposure to SN38 from the parent gastric cancer cell lines OCUM-2M and OCUM-8. The combination effects of two EGFR inhibitors, gefitinib and lapatinib, with SN38 on proliferation, apoptosis, and cell cycle on gastric cancer cells were examined. Results: Gefitinib or lapatinib showed synergistic anti-tumour effects against OCUM-2M/SN38 and OCUM-8/SN38 cells when used in combination with SN38, but not against OCUM-2M or OCUM-8 cells. SN38 increased the expression of EGFR and HER2 in OCUM-2M/SN38 and OCUM-8/SN38 cells. The combination of an EGFR inhibitor and SN38 significantly increased the levels of apoptosis-related molecules, caspase-6, p53, and DAPK-2, and resulted in the induction of apoptosis of irinotecan-resistant cells. The EGFR inhibitors increased the S-phase and decreased the UGT1A1 and ABCG expression in irinotecan-resistant cells. The SN38 plus Lapatinib group more effectively suppressed in vivo tumour growth by OCUM-2M/SN38 cells than either alone group. Conclusion: The combination treatment with an EGFR inhibitor and irinotecan might produce synergistic anti-tumour effects for irinotecan-refractory gastric cancer cells. The regulation of SN38 metabolism-related genes and cell cycle by EGFR inhibitors might be responsible for the synergism. PMID:21997136

  20. β-SiH-containing tris(silazido) rare-earth complexes as homogeneous and grafted single-site catalyst precursors for hydroamination

    DOE PAGES

    Eedugurala, Naresh; Wang, Zhuoran; Yan, KaKing; ...

    2017-01-25

    A series of homoleptic rare-earth silazido compounds and their silica-grafted derivatives were prepared to compare spectroscopic and catalytic features under homogeneous and interfacial conditions. Trivalent tris(silazido) compounds Ln{N(SiHMe 2) tBu} 3 (Ln = Sc (1), Y (2), Lu (3)) are prepared in high yield by salt metathesis reactions. Solution-phase and solid-state characterization of 1–3 by NMR and IR spectroscopy and X-ray diffraction reveals Ln←H–Si interactions. These features are retained in solvent-coordinated 2·Et 2O, 2·THF, and 3·THF. The change in spectroscopic features characterizing the secondary interactions (ν SiH, 1 J SiH) from the unactivated SiH in the silazane HN(SiHMe 2) tBumore » follows the trend 3 > 2 > 1 ≈ 2·Et 2O > 2·THF ≈ 3·THF. Ligand lability follows the same pattern, with Et 2O readily dissociating from 2·Et 2O while THF is displaced only during surface grafting reactions. 1 and 2·THF graft onto mesoporous silica nanoparticles (MSN) to give Ln{N(SiHMe 2) tBu} n@MSN (Ln = Sc (1@MSN), Y (2@MSN)) along with THF and protonated silazido as HN(SiHMe 2) tBu and H 2N tBu. The surface species are characterized by multinuclear and multidimensional solid-state (SS) NMR spectroscopic techniques, as well as diffuse reflectance FTIR, elemental analysis, and reaction stoichiometry. A key 1 J SiH SSNMR measurement reveals that the grafted sites most closely resemble Ln·THF adducts, suggesting that siloxane coordination occurs in grafted compounds. These species catalyze the hydroamination/bicyclization of aminodialkenes, and both solution-phase and interfacial conditions provide the bicyclized product with equivalent cis:trans ratios. As a result, similar diastereoselectivities mediated by catalytic sites under the two conditions suggest similar effective environments.« less

  1. Novel LC-ESI/MS/MSn Method for the Characterization and Quantification of 2′-Deoxyguanosine Adducts of the Dietary Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine by 2-D Linear Quadrupole Ion Trap Mass Spectrometry

    PubMed Central

    Goodenough, Angela K.; Schut, Herman A. J.; Turesky, Robert J.

    2008-01-01

    An accurate and sensitive liquid chromatography-electrospray ionization/multi-stage mass spectrometry (LC-ESI/MS/MSn) technique has been developed for the characterization and quantification of 2′-deoxyguanosine (dG) adducts of the dietary mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). PhIP is an animal and potential human carcinogen that occurs in grilled meats. Following enzymatic digestion and adduct enrichment by solid-phase extraction (SPE), PhIP—DNA adducts were analyzed by MS/MS and MSn scan modes on a 2-D linear quadrupole ion trap mass spectrometer (QIT/MS). The major DNA adduct, N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (dG-C8-PhIP), was detected in calf thymus (CT) DNA modified in vitro with a bioactivated form of PhIP and in the colon and liver of rats given PhIP as part of the diet. The lower limit of detection (LOD) was 1 adduct per 108 DNA bases, and the limit of quantification (LOQ) was 3 adducts per 108 DNA bases in both MS/MS and MS3 scan modes, using 27 μg of DNA for analysis. Measurements were based on isotope dilution with the internal standard, N-(deoxyguanosin-8-yl)-2-amino-1-(trideutero)methyl-6-phenylimidazo[4,5-b]pyridine (dG-C8-[2H3C]-PhIP). The selected reaction monitoring (SRM) scan mode in MS/MS was employed to monitor the loss of deoxyribose (dR) from the protonated molecules of the adducts ([M + H - 116]+). The consecutive reaction monitoring (CRM) scan modes in MS3 and MS4 were used to measure and further characterize product ions of the aglycone ion (BH2+) (Guanyl-PhIP). The MS3 scan mode was effective in eliminating isobaric interferences observed in the MS/MS scan mode and resulted in an improved signal-to-noise (S/N) ratio. Moreover, the product ion spectra obtained by the MSn scan modes provided rich structural information about the adduct and were used to corroborate the identity of dG-C8-PhIP. In addition, an isomeric dG-PhIP adduct was detected in vivo. This LCESI/MS/MSn method is the first reported application on the use of the MS3 scan mode for the analysis of DNA adducts in vivo. PMID:17305409

  2. Let's Hear It for ...

    ERIC Educational Resources Information Center

    Federoff, Matt; Hicks, Troy; Mangiacapre, Anthony; Reilly, Erin; Imbriale, Ryan; Sheninger, Eric; Meyer, Dan; Langhorst, Eric

    2011-01-01

    If you were transported back to school, what kind of technology would most engage you? This article presents responses from leading technology educators who were asked this question. The following technological tools are highlighted: interactive whiteboards, wikis, teacher-created websites, story creation tools, cell phones, Skype, digital…

  3. Behavioral health care for adolescents with poorly controlled diabetes via Skype: does working alliance remain intact?

    PubMed

    Freeman, Kurt A; Duke, Danny C; Harris, Michael A

    2013-05-01

    Increasingly various technologies are being tested to deliver behavioral health care. Delivering services via videoconferencing shows promise. Given that the patient-provider relationship is a strong predictor of patient adherence to medical regimens, addressing relationship quality when services are not delivered face-to-face is critical. To that end, we compared the therapeutic alliance when behavioral health care was delivered to youth with poorly controlled type 1 diabetes mellitus (T1DM) and their caregivers in-clinic with the same services delivered via Internet-based videoconferencing (i.e., Skype™). Seventy-one adolescents with poorly controlled T1DM (hemoglobin A1c ≥9%) and one of their caregivers received up to 10 sessions of a family-based behavioral health intervention previously shown to improve adherence to diabetes regimens and family functioning; 32 were randomized to the Skype condition. Youth and caregivers completed the working alliance inventory (WAI), a 36-item measure of therapeutic alliance, at the end of treatment. Additionally, the number of behavioral health sessions completed was tracked. No significant differences in WAI scores were found for those receiving behavioral health care via Skype versus in-clinic. Youth WAI goal and total scores were significantly associated with the number of sessions completed for those in the clinic group. Behavioral health can be delivered to youth with T1DM via Internet-based videoconferencing without significantly impacting the therapeutic relationship. Thus, for those adolescents with T1DM who require specialized behavioral health care that targets T1DM management, Internet-based teleconferencing represents a viable alternative to clinic-based care. © 2013 Diabetes Technology Society.

  4. Cost Effective Use of Free-to-Use Apps in Neurosurgery (FAN) in Developing Countries: From Clinical Decision Making to Educational Courses, Strengthening Health Care Delivery.

    PubMed

    Thapa, Amit; Kc, Bidur; Shakya, Bikram

    2016-11-01

    Financial limitations and the scarcity of technological knowledge are a major hurdle to good communication platforms, data storage, and dissemination of medical knowledge in developing countries. Out of necessity we used free-to-use apps in our practice. We studied the applicability and cost effective aspect of a systematic use of these apps in neurosurgery. We designed the Free-to-use apps in neurosurgery (FAN) module in 4 phases at Kathmandu Medical College Teaching Hospital over the last 3 years. We used free apps like Viber, Dropbox, Skype, and VLC media player on 3G and Wi-Fi network. Users were trained in ethics and measures to ensure confidentiality and privacy of patient-related data. Endpoints studied were feasibility, reliability, cost effectiveness, and overall satisfaction of the users. In the FAN module, the Viber app was used to send pictures of digital images via smartphones within 30 minutes, enabling quick decisions by the consultants. Dropbox not only helped store images but also helped quick verification of discharge summaries as early as 15 minutes increasing overall efficiency. With Skype, consultants could be contacted even when they were abroad, and with the use of FAN they remain updated of their patients. By the use of Skype and VLC media player, 2 operative live workshops from abroad were transmitted live with good visual and audio reception, allowing question-and-answer sessions with the faculties. User satisfaction was more than 90%. The FAN module helped in quick reliable decision making, allowing for instantaneous communication and storing data and exchange of knowledge across countries. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Behavioral Health Care for Adolescents with Poorly Controlled Diabetes via Skype: Does Working Alliance Remain Intact?

    PubMed Central

    Freeman, Kurt A.; Duke, Danny C.; Harris, Michael A.

    2013-01-01

    Background: Increasingly various technologies are being tested to deliver behavioral health care. Delivering services via videoconferencing shows promise. Given that the patient–provider relationship is a strong predictor of patient adherence to medical regimens, addressing relationship quality when services are not delivered face-to-face is critical. To that end, we compared the therapeutic alliance when behavioral health care was delivered to youth with poorly controlled type 1 diabetes mellitus (T1DM) and their caregivers in-clinic with the same services delivered via Internet-based videoconferencing (i.e., Skype™). Methods: Seventy-one adolescents with poorly controlled T1DM (hemoglobin A1c ≥9%) and one of their caregivers received up to 10 sessions of a family-based behavioral health intervention previously shown to improve adherence to diabetes regimens and family functioning; 32 were randomized to the Skype condition. Youth and caregivers completed the working alliance inventory (WAI), a 36-item measure of therapeutic alliance, at the end of treatment. Additionally, the number of behavioral health sessions completed was tracked. Results: No significant differences in WAI scores were found for those receiving behavioral health care via Skype versus in-clinic. Youth WAI goal and total scores were significantly associated with the number of sessions completed for those in the clinic group. Conclusion: Behavioral health can be delivered to youth with T1DM via Internet-based videoconferencing without significantly impacting the therapeutic relationship. Thus, for those adolescents with T1DM who require specialized behavioral health care that targets T1DM management, Internet-based teleconferencing represents a viable alternative to clinic-based care. PMID:23759406

  6. A theoretical and mass spectrometry study of the fragmentation of mycosporine-like amino acids

    NASA Astrophysics Data System (ADS)

    Cardozo, Karina H. M.; Vessecchi, Ricardo; Carvalho, Valdemir M.; Pinto, Ernani; Gates, Paul J.; Colepicolo, Pio; Galembeck, Sérgio E.; Lopes, Norberto P.

    2008-06-01

    In the present study, the mycosporine-like amino acids (MAAs) were isolated from the marine red alga Gracilaria tenuistipitata and analysed by high-resolution accurate-mass sequential mass spectrometry (MSn). In addition to the proposed fragmentation mechanism based on the MSn analysis, it is clearly demonstrated that the elimination of mass 15 is a radical processes taking place at the methoxyl substituent of the double bond. This characteristic loss of a methyl radical was studied by theoretical calculations and the homolytic cleavage of the OC bond is suggested to be dependent on the bond weakening. The protonation site of the MAAs was indicated by analysis of the Fukui functions and the relative Gibbs energies of the several possible protonated forms.

  7. Educational opportunities: a nursing school model for medical special-needs sheltering.

    PubMed

    Deal, Belinda; Alfred, Danita; Fountain, Rebecca; Ford, Terri; Chilton, Jennifer

    2010-01-01

    The devastation of New Orleans after Hurricane Katrina increased the awareness of persons who were unable to self-evacuate because of physical and/or mental disabilities. From that awareness, plans emerged to provide a safe haven for those who had special needs. In this article, we describe our efforts as a school of nursing to shelter medical special needs (MSN) evacuees in the wake of a hurricane. After the shelter closed, faculty and students involved in the shelter answered a short survey that included both open- and close-ended questions. The responses are summarized to encourage other schools of nursing to consider caring for MSN evacuees and to share our successes, our failures, and our plans for the future.

  8. A Skype-Buddy Model for Blended Learning

    ERIC Educational Resources Information Center

    Macharaschwili, Carmen E.; Coggin, Linda Skidmore

    2013-01-01

    Online learning in higher education allows distance education students to complete degree requirements in virtual environments. Universities are challenged with providing quality education experiences for these students and meet the students' needs for engagement and challenge within a collaborative framework. This study proposes how Voice over…

  9. Interactive Videoconferencing in Educational Settings: A Case in Primary Education

    ERIC Educational Resources Information Center

    Sáez-López, José-Manuel; Feliz-Murias, Tiberio; Holgueras-González, Ana-Isabel

    2018-01-01

    This research analyzes the use of Interactive Videoconferencing in classroom, analyzing practice and attitudes of 37 teachers and professors from several countries in the first dimension. The second dimension analyzes innovative approaches and Collaborative Learning through Interactive Videoconferencing using "Skype" in a particular…

  10. A New Method to Directly Observe Tuberculosis Treatment: Skype Observed Therapy, a Patient-Centered Approach.

    PubMed

    Buchman, Tavora; Cabello, Celina

    Tuberculosis (TB) treatment completion is in part determined by patient's adherence to long-term drug regimens. To best ensure compliance, directly observed therapy (DOT) is considered the standard of practice. Nassau County Department of Health TB Control is responsible for providing DOT to patients with TB. Tuberculosis Control sought to use and evaluate Skype Observed Therapy (SOT) as an alternative to DOT for eligible patients. The evaluation included analysis of patient's acceptance and adherence to drug regimen using SOT. Tuberculosis Control assessed staff efficiency and cost savings for this program. Percentages of SOT of patients and successful SOT visits, mileage, and travel time savings. Twenty percent of the caseload used SOT and 100% of patients who were eligible opted in. Average SOT success was 79%. Total mileage savings and time saved were $9,929.07 and 614 hours. Because SOT saves cost and time and is a suitable alternative to DOT for patients, it should be considered as part of new policies and practices in TB control programs.

  11. Can Faces Prime a Language?

    PubMed

    Woumans, Evy; Martin, Clara D; Vanden Bulcke, Charlotte; Van Assche, Eva; Costa, Albert; Hartsuiker, Robert J; Duyck, Wouter

    2015-09-01

    Bilinguals have two languages that are activated in parallel. During speech production, one of these languages must be selected on the basis of some cue. The present study investigated whether the face of an interlocutor can serve as such a cue. Spanish-Catalan and Dutch-French bilinguals were first familiarized with certain faces, each of which was associated with only one language, during simulated Skype conversations. Afterward, these participants performed a language production task in which they generated words associated with the words produced by familiar and unfamiliar faces displayed on-screen. When responding to familiar faces, participants produced words faster if the faces were speaking the same language as in the previous Skype simulation than if the same faces were speaking a different language. Furthermore, this language priming effect disappeared when it became clear that the interlocutors were actually bilingual. These findings suggest that faces can prime a language, but their cuing effect disappears when it turns out that they are unreliable as language cues. © The Author(s) 2015.

  12. Internationalising the nursing curriculum using a Community of Inquiry Framework and blended learning.

    PubMed

    Stephens, Melanie; Hennefer, Dawn

    2013-05-01

    The study examined how computer mediated tools, blended with traditional forms of teaching activity supported undergraduate pre-registration nursing students on international placement and for those students unable to go out into the world, how could this world be brought to their home campus? The researchers sought to examine whether synchronous online face to face contact using Skype, improved support and communication for students nursing overseas and if cultural awareness was developed for those nursing students who stayed on native soil. Data was collected using focus groups and online questionnaires. Themes arising from the thematic analysis of the narratives included operational issues, pastoral care, academic and peer support and cultural awareness and development. The use of Blended Learning tools such as Skype and weblogs were found to be extremely beneficial as a form of online communication and support for students undertaking an international placement. In relation to cultural awareness further work is required. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Windows Instant Messaging App Forensics: Facebook and Skype as Case Studies

    PubMed Central

    Yang, Teing Yee; Dehghantanha, Ali; Choo, Kim-Kwang Raymond; Muda, Zaiton

    2016-01-01

    Instant messaging (IM) has changed the way people communicate with each other. However, the interactive and instant nature of these applications (apps) made them an attractive choice for malicious cyber activities such as phishing. The forensic examination of IM apps for modern Windows 8.1 (or later) has been largely unexplored, as the platform is relatively new. In this paper, we seek to determine the data remnants from the use of two popular Windows Store application software for instant messaging, namely Facebook and Skype on a Windows 8.1 client machine. This research contributes to an in-depth understanding of the types of terrestrial artefacts that are likely to remain after the use of instant messaging services and application software on a contemporary Windows operating system. Potential artefacts detected during the research include data relating to the installation or uninstallation of the instant messaging application software, log-in and log-off information, contact lists, conversations, and transferred files. PMID:26982207

  14. Windows Instant Messaging App Forensics: Facebook and Skype as Case Studies.

    PubMed

    Yang, Teing Yee; Dehghantanha, Ali; Choo, Kim-Kwang Raymond; Muda, Zaiton

    2016-01-01

    Instant messaging (IM) has changed the way people communicate with each other. However, the interactive and instant nature of these applications (apps) made them an attractive choice for malicious cyber activities such as phishing. The forensic examination of IM apps for modern Windows 8.1 (or later) has been largely unexplored, as the platform is relatively new. In this paper, we seek to determine the data remnants from the use of two popular Windows Store application software for instant messaging, namely Facebook and Skype on a Windows 8.1 client machine. This research contributes to an in-depth understanding of the types of terrestrial artefacts that are likely to remain after the use of instant messaging services and application software on a contemporary Windows operating system. Potential artefacts detected during the research include data relating to the installation or uninstallation of the instant messaging application software, log-in and log-off information, contact lists, conversations, and transferred files.

  15. Separate responses of karyopherins to glucose and amino acid availability regulate nucleocytoplasmic transport

    PubMed Central

    Huang, Hsiao-Yun; Hopper, Anita K.

    2014-01-01

    The importin-β family members (karyopherins) mediate the majority of nucleocytoplasmic transport. Msn5 and Los1, members of the importin-β family, function in tRNA nuclear export. tRNAs move bidirectionally between the nucleus and the cytoplasm. Nuclear tRNA accumulation occurs upon amino acid (aa) or glucose deprivation. To understand the mechanisms regulating tRNA subcellular trafficking, we investigated whether Msn5 and Los1 are regulated in response to nutrient availability. We provide evidence that tRNA subcellular trafficking is regulated by distinct aa-sensitive and glucose-sensitive mechanisms. Subcellular distributions of Msn5 and Los1 are altered upon glucose deprivation but not aa deprivation. Redistribution of tRNA exportins from the nucleus to the cytoplasm likely provides one mechanism for tRNA nuclear distribution upon glucose deprivation. We extended our studies to other members of the importin-β family and found that all tested karyopherins invert their subcellular distributions upon glucose deprivation but not aa deprivation. Glucose availability regulates the subcellular distributions of karyopherins likely due to alteration of the RanGTP gradient since glucose deprivation causes redistribution of Ran. Thus nuclear–cytoplasmic distribution of macromolecules is likely generally altered upon glucose deprivation due to collapse of the RanGTP gradient and redistribution of karyopherins between the nucleus and the cytoplasm. PMID:25057022

  16. A Feedforward Inhibitory Circuit Mediated by CB1-Expressing Fast-Spiking Interneurons in the Nucleus Accumbens.

    PubMed

    Wright, William J; Schlüter, Oliver M; Dong, Yan

    2017-04-01

    The nucleus accumbens (NAc) gates motivated behaviors through the functional output of principle medium spiny neurons (MSNs), whereas dysfunctional output of NAc MSNs contributes to a variety of psychiatric disorders. Fast-spiking interneurons (FSIs) are sparsely distributed throughout the NAc, forming local feedforward inhibitory circuits. It remains elusive how FSI-based feedforward circuits regulate the output of NAc MSNs. Here, we investigated a distinct subpopulation of NAc FSIs that express the cannabinoid receptor type-1 (CB1). Using a combination of paired electrophysiological recordings and pharmacological approaches, we characterized and compared feedforward inhibition of NAc MSNs from CB1 + FSIs and lateral inhibition from recurrent MSN collaterals. We observed that CB1 + FSIs exerted robust inhibitory control over a large percentage of nearby MSNs in contrast to local MSN collaterals that provided only sparse and weak inhibitory input to their neighboring MSNs. Furthermore, CB1 + FSI-mediated feedforward inhibition was preferentially suppressed by endocannabinoid (eCB) signaling, whereas MSN-mediated lateral inhibition was unaffected. Finally, we demonstrated that CB1 + FSI synapses onto MSNs are capable of undergoing experience-dependent long-term depression in a voltage- and eCB-dependent manner. These findings demonstrated that CB1 + FSIs are a major source of local inhibitory control of MSNs and a critical component of the feedforward inhibitory circuits regulating the output of the NAc.

  17. Nanocomposites based on graphene oxide and mesoporous silica nanoparticles: Preparation, characterization and nanobiointeractions with red blood cells and human plasma proteins

    NASA Astrophysics Data System (ADS)

    Fonseca, Leandro C.; de Araújo, Maciel M.; de Moraes, Ana Carolina M.; da Silva, Douglas S.; Ferreira, Ariane G.; Franqui, Lidiane S.; Martinez, Diego Stéfani T.; Alves, Oswaldo L.

    2018-04-01

    The current work refers to the development of a novel nanocomposite based on graphene oxide (GO) and mesoporous amino silica nanoparticles (H2N-MSNs) and its biological interaction with red blood cells (RBCs) and human blood plasma toward the investigation of nanobiointeractions. Silica nanoparticles and several graphene oxide-based materials are, separately, known for their high hemolytic potential and strong interaction with human plasma proteins. In this context, the GO-MSN interaction and its influence in minimizing the reported effects were investigated. The materials were synthesized by covalently attaching H2N-MSNs onto the surface of GO through an amidation reaction. GO-MSN nanocomposites were obtained by varying the mass of H2N-MSNs and were characterized by FTIR, NMR, XRD, TGA, zeta potential and TEM. The characterization results confirm that nanocomposites were obtained, suggest covalent bond attachment mostly by amine-epoxy reactions and evidence an unexpected reduction reaction of GO by H2N-MSNs, whose mechanism is proposed. Biological assays showed a decrease of hemolysis (RBC lysis) and a minimization of the interaction with human plasma proteins (protein corona formation). These are important findings toward achieving in vivo biocompatibility and understanding the nanobiointeractions. Finally, this work opens possibilities for new nanomedicine applications of GO-MSN nanocomposites, such as drug delivery system.

  18. A Feedforward Inhibitory Circuit Mediated by CB1-Expressing Fast-Spiking Interneurons in the Nucleus Accumbens

    PubMed Central

    Wright, William J; Schlüter, Oliver M; Dong, Yan

    2017-01-01

    The nucleus accumbens (NAc) gates motivated behaviors through the functional output of principle medium spiny neurons (MSNs), whereas dysfunctional output of NAc MSNs contributes to a variety of psychiatric disorders. Fast-spiking interneurons (FSIs) are sparsely distributed throughout the NAc, forming local feedforward inhibitory circuits. It remains elusive how FSI-based feedforward circuits regulate the output of NAc MSNs. Here, we investigated a distinct subpopulation of NAc FSIs that express the cannabinoid receptor type-1 (CB1). Using a combination of paired electrophysiological recordings and pharmacological approaches, we characterized and compared feedforward inhibition of NAc MSNs from CB1+ FSIs and lateral inhibition from recurrent MSN collaterals. We observed that CB1+ FSIs exerted robust inhibitory control over a large percentage of nearby MSNs in contrast to local MSN collaterals that provided only sparse and weak inhibitory input to their neighboring MSNs. Furthermore, CB1+ FSI-mediated feedforward inhibition was preferentially suppressed by endocannabinoid (eCB) signaling, whereas MSN-mediated lateral inhibition was unaffected. Finally, we demonstrated that CB1+ FSI synapses onto MSNs are capable of undergoing experience-dependent long-term depression in a voltage- and eCB-dependent manner. These findings demonstrated that CB1+ FSIs are a major source of local inhibitory control of MSNs and a critical component of the feedforward inhibitory circuits regulating the output of the NAc. PMID:27929113

  19. HSF and Msn2/4p can exclusively or cooperatively activate the yeast HSP104 gene.

    PubMed

    Grably, Melanie R; Stanhill, Ariel; Tell, Osnat; Engelberg, David

    2002-04-01

    In an effort to understand how an accurate level of stress-specific expression is obtained, we studied the promoter of the yeast HSP104 gene. Through 5' deletions, we defined a 334 bp fragment upstream of the first coding AUG as sufficient and essential for maximal basal activity and a 260 bp fragment as sufficient and essential for heat shock responsiveness. These sequences contain heat shock elements (HSEs) and stress response elements (STREs) that cooperate to achieve maximal inducible expression. However, in the absence of one set of factors (e.g. in msn2Deltamsn4Delta cells) proper induction is obtained exclusively through HSEs. We also show that HSP104 is constitutively derepressed in ras2Delta cells. This derepression is achieved exclusively through activation of STREs, with no role for HSEs. Strikingly, in ras2Deltamsn2Deltamsn4Delta cells the HSP104 promoter is also derepressed, but in this strain derepression is mediated through HSEs, showing the flexibility and adaptation of the promoter. Thus, appropriate transcription of HSP104 is usually obtained through cooperation between the Msn2/4/STRE and the HSF/ HSE systems, but each factor could activate the promoter alone, backing up the other. Transcription control of HSP104 is adaptive and robust, ensuring proper expression under extreme conditions and in various mutants.

  20. Telecollaboration, Challenges and Oppportunities

    ERIC Educational Resources Information Center

    Abruquah, Emmanuel; Dosa, Ildiko; Duda, Grazyna

    2016-01-01

    This article discusses some practical ideas associated with a pilot intercultural telecollaboration project. The aim of the project was to connect students from five countries: Estonia, Finland, Hungary, Poland and Spain, and to make them interact using social media, such as Facebook, Skype, Google Hangouts, etc. There were success stories…

  1. Enhancing Practicum Supervision with Asynchronous and Synchronous Technologies

    ERIC Educational Resources Information Center

    Teo, Yiong Hwee; McNamara, Sue; Romeo, Geoff; Gronn, Donna

    2015-01-01

    Three video/web conferencing technologies (Pocket Camcorder, Skype, Adobe Connect) were used in regional schools in Australia to determine whether the technologies are appropriate for the needs of the university supervisor, trainee teachers and supervising teachers with regard to practicum teaching placements. Findings revealed that Pocket…

  2. Prenatal choline deficiency decreases the cross-sectional area of cholinergic neurons in the medial septal nucleus.

    PubMed

    McKeon-O'Malley, Catherine; Siwek, Donald; Lamoureux, Jeffrey A; Williams, Christina L; Kowall, Neil W

    2003-07-11

    Levels of dietary choline in utero influence postnatal cognitive performance. To better understand this phenomenon, forebrain cholinergic neurons were studied in the 8-9 month old offspring of dams fed a control or choline-deficient diet from EDs 11-17. Serial sections were immunostained with antibodies against p75, a cholinergic marker. Neuronal morphology was analyzed in the basal forebrain, a heterogeneous area composed of several structures including the medial septal nucleus (MSN), nucleus of the diagonal band (DB), and the nucleus basalis of Meynert (NB). Neuronal cross-sectional areas were selectively reduced in the MSN of choline-deficient animals, compared to controls, but cell counts were not altered. Our findings suggest that cholinergic medial septal neurons may be selectively vulnerable to in utero choline deficiency.

  3. Development and application of multi-functionalized mesoporous silica nanomaterials in intracellular drug delivery and heterogeneous catalysis

    NASA Astrophysics Data System (ADS)

    Tsai, Chih-Hsiang

    This dissertation presents research on the development of mesoporous silica nanomaterials and their applications on the fields of drug delivery system and heterogeneous catalysis. Mesoporous silica nanoparticles (MSNs) featuring several particular physicochemical properties are of great interest in material science and applied chemistry. With high biocompatibility and large pore size, MSNs have been regarded as a highly promising platform for intracellular controlled release of drugs and biomolecules. On the other hand, the robust silica framework and easy surface functionalization make MSNs decent solid supports for various types of heterogeneous catalysis. A newly developed surfactant-assistant drug delivery system is investigated. A series of biocompatible phosphate monoester surfactant (PMES) containing PMES-MSN were synthesized and well characterized. The formation mechanism of these special radially-aligned mesostructure was systematic studied by TEM technique and carbon nanocasting. We found that the particle size and shape as well as the structural integrity can be tuned by the ratio of aminopropyltrimethoxysilane (APTMS) and PMES. For biological application, the controlled release of the hydrophobic drug, resveratrol, was tested both in solution and in vitro. It showed that the surfactant-containing PMES-MSNs has a loading capacity around 4 times higher than its surfactant-free counterpart. In addition, a sustained release pattern was observed in the PMES-MSNs release system, indicating the feature of surfactant-assistance. The in vitro study in HeLa cells demonstrated that PMES-MSNs can be efficiently endocytosed. We also observed an endosomal escape of PMES-MSNs within the HeLa cells probably due to proton sponge effect and the assistance of PMES. A series of bifunctionalized MSN catalysts with diarylammonium triflate groups (DAT) as active acid sites and pentafluorophenyl groups (PFP) as secondary functional groups for the catalysis of esterification were synthesized and well characterized. We found that the higher PFP to DAT ratio the higher the reactivity. This phenomenon is resulting from the extreme hydrophobicity of PFP groups which help expel the sole byproduct "water" out of the mesopores, pushing the equilibrium reaction to the product end. It has also shown that our DAT/PFP-MSN catalysts can be recycled at least five times with identical yields. A sequential impregnation method was developed to synthesize supported bimetallic Pd-Au@MSN catalysts with homogeneous distribution of metal nanoparticles. The tandem catalysis of aerobic oxidative esterification of primary alcohols was applied to examine the catalytic performance of these bimetallic Pd-Au@MSN catalysts. A synergistic effect was observed in the case of bimetallic catalyst system, in which the reactivity and selectivity are much higher than its counter monometallic catalysts. Catalysts recyclability and reasons for their deactivation were also studied and discussed in Chapter 4.

  4. A Usability Evaluation of Academic Virtual Reference Services

    ERIC Educational Resources Information Center

    Chow, Anthony S.; Croxton, Rebecca A.

    2014-01-01

    This study examined the usability of five virtual reference services--instant messenger chat, e-mail, telephone, text messaging, and Skype videoconferencing--by having 31 undergraduate and graduate students evaluate the usability of the virtual reference services of two different universities. The study's results suggest that user preference and…

  5. Pan-American Teletandem Language Exchange Project

    ERIC Educational Resources Information Center

    Castillo-Scott, Aurora

    2015-01-01

    This paper describes a TeleTandem language exchange project between English speaking Spanish students at Georgia College, USA, and Spanish speaking English students at Universidad de Concepción, Chile. The aim of the project was to promote linguistic skills and intercultural competence through a TeleTandem exchange. Students used Skype and Google…

  6. Virtual Mentoring of Preservice Teachers

    ERIC Educational Resources Information Center

    Reese, Jill

    2016-01-01

    The purpose of the study was to describe music teachers' perceptions of the benefits and challenges they experienced as virtual mentors of preservice music teachers. Each mentor was assigned a cohort of preservice teachers who were enrolled in an elementary general music methods course. Cohorts observed their mentor's teaching via Skype. Mentors…

  7. Bridging the Learning Gap: Cross-Cultural Learning and Teaching through Distance

    ERIC Educational Resources Information Center

    Mullings, Delores V.

    2015-01-01

    This project engaged students, practitioners, and educators from University of Labor and Social Affairs, Cau Giay District, Hanoi and Newfoundland and Labrador, Canada, in a cross-cultural distance learning and teaching collaboration. Two groups met simultaneously through Skype videoconferencing to discuss and learn about field supervision and…

  8. Emerging Technologies Integrating Technology into Study Abroad

    ERIC Educational Resources Information Center

    Godwin-Jones, Robert

    2016-01-01

    "Ready access to travel and to technology-enhanced social networking (e.g., Facebook or Skype) has changed the nature of study abroad to the point where today's experiences are fundamentally different from those of earlier eras" (Kinginger, 2013a, p. 345). In addition to more travel options and greater technology availability, study…

  9. Incorporating Technology in Teaching Musical Instruments

    ERIC Educational Resources Information Center

    Prodan, Angelica

    2017-01-01

    After discussing some of the drawbacks of using Skype for long distance music lessons, Angelica Prodan describes three different types of Artificial Reality (Virtual Reality, Augmented Reality and Mixed or Merged Reality). She goes on to describe the beneficial applications of technology, with results otherwise impossible to achieve in areas such…

  10. Skype Synchronous Interaction Effectiveness in a Quantitative Management Science Course

    ERIC Educational Resources Information Center

    Strang, Kenneth David

    2012-01-01

    An experiment compared asynchronous versus synchronous instruction in an online quantitative course. Mann-Whitney U-tests, correlation, analysis of variance, t tests, and multivariate analysis of covariance (MANCOVA) were utilized to test the hypothesis that more high-quality online experiential learning interactions would increase grade.…

  11. Telecollaboration and Sociopragmatic Awareness in the Foreign Language Classroom

    ERIC Educational Resources Information Center

    Martí, Natalia Morollón; Fernández, Susana S.

