Enhanced Permeability and Binding Activity of Isobutylene‐Grafted Peptides

We present a new peptide‐macrocyclization strategy with an isobutylene graft. The reaction is mild and proceeds rapidly and efficiently both for linear and cyclic peptides. The resulting isobutylene‐grafted peptides possess improved passive membrane permeability due to the shielding of the polar backbone of the amides, as demonstrated by NMR spectroscopy and molecular dynamics simulations. The isobutylene‐stapled structures are fully stable in human plasma and in the presence of glutathione. This strategy can be applied to bioactive cyclic peptides such as somatostatin. Importantly, we found that structural preorganization forced by the isobutylene graft leads to a significant improvement in binding. The combined advantages of directness, selectivity, and smallness could allow application to peptide macrocyclization based on this attachment of the isobutylene graft.     

Representation and analysis of enterprise models with semantic techniques: an application to ArchiMate,e3value and business model canvas

Enterprise models assist the governance and transformation of organizations through the specification, communication and analysis of strategy, goals, processes, information, along with the underlying application and technological infrastructure. Such models cross-cut different concerns and are often conceptualized using domain-specific modelling languages. This paper explores the application of graph-based semantic techniques to specify, integrate and analyse multiple, heterogeneous enterprise models. In particular, the proposal described in this paper (1) specifies enterprise models as ontological schemas, (2) uses transformation mapping functions to integrate the ontological schemas and (3) analyses the integrated schemas with graph querying and logical inference. The proposal is evaluated through a scenario that integrates three distinct enterprise modelling languages: the business model canvas, e3value, and the business layer of the ArchiMate language. The results show, on the one hand, that the graph-based approach is able to handle the specification, integration and analysis of enterprise models represented with different modelling languages and, on the other, that the integration challenge resides in defining appropriate mapping functions between the schemas.     

Modified binary PSO for feature selection using SVM applied to mortality prediction of septic patients

This paper proposes a modified binary particle swarm optimization (MBPSO) method for feature selection with the simultaneous optimization of SVM kernel parameter setting, applied to mortality prediction in septic patients. An enhanced version of binary particle swarm optimization, designed to cope with premature convergence of the BPSO algorithm is proposed. MBPSO control the swarm variability using the velocity and the similarity between best swarm solutions. This paper uses support vector machines in a wrapper approach, where the kernel parameters are optimized at the same time. The approach is applied to predict the outcome (survived or deceased) of patients with septic shock. Further, MBPSO is tested in several benchmark datasets and is compared with other PSO based algorithms and genetic algorithms (GA). The experimental results showed that the proposed approach can correctly select the discriminating input features and also achieve high classification accuracy, specially when compared to other PSO based algorithms. When compared to GA, MBPSO is similar in terms of accuracy, but the subset solutions have less selected features.     

Production scheduling in the context of Industry 4.0: review and trends

Notwithstanding its disruptive potential, which has been the object of considerable debate, Industry4.0 (I4.0) operationalisation still needs significant study. Specifically, scheduling is a key process that should be explored from this perspective. The purpose of this study is to shed light on the issues regarding scheduling that need to be considered in the new I4.0 framework. To achieve this, a two-stage cascade literature review is performed. The review begins with an analysis regarding the opportunities and challenges brought by I4.0 to the scheduling field, outputting a set of critical scheduling areas (CSA) in which development is essential. The second-stage literature review is performed to understand which steps have been taken so far by previous research in the scheduling field to address those challenges. Thus, a first contribution of this work is to provide insight on the influence and expected changes brought by I4.0 to scheduling, while showcasing relevant research. Another contribution is to identify the most promising future lines of research in this field, in which relevant challenges such as holistic scheduling, or increased flexibility requirements are highlighted. Concurrently, CSA such as decentralised decision-making, and human–robot collaboration display large gaps between current practice and the required technological level of development.     

