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These guidelines on oesophageal manometry and gastro-oesophageal reflux monitoring supersede those produced in 2006. Since 2006 there have been significant technological advances, in particular, the development of high resolution manometry (HRM) and oesophageal impedance monitoring. The guidelines were developed by a guideline development group of patients and representatives of all the relevant professional groups using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. A systematic literature search was performed and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) tool was used to evaluate the quality of evidence and decide on the strength of the recommendations made. Key strong recommendations are made regarding the benefit of: (i) HRM over standard manometry in the investigation of dysphagia and, in particular, in characterising achalasia, (ii) adjunctive testing with larger volumes of water or solids during HRM, (iii) oesophageal manometry prior to antireflux surgery, (iv) pH/impedance monitoring in patients with reflux symptoms not responding to high dose proton pump inhibitors and (v) pH monitoring in all patients with reflux symptoms responsive to proton pump inhibitors in whom surgery is planned, but combined pH/impedance monitoring in those not responsive to proton pump inhibitors in whom surgery is planned. This work has been endorsed by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG) under the auspices of the oesophageal section of the BSG.

Background In India the number of registered deaths increased substantially in recent years, improving the potential of the civil registration and vital statistics (CRVS) system to be the primary source of mortality data and providing more families of decedents with the benefits of possessing a death certificate. This study aims to identify whether inequalities in the completeness of death registration between states in India, including by sex, have narrowed during this period of CRVS system strengthening. Methods Data used in this study are registered deaths by state and year from 2000 to 2018 (and by sex from 2009 to 2018) reported in the Civil Registration Reports published by the Office of Registrar General of India. Completeness of death registration is calculated using the empirical completeness method. Levels and trends inequalities in completeness are measured in each state a socio-economic indicator – the Socio-Demographic Index (SDI). Results Estimated completeness of death registration in India increased from 58% in 2000 to 81% in 2018. Male completeness rose from 60% in 2009 to 85% in 2018 and was much higher than female completeness, which increased from 54 to 74% in the same period. Completeness remained very low in some states, particularly from the eastern (e.g. Bihar) and north-eastern regions. However, in states from the northern region (e.g. Uttar Pradesh) completeness increased significantly from a low level. There was a narrowing of inequalities in completeness according to the SDI during the period, however large inequalities between states remain. Conclusions The increase in completeness of death registration in India is a substantial achievement and increases the potential of the death registration system as a routine source of mortality data. Although narrowing of inequalities in completeness demonstrates that the benefits of higher levels of death registration have spread to relatively poorer states of India in recent years, the continued low completeness in some states and for females are concerning. The Indian CRVS system also needs to increase the number of registered deaths with age at death reported to improve their usability for mortality statistics.

Expression of early secreted antigenic target protein 6 (ESAT-6) by Mycobacterium tuberculosis is associated with lower innate immune responses to infection. Here we show that ESAT-6 inhibited activation of transcription factor NF-κB and interferon-regulatory factors (IRFs) after Toll-like receptor (TLR) signaling; inhibition of TLR signaling by ESAT-6 required the kinase Akt. Direct binding of ESAT-6 to TLR2 activated Akt and prevented interaction between the adaptor MyD88 and 'downstream' kinase IRAK4, thus abrogating NF-κB activation. The six carboxy-terminal amino acid residues of ESAT-6 were required and sufficient for the TLR2-mediated inhibitory effect. A critical function for the carboxy-terminal peptide of ESAT-6 in restricting MyD88-dependent TLR signaling emphasizes the possibility that mimetic inhibitory peptides could be used to restrict innate immune responses in situations in which prolonged TLR signaling has deleterious effects.

In this work we have developed a novel rGO-MWCNT (reduced graphene oxide-multiwalled carbon nanotube) nanocomposite material with Poly-L-Lysine functionalization which can be used for detection of biomolecules with enhanced sensitivity. The reduced GO sheets are found to play a major role as a connector and helps in the assembly of bundles of carbon nanotubes (CNTs) which may sometime play a role of upstanding nanostructures. The overall composite structure is further fully functionalized resulting in an overall high density of amino groups that can be used to capture biomolecules. The sensitivity of the as synthesized film is tested by the oxidation of cholesterol through cholesterol oxidase enzyme that is biochemically immobilized over these composite films. The test for the immobilization density of the novel films are carried out by mounting these films on sensitive thin section static micro/nano-cantilever platforms. The platforms have capability to measure cholesterol traces in blood upto an extent of 100 femto molar through deflection /bending of the cantilevers due to surface reaction. The films developed show a promise of high immobilization density which is further confirmed through fluorescence studies using FITC labeling of functionalized MWCNT-PLL and rGO-PLL films respectively.

From an abstract, informational perspective, protein domains appear analogous to words in natural languages in which the rules of word association are dictated by linguistic rules, or grammar. Such rules exist for protein domains as well, because only a small fraction of all possible domain combinations is viable in evolution. We employ a popular linguistic technique, n-gram analysis, to probe the “proteome grammar”—that is, the rules of association of domains that generate various domain architectures of proteins. Comparison of the complexity measures of “protein languages” in major branches of life shows that the relative entropy difference (information gain) between the observed domain architectures and random domain combinations is highly conserved in evolution and is close to being a universal constant, at ∼1.2 bits. Substantial deviations from this constant are observed in only two major groups of organisms: a subset of Archaea that appears to be cells simplified to the limit, and animals that display extreme complexity. We also identify the n-grams that represent signatures of the major branches of cellular life. The results of this analysis bolster the analogy between genomes and natural language and show that a “quasi-universal grammar” underlies the evolution of domain architectures in all divisions of cellular life. The nearly universal value of information gain by the domain architectures could reflect the minimum complexity of signal processing that is required to maintain a functioning cell.

