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Pelleting overcomes the utilization limitation of lignocellulosic biomass due to its low density and related processing costs. Efficiently combining biomass pelleting and enzymatic saccharification is a challenge for applying biomass with low density in a biorefinery. In this study, we propose a novel biomass processing approach involving the addition of surfactant during pelleting and using the pellets for pretreatment and enzymatic saccharification. We investigated the effects of polyethylene glycol (PEG) 6000 assisted pelleting on pelleting specific energy consumption and friction, and on subsequent pretreatment as well as on enzymatic saccharification of the pretreated pellets. The results showed that PEG 6000 assisted pelleting decreased the total pelleting specific energy consumption by about 14% for wheat straw and 18% for pine, and reduced the maximum friction during ejection of pellets by about 34% for wheat straw and 29% for pine. PEG 6000 assisted pelleting enhanced subsequent enzymatic sugar yield effectively for both acid and alkaline pretreated wheat straw and pine, especially for acid-treated pine pellets, where a 256% increase in glucose yield was obtained. The results suggest that PEG 6000 decreases the cleavage of β-O-4′ linkages during pretreatment and thus hinders the formation of phenolic hydroxyl groups, contributing to the enhanced sugar yield in enzymatic saccharification. As surfactants were found to have beneficial effects on both biomass pelleting and the sugar yield obtained from the enzymatic saccharification of the pretreated pellets, it would be advantageous to add surfactants during pelletizing when the pellets are intended for application in a biorefinery.

Members of the genus Populus (i.e., cottonwood, hybrid poplar) represent a promising source of lignocellulosic biomass for biofuels. However, one of the major factors negatively affecting poplar's efficient conversion to biofuel is the inherent recalcitrance to enzymatic saccharification due to cell wall components such as lignin. To this effect, there have been efforts to modify gene expression to reduce biomass recalcitrance by changing cell wall properties. Here, we review recent genetic modifications of poplar that led to change cell wall properties and the resulting effects on subsequent pretreatment efficacy and saccharification. Although genetic engineering's impacts on cell wall properties are not fully predictable, recent studies have shown promising improvement in the biological conversion of transgenic poplar to biofuels.

Densification of lignocellulosic biomass is beneficial for its logistics, and in some situations, also for its application in biorefineries. In this study, industrial pellets and laboratory-made pellets produced at different die temperatures (90, 125 °C) from wheat straw, beech, and pine were pretreated (by dilute acid and alkali) and enzymatically hydrolyzed to study the effects of pelleting on pretreatment and sugar yield. The results showed that industrial pelleting positively affected sugar yield of the three biomasses for both acid and alkaline pretreatments, while laboratory pelleting affected sugar yield differently related to pretreatment types and biomass species. Pelleting disturbed biomass cell wall structure and affected the stability of hemicellulose and β-O-4′ linkages in lignin. The extent of hemicellulose solubility during acid pretreatment and the amount of lignin β-O-4′ ether linkages present in acid pretreated substrates could serve as indicators of the effect of pelleting on sugar yield. The structural modifications caused by pelleting and their effects on the enzymatic sugar yield correlate tightly to pelleting technology, pretreatment method, and biomass species. The discrepant effects between industrial and laboratory pelleting on sugar yield observed in this study should be considered when designing future studies.

BACKGROUND: Frequent and thorough monitoring of patient safety is a requirement of clinical trials research. Safety data are traditionally reported in a tabular or listing format, which often translates into many pages of static displays. This poses the risk that clinically relevant signals will be obscured by the sheer volume of data reported. Interactive graphics enable the delivery of the vast scope of information found in traditional reports, but allow the user to interact with the charts in real time, focusing on signals of interest. METHODS: Clinical research staff, including biostatisticians, project managers, and a medical monitor were consulted to guide the development of a set of interactive data visualizations that enable key safety assessments for participants. The resulting “Safety Explorer” is a set of 6 interactive, web-based, open source tools designed to address the shortcomings of traditional, static reports for safety monitoring. RESULTS: The Safety Explorer is freely available on GitHub as individual JavaScript libraries: Adverse Event Explorer, Adverse Event Timelines, Safety Histogram, Safety Outlier Explorer, Safety Results Over Time, and Safety Shift Plot, or in a single combined framework: Safety Explorer Suite. The suite can also be utilized through its R interface, the safetyexploreR package. CONCLUSIONS: The Safety Explorer provides interactive charts that contain the same information available in standard displays, but the interactive interface allows for improved exploration of patterns and comparisons. Medical Monitors, Safety Review Boards, and Project Teams can use these tools to effectively track and analyze key safety variables and study endpoints.

