Site Selective Antibody-Oligonucleotide Conjugation via Microbial Transglutaminase.

Nucleic Acid Therapeutics (NATs), including siRNAs and AntiSense Oligonucleotides (ASOs), have great potential to drug the undruggable genome. Targeting siRNAs and ASOs to specific cell types of interest has driven dramatic improvement in efficacy and reduction in toxicity. Indeed, conjugation of tris-GalNAc to siRNAs and ASOs has shown clinical efficacy in targeting diseases driven by liver hepatocytes. However, targeting non-hepatic diseases with oligonucleotide therapeutics has remained problematic for several reasons, including targeting specific cell types and endosomal escape. Monoclonal antibody (mAb) targeting of siRNAs and ASOs has the potential to deliver these drugs to a variety of specific cell and tissue types. However, most conjugation strategies rely on random chemical conjugation through lysine or cysteine residues resulting in conjugate heterogeneity and a distribution of Drug:Antibody Ratios (DAR). To produce homogeneous DAR-2 conjugates with two siRNAs per mAb, we developed a novel two-step conjugation procedure involving microbial transglutaminase (MTGase) tagging of the antibody C-terminus with an azide-functionalized linker peptide that can be subsequently conjugated to dibenzylcyclooctyne (DBCO) bearing oligonucleotides through azide-alkyne cycloaddition. Antibody-siRNA (and ASO) conjugates (ARCs) produced using this strategy are soluble, chemically defined targeted oligonucleotide therapeutics that have the potential to greatly increase the number of targetable cell types

Thermal comfort characteristics of knitted fabrics for abaya

Fabric material plays an important role in the thermal comfort of Abaya because it is the outer garment of Muslim women. Abaya is black in colour and covers the whole body except the hands, feet and face. It is mandatory to wear Abaya in the Saudi Arabia and certain parts of Middle East countries irrespective of the outside environmental temperature which could be up to 45°C. Therefore, the thermal transmission characteristics of the abaya are extremely important as human body responds to the external thermal environment through clothing. In a hot environment, it is extremely uncomfortable to wear several layers of clothing under the Abaya. Hence it is essential to enhance the thermal comfort of fabrics used for Abaya. This study investigated five selected knitted fabrics that could be used as Abaya fabrics for thermal resistance, air permeability, thermal comfort and vapour resistance. The results indicated that the fabrics with different knit structures, fibre composition and fabric weight have greater influence on thermal comfort performance

Performance Evaluation of Energy Efficient Protocols in Wireless Sensor Networks

Reducing the energy utilization is an important element in the Wireless Sensor network (WSN). Many protocols have been designed for improving energy efficiency of the network. Clustering protocols have been proved to be one of the energy-efficient protocols in WSN. One of the basic and most popular protocols designed using the clustering approach is the LEACH (Low-Energy Adaptive Clustering Hierarchy).However, LEACH undergoes an issue of bad distribution of cluster heads, which is overcome by implementing a technique of selecting smart cluster head in LEACH known as SCHS (Smart Cluster Head Selection).Also another clustering protocol HEED (Hybrid Energy Efficient Distributed) which follows the principle of LEACH is considered for the study purpose. In this paper, a thorough analysis of three clustering protocols was carried out by keeping the network parameters same so as to conclude which protocol amongst the three utilizes the minimum energy and prolongs the network lifetime

Coordinated analysis of two graphite grains from the CO3.0 LAP 031117 meteorite: First identification of a CO Nova graphite and a presolar iron sulfide subgrain

Presolar grains constitute remnants of stars that existed before the formation of the solar system. In addition to providing direct information on the materials from which the solar system formed, these grains provide ground-truth information for models of stellar evolution and nucleosynthesis. Here we report the in-situ identification of two unique presolar graphite grains from the primitive meteorite LaPaz Icefield 031117. Based on these two graphite grains, we estimate a bulk presolar graphite abundance of 5-3+7 ppm in this meteorite. One of the grains (LAP-141) is characterized by an enrichment in 12C and depletions in 33,34S, and contains a small iron sulfide subgrain, representing the first unambiguous identification of presolar iron sulfide. The other grain (LAP-149) is extremely 13C-rich and 15N-poor, with one of the lowest 12C/13C ratios observed among presolar grains. Comparison of its isotopic compositions with new stellar nucleosynthesis and dust condensation models indicates an origin in the ejecta of a low-mass CO nova. Grain LAP-149 is the first putative nova grain that quantitatively best matches nova model predictions, providing the first strong evidence for graphite condensation in nova ejecta. Our discovery confirms that CO nova graphite and presolar iron sulfide contributed to the original building blocks of the solar system.Peer ReviewedPostprint (author's final draft

