117,364 research outputs found
Mass, Energy, and Cost Balances in Water Distribution Systems with PATs: The Trondheim Network Case Study
In water distribution systems, the substitution of regulating valves by pumps as turbines (PATs) is sustainable if the energy recovery balances the installation and maintenance costs, with a comparable and efficient reduction of the volume lost by leakage. Hence, the installation feasibility and regulation of a PAT require analysis of the introduced effects on the components of the energy, mass, and cost balances. In this paper these effects are explored by means of a case study, i.e., the water distribution system of Trondheim, Norway. Different hydraulic regulations of a PAT are analyzed to maximize the recovered energy, considering the daily variation of the system functioning conditions and the substitution of valves of different kinds, meaning a constant opening degree, a fixed value of pressure at a node of the system, and a control in time of the setting. A feasible solution for the Trondheim network is shown, consisting of the implementation of two twin PATs in parallel with a discontinuous functioning of one of them
Dysregulation of receptor induced apoptosis during human leishmaniasis : a possible mechanism of skin ulceration
Leishmaniasis is endemic in 88 countries and 12 million people per year have been estimated to be at risk of infection. The causative agent, the protozoan Leishmania, is spread by sand-flies and infects macrophages in the mammalian host. Leishmaniasis in humans form a spectrum of clinical presentations. In cutaneous leishmaniasis (CL) caused by L. major, the infection is localised in the skin and manifests as one or several ulcers that typically spontaneously heal within one year after infection, often leaving marked scarring. In visceral leishmaniasis (VL) caused by L. donovani, infected macrophages are found in liver, spleen, bone marrow and lymph-nodes and the infection leads to hepatosplenomegaly, wasting, fever and if not treated, to death. Systemic T-cell deficiency occurs early during VL and leads to uncontrolled parasite replication. In general, solid immunity upon healing occurs after resolved VL and CL.In this thesis, the hypothesis that alterations of death receptor-mediated apoptosis have an impact on the pathogenesis of human leishmaniasis has been explored. During VL, dysregulation of the Fas/FasL pathway was investigated, both at one site of infection, the spleen, and on circulating lymphocytes from the peripheral blood. In the case of CL the hypothesis was that increased death receptor-mediated apoptosis in the microenvironment surrounding infected macrophages may induce bystandard apoptosis of keratinocytes, leading to skin ulceration.Dysiregulation of the Fas/FasL pathway occured during human VL and CL. Levels of soluble Fas (sFas) and soluble Fas ligand (sFasL) were elevated in plasma of patients with active VL and individuals co-infected with VL-HIV-1 compared to healthy controls, and the levels of sFas and sFasL were normalized 6 months after successful treatment. During active VL, the expression of membrane bound Fas, and to a lower extent Fast., was up-regulated on spleen cells, where parasites multiply. In contrast, expression of Fas and Fast- were not altered on peripheral blood mononuclear cells (PBMC) during VL. Furthermore, in vitro infection of macrophages with L. donovani results in up-regulation of Fas expression on the surface of infected cells and increases the levels of sFasL in supernatants from infected cultures. During active CL caused by L. major, a disease mainly localised to the skin, the Fas and Fast- levels were not altered in serum or on PBMCs analysed ex vivo. However, when CL PBMCs were restimulated with L. major, Fas was up-regulated on effector T-cells and high levels of sFasL were detected in the supernatants as compared to control PBMCs.Keratinocyte apoptosis is altered during CL. Dysregulation of the Fas/FasL pathway in the microenvironment surrounding L. major infected macrophages under the skin was visualised in biopsies collected from CL patients. A substantial number of apoptotic keratinocytes were observed in the epidermis of morphologically active and healing CL skin samples. Fas expression was increased on the epidermis in active CL, whereas FasL expressing macrophages and T-cells were found in the subepidermal infiltrate during active disease. Supernatants from re-stimulated CL-PBMC cultures containing high levels of sFasL induced apoptosis in human keratinocyte