It is fifty years since the first chemical synthesis of a dinucleoside phosphate and a dinucleotide with natural 3'-->5'-internucleotide linkages was reported. The main developments in the ...methodology of oligo- and poly-nucleotide synthesis that have taken place since are described.
Tropical cyclones are major disturbances for coastal systems. Hurricane Harvey made landfall in Texas, USA, on August 25, 2017 as a category 4 storm. There were two distinct disturbances associated ...with this storm that were spatially decoupled: (1) high winds causing direct damage and storm surge, and (2) high rains causing scouring floods and significant discharge of fresh water carrying carbon and nutrients to estuaries. Here, we provide a synthesis of the effects of Hurricane Harvey on biogeochemical, hydrographic, and biotic components of freshwater and estuarine systems and their comparative resistance and resilience to wind-and rain-driven disturbances. Wind-driven disturbances were most severe along the coastal barrier islands and lower estuaries, damaging mangroves and seagrass and increasing sediment coarseness. Rain-driven disturbances were most pronounced within freshwater streams and the upper estuaries. Large volumes of freshwater run-off reduced the abundance of riverine fauna and caused hypoxic and hyposaline conditions in the estuaries for over a week. In response to this freshwater input event, benthic fauna diversity and abundance decreased, but mobile fauna such as estuarine fishes did not markedly change. Although hydrographic and biogeochemical components were highly perturbed, they returned to baseline conditions within days. In contrast, biotic components demonstrated lower magnitude changes, but some of these organisms, particularly the sedentary flora and fauna, required weeks to months to return to pre-storm conditions, and some did not recover within the 6 months reported here. Our synthesis illustrates that resistance and resilience of system components may negatively co-vary and that structural components of coastal systems may be the most vulnerable to long-term changes following tropical cyclones.
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•Methods of functionalization of unactivated positions on steroids are reported.•Development of reagents for remote functionalization is mentioned.•Syntheses of biologically active ...steroids from commercially available analogs using remote functionalization are discussed.
Research published between 2001 and 2022 on the functionalization of remote positions of steroids, as well as the use of this technique in the generation of biologically active compounds has been reviewed. In the first section of the analysis established and novel methods for activation of sites deemed to be remote were reported. A series of manganese- (mainly), rhodium-, ruthenium- and osmium-centered porphyrins as catalysts in the presence of PIDA as oxidant have effected hydroxylation at C-1, -5, -6, -7, -11, -14, -15, -16, -17, -20, -24 and -25. Dioxiranes have been utilized in inserting hydroxyl groups at the 5, 12, 14, 15, 16, 17, 20, 24 and 25 positions (tertiary centers for the most part). Alcohols at C-12 and -16 were oxidized further to ketones. The Schönecker oxidation, discovered and developed during the period, has revolutionized the selective functionalization at C-12 of steroids possessing a 17-keto group. In the presence of iron-centered PDP- and MCP-based catalysts, hydrogen peroxide and acetic acid, substrates tended to be hydroxylated at C-6 and -12, with further oxidation to ketones often accompanying this reaction. The hypohalite reaction, utilizing the more modern Suarez conditions (irradiation in the presence of iodine and PIDA), was reported to facilitate the insertion of a hydroxyl moiety five atoms away from an existing alcohol oxygen. Steroidal-3β-diazoacetates tend to decompose on heating with di-rhodium-centered catalysts while activating carbons four or five atoms away. Chromium- and iron-based acetates were observed to functionalize C-5 and -25. Other reactions involving ring cleavage and halogenation, ketone irradiation and α-hydroxylation of ethers were also covered.
The syntheses of compounds with marked biological activity from readily available steroids is described in the second section of the study. Cyclopamine, cephalostatin-1, ritterazine B and three polyhydroxypregnanaes (pergularin, utendin and tomentogenin) were generated in sequences in which a key step required hydroxylation at C-12 using the Schönecker reaction. A crucial stage in the preparation of cortistatin A, the saundersioside core, eurysterol A, 5,6-dihydroglaucogenin C, as well as clinostatins A and B involved the functionalization of C-18 or -19 utilizing hypohalite chemistry. The synthetic route to xestobergsterol A, pavonin-4-aglycone and ouagabagenin included a transformation where ketone irradiation played a part in either producing a Δ14 or a C-19 activated steroid. The radical relay reaction, where a 17α-chloro-steroid was formed, was central in the generation of pythocholic acid. The lead tetraacetate reaction was pivotal in the functionalization of C-19 during the synthesis of cyclocitrinol.
Protein kinase B (PKB) is a proto-oncogene that is activated in signaling pathways initiated by phosphoinositide 3-kinase. Chromatographic separation of brain cytosol revealed a kinase activity that ...phosphorylated and activated PKB only in the presence of phosphatidylinositol-3,4,5-trisphosphate PtdIns(3,4,5)P$_3$. Phosphorylation occurred exclusively on threonine-308, a residue implicated in activation of PKB in vivo. PtdIns(3,4,5)P$_3$ was determined to have a dual role: Its binding to the pleckstrin homology domain of PKB was required to allow phosphorylation by the upstream kinase and it directly activated the upstream kinase.
