Ab initio Designed Antimicrobial Peptides Against Gram-Negative Bacteria

Antimicrobial peptides (AMPs) are ubiquitous amongst living organisms and are part of the innate immune system with the ability to kill pathogens directly or indirectly by modulating the immune system. AMPs have potential as a novel therapeutic against bacteria due to their quick-acting mechanism of action that prevents bacteria from developing resistance. Additionally, there is a dire need for therapeutics with activity specifically against Gram-negative bacterial infections that are intrinsically difficult to treat, with or without acquired drug resistance. Development of new antibiotics has slowed in recent years and novel therapeutics (like AMPs) with a focus against Gram-negative bacteria are needed. We designed eight novel AMPs, termed PHNX peptides, using ab initio computational design (database filtering technology combined with the novel positional analysis on APD3 dataset of AMPs with activity against Gram-negative bacteria) and assessed their theoretical function using published machine learning algorithms, and finally, validated their activity in our laboratory. These AMPs were tested to establish their minimum inhibitory concentration (MIC) and half-maximal effective concentration (EC50) under CLSI methodology against antibiotic resistant and antibiotic susceptible Escherichia coli and Staphylococcus aureus. Laboratory-based experimental results were compared to computationally predicted activities for each of the peptides to ascertain the accuracy of the computational tools used. PHNX-1 demonstrated antibacterial activity (under high and low-salt conditions) against antibiotic resistant and susceptible strains of Gram-positive and Gram-negative bacteria and PHNX-4 to -8 demonstrated low-salt antibacterial activity only. The AMPs were then evaluated for cytotoxicity using hemolysis against human red blood cells and demonstrated some hemolysis which needs to be further evaluated. In this study, we successfully developed a design methodology to create synthetic AMPs with a narrow spectrum of activity where the PHNX AMPs demonstrated higher antibacterial activity against Gram-negative bacteria compared to Gram-positive bacteria. Thus, these peptides present novel synthetic peptides with a potential for therapeutic use. Based on our findings, we propose upfront selection of the peptide dataset for analysis, an additional step of positional analysis to add to the ab initio database filtering technology (DFT) method, and we present laboratory data on the novel, synthetically designed AMPs to validate the results of the computational approach. We aim to conduct future in vivo studies which could establish these AMPs for clinical use.

Peak Running Intensities in Field Hockey - a Positional Analysis

The aim of this study was to investigate the positional mean peak running periods during a field hockey match using a moving average method. The secondary aim was to investigate how the peak periods changed between quarters and playing positions. The moving average method was used to analyse the data because of the nature of field hockey, which has natural fluctuations of high and low intensity periods of play. The time periods included periods from 1 to 10 minutes. The level of significance for results was set at p ≤ 0.05. The study found that forwards had a peak running intensity of 194 ± 24.2 m·min-1, midfielders 189 ± 11.9 m·min-1, and defenders 182.6 ± 17.9 m·min-1. These results showed that forwards had the highest maximum running speed, with defenders having the lowest one (p = 0.0025). Additionally, running output started to plateau after 7/8-min periods for each of the three positions. Forwards did not show any statistically significant changes across the four quarters. Midfielders showed effect sizes ranging from >0.6 to >2.0 (moderate, large and very large) significance when comparing the first three quarters to the fourth one. Defenders showed >0.6 to <2.0 (moderate to large) effect sizes to occur when comparing the first and second quarter to the fourth. There are three main practical implications from the results of this study: 1) the creation of conditioning drills, 2) substitution patterns, and 3) knowledge to be able to plan and train at or above peak match demands.

Network analysis of collaboration in networked universities

PurposeIn Latin America and the Caribbean, the access of students to higher education has presented an extraordinary growth over the past fifteen years. This rapid growth has presented a challenge for increasing the system resources and capabilities while maintaining its quality. As a result, the networked universities (NUs) organized themselves as a collaborative network, and they have become an interesting model for facing the complexity driven by globalization, rapidly changing technology, dynamic growth of knowledge and highly specialized areas of expertise. In this article, we studied the NU named Red Universitaria Mutis (Red Mutis) with the aim of characterizing the collaboration and integration structure of the network.Design/methodology/approachNetwork analytic methods (visual analysis, positional analysis and a stochastic network method) were used to characterize the organizational structure and robustness of the network, and to identify what variables or structural tendencies are related to the likelihood that specific areas of a university would collaborate.FindingsRed Mutis is a good example of regional NUs that could take advantage of the strengths, partnerships, information and knowledge of the regional and international universities that form the network. Analyses showed that Red Mutis has a differentiated structure consisting of academic and non-academic university areas with a vertical coordination (by steering and management) of the different university areas.Originality/valueThe methodology could be used as a framework to analyze and strengthen other strategic alliances between universities and as a model for the development of other NU in local and global contexts.

