562 research outputs found

    Novel Insights into Membrane Transport from Computational Methodologies

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    Temporal Variations of Shallow Subtidal Meiofauna in Los Cristianos Bay (Tenerife, Canary Islands, Ne Atlantic Ocean)

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    As assembleias da meiofauna de Los Cristianos Bay, Tenerife, Ilhas Canárias, foi amostrada de maio de 2000 a abril de 2001 a 3 m de profundidade. Nematoda dominou durante todo o período de estudo, variando entre 84.52% em maio de 2000 a 95.93% em outubro do mesmo ano. Copepoda e Polychaeta foram o segundo e terceiro grupos mais abundantes, respectivamente. A densidade apresentou diferenças significativas ao longo do período, com valores mínimos na primavera-verão (maio-julho) e máximos no inverno (janeiro e fevereiro). Essa sazonalidade está sendo atribuída principalmente às variações temporais das espécies mais abundantes de nemátodes (Daptonema hirsutum e Pomponema sedecima). A meiofauna apresentou ainda diferenças na composição e abundância em maio e junho de 2000 quando comparado com os meses restantes do estudo. As variáveis ambientais explicaram parcialmente as variações na estrutura da comunidade e o tipo sedimentar areia muito fina destacou-se entre os mais importantes, juntamente com outras variáveis, tais como nitrogênio e conteúdo de matéria orgânica.A subtidal meiofaunal assemblage in Los Cristianos Bay, Tenerife, Canary Islands was sampled from May 2000 to April 2001, at 3 m depth. Nematodes dominated overwhelmingly during the study period, ranging from 84.52% in May 2000 to 95.93% in October 2000. Copepods and polychaetes were the second and the third most abundant groups, respectively. Meiofaunal densities showed significant differences throughout the study period, with minimum abundances during the spring-summer months (May-July) and highest densities in winter (January and February). This seasonality is mainly due to the temporal variations of the most abundant species (nematodes Daptonema hirsutum and Pomponema sedecima), with differences in meiofauna species composition and abundance during May and June 2000 as compared to the remaining months of the study period. Environmental variables partly explained meiofaunal community structure, being the sedimentary type of very fine sands the most important, jointly with other variables, such as nitrogen and organic matter content

    PERFORMANCE OF FISH LARVAE: EFFECTS OF ATRAZINE,

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    To my husband, Rafael Perez, to whom I owe everything, who has been with me through the “good and the bad”. To my son, Diego T. Perez, and my daughter, Cecilia A. Perez, who have always brightened my day with laughter and love. And to my parents, Alvaro Alvarez and Marie Cecilie d’Otreppe de Bouvette, who, without ever a doubt, have supported me on every decision I have made. Thank you. Acknowledgements I wish to thank my adviser Dr. Lee A. Fuiman, for his guidance, support, and encouragement. I am also grateful to the members of my committee, Dr. David P. Crews, Dr. G. Joan Holt, Dr. B. Scott Nunez and Dr. Peter Thomas for their helpful suggestions and critical review of this dissertation. Thanks to my laboratory mates; Hunter Samberson and Brie Sarkisian for their help with fish rearing; Ian McCarthy for helping with fish rearing and collection of data, and Kiersten Madden for her support and critique of this work. My special thanks to Rafael Perez, Scott Applebaum, and Ian McCarthy for discussion in the development of the research presented here. I am sincerely thankful to all my friends at the Marine Science Institute and Port Aransas for their help and support, without whom this dissertation would not have happened. v SIGNIFICANCE OF ENVIRONMENTALLY REALISTI

    Thermodynamic analysis of absorption refrigeration cycles by parabolic trough collectors

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    "The purpose of this study is to numerically investigate the performance of a solar physical surface absorption cooling system, in which activated carbon/methanol is used as a working pair, which is placed inside a parabolic-shaped solar collector. The governing mathematical model of this issue is based on the equations of conservation of mass, conservation of energy, and thermodynamics of the physical surface absorption process. The equations are discretized using the fully implicit finite difference method, and the Fortran computer program was simulated. A comparison with the results of previous laboratory and numerical studies validated this model. At each point in the bed, the temperature, pressure, and mass of the refrigerant absorbed during the physical surface absorption/discharge process were calculated. In addition, the effects of the bed diameter, amount of solar radiation, source temperature, temperature, and pressure of the evaporator and condenser were investigated on the solar performance coefficient and the specific cooling power of the system. According to the built laboratory model and the working conditions of the system, the solar performance coefficient and the specific cooling capacity of the system are equal to 0.12 and 45.6 W/kg, respectively.