cell line (HaCaT), and apoptosis could be inhibited in 213 supernatants by blocking Fas. A commercial apoptosis-specific microarray was used to assess alterations in keratinocyte RNAexpression during exposure to supernatants from L. major infected PBMCs. Fas and TRAIL mRNA and protein expression were significantly up-regulated compared to untreated keratinocytes. Supernatant induced apoptosis of keratinocytes was partly inhibited through blocking Fas or FasL, and more efficiently through inhibition of TRAIL by neutralising antibodies or soluble TRAIL-R. Furthermore, TRAIL expressing keratinocytes were detected in skin biopsies from CL cases.Blocking the Fas/FasL pathway in vivo may reduce ulceration during murine CL. In order to obtain the proof of the concept that Fas/FasL signalling is involved in keratinocyte-apoptosis leading to ulceration in the skin during CL, the Fas/FasL pathway was blocked in a murine model of CL by intraperitoneal treatment with Fast- neutralising antibodies (MFL-4). Skin inflammation, skin ulceration and ulcer size were followed weekly and compared to infected, untreated mice. Our results suggests that blocking Fas/FasL signalling during murine CL lead to less apoptotic keratinocytes and diminished ulceration. During treatment, the number of IFNgammaproducing CD8+CD3+ cells was increased at the site of infection when Fast- was neutralised which is suggestive of efficient parasite eradication. However, there was no reduction of parasite load at the site of infection or in draining lymph nodes and parasite replication was high upon discontinuation of anti-FasL treatment.Conclusion: The Fas/FasL pathway was shown to be dysregulated both in human VL and CL. A possible mechanism of ulcer formation during CL was proposed by apoptotic death of keratinocytes through enhanced Fast- and TRAIL signalling. This data was further strengthened in a treatment experiment in a murine model of CL, where blocking the Fas/FasL system reduced ulcer formation during L. major infection.List of scientific papersI. Eidsmo L, Wolday D, Berhe N, Sabri F, Satti I, El Hassan AM, Sundar S, Chiodi F, Akuffo H (2002). Alteration of Fas and Fas ligand expression during human visceral leishmaniasis. Clin Exp Immunol. 130(2): 307-13. https://doi.org/10.1046/j.1365-2249.2002.01976.x II. Eidsmo L, Nylen S, Khamesipour A, Hedblad MA, Chiodi F, Akuffo H (2005). The contribution of the Fas/FasL apoptotic pathway in ulcer formation during Leishmania major-induced cutaneous Leishmaniasis. Am J Pathol. 166(4): 1099-108. https://doi.org/10.1016/S0002-9440(10)62330-9 III. Eidsmo L, Fluur C, Eriksson Ygberg S, DeMilito A, Rethi B, Akuffo H, Chiodi F (2006). FasL and TRAIL induced epidermal apoptosis and skin ulceration upon exposure to Leishmania major infection. [Submitted]IV. Eidsmo L, Nylen Spoormaker S, Lieke T, Peters N, Yagita H, Sacks D, Akuffo H, Chiodi F (2006). The effect of neutralisation of FasL on skin ulceration in murine models of cutaneous leishmaniasis. [Manuscript]</p
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Square Dancing with the Stars to Enhance Dynamic Hirschman Linkages?
In this Presidential Address, the author takes the reader on a reconnaissance of his life and time as a regional scientist. He points out scenery he found scintillating along the way, hoping that some may pick up the banner and chew on a few of the ideas for a while. He suggests a revisit to Albert O. Hirschman’s notion of key sectors and more empirical analysis related to Marcus Berliant’s and Masahisa Fujita’s notion of knowledge creation and transfer.Presidential Address, San Antonio, Texas, March 29, 2014 (53rd Meetings of the Southern Regional Science Association
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Letter from unknown writer to Jesse L. Boyce
Letter to Jesse L. Boyce from unknown author (possibly Jack) about the investigation into the powder magazine located in the Grand Canyon. Some personal news is included in the letter such as the writer's marriage to the daughter of C.A. Taylor, former Supervisor of Cochise County
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Sarah L. Blum Author Visit - Warrior Nurse: PTSD and Healing
Hear Sarah L. Blum, author of Women Under Fire: Abuse in the Military, discuss her newest book, Warrior Nurse: PTSD and Healing followed by a Q&A and book signing.
Sarah L. Blum is a decorated Vietnam veteran who served as an operating room nurse during the intense fighting of 1967. In recognition of her service, she was awarded the Army Commendation Medal.
