The field of dark matter detection is a highly visible and highly competitive one. In this paper, we propose recommendations for presenting dark matter direct detection results particularly suited ...for weak-scale dark matter searches, although we believe the spirit of the recommendations can apply more broadly to searches for other dark matter candidates, such as very light dark matter or axions. To translate experimental data into a final published result, direct detection collaborations must make a series of choices in their analysis, ranging from how to model astrophysical parameters to how to make statistical inferences based on observed data. While many collaborations follow a standard set of recommendations in some areas, for example the expected flux of dark matter particles (to a large degree based on a paper from Lewin and Smith in 1995), in other areas, particularly in statistical inference, they have taken different approaches, often from result to result by the same collaboration. We set out a number of recommendations on how to apply the now commonly used Profile Likelihood Ratio method to direct detection data. In addition, updated recommendations for the Standard Halo Model astrophysical parameters and relevant neutrino fluxes are provided. The authors of this note include members of the DAMIC, DarkSide, DARWIN, DEAP, LZ, NEWS-G, PandaX, PICO, SBC, SENSEI, SuperCDMS, and XENON collaborations, and these collaborations provided input to the recommendations laid out here. Wide-spread adoption of these recommendations will make it easier to compare and combine future dark matter results.
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The combustion of organic matter is perhaps the oldest and most common chemical transformation utilized by mankind. The generation of a C–O bond at the expense of a C–H bond during this process may ...be considered the most basic form of C–H functionalization. This illustrates the extreme generality of the term “C–H functionalization”, because it can describe the conversion of literally any C–H bond into a C–X bond (X being anything except H). Therefore, it may be of use to distinguish between what, in our view, are two distinct categories of C–H functionalization logic: “guided” and “innate”. Guided C–H functionalizations, as the name implies, are guided by external reagents or directing groups (covalently or fleetingly bound) to install new functional groups at the expense of specifically targeted C–H bonds. Conversely, innate C–H functionalizations may be broadly defined as reactions that exchange C–H bonds for new functional groups based solely on natural reactivity patterns in the absence of other directing forces. Two substrates that illustrate this distinction are dihydrojunenol and isonicotinic acid. The C–H functionalization processes of hydroxylation or arylation, respectively, can take place at multiple locations on each molecule. Innate functionalizations lead to substitution patterns that are dictated by the inherent bias (steric or electronic) of the substrate undergoing C–H cleavage, whereas guided functionalizations lead to substitution patterns that are controlled by external directing forces such as metal complexation or steric bias of the reagent. Although the distinction between guided and innate C–H functionalizations may not always be clear in cases that do not fit neatly into a single category, it is a useful convention to consider when analyzing reactivity patterns and strategies for synthesis. We must emphasize that although a completely rigorous distinction between guided and innate C–H functionalization may not be practical, we have nonetheless found it to be a useful tool at the planning stage of synthesis. In this Account, we trace our own studies in the area of C–H functionalization in synthesis through the lens of “guided” and “innate” descriptors. We show how harnessing innate reactivity can be beneficial for achieving unique bond constructions between heterocycles and carbonyl compounds, enabling rapid and scalable total syntheses. Guided and innate functionalizations were used synergistically to create an entire family of terpenes in a controlled fashion. We continue with a discussion of the synthesis of complex alkaloids with high nitrogen content, which required the invention of a uniquely chemoselective innate C–H functionalization protocol. These findings led us to develop a series of innate C–H functionalization reactions for forging C–C bonds of interest to the largest body of practicing organic chemists: medicinal chemists. Strategic use of C–H functionalization logic can have a dramatically positive effect on the efficiency of synthesis, whether guided or innate.
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Thyroid hormones influence heart rate, serum lipids, metabolic rate, body weight and multiple aspects of lipid, carbohydrate, protein and mineral metabolism. Although increased thyroid hormone levels ...can improve serum lipid profiles and reduce fat, these positive effects are counterbalanced by harmful effects on the heart, muscle and bone. Thus, attempts to use thyroid hormones for cholesterol-lowering and weight loss purposes have so far been limited. However, over the past decade, thyroid hormone analogues that are capable of uncoupling beneficial effects from deleterious effects have been developed. Such drugs could serve as powerful new tools to address two of the largest medical problems in developed countries--atherosclerosis and obesity.
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5.
A New Reagent for Direct Difluoromethylation Fujiwara, Yuta; Dixon, Janice A; Rodriguez, Rodrigo A ...
Journal of the American Chemical Society,
01/2012, Volume:
134, Issue:
3
Journal Article
Peer reviewed
Open access
Molecular scaffolds containing alkylfluorine substituents are desired in many areas of chemical research from materials to pharmaceuticals. Herein, we report the invention of a new reagent ...(Zn(SO2CF2H)2, DFMS) for the innate difluoromethylation of organic substrates via a radical process. This mild, operationally simple, chemoselective, and scalable difluoromethylation method is compatible with a range of nitrogen-containing heteroarene substrates of varying complexity as well as select classes of conjugated π-systems and thiols. Regiochemical comparisons suggest that the CF2H radical generated from the new reagent possesses nucleophilic character.
