Discovery of new diketopiperazines inhibiting Burkholderia cenocepacia quorum sensing in vitro and in vivo

Burkholderia cenocepacia, an opportunistic respiratory pathogen particularly relevant for cystic fibrosis patients, is difficult to eradicate due to its high level of resistance to most clinically relevant antimicrobials. Consequently, the discovery of new antimicrobials as well as molecules capable of inhibiting its virulence is mandatory. In this regard quorum sensing (QS) represents a good target for anti-virulence therapies, as it has been linked to biofilm formation and is important for the production of several virulence factors, including proteases and siderophores. Here, we report the discovery of new diketopiperazine inhibitors of the B. cenocepacia acyl homoserine lactone synthase CepI, and report their anti-virulence properties. Out of ten different compounds assayed against recombinant CepI, four were effective inhibitors, with IC50 values in the micromolar range. The best compounds interfered with protease and siderophore production, as well as with biofilm formation, and showed good in vivo activity in a Caenorhabditis elegans infection model. These molecules were also tested in human cells and showed very low toxicity. Therefore, they could be considered for in vivo combined treatments with established or novel antimicrobials, to improve the current therapeutic strategies against B. cenocepacia

A simple method for the production of large volume 3D macroporous hydrogels for advanced biotechnological, medical and environmental applications

The development of bulk, three-dimensional (3D), macroporous polymers with high permeability, large surface area and large volume is highly desirable for a range of applications in the biomedical, biotechnological and environmental areas. The experimental techniques currently used are limited to the production of small size and volume cryogel material. In this work we propose a novel, versatile, simple and reproducible method for the synthesis of large volume porous polymer hydrogels by cryogelation. By controlling the freezing process of the reagent/polymer solution, large-scale 3D macroporous gels with wide interconnected pores (up to 200??m in diameter) and large accessible surface area have been synthesized. For the first time, macroporous gels (of up to 400?ml bulk volume) with controlled porous structure were manufactured, with potential for scale up to much larger gel dimensions. This method can be used for production of novel 3D multi-component macroporous composite materials with a uniform distribution of embedded particles. The proposed method provides better control of freezing conditions and thus overcomes existing drawbacks limiting production of large gel-based devices and matrices. The proposed method could serve as a new design concept for functional 3D macroporous gels and composites preparation for biomedical, biotechnological and environmental applications

On-Orbit Evaluation of a New Treadmill Harness for Improved Crewmember Comfort and Load Distribution

The current design of the International Space Station (ISS) Treadmill Harness has been reported to cause pain and discomfort to crewmembers during exercise. The Harness Station Development Test Objective (SDTO) provided participating crewmembers (n = 6) with a new harness design, the "Glenn Harness," to evaluate for comfort and loading as compared to the current Treadmill Harness. A novel suite of load-sensing instrumentation was developed to noninvasively measure load distribution and provided a first-ever quantification of actual dynamic loads during treadmill exercise. In addition, crew debriefs provided feedback on harness preference and overall impressions. Conclusions: Post-flight analysis in returned Glenn Harnesses (n = 3) showed minimal wear and tear. Four of the six subjects found the Glenn Harness to be more comfortable in this on-orbit, side-by-side comparison as measured by the crew comfort questionnaire and crew debriefs. Specific areas for improvement have been identified, and forward recommendations will be provided to the Human Research Program. The protocol developed for the SDTO provided valuable insight into crew comfort issues, design improvements, and loading preferences for exercise harnessing, which lays the groundwork for better harnessing systems and training protocols

Intentional Observational Clinical Research Design : Innovative Design for Complex Clinical Research Using Advanced Technology

The growing use of robots in nursing and healthcare facilities has prompted increasing research on human–robot interactions. However, specific research designs that can guide researchers to conduct rigorous investigations on human–robot interactions are limited. This paper aims to discuss the development and application of a new research design—the Intentional Observational Clinical Research Design (IOCRD). Data sources to develop the IOCRD were derived from surveyed literature of the past decade, focusing on clinical nursing research and theories relating robotics to nursing and healthcare practice. The distinction between IOCRD and other research design is the simultaneous data generation collected using advanced technological devices, for example, the wireless Bonaly-light electrocardiogram (ECG) to track heart rate variability of research subjects, robot application programs on the iPad mini to control robot speech and gestures, and Natural Language Processing programs. Even though IOCRD was developed for human–robot research, there remain vast opportunities for its use in nursing practice and healthcare. With the unique feature of simultaneous data generation and analysis, an interdisciplinary collaborative research team is strongly suggested. The IOCRD is expected to contribute guidance for researchers in conducting clinical research related to robotics in nursing and healthcare

