Method for Treating Cytokine Mediated Hepatic Injury

A method of modulating cytokine mediated hepatic injury by administering compound-D SEQ ID NO:1 to a mammal. A concentration of the compound in the range of about 0.5 mg/kg to about 20 mg/kg in a physiologically acceptable formulation blocks a cytokine cascade. A therapeutic method of modulating cytokine mediated acute inflammatory, trauma induced and toxin induced hepatic injury, particularly via tumor necrosis factor modulation, is thus disclosed

Method for Treating a Viral Infection Related or a Chemical Toxin Related Hepatic Injury with Deltorphin D

A method of modulating cytokine mediated hepatic injury by administering compound-D SEQ ID NO:1 to a mammal. A concentration of the compound in the range of about 0.5 mg/kg to about 20 mg/kg in a physiologically acceptable formulation blocks a cytokine cascade. A therapeutic method of modulating cytokine mediated acute inflammatory, trauma induced and toxin induced hepatic injury, particularly via tumor necrosis factor modulation, is thus disclosed

Method for Treating Cytokine Mediated Hepatic Injury

A method of modulating cytokine mediated hepatic injury by administering deltorphins to a mammal. Deltorphin I SEQ ID NO:1, deltorphin II SEQ ID NO:2 or combinations of deltorphins I SEQ ID NO:1 and II SEQ ID NO:2 may be administered. A deltorphin concentration in the range of about 0.5 mg/kg to about 20 mg/kg in a physiologically acceptable formulation blocks a cytokine cascade in a murine model of septic shock. A therapeutic method of modulating cytokine mediated acute inflammatory, trauma induced and toxin induced hepatic injury, particularly via tumor necrosis factor modulation, is thus disclosed

Intelligent Front-End Sample Preparation Tool Using Acoustic Streaming

We have successfully developed a nucleic acid extraction system based on a microacoustic lysis array coupled to an integrated nucleic acid extraction system all on a single cartridge. The microacoustic lysing array is based on 36{sup o} Y cut lithium niobate, which couples bulk acoustic waves (BAW) into the microchannels. The microchannels were fabricated using Mylar laminates and fused silica to form acoustic-fluidic interface cartridges. The transducer array consists of four active elements directed for cell lysis and one optional BAW element for mixing on the cartridge. The lysis system was modeled using one dimensional (1D) transmission line and two dimensional (2D) FEM models. For input powers required to lyse cells, the flow rate dictated the temperature change across the lysing region. From the computational models, a flow rate of 10 {micro}L/min produced a temperature rise of 23.2 C and only 6.7 C when flowing at 60 {micro}L/min. The measured temperature changes were 5 C less than the model. The computational models also permitted optimization of the acoustic coupling to the microchannel region and revealed the potential impact of thermal effects if not controlled. Using E. coli, we achieved a lysing efficacy of 49.9 {+-} 29.92 % based on a cell viability assay with a 757.2 % increase in ATP release within 20 seconds of acoustic exposure. A bench-top lysing system required 15-20 minutes operating up to 58 Watts to achieve the same level of cell lysis. We demonstrate that active mixing on the cartridge was critical to maximize binding and release of nucleic acid to the magnetic beads. Using a sol-gel silica bead matrix filled microchannel the extraction efficacy was 40%. The cartridge based magnetic bead system had an extraction efficiency of 19.2%. For an electric field based method that used Nafion films, a nucleic acid extraction efficiency of 66.3 % was achieved at 6 volts DC. For the flow rates we tested (10-50 {micro}L/min), the nucleic acid extraction time was 5-10 minutes for a volume of 50 {micro}L. Moreover, a unique feature of this technology is the ability to replace the cartridges for subsequent nucleic acid extractions

Regional to Global Assessments of Phytoplankton Dynamics From The SeaWiFS Mission