A fractional calculus approach for the evaluation of the golf lip-out

Golf is a sport in which competing players need to introduce the ball into the hole using the fewest number of strikes. However, this goal can sometimes be compromised when the ball suffers from lip-out phenomenon, that is, when the ball surrounds the hole??s edge without dropping in. Although some techniques may be presented in the literature to assess golfers?? performance (e.g., evaluation of the ball??s final position to the hole), none takes in consideration the putting lip-out. With this in mind, this article proposes a correction metric based on fractional calculus that considers past events in ball??s trajectory, thus slightly increasing player??s performance when putting lip-out occurs. On the opposite of integer derivatives which are considered as ??local?? operators, fractional derivatives implicitly have ??memory?? of all past events being well suited to describe the dynamic phenomena of ball??s trajectory. Therefore, this novel correction metric will provide a new virtual position of the ball based on its trajectory induced by the putting lip-out. This metric was evaluated analyzing the performance of 10 expert subjects who performed a total of 30 trials, with the lip-out occurring in 29 out of the 300 considered. Experimental results show an average improvement of 19.6?% in trials where the lip-out occurred and an average overall improvement of 1.82?% in player??s performances, when applying the correction metric.     

Prejunctional effect of quaternary derivatives of l-hyoscyamine at the rat neuromuscular junction. A structure-activity relationship study

1. The effects of phenthonium and related compounds on the spontaneous release of acetylcholine (ACh) were investigated with electrophysiological and radiolabelled techniques to correlate the prejunctional effect with their cholinolytic activities and to determine the structure-activity relationship. 2. Phenthonium and endophen are N-(4-phenyl)-phenacyl derivatives of l-hyoscyamine in "exo" and "endo" conformation, respectively. Tropol is N-(4-phenyl) phenacyl tropan-3-ol whereas ipratropium is 8-isopropyl-noratropine. 3. Only phenthonium increased the frequency of miniature endplate potentials and the resting efflux of spontaneous [3H]-ACh in rat diaphragm muscles. 4. The rank order of the antimuscarinic potency was: ipratropium > atropine > phenthonium = endophen > tropol. The rank order of the antinicotinic activity was: phenthonium = endophen > tropol > atropine > ipratropium. 5. It is concluded that the prejunctional facilitatory effect of phenthonium is associated with the N-phenyl-phenacyl group at "exo" conformation but the effect is unrelated to its cholinolytic properties.     

Histomorphometric Evaluation of the Small Coronary Arteries in Rats Exposed to Industrial Noise

Morphological changes induced by industrial noise (IN) have been experimentally observed in several organs. Histological observations of the coronary arteries showed prominent perivascular tissue and fibrosis among IN-exposed rats. The effects on the small arteries are unknown. Objective: To evaluate the histomorphometric changes induced by IN on rat heart small arteries. Methods: Twenty Wistar rats exposed to IN during a maximum period of seven months and 20 age-matched controls were studied. Hearts were transversely sectioned from ventricular apex to atria and a mid-ventricular fragment was selected for analysis. The histological images were obtained with an optical microscope using 400× magnifications. A total of 634 arterial vessels (298 IN-exposed and 336 controls) were selected. The mean lumen-to-vessel wall (L/W) and mean vessel wall-to-perivascular tissue (W/P) ratios were calculated using image J software. Results: There were no differences between exposed and control animals in their L/W ratios (p = 0.687) and time variations in this ratio were non-significant (p = 0.110). In contrast, exposed animals showed lower W/P ratios than control animals (p < 0.001), with significant time variations (p = 0.004). Conclusions: Industrial noise induced an increase in the perivascular tissue of rat small coronary arteries, with significant development of periarterial fibrosis.     

Comparison of Electrophoretic Protein Profiles from Sheep and Goat Parotid Saliva

Saliva provides a medium for short-term adaptation to changes in diet composition, namely, the presence of plant secondary metabolites. Salivary proteins have biological functions that have particular influence on oral homeostasis, taste, and digestive function. Some salivary proteins, such as proline-rich proteins, are present in browsers but absent in grazers. Despite the significance of salivary proteins, their expression patterns in many herbivores are unknown. We investigated the sodium dodecyl sulfate-polyacrylamide gel electrophoresis profile of parotid salivary proteins from two domesticated species, one a grazer, the sheep, Ovis aries, and the other a mixed feeder, the goat, Capra hircus, both fed on the same conventional diet. With 12.5% polyacrylamide linear gels, we observed uniform patterns of salivary proteins within the two species. In the goat profile, 21 major bands were observed, and 19 in the sheep profile. Each band was subjected to peptide mass fingerprinting for purposes of identification, allowing for 16 successful protein identifications. Marked differences were observed between the species in the region of 25–35 kDa molecular weights: one band was present in significantly different intensities; three bands were present only in goats; and one band was present only in sheep. This is the first report of a comparison of the protein salivary composition of sheep and goats and suggests that future research should be conducted to reveal a physiological function for salivary proteins related to the differences in feeding behavior of these species.