Summary
High throughput sequencing of 16S ribosomal RNA gene amplicons is a cost‐effective method for characterization of oral bacterial communities. However, before undertaking large‐scale studies, ...it is necessary to understand the technique‐associated limitations and intrinsic variability of the oral ecosystem. In this work we evaluated bias in species representation using an in vitro‐assembled mock community of oral bacteria. We then characterized the bacterial communities in saliva and buccal mucosa of five healthy subjects to investigate the power of high throughput sequencing in revealing their diversity and biogeography patterns. Mock community analysis showed primer and DNA isolation biases and an overestimation of diversity that was reduced after eliminating singleton operational taxonomic units (OTUs). Sequencing of salivary and mucosal communities found a total of 455 OTUs (0.3% dissimilarity) with only 78 of these present in all subjects. We demonstrate that this variability was partly the result of incomplete richness coverage even at great sequencing depths, and so comparing communities by their structure was more effective than comparisons based solely on membership. With respect to oral biogeography, we found inter‐subject variability in community structure was lower than site differences between salivary and mucosal communities within subjects. These differences were evident at very low sequencing depths and were mostly caused by the abundance of Streptococcus mitis and Gemella haemolysans in mucosa. In summary, we present an experimental and data analysis framework that will facilitate design and interpretation of pyrosequencing‐based studies. Despite challenges associated with this technique, we demonstrate its power for evaluation of oral diversity and biogeography patterns.
Abstract
Background
Reproductive and sexual health (RSH) concerns are common and distressing for young adults diagnosed with breast and gynecologic cancer and their partners. This study evaluates the ...efficacy of a virtual couple-based intervention called Opening the Conversation (OC). The OC intervention is grounded in theory and evidence-based practice and was adapted to improve coping and communication specifically in relation to RSH concerns after cancer.
Methods
This Phase III trial is conducted in a fully remote setting and enrolls young adult couples (current age 18–44 years) with a history of breast or gynecologic cancer (stage 1–4, diagnosed under age 40) within the past 6 months to 5 years. Eligible dyads are recruited from across the USA. The target sample size is 100 couples. Dyads are randomly assigned to receive either the 5-session OC intervention or a 4-session active control intervention (Side by Side). The primary outcomes are change in reproductive distress and sexual distress. Secondary outcomes include communication about reproductive concerns, communication about sexual concerns, depressive symptoms, sexual function, relationship quality, relationship intimacy, sexual satisfaction, self-efficacy to communicate about sex and intimacy, and quality of life. An exploratory aim examines whether dyadic coping and communication quality mediate intervention effects on survivors’ and partners’ reproductive distress or sexual distress. Self-report outcome measures are assessed for both groups at baseline (T1), 2 weeks post-treatment (T2), and 3 months post-treatment (T3).
Discussion
Despite the importance of RSH for quality of life for young adult cancer survivors and their partners, evidence-based interventions that help couples navigate RSH concerns are lacking. This randomized controlled trial will determine the efficacy of a novel couple-based intervention to reduce distress related to RSH concerns for younger couples after breast or gynecologic cancer, in comparison to an active control intervention.
Trial registration
ClinicalTrials.gov
NCT04806724. Registered on Mar 19, 2021.
There is considerable focus on technology manufacturing locations and the value in funding innovation when upstream products are not manufactured within a domestic economy. Light-emitting diodes ...(LEDs) are such an upstream product. Here, we evaluate the value added along the supply chain of luminaires, a product that utilizes LEDs, using bottom-up cost modelling. Coupling the results with analysis of shipping cost and time, this analysis examines how advances in LEDs can incentivize LED luminaire adoption leading to the potential for significant domestic manufacturing effects even if the upstream products are produced in other economies.
The CMB-S4 experiment is developing next-generation ground-based microwave telescopes to observe the cosmic microwave background with unprecedented sensitivity. This will require an order of ...magnitude increase in the 100-mK detector count, which, in turn, increases the demands on the readout system. The CMB-S4 readout will use time-division multiplexing (TDM), taking advantage of faster switches and amplifiers in order to achieve an increased multiplexing factor. To facilitate the design of the new readout system, we have developed a model that predicts the bandwidth and noise performance of this circuitry and its interconnections. This is then used to set requirements on individual components in order to meet the performance necessary for the full system. We present an overview of this model and compare the model results to the performance of both legacy and prototype readout hardware.
Even before the COVID-19 pandemic, telebehavioral health (TBH) was proving itself to be a valuable, effective tool for service delivery. The widespread adoption of its use over the past 2 years for ...continuity of care should be considered one of the silver linings of the pandemic. It has the potential to be a particularly powerful tool for providing more equitable access to care for those in rural communities if barriers to broadband access can be addressed. In addition to providing an attractive, flexible method of service delivery for patients and families, TBH holds appeal to the workforce as well.
Abstract
A field study was conducted of flows in the Birch Creek Valley in eastern Idaho. There is a distinct topographic constriction in the Birch Creek Valley that creates two subbasins: an upper ...and lower valley. The data were classified into one of three groups based on synoptic influence (weak/absent, high wind speeds, and other evidence of synoptic influence). Gap flows commonly developed downwind of the constriction in association with the weak/absent group but also occurred in association with the two synoptic groups suggesting the potential for more diverse origins. In general, the frequency and strength of gap flows appeared to be linked to the development of the requisite thermal regime and minimization of any synoptically driven southerly winds that would suppress outflows. Gap flows were characterized by high wind speeds with jetlike vertical profiles along the axis of the lower valley. For all three groups the morning transition in the upper valley and western sidewall usually proceeded slightly ahead of the lower valley, consistent with the principles of the topographic amplification factor. The persistence of southerly winds in the lower valley past evening transition inhibited the development of gap flows, promoted strong nighttime inversions, and delayed the onset of morning transition relative to the upper valley. Nocturnal temperature inversions in the lower valley were largely eliminated with the onset of strong gap flows resulting in earlier morning transitions there. The form for a method of predicting gap flow wind speeds is proposed.
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