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Abstract Immunity is the state of protection against infectious disease conferred either through an immune response generated by immunization or previous infection or by other non-immunological ...factors. This article reviews active and passive immunity and the differences between them: it also describes the four different commercially available vaccine types (live attenuated, killed/inactivated, subunit and toxoid): it also looks at how these different vaccines generate an adaptive immune response.
An efficient and general method for the C–H alkylation of heteroarenes using unprotected amino acids as stable alkyl radical precursors is reported. This one-pot procedure is performed open to air ...under aqueous conditions and is effective for several natural and unnatural amino acids. Heterocycles of varying structure are suitably functionalized, and reactivity trends reflect the nucleophilic character of the radical species generated.
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Nitrogen-rich heterocyclic compounds have had a profound effect on human health because these chemical motifs are found in a large number of drugs used to combat a broad range of diseases and ...pathophysiological conditions. Advances in transition-metal-mediated cross-coupling have simplified the synthesis of such molecules; however, C-H functionalization of medicinally important heterocycles that does not rely on pre-functionalized starting materials is an underdeveloped area. Unfortunately, the innate properties of heterocycles that make them so desirable for biological applications--such as aqueous solubility and their ability to act as ligands--render them challenging substrates for direct chemical functionalization. Here we report that zinc sulphinate salts can be used to transfer alkyl radicals to heterocycles, allowing for the mild (moderate temperature, 50 °C or less), direct and operationally simple formation of medicinally relevant C-C bonds while reacting in a complementary fashion to other innate C-H functionalization methods (Minisci, borono-Minisci, electrophilic aromatic substitution, transition-metal-mediated C-H insertion and C-H deprotonation). We prepared a toolkit of these reagents and studied their reactivity across a wide range of heterocycles (natural products, drugs and building blocks) without recourse to protecting-group chemistry. The reagents can even be used in tandem fashion in a single pot in the presence of water and air.
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Innate C-H trifluoromethylation of heterocycles Ji, Yining; Brueckl, Tobias; Baxter, Ryan D ...
Proceedings of the National Academy of Sciences - PNAS,
08/2011, Volume:
108, Issue:
35
Journal Article
Peer reviewed
Open access
Direct methods for the trifluoromethylation of heteroaromatic systems are in extremely high demand in nearly every sector of chemical industry. Here we report the discovery of a general procedure ...using a benchtop stable trifluoromethyl radical source that functions broadly on a variety of electron deficient and rich heteroaromatic systems and demonstrates high functional group tolerance. This C-H trifluoromethylation protocol is operationally simple (avoids gaseous CF3I), scalable, proceeds at ambient temperature, can be used directly on unprotected molecules, and is demonstrated to proceed at the innately reactive positions of the substrate. The unique and orthogonal reactivity of the trifluoromethyl radical relative to aryl radicals has also been investigated on both a complex natural product and a pharmaceutical agent. Finally, preliminary data suggest that the regioselectivity of C-H trifluoromethylation can be fine-tuned simply by judicious solvent choice.
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Background
Lipoprotein(a) Lp(a) is a highly atherogenic lipoprotein and is minimally effected by lifestyle changes. While some drugs can reduce Lp(a), diet has not consistently shown definitive ...reduction of this biomarker. The effect of consuming a plant‐based diet on serum Lp(a) concentrations have not been previously evaluated.
Hypothesis
Consumption of a defined, plant‐based for 4 weeks reduces Lp(a).
Methods
Secondary analysis of a previous trial was conducted, in which overweight and obese individuals (n = 31) with low‐density lipoprotein cholesterol concentrations >100 mg/dL consumed a defined, plant‐based diet for 4 weeks. Baseline and 4‐week labs were collected. Data were analyzed using a paired samples t‐test.
Results
Significant reductions were observed for serum Lp(a) (−32.0 ± 52.3 nmol/L, P = 0.003), apolipoprotein B (−13.2 ± 18.3 mg/dL, P < 0.0005), low‐density lipoprotein (LDL) particles (−304.8 ± 363.0 nmol/L, P < 0.0005) and small‐dense LDL cholesterol (−10.0 ± 9.2 mg/dL, P < 0.0005). Additionally, serum interleukin‐6 (IL‐6), total white blood cells, lipoprotein‐associated phospholipase A2 (Lp‐PLA2), high‐sensitivity c‐reactive protein (hs‐CRP), and fibrinogen were significantly reduced (P ≤ 0.004).
Conclusions
A defined, plant‐based diet has a favorable impact on Lp(a), inflammatory indicators, and other atherogenic lipoproteins and particles. Lp(a) concentration was previously thought to be only minimally altered by dietary interventions. In this protocol however, a defined plant‐based diet was shown to substantially reduce this biomarker. Further investigation is required to elucidate the specific mechanisms that contribute to the reductions in Lp(a) concentrations, which may include alterations in gene expression.
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