    CA125-Guided Diuretic Treatment Versus Usual Care in Patients With Acute Heart Failure and Renal Dysfunction

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    Background: The optimal diuretic treatment strategy for patients with acute heart failure and renal dysfunction remains unclear. Plasma carbohydrate antigen 125 (CA125) is a surrogate of fluid overload and a potentially valuable tool for guiding decongestion therapy. The aim of this study was to determine if a CA125-guided diuretic strategy is superior to usual care in terms of short-term renal function in patients with acute heart failure and renal dysfunction at presentation. Methods: This multicenter, open-label study randomized 160 patients with acute heart failure and renal dysfunction into 2 groups (1:1). Loop diuretics doses were established according to CA125 levels in the CA125-guided group (n = 79) and in clinical evaluation in the usual-care group (n = 81). Changes in estimated glomerular filtration rate (eGFR) at 72 and 24 hours were the co-primary endpoints, respectively. Results: The mean age was 78 ± 8 years, the median amino-terminal pro-brain natriuretic peptide was 7765 pg/mL, and the mean eGFR was 33.7 ± 11.3 mL/min/1.73m2. Over 72 hours, the CA125-guided group received higher furosemide equivalent dose compared to usual care (P = 0.011), which translated into higher urine volume (P = 0.042). Moreover, patients in the active arm with CA125 >35 U/mL received the highest furosemide equivalent dose (P <0.001) and had higher diuresis (P = 0.013). At 72 hours, eGFR (mL/min/1.73m2) significantly improved in the CA125-guided group (37.5 vs 34.8, P = 0.036), with no significant changes at 24 hours (35.8 vs 39.5, P = 0.391). Conclusion: A CA125-guided diuretic strategy significantly improved eGFR and other renal function parameters at 72 hours in patients with acute heart failure and renal dysfunction

    Head-to-Head Comparison of Three Vaccination Strategies Based on DNA and Raw Insect-Derived Recombinant Proteins against Leishmania

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    Parasitic diseases plague billions of people among the poorest, killing millions annually, and causing additional millions of disability-adjusted life years lost. Leishmaniases affect more than 12 million people, with over 350 million people at risk. There is an urgent need for efficacious and cheap vaccines and treatments against visceral leishmaniasis (VL), its most severe form. Several vaccination strategies have been proposed but to date no head-to-head comparison was undertaken to assess which is the best in a clinical model of the disease. We simultaneously assayed three vaccination strategies against VL in the hamster model, using KMPII, TRYP, LACK, and PAPLE22 vaccine candidate antigens. Four groups of hamsters were immunized using the following approaches: 1) raw extracts of baculovirus-infected Trichoplusia ni larvae expressing individually one of the four recombinant proteins (PROT); 2) naked pVAX1 plasmids carrying the four genes individually (DNA); 3) a heterologous prime-boost (HPB) strategy involving DNA followed by PROT (DNA-PROT); and 4) a Control including empty pVAX1 plasmid followed by raw extract of wild-type baculovirus-infected T. ni larvae. Hamsters were challenged with L. infantum promastigotes and maintained for 20 weeks. While PROT vaccine was not protective, DNA vaccination achieved protection in spleen. Only DNA-PROT vaccination induced significant NO production by macrophages, accompanied by a significant parasitological protection in spleen and blood. Thus, the DNA-PROT strategy elicits strong immune responses and high parasitological protection in the clinical model of VL, better than its corresponding naked DNA or protein versions. Furthermore, we show that naked DNA coupled with raw recombinant proteins produced in insect larvae biofactories -the cheapest way of producing DNA-PROT vaccines-is a practical and cost-effective way for potential "off the shelf" supplying vaccines at very low prices for the protection against leishmaniases, and possibly against other parasitic diseases affecting the poorest of the poor.Spanish GovernmentSpanish Government [AGL2008-00748, AGL2010-16678-GAN]Generalitat de Catalunya [2005 FI 01116]Generalitat de Cataluny

    Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

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    Antibody recognition of the glycoprotein g of viral haemorrhagic septicemia virus (VHSV) purified in large amounts from insect larvae

