Neoproterozoic to early Paleozoic extensional and compressional history of East Laurentian margin sequences: The Moine Supergroup, Scottish Caledonides

Neoproterozoic siliciclastic-dominated sequences are widespread along the eastern margin of Laurentia and are related to rifting associated with the breakout of Laurentia from the supercontinent Rodinia. Detrital zircons from the Moine Supergroup, NW Scotland, yield Archean to early Neoproterozoic U-Pb ages, consistent with derivation from the Grenville-Sveconorwegian orogen and environs and accumulation post–1000 Ma. U-Pb zircon ages for felsic and associated mafic intrusions confirm a widespread pulse of extension-related magmatism at around 870 Ma. Pegmatites yielding U-Pb zircon ages between 830 Ma and 745 Ma constrain a series of deformation and metamorphic pulses related to Knoydartian orogenesis of the host Moinerocks. Additional U-Pb zircon and monazite data, and 40Ar/39Ar ages for pegmatites and host gneisses indicate high-grade metamorphic events at ca. 458–446 Ma and ca. 426 Maduring the Caledonian orogenic cycle.The presence of early Neoproterozoic silici clastic sedimentation and deformation in the Moine and equivalent successions around the North Atlantic and their absence along strike in eastern North America reflect contrasting Laurentian paleogeography during the breakup of Rodinia. The North Atlantic realm occupied an external location on the margin of Laurentia, and this region acted as a locus for accumulation of detritus (Moine Supergroup and equivalents) derived from the Grenville-Sveconorwegian orogenic welt, which developed as a consequence of collisional assembly of Rodinia. Neoproterozoic orogenic activity corresponds with theinferred development of convergent platemargin activity along the periphery of the supercontinent. In contrast in eastern North America, which lay within the internal parts of Rodinia, sedimentation did not commence until the mid-Neoproterozoic (ca. 760 Ma) during initial stages of supercontinent fragmentation. In the North Atlantic region, this time frame corresponds to a second pulse of extension represented by units such as the Dalradian Supergroup, which unconformably overlies the predeformed Moine succession

Emergency Bipap Ventilator For Breathing Assistance

Journal ArticleThe paper proposes the concept of a simplified ventilation device that meets the requirements for the South African Health Products Regulatory Authority (SAHPRA) approval and may be manufactured in large numbers at moderate cost to meet the requirements of the current or future pneumonic type pandemics. The paper further describes the development of such a device and presents descriptions of the final prototype. The philosophy behind the design was to take an engineering view of the problem of safe ventilation, which also meets World Health Organisation (WHO) guideline ‘Technical specifications for invasive and non-invasive ventilators for COVID-19’ (2020), whilst using the human biological responses to control the aspiration boundaries, thereby avoiding the very complex processes which simulate the breathing mechanism. The methodology employed was a conceptual design phase followed by an engineering design phase, prototyping, testing, and further developments. The concept was based on guidelines from WHO, 2020: Technical specifications for invasive and non-invasive ventilators for COVID-19: Interim guidance: paragraphs 2.1.2 and 2.2.2.(2020) and measured against the UK standard of the Medicines and Healthcare Products Regulatory Agency (MHPRA) ‘Rapidly manufactured ventilator system’ (2020). Each component of the conceptual design was developed in this way and a final prototype was assembled for independent evaluation and eventual SAHPRA evaluation. The finished prototype meets WHO guidelines for a Bi-level Positive Airway Pressure (BiPAP) system and also meets the guideline requirements for portability. The prototype also meets the initial intent regarding simplicity, functionality and cost. The further developments to mass production will reduce the part count and assembly processes, with some components to be reconfigured as disposable items, not for sterilisation or re-use. The project has shown that specialised equipment may be viewed pragmatically according to the requirement — to treat all breathing difficulties with a full specification ventilator is not possible or necessary; to assist the majority of ostensibly minor cases with a Bi-PAP system is both practical and more affordable. The intent is not to compete with the high technology commercially sourced equipment, or even the rapidly prototyped re-purposed industrial efforts worldwide, but rather to initiate some progress in the Republic of South Africa to quickly produce an abundance of these machines, to cope with the possible deficit of medical ventilators expected in future. The solution lies in a simple but failsafe device that provides assisted breathing with the option of oxygen enrichment. It is intended to be locally manufactured with the minimum of skills and is easily maintained and sterilised