The creation of affordable high speed optical communications using standard semiconductor manufacturing technology is a principal aim of silicon photonics research. This would involve replacing copper connections with optical fibres or waveguides, and electrons with photons. With applications such as telecommunications and information processing, light detection, spectroscopy, holography and robotics, silicon photonics has the potential to revolutionise electronic-only systems. Providing an overview of the physics, technology and device operation of photonic devices using exclusively silicon and related alloys, the book includes: * Basic Properties of Silicon * Quantum Wells, Wires, Dots and Superlattices * Absorption Processes in Semiconductors * Light Emitters in Silicon * Photodetectors, Photodiodes and Phototransistors * Raman Lasers including Raman Scattering * Guided Lightwaves * Planar Waveguide Devices * Fabrication Techniques and Material Systems Silicon Photonics: Fundamentals and Devices outlines the basic principles of operation of devices, the structures of the devices, and offers an insight into state-of-the-art and future developments.

It is important to isolate exosomes (<150 nm) from biofluid for diagnosis or prognosis purposes, followed by sensing of exosomal proteins. In the present work, exosomes are isolated from human serum by immobilizing on a Screen-Printed Electrode (SPE) followed by electric field lysis and electrochemical impedance spectroscopy (EIS)-based sensing of relevant exosomal proteins (HSP70 and HER2). Upon immobilization of exosomes on the surface, the role of different electrical signals (sinusoidal and square wave) in the lysis of exosomes was studied by varying the frequency and voltage. HSP70 was used for EIS to determine the optimal voltage and frequency for lysing the exosomes. It was observed that the low frequencies and, specifically, sinusoidal signals are ideal for lysing exosomes as compared to square signals. The relative quantity of HSP70 obtained by lysing with different voltages (sinusoidal waveform) was compared using Western blotting. After electric field lysis of the exosome with an optimized signal, HER2, a breast cancer biomarker, was detected successfully from serum by EIS. In the proposed technique, 3.5 × 108 exosomes/mL were isolated from serum. With the limit of detection of 10 pg, the designed cell showed a linear detection of HER2 from 0.1 ng to 1 µg. It was observed from the results that the electric field lysis of exosomes not only plays a significant role in releasing the cargo protein but also improves the sensing of surface proteins associated with exosomes.

Alternative splicing (AS) is involved in cell fate decisions and embryonic development. However, regulation of these processes is poorly understood. Here, we have identified the serine threonine kinase receptor-associated protein (STRAP) as a putative spliceosome-associated factor. Upon Strap deletion, there are numerous AS events observed in mouse embryoid bodies (EBs) undergoing a neuroectoderm-like state. Global mapping of STRAP-RNA binding in mouse embryos by enhanced-CLIP sequencing (eCLIP-seq) reveals that STRAP preferably targets transcripts for nervous system development and regulates AS through preferred binding positions, as demonstrated for two neuronal-specific genes, Nnat and Mark3 . We have found that STRAP involves in the assembly of 17S U2 snRNP proteins. Moreover, in Xenopus , loss of Strap leads to impeded lineage differentiation in embryos, delayed neural tube closure, and altered exon skipping. Collectively, our findings reveal a previously unknown function of STRAP in mediating the splicing networks of lineage commitment, alteration of which may be involved in early embryonic lethality in mice. STRAP (serine threonine kinase receptor-associated protein) promotes tumorigenicity. Here the authors report that STRAP associates with spliceosome and regulates alternative splicing during embryonic stem cell lineage commitment and early mouse embryo organogenesis.

Background A new family of natural products has been described in which cysteine, serine and threonine from ribosomally-produced peptides are converted to thiazoles, oxazoles and methyloxazoles, respectively. These metabolites and their biosynthetic gene clusters are now referred to as thiazole/oxazole-modified microcins (TOMM). As exemplified by microcin B17 and streptolysin S, TOMM precursors contain an N-terminal leader sequence and C-terminal core peptide. The leader sequence contains binding sites for the posttranslational modifying enzymes which subsequently act upon the core peptide. TOMM peptides are small and highly variable, frequently missed by gene-finders and occasionally situated far from the thiazole/oxazole forming genes. Thus, locating a substrate for a particular TOMM pathway can be a challenging endeavor. Results Examination of candidate TOMM precursors has revealed a subclass with an uncharacteristically long leader sequence closely related to the enzyme nitrile hydratase. Members of this nitrile hydratase leader peptide (NHLP) family lack the metal-binding residues required for catalysis. Instead, NHLP sequences display the classic Gly-Gly cleavage motif and have C-terminal regions rich in heterocyclizable residues. The NHLP family exhibits a correlated species distribution and local clustering with an ABC transport system. This study also provides evidence that a separate family, annotated as Nif11 n i trogen-fixing proteins, can serve as natural product precursors (N11P), but not always of the TOMM variety. Indeed, a number of cyanobacterial genomes show extensive N11P paralogous expansion, such as Nostoc , Prochlorococcus and Cyanothece , which replace the TOMM cluster with lanthionine biosynthetic machinery. Conclusions This study has united numerous TOMM gene clusters with their cognate substrates. These results suggest that two large protein families, the nitrile hydratases and Nif11, have been retailored for secondary metabolism. Precursors for TOMMs and lanthionine-containing peptides derived from larger proteins to which other functions are attributed, may be widespread. The functions of these natural products have yet to be elucidated, but it is probable that some will display valuable industrial or medical activities.