128 research outputs found
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Chemical Architecture and Applications of Nucleic Acid Derivatives Containing 1,2,3-Triazole Functionalities Synthesized via Click Chemistry
There is considerable attention directed at chemically modifying nucleic acids with robust functional groups in order to alter their properties. Since the breakthrough of copper-assisted azide-alkyne cycloadditions (CuAAC), there have been several reports describing the synthesis and properties of novel triazole-modified nucleic acid derivatives for potential downstream DNA- and RNA-based applications. This review will focus on highlighting representative novel nucleic acid molecular structures that have been synthesized via the “click” azide-alkyne cycloaddition. Many of these derivatives show compatibility for various applications that involve enzymatic transformation, nucleic acid hybridization, molecular tagging and purification, and gene silencing. The details of these applications are discussed. In conclusion, the future of nucleic acid analogues functionalized with triazoles is promising
Diffusion as the main process for mass transport in very low water content argillites: 2. Fluid flow and mass transport modeling
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94838/1/wrcr9843.pd
Fracture-fill calcite as a record of microbial methanogenesis and fluid migration: a case study from the Devonian Antrim Shale, Michigan Basin
The Devonian Antrim Shale is an organic-rich, naturally fractured black shale in the Michigan Basin that serves as both a source and reservoir for natural gas. A well-developed network of major, through-going vertical fractures controls reservoir-scale permeability in the Antrim Shale. Many fractures are open, but some are partially sealed by calcite cements that retain isotopic evidence of widespread microbial methanogenesis. Fracture filling calcite displays an unusually broad spectrum of ÎŽ 13 C values (+34 to â41â° PDB), suggesting that both aerobic and anaerobic bacterial processes were active in the reservoir. Calcites with high ÎŽ 13 C values (>+15â°) record cementation of fractures from dissolved inorganic carbon (DIC) generated during bacterial methanogenesis. Calcites with low ÎŽ 13 C values (<â32â°) are solely associated with outcrop samples and record methane oxidation during cement precipitation. Fracture-fill calcite with ÎŽ 13 C values between â10 and â30â° can be attributed to variable organic matter oxidation pathways, methane oxidation, and carbonate rock buffering. Identification of 13 C-rich calcite provides unambiguous evidence of biogenic methane generation and may be used to identify gas deposits in other sedimentary basins. It is likely that repeated glacial advances and retreats exposed the Antrim Shale at the basin margin, enhanced meteoric recharge into the shallow part of the fractured reservoir, and initiated multiple episodes of bacterial methanogenesis and methanotrophic activity that were recorded in fracture-fill cements. The ÎŽ 18 O values in both formation waters and calcite cements increase with depth in the basin (â12 to â4â° SMOW, and +21 to +27â° PDB, respectively). Most fracture-fill cements from outcrop samples have ÎŽ 13 C values between â41 and â15â° PDB. In contrast, most cement in cores have ÎŽ 13 C values between +15 and +34â° PDB. Radiocarbon and 230 Th dating of fracture-fill calcite indicates that the calcite formed between 33 and 390âka, well within the Pleistocene Epoch.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75720/1/j.1468-8123.2002.00036.x.pd
Workforce scheduling and routing problems: literature survey and computational study
In the context of workforce scheduling, there are many scenarios in which personnel must carry out tasks at different locations hence requiring some form of transportation. Examples of these type of scenarios include nurses visiting patients at home, technicians carrying out repairs at customersâ locations and security guards performing rounds at different premises, etc. We refer to these scenarios as workforce scheduling and routing problems (WSRP) as they usually involve the scheduling of personnel combined with some form of routing in order to ensure that employees arrive on time at the locations where tasks need to be performed. The first part of this paper presents a survey which attempts to identify the common features of WSRP scenarios and the solution methods applied when tackling these problems. The second part of the paper presents a study on the computational difficulty of solving these type of problems. For this, five data sets are gathered from the literature and some adaptations are made in order to incorporate the key features that our survey identifies as commonly arising in WSRP scenarios. The computational study provides an insight into the structure of the adapted test instances, an insight into the effect that problem features have when solving the instances using mathematical programming, and some benchmark computation times using the Gurobi solver running on a standard personal computer
Monosodium urate crystals promote innate anti-mycobacterial immunity and improve BCG efficacy as a vaccine against tuberculosis
A safer and more effective anti-Tuberculosis vaccine is still an urgent need. We probed the effects of monosodium urate crystals (MSU) on innate immunity to improve the Bacille Calmette-Guerin (BCG) vaccination. Results showed that in vitro MSU cause an enduring macrophage stimulation of the anti-mycobacterial response, measured as intracellular killing, ROS production and phagolysosome maturation. The contribution of MSU to anti-mycobacterial activity was also shown in vivo. Mice vaccinated in the presence of MSU showed a lower number of BCG in lymph nodes draining the vaccine inoculation site, in comparison to mice vaccinated without MSU. Lastly, we showed that MSU improved the efficacy of BCG vaccination in mice infected with Mycobacterium tuberculosis (MTB), measured in terms of lung and spleen MTB burden. These results demonstrate that the use of MSU as adjuvant may represent a novel strategy to enhance the efficacy of BCG vaccination
Ecogenetics of mercury: From genetic polymorphisms and epigenetics to risk assessment and decisionâmaking
The risk assessment of mercury (Hg), in both humans and wildlife, is made challenging by great variability in exposure and health effects. Although disease risk arises following complex interactions between genetic (ânatureâ) and environmental (ânurtureâ) factors, most Hg studies thus far have focused solely on environmental factors. In recent years, ecogeneticâbased studies have emerged and have started to document genetic and epigenetic factors that may indeed influence the toxicokinetics or toxicodynamics of Hg. The present study reviews these studies and discusses their utility in terms of Hg risk assessment, management, and policy and offers perspectives on fruitful areas for future research. In brief, epidemiological studies on populations exposed to inorganic Hg (e.g., dentists and miners) or methylmercury (e.g., fish consumers) are showing that polymorphisms in a number of environmentally responsive genes can explain variations in Hg biomarker values and health outcomes. Studies on mammals (wildlife, humans, rodents) are showing Hg exposures to be related to epigenetic marks such as DNA methylation. Such findings are beginning to increase understanding of the mechanisms of action of Hg, and in doing so they may help identify candidate biomarkers and pinpoint susceptible groups or life stages. Furthermore, they may help refine uncertainty factors and thus lead to more accurate risk assessments and improved decisionâmaking. Environ Toxicol Chem 2014;33:1248â1258. © 2013 SETACPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106903/1/etc2375.pd
Signalling versatility following self and non-self sensing by myeloid C-type lectin receptors
AbstractAmong myeloid immune receptors, C-type lectin receptors (CLRs) have a remarkable capacity to sense a variety of self and non-self ligands. The coupling of CLRs to different signal transduction modules is influenced not only by the receptor, but also by the nature, density and architecture of the ligand, which can affect the rate of receptor internalization and trafficking to diverse intracellular compartments. Understanding how the variety of self and non-self ligands triggers differential CLR signalling and function presents a fascinating biological challenge. Non-self ligands usually promote inflammation and immunity, whereas self ligands are frequently involved in communication and tolerance. But pathogens can mimic self-inhibitory signals to escape immune surveillance, and endogenous ligands can contribute to the sensing of pathogens through CLRs. In this review, we survey the complexity and flexibility in functional outcome found in the myeloid CLRs, which is not only based on their differing intracellular motifs, but is also conditioned by the physical nature, affinity and avidity of the ligand
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