Bioorthogonal, Bifunctional Linker for Engineering Synthetic Glycoproteins

Post-translational glycosylation of proteins results in complex mixtures of heterogeneous protein glycoforms. Glycoproteins have many potential applications from fundamental studies of glycobiology to potential therapeutics, but generating homogeneous recombinant glycoproteins using chemical or chemoenzymatic reactions to mimic natural glycoproteins or creating homogeneous synthetic neoglycoproteins is a challenging synthetic task. In this work, we use a site-specific bioorthogonal approach to produce synthetic homogeneous glycoproteins. We develop a bifunctional, bioorthogonal linker that combines oxime ligation and strain-promoted azide–alkyne cycloaddition chemistry to functionalize reducing sugars and glycan derivatives for attachment to proteins. We demonstrate the utility of this minimal length linker by producing neoglycoprotein inhibitors of cholera toxin in which derivatives of the disaccharide lactose and GM1os pentasaccharide are attached to a nonbinding variant of the cholera toxin B-subunit that acts as a size- and valency-matched multivalent scaffold. The resulting neoglycoproteins decorated with GM1 ligands inhibit cholera toxin B-subunit adhesion with a picomolar IC50

Tectonic settings of continental crust formation:Insights from Pb isotopes in feldspar inclusions in zircon

International audienceMost crustal rocks derive from preexisting crust, and so the composition of newly generated (juvenile) continental crust, and hence the tectonic settings of its formation, have remained difficult to determine, especially for the first billion years of Earth’s evolution. Modern primitive mantle–derived magmas have distinct U/Pb ratios, depending on whether they are generated in intraplate (mean U/Pb = 0.37) or in subduction settings (mean U/Pb = 0.10). The U/Pb ratio can therefore be used as a proxy for the tectonic settings in which juvenile continental crust is generated. This paper presents a new way to see back to the U/Pb ratios of juvenile continental crust that formed hundreds to thousands of millions of years ago, based on ion probe analysis of Pb isotopes in alkali feldspar and plagioclase inclusions within well-dated zircons. Pb isotope data are used to calculate the time-integrated U/Pb ratios (i.e., 238U/204Pb = µ) for the period between the Hf model age and the U-Pb crystallization age of the zircons. These time-integrated ratios reflect the composition of the juvenile continental crust at the time it was extracted from the mantle, and so they can be used as a proxy for the tectonic setting of formation of that crust. Two test samples with Proterozoic Hf model ages and Paleozoic crystallization ages have feldspar inclusions with measured Pb isotope ratios that overlap within analytical error for each sample. Sample Z7.3.1 from Antarctica has Pb isotope ratios (mean 206Pb/204Pb = 16.88 ± 0.08, 1σ) that indicate it was derived from source rocks with low U/Pb ratios (∼0.11), similar to those found in subduction-related settings. Sample Temora 2 from Australia has more radiogenic Pb isotope ratios (mean 206Pb/204Pb = 19.11 ± 0.23, 1σ) indicative of a source with higher U/Pb ratios (∼0.36), similar to magmas generated in intraplate settings. Analysis of detrital populations with a range of Hf model ages (e.g., Hadean to Phanerozoic), and for which zircons and their inclusions represent the only archive of their parent magmas, should ultimately open new avenues to our understanding of the formation and the evolution of the continental crust through time

Comment on ‘New palaeomagnetic result from Vendian red sediments in Cisbaikalia and the problem of the relationship of Siberia and Laurentia in the Vendian’ by S. A. Pisarevsky, R. A. Komissarova and A. N. Khramov

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73333/1/j.0956-540x.2001.01474.x.pd

Amino acid formula containing synbiotics in infants with cow’s milk protein allergy: a systematic review and meta-analysis