Photosynthetic production of organic matter by microscopic oceanic phytoplankton fuels ocean ecosystems and contributes roughly half of the Earth's net primary production. For 13 years, the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) mission provided the first consistent, synoptic observations of global ocean ecosystems. Changes in the surface chlorophyll concentration, the primary biological property retrieved from SeaWiFS, have traditionally been used as a metric for phytoplankton abundance and its distribution largely reflects patterns in vertical nutrient transport. On regional to global scales, chlorophyll concentrations covary with sea surface temperature (SST) because SST changes reflect light and nutrient conditions. However, the oceanmay be too complex to be well characterized using a single index such as the chlorophyll concentration. A semi-analytical bio-optical algorithm is used to help interpret regional to global SeaWiFS chlorophyll observations from using three independent, well-validated ocean color data products; the chlorophyll a concentration, absorption by CDM and particulate backscattering. First, we show that observed long-term, global-scale trends in standard chlorophyll retrievals are likely compromised by coincident changes in CDM. Second, we partition the chlorophyll signal into a component due to phytoplankton biomass changes and a component caused by physiological adjustments in intracellular chlorophyll concentrations to changes in mixed layer light levels. We show that biomass changes dominate chlorophyll signals for the high latitude seas and where persistent vertical upwelling is known to occur, while physiological processes dominate chlorophyll variability over much of the tropical and subtropical oceans. The SeaWiFS data set demonstrates complexity in the interpretation of changes in regional to global phytoplankton distributions and illustrates limitations for the assessment of phytoplankton dynamics using chlorophyll retrievals alone

Benthic Biofilm Controls on Fine Particle Dynamics in Streams

Este artículo contiene 15 páginas, 7 figuras, 3 tablas.Benthic (streambed) biofilms metabolize a substantial fraction of particulate organic matter and nutrient inputs to streams. These microbial communities comprise a significant proportion of overall biomass in headwater streams, and they present a primary control on the transformation and export of labile organic carbon. Biofilm growth has been linked to enhanced fine particle deposition and retention, a feedback that confers a distinct advantage for the acquisition and utilization of energy sources. We quantified the influence of biofilm structure on fine particle deposition and resuspension in experimental stream mesocosms. Biofilms were grown in identical 3 m recirculating flumes over periods of 18–47 days to obtain a range of biofilm characteristics. Fluorescent, 8 mm particles were introduced to each flume, and their concentrations in the water column were monitored over a 30 min period. We measured particle concentrations using a flow cytometer and mesoscale (10 mm to 1 cm) biofilm structure using optical coherence tomography. Particle deposition-resuspension dynamics were determined by fitting results to a stochastic mobile-immobile model, which showed that retention timescales for particles within the biofilm-covered streambeds followed a power-law residence time distribution. Particle retention times increased with biofilm areal coverage, biofilm roughness, and mean biofilm height. Our findings suggest that biofilm structural parameters are key predictors of particle retention in streams and rivers.This study was funded by a Marie Curie Intra- European Fellowship to WRH (FP7- PEOPLE-2011-IEF-302297) and an Austrian Science Fund grant to T.J.B. (START Y420-B17). K.R.R. was supported by a CUAHSI Pathfinder fellowship and U.S. NSF Graduate Research Fellowship. J.D.D. was supported by a Fulbright-Spain fellowship. The modeling effort was supported by U.S. NSF grants EAR- 1215898 and EAR-1344280 to AIP. Supporting data are provided at doi:10.6084/m9.figshare.4252193.Peer reviewe

Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations

BACKGROUND: Progressive supranuclear palsy (PSP) -Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP. OBJECTIVES: To determine contributions of each domain of the PSP Rating Scale to overall severity and characterize the probable sequence of clinical progression of PSP as compared to CBS. METHODS: Multicenter clinical trial and natural history study data were analyzed from 545 patients with PSP and 49 with CBS. Proportional odds models were applied to model normalized cross-sectional PSP Rating Scale, estimating the probability that a patient would experience impairment in each domain using the PSP Rating Scale total score as the index of overall disease severity. RESULTS: The earliest symptom domain to demonstrate impairment in PSP patients was most likely to be Ocular Motor, followed jointly by Gait/Midline and Daily Activities, then Limb Motor and Mentation, and finally Bulbar. For CBS, Limb Motor manifested first and ocular showed less probability of impairment throughout the disease spectrum. An online tool to visualize predicted disease progression was developed to predict relative disability on each subscale per overall disease severity. CONCLUSION: The PSP Rating Scale captures disease severity in both PSP and CBS. Modelling how domains change in relation to one other at varying disease severities may facilitate detection of therapeutic effects in future clinical trials

A framework for the development of a global standardised marine taxon reference image database (SMarTaR-ID) to support image-based analyses

Video and image data are regularly used in the field of benthic ecology to document biodiversity. However, their use is subject to a number of challenges, principally the identification of taxa within the images without associated physical specimens. The challenge of applying traditional taxonomic keys to the identification of fauna from images has led to the development of personal, group, or institution level reference image catalogues of operational taxonomic units (OTUs) or morphospecies. Lack of standardisation among these reference catalogues has led to problems with observer bias and the inability to combine datasets across studies. In addition, lack of a common reference standard is stifling efforts in the application of artificial intelligence to taxon identification. Using the North Atlantic deep sea as a case study, we propose a database structure to facilitate standardisation of morphospecies image catalogues between research groups and support future use in multiple front-end applications. We also propose a framework for coordination of international efforts to develop reference guides for the identification of marine species from images. The proposed structure maps to the Darwin Core standard to allow integration with existing databases. We suggest a management framework where high-level taxonomic groups are curated by a regional team, consisting of both end users and taxonomic experts. We identify a mechanism by which overall quality of data within a common reference guide could be raised over the next decade. Finally, we discuss the role of a common reference standard in advancing marine ecology and supporting sustainable use of this ecosystem

A blueprint for an inclusive, global deep-sea Ocean Decade field programme

The ocean plays a crucial role in the functioning of the Earth System and in the provision of vital goods and services. The United Nations (UN) declared 2021–2030 as the UN Decade of Ocean Science for Sustainable Development. The Roadmap for the Ocean Decade aims to achieve six critical societal outcomes (SOs) by 2030, through the pursuit of four objectives (Os). It specifically recognizes the scarcity of biological data for deep-sea biomes, and challenges the global scientific community to conduct research to advance understanding of deep-sea ecosystems to inform sustainable management. In this paper, we map four key scientific questions identified by the academic community to the Ocean Decade SOs: (i) What is the diversity of life in the deep ocean? (ii) How are populations and habitats connected? (iii) What is the role of living organisms in ecosystem function and service provision? and (iv) How do species, communities, and ecosystems respond to disturbance? We then consider the design of a global-scale program to address these questions by reviewing key drivers of ecological pattern and process. We recommend using the following criteria to stratify a global survey design: biogeographic region, depth, horizontal distance, substrate type, high and low climate hazard, fished/unfished, near/far from sources of pollution, licensed/protected from industry activities. We consider both spatial and temporal surveys, and emphasize new biological data collection that prioritizes southern and polar latitudes, deeper (> 2000 m) depths, and midwater environments. We provide guidance on observational, experimental, and monitoring needs for different benthic and pelagic ecosystems. We then review recent efforts to standardize biological data and specimen collection and archiving, making “sampling design to knowledge application” recommendations in the context of a new global program. We also review and comment on needs, and recommend actions, to develop capacity in deep-sea research; and the role of inclusivity - from accessing indigenous and local knowledge to the sharing of technologies - as part of such a global program. We discuss the concept of a new global deep-sea biological research program ‘Challenger 150,’ highlighting what it could deliver for the Ocean Decade and UN Sustainable Development Goal 14