    2016-01-01

    This paper discusses the design and implementation of a pedagogical intervention aimed at raising sociopragmatic awareness in the context of Spanish as a foreign language in Denmark. The intervention consists of a blended-learning environment where the three main components are synchronous telecollaboration via Skype, reflection sessions in groups…

  12. DOTI: Databank of Oral Teletandem Interactions

    ERIC Educational Resources Information Center

    Aranha, Solange; Leone, Paola

    2016-01-01

    This contribution aims at (1) discussing the characteristics of collecting, filing and storing data to have a databank of oral interactions between university students whose main objective is the learning of a second language through teletandem; and (2) defining the steps for further collections and storage. Our data are Skype sessions of foreign…

  13. Time Management in the Digital Era

    ERIC Educational Resources Information Center

    Wodarz, Nan

    2013-01-01

    School business officials can strike a balance between setting a long-term strategy and responding to short-term situations by implementing time management strategies. This article presents tips for time management that could help boost productivity and save time in this digital era. Tips include decreasing meeting times via Skype or…

  14. Geometrically confined ultrasmall gadolinium oxide nanoparticles boost the T1 contrast ability

    NASA Astrophysics Data System (ADS)

    Ni, Kaiyuan; Zhao, Zhenghuan; Zhang, Zongjun; Zhou, Zijian; Yang, Li; Wang, Lirong; Ai, Hua; Gao, Jinhao

    2016-02-01

    High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon-Bloembergen-Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM-1 s-1. Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy provides new guidance for developing various high-performance T1 contrast agents for sensitive imaging and disease diagnosis.High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon-Bloembergen-Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM-1 s-1. Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy provides new guidance for developing various high-performance T1 contrast agents for sensitive imaging and disease diagnosis. Electronic supplementary information (ESI) available: Supplementary Fig. S1-S6. See DOI: 10.1039/c5nr08402d

  15. Nursing: What's a Nurse Practitioner?

    MedlinePlus

    ... nurses, or APNs) have a master's degree in nursing (MS or MSN) and board certification in their ... Nurse Practitioners (NAPNAP) and through local hospitals or nursing schools. Also, many doctors share office space with ...

  16. Multifunctional mesoporous silica catalyst

    DOEpatents

    Lin, Victor Shang-Yi; Tsai, Chih-Hsiang; Chen, Hung-Ting; Pruski, Marek; Kobayashi, Takeshi

    2015-03-31

    The present invention provides bifunctional silica mesoporous materials, including mesoporous silica nanoparticles ("MSN"), having pores modified with diarylammonium triflate and perfluoroaryl moieties, that are useful for the acid-catalyzed esterification of organic acids with organic alcohols.

  17. Preparation of a mesoporous silica-based nano-vehicle for dual DOX/CPT pH-triggered delivery.

    PubMed

    Llinàs, Maria C; Martínez-Edo, Gabriel; Cascante, Anna; Porcar, Irene; Borrós, Salvador; Sánchez-García, David

    2018-11-01

    A dual doxorubicin/camptothecin (DOX/CPT) pH-triggered drug delivery mesoporous silica nanoparticle (MSN)-based nano-vehicle has been prepared. In this drug-delivery system (DDS), CPT is loaded inside the pores of the MSNs, while DOX is covalently attached to the surface of an aldehyde-functionalized MSN through a dihydrazide-polyethylene glycol chain. Thus, DOX and the linker act as pH-sensitive gatekeeper. The system is versatile and easy to assemble, not requiring the chemical modification of the drugs. While at physiological conditions the release of the drugs is negligible, at acidic pH a burst release of DOX and a gradual release of CPT take place. In vitro cytotoxicity tests have demonstrated that this DDS can deliver efficiently DOX and CPT for combination therapy.

  18. Nucleus Accumbens Microcircuit Underlying D2-MSN-Driven Increase in Motivation.

    PubMed

    Soares-Cunha, Carina; Coimbra, Bárbara; Domingues, Ana Verónica; Vasconcelos, Nivaldo; Sousa, Nuno; Rodrigues, Ana João

    2018-01-01

    The nucleus accumbens (NAc) plays a central role in reinforcement and motivation. Around 95% of the NAc neurons are medium spiny neurons (MSNs), divided into those expressing dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R). Optogenetic activation of D2-MSNs increased motivation, whereas inhibition of these neurons produced the opposite effect. Yet, it is still unclear how activation of D2-MSNs affects other local neurons/interneurons or input terminals and how this contributes for motivation enhancement. To answer this question, in this work we combined optogenetic modulation of D2-MSNs with in loco pharmacological delivery of specific neurotransmitter antagonists in rats. First, we showed that optogenetic activation of D2-MSNs increases motivation in a progressive ratio (PR) task. We demonstrated that this behavioral effect relies on cholinergic-dependent modulation of dopaminergic signalling of ventral tegmental area (VTA) terminals, which requires D1R and D2R signalling in the NAc. D2-MSN optogenetic activation decreased ventral pallidum (VP) activity, reducing the inhibitory tone to VTA, leading to increased dopaminergic activity. Importantly, optogenetic activation of D2-MSN terminals in the VP was sufficient to recapitulate the motivation enhancement. In summary, our data suggests that optogenetic stimulation of NAc D2-MSNs indirectly modulates VTA dopaminergic activity, contributing for increased motivation. Moreover, both types of dopamine receptors signalling in the NAc are required in order to produce the positive behavioral effects.

  19. Nucleus Accumbens Microcircuit Underlying D2-MSN-Driven Increase in Motivation

    PubMed Central

    Soares-Cunha, Carina; Coimbra, Bárbara; Domingues, Ana Verónica; Vasconcelos, Nivaldo; Sousa, Nuno

    2018-01-01

    Abstract The nucleus accumbens (NAc) plays a central role in reinforcement and motivation. Around 95% of the NAc neurons are medium spiny neurons (MSNs), divided into those expressing dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R). Optogenetic activation of D2-MSNs increased motivation, whereas inhibition of these neurons produced the opposite effect. Yet, it is still unclear how activation of D2-MSNs affects other local neurons/interneurons or input terminals and how this contributes for motivation enhancement. To answer this question, in this work we combined optogenetic modulation of D2-MSNs with in loco pharmacological delivery of specific neurotransmitter antagonists in rats. First, we showed that optogenetic activation of D2-MSNs increases motivation in a progressive ratio (PR) task. We demonstrated that this behavioral effect relies on cholinergic-dependent modulation of dopaminergic signalling of ventral tegmental area (VTA) terminals, which requires D1R and D2R signalling in the NAc. D2-MSN optogenetic activation decreased ventral pallidum (VP) activity, reducing the inhibitory tone to VTA, leading to increased dopaminergic activity. Importantly, optogenetic activation of D2-MSN terminals in the VP was sufficient to recapitulate the motivation enhancement. In summary, our data suggests that optogenetic stimulation of NAc D2-MSNs indirectly modulates VTA dopaminergic activity, contributing for increased motivation. Moreover, both types of dopamine receptors signalling in the NAc are required in order to produce the positive behavioral effects. PMID:29780881

  20. Folate receptor-specific, redox-responsive mesoporous silica nanoparticles for the simultaneous delivery of cisplatin and gemcitabine to treat cancer

    NASA Astrophysics Data System (ADS)

    Fink, Eric Douglas

    Nanoparticles are an innovative platform for cancer treatment that reduces systemic toxicity and allows for active targeting of tumor sites to enhance the therapeutic efficacy. Mesoporous silica nanoparticles (MSNs) have emerged as an attractive drug delivery system due to their high surface area, vast functionalization potential, and biocompatibility. The main goal of this project is to develop a target-specific stimuli-responsive MSN based drug delivery system for the simultaneous delivery of cisplatin and gemcitabine. Both drugs were chemically attached to the MSNs via stimuli-responsive linkers that respond to the high reducing environment and low pH characteristic of cancer cells. The MSN materials fabricated in this work were successfully synthesized and characterized with a wide variety of spectroscopic and microscopic techniques. The loading of cisplatin and gemcitabine and their release profile under high reducing conditions were determined using atomic absorption (AA) and UV-vis spectroscopy, respectively. In vitro toxicity studies were performed on human cervical cancer (HeLa) cells in the presence of different ratios of cisplatin/gemcitabine drugs to determine the best ratio to kill HeLa cells. Based on this data, MSN materials carrying individual drugs and the corresponding combinatorial nanoparticles were fabricated and their in vitro cytotoxicity evaluated in HeLa and pancreatic cancer cells (AsPC1 and BxPC-3). The next step in this project was to further modify with folic acid to enhance its targeting ability toward cancer cells overexpressing folate receptors.

  1. Cognitive mapping in mental time travel and mental space navigation.

    PubMed

    Gauthier, Baptiste; van Wassenhove, Virginie

    2016-09-01

    The ability to imagine ourselves in the past, in the future or in different spatial locations suggests that the brain can generate cognitive maps that are independent of the experiential self in the here and now. Using three experiments, we asked to which extent Mental Time Travel (MTT; imagining the self in time) and Mental Space Navigation (MSN; imagining the self in space) shared similar cognitive operations. For this, participants judged the ordinality of real historical events in time and in space with respect to different mental perspectives: for instance, participants mentally projected themselves in Paris in nine years, and judged whether an event occurred before or after, or, east or west, of where they mentally stood. In all three experiments, symbolic distance effects in time and space dimensions were quantified using Reaction Times (RT) and Error Rates (ER). When self-projected, participants were slower and were less accurate (absolute distance effects); participants were also faster and more accurate when the spatial and temporal distances were further away from their mental viewpoint (relative distance effects). These effects show that MTT and MSN require egocentric mapping and that self-projection requires map transformations. Additionally, participants' performance was affected when self-projection was made in one dimension but judgements in another, revealing a competition between temporal and spatial mapping (Experiment 2 & 3). Altogether, our findings suggest that MTT and MSN are separately mapped although they require comparable allo- to ego-centric map conversion. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Linkage Determination of Linear Oligosaccharides by MSn (n > 2) Collision-Induced Dissociation of Z1 Ions in the Negative Ion Mode

    NASA Astrophysics Data System (ADS)

    Konda, Chiharu; Bendiak, Brad; Xia, Yu

    2014-02-01

    Obtaining unambiguous linkage information between sugars in oligosaccharides is an important step in their detailed structural analysis. An approach is described that provides greater confidence in linkage determination for linear oligosaccharides based on multiple-stage tandem mass spectrometry (MSn, n >2) and collision-induced dissociation (CID) of Z1 ions in the negative ion mode. Under low energy CID conditions, disaccharides 18O-labeled on the reducing carbonyl group gave rise to Z1 product ions (m/z 163) derived from the reducing sugar, which could be mass-discriminated from other possible structural isomers having m/z 161. MS3 CID of these m/z 163 ions showed distinct fragmentation fingerprints corresponding to the linkage types and largely unaffected by sugar unit identities or their anomeric configurations. This unique property allowed standard CID spectra of Z1 ions to be generated from a small set of disaccharide samples that were representative of many other possible isomeric structures. With the use of MSn CID (n = 3 - 5), model linear oligosaccharides were dissociated into overlapping disaccharide structures, which were subsequently fragmented to form their corresponding Z1 ions. CID data of these Z1 ions were collected and compared with the standard database of Z1 ion CID using spectra similarity scores for linkage determination. As the proof-of-principle tests demonstrated, we achieved correct determination of individual linkage types along with their locations within two trisaccharides and a pentasaccharide.

  3. Becoming Music Teacher Educators: Learning from and with Each Other in a Professional Development Community

    ERIC Educational Resources Information Center

    Pellegrino, Kristen; Sweet, Bridget; Derges Kastner, Julie; Russell, Heather A.; Reese, Jill

    2014-01-01

    During this heuristic phenomenological inquiry, we examined our lived experiences as five women (three doctoral students, two early career faculty) in the process of becoming music teacher educators participating in a year-long, online, group-facilitated professional development community (PDC). Data included recorded meetings via Skype, journal…

  4. Intercultural Competence in Synchronous Communication between Native and Non-Native Speakers of Spanish

    ERIC Educational Resources Information Center

    Fernández, Susana S.; Pozzo, María Isabel

    2017-01-01

    This paper discusses to what extent synchronous communication via Skype by Argentine university students of History and Danish university students of Spanish contributed to fostering intercultural competence in the two groups of participants. Intercultural gains are considered both as part of the planned tasks to be solved by the participants…

  5. Teaching and Assessing Doctor-Patient Communication Using Remote Standardized Patients and SKYPE: Feedback from Medical Residents

    ERIC Educational Resources Information Center

    Horber, Dot; Langenau, Erik E.; Kachur, Elizabeth

    2014-01-01

    Teaching and assessing doctor-patient communication has become a priority in medical education. This pilot study evaluated resident physicians' perceptions of teaching and assessing doctor-patient communication skills related to pain management using a web-based format. Fifty-nine resident physicians completed four doctor-patient clinical…

  6. How Social Media Can and Should Impact Higher Education

    ERIC Educational Resources Information Center

    Blankenship, Mark

    2011-01-01

    Interactive, community-focused online tools--like Skype, Twitter, Facebook, YouTube, blogs, wikis, and the educational software Blackboard--are becoming so dominant in the classroom that it's hard to imagine any professor or student making it through a week without them. Consider a recent survey conducted by the Babson Survey Research Group in…

  7. Bridging the Hemispheres through the Use of Technology: International Collaboration in Social Work Training

    ERIC Educational Resources Information Center

    Rautenbach, John Victor; Black-Hughes, Christine

    2012-01-01

    The social work programs of the University of Fort Hare, East London, South Africa, and Minnesota State University, Mankato, United States, began using various technologies in 2007 to facilitate interaction. This project included conducting practicum supervision and seminars via videoconferencing (using Breeze, Adobe Connect, and Skype) and…

  8. Teaching Lab Science Courses Online: Resources for Best Practices, Tools, and Technology

    ERIC Educational Resources Information Center

    Jeschofnig, Linda; Jeschofnig, Peter

    2011-01-01

    "Teaching Lab Science Courses Online" is a practical resource for educators developing and teaching fully online lab science courses. First, it provides guidance for using learning management systems and other web 2.0 technologies such as video presentations, discussion boards, Google apps, Skype, video/web conferencing, and social media…

  9. Crossing the Aisle: Conversations about Collaboration

    ERIC Educational Resources Information Center

    Powell, Mark

    2011-01-01

    This article presents edited transcripts of separate Skype conversations with Richard Ungerer, AMS executive director, in his office at AMS headquarters in New York and Andre Roberfroid, president of AMI, at his home in Vetraz-Monthoux, France. It also presents a discussion of the ways the two organizations can join forces to strengthen the…

  10. Mutually Beneficial Foreign Language Learning: Creating Meaningful Interactions through Video-Synchronous Computer-Mediated Communication

    ERIC Educational Resources Information Center

    Kato, Fumie; Spring, Ryan; Mori, Chikako

    2016-01-01

    Providing learners of a foreign language with meaningful opportunities for interactions, specifically with native speakers, is especially challenging for instructors. One way to overcome this obstacle is through video-synchronous computer-mediated communication tools such as Skype software. This study reports quantitative and qualitative data from…

  11. Internet Audio Products (3/3)

    ERIC Educational Resources Information Center

    Schwartz, Linda; de Schutter, Adrienne; Fahrni, Patricia; Rudolph, Jim

    2004-01-01

    Two contrasting additions to the online audio market are reviewed: "iVocalize", a browser-based audio-conferencing software, and "Skype", a PC-to-PC Internet telephone tool. These products are selected for review on the basis of their success in gaining rapid popular attention and usage during 2003-04. The "iVocalize" review emphasizes the…

  12. Telehealth: Families Finding Ways to Connect in Rural Colorado

    ERIC Educational Resources Information Center

    Kaiser, Kristen

    2011-01-01

    JFK Partners, at the University of Colorado Denver, School of Medicine, is currently implementing a study on the use of telehealth (receiving treatment or services using videoconferencing technology, such as Skype) and youth with autism spectrum disorder (ASD) and anxiety. The study is an exploratory grant from Health Resources and Services…

  13. Skype Me! Socially Contingent Interactions Help Toddlers Learn Language

    ERIC Educational Resources Information Center

    Roseberry, Sarah; Hirsh-Pasek, Kathy; Golinkoff, Roberta M.

    2014-01-01

    Language learning takes place in the context of social interactions, yet the mechanisms that render social interactions useful for learning language remain unclear. This study focuses on whether social contingency might support word learning. Toddlers aged 24-30 months (N = 36) were exposed to novel verbs in one of three conditions: live…

  14. Exploring Global Competence with Managers in India, Japan, and the Netherlands: A Qualitative Study

    ERIC Educational Resources Information Center

    Ras, Gerard J. M.

    2011-01-01

    This qualitative study explores the meaning of global competence for global managers in three different countries. Thirty interviews were conducted with global managers in India, Japan and the Netherlands through Skype, an internet based software. Findings are reported by country in five major categories: country background, personal…

  15. [The support system for dementia patient and their caregiver with Skype and webcam].

    PubMed

    Hori, Miyako; Kubota, Masakazu; Kinoshita, Ayae

    2008-12-01

    The increase in the number of people suffering from dementia because of aging is a serious problem for caregivers since the feature of this pathology is irreversible and advancing. We designed an intervention study with Skype and webcam for patient with dementia being cared at home by their caregiver to prevent a further memory deterioration (seriousness of dementia) and to reduce a care burden as well. For a period of 12 weeks, a 4-patient-caregiver pair communicated with a hospital nurse through the computer for 30 minutes once a week. The patient and the caregiver worked as a pair. From the beginning of the intervention period, the intervention group and control group (n = 4) were assessed with cognitive scale, ADL scale, care burden scale and depression scale for the caregiver, and the like once in 4 weeks for 12 weeks. The initial report on the 8th week showed signs of improvement on the intervention group in HDS-R, also it improved the scale of moral of the caregiver as their scale of depression decreased.

  16. Direct Analysis in Real Time-Mass Spectrometry for the Rapid Detection of Metabolites of Aconite Alkaloids in Intestinal Bacteria

    NASA Astrophysics Data System (ADS)

    Li, Xue; Hou, Guangyue; Xing, Junpeng; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

    2014-12-01

    In the present work, direct analysis of real time ionization combined with multi-stage tandem mass spectrometry (DART-MSn) was used to investigate the metabolic profile of aconite alkaloids in rat intestinal bacteria. A total of 36 metabolites from three aconite alkaloids were identified by using DART-MSn, and the feasibility of quantitative analysis of these analytes was examined. Key parameters of the DART ion source, such as helium gas temperature and pressure, the source-to-MS distance, and the speed of the autosampler, were optimized to achieve high sensitivity, enhance reproducibility, and reduce the occurrence of fragmentation. The instrument analysis time for one sample can be less than 10 s for this method. Compared with ESI-MS and UPLC-MS, the DART-MS is more efficient for directly detecting metabolic samples, and has the advantage of being a simple, high-speed, high-throughput method.

  17. Simultaneous Analysis of Anthocyanin and Non-Anthocyanin Flavonoid in Various Tissues of Different Lotus (Nelumbo) Cultivars by HPLC-DAD-ESI-MSn

    PubMed Central

    Chen, Sha; Xiang, Yue; Deng, Jiao; Liu, Yanling; Li, Shaohua

    2013-01-01

    A validated HPLC-DAD-ESI-MSn method for the analysis of non-anthocyanin flavonoids was applied to nine different tissues of twelve lotus genotypes of Nelumbo nucifera and N. lutea, together with an optimized anthocyanin extraction and separation protocol for lotus petals. A total of five anthocyanins and twenty non-anthocyanin flavonoids was identified and quantified. Flavonoid contents and compositions varied with cultivar and tissue and were used as a basis to divide tissues into three groups characterized by kaempferol and quercetin derivatives. Influences on flower petal coloration were investigated by principal components analyses. High contents of kaempferol glycosides were detected in the petals of N. nucifera while high quercetin glycoside concentrations occurred in N. lutea. Based on these results, biosynthetic pathways leading to specific compounds in lotus tissues are deduced through metabolomic analysis of different genotypes and tissues and correlations among flavonoid compounds. PMID:23646125

  18. Characterization of primaquine imidazolidin-4-ones with antimalarial activity by electrospray ionization-ion trap mass spectrometry

    NASA Astrophysics Data System (ADS)

    Vale, Nuno; Moreira, Rui; Gomes, Paula

    2008-02-01

    The extensive characterization by electrospray ionization-ion trap mass spectrometry (ESI-MSn) of 20 imidazolidin-4-ones derived from the antimalarial primaquine was well obtained. These compounds are being under investigation as potential antimalarials, as they have been previously found to be active against rodent P. berghei malaria and to be highly stable under physiological conditions. Experiments by collision-induced dissociation (CID) in the nozzle-skimmer region or by tandem-MS have shown the title compounds to be remarkably stable. Mechanisms are proposed to explain the major fragmentations observed in ESI-MSn experiments. Overall, this work represents an unprecedented contribution to a deeper insight into imidazolidin-4-one antimalarials based on a classic 8-aminoquinolinic scaffold. Data herein reported and discussed may be an useful guide for future studies on therapeutically relevant molecules possessing either the 8-aminoquinoline or the imidazolidin-4-one motifs.

  19. Evaluation and comparison of health care Work Environment Scale in military settings.

    PubMed

    Maloney, J P; Anderson, F D; Gladd, D L; Brown, D L; Hardy, M A

    1996-05-01

    The purpose of this study was to describe health care providers' perceptions of their work environment at a large U.S. Army medical center, and to compare the findings to other military medical centers. The sample (N = 112) consisted of the professional nursing staff working on the nine inpatient units. The Work Environmental Scale (WES) was used to measure perceptions of the workplace relative to gender, position (head nurses, staff nurses, and agency nurses), specialty nursing (intensive care unit [ICU] versus non-ICU), education (MSN, BSN, and ADN), and patterns of differences between the WES subscales of four military medical centers. Results of the study indicate that there were no significant gender differences. Head nurses, non-ICU nurses, and MSN nurses perceived their environment more positively. There were significant differences in the WES subscales between the military hospitals. Implications for nursing using the WES were recommended.

  20. Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors.

    PubMed

    Quintana, Albert; Sanz, Elisenda; Wang, Wengang; Storey, Granville P; Güler, Ali D; Wanat, Matthew J; Roller, Bryan A; La Torre, Anna; Amieux, Paul S; McKnight, G Stanley; Bamford, Nigel S; Palmiter, Richard D

    2012-11-01

    The striatum regulates motor control, reward and learning. Abnormal function of striatal GABAergic medium spiny neurons (MSNs) is believed to contribute to the deficits in these processes that are observed in many neuropsychiatric diseases. The orphan G protein-coupled receptor GPR88 is robustly expressed in MSNs and is regulated by neuropharmacological drugs, but its contribution to MSN physiology and behavior is unclear. We found that, in the absence of GPR88, MSNs showed increased glutamatergic excitation and reduced GABAergic inhibition, which promoted enhanced firing rates in vivo, resulting in hyperactivity, poor motor coordination and impaired cue-based learning in mice. Targeted viral expression of GPR88 in MSNs rescued the molecular and electrophysiological properties and normalized behavior, suggesting that aberrant MSN activation in the absence of GPR88 underlies behavioral deficits and its dysfunction may contribute to behaviors observed in neuropsychiatric disease.

  1. Task-Based Oral Computer-Mediated Communication and L2 Vocabulary Acquisition

    ERIC Educational Resources Information Center

    Yanguas, Inigo

    2012-01-01

    The present study adds to the computer-mediated communication (CMC) literature by exploring oral learner-to-learner interaction using Skype, a free and widely used Internet software program. In particular, this task-based study has a two-fold goal. Firstly, it explores possible differences between two modes of oral CMC (audio and video) and…

  2. Text Chat during Video/Audio Conferencing Lessons: Scaffolding or Getting in the Way?

    ERIC Educational Resources Information Center

    Kozar, Olga

    2016-01-01

    Private online language tutoring is growing in popularity. An important prerequisite for development of effective pedagogies in this context is a good understanding of how different modalities can be combined. This study provides a detailed account of how several experienced private online teachers use text chat in their Skype-based English…

  3. The Use of the Webcam for Teaching a Foreign Language in a Desktop Videoconferencing Environment

    ERIC Educational Resources Information Center

    Develotte, Christine; Guichon, Nicolas; Vincent, Caroline

    2010-01-01

    This paper explores how language teachers learn to teach with a synchronous multimodal setup ("Skype"), and it focuses on their use of the webcam during the pedagogical interaction. First, we analyze the ways that French graduate students learning to teach online use the multimodal resources available in a desktop videoconferencing (DVC)…

  4. Teaching a Foreign Language in a Desktop Videoconferencing Environment

    ERIC Educational Resources Information Center

    Kotula, Krzysztof

    2016-01-01

    This paper aims to explore how language instructors teach with a synchronous multimodal setup (Skype). It reports on findings from research which evaluated how teachers use technologies to enable them to work in distance learning contexts. A total of 124 teachers (86 female and 38 male), offering online private lessons, were asked to complete a…

  5. Can You Skype Me Now? Developing Teachers' Classroom Management Practices through Virtual Coaching

    ERIC Educational Resources Information Center

    Rock, Marcia L.; Schoenfeld, Naomi; Zigmond, Naomi; Gable, Robert A.; Gregg, Madeleine; Ploessl, Donna M.; Salter, Ashley

    2013-01-01

    In this article, situated within the context of a larger ongoing study on the efficacy of Web-based virtual coaching, these authors describe a virtual coaching model for maximizing pre- and in-service teachers' effective use of evidence-based classroom management practices. They also provide a brief summary of previous results obtained…

  6. Integrating Social Media into the Classroom Curriculum

    ERIC Educational Resources Information Center

    Abe, Paige; Jordan, Nickolas A.

    2013-01-01

    Over the past decade, social media and technology have become prevalent in the day-to-day life of many college and university students. From Skype to Twitter to Facebook, these modes of social media are often used as tools to keep in touch with friends and family, socialize, and share personal opinions. Considering that such a high percentage of…

  7. Teaching and Learning Foreign Languages via System of "Voice over Internet Protocol" and Language Interactions Case Study: Skype

    ERIC Educational Resources Information Center

    Wahid, Wazira Ali Abdul; Ahmed, Eqbal Sulaiman; Wahid, Muntaha Ali Abdul

    2015-01-01

    This issue expresses a research study based on the online interactions of English teaching specially conversation through utilizing VOIP (Voice over Internet Protocol) and cosmopolitan online theme. Data has been achieved by interviews. Simplifiers indicate how oral tasks require to be planned upon to facilitate engagement models propitious to…

  8. Using Digital Video Production to Meet the Common Core Standards

    ERIC Educational Resources Information Center

    Nichols, Maura

    2012-01-01

    The implementation of the Common Core Standards has just begun and these standards will impact a generation that communicates with technology more than anything else. Texting, cell phones, Facebook, YouTube, Skype, etc. are the ways they speak with their friends and the world. The Common Core Standards recognize this. According to the Common Core…

  9. Communication Strategies in a Telecollaboration Project with a Focus on Latin American History

    ERIC Educational Resources Information Center

    Fernández, Susana S.

    2016-01-01

    This paper will present and discuss the linguistic challenges that Argentinian university students of history and Danish university students of Spanish met during the course of a telecollaboration project based on synchronous communication in Skype. The purpose of this discussion is to identify linguistic pitfalls and the solutions adopted by both…

  10. The Effects of Virtual Coaching on Teacher Candidates' Perceptions and Concerns Regarding On-Demand Corrective Feedback

    ERIC Educational Resources Information Center

    Wake, Donna; Dailey, Debbie; Cotabish, Alicia; Benson, Tammy

    2017-01-01

    A virtual coaching intervention utilizing Skype and Bluetooth (Bug-in-the-Ear) technology provided immediate corrective feedback to non-traditional teacher candidates during a semester-long internship experience. Participants completed their student teaching internship as a requirement of a teacher preparation program at a mid-size Southeastern…

  11. YouTube, Fanvids, Forums, Vlogs and Blogs: Informal Music Learning in a Convergent on- and Offline Music Community

    ERIC Educational Resources Information Center

    Waldron, Janice

    2013-01-01

    In this paper I examine the music learning and teaching in the Banjo Hangout online music community (www.banjohangout.org/) using cyber ethnographic methods of interview and participant observation conducted entirely through computer-mediated communication, which includes Skype and written narrative texts--forum posts, email, chat room…

  12. Perceptions of Webcam Use by Experienced Online Teachers and Learners: A Seeming Disconnect between Research and Practice

    ERIC Educational Resources Information Center

    Kozar, Olga

    2016-01-01

    Videoconferencing tools, like Skype, etc., are being increasingly used in language education worldwide. Despite assumed socio-affective and pedagogical benefits of using webcams in synchronous online language lessons, such as the feeling of co-presence or the possibilities of non-verbal communication, little is known about attitudes held by…

  13. Reframing Pedagogy While Teaching about Teaching Online: A Collaborative Self-Study

    ERIC Educational Resources Information Center

    Fletcher, Tim; Bullock, Shawn M.

    2015-01-01

    The purpose of this paper is to use collaborative self-study to analyze and describe our experiences of teaching about teaching in a digital, online environment. Data were gathered from reflective journal entries, emails and monthly Skype calls. Our findings indicate that the perceived disembodiment of teaching and learning online affected how we…

  14. Facilitating Second Language Learners' Listening Comprehension with Second Life and Skype

    ERIC Educational Resources Information Center

    Levak, Natasha; Son, Jeong-Bae

    2017-01-01

    Learning how to comprehend while listening to a second language is often considered by learners to be a difficult process that can lead to anxiety when trying to communicate (Graham, 2006; Graham & Macaro, 2008). Computer-mediated communication (CMC) can be used to assist in increasing access to native speakers and opportunities to listen.…

  15. Investigating the ICT Use and Needs of "Digital Natives" in Learning English at a Taiwanese University

    ERIC Educational Resources Information Center

    Ko, Chao-Jung; Thang, Siew Ming; Ou, Shu-chen

    2014-01-01

    This article reports key findings of a study which investigated the use of technology by 569 "digital natives" students for English Language learning and recreational purposes. Their views on the applicability of technological tools such as Facebook, blogging and Skype for English Language teaching and learning were also investigated.…

  16. The Effects of Medium Spiny Neuron Morphologcial Changes on Basal Ganglia Network under External Electric Field: A Computational Modeling Study.

    PubMed

    Zhang, Xiaohan; Liu, Shenquan; Zhan, Feibiao; Wang, Jing; Jiang, Xiaofang

    2017-01-01

    The damage of dopaminergic neurons that innervate the striatum has been considered to be the proximate cause of Parkinson's disease (PD). In the dopamine-denervated state, the loss of dendritic spines and the decrease of dendritic length may prevent medium spiny neuron (MSN) from receiving too much excitatory stimuli from the cortex, thereby reducing the symptom of Parkinson's disease. However, the reduction in dendritic spine density obtained by different experiments is significantly different. We developed a biological-based network computational model to quantify the effect of dendritic spine loss and dendrites tree degeneration on basal ganglia (BG) signal regulation. Through the introduction of error index (EI), which was used to measure the attenuation of the signal, we explored the amount of dendritic spine loss and dendritic trees degradation required to restore the normal regulatory function of the network, and found that there were two ranges of dendritic spine loss that could reduce EI to normal levels in the case of dopamine at a certain level, this was also true for dendritic trees. However, although these effects were the same, the mechanisms of these two cases were significant difference. Using the method of phase diagram analysis, we gained insight into the mechanism of signal degradation. Furthermore, we explored the role of cortex in MSN morphology changes dopamine depletion-induced and found that proper adjustments to cortical activity do stop the loss in dendritic spines induced by dopamine depleted. These results suggested that modifying cortical drive onto MSN might provide a new idea on clinical therapeutic strategies for Parkinson's disease.

  17. The Effect of Dynamic Assessment in Synchronous Computer-Mediated Communication on Iranian EFL Learners' Listening Comprehension Ability at Upper-Intermediate Level

    ERIC Educational Resources Information Center

    Heidar, Davood Mashhadi; Afghari, Akbar

    2015-01-01

    The present paper concentrates on a web-based inquiry in the synchronous computer-mediated communication (SCMC) via Web 2.0 technologies of Talk and Write and Skype. It investigates EFL learners' socio-cognitive progress through dynamic assessment (DA), which follows Vygotsky's inclination for supportive interchange in the zone of proximal…

  18. "Supersizing" the College Classroom: How One Instructor Teaches 2,670 Students

    ERIC Educational Resources Information Center

    Parry, Marc

    2012-01-01

    In October, Myanmar's pro-democracy leader, Aung San Suu Kyi, got a quirky request on YouTube. A hyperactive instructor in a plaid jacket posted a video inviting her to do a Skype interview with his "World Regions" geography class at Virginia Tech. Ms. Suu Kyi, a Nobel Peace Prize laureate often compared to Nelson Mandela, might have…

  19. Attending a Presentation at a Distance in Real-Time via Skype

    ERIC Educational Resources Information Center

    Michels, Barbara J.; Chang, Ching-Wen

    2010-01-01

    "Necessity is the mother of invention," as the saying goes, and in this case, it surely was. A telecommuting faculty for a Midwest public university wanted to see a graduate student's presentation as a guest speaker in an instructional technology course on campus. However, this faculty lives in another state, so that was impossible. As a daily…

  20. Focusing on Culture-Related Episodes in a Teletandem Interaction between a Brazilian and an American Student

    ERIC Educational Resources Information Center

    Zakir, Maisa A.; Funo, Ludmila B. A.; Telles, João A.

    2016-01-01

    Teletandem is a telecollaborative learning context that involves pairs of native (or competent) speakers of different languages interacting through voice, text and webcam image. Using Skype, each participant plays the role of learner for half an hour, speaking and practising the language of his/her partner. This paper focuses on a teletandem…

  1. Why Teach Abroad: Two American Teachers Explain Their Motivations and Experiences Teaching in Bulgaria

    ERIC Educational Resources Information Center

    Potash, Betsy; Potash, Brett

    2011-01-01

    A Fulbright poster on the bulletin board, a Search Associates flier in the mailbox, a rumor of something different--everyone has heard about teaching abroad. But is it worth filling out all that paperwork, installing Skype on the family's computers, and learning a new language? In this article, two American teachers explain their motivations and…

  2. Applications of Speech-to-Text Recognition and Computer-Aided Translation for Facilitating Cross-Cultural Learning through a Learning Activity: Issues and Their Solutions

    ERIC Educational Resources Information Center

    Shadiev, Rustam; Wu, Ting-Ting; Sun, Ai; Huang, Yueh-Min

    2018-01-01

    In this study, 21 university students, who represented thirteen nationalities, participated in an online cross-cultural learning activity. The participants were engaged in interactions and exchanges carried out on Facebook® and Skype® platforms, and their multilingual communications were supported by speech-to-text recognition (STR) and…

  3. [The effect of videophone communication (with skype and webcam)for elderly patients with dementia and their caregivers].