The relationship between team ability and home advantage in the English football league system

The existence of home advantage (HA) has been found in a variety of team sports including football. There is a paucity of research on the relationship between team ability and HA in domestic football leagues and the findings of previous studies are inconclusive. Using longitudinal data from the top four football divisions in England, this study investigates the influence of team ability on the HA of teams. The data collected for this study spans 24 seasons from 1995/96 to 2018/19 and includes 48,864 matches from the English Premier League (n = 9120), the Championship (n = 13,248), League One (n = 13,248) and League Two (n = 13,248). Team ability was interpreted in two ways: (1) the division in which teams play and (2) their league table position within each division. For both the divisional and positional analysis, HA was calculated as the ratio of home points to total points achieved by teams in each season under review. Evidence of a statistically significant HA was found in all four divisions and for teams of all abilities within each division. Small but statistically significant differences in HA were observed between divisions and between high, moderate and low ability teams within divisions.

Industrial Robot Positioning Performance Measured on Inclined and Parallel Planes by Double Ballbar

Renishaw Ballbar QC20–W is primarily intended for diagnostics of CNC machine tools, but it is also used in connection with industrial robots. In the case of standard measurement, when the measuring plane is parallel to the robot base, not all robot joints move. The purpose of the experiments of the present article was to verify the hypothesis of the motion of all the robot joints when the desired circular path is placed on an inclined plane. In the first part of the conducted experiments is established hypothesis is confirmed, through positional analysis on a simulation model of the robot. They are then carried out practical measurements being evaluated the influence of individual robot joints to deform the circular path, shown as a polar graph. As a result, it is found that in the case of the robot used, changing the configuration of the robot arm has the greatest effect on changing the shape of the polar graph.

An updated detailed characterization of planes of satellites in the MW and M31

ABSTRACT We present a detailed characterization of planes of satellite galaxies in the Milky Way (MW) and M31. For a positional analysis, we introduce an extension to the ‘4-galaxy-normal density plot’ method from Pawlowski, Kroupa & Jerjen. It finds the normal directions to the predominant planar configurations of satellites of a system, yielding for each a collection of planes of increasing member satellites. This allows to quantify the quality of planes in terms of population (Nsat) and spatial flattening (c/a). We apply this method to the latest data for confirmed MW and M31 satellite samples, with 46 and 34 satellites, respectively. New MW satellites form part of planes previously identified from a smaller sample of Nsat= 27: we identify a new plane with Nsat = 39 as thin as the VPOS-3 (c/a ∼ 0.2), and with roughly the same normal direction; so far the most populated plane that thin reported in the Local Group. We introduce a new method to determine, using kinematic data, the axis of maximum co-orbitation of MW satellites. Interestingly, this axis approximately coincides with the normal to the former plane: $\ge 45\pm 5{{\ \rm per\ cent}}$ of satellites co-orbit. In M31 we discover a plane with Nsat = 18 and c/a ∼ 0.15, i.e. quality comparable to the GPoA, and perpendicular to it. This structure is viewed face-on from the Sun making it susceptible to M31 satellite distance uncertainties. An estimation of the perpendicular velocity dispersion suggests that it is dynamically unstable. Finally we find that mass is not a property determining a satellite’s membership to good quality planes.

Сategories of analysis within activity-oriented counseling

This paper aims to provide an analysis of the theoretical and methodological grounds of Activity-oriented models of psychological counseling practice, along with an author's model of counseling interaction between a psychologist and a client within the framework of Activity theory. In contrast to majority of psychological theories, Activity theory has not yet been fully reflected in psychotherapeutic and counseling practice. As a consequence, we can see the gap in the relevant methodology of psychological care, despite of multiple theoretical and empirical research, conducted within Activity framework. The structure and procedure of Activity-oriented counselling is based on major categories of Activity theory, developed by S. Rubinstein, A. Leontiev, F. Vasilyuk, G. Schedrovitsky, namely: i) unity of consciousness and activity; ii) experiencing as a form of personal activity; iii) categories of activity analysis. Since the subject of counseling is the problem situation experienced by a client, the main purpose of psychological counseling is to convert the problem into achievable tasks, which requires setting a clear logic and sequencing stages of consultative process. It is shown that the consultant guides the client through a series of stages, which involve consistent changes. Those stages include following: situation scanning; positional analysis; problematizing and capturing of contradictions, repositioning and designing of new activity schemes. Activity-oriented counseling offers a comprehensive, context-sensitive method of client`s life story exploration and highly structured procedure, which allows psychologist and the client to retain its overall meaning and logic. Certainly, an active approach in the psychological practice of counselling requires further methodological developments: in particular, the development of protocols of counseling sessions and non-parametric methods of diagnosis of client advancement.