Sponsored by CWU Veterans Center and CWU Libraries.https://digitalcommons.cwu.edu/libraryevents/1252/thumbnail.jp
Dysregulation of receptor induced apoptosis during human leishmaniasis : a possible mechanism of skin ulceration [Elektronisk resurs]
Leishmaniasis is endemic in 88 countries and 12 million people per year have been estimated to be at risk of infection. The causative agent, the protozoan Leishmania, is spread by sand-flies and infects macrophages in the mammalian host. Leishmaniasis in humans form a spectrum of clinical presentations. In cutaneous leishmaniasis (CL) caused by L. major, the infection is localised in the skin and manifests as one or several ulcers that typically spontaneously heal within one year after infection, often leaving marked scarring. In visceral leishmaniasis (VL) caused by L. donovani, infected macrophages are found in liver, spleen, bone marrow and lymph-nodes and the infection leads to hepatosplenomegaly, wasting, fever and if not treated, to death. Systemic T-cell deficiency occurs early during VL and leads to uncontrolled parasite replication. In general, solid immunity upon healing occurs after resolved VL and CL. In this thesis, the hypothesis that alterations of death receptor-mediated apoptosis have an impact on the pathogenesis of human leishmaniasis has been explored. During VL, dysregulation of the Fas/FasL pathway was investigated, both at one site of infection, the spleen, and on circulating lymphocytes from the peripheral blood. In the case of CL the hypothesis was that increased death receptor-mediated apoptosis in the microenvironment surrounding infected macrophages may induce bystandard apoptosis of keratinocytes, leading to skin ulceration. Dysiregulation of the Fas/FasL pathway occured during human VL and CL. Levels of soluble Fas (sFas) and soluble Fas ligand (sFasL) were elevated in plasma of patients with active VL and individuals co-infected with VL-HIV-1 compared to healthy controls, and the levels of sFas and sFasL were normalized 6 months after successful treatment. During active VL, the expression of membrane bound Fas, and to a lower extent Fast., was up-regulated on spleen cells, where parasites multiply. In contrast, expression of Fas and Fast- were not altered on peripheral blood mononuclear cells (PBMC) during VL. Furthermore, in vitro infection of macrophages with L. donovani results in up-regulation of Fas expression on the surface of infected cells and increases the levels of sFasL in supernatants from infected cultures. During active CL caused by L. major, a disease mainly localised to the skin, the Fas and Fast- levels were not altered in serum or on PBMCs analysed ex vivo. However, when CL PBMCs were restimulated with L. major, Fas was up-regulated on effector T-cells and high levels of sFasL were detected in the supernatants as compared to control PBMCs. Keratinocyte apoptosis is altered during CL. Dysregulation of the Fas/FasL pathway in the microenvironment surrounding L. major infected macrophages under the skin was visualised in biopsies collected from CL patients. A substantial number of apoptotic keratinocytes were observed in the epidermis of morphologically active and healing CL skin samples. Fas expression was increased on the epidermis in active CL, whereas FasL expressing macrophages and T-cells were found in the subepidermal infiltrate during active disease. Supernatants from re-stimulated CL-PBMC cultures containing high levels of sFasL induced apoptosis in human keratinocyte cell line (HaCaT), and apoptosis could be inhibited in 213 supernatants by blocking Fas. A commercial apoptosis-specific microarray was used to assess alterations in keratinocyte RNAexpression during exposure to supernatants from L. major infected PBMCs. Fas and TRAIL mRNA and protein expression were significantly up-regulated compared to untreated keratinocytes. Supernatant induced apoptosis of keratinocytes was partly inhibited through blocking Fas or FasL, and more efficiently through inhibition of TRAIL by neutralising antibodies or soluble TRAIL-R. Furthermore, TRAIL expressing keratinocytes were detected in skin biopsies from CL cases. Blocking the Fas/FasL pathway in vivo may reduce ulceration during murine CL. In order to obtain the proof of the concept that Fas/FasL signalling is involved in keratinocyte-apoptosis leading to ulceration in the skin during CL, the Fas/FasL pathway was blocked in a murine model of CL by intraperitoneal treatment with Fast- neutralising antibodies (MFL-4). Skin inflammation, skin ulceration and ulcer size were followed weekly and compared to infected, untreated mice. Our results suggests that blocking Fas/FasL signalling during murine CL lead to less apoptotic keratinocytes and diminished ulceration. During treatment, the number of IFNgammaproducing CD8+CD3+ cells was increased at the site of infection when Fast- was neutralised which is suggestive of efficient parasite eradication. However, there was no reduction of parasite load at the site of infection or in draining lymph nodes and parasite replication was high upon discontinuation of anti-FasL treatment. Conclusion: The Fas/FasL pathway was shown to be dysregulated both in human VL and CL. A possible mechanism of ulcer formation during CL was proposed by apoptotic death of keratinocytes through enhanced Fast- and TRAIL signalling. This data was further strengthened in a treatment experiment in a murine model of CL, where blocking the Fas/FasL system reduced ulcer formation during L. major infection
Lillian L. Lambert, Author, Speaker, and Entrepreneur
Lillian L. Lambert, Author, Speaker, and Entrepreneu
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