    PubMed

    Hori, Miyako; Kubota, Masakazu; Ando, Koichi; Kihara, Takeshi; Takahashi, Ryosuke; Kinoshita, Ayae

    2009-12-01

    We conducted an intervention study to clarify how effectively videophone (Skype) was used in the communication for elderly patients with dementia cared at home and their caregivers. For a period of 12 weeks, a patient-caregiver pair(n = 6) communicated with a nurse via computer for 30 minutes once a week. The patient and the caregiver worked as a pair. Before and after the 12-week study period started, the intervention and control group (n = 7) patients were assessed with a cognitive scale (HDS-R), VAS, and a depression scale (SDS) for caregivers. The result on the 12th week showed signs of improvement on the intervention group in HDS-R and SDS. The intervention group kept no change in VAS, an expression of subjective feelings of happiness. Meanwhile, the control group significantly decreased in VAS. By the questionnaire for caregivers, many said that the videophone communication was a pleasure of the family and resulted in more family exchanges. Therefore, we consider that a videophone communication is useful for cognitive rehabilitation and the feelings of the patient, and it is also good for a satisfaction of the family.

  4. An online positive parenting skills programme for paediatric traumatic brain injury: feasibility and parental satisfaction.

    PubMed

    Antonini, Tanya N; Raj, Stacey P; Oberjohn, Karen S; Wade, Shari L

    2012-09-01

    We examined the feasibility of and parental satisfaction with a training programme for parents with children who had suffered traumatic brain injury (TBI). Families who did not have a home computer and/or webcam were loaned the necessary equipment. Skype was used for videoconferencing. After the initial treatment session in the family's home, the remaining nine sessions were conducted online. Each session had two parts: (1) a self-guided web session with information about a particular skill; (2) a videoconference session with the therapist. Three of the 20 families (15%) dropped out prior to the final 6-month follow-up visit. Of the remaining 17 families, 13 (65% of those enrolled) completed 9-14 sessions. Almost all of the caregivers (87%) said that the Skype sessions were helpful compared to a conventional office visit. Almost all parents were satisfied with the programme and the technology that was used. Parental satisfaction with the programme was not influenced by prior computer ownership or comfort with technology. The programme appears to be feasible for a wide range of parents of children with TBI and provides an alternative to conventional office-based sessions that may not be accessible to all families.

  5. [At-home music therapy intervention using video phone (Skype) for elderly people with dementia].

    PubMed

    Hori, Miyako; Iizuka, Mieko; Nakamura, Michikazu; Aiba, Ikuko; Saito, Yufuko; Kubota, Masakazu; Urabe, Mie; Kinoshita, Ayae

    2014-12-01

    There are various nonpharmacological therapies available for elderly people with dementia, and these can improve quality of life and the behavioral and psychological symptoms of dementia (BPSD) that appear throughout the progression of the disease. Since a substantial number of effects have been reported for music therapy, we focused on this nonpharmacological intervention. Generally, musical therapy is provided collectively in facilities. However, the music used in this context may not consider the preferences and music abilities of each person. Therefore, in this study we created made-to-order music CDs that accounted for each participant's musical preferences and abilities. Utilizing the CDs, we conducted an intervention study of music therapy using a video phone (Skype) that elderly people with dementia can use at home. An advantage of conducting music therapy for individuals with dementia using a video phone is that those who have difficulty going to the hospital or participating in dementia-related therapy groups can participate in therapy in a familiar place. The results of this intervention showed that participants demonstrated signs of improvement as measured by the smile degree(Smile scan)and Behavior Pathology in Alzheimer's Disease (BEHAVE-AD) scale.

  6. Introducing technology into medical education: two pilot studies.

    PubMed

    George, Paul; Dumenco, Luba; Dollase, Richard; Taylor, Julie Scott; Wald, Hedy S; Reis, Shmuel P

    2013-12-01

    Educators are integrating new technology into medical curriculum. The impact of newer technology on educational outcomes remains unclear. We aimed to determine if two pilot interventions, (1) introducing iPads into problem-based learning (PBL) sessions and (2) online tutoring would improve the educational experience of our learners. We voluntarily assigned 26 second-year medical students to iPad-based PBL sessions. Five students were assigned to Skype for exam remediation. We performed a mixed-method evaluation to determine efficacy. Pilot 1: Seventeen students completed a survey following their use of an iPad during the second-year PBL curriculum. Students noted the iPad allows for researching information in real time, annotating lecture notes, and viewing sharper images. Data indicate that iPads have value in medical education and are a positive addition to the curriculum. Pilot 2: Students agreed that online tutoring is at least or more effective than in-person tutoring. In our pilot studies, students experienced that iPads and Skype are beneficial in medical education and can be successfully employed in areas such as PBL and remediation. Educators should continue to further examine innovative opportunities for introducing technology into medical education. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. A pilot study of audiovisual family meetings in the intensive care unit.

    PubMed

    de Havenon, Adam; Petersen, Casey; Tanana, Michael; Wold, Jana; Hoesch, Robert

    2015-10-01

    We hypothesized that virtual family meetings in the intensive care unit with conference calling or Skype videoconferencing would result in increased family member satisfaction and more efficient decision making. This is a prospective, nonblinded, nonrandomized pilot study. A 6-question survey was completed by family members after family meetings, some of which used conference calling or Skype by choice. Overall, 29 (33%) of the completed surveys came from audiovisual family meetings vs 59 (67%) from control meetings. The survey data were analyzed using hierarchical linear modeling, which did not find any significant group differences between satisfaction with the audiovisual meetings vs controls. There was no association between the audiovisual intervention and withdrawal of care (P = .682) or overall hospital length of stay (z = 0.885, P = .376). Although we do not report benefit from an audiovisual intervention, these results are preliminary and heavily influenced by notable limitations to the study. Given that the intervention was feasible in this pilot study, audiovisual and social media intervention strategies warrant additional investigation given their unique ability to facilitate communication among family members in the intensive care unit. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Optimizing Conferencing Freeware

    ERIC Educational Resources Information Center

    Baggaley, Jon; Klaas, Jim; Wark, Norine; Depow, Jim

    2005-01-01

    The increasing range of options provided by two popular conferencing freeware products, "Yahoo Messenger" and "MSN Messenger," are discussed. Each tool contains features designed primarily for entertainment purposes, which can be customized for use in online education. This report provides suggestions for optimizing the educational potential of…

  9. Input dependent cell assembly dynamics in a model of the striatal medium spiny neuron network.

    PubMed

    Ponzi, Adam; Wickens, Jeff

    2012-01-01

    The striatal medium spiny neuron (MSN) network is sparsely connected with fairly weak GABAergic collaterals receiving an excitatory glutamatergic cortical projection. Peri-stimulus time histograms (PSTH) of MSN population response investigated in various experimental studies display strong firing rate modulations distributed throughout behavioral task epochs. In previous work we have shown by numerical simulation that sparse random networks of inhibitory spiking neurons with characteristics appropriate for UP state MSNs form cell assemblies which fire together coherently in sequences on long behaviorally relevant timescales when the network receives a fixed pattern of constant input excitation. Here we first extend that model to the case where cortical excitation is composed of many independent noisy Poisson processes and demonstrate that cell assembly dynamics is still observed when the input is sufficiently weak. However if cortical excitation strength is increased more regularly firing and completely quiescent cells are found, which depend on the cortical stimulation. Subsequently we further extend previous work to consider what happens when the excitatory input varies as it would when the animal is engaged in behavior. We investigate how sudden switches in excitation interact with network generated patterned activity. We show that sequences of cell assembly activations can be locked to the excitatory input sequence and outline the range of parameters where this behavior is shown. Model cell population PSTH display both stimulus and temporal specificity, with large population firing rate modulations locked to elapsed time from task events. Thus the random network can generate a large diversity of temporally evolving stimulus dependent responses even though the input is fixed between switches. We suggest the MSN network is well suited to the generation of such slow coherent task dependent response which could be utilized by the animal in behavior.

  10. Input Dependent Cell Assembly Dynamics in a Model of the Striatal Medium Spiny Neuron Network

    PubMed Central

    Ponzi, Adam; Wickens, Jeff

    2012-01-01

    The striatal medium spiny neuron (MSN) network is sparsely connected with fairly weak GABAergic collaterals receiving an excitatory glutamatergic cortical projection. Peri-stimulus time histograms (PSTH) of MSN population response investigated in various experimental studies display strong firing rate modulations distributed throughout behavioral task epochs. In previous work we have shown by numerical simulation that sparse random networks of inhibitory spiking neurons with characteristics appropriate for UP state MSNs form cell assemblies which fire together coherently in sequences on long behaviorally relevant timescales when the network receives a fixed pattern of constant input excitation. Here we first extend that model to the case where cortical excitation is composed of many independent noisy Poisson processes and demonstrate that cell assembly dynamics is still observed when the input is sufficiently weak. However if cortical excitation strength is increased more regularly firing and completely quiescent cells are found, which depend on the cortical stimulation. Subsequently we further extend previous work to consider what happens when the excitatory input varies as it would when the animal is engaged in behavior. We investigate how sudden switches in excitation interact with network generated patterned activity. We show that sequences of cell assembly activations can be locked to the excitatory input sequence and outline the range of parameters where this behavior is shown. Model cell population PSTH display both stimulus and temporal specificity, with large population firing rate modulations locked to elapsed time from task events. Thus the random network can generate a large diversity of temporally evolving stimulus dependent responses even though the input is fixed between switches. We suggest the MSN network is well suited to the generation of such slow coherent task dependent response which could be utilized by the animal in behavior. PMID:22438838

  11. Quality and relevance of master degree education for the professional development of nurses and midwives.

    PubMed

    Massimi, Azzurra; Marzuillo, Carolina; Di Muzio, Marco; Vacchio, Maria Rosaria; D'Andrea, Elvira; Villari, Paolo; De Vito, Corrado

    2017-06-01

    Advanced education in nursing is essential to provide safe, high quality and efficient health services in line with population needs. However, there is an almost complete lack of studies on how nurses view the usefulness of post-graduate education for their current employment and for professional advancement. To evaluate how nurse graduates view the quality, relevance and applicability of the knowledge and skills acquired during the Master of Science in Nursing (MSN) degree. Multicentre cross-sectional study. A multicenter cross-sectional study was carried out through an online questionnaire mailed (July 2014-June 2015) to 560 nurses who obtained the MSN degree from 23 Italian universities in the academic year 2010-2011. A total of 426 nurses completed the survey (response rate 76.1%), 80% of whom believed they had acquired knowledge and skills useful in their professional life after graduation. A multiple logistic regression model highlighted the characteristics of nurse graduates who judged the master's course relevant for their present role. In brief, they are expert nurses (OR=3.41, 95% CI=1.54-7.54) who achieved professional growth after the course (OR=5.25, 95% CI=2.67-10.33) and who judged the course very good or excellent (OR=2.16, 95% CI=1.04-4.52). Only 8% of the respondents achieved a full professional growth after the course. In Italy, MSN courses are able to provide a high level of skills and competencies. However, given the low rate of professional growth after the course, specific policies should increase the employment rates of new master's graduate nurses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Structural characterization of constituents with molecular diversity in fractions from Lysidice brevicalyx by liquid chromatography/diode-array detection/electrospray ionization tandem mass spectrometry and liquid chromatography/nuclear magnetic resonance.

    PubMed

    Qu, Jing; Hu, You-cai; Li, Jian-bei; Wang, Ying-hong; Zhang, Jin-lan; Abliz, Zeper; Yu, Shi-shan; Liu, Yun-bao

    2008-01-01

    A combination of electrospray ionization tandem mass spectrometry with high-performance liquid chromatography (HPLC/ESI-MSn), and hyphenation of liquid chromatography to nuclear magnetic resonance spectroscopy (HPLC/NMR), have been extensively utilized for on-line analysis of natural products, analyzing metabolite and drug impurity. In our last paper, we reported an on-line analytical method for structural identification of trace alkaloids in the same class. However, the structural types of the constituents in plants were various, such as flavanoids, terpenoids and steroids. It is important to establish an effective analytical method for on-line structural identification of constituents with molecular diversity in extracts of plants. So, in the present study, the fragmentation patterns of some isolated stilbenes, phloroglucinols and flavanoids from Lysidice rhodostegia were investigated by ESI-MSn. Their fragmentation rules and UV characteristics are summarized, and the relationship between the spectral characteristics, rules and the structures is described. According to the fragmentation rules, NMR and UV spectral characteristics, 24 constituents of different types in the fractions from L. brevicalyx of the same genus were structurally characterized on the basis of HPLC/HRMS, HPLC-UV/ESI-MSn, HPLC/1H NMR and HPLC/1H-1H COSY rapidly. Of these, six (10, 13, 14, 16, 17 and 23) are new compounds and all of them are reported from L. brevicalyx for the first time. The aim is to develop an effective analytical method for on-line structural identification of natural products with molecular diversity in plants, and to guide the rapid and direct isolation of novel compounds by chemical screening.

  13. Synchrony of forest responses to climate from the aspect of tree mortality in South Korea

    NASA Astrophysics Data System (ADS)

    Kim, M.; Lee, W. K.; Piao, D.; Choi, G. M.; Gang, H. U.

    2016-12-01

    Mortality is a key process in forest-stand dynamics. However, tree mortality is not well understood, particularly in relation to climatic factors. The objectives of this study were to: (i) determine the patterns of maximum stem number (MSN) per ha over dominant tree height from 5-year remeasurements of the permanent sample plots for temperate forests [Red pine (Pinus densiflora), Japanese larch (Larix kaempferi), Korean pine (Pinus koraiensis), Chinese cork oak (Quercus variabilis), and Mongolian oak (Quercus mongolica)] using Sterba's theory and Korean National Forest Inventory (NFI) data, (ii) develop a stand-level mortality (self-thinning) model using the MSN curve, and (iii) assess the impact of temperature on tree mortality in semi-variogram and linear regression models. The MSN curve represents the upper range of observed stem numbers per ha. The mortality model and validation statistic reveal significant differences between the observed data and the model predictions (R2 = 0.55-0.81), and no obvious dependencies or patterns that indicate systematic trends between the residuals and the independent variable. However, spatial autocorrelation was detected from residuals of coniferous species (Red pine, Japanese larch and Korean pine), but not of oak species (Chinese cork oak and Mongolian oak). Based on linear regression from residuals, we found that the mortality of coniferous forests tended to increase when the annual mean temperature increased. Conversely, oak mortality nonsignificantly decreased with increasing temperature. These findings indicate that enhanced tree mortality due to rising temperatures in response to climate change is possible, especially in coniferous forests, and are expected to contribute to policy decisions to support and forest management practices.

  14. Multilayer encapsulated mesoporous silica nanospheres as an oral sustained drug delivery system for the poorly water-soluble drug felodipine.

    PubMed

    Hu, Liang; Sun, Hongrui; Zhao, Qinfu; Han, Ning; Bai, Ling; Wang, Ying; Jiang, Tongying; Wang, Siling

    2015-02-01

    We used a combination of mesoporous silica nanospheres (MSN) and layer-by-layer (LBL) self-assembly technology to establish a new oral sustained drug delivery system for the poorly water-soluble drug felodipine. Firstly, the model drug was loaded into MSN, and then the loaded MSN were repeatedly encapsulated by chitosan (CHI) and acacia (ACA) via LBL self-assembly method. The structural features of the samples were studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption. The encapsulating process was monitored by zeta-potential and surface tension measurements. The physical state of the drug in the samples was characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). The influence of the multilayer with different number of layers on the drug release rate was studied using thermal gravimetric analysis (TGA) and surface tension measurement. The swelling effect and the structure changes of the multilayer were investigated to explore the relationship between the drug release behavior and the state of the multilayer under different pH conditions. The stability and mucosa adhesive ability of the prepared nanoparticles were also explored. After multilayer coating, the drug release rate was effectively controlled. The differences in drug release behavior under different pH conditions could be attributed to the different states of the multilayer. And the nanoparticles possessed good stability and strong mucosa adhesive ability. We believe that this combination offers a simple strategy for regulating the release rate of poorly water-soluble drugs and extends the pharmaceutical applications of inorganic materials and polymers. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. The Effects of Medium Spiny Neuron Morphologcial Changes on Basal Ganglia Network under External Electric Field: A Computational Modeling Study

    PubMed Central

    Zhang, Xiaohan; Liu, Shenquan; Zhan, Feibiao; Wang, Jing; Jiang, Xiaofang

    2017-01-01

    The damage of dopaminergic neurons that innervate the striatum has been considered to be the proximate cause of Parkinson's disease (PD). In the dopamine-denervated state, the loss of dendritic spines and the decrease of dendritic length may prevent medium spiny neuron (MSN) from receiving too much excitatory stimuli from the cortex, thereby reducing the symptom of Parkinson's disease. However, the reduction in dendritic spine density obtained by different experiments is significantly different. We developed a biological-based network computational model to quantify the effect of dendritic spine loss and dendrites tree degeneration on basal ganglia (BG) signal regulation. Through the introduction of error index (EI), which was used to measure the attenuation of the signal, we explored the amount of dendritic spine loss and dendritic trees degradation required to restore the normal regulatory function of the network, and found that there were two ranges of dendritic spine loss that could reduce EI to normal levels in the case of dopamine at a certain level, this was also true for dendritic trees. However, although these effects were the same, the mechanisms of these two cases were significant difference. Using the method of phase diagram analysis, we gained insight into the mechanism of signal degradation. Furthermore, we explored the role of cortex in MSN morphology changes dopamine depletion-induced and found that proper adjustments to cortical activity do stop the loss in dendritic spines induced by dopamine depleted. These results suggested that modifying cortical drive onto MSN might provide a new idea on clinical therapeutic strategies for Parkinson's disease. PMID:29123477

  16. Separate responses of karyopherins to glucose and amino acid availability regulate nucleocytoplasmic transport.

    PubMed

    Huang, Hsiao-Yun; Hopper, Anita K

    2014-09-15

    The importin-β family members (karyopherins) mediate the majority of nucleocytoplasmic transport. Msn5 and Los1, members of the importin-β family, function in tRNA nuclear export. tRNAs move bidirectionally between the nucleus and the cytoplasm. Nuclear tRNA accumulation occurs upon amino acid (aa) or glucose deprivation. To understand the mechanisms regulating tRNA subcellular trafficking, we investigated whether Msn5 and Los1 are regulated in response to nutrient availability. We provide evidence that tRNA subcellular trafficking is regulated by distinct aa-sensitive and glucose-sensitive mechanisms. Subcellular distributions of Msn5 and Los1 are altered upon glucose deprivation but not aa deprivation. Redistribution of tRNA exportins from the nucleus to the cytoplasm likely provides one mechanism for tRNA nuclear distribution upon glucose deprivation. We extended our studies to other members of the importin-β family and found that all tested karyopherins invert their subcellular distributions upon glucose deprivation but not aa deprivation. Glucose availability regulates the subcellular distributions of karyopherins likely due to alteration of the RanGTP gradient since glucose deprivation causes redistribution of Ran. Thus nuclear-cytoplasmic distribution of macromolecules is likely generally altered upon glucose deprivation due to collapse of the RanGTP gradient and redistribution of karyopherins between the nucleus and the cytoplasm. © 2014 Huang and Hopper. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  17. A Strategy Combining Higher Energy C-Trap Dissociation with Neutral Loss- and Product Ion-Based MSn Acquisition for Global Profiling and Structure Annotation of Fatty Acids Conjugates

    NASA Astrophysics Data System (ADS)

    Bi, Qi-rui; Hou, Jin-jun; Yang, Min; Shen, Yao; Qi, Peng; Feng, Rui-hong; Dai, Zhuo; Yan, Bing-peng; Wang, Jian-wei; Shi, Xiao-jian; Wu, Wan-ying; Guo, De-an

    2017-03-01

    Fatty acids conjugates (FACs) are ubiquitous but found in trace amounts in the natural world. They are composed of multiple unknown substructures and side chains. Thus, FACs are difficult to be analyzed by traditional mass spectrometric methods. In this study, an integrated strategy was developed to global profiling and targeted structure annotation of FACs in complex matrix by LTQ Orbitrap. Dicarboxylic acid conjugated bufotoxins (DACBs) in Venenum bufonis (VB) were used as model compounds. The new strategy (abbreviated as HPNA) combined higher-energy C-trap dissociation (HCD) with product ion- (PI), neutral loss- (NL) based MSn (n ≥ 3) acquisition in both positive-ion mode and negative-ion mode. Several advantages are presented. First, various side chains were found under HCD in negative-ion mode, which included both known and unknown side chains. Second, DACBs with multiple side chains were simultaneously detected in one run. Compared with traditional quadrupole-based mass method, it greatly increased analysis throughput. Third, the fragment ions of side chain and steroids substructure could be obtained by PI- and NL-based MSn acquisition, respectively, which greatly increased the accuracy of the structure annotation of DACBs. In all, 78 DACBs have been discovered, of which 68 were new compounds; 25 types of substructure formulas and seven dicarboxylic acid side chains were found, especially five new side chains, including two saturated dicarboxylic acids [(azelaic acid (C9) and sebacic acid (C10)] and three unsaturated dicarboxylic acids (u-C8, u-C9, and u-C10). All these results greatly enriched the structures of DACBs in VB.

  18. Regulation of Manganese Antioxidants by Nutrient Sensing Pathways in Saccharomyces cerevisiae

    PubMed Central

    Reddi, Amit R.; Culotta, Valeria C.

    2011-01-01

    In aerobic organisms, protection from oxidative damage involves the combined action of enzymatic and nonproteinaceous cellular factors that collectively remove harmful reactive oxygen species. One class of nonproteinaceous antioxidants includes small molecule complexes of manganese (Mn) that can scavenge superoxide anion radicals and provide a backup for superoxide dismutase enzymes. Such Mn antioxidants have been identified in diverse organisms; however, nothing regarding their physiology in the context of cellular adaptation to stress was known. Using a molecular genetic approach in Bakers’ yeast, Saccharomyces cerevisiae, we report that the Mn antioxidants can fall under control of the same pathways used for nutrient sensing and stress responses. Specifically, a serine/threonine PAS-kinase, Rim15p, that is known to integrate phosphate, nitrogen, and carbon sensing, can also control Mn antioxidant activity in yeast. Rim15p is negatively regulated by the phosphate-sensing kinase complex Pho80p/Pho85p and by the nitrogen-sensing Akt/S6 kinase homolog, Sch9p. We observed that loss of either of these upstream kinase sensors dramatically inhibited the potency of Mn as an antioxidant. Downstream of Rim15p are transcription factors Gis1p and the redundant Msn2/Msn4p pair that typically respond to nutrient and stress signals. Both transcription factors were found to modulate the potency of the Mn antioxidant but in opposing fashions: loss of Gis1p was seen to enhance Mn antioxidant activity whereas loss of Msn2/4p greatly suppressed it. Our observed roles for nutrient and stress response kinases and transcription factors in regulating the Mn antioxidant underscore its physiological importance in aerobic fitness. PMID:21926297

  19. Structural characterization by both positive and negative electrospray ion trap mass spectrometry of oligogalacturonates purified by high-performance anion-exchange chromatography.

    PubMed

    Quéméner, Bernard; Désiré, Cédric; Debrauwer, Laurent; Rathahao, Estelle

    2003-01-17

    The off-line coupling of high-performance anion-exchange chromatography to electrospray ion trap mass spectrometry (ESI-IT-MS) is described. Two sets of isocratic conditions were optimised for the semi-preparative purification of oligogalacturonates of degree of polymerisation from 4 to 6 by monitoring eluates with either pulsed amperometric detection or evaporative light scattering detection in the presence of an online Dionex Carbohydrate Membrane Desalter (CMD). In these conditions, purified oligogalacturonate solutions were suitable, without further desalting steps, for infusion ESI-IT-MS experiments. This paper provides some interesting features of positive and negative ESI-IT-multiple MS (MSn) of these acidic oligosaccharides. The spectra acquired in both ion modes show characteristic fragments resulting from glycosidic bond and cross-ring cleavages. Under negative ionization conditions, the fragmentation of the singly-charged [M-H]- ions, as well as the Ci-, and Zi-, fragment ions through sequential MSn experiments, was always dominated by product ions from C- and Z-type glycosidic cleavages. All spectra also displayed 0.2 A-type cross-ring cleavage ions which carry linkage information. Collision-induced dissociation (CID) spectra of sodium-cationized species obtained under positive ionization conditions were more complex. Successive MSn experiments also led to the 0.2 A-type cross-ring cleavage ions observed together with B- and Y-type ions. The presence of the 0.2 A ion series was related to Mr 60 (C2H4O2) losses. Combined with the absence of the Mr 30 (CH2O) and the Mr 90 (C3H6O3) ions, these ions were indicative of 1-4 type glycosidic linkage.

  20. Prolonged withdrawal from cocaine self-administration affects prefrontal cortex- and basolateral amygdala-nucleus accumbens core circuits but not accumbens GABAergic local interneurons.

    PubMed

    Purgianto, Anthony; Weinfeld, Michael E; Wolf, Marina E

    2017-11-01

    Withdrawal from extended-access cocaine self-administration leads to progressive intensification ('incubation') of cocaine craving. After prolonged withdrawal (1-2 months), when craving is high, expression of incubation depends on strengthening of excitatory inputs to medium spiny neurons (MSN) of the nucleus accumbens (NAc). These excitatory inputs interact with the intra-NAc GABAergic 'microcircuit', composed of MSN axon collaterals and GABAergic interneurons. Here, we investigated whether the increased glutamatergic neurotransmission observed after prolonged withdrawal is accompanied by altered GABAergic neurotransmission, focusing on NAc core. Rats self-administered cocaine or saline (6 hours/day) and then underwent >40 days of withdrawal. First, we investigated parvalbumin positive (PV+) interneurons, GABAergic fast-spiking interneurons that regulate MSN activity. Immunohistochemical studies revealed no significant change in PV signal intensity or the number of PV+ cells in cocaine rats versus saline controls. We then screened PV and other interneuron markers using immunoblotting. We detected no changes in levels of PV, calretinin, calbindin or neuronal nitric oxide synthase. Because expression of these markers is activity dependent, our results suggest no marked changes in interneuron activity. Finally, we utilized local field potential recording, which can detect GABA-mediated alterations at the circuit level, to investigate potential changes in two circuits implicated in cocaine craving: prelimbic prefrontal cortex to NAc core and basolateral amygdala to NAc core. We detected differential adaptations in these circuits, some of which may involve GABA. Overall, our results suggest that alterations in GABA transmission may accompany incubation of cocaine craving, but they are circuit specific and less pronounced than alterations in glutamate transmission. © 2016 Society for the Study of Addiction.

  1. Very low amounts of glucose cause repression of the stress-responsive gene HSP12 in Saccharomyces cerevisiae.

    PubMed

    de Groot, E; Bebelman, J P; Mager, W H; Planta, R J

    2000-02-01

    Changing the growth mode of Saccharomyces cerevisiae by adding fermentable amounts of glucose to cells growing on a non-fermentable carbon source leads to rapid repression of general stress-responsive genes like HSP12. Remarkably, glucose repression of HSP12 appeared to occur even at very low glucose concentrations, down to 0.005%. Although these low levels of glucose do not induce fermentative growth, they do act as a growth signal, since upon addition of glucose to a concentration of 0.02%, growth rate increased and ribosomal protein gene transcription was up-regulated. In an attempt to elucidate how this type of glucose signalling may operate, several signalling mutants were examined. Consistent with the low amounts of glucose that elicit HSP12 repression, neither the main glucose-repression pathway nor cAMP-dependent activation of protein kinase A appeared to play a role in this regulation. Using mutants involved in glucose metabolism, evidence was obtained suggesting that glucose 6-phosphate serves as a signalling molecule. To identify the target for glucose repression on the promoter of the HSP12 gene, a promoter deletion series was used. The major transcription factors governing (stress-induced) transcriptional activation of HSP12 are Msn2p and Msn4p, binding to the general stress-responsive promoter elements (STREs). Surprisingly, glucose repression of HSP12 appeared to be independent of Msn2/4p: HSP12 transcription in glycerol-grown cells was unaffected in a deltamsn2deltamsn4 strain. Nevertheless, evidence was obtained that STRE-mediated transcription is the target of repression by low amounts of glucose. These data suggest that an as yet unidentified factor is involved in STRE-mediated transcriptional regulation of HSP12.

  2. 76 FR 61361 - Findings of Research Misconduct

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-04

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Findings of Research Misconduct... Research Integrity (ORI) has taken final action in the following case: Scott Weber, Ed.D., MSN, University of Pittsburgh: Based on the letters from the Research Integrity Officer at the University of...

  3. High-throughput microfluidics to control and measure signaling dynamics in single yeast cells

    PubMed Central

    Hansen, Anders S.; Hao, Nan; O'Shea, Erin K.

    2015-01-01

    Microfluidics coupled to quantitative time-lapse fluorescence microscopy is transforming our ability to control, measure, and understand signaling dynamics in single living cells. Here we describe a pipeline that incorporates multiplexed microfluidic cell culture, automated programmable fluid handling for cell perturbation, quantitative time-lapse microscopy, and computational analysis of time-lapse movies. We illustrate how this setup can be used to control the nuclear localization of the budding yeast transcription factor Msn2. Using this protocol, we generate oscillations of Msn2 localization and measure the dynamic gene expression response of individual genes in single cells. The protocol allows a single researcher to perform up to 20 different experiments in a single day, whilst collecting data for thousands of single cells. Compared to other protocols, the present protocol is relatively easy to adopt and higher-throughput. The protocol can be widely used to control and monitor single-cell signaling dynamics in other signal transduction systems in microorganisms. PMID:26158443

  4. The language of business: a key nurse executive competency.

    PubMed

    Thomas, Joan; Collins, Allison; Collins, Denton; Herrin, Donna; Dafferner, Deborah; Gabriel, Julie

    2008-01-01

    The ability to interpret fiscal data pertaining to patient outcomes, human resources, customer satisfaction, and financial positions is a vital evidenced-based nurse executive competency. The ability of nurse leaders to influence and contribute in health system executive decision making requires fluency in accounting, "the language of business." After examining challenges faced by nurse executives, faculty at the Loewenberg School of Nursing at the University of Memphis integrated intensive accounting education into a new executive MSN program. Woven throughout the management accounting course is the concept that accounting data must be relevant and accurate for use by organization decision makers. Evidence-based decision making is emphasized when teaching planning and control activities. In addition, fluency in accounting is enhanced which leads to greater skill in patient and nursing advocacy. As competency in management accounting increases through the semester, executive MSN students are encouraged to apply cost accounting course content to their practice settings and to analyze how planning or control activities improve quality outcomes.

  5. You Are There: No Budget for Travel? Try Video Chat

    ERIC Educational Resources Information Center

    Langhorst, Eric

    2009-01-01

    The author discusses how he used video chat as an alternative to a physical trip. Any teacher with an Internet hookup and a $30 webcam can connect with anyone in the world using video chat. Programs like Skype Video and the Google Mail's video chat function make it easy and, best of all, are completely free. The author discusses how to get started…

  6. "Let's Do Some Jumping Together": Intergenerational Participation in the Use of Remote Technology to Co-Construct Social Relations over Distance

    ERIC Educational Resources Information Center

    Kelly, Clare

    2015-01-01

    This article discusses a small-scale study that explores how members of one family based in Australia and the United Kingdom use remote technology to develop and maintain family relationships across generations and distance. Of particular interest was the manner in which Skype computer software was mediated to develop intersubjectivity between a…

  7. Talk Is Cheap: Skype Can Make VoIP a Very Real Communication Option for Your School

    ERIC Educational Resources Information Center

    Branzburg, Jeffrey

    2007-01-01

    There have been many tools that people can use to get connected with each other worldwide. Cell phones, blogs, wikis, podcasts, e-mail--the world hinges upon people's ability to connect, share, collaborate, and communicate. Voice over Internet Protocol (VoIP) is another tool schools can use to help their students get connected with the world. One…

  8. How Does Disaggregating a Pooled Inventory Affect a Marine Aircraft Group?

    DTIC Science & Technology

    2014-12-01

    Submitted in partial fulfillment of the requirements for the degree of MASTER OF BUSINESS ADMINISTRATION from the NAVAL...Kang Dr. William R. Gates, Dean Graduate School of Business and Public Policy iv THIS PAGE INTENTIONALLY LEFT BLANK v HOW DOES...Kenneth Doerr and Dr. Keebom Kang, for their guidance and patience throughout the thesis process. Dr. Doerr, thanks for all the Skype chats. Our

  9. Using a Simple, Free Voice-over-Internet Protocol Service to Add Interest to Lectures and Enhance Student Engagement

    ERIC Educational Resources Information Center

    Beaton, Susan J.; Forster, Peter M.

    2013-01-01

    A large proportion of students in higher education report feeling bored during lectures, for example, Mann and Robinson (2009) put this figure at 60 per cent. This short article reviews our experiences of using a simple, free Voice-over-Internet Protocol (VoIP) service, Skype, to enhance the interest and engagement of students by holding a…

  10. Microsoft Office 365 Deployment Continues through June at NCI at Frederick | Poster

    Cancer.gov

    The latest Microsoft suite, Office 365 (O365), is being deployed to all NCI at Frederick computers during the months of May and June to comply with federal mandates. The suite includes the latest versions of Word, Excel, Outlook, PowerPoint, and Skype for Business, along with cloud-based capabilities. These cloud-based capabilities will help meet the federal mandates that

  11. Met Any Good Authors Lately? Classroom Author Visits Can Happen via Skype (Here's a List of Those Who Do It for Free)

    ERIC Educational Resources Information Center

    Messner, Kate

    2009-01-01

    In May 2007, the faculty book club that the author facilitates read Chris Bohjalian's novel "The Double Bind" (Shaye Areheart: Harmony, 2007). Bohjalian, a local author, agreed to meet them in Burlington for drinks and conversation. When he arrived, the author and her class introduced themselves, passed around some nachos, and began their…

  12. A Comparison between the Occurrence of Pauses, Repetitions and Recasts under Conditions of Face-to-Face and Computer-Mediated Communication: A Preliminary Study

    ERIC Educational Resources Information Center

    Cabaroglu, Nese; Basaran, Suleyman; Roberts, Jon

    2010-01-01

    This study compares pauses, repetitions and recasts in matched task interactions under face-to-face and computer-mediated conditions. Six first-year English undergraduates at a Turkish University took part in Skype-based voice chat with a native speaker and face-to-face with their instructor. Preliminary quantitative analysis of transcripts showed…

  13. Interview: Professor Helle Neergaard, President of the European Council for Small Business and Entrepreneurship, on the Nature of Creativity, Innovation and Entrepreneurship

    ERIC Educational Resources Information Center

    Industry and Higher Education, 2015

    2015-01-01

    On August 13, 2014, Rita G. Klapper conducted a Skype interview with Helle Neergaard. Neergaard is not only President of the European Council for Small Business and Entrepreneurship, but also Docent at the Hanken School of Economics, and Professor at iCARE, Department of Business Administration, School of Business and Social Sciences, University…

  14. Collaboration through Flickr & Skype: Can Web 2.0 Technology Substitute the Traditional Design Studio in Higher Design Education?