Introduction Magnetic resonance imaging (MRI) was used to monitor changes in the transverse relaxation time constant (T2) in lower hindlimb muscles of mdx mice at different ages. Methods Young (5 weeks), adult (44 weeks), and old mdx (96 weeks), and age-matched control mice were studied. Young mdx mice were imaged longitudinally, whereas adult and old mdx mice were imaged at a single time-point. Results Mean muscle T2 and percent of pixels with elevated T2 were significantly different between mdx and control mice at all ages. In young mdx mice, mean muscle T2 peaked at 7–8 weeks and declined at 9–11 weeks. In old mdx mice, mean muscle T2 was decreased compared with young and adult mice, which could be attributed to fibrosis. Conclusions MRI captured longitudinal changes in skeletal muscle integrity of mdx mice. This information will be valuable for pre-clinical testing of potential therapeutic interventions for muscular dystrophy. Muscle Nerve 53: 84–90, 2016

Webcharts is a JavaScript library built on top of D3.js that creates reusable, flexible, interactive charts that are highly customizable. Webcharts provides a method for creating commonly-used charts, including bar charts, scatterplots, and timelines, through a simple configuration scheme. Charts created with Webcharts allow users to dynamically manipulate chart data, appearance, and behavior both through callback functions and input elements that are tied to chart objects. This approach allows users to create reusable charts that range from simple static graphics to complex interactive data exploration tools with custom user interfaces, all using the same library.

Received 11 March 2005/Accepted 25 May 2005 Two strains of the parvovirus minute virus of mice (MVM), the immunosuppressive (MVMi) and the prototype (MVMp) strains, display disparate in vitro tropism and in vivo pathogenicity. We report the crystal structures of MVMp virus-like particles (MVMpb) and native wild-type (wt) empty capsids (MVMpe), determined and refined to 3.25 and 3.75 A resolution, respectively, and their comparison to the structure of MVMi, also refined to 3.5 A resolution in this study. A comparison of the MVMpb and MVMpe capsids showed their structures to be the same, providing structural verification that some heterologously expressed parvovirus capsids are indistinguishable from wt capsids produced in host cells. The structures of MVMi and MVMp capsids were almost identical, but local surface conformational differences clustered from symmetry-related capsid proteins at three specific domains: (i) the icosahedral fivefold axis, (ii) the “shoulder” of the protrusion at the icosahedral threefold axis, and (iii) the area surrounding the depression at the icosahedral twofold axis. The latter two domains contain important determinants of MVM in vitro tropism (residues 317 and 321) and forward mutation residues (residues 399, 460, 553, and 558) conferring fibrotropism on MVMi. Furthermore, these structural differences between the MVM strains colocalize with tropism and pathogenicity determinants mapped for other autonomous parvovirus capsids, highlighting the importance of common parvovirus capsid regions in the control of virus-host interactions. Viral tissue tropism and pathogenesis are highly dependent on well-orchestrated and defined interactions that occur between the viral pathogen and its host. The single-stranded Parvoviridae infect a broad range of natural hosts that include invertebrates and mammals, and pathogenic members cause serious disease in the young and immunocompromised adults. However, disparities in tissue tropism and in vivo pathogenicity can be observed between highly homologous strains for several members of the Parvoviridae. The combination of molecular analysis with disease outcomes for a number of strains of the Aleutian mink disease parvovirus (AMDV) (9, 10), canine parvovirus (CPV), and feline panleukopenia virus (FPV) (46, 61, 62), and for porcine parvovirus (PPV) (8, 41), has provided

Cyclopropyl analogues of melatonin can be readily synthesized in high yields by Rh(II)-catalysed decomposition of aryldiazoacetates in the presence of N-vinylacetamide or vinyl acetate. The reaction is highly trans selective.

