ASAP-SML: An Antibody Sequence Analysis Pipeline Using Statistical Testing and Machine Learning

Antibodies are capable of potently and specifically binding individual antigens and, in some cases, disrupting their functions. The key challenge in generating antibody-based inhibitors is the lack of fundamental information relating sequences of antibodies to their unique properties as inhibitors. We develop a pipeline, Antibody Sequence Analysis Pipeline using Statistical testing and Machine Learning (ASAP-SML), to identify features that distinguish one set of antibody sequences from antibody sequences in a reference set. The pipeline extracts feature fingerprints from sequences. The fingerprints represent germline, CDR canonical structure, isoelectric point and frequent positional motifs. Machine learning and statistical significance testing techniques are applied to antibody sequences and extracted feature fingerprints to identify distinguishing feature values and combinations thereof. To demonstrate how it works, we applied the pipeline on sets of antibody sequences known to bind or inhibit the activities of matrix metalloproteinases (MMPs), a family of zinc-dependent enzymes that promote cancer progression and undesired inflammation under pathological conditions, against reference datasets that do not bind or inhibit MMPs. ASAP-SML identifies features and combinations of feature values found in the MMP-targeting sets that are distinct from those in the reference sets

Introduction of an Aliphatic Ketone into Recombinant Proteins in a Bacterial Strain that Overexpresses an Editing-Impaired Leucyl-tRNA Synthetase

Like leucine? A leucine analogue containing a ketone has been incorporated into proteins in E. coli. Only E. coli strains overexpressing an editing-deficient leucyl-tRNA synthetase were capable of synthesizing proteins with the aliphatic ketone amino acid. Modification of ketone-containing proteins under mild conditions has been demonstrated

Cell Surface Display Yields Evolvable, Clickable Antibody Fragments

Non-canonical amino acids (ncAAs) provide powerful tools for engineering the chemical and physical properties of proteins. However, introducing ncAAs into proteins can affect protein properties in unpredictable ways, thus necessitating screening efforts to identify mutants with desirable properties. In this work, we describe an Escherichia coli cell surface display platform for the directed evolution of clickable antibody fragments. This platform enabled isolation of antibody fragments with improved digoxigenin binding and modest affinity maturation in several different ncAA contexts. Azide-functionalized fragments exhibited improved binding kinetics relative to their methionine counterparts, facile chemical modification through azide–alkyne cycloaddition, and retention of binding properties after modification. The results described here suggest new possibilities for protein engineering, including modulation of molecular recognition events by ncAAs and direct screening of libraries of chemically modified proteins

Residue-specific incorporation of non-canonical amino acids into proteins: recent developments and applications

Residue-specific incorporation of non-canonical amino acids into proteins allows facile alteration and enhancement of protein properties. In this review, we describe recent technical developments and applications of residue-specific incorporation to problems ranging from elucidation of biochemical mechanisms to engineering of protein-based biomaterials. We hope to inform the reader of the ease and broad utility of residue-specific non-canonical amino acid incorporation with the goal of inspiring investigators outside the field to consider applying this tool to their own research

Phase shift keyed systems based on a gain switched laser transmitter

Return-to-Zero (RZ) and Non-Return-to-Zero (NRZ) Differential Phase Shift Keyed (DPSK) systems require cheap and optimal transmitters for widespread implementation. The authors report on a gain switched Discrete Mode (DM) laser that can be employed as a cost efficient transmitter in a 10.7 Gb/s RZ DPSK system and compare its performance to that of a gain switched Distributed Feed-Back (DFB) laser. Experimental results show that the gain switched DM laser readily provides error free performance and a receiver sensitivity of -33.1 dBm in the 10.7 Gbit/s RZ DPSK system. The standard DFB laser on the other hand displays an error floor at 10(-1) in the same RZ DPSK system. The difference in performance, between the two types of gain switched transmitters, is analysed by investigating their linewidths. We also demonstrate, for the first time, the generation of a highly coherent gain switched pulse train which displays a spectral comb of approximately 13 sidebands spaced by the 10.7 GHz modulation frequency. The filtered side-bands are then employed as narrow linewidth Continuous Wave (CW) sources in a 10.7 Gb/s NRZ DPSK system

A metaphysical and neuropsychological assessment of musical tones to affect the brain, relax the mind and heal the body

It has been empirically established through many controlled studies that one of the most rewarding experiences known to humanity is listening to music, especially because it affects various parts of the brain and causes emotional arousal. The aim of this article is to do a succinct study on music and its effect on, especially, the nervous system, by referring to various empirical studies undertaken on the subject. The article, therefore, has a twofold purpose: (1) to show that throughout history, music has played a special role in various cultures and religions, especially as a healing tool and (2) to demonstrate that sound frequencies and vibrations found in music have the potential to realign the emotions of the nervous system and bring the body back into harmony by reducing stress. INTRADISCIPLINARY AND/OR INTERDISCIPLINARY IMPLICATIONS : The article’s challenge and purpose are to show that science and religion are not in conflict, but rather that together they can benefit both disciplines and make better sense of complicated topics, especially those related to how natural science and religion deal with the human body and health, and its relationship to the mind.Please note that the author has included information from his previously published article entitled ‘Sound: Conceivably the creative language of god, holding all of creation in concert’ published by Verbum et Ecclesia, University of Pretoria. http://www.ve.org. za/index.php/VE/article/view/485. This article is a supplement to it.Issachar Fund Sabbatical Writer’s Retreathttp://www.ve.org.zaam2018Dogmatics and Christian Ethic

Evaluation of an Unsuccessful Brook Trout Electrofishing Removal Project in a Small Rocky Mountain Stream.

In the western United States, exotic brook trout Salvelinus fontinalis frequently have a deleterious effect on native salmonids, and biologists often attempt to remove brook trout from streams by means of electrofishing. Although the success of such projects typically is low, few studies have assessed the underlying mechanisms of failure, especially in terms of compensatory responses. A multiagency watershed advisory group (WAG) conducted a 3-year removal project to reduce brook trout and enhance native salmonids in 7.8 km of a southwestern Idaho stream. We evaluated the costs and success of their project in suppressing brook trout and looked for brook trout compensatory responses, such as decreased natural mortality, increased growth, increased fecundity at length, and earlier maturation. The total number of brook trout removed was 1,401 in 1998, 1,241 in 1999, and 890 in 2000; removal constituted an estimated 88% of the total number of brook trout in the stream in 1999 and 79% in 2000. Although abundance of age-1 and older brook trout declined slightly during and after the removals, abundance of age-0 brook trout increased 789% in the entire stream 2 years after the removals ceased. Total annual survival rate for age-2 and older brook trout did not decrease during the removals, and the removals failed to produce an increase in the abundance of native redband trout Oncorhynchus mykiss gairdneri. Lack of a meaningful decline and unchanged total mortality for older brook trout during the removals suggest that a compensatory response occurred in the brook trout population via reduced natural mortality, which offset the removal of large numbers of brook trout. Although we applaud WAG personnel for their goal of enhancing native salmonids by suppressing brook trout via electrofishing removal, we conclude that their efforts were unsuccessful and suggest that similar future projects elsewhere over such large stream lengths would be costly, quixotic enterprises