    ERIC Educational Resources Information Center

    Fleischmann, Katja

    2014-01-01

    Technology has not only changed the work practice of designers but also how design is taught and learned. The emergence of digital technology has made computer labs a central learning space for design students. Since this change, studio-based learning in its traditional sense appears to be in decline in higher education institutions. This is in…

  15. A randomized controlled study about the use of eHealth in the home health care of premature infants.

    PubMed

    Gund, Anna; Sjöqvist, Bengt Arne; Wigert, Helena; Hentz, Elisabet; Lindecrantz, Kaj; Bry, Kristina

    2013-02-09

    One area where the use of information and communication technology (ICT), or eHealth, could be developed is the home health care of premature infants. The aim of this randomized controlled study was to investigate whether the use of video conferencing or a web application improves parents' satisfaction in taking care of a premature infant at home and decreases the need of home visits. In addition, nurses' attitudes regarding the use of these tools were examined. Thirty-four families were randomized to one of three groups before their premature infant was discharged from the hospital to home health care: a control group receiving standard home health care (13 families); a web group receiving home health care supplemented with the use of a web application (12 families); a video group with home health care supplemented with video conferencing using Skype (9 families). Families and nursing staff answered questionnaires about the usefulness of ICT. In addition, semi-structured interviews were conducted with 16 families. All the parents in the web group found the web application easy to use. 83% of the families thought it was good to have access to their child's data through the application. All the families in the video group found Skype easy to use and were satisfied with the video calls. 88% of the families thought that video calls were better than ordinary phone calls. 33% of the families in the web group and 75% of those in the video group thought the need for home visits was decreased by the web application or Skype. 50% of the families in the web group and 100% of those in the video group thought the web application or the video calls had helped them feel more confident in caring for their child. Most of the nurses were motivated to use ICT but some were reluctant and avoided using the web application and video conferencing. The families were satisfied with both the web application and video conferencing. The families readily embraced the use of ICT, whereas motivating some of the nurses to accept and use ICT was a major challenge.

  16. A randomized controlled study about the use of eHealth in the home health care of premature infants

    PubMed Central

    2013-01-01

    Background One area where the use of information and communication technology (ICT), or eHealth, could be developed is the home health care of premature infants. The aim of this randomized controlled study was to investigate whether the use of video conferencing or a web application improves parents’ satisfaction in taking care of a premature infant at home and decreases the need of home visits. In addition, nurses’ attitudes regarding the use of these tools were examined. Method Thirty-four families were randomized to one of three groups before their premature infant was discharged from the hospital to home health care: a control group receiving standard home health care (13 families); a web group receiving home health care supplemented with the use of a web application (12 families); a video group with home health care supplemented with video conferencing using Skype (9 families). Families and nursing staff answered questionnaires about the usefulness of ICT. In addition, semi-structured interviews were conducted with 16 families. Results All the parents in the web group found the web application easy to use. 83% of the families thought it was good to have access to their child’s data through the application. All the families in the video group found Skype easy to use and were satisfied with the video calls. 88% of the families thought that video calls were better than ordinary phone calls. 33% of the families in the web group and 75% of those in the video group thought the need for home visits was decreased by the web application or Skype. 50% of the families in the web group and 100% of those in the video group thought the web application or the video calls had helped them feel more confident in caring for their child. Most of the nurses were motivated to use ICT but some were reluctant and avoided using the web application and video conferencing. Conclusion The families were satisfied with both the web application and video conferencing. The families readily embraced the use of ICT, whereas motivating some of the nurses to accept and use ICT was a major challenge. PMID:23394465

  17. Anthocyanidins and polyphenols in five brassica species microgreens: analysis by UHPLC-PDA-ESI/HRMS/MSn

    USDA-ARS?s Scientific Manuscript database

    Brassica vegetables are known to contain relatively high concentrations of bioactive compounds associated with human health. A comprehensive profiling of polyphenols from five Brassica species microgreens was conducted using ultra high-performance liquid chromatography photo diode array high-resolu...

  18. The Effects of Multiple Deployments on Army Adolescents

    DTIC Science & Technology

    2010-01-01

    commonly associated with soldier morale—was broad and generally supportive. In contrast, American public support for the wars in Iraq and Afghanistan has...Deep Communication. Communication between the war zone and the homefront has evolved from postal letters to email to cell phones to Skype webcam...communication and child stress; from the child’s perspective, more and deeper communication between the homefront and the war zone may not always

  19. Applying Role-Playing Strategy to Enhance Learners' Writing and Speaking Skills in EFL Courses Using Facebook and Skype as Learning Tools: A Case Study in Taiwan

    ERIC Educational Resources Information Center

    Yen, Yen-Chen; Hou, Huei-Tse; Chang, Kuo En

    2015-01-01

    English as a foreign language (EFL) instruction faces many challenges in Asia because of many cultural and environmental factors, such as the lack of interactive speaking environments, emphasis placed on test scores, and foreign language anxiety. The purpose of this research is to conduct an EFL instructional course by integrating Facebook…

  20. The Impact of Utilizing Skype as a Social Tool Network Community on Developing English Major Students' Discourse Competence in the English Language Syllables

    ERIC Educational Resources Information Center

    Hussein, Nadhim Obaid; Elttayef, Ahmed Ibrahim

    2016-01-01

    The importance of this study comes from the fact that foreign language learners suffer from traditional ways and methods of teaching and learning. They are looking for new ways of teaching and learning specially methods which integrated with technology. What makes this study important is that using one of the most familiar software for learners…

  1. A web-based programme for person-centred learning and support designed for preschool children with long-term illness: a pilot study of a new intervention.

    PubMed

    Hellström, Anna-Lena; Simeonsdotter Svensson, Agneta; Pramling Samuelsson, Ingrid; Jenholt Nolbris, Margaretha

    2012-01-01

    For children living with long-term illness, school age is a risk period with regard to psychosocial ill health and poor compliance with treatment. There is a need for methods to promote health, well-being, and self-esteem. This study describes a new concept for supporting children, person-centred web-based learning and support, which has been tested in 12 preschool children and incorporates learning about feelings, relationships, and the right to integrity. SKYPE was used for conversations between the child and the web teacher. Methods. The programme was developed and tested in two steps. The conversations were tape-recorded and analysed using phenomenography. The questions addressed concerned the quality of the intervention process: accessibility of intervention, learning content and support, and identification of measurable items and patterns. Findings. The children found it interesting to communicate with their web teacher using SKYPE. The story about Max and Sara served as a good basis for discussion, and development was found in the learning process. The children were able to talk about relations and feelings and developed an understanding for use in new situations in their daily lives. Items and patterns that are useful for research and documentation were identified, for example, well-being, resources, needs, and wishes.

  2. Supporting Collaboration and Creativity Through Mobile P2P Computing

    NASA Astrophysics Data System (ADS)

    Wierzbicki, Adam; Datta, Anwitaman; Żaczek, Łukasz; Rzadca, Krzysztof

    Among many potential applications of mobile P2P systems, collaboration applications are among the most prominent. Examples of applications such as Groove (although not intended for mobile networks), collaboration tools for disaster recovery (the WORKPAD project), and Skype's collaboration extensions, all demonstrate the potential of P2P collaborative applications. Yet, the development of such applications for mobile P2P systems is still difficult because of the lack of middleware.

  3. Can Social Networks Assist Analysts Fight Terrorism?

    DTIC Science & Technology

    2011-06-01

    protecting America from terrorism in a 2007 article. He proposed the intelligence community ought to build a social networking database to track... filming the event, mostly with mobile phones (Shirky 2009). BBC and the U.S. Geological Survey agencies learned of the event from Twitter minutes...North America , Facebook has over 500,000 unique users visit its site every month (eBizMBA 2011). Third only to QQ, China’s top social network, and Skype

  4. MSN Program Development at a Southwestern Pennsylvania University: A Needs Assessment

    ERIC Educational Resources Information Center

    Pallone, Judith P.

    2014-01-01

    The American Association of Colleges of Nursing (AACN) requires a master's degree for nurse educators as well as for direct patient care providers such as nurse practitioners, nurse midwives, nurse anesthetists and clinical nurse specialists. Advanced Practice Nurses (APNs) are expected to play a major role in providing patient care since the…

  5. Exploring Malaysian Trainee Teachers' Adoption of the Internet as Information Tool

    ERIC Educational Resources Information Center

    Teck-Chai, Lau; Kim-Hong, Yeoh; Ching-Ching, Choong

    2010-01-01

    This study reports the usage of three commercial Internet search engines in information seeking among trainee teachers at a teacher training institute in Malaysia. It attempts to investigate the information seeking behavior of the trainees via three Internet search engines (Google, Yahoo and MSN) as gateways to information for research in academic…

  6. Messenger in the Barn: Networking in a Learning Environment

    ERIC Educational Resources Information Center

    Rutter, Malcolm

    2009-01-01

    This case study describes the use of a synchronous communication application (MSN Messenger) in a large academic computing environment. It draws on data from interviews, questionnaires and student marks to examine the link between use of the application and success measured through module marks. The relationship is not simple. Total abstainers and…

  7. Internet Search Engines - Fluctuations in Document Accessibility.

    ERIC Educational Resources Information Center

    Mettrop, Wouter; Nieuwenhuysen, Paul

    2001-01-01

    Reports an empirical investigation of the consistency of retrieval through Internet search engines. Evaluates 13 engines: AltaVista, EuroFerret, Excite, HotBot, InfoSeek, Lycos, MSN, NorthernLight, Snap, WebCrawler, and three national Dutch engines: Ilse, Search.nl and Vindex. The focus is on a characteristic related to size: the degree of…

  8. High Yield Production and Radiochemical Isolation of Isotopically Pure Arsenic-72 and Novel Radioarsenic Labeling Strategies for the Development of Theranostic Radiopharmaceuticals.

    PubMed

    Ellison, Paul A; Barnhart, Todd E; Chen, Feng; Hong, Hao; Zhang, Yin; Theuer, Charles P; Cai, Weibo; Nickles, Robert J; DeJesus, Onofre T

    2016-01-20

    Radioisotopes of arsenic are of considerable interest to the field of nuclear medicine with unique nuclear and chemical properties making them well-suited for use in novel theranostic radiopharmaceuticals. However, progress must still be made in the production of isotopically pure radioarsenic and in its stable conjugation to biological targeting vectors. This work presents the production and irradiation of isotopically enriched (72)Ge(m) discs in an irrigation-cooled target system allowing for the production of isotopically pure (72)As with capability on the order of 10 GBq. A radiochemical separation procedure isolated the reactive trivalent radioarsenic in a small volume buffered aqueous solution, while reclaiming (72)Ge target material. The direct thiol-labeling of a monoclonal antibody resulted in a conjugate exhibiting exceptionally poor in vivo stability in a mouse model. This prompted further investigations to alternative radioarsenic labeling strategies, including the labeling of the dithiol-containing chelator dihydrolipoic acid, and thiol-modified mesoporous silica nanoparticles (MSN-SH). Radioarsenic-labeled MSN-SH showed exceptional in vivo stability toward dearsenylation.

  9. High Yield Production and Radiochemical Isolation of Isotopically Pure Arsenic-72 and Novel Radioarsenic Labeling Strategies for the Development of Theranostic Radiopharmaceuticals

    PubMed Central

    Ellison, Paul A.; Barnhart, Todd E.; Chen, Feng; Hong, Hao; Zhang, Yin; Theuer, Charles P.; Cai, Weibo; Nickles, Robert J.; DeJesus, Onofre T.

    2016-01-01

    Radioisotopes of arsenic are of considerable interest to the field of nuclear medicine with unique nuclear and chemical properties making them well-suited for use in novel theranostic radiopharmaceuticals. However, progress must still be made in the production of isotopically pure radioarsenic and in its stable conjugation to biological targeting vectors. This work presents the production and irradiation of isotopically enriched 72Ge(m) discs in an irrigation-cooled target system allowing for the production of isotopically pure 72As with capability on the order of 10 GBq. A radiochemical separation procedure isolated the reactive trivalent radioarsenic in a small volume buffered aqueous solution, while reclaiming 72Ge target material. The direct thiol-labeling of a monoclonal antibody resulted in a conjugate exhibiting exceptionally poor in vivo stability in a mouse model. This prompted further investigations to alternative radioarsenic labeling strategies, including the labeling of the dithiol-containing chelator dihydrolipoic acid, and thiol-modified mesoporous silica nanoparticles (MSN-SH). Radioarsenic-labeled MSN-SH showed exceptional in vivo stability toward dearsenylation. PMID:26646989

  10. The biodistribution and dosimetry of {sup 117m}Sn DTPA with special emphasis on active marrow absorbed doses

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stubbs, J.; Atkins, H.

    1999-01-01

    {sup 117m}Sn(4+) DTPA is a new radiopharmaceutical for the palliation of pain associated with metastatic bone cancer. Recently, the Phase 2 clinical trials involving 47 patients were completed. These patients received administered activities in the range 6.7--10.6 MBq/kg of body mass. Frequent collections of urine were acquired over the first several hours postadministration and daily cumulative collections were obtained for the next 4--10 days. Anterior/posterior gamma camera images were obtained frequently over the initial 10 days. Radiation dose estimates were calculated for 8 of these patients. Each patient`s biodistribution data were mathematically simulated using a multicompartmental model. The model consistedmore » of the following compartments: central, bone, kidney, other tissues, and cumulative urine. The measured cumulative urine data were used as references for the cumulative urine excretion compartment. The total-body compartment (sum of the bone surfaces, central, kidney, and other tissues compartments) was reference to all activity not excreted in the urine.« less

  11. MSN anti-cancer nanomedicines: chemotherapy enhancement, overcoming of drug resistance, and metastasis inhibition.

    PubMed

    He, Qianjun; Shi, Jianlin

    2014-01-22

    In the anti-cancer war, there are three main obstacles resulting in high mortality and recurrence rate of cancers: the severe toxic side effect of anti-cancer drugs to normal tissues due to the lack of tumor-selectivity, the multi-drug resistance (MDR) to free chemotherapeutic drugs and the deadly metastases of cancer cells. The development of state-of-art nanomedicines based on mesoporous silica nanoparticles (MSNs) is expected to overcome the above three main obstacles. In the view of the fast development of anti-cancer strategy, this review highlights the most recent advances of MSN anti-cancer nanomedicines in enhancing chemotherapeutic efficacy, overcoming the MDR and inhibiting metastasis. Furthermore, we give an outlook of the future development of MSNs-based anti-cancer nanomedicines, and propose several innovative and forward-looking anti-cancer strategies, including tumor tissue-cell-nuclear successionally targeted drug delivery strategy, tumor cell-selective nuclear-targeted drug delivery strategy, multi-targeting and multi-drug strategy, chemo-/radio-/photodynamic-/ultrasound-/thermo-combined multi-modal therapy by virtue of functionalized hollow/rattle-structured MSNs. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Expression of Candida glabrata adhesins following exposure to chemical preservatives

    PubMed Central

    Mundy, Renee Domergue; Cormack, Brendan

    2014-01-01

    In Candida glabrata, an opportunistic yeast pathogen, adherence to host cells is mediated in part by the Epa family of adhesins, which are encoded largely at subtelomeric loci where they are subject to transcriptional silencing. In analyzing the regulation of the subtelomeric EPA6 gene, we found that its transcription is highly induced after exposure to methylparaben, propylparaben or sorbate. These weak acid-related chemicals are widely used as antifungal preservatives in many consumer goods, including over-the-counter (OTC) vaginal products. Culture of C. glabrata in a variety of vaginal products induced expression of EPA6, leading to increased adherence to cultured human cells as well as primary human vaginal epithelial cells. We present evidence that paraben/sorbate-induction of EPA6 expression involves both preservative stress and growth under hypoxic conditions. We further show that activation of EPA6 transcription depends on the Flo8 and Mss11 transcription factors and does not require the classical weak acid transcription factors War1 or Msn2/Msn4. We conclude that exposure of C. glabrata to commonly used preservatives can alter expression of virulence-related genes. PMID:19426114

  13. Striatopallidal neurons control avoidance behavior in exploratory tasks.

    PubMed

    LeBlanc, Kimberly H; London, Tanisha D; Szczot, Ilona; Bocarsly, Miriam E; Friend, Danielle M; Nguyen, Katrina P; Mengesha, Marda M; Rubinstein, Marcelo; Alvarez, Veronica A; Kravitz, Alexxai V

    2018-04-25

    The dorsal striatum has been linked to decision-making under conflict, but the mechanism by which striatal neurons contribute to approach-avoidance conflicts remains unclear. We hypothesized that striatopallidal dopamine D2 receptor (D2R)-expressing neurons promote avoidance, and tested this hypothesis in two exploratory approach-avoidance conflict paradigms in mice: the elevated zero maze and open field. Genetic elimination of D2Rs on striatopallidal neurons (iMSNs), but not other neural populations, increased avoidance of the open areas in both tasks, in a manner that was dissociable from global changes in movement. Population calcium activity of dorsomedial iMSNs was disrupted in mice lacking D2Rs on iMSNs, suggesting that disrupted output of iMSNs contributes to heightened avoidance behavior. Consistently, artificial disruption of iMSN output with optogenetic stimulation heightened avoidance of open areas of these tasks, while inhibition of iMSN output reduced avoidance. We conclude that dorsomedial striatal iMSNs control approach-avoidance conflicts in exploratory tasks, and highlight this neural population as a potential target for reducing avoidance in anxiety disorders.

  14. From tiger to panda: animal head detection.

    PubMed

    Zhang, Weiwei; Sun, Jian; Tang, Xiaoou

    2011-06-01

    Robust object detection has many important applications in real-world online photo processing. For example, both Google image search and MSN live image search have integrated human face detector to retrieve face or portrait photos. Inspired by the success of such face filtering approach, in this paper, we focus on another popular online photo category--animal, which is one of the top five categories in the MSN live image search query log. As a first attempt, we focus on the problem of animal head detection of a set of relatively large land animals that are popular on the internet, such as cat, tiger, panda, fox, and cheetah. First, we proposed a new set of gradient oriented feature, Haar of Oriented Gradients (HOOG), to effectively capture the shape and texture features on animal head. Then, we proposed two detection algorithms, namely Bruteforce detection and Deformable detection, to effectively exploit the shape feature and texture feature simultaneously. Experimental results on 14,379 well labeled animals images validate the superiority of the proposed approach. Additionally, we apply the animal head detector to improve the image search result through text based online photo search result filtering.

  15. A Comprehensive Strategy to Construct In-house Database for Accurate and Batch Identification of Small Molecular Metabolites.

    PubMed

    Zhao, Xinjie; Zeng, Zhongda; Chen, Aiming; Lu, Xin; Zhao, Chunxia; Hu, Chunxiu; Zhou, Lina; Liu, Xinyu; Wang, Xiaolin; Hou, Xiaoli; Ye, Yaorui; Xu, Guowang

    2018-05-29

    Identification of the metabolites is an essential step in metabolomics study to interpret regulatory mechanism of pathological and physiological processes. However, it is still a big headache in LC-MSn-based studies because of the complexity of mass spectrometry, chemical diversity of metabolites, and deficiency of standards database. In this work, a comprehensive strategy is developed for accurate and batch metabolite identification in non-targeted metabolomics studies. First, a well defined procedure was applied to generate reliable and standard LC-MS2 data including tR, MS1 and MS2 information at a standard operational procedure (SOP). An in-house database including about 2000 metabolites was constructed and used to identify the metabolites in non-targeted metabolic profiling by retention time calibration using internal standards, precursor ion alignment and ion fusion, auto-MS2 information extraction and selection, and database batch searching and scoring. As an application example, a pooled serum sample was analyzed to deliver the strategy, 202 metabolites were identified in the positive ion mode. It shows our strategy is useful for LC-MSn-based non-targeted metabolomics study.

  16. The Synthesis and Structural Characterization of Graft Copolymers Composed of γ-PGA Backbone and Oligoesters Pendant Chains

    NASA Astrophysics Data System (ADS)

    Kwiecień, Iwona; Radecka, Iza; Kowalczuk, Marek; Jelonek, Katarzyna; Orchel, Arkadiusz; Adamus, Grażyna

    2017-10-01

    The novel copolymers composed of poly-γ-glutamic acid (γ-PGA) and oligoesters have been developed. The structures of the obtained copolymers including variety of end groups were determined at the molecular level with the aid of electrospray ionization multistage mass spectrometry (ESI-MSn). The fragmentation experiment performed for the selected sodium adducts of the copolymers confirmed that the developed methods lead to the formation of graft copolymers composed of poly-γ-glutamic acid (γ-PGA) backbone and oligoesters pendant chains. Moreover, it was established that fragmentation of selected sodium adducts of graft copolymers proceeded via random breakage of amide bonds along the backbone and ester bonds of the oligoesters pendant chains. Considering potential applications of the synthesized copolymers in the area of biomaterials, the hydrolytic degradation under laboratory conditions and in vitro cytotoxicity tests were performed. The ESI-MSn technique applied in this study has been proven to be a useful tool in structural studies of novel graft copolymers as well as their degradation products. [Figure not available: see fulltext.

  17. Profiling and Distribution of Metabolites of Procyanidin B2 in Mice by UPLC-DAD-ESI-IT-TOF-MSn Technique

    PubMed Central

    Xiao, Ying; Hu, Zhongzhi; Yin, Zhiting; Zhou, Yiming; Liu, Taiyi; Zhou, Xiaoli; Chang, Dawei

    2017-01-01

    The metabolite profiles and distributions of procyanidin B2 were qualitatively described using UPLC-DAD-ESI-IT-TOF-MSn without help of reference standards, and a possible metabolic pathway was proposed in the present study. Summarily, 53 metabolites (24 new metabolites) were detected as metabolites of procyanidin B2, and 45 of them were tentatively identified. Twenty seven metabolites were assigned as similar metabolites of (−)-epicatechin by scission of the flavanol interflavanic bond C4–C8, including 16 aromatic metabolites, 5 conjugated metabolites, 3 ring-cleavage metabolites, and 2 phenylvalerolactone metabolites. Additionally, 14 metabolites were conjugates of free procyanidin B2, comprising 9 methylation metabolites, 8 sulfation metabolites, 5 hydration metabolites, 2 hydroxylation metabolites, 1 hydrogenation metabolites, and 1 glucuronidation metabolites. The results of metabolite distributions in organs indicated that the conjugated reaction of free procyanidin B2 mainly occurred in liver and diversified metabolites forms were observed in small intestine. The metabolic components of procyanidin B2 identified in mice provided useful information for further study of the bioactivity and mechanism of its action. PMID:28522973

  18. Technetium-99m(Sn2+)pyrophosphate in ischemic and infarcted dog myocardium in early stages of acute coronary occlusion: histochemical and tissue-counting comparisons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bianco, J.A.; Kemper, A.J.; Taylor, A.

    1983-06-01

    We have investigated the pattern of accumulation of Tc-99m(Sn2+)pyrophosphate (Tc-99m PPi) in myocardial tissue of dogs during the early stages of acute occlusion of the left anterior descending coronary artery. Three groups were studied after: (a) 40 min occlusion followed by 6 hr reperfusion (n . 6); (b) 6 hr occlusion followed by one hour reperfusion (n . 5); and (c) 7 hr occlusion with no reperfusion (n . 4). Areas of myocardial infarction were defined with triphenyl-tetrazolium chloride (TTC) staining, and blood flow was determined with 9-mu radioactive microspheres. In Group C uptake in infarcted and peri-infarct areas wasmore » not enhanced, most likely owing to low flow. In Group B, with late reperfusion, Tc-99m PPi sequestration was increased in both infarcted and peri-infarcted tissues. In Group A, areas ischemic during occlusion but with normal flow and viability by TTC after 6 hr of reperfusion showed significant uptake of Tc-99m PPi (twice the uptake of nonischemic regions).« less

  19. Functional analysis of the stress response element and its role in the multistress response of Saccharomyces cerevisiae.

    PubMed

    Treger, J M; Magee, T R; McEntee, K

    1998-02-04

    The DDR2 gene of Saccharomyces cerevisiae is a multistress response gene whose transcription is rapidly and strongly induced by a diverse array of xenobiotic agents, and environmental and physiological conditions. The multistress response of this gene requires the pentanucleotide, 5' CCCCT, (C4T;STRE (STress Response Element)) and the zinc-finger transcription factors, Msn2p and Msn4p. A 51bp oligonucleotide (oligo 31/32) containing two STREs from the DDR2 promoter region was previously shown to direct heat shock activation of a lacZ reporter gene. In this work we demonstrate that the same element conferred a complete multistress response to an E. coli galK reporter gene introduced into yeast cells. A variant oligonucleotide in which both the STRE spacing and neighboring sequences were altered responded to the same spectrum of stresses, while substitution of nucleotides within the pentanucleotide completely abolished the multistress response. These results directly demonstrate that STREs are not only necessary but are sufficient for mediating a transcriptional response to a surprisingly diverse set of environmental and physiological conditions.

  20. Mesoporous Silica Nanoparticle-Supported Lipid Bilayers (Protocells) for Active Targeting and Delivery to Individual Leukemia Cells

    DOE PAGES

    Durfee, Paul N.; Lin, Yu-Shen; Dunphy, Darren R.; ...

    2016-07-15

    Many nanocarrier cancer therapeutics currently under development, as well as those used in the clinical setting, rely upon the enhanced permeability and retention (EPR) effect to passively accumulate in the tumor microenvironment and kill cancer cells. In leukemia, where leukemogenic stem cells and their progeny circulate within the peripheral blood or bone marrow, the EPR effect may not be operative. Thus, for leukemia therapeutics, it is essential to target and bind individual circulating cells. Here in this research, we investigate mesoporous silica nanoparticle (MSN)-supported lipid bilayers (protocells), an emerging class of nanocarriers, and establish the synthesis conditions and lipid bilayermore » composition needed to achieve highly monodisperse protocells that remain stable in complex media as assessed in vitro by dynamic light scattering and cryo-electron microscopy and ex ovo by direct imaging within a chick chorioallantoic membrane (CAM) model. We show that for vesicle fusion conditions where the lipid surface area exceeds the external surface area of the MSN and the ionic strength exceeds 20 mM, we form monosized protocells (polydispersity index <0.1) on MSN cores with varying size, shape, and pore size, whose conformal zwitterionic supported lipid bilayer confers excellent stability as judged by circulation in the CAM and minimal opsonization in vivo in a mouse model. Having established protocell formulations that are stable colloids, we further modified them with anti-EGFR antibodies as targeting agents and reverified their monodispersity and stability. Then, using intravital imaging in the CAM, we directly observed in real time the progression of selective targeting of individual leukemia cells (using the established REH leukemia cell line transduced with EGFR) and delivery of a model cargo. In conclusion, overall we have established the effectiveness of the protocell platform for individual cell targeting and delivery needed for leukemia and other disseminated disease.« less

  1. Utp22p acts in concert with Utp8p to channel aminoacyl-tRNA from the nucleolus to the nuclear tRNA export receptor Los1p but not Msn5p.

    PubMed

    Eswara, Manoja B K; Clayton, Ashley; Mangroo, Dev

    2012-12-01

    Utp8p is an essential nucleolar protein that channels aminoacyl-tRNAs from aminoacyl-tRNA synthetases in the nucleolus to the nuclear tRNA export receptors located in the nucleoplasm and nuclear pore complex in Saccharomyces cerevisiae. Utp8p is also part of the U3 snoRNA-associated protein complex involved in 18S rRNA biogenesis in the nucleolus. We report that Utp22p, which is another member of the U3 snoRNA-associated protein complex, is also an intranuclear component of the nuclear tRNA export machinery. Depletion of Utp22p results in nuclear retention of mature tRNAs derived from intron-containing and intronless precursors. Moreover, Utp22p copurifies with the nuclear tRNA export receptor Los1p, the aminoacyl-tRNA synthetase Tys1p and Utp8p, but not with the RanGTPase Gsp1p and the nuclear tRNA export receptor Msn5p. Utp22p interacts directly with Utp8p and Los1p in a tRNA-independent manner in vitro. Utp22p also interacts directly with Tys1p, but this binding is stimulated when Tys1p is bound to tRNA. However, Utp22p, unlike Utp8p, does not bind tRNA saturably. These data suggest that Utp22p recruits Utp8p to aminoacyl-tRNA synthetases in the nucleolus to collect aminoacyl-tRNA and then accompanies the Utp8p-tRNA complex to deliver the aminoacyl-tRNAs to Los1p but not Msn5p. It is possible that Nrap/Nol6, the mammalian orthologue of Utp22p, plays a role in channelling aminoacyl-tRNA to the nuclear tRNA export receptor exportin-t.

  2. Mesoporous Silica Nanoparticle-Supported Lipid Bilayers (Protocells) for Active Targeting and Delivery to Individual Leukemia Cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Durfee, Paul N.; Lin, Yu-Shen; Dunphy, Darren R.

    Many nanocarrier cancer therapeutics currently under development, as well as those used in the clinical setting, rely upon the enhanced permeability and retention (EPR) effect to passively accumulate in the tumor microenvironment and kill cancer cells. In leukemia, where leukemogenic stem cells and their progeny circulate within the peripheral blood or bone marrow, the EPR effect may not be operative. Thus, for leukemia therapeutics, it is essential to target and bind individual circulating cells. Here in this research, we investigate mesoporous silica nanoparticle (MSN)-supported lipid bilayers (protocells), an emerging class of nanocarriers, and establish the synthesis conditions and lipid bilayermore » composition needed to achieve highly monodisperse protocells that remain stable in complex media as assessed in vitro by dynamic light scattering and cryo-electron microscopy and ex ovo by direct imaging within a chick chorioallantoic membrane (CAM) model. We show that for vesicle fusion conditions where the lipid surface area exceeds the external surface area of the MSN and the ionic strength exceeds 20 mM, we form monosized protocells (polydispersity index <0.1) on MSN cores with varying size, shape, and pore size, whose conformal zwitterionic supported lipid bilayer confers excellent stability as judged by circulation in the CAM and minimal opsonization in vivo in a mouse model. Having established protocell formulations that are stable colloids, we further modified them with anti-EGFR antibodies as targeting agents and reverified their monodispersity and stability. Then, using intravital imaging in the CAM, we directly observed in real time the progression of selective targeting of individual leukemia cells (using the established REH leukemia cell line transduced with EGFR) and delivery of a model cargo. In conclusion, overall we have established the effectiveness of the protocell platform for individual cell targeting and delivery needed for leukemia and other disseminated disease.« less

  3. Maternal choline supplementation in a mouse model of Down syndrome: effects on attention and nucleus basalis/substantia innominata neuron morphology in adult offspring

    PubMed Central

    Powers, Brian E.; Kelley, Christy M.; Velazquez, Ramon; Ash, Jessica A.; Strawderman, Myla S.; Alldred, Melissa J.; Ginsberg, Stephen D.; Mufson, Elliott J.; Strupp, Barbara J.

    2016-01-01

    The Ts65Dn mouse model of Down syndrome (DS) and Alzheimer’s disease (AD) exhibits cognitive impairment and degeneration of basal forebrain cholinergic neurons (BFCNs). Our prior studies demonstrated that maternal choline supplementation (MCS) improves attention and spatial cognition in Ts65Dn offspring, normalizes hippocampal neurogenesis, and lessens BFCN degeneration in the medial septal nucleus (MSN). Here we determined whether (i) BFCN degeneration contributes to attentional dysfunction, and (ii) whether the attentional benefits of perinatal MCS are due to changes in BFCN morphology. Ts65Dn dams were fed either a choline-supplemented or standard diet during pregnancy and lactation. Ts65Dn and disomic (2N) control offspring were tested as adults (12–17 months of age) on a series of operant attention tasks, followed by morphometric assessment of BFCNs. Ts65Dn mice demonstrated impaired learning and attention relative to 2N mice, and MCS significantly improved these functions in both genotypes. We also found, for the first time, that the number of BFCNs in the nucleus basalis of Meynert/substantia innominata (NBM/SI) was significantly increased in Ts65Dn mice relative to controls. In contrast, the number of BFCNs in the MSN was significantly decreased. Another novel finding was that the volume of BFCNs in both basal forebrain regions was significantly larger in Ts65Dn mice. MCS did not normalize any of these morphological abnormalities in the NBM/SI or MSN. Finally, correlational analysis revealed that attentional performance was inversely associated with BFCN volume, and positively associated with BFCN density. These results support the lifelong attentional benefits of MCS for Ts65Dn and 2N offspring and have profound implications for translation to human DS and pathology attenuation in AD. PMID:27840230

  4. Maternal choline supplementation in a mouse model of Down syndrome: Effects on attention and nucleus basalis/substantia innominata neuron morphology in adult offspring.

    PubMed

    Powers, Brian E; Kelley, Christy M; Velazquez, Ramon; Ash, Jessica A; Strawderman, Myla S; Alldred, Melissa J; Ginsberg, Stephen D; Mufson, Elliott J; Strupp, Barbara J

    2017-01-06

    The Ts65Dn mouse model of Down syndrome (DS) and Alzheimer's disease (AD) exhibits cognitive impairment and degeneration of basal forebrain cholinergic neurons (BFCNs). Our prior studies demonstrated that maternal choline supplementation (MCS) improves attention and spatial cognition in Ts65Dn offspring, normalizes hippocampal neurogenesis, and lessens BFCN degeneration in the medial septal nucleus (MSN). Here we determined whether (i) BFCN degeneration contributes to attentional dysfunction, and (ii) whether the attentional benefits of perinatal MCS are due to changes in BFCN morphology. Ts65Dn dams were fed either a choline-supplemented or standard diet during pregnancy and lactation. Ts65Dn and disomic (2N) control offspring were tested as adults (12-17months of age) on a series of operant attention tasks, followed by morphometric assessment of BFCNs. Ts65Dn mice demonstrated impaired learning and attention relative to 2N mice, and MCS significantly improved these functions in both genotypes. We also found, for the first time, that the number of BFCNs in the nucleus basalis of Meynert/substantia innominata (NBM/SI) was significantly increased in Ts65Dn mice relative to controls. In contrast, the number of BFCNs in the MSN was significantly decreased. Another novel finding was that the volume of BFCNs in both basal forebrain regions was significantly larger in Ts65Dn mice. MCS did not normalize any of these morphological abnormalities in the NBM/SI or MSN. Finally, correlational analysis revealed that attentional performance was inversely associated with BFCN volume, and positively associated with BFCN density. These results support the lifelong attentional benefits of MCS for Ts65Dn and 2N offspring and have profound implications for translation to human DS and pathology attenuation in AD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Ventrolateral Striatal Medium Spiny Neurons Positively Regulate Food-Incentive, Goal-Directed Behavior Independently of D1 and D2 Selectivity.