Introduction—This study compared the effects of downhill or horizontal treadmill running on the magnetic resonance imaging (MRI) transverse relaxation time constant (T2) in mdx mice. Methods—Mice underwent either downhill (n=11 mdx, n=6 controls) or horizontal running (n=9, mdx only) on a treadmill. MRI was conducted prior to exercise, immediately afterwards (~20 min), 24, and 48 hours following exercise. Results—A higher percentage of pixels with elevated T2 in the lower hindlimb muscles was observed in the mdx mice compared to controls both pre-exercise (p < 0.001) and at each time point following downhill running (p < 0.05), but not with horizontal running. The medial compartment muscles appeared to be the most susceptible to increased T2. Discussion—Downhill running provides a stimulus for inducing acute changes in muscle T2 in mdx mice. MRI is a non-invasive approach for examining acute muscle damage and recovery in multiple muscle groups simultaneously.

This document presents a summary and framework of available transport data and other information directly relevant to the development of the Rainier Mesa/Shoshone Mountain (RMSM) Corrective Action Unit (CAU) 99 groundwater transport model. Where appropriate, data and information documented elsewhere are briefly summarized with reference to the complete documentation.

Limb girdle muscular dystrophy (LGMD) describes a group of inherited diseases resulting from mutations in genes encoding proteins involved in maintaining skeletal muscle membrane stability. LGMD type-2D is caused by mutations in alpha-sarcoglycan (sgca). Here we describe muscle-specific gene delivery of the human sgca gene into dystrophic muscle using an adeno-associated virus 1 (AAV1) capsid and creatine kinase promoter. Delivery of this construct to adult sgca(-/-) mice resulted in localization of the sarcoglycan complex to the sarcolemma and a reduction in muscle fiber damage. Sgca expression prevented disease progression as observed in vivo by T(2)-weighted magnetic resonance imaging (MRI) and confirmed in vitro by decreased Evan's blue dye accumulation. The ability of recombinant AAV-mediated gene delivery to restore normal muscle mechanical properties in sgca(-/-) mice was verified by in vitro force mechanics on isolated extensor digitorum longus (EDL) muscles, with a decrease in passive resistance to stretch as compared with untreated controls. In summary, AAV/AAV-sgca gene transfer provides long-term muscle protection from LGMD and can be non-invasively evaluated using magnetic resonance imaging.

The role of receptor recognition in the emergence of virulent viruses was investigated in the infection of severe combined immunodeficient (SCID) mice by the apathogenic prototype strain of the parvovirus minute virus of mice (MVMp). Genetic analysis of isolated MVMp viral clones ( n = 48) emerging in mice, including lethal variants, showed only one of three single changes (V325M, I362S, or K368R) in the common sequence of the two capsid proteins. As was found for the parental isolates, the constructed recombinant viruses harboring the I362S or the K368R single substitutions in the capsid sequence, or mutations at both sites, showed a large-plaque phenotype and lower avidity than the wild type for cells in the cytotoxic interaction with two permissive fibroblast cell lines in vitro and caused a lethal disease in SCID mice when inoculated by the natural oronasal route. Significantly, the productive adsorption of MVMp variants carrying any of the three mutations selected through parallel evolution in mice showed higher sensitivity to the treatment of cells by neuraminidase than that of the wild type, indicating a lower affinity of the viral particle for the sialic acid component of the receptor. Consistent with this, the X-ray crystal structure of the MVMp capsids soaked with sialic acid ( N -acetyl neuraminic acid) showed the sugar allocated in the depression at the twofold axis of symmetry (termed the dimple), immediately adjacent to residues I362 and K368, which are located on the wall of the dimple, and approximately 22 Å away from V325 in a threefold-related monomer. This is the first reported crystal structure identifying an infectious receptor attachment site on a parvovirus capsid. We conclude that the affinity of the interactions of sialic-acid-containing receptors with residues at or surrounding the dimple can evolutionarily regulate parvovirus pathogenicity and adaptation to new hosts.

This report documents pertinent transport data and data analyses as part of the Phase II Corrective Action Investigation (CAI) for Frenchman Flat (FF) Corrective Action Unit (CAU) 98. The purpose of this data compilation and related analyses is to provide the primary reference to support parameterization of the Phase II FF CAU transport model.