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    <p>Abstract</p> <p>Background</p> <p>There are currently no purification methods capable of producing the large amounts of fish rhabdoviral glycoprotein G (gpG) required for diagnosis and immunisation purposes or for studying structure and molecular mechanisms of action of this molecule (ie. pH-dependent membrane fusion). As a result of the unavailability of large amounts of the gpG from viral haemorrhagic septicaemia rhabdovirus (VHSV), one of the most dangerous viruses affecting cultured salmonid species, research interests in this field are severely hampered. Previous purification methods to obtain recombinant gpG from VHSV in <it>E. coli</it>, yeast and baculovirus grown in insect cells have not produced soluble conformations or acceptable yields. The development of large-scale purification methods for gpGs will also further research into other fish rhabdoviruses, such as infectious haematopoietic necrosis virus (IHNV), spring carp viremia virus (SVCV), hirame rhabdovirus (HIRRV) and snakehead rhabdovirus (SHRV).</p> <p>Findings</p> <p>Here we designed a method to produce milligram amounts of soluble VHSV gpG. Only the transmembrane and carboxy terminal-deleted (amino acid 21 to 465) gpG was efficiently expressed in insect larvae. Recognition of G21-465 by ß-mercaptoethanol-dependent neutralizing monoclonal antibodies (N-MAbs) and pH-dependent recognition by sera from VHSV-hyperimmunized or VHSV-infected rainbow trout (<it>Oncorhynchus mykiss</it>) was demonstrated.</p> <p>Conclusions</p> <p>Given that the purified G21-465 conserved some of its most important properties, this method might be suitable for the large-scale production of fish rhabdoviral gpGs for use in diagnosis, fusion and antigenicity studies.</p

    Divergent Genomic and Epigenomic Landscapes of Lung Cancer Subtypes Underscore the Selection of Different Oncogenic Pathways during Tumor Development

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    For therapeutic purposes, non-small cell lung cancer (NSCLC) has traditionally been regarded as a single disease. However, recent evidence suggest that the two major subtypes of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SqCC) respond differently to both molecular targeted and new generation chemotherapies. Therefore, identifying the molecular differences between these tumor types may impact novel treatment strategy. We performed the first large-scale analysis of 261 primary NSCLC tumors (169 AC and 92 SqCC), integrating genome-wide DNA copy number, methylation and gene expression profiles to identify subtype-specific molecular alterations relevant to new agent design and choice of therapy. Comparison of AC and SqCC genomic and epigenomic landscapes revealed 778 altered genes with corresponding expression changes that are selected during tumor development in a subtype-specific manner. Analysis of >200 additional NSCLCs confirmed that these genes are responsible for driving the differential development and resulting phenotypes of AC and SqCC. Importantly, we identified key oncogenic pathways disrupted in each subtype that likely serve as the basis for their differential tumor biology and clinical outcomes. Downregulation of HNF4α target genes was the most common pathway specific to AC, while SqCC demonstrated disruption of numerous histone modifying enzymes as well as the transcription factor E2F1. In silico screening of candidate therapeutic compounds using subtype-specific pathway components identified HDAC and PI3K inhibitors as potential treatments tailored to lung SqCC. Together, our findings suggest that AC and SqCC develop through distinct pathogenetic pathways that have significant implication in our approach to the clinical management of NSCLC

    A pan-European epidemiological study reveals honey bee colony survival depends on beekeeper education and disease control

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    Reports of honey bee population decline has spurred many national efforts to understand the extent of the problem and to identify causative or associated factors. However, our collective understanding of the factors has been hampered by a lack of joined up trans-national effort. Moreover, the impacts of beekeeper knowledge and beekeeping management practices have often been overlooked, despite honey bees being a managed pollinator. Here, we established a standardised active monitoring network for 5 798 apiaries over two consecutive years to quantify honey bee colony mortality across 17 European countries. Our data demonstrate that overwinter losses ranged between 2% and 32%, and that high summer losses were likely to follow high winter losses. Multivariate Poisson regression models revealed that hobbyist beekeepers with small apiaries and little experience in beekeeping had double the winter mortality rate when compared to professional beekeepers. Furthermore, honey bees kept by professional beekeepers never showed signs of disease, unlike apiaries from hobbyist beekeepers that had symptoms of bacterial infection and heavy Varroa infestation. Our data highlight beekeeper background and apicultural practices as major drivers of honey bee colony losses. The benefits of conducting trans-national monitoring schemes and improving beekeeper training are discussed
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