    PubMed

    Natsubori, Akiyo; Tsutsui-Kimura, Iku; Nishida, Hiroshi; Bouchekioua, Youcef; Sekiya, Hiroshi; Uchigashima, Motokazu; Watanabe, Masahiko; de Kerchove d'Exaerde, Alban; Mimura, Masaru; Takata, Norio; Tanaka, Kenji F

    2017-03-08

    The ventral striatum is involved in motivated behavior. Akin to the dorsal striatum, the ventral striatum contains two parallel pathways: the striatomesencephalic pathway consisting of dopamine receptor Type 1-expressing medium spiny neurons (D1-MSNs) and the striatopallidal pathway consisting of D2-MSNs. These two genetically identified pathways are thought to encode opposing functions in motivated behavior. It has also been reported that D1/D2 genetic selectivity is not attributed to the anatomical discrimination of two pathways. We wanted to determine whether D1- and D2-MSNs in the ventral striatum functioned in an opposing manner as previous observations claimed, and whether D1/D2 selectivity corresponded to a functional segregation in motivated behavior of mice. To address this question, we focused on the lateral portion of ventral striatum as a region implicated in food-incentive, goal-directed behavior, and recorded D1 or D2-MSN activity by using a gene-encoded ratiometric Ca 2+ indicator and by constructing a fiberphotometry system, and manipulated their activities via optogenetic inhibition during ongoing behaviors. We observed concurrent event-related compound Ca 2+ elevations in ventrolateral D1- and D2-MSNs, especially at trial start cue-related and first lever press-related times. D1 or D2 selective optogenetic inhibition just after the trial start cue resulted in a reduction of goal-directed behavior, indicating a shared coding of motivated behavior by both populations at this time. Only D1-selective inhibition just after the first lever press resulted in the reduction of behavior, indicating D1-MSN-specific coding at that specific time. Our data did not support opposing encoding by both populations in food-incentive, goal-directed behavior. SIGNIFICANCE STATEMENT An opposing role of dopamine receptor Type 1 or Type 2-expressing medium spiny neurons (D1-MSNs or D2-MSNs) on striatum-mediated behaviors has been widely accepted. However, this idea has been questioned by recent reports. In the present study, we measured concurrent Ca 2+ activity patterns of D1- and D2-MSNs in the ventrolateral striatum during food-incentive, goal-directed behavior in mice. According to Ca 2+ activity patterns, we conducted timing-specific optogenetic inhibition of each type of MSN. We demonstrated that both D1- and D2-MSNs in the ventrolateral striatum commonly and positively encoded action initiation, whereas only D1-MSNs positively encoded sustained motivated behavior. These findings led us to reconsider the prevailing notion of a functional segregation of MSN activity in the ventral striatum. Copyright © 2017 the authors 0270-6474/17/372724-11$15.00/0.

  6. Distress improves after mindfulness training for progressive MS: A pilot randomised trial.

    PubMed

    Bogosian, A; Chadwick, P; Windgassen, S; Norton, S; McCrone, P; Mosweu, I; Silber, E; Moss-Morris, R

    2015-08-01

    Mindfulness-based interventions have been shown to effectively reduce anxiety, depression and pain in patients with chronic physical illnesses. We assessed the potential effectiveness and cost-effectiveness of a specially adapted Skype distant-delivered mindfulness intervention, designed to reduce distress for people affected by primary and secondary progressive MS. Forty participants were randomly assigned to the eight-week intervention (n = 19) or a waiting-list control group (n = 21). Participants completed standardised questionnaires to measure mood, impact of MS and symptom severity, quality of life and service costs at baseline, post-intervention and three-month follow-up. Distress scores were lower in the intervention group compared with the control group at post-intervention and follow-up (p < 0.05), effect size -0.67 post-intervention and -0.97 at follow-up. Mean scores for pain, fatigue, anxiety, depression and impact of MS were reduced for the mindfulness group compared with control group at post-therapy and follow-up; effect sizes ranged from -0.27 to -0.99 post-intervention and -0.29 to -1.12 at follow-up. There were no differences in quality-adjusted life years, but an 87.4% probability that the intervention saves on service costs and improves outcome. A mindfulness intervention delivered through Skype video conferences appears accessible, feasible and potentially effective and cost-effective for people with progressive MS. © The Author(s), 2015.

  7. A Web-Based Programme for Person-Centred Learning and Support Designed for Preschool Children with Long-Term Illness: A Pilot Study of a New Intervention

    PubMed Central

    Hellström, Anna-Lena; Simeonsdotter Svensson, Agneta; Pramling Samuelsson, Ingrid; Jenholt Nolbris, Margaretha

    2012-01-01

    For children living with long-term illness, school age is a risk period with regard to psychosocial ill health and poor compliance with treatment. There is a need for methods to promote health, well-being, and self-esteem. This study describes a new concept for supporting children, person-centred web-based learning and support, which has been tested in 12 preschool children and incorporates learning about feelings, relationships, and the right to integrity. SKYPE was used for conversations between the child and the web teacher. Methods. The programme was developed and tested in two steps. The conversations were tape-recorded and analysed using phenomenography. The questions addressed concerned the quality of the intervention process: accessibility of intervention, learning content and support, and identification of measurable items and patterns. Findings. The children found it interesting to communicate with their web teacher using SKYPE. The story about Max and Sara served as a good basis for discussion, and development was found in the learning process. The children were able to talk about relations and feelings and developed an understanding for use in new situations in their daily lives. Items and patterns that are useful for research and documentation were identified, for example, well-being, resources, needs, and wishes. PMID:23326654

  8. [Supervised administration of Alzheimer's patients using information communication technology].

    PubMed

    Noda, Yasuha; Sakata, Yoshifumi; Kubota, Masakazu; Uemura, Kengo; Kihara, Takeshi; Kimura, Toru; Ino, Masashi; Tsuji, Teruyuki; Hayashi, Michiyuki; Kinoshita, Ayae

    2014-12-01

    Drug adherence is central to the treatment of dementia, which might reduce compliance due to memory loss, particularly among home-based patients with dementia. In order to improve drug adherence, we suggest the efficient and effective supervised administration by use of information communication technology(ICT). ICT makes face-to-face real-time communication possible, and it also enables picture sharing. Therefore, it might be useful to apply ICT to controlling and supervising medication for patients with dementia to improve drug adherence. Accordingly, we enrolled patients who were supposed to take a newly prescribed anti-dementia patch containing the choline esterase inhibitor rivastigmine(Rivastach®)and investigated the effect of ICT-based intervention for drug adherence, emotional change, and cognitive change, utilizing Skype, a free communication software program. Scheduled Skype interventions increased drug adherence ratio, levels of subjective satisfaction, and instrumental activities of daily living(IADL). Furthermore, we can provide patients and their caregivers with a feeling of safety through regular bidirectional communication, as patients can easily consult medical staff regarding the adverse effects of newly prescribed drugs. Instead of frequent visits to their primary physicians, ICT-based communications can be used as a substitute for supervision of medication, given the availability of the telecommunication system. By directly connecting the medical institution to the home, we expect that this ICT-based system will expand into the geriatric care field, including the care of elderly individuals living alone.

  9. South Africa calls Italy: effective exchange activity through costless (Skype like) connections in the framework of the EU UNAWE project

    NASA Astrophysics Data System (ADS)

    Zanazzi, A.; Albanese, L.; Naidoo, T.

    2014-10-01

    In summer 2012 the Italian EU-UNAWE team joined with the South African team in Cape Town, working with the township schools organizing activities at school and also a teachers' training event at the SAAO Observatory. In order to involve in the exchange not only the project's experts but also to the teachers and the children, we organized Skype connections between the Cape town teachers participating in the project and the teachers in Sicily (South Italy) that also participated in one of the Italian training sessions and later between the children of the Italian school and those in Zanemfundo School (Cape Town). Thanks to this chance of seeing each other and talking directly, children have - with huge interest and participation - shared and learned methods, experiences, curiosities. They shared their prepared actual science researches, in order to understand why an equal gnomon cast different shadows at the same time in the two countries. The teachers confronted on curricula, didactic methodologies such as working with a background story during the whole school year, interdisciplinary uses of astronomy, languages etc. The EU-UNAWE project and International or Regional conferences such as LARIM are perfect chances to create exchanges between countries all around the World, and this simple communication model between children and teachers appears like an enormous resource yet to be fully exploited.

  10. Reporters on the Battlefield. The Embedded Press System in Historical Context

    DTIC Science & Technology

    2004-01-01

    Jack, “Embeds and Unilaterals,” Slate, May 1, 2003. Online at http://slate.msn. com/id/2082412 (as of June 25, 2003). 65 Kurtz, Howard, “ Unembedded ...Kurtz, Howard, “Media Notes: A Battle Plan for the ’03 Campaign,” Wash- ington Post, January 20, 2003. Kurtz, Howard, “ Unembedded Journalist’s Report

  11. 76 FR 41657 - Airworthiness Directives; Airbus Model A330-342 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-15

    ... production. As a result, ALI [Airworthiness Limitation Item] task 533105-01- 02 has not been performed on the... products. The MCAI states: Airworthiness Limitation Item (ALI) task 533105-01-02 is applicable to... embodied in production. As a result, ALI task 533105-01-02 has not been performed on the MSN listed in the...

  12. Users guide to the Most Similar Neighbor Imputation Program Version 2

    Treesearch

    Nicholas L. Crookston; Melinda Moeur; David Renner

    2002-01-01

    The Most Similar Neighbor (MSN, Moeur and Stage 1995) program is used to impute attributes measured on some sample units to sample units where they are not measured. In forestry applications, forest stands or vegetation polygons are examples of sample units. Attributes from detailed vegetation inventories are imputed to sample units where that information is not...

  13. Admission Criteria, Program Outcomes, and NCLEX-RN(RTM) Success in Second Degree Students

    ERIC Educational Resources Information Center

    Rowland, Janet Wedge

    2013-01-01

    The purpose of this retrospective study was to examine the outcome performance of second degree students in an Accelerated BSN (ABSN) and an Entry Level MSN (ELMSN) program. In addition to student demographics (ethnicity/race, age, and gender), study variables included admission and end-of-program indicators. Admission criteria included the…

  14. Afghanistan: Post-Taliban Governance, Security, and U.S. Policy

    DTIC Science & Technology

    2010-07-21

    presidency, but later joined Rabbani’s 5 A pharmaceutical plant in Sudan (Al Shifa... plant was strictly civilian in nature. 6 http://www.msnbc.msn.com/id/4540958. Afghanistan: Post-Taliban Governance, Security, and U.S. Policy...commercially profitable for China Metallurgical Group, includes construction of two coal-fired electric power plant (one of which will supply more

  15. Defense Horizons. Number 25, March 2003. Biology and the Battlefield

    DTIC Science & Technology

    2003-03-01

    Joint Task Force is notified that they will deploy to Southwest Asia within 36 hours. The team will insert 65 miles behind enemy forces, in the...10 Ibid. 11 Carol Ezzell , “Proteins Rule,” Scientific American 286, no. 4 (April 2002), 40–47. 12 “Protein,” accessed at <http://encarta.msn.com/encnet

  16. The Impact of Virtual Patient Simulation on the Self-Efficacy and Performance Levels of MSN Nursing Students

    ERIC Educational Resources Information Center

    Rota, Matthew Jones

    2017-01-01

    The relationship between experience and learning is a growing phenomenon of interest to scholars of teaching and learning. In 1938, John Dewey stated that, "all genuine education comes about through experience." Self-efficacy is the belief in one's own capabilities to produce clear levels of performance around certain tasks. Virtual…

  17. Differentiation of whole grain from refined wheat (T. aestivum) flour using lipid profile of wheat bran, germ, and endosperm with UHPLC-HRAM mass spectrometry”

    USDA-ARS?s Scientific Manuscript database

    A comprehensive analysis of wheat lipids from milling fractions of bran, germ, and endosperm were performed using ultra high-performance liquid chromatography high-resolution accurate-mass multi-stage mass spectrometry (UHPLC-HRAM-MSn) with electrospray ionization (ESI) and atmospheric pressure chem...

  18. 75 FR 5695 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-04

    ... airworthiness information (MCAI) issued by an aviation authority of another country to identify and correct an... confirm the low stress level in that area, a reinforcement of the ``0'' pressure bulkhead is suggested to... aircraft from MSN 1106 up to 1189 could have the same cracks. Although calculations confirm the low stress...

  19. Afghanistan: Post-Taliban Governance, Security, and U.S. Policy

    DTIC Science & Technology

    2010-06-25

    during his 1992-96 presidency, but later joined Rabbani’s 5 A pharmaceutical plant in...assertions that the plant was strictly civilian in nature. 6 http://www.msnbc.msn.com/id/4540958. Afghanistan: Post-Taliban Governance, Security, and...profitable for China Metallurgical Group, includes construction of two coal-fired electric power plant (one of which will supply more electricity to

  20. Defense.gov Special Report: 2011 ESGR Employer Support Freedom Awards

    Science.gov Websites

    dating to 1919 when the American Legion was first established in St. Louis at the utility's headquarters fact, 3M's CEO and president personally requested to be the executive sponsor when MSN was founded. The when I returned." More Hide Story U.S. Army National Guard Command Sergeant Major John Gipe, in

  1. Examining the Impact of Off-Task Multi-Tasking with Technology on Real-Time Classroom Learning

    ERIC Educational Resources Information Center

    Wood, Eileen; Zivcakova, Lucia; Gentile, Petrice; Archer, Karin; De Pasquale, Domenica; Nosko, Amanda

    2012-01-01

    The purpose of the present study was to examine the impact of multi-tasking with digital technologies while attempting to learn from real-time classroom lectures in a university setting. Four digitally-based multi-tasking activities (texting using a cell-phone, emailing, MSN messaging and Facebook[TM]) were compared to 3 control groups…

  2. BetterThanPin: Empowering Users to Fight Phishing (Poster)

    NASA Astrophysics Data System (ADS)

    Tan, Teik Guan

    The BetterThanPin concept is an online security service that allows users to enable almost any Cloud or Web-based account (e.g. Gmail, MSN, Yahoo, etc) to be protected with "almost" 2-factor authentication (2FA). The result is that users can now protect their online accounts with better authentication, without waiting for the service or cloud provider.

  3. A Service Value Model for Continued Use of Online Services: Conceptual Development and Empirical Examination

    ERIC Educational Resources Information Center

    Hu, Tao

    2009-01-01

    Online services (OLS) provide billions of Internet users with a variety of opportunities to exchange goods, share information, and develop or maintain relationships. Popular examples of OLS web sites include eBay.com, Amazon.com, Dell.com, Craigslist.com, MSN.com, Yahoo.com, LinkedIn.com, Zillow.com, Facebook.com, Wikipedia.com, and Twitter.com.…

  4. Browser-Based Online Applications: Something for Everyone!

    ERIC Educational Resources Information Center

    Descy, Don E.

    2007-01-01

    Just as many people log onto a Web mail site (Gmail, Yahoo, MSN, etc.) to read, write and store their email, there are Web sites out there with word processing, database, and a myriad of other software applications that are not downloadable but used on the site through a Web browser. The user does not have to download the applications to a…

  5. Corrigendum to "Nearest neighbor imputation of species-level, plot-scale forest structure attributes from LiDAR data"

    Treesearch

    Andrew T. Hudak; Nicholas L. Crookston; Jeffrey S. Evans; David E. hall; Michael J. Falkowski

    2009-01-01

    The authors regret that an error was discovered in the code within the R software package, yaImpute (Crookston & Finley, 2008), which led to incorrect results reported in the above article. The Most Similar Neighbor (MSN) method computes the distance between reference observations and target observations in a projected space defined using canonical correlation...

  6. The Diet Composition of Beaked Whales and Melon-Headed Whales from the North Pacific

    DTIC Science & Technology

    2015-09-30

    Marine Mammal Laboratory Alaska Fisheries Science Center...National Marine Fisheries Service, NOAA 7600 Sand Point Way N.E. Seattle, Washington 98115 phone: (206) 463-3860 email: mindwalk@msn.com...electra). Marine Mammal Science 28:638-647. Young, R.E. 1987. Vertical distribution and photosensitive vesicles of pelagic cephalopods from Hawaiian waters. Fishery Bulletin 76:583-615.

  7. Visionary leader 2009: Deborah Kumar.

    PubMed

    Zuppa, Barbara

    2010-01-01

    The following manuscript is the winning Visionary Leader 2009 entry submitted to Nursing Management in recognition of Deborah Kumar, MSN, RN, NEA-BC, Director, Medical Division, The Reading Hospital and Medical Center, West Reading, Pa. Deborah was formally recognized for her achievements during the opening ceremony of Congress 2009, September 9, in Chicago, Ill. There, she received the award, sponsored this year by B.E. Smith.

  8. Identification and characterization of chlorogenic acids, chlorogenic acid glycosides and flavonoids from Lonicera henryi L. (Caprifoliaceae) leaves by LC-MSn.

    PubMed

    Jaiswal, Rakesh; Müller, Heiko; Müller, Anja; Karar, Mohamed Gamaleldin Elsadig; Kuhnert, Nikolai

    2014-12-01

    The chlorogenic acids, chlorogenic acid glycosides and flavonoids of the leaves of Lonicera henryi L. (Caprifoliaceae) were investigated qualitatively by liquid chromatography tandem mass spectrometry. Thirty-one chlorogenic acids and their glycosides were detected and characterized to their regioisomeric level on the basis of their unique fragmentation pattern in the negative ion mode tandem MS spectra. All of them were extracted for the first time from this source and thirteen of them were not reported previously in nature. For the positive identification of chlorogenic acid glycosides by LC-MS(n), multiple reaction monitoring and targeted MS(n) experiments were performed. We have developed an LC-MS(n) method for the systematic identification of chlorogenic acid glycosides and were also able to discriminate between chlorogenic acids and their isobaric glycosides. It was also possible to discriminate between 5-O-(3'-O-caffeoyl glucosyl)quinic acid and 5-O-(4'-O-caffeoyl glucosyl)quinic acid by LC-MS(n). This method can be applied for the rapid and positive identification of chlorogenic acids and their glycosides in plant materials, food and beverages. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Phlorotannin Extracts from Fucales Characterized by HPLC-DAD-ESI-MSn: Approaches to Hyaluronidase Inhibitory Capacity and Antioxidant Properties

    PubMed Central

    Ferreres, Federico; Lopes, Graciliana; Gil-Izquierdo, Angel; Andrade, Paula B.; Sousa, Carla; Mouga, Teresa; Valentão, Patrícia

    2012-01-01

    Purified phlorotannin extracts from four brown seaweeds (Cystoseira nodicaulis (Withering) M. Roberts, Cystoseira tamariscifolia (Hudson) Papenfuss, Cystoseira usneoides (Linnaeus) M. Roberts and Fucus spiralis Linnaeus), were characterized by HPLC-DAD-ESI-MSn. Fucophloroethol, fucodiphloroethol, fucotriphloroethol, 7-phloroeckol, phlorofucofuroeckol and bieckol/dieckol were identified. The antioxidant activity and the hyaluronidase (HAase) inhibitory capacity exhibited by the extracts were also assessed. A correlation between the extracts activity and their chemical composition was established. F. spiralis, the species presenting higher molecular weight phlorotannins, generally displayed the strongest lipid peroxidation inhibitory activity (IC50 = 2.32 mg/mL dry weight) and the strongest HAase inhibitory capacity (IC50 = 0.73 mg/mL dry weight). As for superoxide radical scavenging, C. nodicaulis was the most efficient species (IC50 = 0.93 mg/mL dry weight), followed by F. spiralis (IC50 = 1.30 mg/mL dry weight). These results show that purified phlorotannin extracts have potent capabilities for preventing and slowing down the skin aging process, which is mainly associated with free radical damage and with the reduction of hyaluronic acid concentration, characteristic of the process. PMID:23222802

  10. Use of Medicare summary notice inserts to generate interest in the Medicare stop smoking program.

    PubMed

    Maglione, Margaret; Larson, Carrie; Giannotti, Tierney; Lapin, Pauline

    2007-01-01

    Evaluations of outreach strategies that effectively and efficiently reach the senior population often go unreported. The Medicare Stop Smoking Program (MSSP) was a seven-state demonstration project funded by the Centers for Medicare and Medicaid Services. The 1-year recruitment plan for MSSP included a multifaceted paid media campaign; however, enrollment was slower than anticipated. The purpose of this substudy was to test the effects of including envelope-sized advertisement inserts with Medicare Summary Notices (MSNs) as a supplemental recruitment strategy. Information obtained from enrollees on where they had learned about the program as well as overall enrollment rates were analyzed and compared with the time periods during which the inserts were included in MSN mailings. Average call volume to the enrollment center increased by 65.7% in Alabama, the pilot state, and by more than 200% in the subsequent demonstration states. Despite the introduction of the MSN inserts late in the recruitment period, 32.2 % of the 7354 total enrollees stated that they learned about the project through the inserts. This recruitment method is highly recommended as a cost-effective way to reach the senior population.

  11. Recent Advance on Mesoporous Silica Nanoparticles-Based Controlled Release System: Intelligent Switches Open up New Horizon

    PubMed Central

    Sun, Ruijuan; Wang, Wenqian; Wen, Yongqiang; Zhang, Xueji

    2015-01-01

    Mesoporous silica nanoparticle (MSN)-based intelligent transport systems have attracted many researchers’ attention due to the characteristics of uniform pore and particle size distribution, good biocompatibility, high surface area, and versatile functionalization, which have led to their widespread application in diverse areas. In the past two decades, many kinds of smart controlled release systems were prepared with the development of brilliant nano-switches. This article reviews and discusses the advantages of MSN-based controlled release systems. Meanwhile, the switching mechanisms based on different types of stimulus response are systematically analyzed and summarized. Additionally, the application fields of these devices are further discussed. Obviously, the recent evolution of smart nano-switches promoted the upgrading of the controlled release system from the simple “separated” switch to the reversible, multifunctional, complicated logical switches and selective switches. Especially the free-blockage switches, which are based on hydrophobic/hydrophilic conversion, have been proposed and designed in the last two years. The prospects and directions of this research field are also briefly addressed, which could be better used to promote the further development of this field to meet the needs of mankind. PMID:28347110

  12. RoCoMAR: robots' controllable mobility aided routing and relay architecture for mobile sensor networks.

    PubMed

    Le, Duc Van; Oh, Hoon; Yoon, Seokhoon

    2013-07-05

    In a practical deployment, mobile sensor network (MSN) suffers from a low performance due to high node mobility, time-varying wireless channel properties, and obstacles between communicating nodes. In order to tackle the problem of low network performance and provide a desired end-to-end data transfer quality, in this paper we propose a novel ad hoc routing and relaying architecture, namely RoCoMAR (Robots' Controllable Mobility Aided Routing) that uses robotic nodes' controllable mobility. RoCoMAR repeatedly performs link reinforcement process with the objective of maximizing the network throughput, in which the link with the lowest quality on the path is identified and replaced with high quality links by placing a robotic node as a relay at an optimal position. The robotic node resigns as a relay if the objective is achieved or no more gain can be obtained with a new relay. Once placed as a relay, the robotic node performs adaptive link maintenance by adjusting its position according to the movements of regular nodes. The simulation results show that RoCoMAR outperforms existing ad hoc routing protocols for MSN in terms of network throughput and end-to-end delay.

  13. Electron exchange between tin impurity U{sup –} centers in PbS{sub z}Se{sub 1–z} alloys

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Marchenko, A. V.; Terukov, E. I.; Seregin, P. P., E-mail: ppseregin@mail.ru

    2016-07-15

    Using emission {sup 119mm}Sn({sup 119m}Sn) and {sup 119}Sb({sup 119m}Sn) Mössbauer spectroscopy, it is shown that impurity tin atoms in PbS{sub z}Se{sub 1–z} alloys substitute lead atoms and are two-electron donors with negative correlation energy (U{sup –} centers). It is found that the energy levels related to impurity tin atoms are in the lower half of the band gap at z ≥ 0.5 against the background of allowed valence-band states at z ≤ 0.4. The electron exchange between neutral and doubly ionized tin U{sup –} centers in partially compensated Pb{sub 0.99}Sn{sub 0.005}Na{sub 0.005}S{sub z}Se{sub 1–z} alloys is studied. The activation energymore » of this process decreases from 0.111(5) eV for a composition with z = 1 to 0.049(5) eV for compositions with c ≤ 0. For all z, the exchange is implemented via the simultaneous transfer of two electrons using delocalized valence-band states.« less

  14. Distributed and dynamic intracellular organization of extracellular information.

    PubMed

    Granados, Alejandro A; Pietsch, Julian M J; Cepeda-Humerez, Sarah A; Farquhar, Iseabail L; Tkačik, Gašper; Swain, Peter S

    2018-06-05

    Although cells respond specifically to environments, how environmental identity is encoded intracellularly is not understood. Here, we study this organization of information in budding yeast by estimating the mutual information between environmental transitions and the dynamics of nuclear translocation for 10 transcription factors. Our method of estimation is general, scalable, and based on decoding from single cells. The dynamics of the transcription factors are necessary to encode the highest amounts of extracellular information, and we show that information is transduced through two channels: Generalists (Msn2/4, Tod6 and Dot6, Maf1, and Sfp1) can encode the nature of multiple stresses, but only if stress is high; specialists (Hog1, Yap1, and Mig1/2) encode one particular stress, but do so more quickly and for a wider range of magnitudes. In particular, Dot6 encodes almost as much information as Msn2, the master regulator of the environmental stress response. Each transcription factor reports differently, and it is only their collective behavior that distinguishes between multiple environmental states. Changes in the dynamics of the localization of transcription factors thus constitute a precise, distributed internal representation of extracellular change. We predict that such multidimensional representations are common in cellular decision-making.

  15. RoCoMAR: Robots' Controllable Mobility Aided Routing and Relay Architecture for Mobile Sensor Networks

    PubMed Central

    Van Le, Duc; Oh, Hoon; Yoon, Seokhoon

    2013-01-01

    In a practical deployment, mobile sensor network (MSN) suffers from a low performance due to high node mobility, time-varying wireless channel properties, and obstacles between communicating nodes. In order to tackle the problem of low network performance and provide a desired end-to-end data transfer quality, in this paper we propose a novel ad hoc routing and relaying architecture, namely RoCoMAR (Robots' Controllable Mobility Aided Routing) that uses robotic nodes' controllable mobility. RoCoMAR repeatedly performs link reinforcement process with the objective of maximizing the network throughput, in which the link with the lowest quality on the path is identified and replaced with high quality links by placing a robotic node as a relay at an optimal position. The robotic node resigns as a relay if the objective is achieved or no more gain can be obtained with a new relay. Once placed as a relay, the robotic node performs adaptive link maintenance by adjusting its position according to the movements of regular nodes. The simulation results show that RoCoMAR outperforms existing ad hoc routing protocols for MSN in terms of network throughput and end-to-end delay. PMID:23881134

  16. Characterization of alkaloids in Sophora flavescens Ait. by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.

    PubMed

    Liu, Guoqiang; Dong, Jing; Wang, Hong; Hashi, Yuki; Chen, Shizhong

    2011-04-05

    Sophora flavescens Ait., a well-known Chinese herbal medicine, is widely used in clinical practice for the treatment of viral hepatitis, cancer, gastrointestinal hemorrhage, and skin diseases. This paper is the first report on a method based on the combined use of high-performance liquid chromatography, photodiode array detection, and electrospray ionization tandem mass spectrometry for the comprehensive and systematic separation and characterization of bioactive alkaloids in Sophora flavescens Ait. A total of 22 constituents were identified on the basis of the extracted ion chromatograms for different [M+H](+) ions of the alkaloids present in S. flavescens Ait. Among these, 5 constituents were unambiguously identified by comparing the experimental data on their retention times and MS(n) spectra with those of the authentic compounds, and 17 other constituents were tentatively identified on the basis of their MS(n) fragmentation behaviors and/or molecular weight information from literatures. Furthermore, some characteristic fragmentation pathways of the alkaloids in S. flavescens Ait. were detected and examined. This information may be useful for characterizing the bioactive alkaloids present in S. flavescens Ait. and for possible applications in formulations. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Mental health practitioners' use and attitudes regarding the Internet and social media.

    PubMed

    Deen, Serina R; Withers, Amy; Hellerstein, David J

    2013-11-01

    Internet-based technologies, such as email and social media, are being increasingly used by mental health providers. The authors created a survey to better understand mental health providers' practices and attitudes regarding these platforms. Psychiatrists and psychologists at Columbia and the New York State Psychiatric Institute completed a 24-item multiple choice and free-text survey about their use of and attitudes toward Internet technologies. One hundred and thirty faculty responded to the survey: 70% percent of respondents reported that they were somewhat or more familiar with social media; 20% reported that they sometimes or often searched for information about their patients online; and 60% said that searching for patients online could have a positive role in ongoing psychiatric care. Respondents with fewer years of practice were significantly more likely to use Facebook/Google Plus, texting, and instant messenger in their personal lives, while those with more years of practice were more likely to use Skype professionally. Practitioners who worked in hospital settings were more likely to search online for information about their patients. Practitioners working in outpatient clinics, private practices, and research settings were more likely to use websites, email, and Skype in their practices. Mental health care professionals are starting to incorporate Internet technologies into their professional lives, but they remain divided on the ethics and utility of using these technologies in clinical care. There appear to be differences in practices and attitudes toward the Internet among clinicians with different levels of experience and in different practice settings.

  18. [The effect of telecommunication(with Skype)to improve a cognitive function for elderly patients with dementia and to reduce a care burden for their care givers].

    PubMed

    Hori, Miyako; Furuya, Ayana; Kubota, Masakazu; Koike, Akihiko; Kinoshita, Ayae

    2011-12-01

    We conducted an intervention study to clarify how effectively videophone(Skype)was used in the communication for elderly patients with dementia being cared at home and their caregivers. For a period of 12 weeks, a patient-caregiver pair(n =8)communicated with a nurse via computer for 30 minutes once a week. The patient and caregiver worked as a pair. Before and after 12-week study period started, the intervention and control group(n=8)patients were assessed on cognitive scale(HDS-R), ADL, care burden scale(J-ZBI_8)and hours of sleep for caregivers. The result on the 12th week showed a significant improvement in hours of sleep on the intervention group of caregivers, and signs of improvement on the intervention group of patients in HDS-R. According to a questionnaire survey for caregivers, many of them said that a videophone communication was a pleasant experience for the family, and it is also useful for information gathering. Therefore, we think that the videophone communication is useful for a cognitive rehab work and giving good feelings for the patient. It also gives a good satisfaction for the family. Furthermore, a patient who had an intervention for 3 times in 2 years showed a sign of improvements in the cognitive function and care burden scale during the intervention period. However, the score dropped for several months. Therefore, it is important that a continuous intervention is necessary.

  19. The Lantern: The Journal of Nursing Stories. Winter 2010

    DTIC Science & Technology

    2010-01-01

    Page 2 Articles: Storytelling and The Lantern Page 3 by Loretta Aiken, MSN, RN The Girl ...general, and most little girls throughout the world knew about what Florence had ac- complished for womankind. The Times in England wrote: “She is...little girls still play with Florence Nightingale dolls. The lamp itself has become a universal symbol for nursing and for over 100 years, nurses

  20. New Psychoactive Substances 3-Methoxyphencyclidine (3-MeO-PCP) and 3-Methoxyrolicyclidine (3-MeO-PCPy): Metabolic Fate Elucidated with Rat Urine and Human Liver Preparations and their Detectability in Urine by GC-MS, "LC-(High Resolution)-MSn" and "LC-(High Resolution)-MS/MS".

    PubMed

    A Michely, Julian A; Manier, Sascha K; Caspar, Achim T; Brandt, Simon D; Wallach, Jason; Maurer, Hans H

    2017-01-01

    3-Methoxyphencyclidine (3-MeO-PCP) and 3-methoxyrolicyclidine (3-MeOPCPy) are two new psychoactive substances (NPS). The aims of the present study were the elucidation of their metabolic fate in rat and pooled human liver microsomes (pHLM), the identification of the cytochrome P450 (CYP) isoenzymes involved, and the detectability using standard urine screening approaches (SUSA) after intake of common users' doses using gas chromatography-mass spectrometry (GC-MS), liquid chromatography-multi-stage mass spectrometry (LC-MSn), and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS). For metabolism studies, rat urine samples were treated by solid phase extraction or simple precipitation with or without previous enzymatic conjugate cleavage. After analyses via LC-HR-MSn, the phase I and II metabolites were identified. Both drugs showed multiple aliphatic hydroxylations at the cyclohexyl ring and the heterocyclic ring, single aromatic hydroxylation, carboxylation after ring opening, O-demethylation, and glucuronidation. The transferability from rat to human was investigated by pHLM incubations, where Odemethylation and hydroxylation were observed. The involvement of the individual CYP enzymes in the initial metabolic steps was investigated after single CYP incubations. For 3-MeO-PCP, CYP 2B6 was responsible for aliphatic hydroxylations and CYP 2C19 and CYP 2D6 for O-demethylation. For 3-MeO-PCPy, aliphatic hydroxylation was again catalyzed by CYP 2B6 and O-demethylation by CYP 2C9 and CYP 2D6 Conclusions: As only polymorphically expressed enzymes were involved, pharmacogenomic variations might occur, but clinical data are needed to confirm the relevance. The detectability studies showed that the authors' SUSAs were suitable for monitoring the intake of both drugs using the identified metabolites. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. The ins and outs of nuclear re-export of retrogradely transported tRNAs in Saccharomyces cerevisiae

    PubMed Central

    Pierce, Jacqueline B; Eswara, Manoja BK

    2010-01-01

    In Saccharomyces cerevisiae intron-containing pre-tRNAs are exported from the nucleus to the cytoplasm for removal of the introns, and the spliced tRNAs are returned to the nucleus for reasons that are not understood. The re-imported spliced tRNAs are then subjected to aminoacylation in the nucleolus to ensure that they are functional prior to re-export to the cytoplasm. Previous studies have shown that re-imported spliced tRNAs and mature tRNAs made entirely in the nucleus from intronless precursors are retained in the nucleus of S. cerevisiae in response to glucose, amino acid, nitrogen or inorganic phosphate deprivation. Contrary to these studies, we recently reported that starvation of S. cerevisiae of amino acids or nitrogen results in nuclear accumulation of re-imported spliced tRNAs, but not tRNAs made from intronless precursors. This finding suggests that separate pathways are used for nuclear export of retrogradely transported spliced tRNAs and tRNAs made from intronless pre-tRNAs. In addition, the data support the conclusion that the nuclear re-export pathway for retrogradely transported spliced tRNAs, but not the pathway responsible for nuclear export of tRNAs derived from intronless precursors is regulated during amino acid or nitrogen starvation. This regulation appears to occur at a step after the re-imported spliced tRNAs have undergone aminoacylation quality assurance and, in part, involves the TORC1 signalling pathway. Moreover, it was established that Utp9p is an intranuclear component that only facilitates nuclear re-export of retrogradely transported spliced tRNAs by the β-karyopherin Msn5p. Utp9p acts in concert with Utp8p, a key player in nuclear tRNA export in S. cerevisiae, to translocate aminoacylated re-imported spliced tRNAs from the nucleolus to Msn5p and assist with formation of the Msn5p-tRNA-Gsp1p-GTP export complex. This pathway, however, is not the only one responsible for nuclear re-export of retrogradely transported spliced tRNAs. PMID:21327067

  2. The capacity of Aspergillus niger to sense and respond to cell wall stress requires at least three transcription factors: RlmA, MsnA and CrzA.