Cow’s milk protein allergy (CMPA) is associated with dysbiosis of the infant gut microbiome, with allergic and immune development implications. Studies show benefits of combining synbiotics with hypoallergenic formulae, although evidence has never been systematically examined. This review identified seven publications of four randomised controlled trials comparing an amino acid formula (AAF) with an AAF containing synbiotics (AAF-Syn) in infants with CMPA (mean age 8.6 months; 68% male, mean intervention 27.3 weeks, n = 410). AAF and AAF-Syn were equally effective in managing allergic symptoms and promoting normal growth. Compared to AAF, significantly fewer infants fed AAF-Syn had infections (OR 0.35 (95% CI 0.19–0.67), p = 0.001). Overall medication use, including antibacterials and antifectives, was lower among infants fed AAF-Syn. Significantly fewer infants had hospital admissions with AAF-Syn compared to AAF (8.8% vs. 20.2%, p = 0.036; 56% reduction), leading to potential cost savings per infant of £164.05–£338.77. AAF-Syn was associated with increased bifidobacteria (difference in means 31.75, 95% CI 26.04–37.45, p 0.0001); reduced Eubacterium rectale and Clostridium coccoides (difference in means −19.06, 95% CI −23.15 to −14.97, p 0.0001); and reduced microbial diversity (p 0.05), similar to that described in healthy breastfed infants, and may be associated with the improved clinical outcomes described. This review provides evidence that suggests combining synbiotics with AAF produces clinical benefits with potential economic implications

Sinus lifting before Le Fort I maxillary osteotomy: a suitable method for oral rehabilitation of edentulous patients with skelettal class-III conditions: review of the literature and report of a case

BACKGROUND: Functional rehabilitation of patients afflicted with severe mandibular and maxillary alveolar atrophy might be challenging especially in malformed patients. METHODS: Treatment planning using sinus lifting and implant placement before Le Fort I maxillary osteotomy in a patient with severe mandibular and posterior maxillary alveolar atrophy and skelettal class-III conditions due to cleft palate are described. RESULTS: A full functional and esthetic rehabilitation of the patient was achieved by a stepwise surgical approach performed through sinus lifting as the primary approach followed by implant placement and subsequent Le Fort I maxillary osteotomy to correct the maxillo-mandibular relation. CONCLUSION: Stabilisation of the maxillary complex by a sinus lifting procedure in combination with computer aided implant placement as preorthodontic planning procedure before Le Fort I maxillary osteotomy seems to be suitable in order to allow ideal oral rehabilitation especially in malformed patients

MicroRNA Controlled Adenovirus Mediates Anti-Cancer Efficacy without Affecting Endogenous MicroRNA Activity

MicroRNAs are small non-coding RNA molecules that regulate mRNA translation and stability by binding to complementary sequences usually within the 3′ un-translated region (UTR). We have previously shown that the hepatic toxicity caused by wild-type Adenovirus 5 (Ad5WT) in mice can be prevented by incorporating 4 binding sites for the liver-specific microRNA, mir122, into the 3′ UTR of E1A mRNA. This virus, termed Ad5mir122, is a promising virotherapy candidate and causes no obvious liver pathology. Herein we show that Ad5mir122 maintains wild-type lytic activity in cancer cells not expressing mir122 and assess any effects of possible mir122 depletion in host cells. Repeat administration of 2×1010 viral particles of Admir122 to HepG2 tumour bearing mice showed significant anti-cancer efficacy. RT-QPCR showed that E1A mRNA was down-regulated 29-fold in liver when compared to Ad5WT. Western blot for E1A confirmed that all protein variants were knocked down. RT-QPCR for mature mir122 in infected livers showed that quantity of mir122 remained unaffected. Genome wide mRNA microarray profiling of infected livers showed that although the transcript level of >3900 different mRNAs changed more than 2-fold following Ad5WT infection, less than 600 were changed by Ad5mir122. These were then filtered to select mRNAs that were only altered by Ad5mir122 and the remaining 21 mRNAs were compared to predicted mir122 targets. No mir122 target mRNAs were affected by Ad5 mir122. These results demonstrate that the exploitation of microRNA regulation to control virus replication does not necessarily affect the level of the microRNA or the endogenous mRNA targets