Spherical Casimir energies and Dedekind sums

Casimir energies on space-times having general lens spaces as their spatial sections are shown to be given in terms of generalised Dedekind sums related to Zagier's. These are evaluated explicitly in certain cases as functions of the order of the lens space. An easily implemented recursion approach is used.Comment: 18 pages, 2 figures, v2:typos corrected, inessential equation in Discussion altered. v3:typos corrected, 1 reference and comments added. v4:typos corrected. Ancillary results added in an appendi

In silico comparative study of epitopes predicted from different strains of genus parvovirus.

Parvoviruses are typically linear, non-segmented single-stranded DNA viruses, with an average genome size of 5000 nucleotides. Parvoviruses are some of the smallest viruses found in nature. Some have been found as small as 23 nm. Many types of mammalian species have a strain of parvovirus associated with them. Parvoviruses tend to be specific about the taxon of animal they will infect, but this is a somewhat flexible characteristic. Thus, all strains of parvovirus will affect dogs, wolves, and foxes, but only some of them will infect human. Parvovirus is treated with the help of vaccines but the traditional vaccine development process is very expensive and unsafe, with the help of insilico software tools and databases we can predict the epitopes of parvovirus species such as Canine parvovirus, Feline panleukopenia virus, H-1 virus, LUIII virus, Mink enteritis virus, Minute virus of mice, Porcine parvovirus, Raccoon parvovirus, by using Bepipred, CTLpred. These predictions will be useful for reverse vaccinology against parvoviruses infections for cattle and mankind

Impact of proctoring on success rates for percutaneous revascularisation of coronary chronic total occlusions.

OBJECTIVE: To assess the impact of proctoring for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in six UK centres. METHODS: We retrospectively analysed 587 CTO procedures from six UK centres and compared success rates of operators who had received proctorship with success rates of the same operators before proctorship (pre-proctored) and operators in the same institutions who had not been proctored (non-proctored). There were 232 patients in the pre-proctored/non-proctored group and 355 patients in the post-proctored group. Complexity was assessed by calculating the Japanese CTO (JCTO) score for each case. RESULTS: CTO PCI success was greater in the post-proctored compared with the pre-proctored/non-proctored group (77.5% vs 62.1%, p<0.0001). In more complex cases where JCTO≥2, the difference in success was greater (70.7% vs 49.5%, p=0.0003). After proctoring, there was an increase in CTO PCI activity in centres from 2.5% to 3.5%, p<0.0001 (as a proportion of total PCI), and the proportion of very difficult cases with JCTO score ≥3 increased from 15.3% (35/229) to 29.7% (105/354), p<0.0001. CONCLUSIONS: Proctoring resulted in an increase in procedural success for CTO PCI, an increase in complex CTO PCI and an increase in total CTO PCI activity. Proctoring may be a valuable way to improve access to CTO PCI and the likelihood of procedural success

MinMax Radon Barcodes for Medical Image Retrieval

Content-based medical image retrieval can support diagnostic decisions by clinical experts. Examining similar images may provide clues to the expert to remove uncertainties in his/her final diagnosis. Beyond conventional feature descriptors, binary features in different ways have been recently proposed to encode the image content. A recent proposal is "Radon barcodes" that employ binarized Radon projections to tag/annotate medical images with content-based binary vectors, called barcodes. In this paper, MinMax Radon barcodes are introduced which are superior to "local thresholding" scheme suggested in the literature. Using IRMA dataset with 14,410 x-ray images from 193 different classes, the advantage of using MinMax Radon barcodes over \emph{thresholded} Radon barcodes are demonstrated. The retrieval error for direct search drops by more than 15\%. As well, SURF, as a well-established non-binary approach, and BRISK, as a recent binary method are examined to compare their results with MinMax Radon barcodes when retrieving images from IRMA dataset. The results demonstrate that MinMax Radon barcodes are faster and more accurate when applied on IRMA images.Comment: To appear in proceedings of the 12th International Symposium on Visual Computing, December 12-14, 2016, Las Vegas, Nevada, US