    PubMed

    Fiedler, Markus Rm; Lorenz, Annett; Nitsche, Benjamin M; van den Hondel, Cees Amjj; Ram, Arthur Fj; Meyer, Vera

    2014-01-01

    Cell wall integrity, vesicle transport and protein secretion are key factors contributing to the vitality and productivity of filamentous fungal cell factories such as Aspergillus niger . In order to pioneer rational strain improvement programs, fundamental knowledge on the genetic basis of these processes is required. The aim of the present study was thus to unravel survival strategies of A. niger when challenged with compounds interfering directly or indirectly with its cell wall integrity: calcofluor white, caspofungin, aureobasidin A, FK506 and fenpropimorph. Transcriptomics signatures of A. niger and phenotypic analyses of selected null mutant strains were used to predict regulator proteins mediating the survival responses against these stressors. This integrated approach allowed us to reconstruct a model for the cell wall salvage gene network of A. niger that ensures survival of the fungus upon cell surface stress. The model predicts that (i) caspofungin and aureobasidin A induce the cell wall integrity pathway as a main compensatory response via induction of RhoB and RhoD, respectively, eventually activating the mitogen-activated protein kinase kinase MkkA and the transcription factor RlmA. (ii) RlmA is the main transcription factor required for the protection against calcofluor white but it cooperates with MsnA and CrzA to ensure survival of A. niger when challenged with caspofungin and aureobasidin A. (iii) Membrane stress provoked by aureobasidin A via disturbance of sphingolipid synthesis induces cell wall stress, whereas fenpropimorph-induced disturbance of ergosterol synthesis does not. The present work uncovered a sophisticated defence system of A. niger which employs at least three transcription factors - RlmA, MsnA and CrzA - to protect itself against cell wall stress. The transcriptomic data furthermore predicts a fourth transfactor, SrbA, which seems to be specifically important to survive fenpropimorph-induced cell membrane stress. Future studies will disclose how these regulators are interlocked in different signaling pathways to secure survival of A. niger under different cell wall stress conditions.

  3. An anthropologist in unexpected places

    PubMed Central

    Knutsen, Johan Henrik

    2014-01-01

    Much contemporary anthropology has turned away from exclusive focus on so-called “primitive” tribes in far-away places. The study of urban people has become more prominent, and some researchers have also turned their gaze towards marginalized minorities in their communities. Philippe Bourgois is an example of this. He is well known for studying crack dealers in East Harlem, New York ( In Search of Respect) and homeless heroin addicts in San Francisco (Righteous Dopefiend). Kula Kula was lucky enough to catch him in his office, and had a chat via skype. PMID:25436019

  4. A Summer Research Experience in Particle Physics Using Skype

    NASA Astrophysics Data System (ADS)

    Johnston, Curran; Alexander, Steven; Mahmood, A. K.

    2012-10-01

    This last summer I did research in particle physics as part of a ``remote REU.'' This poster will describe that experience and the results of my project which was to experimentally verify the mass ranges of the Z' boson. Data from the LHC's Atlas detector was filtered by computers to select for likely Z boson decays; my work was in noting all instances of Z or Z' boson decays in one thousand events and their masses, separating the Z from Z' bosons, and generating histograms of the masses.

  5. [Social networks and medicine].

    PubMed

    Bastardot, F; Vollenweider, P; Marques-Vidal, P

    2015-11-04

    Social networks (social media or #SoMe) have entered medical practice within the last few years. These new media--like Twitter or Skype--enrich interactions among physicians (telemedicine), among physicians and patients (virtual consultations) and change the way of teaching medicine. They also entail new ethical, deontological and legal issues: the extension of the consultation area beyond the medical office and the access of information by third parties were recently debated. We develop here a review of some social networks with their characteristics, applications for medicine and limitations, and we offer some recommendations of good practice.

  6. Influence of Nursing Faculty Discussion Presence on Student Learning and Satisfaction in Online Courses.

    PubMed

    Claywell, Lora; Wallace, Cara; Price, Jill; Reneau, Margaret; Carlson, Kathleen

    2016-01-01

    This study determined the relationships between faculty participation in online discussions with student satisfaction and perceived learning in online RN-BSN and MSN courses. Analysis of faculty participation in online courses (n = 280) demonstrated a relationship between faculty participation and student satisfaction and perceived learning. The results of this study offer guidance on the minimal faculty participation necessary in online discussions in nursing courses.

  7. Afghanistan: Post-Taliban Governance, Security, and U.S. Policy

    DTIC Science & Technology

    2010-09-17

    plant in Sudan (Al Shifa) believe to be producing chemical weapons for Al Qaeda also was struck that day, although U.S. reviews later corroborated...Sudan’s assertions that the plant was strictly civilian in nature. 6 http://www.msnbc.msn.com/id/4540958. Afghanistan: Post-Taliban Governance...point where it might not be commercially profitable for China Metallurgical Group, includes construction of two coal-fired electric power plant (one

  8. "MSN Was the next Big Thing after Beanie Babies": Children's Virtual Experiences as an Interface to Their Identities and Their Everyday Lives

    ERIC Educational Resources Information Center

    Thomas, Angela

    2006-01-01

    In this article the author explores the seamlessness between children's online and offline worlds. For children, there is no dichotomy of online and offline, or virtual and real; the digital is so much intertwined into their lives and psyche that the one is entirely enmeshed with the other. Despite early research pointing to the differences that…

  9. Genomewide mechanisms of chronological longevity by dietary restriction in budding yeast.

    PubMed

    Campos, Sergio E; Avelar-Rivas, J Abraham; Garay, Erika; Juárez-Reyes, Alejandro; DeLuna, Alexander

    2018-06-01

    Dietary restriction is arguably the most promising nonpharmacological intervention to extend human life and health span. Yet, only few genetic regulators mediating the cellular response to dietary restriction are known, and the question remains which other regulatory factors are involved. Here, we measured at the genomewide level the chronological lifespan of Saccharomyces cerevisiae gene deletion strains under two nitrogen source regimens, glutamine (nonrestricted) and γ-aminobutyric acid (restricted). We identified 473 mutants with diminished or enhanced extension of lifespan. Functional analysis of such dietary restriction genes revealed novel processes underlying longevity by the nitrogen source quality, which also allowed us to generate a prioritized catalogue of transcription factors orchestrating the dietary restriction response. Importantly, deletions of transcription factors Msn2, Msn4, Snf6, Tec1, and Ste12 resulted in diminished lifespan extension and defects in cell cycle arrest upon nutrient starvation, suggesting that regulation of the cell cycle is a major mechanism of chronological longevity. We further show that STE12 overexpression is enough to extend lifespan, linking the pheromone/invasive growth pathway with cell survivorship. Our global picture of the genetic players of longevity by dietary restriction highlights intricate regulatory cross-talks in aging cells. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  10. Evaluation of the effect of roasting on the structure of coffee galactomannans using model oligosaccharides.

    PubMed

    Moreira, Ana S P; Coimbra, Manuel A; Nunes, Fernando M; Simões, Joana; Domingues, M Rosário M

    2011-09-28

    The roasting process induces structural changes in coffee galactomannans. To know more about the reaction pathways that occur during the roasting of coffee, mannosyl and galactomannosyl oligosaccharides, having a degree of polymerization (DP) between 3 and 4, were used as models for galactomannans. These compounds were dry-heated under air atmosphere from room temperature to 200 °C, being maintained at 200 °C for different periods of time. The roasted materials were analyzed by mass spectrometry (ESI-MS, MALDI-MS, and ESI-MSn) and methylation analysis. In the MS spectra were identified several [M+Na]+ ions belonging to a series from a single hexose to 10 hexose residues ([Hex1-10+Na]+). The ions corresponding to their respective mono- and tridehydrated derivatives ([Hex2-10-H2O+Na]+ and [Hex2-10-3H2O+Na]+, respectively) were also identified. ESI-MSn as well as deuterium-labeling and alditol derivatization experiments showed that the tridehydrations occur at the reducing end of the oligosaccharides. The identification of (1→2)- and (1→6)-linked mannose residues and (1→4)-linked glucose residues by methylation analysis allowed the conclusion that transglycosylation and isomerization reactions occur during dry thermal processing.

  11. Mapping growing stock volume and forest live biomass: a case study of the Polissya region of Ukraine

    NASA Astrophysics Data System (ADS)

    Bilous, Andrii; Myroniuk, Viktor; Holiaka, Dmytrii; Bilous, Svitlana; See, Linda; Schepaschenko, Dmitry

    2017-10-01

    Forest inventory and biomass mapping are important tasks that require inputs from multiple data sources. In this paper we implement two methods for the Ukrainian region of Polissya: random forest (RF) for tree species prediction and k-nearest neighbors (k-NN) for growing stock volume and biomass mapping. We examined the suitability of the five-band RapidEye satellite image to predict the distribution of six tree species. The accuracy of RF is quite high: ~99% for forest/non-forest mask and 89% for tree species prediction. Our results demonstrate that inclusion of elevation as a predictor variable in the RF model improved the performance of tree species classification. We evaluated different distance metrics for the k-NN method, including Euclidean or Mahalanobis distance, most similar neighbor (MSN), gradient nearest neighbor, and independent component analysis. The MSN with the four nearest neighbors (k = 4) is the most precise (according to the root-mean-square deviation) for predicting forest attributes across the study area. The k-NN method allowed us to estimate growing stock volume with an accuracy of 3 m3 ha-1 and for live biomass of about 2 t ha-1 over the study area.

  12. Mesoporous silica nanoparticle-based intelligent drug delivery system for bienzyme-responsive tumour targeting and controlled release.

    PubMed

    Zhang, Yang; Xu, Juan

    2018-01-01

    This paper proposes a novel type of multifunctional envelope-type mesoporous silica nanoparticle (MSN) to achieve cancer cell targeting and drug-controlled release. In this system, MSNs were first modified by active targeting moiety hyaluronic acid (HA) for breast cancer cell targeting and hyaluronidases (Hyal)-induced intracellular drug release. Then gelatin, a proteinaceous biopolymer, was grafted onto the MSNs to form a capping layer via glutaraldehyde-mediated cross-linking. To shield against unspecific uptake of cells and prolong circulation time, the nanoparticles were further decorated with poly(ethylene glycol) polymers (PEG) to obtain MSN@HA-gelatin-PEG (MHGP). Doxorubicin (DOX), as a model drug, was loaded into PEMSN to assess the breast cancer cell targeting and drug release behaviours. In vitro study revealed that PEG chains protect the targeting ligand and shield against normal cells. After reaching the breast cancer cells, MMP-2 overpressed by cells hydrolyses gelatin layer to deshield PEG and switch on the function of HA. As a result, DOX-loaded MHGP was selectively trapped by cancer cells through HA receptor-mediated endocytosis and subsequently release DOX due to Hyal-catalysed degradation of HA. This system presents successful bienzyme-responsive targeting drug delivery in an optimal fashion and provides potential applications for targeted cancer therapy.

  13. tLyP-1-conjugated mesoporous silica nanoparticles for tumor targeting and penetrating hydrophobic drug delivery

    NASA Astrophysics Data System (ADS)

    Xu, Baiyao; Ju, Yang; Song, Guanbin; Cui, Yanbin

    2013-12-01

    Mesoporous silica nanoparticles (MSNs) are among the most appealing candidates for targeted drug delivery, a process for which it is essential that nanoparticles be internalized into targeted cells with high speed and efficiency. Therefore, it is necessary to conjugate a targeting ligand to the surface of a nanocarrier in order to trigger rapid receptor-mediated endocytosis and effective cellular uptake, which occurs following recognition and selective binding to a target cell's membrane receptor. Here, a tumor targeting and penetrating drug delivery system (DDS) based on MSNs ( 100 nm in size) is described. The MSNs were functionalized by engrafting with the tumor-homing and penetrating peptide tLyP-1. The fabricated MSN-tLyP-1 loaded with camptothecin (CPT) showed a robust targeting and penetrating efficiency to HeLa cells and MCF-7 cells and induced the death of these cells. Moreover, the adverse side effect of CPT on human mesenchymal stem cells (hMSCs) was minimized, because the nanoparticles were selectively targeted to the tumor cells, and little hydrophobic CPT was released into the culture medium or blood. The results indicate that the MSN-tLyP-1 DDS has great potential for the delivery of hydrophobic anticancer drugs to target tumors.

  14. Can people find patient decision aids on the Internet?

    PubMed

    Morris, Debra; Drake, Elizabeth; Saarimaki, Anton; Bennett, Carol; O'Connor, Annette

    2008-12-01

    To determine if people could find patient decision aids (PtDAs) on the Internet using the most popular general search engines. We chose five medical conditions for which English language PtDAs were available from at least three different developers. The search engines used were: Google (www.google.com), Yahoo! (www.yahoo.com), and MSN (www.msn.com). For each condition and search engine we ran six searches using a combination of search terms. We coded all non-sponsored Web pages that were linked from the first page of the search results. Most first page results linked to informational Web pages about the condition, only 16% linked to PtDAs. PtDAs were more readily found for the breast cancer surgery decision (our searches found seven of the nine developers). The searches using Yahoo and Google search engines were more likely to find PtDAs. The following combination of search terms: condition, treatment, decision (e.g. breast cancer surgery decision) was most successful across all search engines (29%). While some terms and search engines were more successful, few resulted in direct links to PtDAs. Finding PtDAs would be improved with use of standardized labelling, providing patients with specific Web site addresses or access to an independent PtDA clearinghouse.

  15. Multiple independent regulatory pathways control UBI4 expression after heat shock in Saccharomyces cerevisiae.

    PubMed

    Simon, J R; Treger, J M; McEntee, K

    1999-02-01

    Transcription of the polyubiquitin gene UBI4 of Saccharomyces cerevisiae is strongly induced by a variety of environmental stresses, such as heat shock, nutrient depletion and exposure to DNA-damaging agents. This transcriptional response of UBI4 is likely to be the primary mechanism for increasing the pool of ubiquitin for degradation of stress-damaged proteins. Deletion and promoter fusion studies of the 5' regulatory sequences indicated that two different elements, heat shock elements (HSEs) and stress response element (STREs), contributed independently to heat shock regulation of the UBI4 gene. In the absence of HSEs, STRE sequences localized to the intervals -264 to -238 and -215 to -183 were needed for stress control of transcription after heat shock. Site-directed mutagenesis of the STRE (AG4) at -252 to -248 abolished heat shock induction of UBI4 transcription. Northern analysis demonstrated that cells containing either a temperature-sensitive HSF or non-functional Msn2p/Msn4p transcription factors induced high levels of UBI4 transcripts after heat shock. In cells deficient in both heat stress pathways, heat-induced UBI4 transcript levels were considerably lower but not abolished, suggesting a role for another factor(s) in stress control of its expression.

  16. "I did a lot of Googling": A qualitative study of exclusive breastfeeding support through social media.

    PubMed

    Alianmoghaddam, Narges; Phibbs, Suzanne; Benn, Cheryl

    2018-06-16

    Little qualitative research has been done to explore the quality of breastfeeding support through social media in New Zealand. This article aims to explore the influence of social media on exclusive breastfeeding practice. A qualitative study involving face-to-face postpartum interviews with 30 mothers who were recruited from the lower North Island of New Zealand. Each participant was followed via short monthly audio-recorded telephone interviews until giving up exclusive breastfeeding or until six months after the birth. The theories "strength of weak ties" and "landscapes of care" are applied to the thematic analysis of the interview material to illuminate the influence of social media on breastfeeding practices. Qualitative analysis of the interview material identified four themes: 1) Mothers need reliable online infant feeding information; 2) Smartphone apps can be a good option for promoting breastfeeding; 3) Information is accessed through weak ties among breastfeeding mothers on Facebook, and 4) the utility of geographically distant infant feeding support via Skype. Most participants sourced post-partum information and advice to support breastfeeding through the Internet, while those with geographically distant family members accessed emotional and practical breastfeeding support via Skype. Breastfeeding advocates should use social media to promote and support exclusive breast-feeding practice. The influence of social media on breastfeeding points to the relational nature of breastfeeding which is embedded in 'real' world and virtual social networks as well as the cultural, geographic and social contexts of a mother's life. Copyright © 2018 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  17. Can online conference systems improve veterinary education? A study about the capability of online conferencing and its acceptance.

    PubMed

    Koch, Michael; Fischer, Martin R; Tipold, Andrea; Ehlers, Jan P

    2012-01-01

    In veterinary medicine, there is an ongoing need for students, educators, and veterinarians to exchange the latest knowledge in their respective fields and to learn about unusual cases, emerging diseases, and treatment. Networking among veterinary faculties is developing rapidly, but conferences and meetings can be difficult to attend because of time limitations and travel costs. The current study examines acceptance of synchronous online conferences, seminars, meetings, and lectures by veterinarians and students. First, an online survey on the use of communication technology in veterinary medicine was made available for 15 weeks to every German-speaking veterinary university and via professional journals and an online veterinary forum. A total of 1,776 persons (620 veterinarians and 1,156 students) participated. Most reported using the Internet at least once per day; more than half reported using instant messengers. Most participants used the Internet for communication, but less than half used Skype. Second, to test the spectrum of tools for online conferences, a variety of "virtual classroom" systems (netucate systems iLinc, Adobe Acrobat Connect Pro, Cisco WebEx, Skype) were used to deliver student lectures, veterinary continuing-education courses, and academic conferences at the University of Veterinary Medicine, Hannover (TiHo). Of 591 participants in 63 online events, 99.4% rated the virtual events as enjoyable, 96.1% found them useful, and 92.4% said that they learned a lot. Participants noted that the courses were not tied to a certain place, and thus saved time and travel costs. Online conference systems thus offer new opportunities to provide information in veterinary medicine.

  18. Transporting Patients with Lethal Contagious Infections

    DTIC Science & Technology

    2002-04-01

    will be analyzed. If the patient requires a BSL-4 patient care room, he or she must be transported to the US Army Medical Research Institute of...consists of a physician, a registered nurse, and 4 to 6 medics who can manage one patient (Figure 2). The team can provide emer- gency care, such as airway...CLINICAL DECISIONS Section Editor: Colleen Swartz, RN, MSN, CCRN Transporting Patients with Lethal Contagious Infections Q If a trauma patient is

  19. Afghanistan: Post-Taliban Governance, Security, and U.S. Policy

    DTIC Science & Technology

    2010-04-04

    recent projects include Bagrami office park, Herat Industrial Park, Coca Cola plant , Safi mall in Kabul; Aynak copper mine in Lowgar (China); an...5 A pharmaceutical plant in Sudan (Al Shifa) believe to be producing chemical weapons for Al Qaeda also was struck that day, although U.S. reviews...later corroborated Sudan’s assertions that the plant was strictly civilian in nature. 6 http://www.msnbc.msn.com/id/4540958 Afghanistan: Post

  20. Dumbing Down the Net

    NASA Astrophysics Data System (ADS)

    Jamison, Mark A.; Hauge, Janice A.

    It is commonplace for sellers of goods and services to enhance the value of their products by paying extra for premium delivery service. For example, package delivery services such as Federal Express and the US Postal Service offer shippers a variety of delivery speeds and insurance programs. Web content providers such as Yahoo! and MSN Live Earth can purchase web-enhancing services from companies such as Akamai to speed the delivery of their web content to customers.1

  1. An FPGA-Based System for Tracking Digital Information Transmitted Via Peer-to-Peer Protocols

    DTIC Science & Technology

    2009-03-01

    Sullivan. ISPs are Pressed to Become Child Porn Cops, October 2008. http://www.msnbc.msn.com/id/27198621. DVR07. Hamza Dahmouni, Sandrine Vaton, and David...of child pornography. The Federal Bureau of Investigation’s (FBI) Re- gional Computer Forensics Laboratory states in its 2007 annual report that...cyber- crime, which includes crimes against children and child pornography, is the offense for which law enforcement requested assistance most often

  2. FINAL REPORT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    PETER, GARY F.

    2014-07-16

    Excellent progress was made in standardizing three complementary methods: Magnetic resonance imaging, x-ray micro CT, and MALDI imaging linear ion trap mass spectroscopy to image biomass and chemical, anatomical and functional changes that occur during pretreatment and hydrolysis. Magnetic resonance microscopy provides excellent images with as low as 5 uM resolution with hydrated biomass samples. We visualized dramatic changes in signal associated with the hydrolysis of the carbohydrates by strong acids. Quantitative diffusion approaches were used to probe more subtle structural changes in biomass. Diffusion tensor calculations reflect diffusion anisotropy and fractional anisotropy maps clearly show the longer range diffusionmore » within the vessels compared to within the fiber cells. The diffusion is increased along the cell walls of the vessels. Suggesting that further research with NMR imaging should be pursued. X-ray CT provides excellent images at as low as 3.5 uM resolution from dried biomass. Small increases in surface area, and decreases in local density have been quantified in with wood after mild pretreatments; these changes are expected to be underestimates of the hydrated wood, due to the ~12% shrinkage that occurs upon drying untreated wood. MALDI-MS spectra show high ion intensities at most mass to charge ratios in untreated and pretreated woody material. MALDI-MSn is required to improve specificity and reduce background for imaging. MALDI-TOF is not specific enough for carbohydrate identification. Using MALDI-LIT/MSn we can readily identify oligomeric glucans and xylans and their fragmentation patterns as well as those of the glucuronic acid side chains of birch 4-O-methyl glucuronxylan. Imaging of glucan and xylan oligomers show that many contain isobaric ions with different distributions, indicating again that MSn is needed for accurate imaging of lignocellulosic materials. We are now starting to integrate the three imaging methods by using the same set of biomass samples imaged with all three methods, and using common analytical software to quantify parameters from the three dimensional images. In addition to the proposed experiments, we conducted imaging studies with a novel TOF-SIMS instrument available through collaborations with the AMOLF goup led by Ron Heeren at the FOM Institute in Amersterdam, Netherlands. ToF-SIMS was used to image intact cross sections of Populus stems with high spatial resolution, chemically selectivity. ToF-SIMS images were correlated with fluorescence microscopy which allowed for more positive ion identification.« less

  3. Theoretical investigation of M@Pb122- and M@Sn122- Zintl clusters (M = Lrn+, Lun+, La3+, Ac3+ and n = 0, 1, 2, 3).

    PubMed

    Joshi, Meenakshi; Chandrasekar, Aditi; Ghanty, Tapan K

    2018-06-06

    The positions of lawrencium (Lr), lutetium (Lu), actinium (Ac) and lanthanum (La) in the periodic table have been a controversial topic for quite some time. According to studies carried out by different groups with their justifications, these elements may potentially be placed in the d-block, p-block or all four in a 15 element f-block. The present work looks into this issue from a new perspective, which involves encapsulation of these four elements into Zintl ion clusters, Pb122- and Sn122-, followed by the determination of the structural, thermodynamic and electronic properties of these endohedral M@Pb122- and M@Sn122- clusters (M = Lrn+, Lun+ with n = 0, 1, 2, 3) using first principles based density functional theory (DFT). These parameters are compared with similar clusters encapsulated La3+ and Ac3+ ions in order to seek out similarities and differences to draw conclusions about their placement in the periodic table. For the first time the structural, energetic, and electronic properties of these metal atom/ion encapsulated Pb122- and Sn122- clusters have been investigated thoroughly. Structural parameters such as bond distances, geometry and symmetry, electronic properties viz. the density of states, the molecular orbital ordering, the electron localization function, bond critical point properties and charge distributions have been analyzed. Additionally, the thermodynamic property of the binding energy during the encapsulation process has also been calculated. All M@Pb12+ and M@Sn12+ (M = Lr and Lu) clusters form stable 18 bonding electron magic number systems with shell closing. They show negative values of binding energy and relatively large HOMO-LUMO energy gaps indicating the stability of such clusters. All the calculated parameters for Lr encapsulated clusters closely match with the corresponding calculated parameters of Lu encapsulated clusters, confirming the similarity between Lr and Lu metal atoms in various oxidation states, though their atomic ground state valence electronic configurations are different. The effect of spin orbit coupling has also been investigated using the ZORA approach. It is interesting to discover that La and Ac showed striking similarities to Lr and Lu with respect to all the properties investigated and have formed a stable 18-electron system.

  4. The Future Role and Need for Nuclear Weapons in the 21st Century

    DTIC Science & Technology

    2007-01-01

    program, the Manhattan Project : Einstein‘s letter to Roosevelt in 1939 regarding the use of the energy from uranium for bombs, ―the imaginary German...succeed, nuclear weapons were introduced by the US into our world in 1945. The Manhattan Project efforts produced four bombs within its first three...Proceedings‖ (Livermore, CA: Lawrence Livermore National Laboratory, 1991), 14. 6 Ibid. , 12. 7 ― Manhattan Project ,‖ MSN Encarta, 2, http://encarta

  5. Ni-Co bimetal nanowires filled multiwalled carbon nanotubes for the highly sensitive and selective non-enzymatic glucose sensor applications

    PubMed Central

    Ramachandran, K.; Raj kumar, T.; Babu, K. Justice; Gnana kumar, G.

    2016-01-01

    The facile, time and cost efficient and environmental benign approach has been developed for the preparation of Nickel (Ni)-Cobalt (Co) alloy nanowires filled multiwalled carbon nanotubes (MWCNTs) with the aid of mesoporous silica nanoparticles (MSN)/Ni-Co catalyst. The controlled incorporation of Ni-Co nanostructures in the three dimensional (3D) pore structures of MSN yielded the catalytically active system for the MWCNT growth. The inner surface of MWCNTs was quasi-continuously filled with face-centered cubic (fcc) structured Ni-Co nanowires. The as-prepared nanostructures were exploited as non-enzymatic electrochemical sensor probes for the reliable detection of glucose. The electrochemical measurements illustrated that the fabricated sensor exhibited an excellent electrochemical performance toward glucose oxidation with a high sensitivity of 0.695 mA mM−1 cm−2, low detection limit of 1.2 μM, a wide linear range from 5 μM–10 mM and good selectivity. The unprecedented electrochemical performances obtained for the prepared nanocomposite are purely attributed to the synergistic effects of Ni-Co nanowires and MWCNTs. The constructed facile, selective and sensitive glucose sensor has also endowed its reliability in analyzing the human serum samples, which wide opened the new findings for exploring the novel nanostructures based glucose sensor devices with affordable cost and good stability. PMID:27833123

  6. Genome-wide investigation of the role of the tRNA nuclear-cytoplasmic trafficking pathway in regulation of the yeast Saccharomyces cerevisiae transcriptome and proteome.

    PubMed

    Chu, Hui-Yi; Hopper, Anita K

    2013-11-01

    In eukaryotic cells, tRNAs are transcribed and partially processed in the nucleus before they are exported to the cytoplasm, where they have an essential role in protein synthesis. Surprisingly, mature cytoplasmic tRNAs shuttle between nucleus and cytoplasm, and tRNA subcellular distribution is nutrient dependent. At least three members of the β-importin family, Los1, Mtr10, and Msn5, function in tRNA nuclear-cytoplasmic intracellular movement. To test the hypothesis that the tRNA retrograde pathway regulates the translation of particular transcripts, we compared the expression profiles from nontranslating mRNAs and polyribosome-associated translating mRNAs collected from msn5Δ, mtr10Δ, and wild-type cells under fed or acute amino acid depletion conditions. Our microarray data revealed that the methionine, arginine, and leucine biosynthesis pathways are targets of the tRNA retrograde process. We confirmed the microarray data by Northern and Western blot analyses. The levels of some of the particular target mRNAs were reduced, while others appeared not to be affected. However, the protein levels of all tested targets in these pathways were greatly decreased when tRNA nuclear import or reexport to the cytoplasm was disrupted. This study provides information that tRNA nuclear-cytoplasmic dynamics is connected to the biogenesis of proteins involved in amino acid biosynthesis.

  7. Genome-Wide Investigation of the Role of the tRNA Nuclear-Cytoplasmic Trafficking Pathway in Regulation of the Yeast Saccharomyces cerevisiae Transcriptome and Proteome

    PubMed Central

    Chu, Hui-Yi

    2013-01-01

    In eukaryotic cells, tRNAs are transcribed and partially processed in the nucleus before they are exported to the cytoplasm, where they have an essential role in protein synthesis. Surprisingly, mature cytoplasmic tRNAs shuttle between nucleus and cytoplasm, and tRNA subcellular distribution is nutrient dependent. At least three members of the β-importin family, Los1, Mtr10, and Msn5, function in tRNA nuclear-cytoplasmic intracellular movement. To test the hypothesis that the tRNA retrograde pathway regulates the translation of particular transcripts, we compared the expression profiles from nontranslating mRNAs and polyribosome-associated translating mRNAs collected from msn5Δ, mtr10Δ, and wild-type cells under fed or acute amino acid depletion conditions. Our microarray data revealed that the methionine, arginine, and leucine biosynthesis pathways are targets of the tRNA retrograde process. We confirmed the microarray data by Northern and Western blot analyses. The levels of some of the particular target mRNAs were reduced, while others appeared not to be affected. However, the protein levels of all tested targets in these pathways were greatly decreased when tRNA nuclear import or reexport to the cytoplasm was disrupted. This study provides information that tRNA nuclear-cytoplasmic dynamics is connected to the biogenesis of proteins involved in amino acid biosynthesis. PMID:23979602

  8. Nutritional Composition and Antioxidant Capacity in Edible Flowers: Characterisation of Phenolic Compounds by HPLC-DAD-ESI/MSn

    PubMed Central

    Navarro-González, Inmaculada; González-Barrio, Rocío; García-Valverde, Verónica; Bautista-Ortín, Ana Belén; Periago, María Jesús

    2014-01-01

    Edible flowers are commonly used in human nutrition and their consumption has increased in recent years. The aim of this study was to ascertain the nutritional composition and the content and profile of phenolic compounds of three edible flowers, monks cress (Tropaeolum majus), marigold (Tagetes erecta) and paracress (Spilanthes oleracea), and to determine the relationship between the presence of phenolic compounds and the antioxidant capacity. Proximate composition, total dietary fibre (TDF) and minerals were analysed according to official methods: total phenolic compounds (TPC) were determined with Folin-Ciocalteu’s reagent, whereas antioxidant capacity was evaluated using Trolox Equivalent Antioxidant Capacity (TEAC) and Oxygen Radical Absorbance Capacity (ORAC) assays. In addition, phenolic compounds were characterised by HPLC-DAD-MSn. In relation to the nutritional value, the edible flowers had a composition similar to that of other plant foods, with a high water and TDF content, low protein content and very low proportion of total fat—showing significant differences among samples. The levels of TPC compounds and the antioxidant capacity were significantly higher in T. erecta, followed by S. oleracea and T. majus. Thirty-nine different phenolic compounds were tentatively identified, with flavonols being the major compounds detected in all samples, followed by anthocyanins and hydroxycynnamic acid derivatives. In T. erecta small proportions of gallotannin and ellagic acid were also identified. PMID:25561232

  9. Imaging MS Methodology for More Chemical Information in Less Data Acquisition Time Utilizing a Hybrid Linear Ion Trap-Orbitrap Mass Spectrometer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Perdian, D. C.; Lee, Young Jin

    2010-11-15

    A novel mass spectrometric imaging method is developed to reduce the data acquisition time and provide rich chemical information using a hybrid linear ion trap-orbitrap mass spectrometer. In this method, the linear ion trap and orbitrap are used in tandem to reduce the acquisition time by incorporating multiple linear ion trap scans during an orbitrap scan utilizing a spiral raster step plate movement. The data acquisition time was decreased by 43-49% in the current experiment compared to that of orbitrap-only scans; however, 75% or more time could be saved for higher mass resolution and with a higher repetition rate laser.more » Using this approach, a high spatial resolution of 10 {micro}m was maintained at ion trap imaging, while orbitrap spectra were acquired at a lower spatial resolution, 20-40 {micro}m, all with far less data acquisition time. Furthermore, various MS imaging methods were developed by interspersing MS/MS and MSn ion trap scans during orbitrap scans to provide more analytical information on the sample. This method was applied to differentiate and localize structural isomers of several flavonol glycosides from an Arabidopsis flower petal in which MS/MS, MSn, ion trap, and orbitrap images were all acquired in a single data acquisition.« less

  10. Synthesis and characterization of pore size-tunable magnetic mesoporous silica nanoparticles.

    PubMed

    Zhang, Jixi; Li, Xu; Rosenholm, Jessica M; Gu, Hong-chen

    2011-09-01

    Magnetic mesoporous silica nanoparticles (M-MSNs) are emerging as one of the most appealing candidates for theranostic carriers. Herein, a simple synthesis method of M-MSNs with a single Fe(3)O(4) nanocrystal core and a mesoporous shell with radially aligned pores was elaborated using tetraethyl orthosilicate (TEOS) as silica source, cationic surfactant CTAB as template, and 1,3,5-triisopropylbenzene (TMB)/decane as pore swelling agents. Due to the special localization of TMB during the synthesis process, the pore size was increased with added TMB amount within a limited range, while further employment of TMB lead to severe particle coalescence and not well-developed pore structure. On the other hand, when a proper amount of decane was jointly incorporated with limited amounts of TMB, effective pore expansion of M-MSNs similar to that of analogous mesoporous silica nanoparticles was realized. The resultant M-MSN materials possessed smaller particle size (about 40-70 nm in diameter), tunable pore sizes (3.8-6.1 nm), high surface areas (700-1100 m(2)/g), and large pore volumes (0.44-1.54 cm(3)/g). We also demonstrate their high potential in conventional DNA loading. Maximum loading capacity of salmon sperm DNA (375 mg/g) was obtained by the use of the M-MSN sample with the largest pore size of 6.1 nm. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Large pore mesoporous silica nanomaterials for application in delivery of biomolecules

    NASA Astrophysics Data System (ADS)

    Knežević, Nikola Ž.; Durand, Jean-Olivier

    2015-01-01

    Various approaches for the synthesis of mesoporous silicate nanoparticles (MSN) with large pore (LP) diameters (in the range of 3-50 nm) are reviewed in this article. The work also covers the construction of magnetic analogues of large pore-mesoporous silica nanoparticles (LPMMSN) and their biomedical applications. The constructed materials exhibit vast potential for application in the loading and delivery of large drug molecules and biomolecules. Literature reports on the application of LPMSN and LPMMSN materials for the adsorption and delivery of proteins, enzymes, antibodies, and nucleic acids are covered in depth, which exemplify their highly potent characteristics for use in drug and biomolecule delivery to diseased tissues.Various approaches for the synthesis of mesoporous silicate nanoparticles (MSN) with large pore (LP) diameters (in the range of 3-50 nm) are reviewed in this article. The work also covers the construction of magnetic analogues of large pore-mesoporous silica nanoparticles (LPMMSN) and their biomedical applications. The constructed materials exhibit vast potential for application in the loading and delivery of large drug molecules and biomolecules. Literature reports on the application of LPMSN and LPMMSN materials for the adsorption and delivery of proteins, enzymes, antibodies, and nucleic acids are covered in depth, which exemplify their highly potent characteristics for use in drug and biomolecule delivery to diseased tissues. Dedicated to Professor Jeffrey I. Zink on the occasion of his 70th birthday.

  12. Multi-stage Mass Spectrometry of Poly(vinyl pyrrolidone) and Its Vinyl Succinimide Copolymer Formed upon Exposure to Sodium Hypochlorite

    PubMed Central

    Fouquet, Thierry; Torimura, Masaki; Sato, Hiroaki

    2016-01-01

    The degradation routes of poly(vinyl pyrrolidone) (PVP) exposed to sodium hypochlorite (bleach) have been previously investigated using chemical analyses such as infrared spectroscopy. So far, no reports have proposed mass spectrometry (MS) as an alternative tool despite its capability to provide molecular and structural information using its single stage electrospray (ESI) or matrix assisted laser desorption ionization (MALDI) and multi stage (MSn) configurations, respectively. The present study thus reports on the characterization of PVP after its exposure to bleach by high resolution MALDI spiralTOF-MS and Kendrick mass defect analysis providing clues as to the formation of a vinyl pyrrolidone/vinyl succinimide copolymeric degradation product. A thorough investigation of the fragmentation pathways of PVP adducted with sodium and proton allows one main route to be described—namely the release of the pyrrolidone pendant group in a charge remote and charge driven mechanism, respectively. Extrapolating this fragmentation pathway, the oxidation of vinyl pyrrolidone into vinyl succinimide hypothesized from the single stage MS is validated by the detection of an alternative succinimide neutral loss in lieu of the pyrrolidone release in the ESI-MSn spectra of the aged PVP sample. It constitutes an example of application of multi-stage mass spectrometry for the characterization of the degradation of polymeric samples at a molecular level. PMID:27800293

  13. Ni-Co bimetal nanowires filled multiwalled carbon nanotubes for the highly sensitive and selective non-enzymatic glucose sensor applications

    NASA Astrophysics Data System (ADS)

    Ramachandran, K.; Raj Kumar, T.; Babu, K. Justice; Gnana Kumar, G.

    2016-11-01

    The facile, time and cost efficient and environmental benign approach has been developed for the preparation of Nickel (Ni)-Cobalt (Co) alloy nanowires filled multiwalled carbon nanotubes (MWCNTs) with the aid of mesoporous silica nanoparticles (MSN)/Ni-Co catalyst. The controlled incorporation of Ni-Co nanostructures in the three dimensional (3D) pore structures of MSN yielded the catalytically active system for the MWCNT growth. The inner surface of MWCNTs was quasi-continuously filled with face-centered cubic (fcc) structured Ni-Co nanowires. The as-prepared nanostructures were exploited as non-enzymatic electrochemical sensor probes for the reliable detection of glucose. The electrochemical measurements illustrated that the fabricated sensor exhibited an excellent electrochemical performance toward glucose oxidation with a high sensitivity of 0.695 mA mM-1 cm-2, low detection limit of 1.2 μM, a wide linear range from 5 μM-10 mM and good selectivity. The unprecedented electrochemical performances obtained for the prepared nanocomposite are purely attributed to the synergistic effects of Ni-Co nanowires and MWCNTs. The constructed facile, selective and sensitive glucose sensor has also endowed its reliability in analyzing the human serum samples, which wide opened the new findings for exploring the novel nanostructures based glucose sensor devices with affordable cost and good stability.

  14. Beyond Social Media: A Cross-Sectional Survey of Other Internet and Mobile Phone Applications in a Community Psychiatry Population.

    PubMed

    Colder Carras, Michelle; Mojtabai, Ramin; Cullen, Bernadette

    2018-03-01

    Popular media applications have been shown to benefit people with severe mental illness by facilitating communication and social support, helping patients cope with or manage symptoms, and providing a way to monitor or predict mental health states. Although many studies of technology use by individuals with severe mental illness have focused primarily on use of social media, this study provides additional information about use of Internet applications such as blogs, wikis (websites that allow collaborative editing of content and structure by users), video games, and Skype by a community psychiatry population. All English-speaking patients attending an outpatient program during a 4-week period in 2011 (N=274) were surveyed about their technology use and demographic information; 189 patients provided demographic data and comprised the sample. Among Internet users (n=112), rates of use of message boards, wikis, Skype, role-playing games, and blogs ranged from 26.8% to 34.8%. Among mobile phone users (n=162), 41.4% used their phones to access the Internet and 25.3% used Twitter on their phones. In multivariate analysis, patients who had attended or completed college had much greater odds of accessing the Internet on mobile phones. Older patients were much less likely to access the Internet or use Twitter. Our findings indicate that use of several popular forms of media is not uncommon in a community psychiatry population, but that rates of use differ on the basis of age and education. As the digital divide between people with severe mental illness and the general population is lessening, further research is needed to determine how to best leverage various types of media to support mental health recovery and complement clinical care.

  15. A Randomized Double-Blind Controlled Trial Comparing Davanloo Intensive Short-Term Dynamic Psychotherapy as Internet-Delivered Vs Treatment as Usual for Medically Unexplained Pain: A 6-Month Pilot Study.

    PubMed

    Chavooshi, Behzad; Mohammadkhani, Parvaneh; Dolatshahi, Behrouz

    2016-01-01

    Research has shown that Intensive Short-Term Dynamic Psychotherapy (ISTDP) can effectively decrease pain intensity and improve quality of life in patients with medically unexplained pain. Understanding that not all patients with medically unexplained pain have access to in-person ISTDP, this study aims to investigate the efficacy of an Internet-delivered ISTDP for individuals with medically unexplained pain using Skype in comparison with treatment as usual. In this randomized controlled trial, 100 patients were randomly allocated into Internet-delivered ISTDP (n = 50) and treatment-as- usual (n = 50) groups. Treatment intervention consisted of 16 weekly, hour-long therapy sessions. The primary outcome was perceived pain assessed using the Numeric Pain Rating Scale. The secondary outcome included Depression Anxiety Stress Scale-21, Emotion Regulation Questionnaire, Mindful Attention Awareness Scale, and Quality-of-Life Inventory. Blind assessments were conducted at the baseline, posttreatment, and at a 6-month follow-up. In the intention-to-treat analysis, pain symptoms in the intervention group were significantly reduced (p < 0.001), whereas a reduction was not observed in the treatment as usual group (p = 0.651). Moreover, there were significant decreases in depression, anxiety, and stress, as well as a greater increase in emotion regulation functioning, mindfulness, and quality of life observed in the intervention group 6 months after the treatment compared with the treatment as usual condition. The results of this pilot trial demonstrate that 16 weeks of ISTDP delivered by Skype can significantly improve pain intensity and clinical symptoms of medically unexplained pain. Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

  16. Energy Security: The Pathway to a Cost-Effective, Efficient, and Reliable Energy Future

    DTIC Science & Technology

    2010-03-12

    mention of these facilities is likely to incite talk of grisly death and destruction of biblical proportion. Such is the plight of the nuclear...gulf-of-mexico/,. (accessed January 12, 2010)0 31 John W Schoen, "Can Technology Help find Oil Fast Enough?", msnbc.com, December 20, 2004, http:l...John W. "Can Technology Help find Oil Fast Enough?", msnbc.com, December 20, 2004, http://www.msnbc.msn.com/id/6072980/, (accessed January 11, 2010

  17. Efficacy of the Direct Instruction Language for Learning (DI-LL) Program to Promote Expressive and Receptive Language in Children with Autism Spectrum Disorder

    DTIC Science & Technology

    2016-07-01

    Receptive Language in Children with Autism Spectrum Disorder PRINCIPAL INVESTIGATOR: Lawrence Scahill, MSN, PhD CONTRACTING ORGANIZATION: Emory...REPORT TYPE Annual 3. DATES COVERED 15Jun2015 - 14Jun2016 4. TITLE AND SUBTITLE Receptive Language in Children with Autism Spectrum Disorder 5a...indicates that as many as 75% of children with autism spectrum disorder (ASD) have language delay ranging from mild to severe. Many interventions have

  18. Pharmacological and Behavioral Enhancement of Neuroplasticity in the MPTP-Lesioned Mouse and Nonhuman Primate

    DTIC Science & Technology

    2009-05-01

    neurabin co-localization with eGFP. Figure 2. Neurabin Knock Down In Vitro: 293T cells were employed to test the effect of eGFP+shRNAmir 73 FUGW-VSVG...adults: a review of health benefits and the effectiveness of interventions. J Sports Sci 2004; 22 :703-25. 7. Gibbons RJ, Balady GJ, Bricker JT, et al...neurons (MSN) of the striatum, dictating the electrophysiological properties of these cells . 22 , 23 There is compelling data that the loss of nigral

  19. Radionuclide development at BNL for nuclear medicine therapy.

    PubMed

    Mausner, L F; Kolsky, K L; Joshi, V; Srivastava, S C

    1998-04-01

    Radionuclides with medium energy beta emission and a several day half-life have often been viewed as attractive candidates for radioimmunotherapy. Among the most promising in this category are 47Sc, 67Cu, 153Sm, 188Re, and 199Au. The production of 67Cu, 153Sm, 199Au at BNL is summarized and the development of the latest candidate for this application, 47Sc, is described in detail. We also summarize the development of another important therapeutic radionuclide, 117mSn for bone pain palliation.

  20. Center for the Study of Traumatic Stress 2010 Annual Report: Improving Psychological Health and Resilience Through Trauma Research, Education and Consultation

    DTIC Science & Technology

    2011-01-01

    Health Sciences 4301 Jones Bridge Road Bethesda, MD 20814-4799 Craig H. Llewellyn , M.D. professor Department of Military and emergency Medicine F...Health Sciences,4301 Jones Bridge Road,Bethesda,MD,20814-4799 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND...F. edward Hebert School of Medicine uniformed Services university 4301 Jones Bridge Road Bethesda, MD20814-4799 BG (ret) William T. Bester, RN, MSN

  1. Iraq: Oil and Gas Legislation, Revenue Sharing, and U.S. Policy

    DTIC Science & Technology

    2008-10-01

    the Kurdistan Regional Government as an official English draft version. It is available online at [h t t p : / /www. kr g . o r g / u p l o a d s...law states that contract holders may be given exclusive rights to exploration, development, production, and marketing of Iraqi oil for specified periods...Speaking: Amb. Samir Sumaidaie” Newsweek Online , September 24, 2007. Available at [http://www.msnbc.msn.com/id/20958064/site/newsweek/page/0/]. 20

  2. Nup100 regulates Saccharomyces cerevisiae replicative life span by mediating the nuclear export of specific tRNAs

    PubMed Central

    Lord, Christopher L.; Ospovat, Ophir; Wente, Susan R.

    2017-01-01

    Nuclear pore complexes (NPCs), which are composed of nucleoporins (Nups) and regulate transport between the nucleus and cytoplasm, significantly impact the replicative life span (RLS) of Saccharomyces cerevisiae. We previously reported that deletion of the nonessential gene NUP100 increases RLS, although the molecular basis for this effect was unknown. In this study, we find that nuclear tRNA accumulation contributes to increased longevity in nup100Δ cells. Fluorescence in situ hybridization (FISH) experiments demonstrate that several specific tRNAs accumulate in the nuclei of nup100Δ mutants. Protein levels of the transcription factor Gcn4 are increased when NUP100 is deleted, and GCN4 is required for the elevated life spans of nup100Δ mutants, similar to other previously described tRNA export and ribosomal mutants. Northern blots indicate that tRNA splicing and aminoacylation are not significantly affected in nup100Δ cells, suggesting that Nup100 is largely required for nuclear export of mature, processed tRNAs. Distinct tRNAs accumulate in the nuclei of nup100Δ and msn5Δ mutants, while Los1-GFP nucleocytoplasmic shuttling is unaffected by Nup100. Thus, we conclude that Nup100 regulates tRNA export in a manner distinct from Los1 or Msn5. Together, these experiments reveal a novel Nup100 role in the tRNA life cycle that impacts the S. cerevisiae life span. PMID:27932586

  3. The localization of nuclear exporters of the importin-beta family is regulated by Snf1 kinase, nutrient supply and stress.

    PubMed

    Quan, XinXin; Yu, Jennifer; Bussey, Howard; Stochaj, Ursula

    2007-07-01

    In the budding yeast Saccharomyces cerevisiae, four members of the importin-beta family of nuclear carriers, Xpo1p/Crm1p, Cse1p, Msn5p and Los1p, function as exporters of protein and tRNA. Under normal growth conditions GFP-tagged exporters are predominantly associated with nuclei. The presence of Snf1 kinase, a key regulator of cell growth and a metabolic sensor, controls the localization of GFP-exporters. Additional glucose-dependent, but Snf1-independent, mechanisms regulate carrier distribution and a switch from fermentable to non-fermentable carbon sources relocates all of the carriers, suggesting a link to the nutritional status of the cell. Moreover, stress controls the proper localization of GFP-exporters, which mislocalize upon exposure to heat, ethanol and starvation. Stress may activate the MAPK cell integrity cascade, and we tested the role of this pathway in exporter localization. Under non-stress conditions, the proper distribution of GFP-Cse1p and Xpo1p/Crm1p-GFP requires kinases of the cell integrity cascade. By contrast, Msn5p-GFP and Los1p-GFP rely on the MAPK module to relocate to the cytoplasm when cells are stressed with ethanol. Our results indicate that the association of nuclear exporters with nuclei is controlled by multiple mechanisms that are organized in a hierarchical fashion and linked to the physiological state of the cell.

  4. Secure Authentication for Remote Patient Monitoring with Wireless Medical Sensor Networks †

    PubMed Central

    Hayajneh, Thaier; Mohd, Bassam J; Imran, Muhammad; Almashaqbeh, Ghada; Vasilakos, Athanasios V.

    2016-01-01

    There is broad consensus that remote health monitoring will benefit all stakeholders in the healthcare system and that it has the potential to save billions of dollars. Among the major concerns that are preventing the patients from widely adopting this technology are data privacy and security. Wireless Medical Sensor Networks (MSNs) are the building blocks for remote health monitoring systems. This paper helps to identify the most challenging security issues in the existing authentication protocols for remote patient monitoring and presents a lightweight public-key-based authentication protocol for MSNs. In MSNs, the nodes are classified into sensors that report measurements about the human body and actuators that receive commands from the medical staff and perform actions. Authenticating these commands is a critical security issue, as any alteration may lead to serious consequences. The proposed protocol is based on the Rabin authentication algorithm, which is modified in this paper to improve its signature signing process, making it suitable for delay-sensitive MSN applications. To prove the efficiency of the Rabin algorithm, we implemented the algorithm with different hardware settings using Tmote Sky motes and also programmed the algorithm on an FPGA to evaluate its design and performance. Furthermore, the proposed protocol is implemented and tested using the MIRACL (Multiprecision Integer and Rational Arithmetic C/C++) library. The results show that secure, direct, instant and authenticated commands can be delivered from the medical staff to the MSN nodes. PMID:27023540

  5. Differential excitability and modulation of striatal medium spiny neuron dendrites

    PubMed Central

    Day, Michelle; Wokosin, David; Plotkin, Joshua L.; Tian, Xinyoung; Surmeier, D. James

    2011-01-01

    The loss of striatal dopamine (DA) in Parkinson's disease (PD) models triggers a cell-type specific reduction in the density of dendritic spines in D2 receptor-expressing striatopallidal medium spiny neurons (D2 MSNs). How the intrinsic properties of MSN dendrites, where the vast majority of DA receptors are found, contribute to this adaptation is not clear. To address this question, two-photon laser scanning microscopy (2PLSM) was performed in patch-clamped mouse MSNs identified in striatal slices by expression of green fluorescent protein (eGFP) controlled by DA receptor promoters. These studies revealed that single back-propagating action potentials (bAP) produced more reliable elevations in cytosolic Ca2+ concentration at distal dendritic locations in D2 MSNs than at similar locations in D1 receptor-expressing striatonigral MSNs (D1 MSNs). In both cell types, the dendritic Ca2+ entry elicited by bAPs was enhanced by pharmacological blockade of Kv4, but not Kv1 K+ channels. Local application of DA depressed dendritic bAP-evoked Ca2+ transients, whereas application of ACh increased these Ca2+ transients in D2 MSNs—but not in D1 MSNs. Following DA depletion, bAP-evoked Ca2+ transients were enhanced in distal dendrites and spines in D2 MSNs. Taken together, these results suggest that normally D2 MSN dendrites are more excitable than those of D1 MSNs and that DA depletion exaggerates this asymmetry, potentially contributing to adaptations in PD models. PMID:18987196

  6. The oxidative stress response of the opportunistic fungal pathogen Candida glabrata.

    PubMed

    Briones-Martin-Del-Campo, Marcela; Orta-Zavalza, Emmanuel; Juarez-Cepeda, Jacqueline; Gutierrez-Escobedo, Guadalupe; Cañas-Villamar, Israel; Castaño, Irene; De Las Peñas, Alejandro

    2014-01-01

    Organisms have evolved different strategies to respond to oxidative stress generated as a by-product of aerobic respiration and thus maintain the redox homeostasis within the cell. In particular, fungal pathogens are exposed to reactive oxygen species (ROS) when they interact with the phagocytic cells of the host which are the first line of defense against fungal infections. These pathogens have co-opted the enzymatic (catalases, superoxide dismutases (SODs), and peroxidases) and non-enzymatic (glutathione) mechanisms used to maintain the redox homeostasis within the cell, to resist oxidative stress and ensure survival within the host. Several virulence factors have been related to the response to oxidative stress in pathogenic fungi. The opportunistic fungal pathogen Candida glabrata (C. glabrata) is the second most common cause of candidiasis after Candida albicans (C. albicans). C. glabrata has a well defined oxidative stress response (OSR), which include both enzymatic and non-enzymatic mechanisms. C. glabrata OSR is controlled by the well-conserved transcription factors Yap1, Skn7, Msn2 and Msn4. In this review, we describe the OSR of C. glabrata, what is known about its core elements, its regulation and how C. glabrata interacts with the host. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  7. The karyopherin Kap95 and the C-termini of Rfa1, Rfa2, and Rfa3 are necessary for efficient nuclear import of functional RPA complex proteins in Saccharomyces cerevisiae.

    PubMed

    Belanger, Kenneth D; Griffith, Amanda L; Baker, Heather L; Hansen, Jeanne N; Kovacs, Laura A Simmons; Seconi, Justin S; Strine, Andrew C

    2011-09-01

    Nuclear protein import in eukaryotic cells is mediated by karyopherin proteins, which bind to specific nuclear localization signals on substrate proteins and transport them across the nuclear envelope and into the nucleus. Replication protein A (RPA) is a nuclear protein comprised of three subunits (termed Rfa1, Rfa2, and Rfa3 in Saccharomyces cerevisiae) that binds single-stranded DNA and is essential for DNA replication, recombination, and repair. RPA associates with two different karyopherins in yeast, Kap95, and Msn5/Kap142. However, it is unclear which of these karyopherins is responsible for RPA nuclear import. We have generated GFP fusion proteins with each of the RPA subunits and demonstrate that these Rfa-GFP chimeras are functional in yeast cells. The intracellular localization of the RPA proteins in live cells is similar in wild-type and msn5Δ deletion strains but becomes primarily cytoplasmic in cells lacking functional Kap95. Truncating the C-terminus of any of the RPA subunits results in mislocalization of the proteins to the cytoplasm and a loss of protein-protein interactions between the subunits. Our data indicate that Kap95 is likely the primary karyopherin responsible for RPA nuclear import in yeast and that the C-terminal regions of Rfa1, Rfa2, and Rfa3 are essential for efficient nucleocytoplasmic transport of each RPA subunit.

  8. Targeting the Oxidative Stress Response System of Fungi with Redox-Potent Chemosensitizing Agents

    PubMed Central

    Kim, Jong H.; Chan, Kathleen L.; Faria, Natália C. G.; Martins, M. de L.; Campbell, Bruce C.

    2012-01-01

    The cellular antioxidant system is a target in the antifungal action of amphotericin B (AMB) and itraconazole (ITZ), in filamentous fungi. The sakAΔ mutant of Aspergillus fumigatus, a mitogen-activated protein kinase (MAPK) gene deletion mutant in the antioxidant system, was found to be more sensitive to AMB or ITZ than other A. fumigatus strains, a wild type and a mpkCΔ mutant (a MAPK gene deletion mutant in the polyalcohol sugar utilization system). Complete fungal kill (≥99.9%) by ITZ or AMB was also achieved by much lower dosages for the sakAΔ mutant than for the other strains. It appears msnA, an Aspergillus ortholog to Saccharomyces cerevisiae MSN2 (encoding a stress-responsive C2H2-type zinc-finger regulator) and sakA and/or mpkC (upstream MAPKs) are in the same stress response network under tert-butyl hydroperoxide (t-BuOOH)-, hydrogen peroxide (H2O2)- or AMB-triggered toxicity. Of note is that ITZ-sensitive yeast pathogens were also sensitive to t-BuOOH, showing a connection between ITZ sensitivity and antioxidant capacity of fungi. Enhanced antifungal activity of AMB or ITZ was achieved when these drugs were co-applied with redox-potent natural compounds, 2,3-dihydroxybenzaldehyde, thymol or salicylaldehyde, as chemosensitizing agents. We concluded that redox-potent compounds, which target the antioxidant system in fungi, possess a chemosensitizing capacity to enhance efficacy of conventional drugs. PMID:22438852

  9. Secure Authentication for Remote Patient Monitoring with Wireless Medical Sensor Networks.

    PubMed

    Hayajneh, Thaier; Mohd, Bassam J; Imran, Muhammad; Almashaqbeh, Ghada; Vasilakos, Athanasios V

    2016-03-24

    There is broad consensus that remote health monitoring will benefit all stakeholders in the healthcare system and that it has the potential to save billions of dollars. Among the major concerns that are preventing the patients from widely adopting this technology are data privacy and security. Wireless Medical Sensor Networks (MSNs) are the building blocks for remote health monitoring systems. This paper helps to identify the most challenging security issues in the existing authentication protocols for remote patient monitoring and presents a lightweight public-key-based authentication protocol for MSNs. In MSNs, the nodes are classified into sensors that report measurements about the human body and actuators that receive commands from the medical staff and perform actions. Authenticating these commands is a critical security issue, as any alteration may lead to serious consequences. The proposed protocol is based on the Rabin authentication algorithm, which is modified in this paper to improve its signature signing process, making it suitable for delay-sensitive MSN applications. To prove the efficiency of the Rabin algorithm, we implemented the algorithm with different hardware settings using Tmote Sky motes and also programmed the algorithm on an FPGA to evaluate its design and performance. Furthermore, the proposed protocol is implemented and tested using the MIRACL (Multiprecision Integer and Rational Arithmetic C/C++) library. The results show that secure, direct, instant and authenticated commands can be delivered from the medical staff to the MSN nodes.

  10. Ingenious pH-sensitive dextran/mesoporous silica nanoparticles based drug delivery systems for controlled intracellular drug release.

    PubMed

    Zhang, Min; Liu, Jia; Kuang, Ying; Li, Qilin; Zheng, Di-Wei; Song, Qiongfang; Chen, Hui; Chen, Xueqin; Xu, Yanglin; Li, Cao; Jiang, Bingbing

    2017-05-01

    In this work, dextran, a polysaccharide with excellent biocompatibility, is applied as the "gatekeeper" to fabricate the pH-sensitive dextran/mesoporous silica nanoparticles (MSNs) based drug delivery systems for controlled intracellular drug release. Dextran encapsulating on the surface of MSNs is oxidized by NaIO 4 to obtain three kinds of dextran dialdehydes (PADs), which are then coupled with MSNs via pH-sensitive hydrazone bond to fabricate three kinds of drug carriers. At pH 7.4, PADs block the pores to prevent premature release of anti-cancer drug doxorubicin hydrochloride (DOX). However, in the weakly acidic intracellular environment (pH∼5.5) the hydrazone can be ruptured; and the drug can be released from the carriers. The drug loading capacity, entrapment efficiency and release rates of the drug carriers can be adjusted by the amount of NaIO 4 applied in the oxidation reaction. And from which DOX@MSN-NH-N=C-PAD 10 is chosen as the most satisfactory one for the further in vitro cytotoxicity studies and cellular uptake studies. The results demonstrate that DOX@MSN-NH-N=C-PAD 10 with an excellent pH-sensitivity can enter HeLa cells to release DOX intracellular due to the weakly acidic pH intracellular and kill the cells. In our opinion, the ingenious pH-sensitive drug delivery systems have application potentials for cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Contrasting online MSn spectra of organic acids in ambient aerosol from the boreal forest at Hyytiälä, Finland and from the mixed forest at the Taunus observatory, Germany

    NASA Astrophysics Data System (ADS)

    Vogel, Alexander L.; Äijälä, Mikko; Ehn, Mikael; Junninen, Heikki; Petäjä, Tuukka; Worsnop, Douglas R.; Kulmala, Markku; Williams, Jonathan; Schneider, Johannes; Hoffmann, Thorsten

    2013-04-01

    Emission of biogenic volatile organic compounds (BVOCs) by the vegetation and subsequent atmospheric oxidation leads to the formation of secondary organic aerosol (SOA). Therefore, forests are a main source of aerosols which have significant impact on the earth's climate.[1] The oxidation of BVOCs results in a variety of mostly unidentified organic species in trace level concentrations, which partition between gas- and particle-phase. Organic acids are of particular importance for the particle-phase fraction, since the higher oxidation state and molecular mass, compared to the corresponding precursors, is accompanied by a much lower volatility. Until now, only limited instrumentation exists for the simultaneous online analysis of organic acids in gas- and particle-phase. Here we show the first field application of an Atmospheric Pressure Chemical Ionization Ion Trap Mass Spectrometer (APCI-IT-MS) in combination with a miniature Versatile Aerosol Concentration Enrichment System (mVACES) for measuring organic acids in gas- and particle-phase[2]. The benefits of the online APCI-IT-MS are soft ionization with low fragmentation, high time resolution and less sampling artifacts than in the common procedure of taking filter samples, extraction and subsequent detection with LC-MS. Furthermore, the capability to perform online MSn of isolated m/z ratios from ambient and laboratory generated aerosol leads to an improved understanding of the composition of secondary organic aerosol. The here described measurements were conducted during the HUMPPA-COPEC 2010 campaign at Hyytiälä, Finland and during the INUIT campaign 2012 on Mt. Kleiner Feldberg, Germany. By merging APCI-IT-MS data with data from the Aerodyné C-ToF-AMS, it can be observed that the gas- to particle-partitioning of organic acids strongly depends on the fraction of aerosol which is organic matter, as it is predicted by a partitioning model[3]. High observed gas-phase concentrations of organic acids at Hyytiälä are a strong hint for unidentified species. This can be supported by MSn observations, where the fragmentation pattern from Hyytiälä show different signals compared to the fragmentation pattern from the same m/z ratio at the Taunus Observatory and from chamber terpene ozonolysis. Literature: [1] Tunved, P. et al. (2006) Science 312, 261-263. [2] Vogel, A. L. et al. (2012) Atmos. Meas. Tech. Discuss. 5, 6147-6182. [3] Pankow, J. F. (1994) Atmos. Env. 28, 189-193.

  12. Mesoporous silica nanoparticle-based substrates for cell directed delivery of Notch signalling modulators to control myoblast differentiation

    NASA Astrophysics Data System (ADS)

    Böcking, Dominique; Wiltschka, Oliver; Niinimäki, Jenni; Shokry, Hussein; Brenner, Rolf; Lindén, Mika; Sahlgren, Cecilia

    2014-01-01

    Biochemical cues are critical to control stem cell function and can be utilized to develop smart biomaterials for stem cell engineering. The challenge is to deliver these cues in a restricted manner with spatial and temporal control. Here we have developed bilayer films of mesoporous silica nanoparticles for delayed cellular delivery of Notch modulators to promote muscle stem cell differentiation. We demonstrate that drug-loaded particles are internalized from the particle-covered surface, which allows for direct delivery of the drug into the cell and a delayed and confined drug release. Substrates of particles loaded with γ-secretase-inhibitors, which block the Notch signalling pathway, promoted efficient differentiation of myoblasts. The particle substrates were fully biocompatible and did not interfere with the inherent differentiation process. We further demonstrate that impregnating commercially available, biocompatible polymer scaffolds with MSNs allows for a free standing substrate for cell directed drug delivery.Biochemical cues are critical to control stem cell function and can be utilized to develop smart biomaterials for stem cell engineering. The challenge is to deliver these cues in a restricted manner with spatial and temporal control. Here we have developed bilayer films of mesoporous silica nanoparticles for delayed cellular delivery of Notch modulators to promote muscle stem cell differentiation. We demonstrate that drug-loaded particles are internalized from the particle-covered surface, which allows for direct delivery of the drug into the cell and a delayed and confined drug release. Substrates of particles loaded with γ-secretase-inhibitors, which block the Notch signalling pathway, promoted efficient differentiation of myoblasts. The particle substrates were fully biocompatible and did not interfere with the inherent differentiation process. We further demonstrate that impregnating commercially available, biocompatible polymer scaffolds with MSNs allows for a free standing substrate for cell directed drug delivery. Electronic supplementary information (ESI) available: (1) Particle characterization. (2) Immunohistochemistry and SEM analyses of C2C12 cells grown on films for 3, 6, 24 and 72 h. Light microscopy and WST1 analyses of cells grown on cover slips and films for 6, 24 and 72 h (3) Quantification of protein levels of C2C12 cells differentiating on cover slips versus MSN films. (4) Stability of MSN films in biological solution and the influence on cell viability. (5) Cell internalization of particles from MSN films and intracellular drug release at 12 and 24 h (6) Cell internalization and intracellular DiI release of MSNs from (3Dtro®) fiber scaffolds impregnated with MSNs. See DOI: 10.1039/c3nr04022d

  13. Getting to the top of Google: search engine optimization.

    PubMed

    Maley, Catherine; Baum, Neil

    2010-01-01

    Search engine optimization is the process of making your Web site appear at or near the top of popular search engines such as Google, Yahoo, and MSN. This is not done by luck or knowing someone working for the search engines but by understanding the process of how search engines select Web sites for placement on top or on the first page. This article will review the process and provide methods and techniques to use to have your site rated at the top or very near the top.

  14. Division B Commission 6: Astronomical Telegrams

    NASA Astrophysics Data System (ADS)

    Yamaoka, H.; Green, D. W. E.; Samus, N. N.; Aksnes, K.; Gilmore, A. C.; Nakano, S.; Sphar, T.; Tichá, J.; Williams, G. V.

    2016-04-01

    IAU Commission 6 ``Astronomical Telegrams'' had a single business meeting during Honolulu General Assembly of the IAU. It took place on Tuesday, 11 August 2015. The meeting was attended by Hitoshi Yamaoka (President), Daniel Green (Director of the Central Bureau for Astronomical Telegrams, CBAT, via Skype), Steven Chesley (JPL), Paul Chodas (JPL), Alan Gilmore (Canterbury University), Shinjiro Kouzuma (Chukyo University), Paolo Mazzali (Co-Chair of the Supernova Working Group), Elena Pian (Scuola Normale Superiore di Pisa), Marion Schmitz (chair IAU Working Group Designations + NED), David Tholen (University of Hawaii), Jana Ticha (Klet Observatory), Milos Tichy (Klet Observatory), Giovanni Valsecchi (INAF\\slash Italy), Gareth Williams (Minor Planet Center). Apologies: Nikolai Samus (General Catalogue of Variable Stars, GCVS).

  15. War diseases revealed by the social media: massive leishmaniasis outbreak in the Syrian Spring

    PubMed Central

    2013-01-01

    Social media introduce pivotal changes to communication between individuals, organizations and communities. A clear example of the power of social media is the spread of the revolutionary outbreaks in the Arabic countries during 2011, where people used Facebook, YouTube and Skype to communicate, organise meetings and protest actions. Here I report how Doctor-Activists use these social media as an alarm system for ‘war disease’ outbreaks in the Syrian Spring. Social media are used as an alarm system to attract the attention of international organizations, which should assume their responsibilities and play their part in controlling the outbreak of such war diseases. PMID:23587258

  16. Is there a place for human fetal-derived stem cells for cell replacement therapy in Huntington's disease?

    PubMed

    Precious, Sophie V; Zietlow, Rike; Dunnett, Stephen B; Kelly, Claire M; Rosser, Anne E

    2017-06-01

    Huntington's disease (HD) is a neurodegenerative disease that offers an excellent paradigm for cell replacement therapy because of the associated relatively focal cell loss in the striatum. The predominant cells lost in this condition are striatal medium spiny neurons (MSNs). Transplantation of developing MSNs taken from the fetal brain has provided proof of concept that donor MSNs can survive, integrate and bring about a degree of functional recovery in both pre-clinical studies and in a limited number of clinical trials. The scarcity of human fetal tissue, and the logistics of coordinating collection and dissection of tissue with neurosurgical procedures makes the use of fetal tissue for this purpose both complex and limiting. Alternative donor cell sources which are expandable in culture prior to transplantation are currently being sought. Two potential donor cell sources which have received most attention recently are embryonic stem (ES) cells and adult induced pluripotent stem (iPS) cells, both of which can be directed to MSN-like fates, although achieving a genuine MSN fate has proven to be difficult. All potential donor sources have challenges in terms of their clinical application for regenerative medicine, and thus it is important to continue exploring a wide variety of expandable cells. In this review we discuss two less well-reported potential donor cell sources; embryonic germ (EG) cells and fetal neural precursors (FNPs), both are which are fetal-derived and have some properties that could make them useful for regenerative medicine applications. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Retinoid quantification by HPLC/MS(n)

    NASA Technical Reports Server (NTRS)

    McCaffery, Peter; Evans, James; Koul, Omanand; Volpert, Amy; Reid, Kevin; Ullman, M. David

    2002-01-01

    Retinoic acid (RA) mediates most of the biological effects of vitamin A that are essential for vertebrate survival. It acts through binding to receptors that belong to the nuclear receptor transcription factor superfamily (Mangelsdorf et al. 1994). It is also a highly potent vertebrate teratogen. To determine the function and effects of endogenous and exogenous RA, it is important to have a highly specific, sensitive, accurate, and precise analytical procedure. Current analyses of RA and other retinoids are labor intensive, of poor sensitivity, have limited specificity, or require compatibility with RA reporter cell lines (Chen et al. 1995. BIOCHEM: Pharmacol. 50: 1257-1264; Creech Kraft et al. 1994. BIOCHEM: J. 301: 111-119; Lanvers et al. 1996. J. Chromatogr. B Biomed. Appl. 685: 233-240; Maden et al. 1998. DEVELOPMENT: 125: 4133-4144; Wagner et al. 1992. DEVELOPMENT: 116: 55-66). This paper describes an HPLC/mass spectrometry/mass spectrometry product ion scan (HPLC/MS(n)) procedure for the analysis of retinoids that employs atmospheric pressure chemical ionization MS. The retinoids are separated by normal-phase column chromatography with a linear hexane-isopropanol-dioxane gradient. Each retinoid is detected by a unique series of MS(n) functions set at optimal collision-induced dissociation energy (30% to 32%) for all MS(n) steps. The scan events are divided into three segments, based on HPLC elution order, to maximize the mass spectrometer duty cycle. The all-trans, 9-cis, and 13-cis RA isomers are separated, if desired, by an isocratic hexane-dioxane-isopropanol mobile phase. This paper describes an HPLC/MS(n) procedure possessing high sensitivity and specificity for retinoids.

  18. Thermo/pH dual-stimuli-responsive drug delivery for chemo-/photothermal therapy monitored by cell imaging.

    PubMed

    Shu, Yang; Song, Rusheng; Zheng, Anqi; Huang, Jingli; Chen, Mingli; Wang, Jianhua

    2018-05-01

    A thermo/pH dual-stimuli-responsive drug delivery system (DDS) based on polymer coated mesoporous silica nanostructures (MSNs) is developed for facilitating chemotherapy and photothermal therapy. Thermo/pH-responsive polymer, poly((N-isopropylacrylamide, NIPAM)-co-methacrylic acid, MA), is grafted onto MSNs by in situ polymerization, followed by loading a chemotherapeutic drug (doxorubicin hydrochloride, DOX) and a near-infrared-absorbing phototherapeutic agent (indocyanine green, ICG) to construct the intelligent drug delivery system, shortly as DOX-ICG-MSN@p(NIPAM-co-MA). At NIR irradiation, the photothermal conversion capability of ICG raises the temperature of the DDS and opens the gatekeeper by shrinkage of the copolymer p(NIPAM-co-MA), which triggers controlled release of DOX at an elevated temperature. On the other hand, drug release is also realized at pH 5.3, a characteristic pH value in cancer cell microenvironment, at which it not only causes the shrinkage of the pH-sensitive polymeric moiety of methacrylic acid in MSN@p(NIPAM-co-MA) but also deteriorates electrostatic interaction of DOX molecules in the mesoporous channel by protonation of silanols. In addition, ICG further ensures photothermal therapy (PTT) and photodynamic therapy (PDT). The cytotoxicity assay of HeLa cells shows obvious synergistic effect by demonstrating that the combined use of DOX and ICG is more effective in killing HeLa cells than free DOX and ICG. The endocytosis of the drug is monitored by cell imaging. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. The value of magnetic resonance imaging in the diagnosis of penile fracture.

    PubMed

    Guler, Ibrahim; Ödev, Kemal; Kalkan, Havva; Simsek, Cihan; Keskin, Suat; Kilinç, Mehmet

    2015-01-01

    We studied the use of magnetic resonance imaging in the diagnosis of penile fracture. Between 1997 and 2012, fifteen patients (age range 17-48 years, mean age 37 years) with suspected penile fracture underwent MRI examinations. Ten patients were injured during sexual intercourse, whereas four patients were traumatized by non-physiological bending of the penis during self manupilation, one patient was traumatized falling from the bed. Investigations were performed with 1.5 T MR unit. With the patient in the supine position, the penis was taped against the abdominal wall and surface coil was placed on the penis. All patients were studied with axial, coronal, sagittal precontrast and postcontrast T1-weighted TSE(TR/TE:538/13 msn) and T2-weighted TSE(5290/110 msn) sequences. All patient underwent surgical exploration. The follow-up ranged from 3 months to 72 months. Clinically all patients showed normal healing process without complications. In 11 patients a shortening and thickening of tunica albuginea was observed. Three patients have post traumatic erectile disfunction. In all patient corpus cavernosum fractures were clearly depicted on a discontinuity of the low signal intensity of tunica albuginea. These findings were most evident on T1WI and also depicted on T2W sequences. Images obtained shortly after contrast medium administration showed considerable enhancement only in rupture site. Subcutaneous extratunical haematoma in all patients were also recognizable on T2 WI. MRI findings were confirmed at surgery. Magnetic resonance imaging is of great value for the diagnosis of penile fracture. Furthermore this method is well suited for visualising the post-operative healing process.

  20. Advances in structure elucidation of small molecules using mass spectrometry

    PubMed Central

    Fiehn, Oliver

    2010-01-01

    The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules. Electronic supplementary material The online version of this article (doi:10.1007/s12566-010-0015-9) contains supplementary material, which is available to authorized users. PMID:21289855

  1. Nup100 regulates Saccharomyces cerevisiae replicative life span by mediating the nuclear export of specific tRNAs.

    PubMed

    Lord, Christopher L; Ospovat, Ophir; Wente, Susan R

    2017-03-01

    Nuclear pore complexes (NPCs), which are composed of nucleoporins (Nups) and regulate transport between the nucleus and cytoplasm, significantly impact the replicative life span (RLS) of Saccharomyces cerevisiae We previously reported that deletion of the nonessential gene NUP100 increases RLS, although the molecular basis for this effect was unknown. In this study, we find that nuclear tRNA accumulation contributes to increased longevity in nup100 Δ cells. Fluorescence in situ hybridization (FISH) experiments demonstrate that several specific tRNAs accumulate in the nuclei of nup100 Δ mutants. Protein levels of the transcription factor Gcn4 are increased when NUP100 is deleted, and GCN4 is required for the elevated life spans of nup100 Δ mutants, similar to other previously described tRNA export and ribosomal mutants. Northern blots indicate that tRNA splicing and aminoacylation are not significantly affected in nup100 Δ cells, suggesting that Nup100 is largely required for nuclear export of mature, processed tRNAs. Distinct tRNAs accumulate in the nuclei of nup100 Δ and msn5 Δ mutants, while Los1-GFP nucleocytoplasmic shuttling is unaffected by Nup100. Thus, we conclude that Nup100 regulates tRNA export in a manner distinct from Los1 or Msn5. Together, these experiments reveal a novel Nup100 role in the tRNA life cycle that impacts the S. cerevisiae life span. © 2017 Lord et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  2. Nuclear Localization of Haa1, Which Is Linked to Its Phosphorylation Status, Mediates Lactic Acid Tolerance in Saccharomyces cerevisiae

    PubMed Central

    Sugiyama, Minetaka; Akase, Shin-Pei; Nakanishi, Ryota; Horie, Hitoshi; Kaneko, Yoshinobu

    2014-01-01

    Improvement of the lactic acid resistance of the yeast Saccharomyces cerevisiae is important for the application of the yeast in industrial production of lactic acid from renewable resources. However, we still do not know the precise mechanisms of the lactic acid adaptation response in yeast and, consequently, lack effective approaches for improving its lactic acid tolerance. To enhance our understanding of the adaptation response, we screened for S. cerevisiae genes that confer enhanced lactic acid resistance when present in multiple copies and identified the transcriptional factor Haa1 as conferring resistance to toxic levels of lactic acid when overexpressed. The enhanced tolerance probably results from increased expression of its target genes. When cells that expressed Haa1 only from the endogenous promoter were exposed to lactic acid stress, the main subcellular localization of Haa1 changed from the cytoplasm to the nucleus within 5 min. This nuclear accumulation induced upregulation of the Haa1 target genes YGP1, GPG1, and SPI1, while the degree of Haa1 phosphorylation observed under lactic acid-free conditions decreased. Disruption of the exportin gene MSN5 led to accumulation of Haa1 in the nucleus even when no lactic acid was present. Since Msn5 was reported to interact with Haa1 and preferentially exports phosphorylated cargo proteins, our results suggest that regulation of the subcellular localization of Haa1, together with alteration of its phosphorylation status, mediates the adaptation to lactic acid stress in yeast. PMID:24682296

  3. Exercise-Induced Neuroprotection of the Nigrostriatal Dopamine System in Parkinson's Disease

    PubMed Central

    Hou, Lijuan; Chen, Wei; Liu, Xiaoli; Qiao, Decai; Zhou, Fu-Ming

    2017-01-01

    Epidemiological studies indicate that physical activity and exercise may reduce the risk of developing Parkinson's disease (PD), and clinical observations suggest that physical exercise can reduce the motor symptoms in PD patients. In experimental animals, a profound observation is that exercise of appropriate timing, duration, and intensity can reduce toxin-induced lesion of the nigrostriatal dopamine (DA) system in animal PD models, although negative results have also been reported, potentially due to inappropriate timing and intensity of the exercise regimen. Exercise may also minimize DA denervation-induced medium spiny neuron (MSN) dendritic atrophy and other abnormalities such as enlarged corticostriatal synapse and abnormal MSN excitability and spiking activity. Taken together, epidemiological studies, clinical observations, and animal research indicate that appropriately dosed physical activity and exercise may not only reduce the risk of developing PD in vulnerable populations but also benefit PD patients by potentially protecting the residual DA neurons or directly restoring the dysfunctional cortico-basal ganglia motor control circuit, and these benefits may be mediated by exercise-triggered production of endogenous neuroprotective molecules such as neurotrophic factors. Thus, exercise is a universally available, side effect-free medicine that should be prescribed to vulnerable populations as a preventive measure and to PD patients as a component of treatment. Future research needs to establish standardized exercise protocols that can reliably induce DA neuron protection, enabling the delineation of the underlying cellular and molecular mechanisms that in turn can maximize exercise-induced neuroprotection and neurorestoration in animal PD models and eventually in PD patients. PMID:29163139

  4. Dopamine synapse is a neuroligin-2–mediated contact between dopaminergic presynaptic and GABAergic postsynaptic structures

    PubMed Central

    Uchigashima, Motokazu; Ohtsuka, Toshihisa; Kobayashi, Kazuto; Watanabe, Masahiko

    2016-01-01

    Midbrain dopamine neurons project densely to the striatum and form so-called dopamine synapses on medium spiny neurons (MSNs), principal neurons in the striatum. Because dopamine receptors are widely expressed away from dopamine synapses, it remains unclear how dopamine synapses are involved in dopaminergic transmission. Here we demonstrate that dopamine synapses are contacts formed between dopaminergic presynaptic and GABAergic postsynaptic structures. The presynaptic structure expressed tyrosine hydroxylase, vesicular monoamine transporter-2, and plasmalemmal dopamine transporter, which are essential for dopamine synthesis, vesicular filling, and recycling, but was below the detection threshold for molecules involving GABA synthesis and vesicular filling or for GABA itself. In contrast, the postsynaptic structure of dopamine synapses expressed GABAergic molecules, including postsynaptic adhesion molecule neuroligin-2, postsynaptic scaffolding molecule gephyrin, and GABAA receptor α1, without any specific clustering of dopamine receptors. Of these, neuroligin-2 promoted presynaptic differentiation in axons of midbrain dopamine neurons and striatal GABAergic neurons in culture. After neuroligin-2 knockdown in the striatum, a significant decrease of dopamine synapses coupled with a reciprocal increase of GABAergic synapses was observed on MSN dendrites. This finding suggests that neuroligin-2 controls striatal synapse formation by giving competitive advantage to heterologous dopamine synapses over conventional GABAergic synapses. Considering that MSN dendrites are preferential targets of dopamine synapses and express high levels of dopamine receptors, dopamine synapse formation may serve to increase the specificity and potency of dopaminergic modulation of striatal outputs by anchoring dopamine release sites to dopamine-sensing targets. PMID:27035941

  5. Iron-Induced Dissociation of the Aft1p Transcriptional Regulator from Target Gene Promoters Is an Initial Event in Iron-Dependent Gene Suppression

    PubMed Central

    Ueta, Ryo; Fujiwara, Naoko; Yamaguchi-Iwai, Yuko

    2012-01-01

    Aft1p is an iron-responsive transcriptional activator that plays a central role in the regulation of iron metabolism in Saccharomyces cerevisiae. Aft1p is regulated by accelerated nuclear export in the presence of iron, mediated by Msn5p. However, the transcriptional activity of Aft1p is suppressed under iron-replete conditions in the Δmsn5 strain, although Aft1p remains in the nucleus. Aft1p dissociates from its target promoters under iron-replete conditions due to an interaction between Aft1p and the monothiol glutaredoxin Grx3p or Grx4p (Grx3/4p). The binding of Grx3/4p to Aft1p is induced by iron repletion and requires binding of an iron-sulfur cluster to Grx3/4p. The mitochondrial transporter Atm1p, which has been implicated in the export of iron-sulfur clusters and related molecules, is required not only for iron binding to Grx3p but also for dissociation of Aft1p from its target promoters. These results suggest that iron binding to Grx3p (and presumably Grx4p) is a prerequisite for the suppression of Aft1p. Since Atm1p plays crucial roles in the delivery of iron-sulfur clusters from the mitochondria to the cytoplasm and nucleus, these results support the previous observations that the mitochondrial iron-sulfur cluster assembly machinery is involved in cellular iron sensing. PMID:23045394

  6. Deleting the 14-3-3 protein Bmh1 extends life span in Saccharomyces cerevisiae by increasing stress response.

    PubMed

    Wang, Chen; Skinner, Craig; Easlon, Erin; Lin, Su-Ju

    2009-12-01

    Enhanced stress response has been suggested to promote longevity in many species. Calorie restriction (CR) and conserved nutrient-sensing target of rapamycin (TOR) and protein kinase A (PKA) pathways have also been suggested to extend life span by increasing stress response, which protects cells from age-dependent accumulation of oxidative damages. Here we show that deleting the yeast 14-3-3 protein, Bmh1, extends chronological life span (CLS) by activating the stress response. 14-3-3 proteins are highly conserved chaperone-like proteins that play important roles in many cellular processes. bmh1Delta-induced heat resistance and CLS extension require the general stress-response transcription factors Msn2, Msn4, and Rim15. The bmh1Delta mutant also displays a decreased reactive oxygen species level and increased heat-shock-element-driven transcription activity. We also show that BMH1 genetically interacts with CR and conserved nutrient-sensing TOR- and PKA-signaling pathways to regulate life span. Interestingly, the level of phosphorylated Ser238 on Bmh1 increases during chronological aging, which is delayed by CR or by reduced TOR activities. In addition, we demonstrate that PKA can directly phosphorylate Ser238 on Bmh1. The status of Bmh1 phosphorylation is therefore likely to play important roles in life-span regulation. Together, our studies suggest that phosphorylated Bmh1 may cause inhibitory effects on downstream longevity factors, including stress-response proteins. Deleting Bmh1 may eliminate the inhibitory effects of Bmh1 on these longevity factors and therefore extends life span.

  7. Good Morning from Barrow, Alaska! Helping K-12 students understand the importance of research

    NASA Astrophysics Data System (ADS)

    Shelton, M.

    2010-12-01

    This presentation focuses on how an educator experiences scientific research and how those experiences can help foster K-12 students’ understanding of research being conducted in Barrow, Alaska. According to Zhang and Fulford (1994), real-time electronic field trips help to provide a sense of closeness and relevance. In combination with experts in the field, the electronic experience can help students to better understand the phenomenon being studied, thus strengthening the student’s conceptual knowledge (Zhang & Fulford, 1994). During a seven day research trip to study the arctic sea ice, five rural Virginia teachers and their students participated in Skype sessions with the participating educator and other members of the Radford University research team. The students were able to view the current conditions in Barrow, listen to members of the research team describe what their contributions were to the research, and ask questions about the research and Alaska in general. Collaborations between students and scientist can have long lasting benefits for both educators and students in promoting an understanding of the research process and understanding why our world is changing. By using multimedia venues such as Skype students are able to interact with researchers both visually and verbally, forming the basis for students’ interest in science. A learner’s level of engagement is affected by the use of multimedia, especially the level of cognitive processing. Visual images alone do no promote the development of good problem solving skills. However, the students are able to develop better problem solving skills when both visual images and verbal interactions are used together. As students form higher confidence levels by improving their ability to problem solve, their interest in science also increases. It is possible that this interest could turn into a passion for science, which could result in more students wanting to become scientists or science teachers.

  8. Telegerontology as a Novel Approach to Address Health and Safety by Supporting Community-Based Rural Dementia Care Triads: Randomized Controlled Trial Protocol

    PubMed Central

    2018-01-01

    Background Telegerontology is an approach using videoconferencing to connect an interdisciplinary team in a regional specialty center to patients in rural communities, which is becoming increasingly practical for addressing current limitations in rural community-based dementia care. Objective Using the remotely-delivered expertise of the Telegerontology dementia care team, we aim to enhance the caregiver/patient/physician triad and thereby provide the necessary support for the person with dementia to “age in place.” Methods This is a cluster randomized feasibility trial with four rural regions in the province of Newfoundland and Labrador, Canada (2 regions randomly assigned to “intervention” and 2 to “control”). The study population includes 22 “dementia triads” that consist of a community-dwelling older Canadian with moderate to late dementia, their family caregivers, and their Primary Care Physician (PCP). Over the 6-month active study period, all participants will be provided an iPad. The intervention is intended as an adjunct to existing PCP care, consisting of weekly Skype-based videoconferencing calls with the Telegerontology physician, and other team members as needed (occupational therapist, physical therapist etc). Control participants receive usual community-based dementia care with their PCP. A baseline (pre-) assessment will be performed during a home visit with the study team. Post intervention, 6- and 12-month follow-up assessments will be collected remotely using specialized dementia monitoring applications and Skype calls. Primary outcomes include admission to long-term care, falls, emergency room visits, hospital stays, and caregiver burden. Results Results will be available in March of 2018. Conclusions Results from this study will demonstrate a novel approach to dementia care that has the potential to impact both rural PCPs, family caregivers, and people with dementia, as well as provide evidence for the utility of Telegerontology in models of eHealth-based care. PMID:29472178

  9. Telegerontology as a Novel Approach to Address Health and Safety by Supporting Community-Based Rural Dementia Care Triads: Randomized Controlled Trial Protocol.

    PubMed

    Wallack, Elizabeth M; Harris, Chelsea; Ploughman, Michelle; Butler, Roger

    2018-02-22

    Telegerontology is an approach using videoconferencing to connect an interdisciplinary team in a regional specialty center to patients in rural communities, which is becoming increasingly practical for addressing current limitations in rural community-based dementia care. Using the remotely-delivered expertise of the Telegerontology dementia care team, we aim to enhance the caregiver/patient/physician triad and thereby provide the necessary support for the person with dementia to "age in place." This is a cluster randomized feasibility trial with four rural regions in the province of Newfoundland and Labrador, Canada (2 regions randomly assigned to "intervention" and 2 to "control"). The study population includes 22 "dementia triads" that consist of a community-dwelling older Canadian with moderate to late dementia, their family caregivers, and their Primary Care Physician (PCP). Over the 6-month active study period, all participants will be provided an iPad. The intervention is intended as an adjunct to existing PCP care, consisting of weekly Skype-based videoconferencing calls with the Telegerontology physician, and other team members as needed (occupational therapist, physical therapist etc). Control participants receive usual community-based dementia care with their PCP. A baseline (pre-) assessment will be performed during a home visit with the study team. Post intervention, 6- and 12-month follow-up assessments will be collected remotely using specialized dementia monitoring applications and Skype calls. Primary outcomes include admission to long-term care, falls, emergency room visits, hospital stays, and caregiver burden. Results will be available in March of 2018. Results from this study will demonstrate a novel approach to dementia care that has the potential to impact both rural PCPs, family caregivers, and people with dementia, as well as provide evidence for the utility of Telegerontology in models of eHealth-based care. ©Elizabeth M. Wallack, Chelsea Harris, Michelle Ploughman, Roger Butler. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 22.02.2018.

  10. Technology Components as Adjuncts to Family-Based Pediatric Obesity Treatment in Low-Income Minority Youth.

    PubMed

    Tripicchio, Gina L; Ammerman, Alice S; Neshteruk, Cody; Faith, Myles S; Dean, Kelsey; Befort, Christie; Ward, Dianne S; Truesdale, Kimberly P; Burger, Kyle S; Davis, Ann

    2017-12-01

    Strategies to treat pediatric obesity are needed, especially among high-need populations. Technology is an innovative approach; however, data on technology as adjuncts to in-person treatment programs are limited. A total of 64 children [body mass index (BMI) ≥85th percentile, mean age = 9.6 ± 3.1 years, 32.8% female, 84.4% Hispanic] were recruited to participate in one of three cohorts of a family-based behavioral group (FBBG) treatment program: FBBG only, TECH1, and TECH2. Rolling, nonrandomized recruitment was used to enroll participants into three cohorts from May 2014 to February 2015. FBBG began in May 2014 and received the standard, in-person 12-week treatment only (n = 21); TECH1 began in September 2014 and received FBBG plus a digital tablet equipped with a fitness app (FITNET) (n = 20); TECH2 began in February 2015 and received FBBG and FITNET, plus five individually tailored TeleMed health-coaching sessions delivered via Skype (n = 23). Child BMI z-score (BMI-z) was assessed at baseline and postintervention. Secondary aims examined weekly FBBG attendance, feasibility/acceptability of FITNET and Skype, and the effect of technology engagement on BMI-z. FBBG and TECH1 participants did not show significant reductions in BMI-z postintervention [FBBG: β = -0.05(0.04), p = 0.25; TECH1: β = -0.006(0.06), p = 0.92], but TECH2 participants did [β = -0.09(0.02), p < 0.001] and TeleMed session participation was significantly associated with BMI-z reduction [β = -0.04(0.01), p = 0.01]. FITNET use and FBBG attendance were not associated with BMI-z in any cohort. Overall, participants rated the technology as highly acceptable. Technology adjuncts are feasible, used by hard-to-reach participants, and show promise for improving child weight status in obesity treatment programs.

  11. SU-F-E-14: Global Radiation Oncology Education and Training in Medical Physics Powered by Information and Communication Technologies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ngwa, W; University Massachusetts Lowell, Lowell, MA; Sajo, E

    Purpose: Recent publications have highlighted the potential of Information and Communication Technologies (ICTs) to catalyze collaborations in cancer care, research and education in global radiation oncology. This work reports on the use of ICTs for global Medical Physics education and training across three countries: USA, Tanzania and Kuwait Methods: An online education platform was established by Radiation Oncology Faculty from Harvard Medical School, and the University of Pennsylvania with integrated Medical Physics Course modules accessible to trainees in Tanzania via partnership with the Muhimbili University of Health and Allied Sciences, and the Ocean Road Cancer Institute. The course modules incorporatedmore » lectures covering Radiation Therapy Physics with videos, discussion board, assessments and grade center. Faculty at Harvard Medical School and the University of Massachusetts Lowell also employed weekly Skype meetings to train/mentor three graduate students, living out-of-state and in Kuwait for up to 9 research credits per semester for over two semesters towards obtaining their graduate degrees Results: Students were able to successfully access the Medical Physics course modules and participate in learning activities, online discussion boards, and assessments. Other instructors could also access/co-teach the course modules from USA and Tanzania. Meanwhile all three graduate students with remote training via Skype and email made major progress in their graduate training with each one of them submitting their research results as abstracts to be presented at the 2016 AAPM conference. One student has also published her work already and all three are developing these abstracts for publication in peer-reviewed journals. Conclusion: Altogether, this work highlights concrete examples/model on how ICTs can be used for capacity building in Medical Physics across continents, for both education and research training needed for Masters/PhD degrees. The developed modules and model will be scaled to benefit many more trainees and other developing countries.« less

  12. Video-calls to reduce loneliness and social isolation within care environments for older people: an implementation study using collaborative action research.

    PubMed

    Zamir, Sonam; Hennessy, Catherine Hagan; Taylor, Adrian H; Jones, Ray B

    2018-03-02

    Older people in care may be lonely with insufficient contact if families are unable to visit. Face-to-face contact through video-calls may help reduce loneliness, but little is known about the processes of engaging people in care environments in using video-calls. We aimed to identify the barriers to and facilitators of implementing video-calls for older people in care environments. A collaborative action research (CAR) approach was taken to implement a video-call intervention in care environments. We undertook five steps of recruitment, planning, implementation, reflection and re-evaluation, in seven care homes and one hospital in the UK. The video-call intervention 'Skype on Wheels' (SoW) comprised a wheeled device that could hold an iPad and handset, and used Skype to provide a free video-call service. Care staff were collaborators who implemented the intervention within the care-setting by agreeing the intervention, recruiting older people and their family, and setting up video-calls. Field notes and reflective diaries on observations and conversations with staff, older people and family were maintained over 15 months, and analysed using thematic analysis. Four care homes implemented the intervention. Eight older people with their respective social contacts made use of video-calls. Older people were able to use SoW with assistance from staff, and enjoyed the use of video-calls to stay better connected with family. However five barriers towards implementation included staff turnover, risk averseness, the SoW design, lack of family commitment and staff attitudes regarding technology. The SoW intervention, or something similar, could aid older people to stay better connected with their families in care environments, but if implemented as part of a rigorous evaluation, then co-production of the intervention at each recruitment site may be needed to overcome barriers and maximise engagement.

  13. Barriers to Care for Transgender People: A Conversation With Dana Hines, PhD, MSN, RN.

    PubMed

    Biederman, Donna J; Hines, Dana

    2016-05-01

    A public health nurse talks about her career trajectory, her entry into nursing research, and her research career in transgender health. Transgender people encounter many health and social disparities, yet medical and nursing professionals are often ill-prepared to care for this population of individuals. The nursing profession is well known for its contributions to population health and for developing nursing-led interventions to improve the health outcomes of marginalized populations. Hines urges nursing to take a more active stance in transgender health and is leading this effort by example.

  14. Introduction

    NASA Astrophysics Data System (ADS)

    Callegati, Franco; Aracil, Javier; López, Víctor

    At the present time, optical transmission systems are capable of sending data over hundreds of wavelengths on a single fiber thanks to dense wavelength division multiplexing (DWDM) technologies, reaching bit rates on the order of gigabits per second per wavelength and terabits per second per fiber. In the last decade the availability of such a huge bandwidth caused transport networks to be considered as having infinite capacity. The recent massive deployment of Asymmetric Digital Subscriber Line (ADSL) and broadband wireless access solutions, as well as the outburst of new multimedia network services (such as Skype, YouTube, Joost, etc.) caused a significant increase of end user traffic and bandwidth demands. Therefore, the apparently “infinite” capacity of optical networks appears much more “finite” today, despite the latest developments in photonic transmission.

  15. Reliability of Videoconferencing Administration of a Communication Questionnaire to People With Traumatic Brain Injury and Their Close Others.

    PubMed

    Rietdijk, Rachael; Power, Emma; Brunner, Melissa; Togher, Leanne

    To compare in-person with videoconferencing administration of a communication questionnaire for people with traumatic brain injury (TBI) and their close others. Repeated-measures design with randomized order of administration. Twenty adults with severe TBI and their close others. Both participants with TBI and their close others completed the La Trobe Communication Questionnaire (LCQ) via interview with a clinician, once via Skype and once during a home visit. Total LCQ score and time taken for completion. There were no significant differences between videoconferencing and in-person conditions in the total scores or time taken to complete the questionnaire. Videoconferencing-based administration of the LCQ is as reliable and efficient as in-person administration.

  16. Forensic analysis of social networking application on iOS devices

    NASA Astrophysics Data System (ADS)

    Zhang, Shuhui; Wang, Lianhai

    2013-12-01

    The increased use of social networking application on iPhone and iPad make these devices a goldmine for forensic investigators. Besides, QQ, Wechat, Sina Weibo and skype applications are very popular in China and didn't draw attention to researchers. These social networking applications are used not only on computers, but also mobile phones and tablets. This paper focuses on conducting forensic analysis on these four social networking applications on iPhone and iPad devices. The tests consisted of installing the social networking applications on each device, conducting common user activities through each application and correlation analysis with other activities. Advices to the forensic investigators are also given. It could help the investigators to describe the crime behavior and reconstruct the crime venue.

  17. Skype me! Socially Contingent Interactions Help Toddlers Learn Language

    PubMed Central

    Roseberry, Sarah; Hirsh-Pasek, Kathy; Golinkoff, Roberta Michnick

    2013-01-01

    Language learning takes place in the context of social interactions, yet the mechanisms that render social interactions useful for learning language remain unclear. This paper focuses on whether social contingency might support word learning. Toddlers aged 24- to 30-months (N=36) were exposed to novel verbs in one of three conditions: live interaction training, socially contingent video training over video chat, and non-contingent video training (yoked video). Results suggest that children only learned novel verbs in socially contingent interactions (live interactions and video chat). The current study highlights the importance of social contingency in interactions for language learning and informs the literature on learning through screen media as the first study to examine word learning through video chat technology. PMID:24112079

  18. Transitions between sleep and feeding states in rat ventral striatum neurons

    PubMed Central

    Tellez, Luis A.; Perez, Isaac O.; Simon, Sidney A.

    2012-01-01

    Neurons in the nucleus accumbens (NAc) have been shown to participate in several behavioral states, including feeding and sleep. However, it is not known if the same neuron participates in both states and, if so, how similar are the responses. In addition, since the NAc contains several cell types, it is not known if each type participates in the transitions associated with feeding and sleep. Such knowledge is important for understanding the interaction between two different neural networks. For these reasons we recorded ensembles of NAc neurons while individual rats volitionally transitioned between the following states: awake and goal directed, feeding, quiet-awake, and sleeping. We found that during both feeding and sleep states, the same neurons could increase their activity (be activated) or decrease their activity (be inactivated) by feeding and/or during sleep, thus indicating that the vast majority of NAc neurons integrate sleep and feeding signals arising from spatially distinct neural networks. In contrast, a smaller population was modulated by only one of the states. For the majority of neurons in either state, we found that when one population was excited, the other was inhibited, suggesting that they act as a local circuit. Classification of neurons into putative interneurons [fast-spiking interneurons (pFSI) and choline acetyltransferase interneurons (pChAT)] and projection medium spiny neurons (pMSN) showed that all three types are modulated by transitions to and from feeding and sleep states. These results show, for the first time, that in the NAc, those putative inhibitory interneurons respond similarly to pMSN projection neurons and demonstrate interactions between NAc networks involved in sleep and feeding. PMID:22745464

  19. ‘Conceptualizing’ the Endometrium: Identification of Conceptus-Derived Proteins During Early Pregnancy in Cattle1

    PubMed Central

    Forde, Niamh; Bazer, Fuller W.; Spencer, Thomas E.; Lonergan, Pat

    2015-01-01

    The aim of this study was to identify conceptus-derived proteins, in addition to IFNT, that may facilitate pregnancy recognition in cattle. Analysis of the protein content of the uterine luminal fluid (ULF) from cyclic heifers on Day 16 by nano liquid chromatography tandem mass spectrometry identified 334 proteins. Comparison of these data with 299 proteins identified in the ULF of pregnant heifers on Day 16 identified 85 proteins only present in the ULF of pregnant heifers. Analysis of Day 16 conceptus-conditioned culture medium revealed the presence of 1005 proteins of which 30 proteins were unique to ULF from Day 16 pregnant heifers. Of these 30 proteins, 12 had mRNA expression values at least 2-fold higher in abundance (P < 0.05) in the conceptus compared to the endometrium (ARPC5L, CAPG, CKMT1, CSTB, HSPA8, HSPE1, LGALS3, MSN, NUTF2, P4HB, PRKAR2A, TKT) as determined by RNA sequencing. In addition, genes that have a significant biological interaction with the proteins (ACO2, CKMT1, CSTB, EEF2, GDI1, GLB1, GPLD1, HNRNPA1, HNRNPA2B1, HNRNPF, HSPA8, HSPE1, IDH2, KRT75, LGALS3, MSN, NUTF2, P4HB, PRKAR2A, PSMA4, PSMB5, PSMC4, SERPINA3, TKT) were differentially expressed in the endometrium of pregnant compared to cyclic heifers during the pregnancy recognition period (Days 16–18). These results indicate that 30 proteins unique to ULF from pregnant heifers and produced by short-term in vitro cultured Day 16 conceptuses could potentially be involved in facilitating the interactions between the conceptus and the endometrium during the pregnancy recognition period. PMID:25947061

  20. Dopamine D2 receptors in striatal output neurons enable the psychomotor effects of cocaine.

    PubMed

    Kharkwal, Geetika; Radl, Daniela; Lewis, Robert; Borrelli, Emiliana

    2016-10-11

    The psychomotor effects of cocaine are mediated by dopamine (DA) through stimulation of striatal circuits. Gabaergic striatal medium spiny neurons (MSNs) are the only output of this pivotal structure in the control of movements. The majority of MSNs express either the DA D1 or D2 receptors (D1R, D2R). Studies have shown that the motor effect of cocaine depends on the DA-mediated stimulation of D1R-expressing MSNs (dMSNs), which is mirrored at the cellular level by stimulation of signaling pathways leading to phosphorylation of ERKs and induction of c-fos Nevertheless, activation of dMSNs by cocaine is necessary but not sufficient, and D2R signaling is required for the behavioral and cellular effects of cocaine. Indeed, cocaine motor effects and activation of signaling in dMSNs are blunted in mice with the constitutive knockout of D2R (D2RKO). Using mouse lines with a cell-specific knockout of D2R either in MSNs (MSN-D2RKO) or in dopaminergic neurons (DA-D2RKO), we show that D2R signaling in MSNs is required and permissive for the motor stimulant effects of cocaine and the activation of signaling in dMSNs. MSN-D2RKO mice show the same phenotype as constitutive D2RKO mice both at the behavioral and cellular levels. Importantly, activation of signaling in dMSNs by cocaine is rescued by intrastriatal injection of the GABA antagonist, bicuculline. These results are in support of intrastriatal connections of D2R + -MSNs (iMSNs) with dMSNs and indicate that D2R signaling in MSNs is critical for the function of intrastriatal circuits.

Top