Techno‐economic assessment and comparison of different plastic recycling pathways: A German case study

Greenhouse gas (GHG) emissions need to be reduced to limit global warming. Plastic production requires carbon raw materials and energy that are associated today with predominantly fossil raw materials and fossil GHG emissions. Worldwide, the plastic demand is increasing annually by 4%. Recycling technologies can help save or reduce GHG emissions, but they require comparative assessment. Thus, we assess mechanical recycling, chemical recycling by means of pyrolysis and a consecutive, complementary combination of both concerning Global Warming Potential (GWP) [CO2e], Cumulative Energy Demand (CED) [MJ/kg], carbon efficiency [%], and product costs [€] in a process‐oriented approach and within defined system boundaries. The developed techno‐economic and environmental assessment approach is demonstrated in a case study on recycling of separately collected mixed lightweight packaging (LWP) waste in Germany. In the recycling paths, the bulk materials polypropylene (PP), polyethylene (PE), polyvinylchloride (PVC), and polystyrene (PS) are assessed. The combined mechanical and chemical recycling (pyrolysis) of LWP waste shows considerable saving potentials in GWP (0.48 kg CO2e/kg input), CED (13.32 MJ/kg input), and cost (0.14 €/kg input) and a 16% higher carbon efficiency compared to the baseline scenario with state‐of‐the‐art mechanical recycling in Germany. This leads to a combined recycling potential between 2.5 and 2.8 million metric tons/year that could keep between 0.8 and 2 million metric tons/year additionally in the (circular) economy instead of incinerating them. This would be sufficient to reach both EU and German recycling rate targets (EC 2018). This article met the requirements for a gold‐silver JIE data openness badge described at http://jie.click/badges

Nucleosynthetic osmium isotope anomalies in acid leachates of the Murchison meteorite

We present osmium isotopic results obtained by sequential leaching of the Murchison meteorite, which reveal the existence of very large internal anomalies of nucleosynthetic origin. The Os isotopic anomalies are correlated, and can be explained by the variable contributions of components derived from the s, r and p-processes of nucleosynthesis. Much of the s-process rich osmium is released by relatively mild leaching, suggesting the existence of an easily leachable s-process rich presolar phase, or alternatively, of a chemically resistant r-process rich phase. The s-process composition of Os released by mild leaching diverges slightly from that released by aggressive digestion techniques, perhaps suggesting that the presolar phases attacked by these differing procedures condensed in different stellar environments. The correlation between 190Os and 188Os can be used to constrain the s-process 190Os/188Os ratio to be 1.275 pm 0.043. Such a ratio can be reproduced in a nuclear reaction network for a MACS value for 190Os of ~200 pm 22 mbarn at 30 keV. We also present evidence for extensive internal variation of 184Os abundances in the Murchison meteorite. This suggests that p process rich presolar grains (e.g., supernova condensates) may be present in meteorites in sufficient quantities to influence the Os isotopic compositions of the leachates.Comment: 40 pages, 9 figures, 2 tables. Accepted for publication in Earth and Planetary Science Letter

Dynamical Jahn-Teller Effect and Berry Phase in Positively Charged Fullerene I. Basic Considerations

We study the Jahn-Teller effect of positive fullerene ions $^2$C$_{60}^{+}$ and $^1$C$_{60}^{2+}$. The aim is to discover if this case, in analogy with the negative ion, possesses a Berry phase or not, and what are the consequences on dynamical Jahn-Teller quantization. Working in the linear and spherical approximation, we find no Berry phase in $^1$C$_{60}^{2+}$, and presence/absence of Berry phase for coupling of one $L=2$ hole to an $L=4$/$L=2$ vibration. We study in particular the special equal-coupling case ($g_2=g_4$), which is reduced to the motion of a particle on a 5-dimensional sphere. In the icosahedral molecule, the final outcome assesses the presence/absence of a Berry phase of $\pi$ for the $h_u$ hole coupled to $G_g$/$H_h$ vibrations. Some qualitative consequences on ground-state symmetry, low-lying excitations, and electron emission from C$_{60}$ are spelled out.Comment: 31 pages (RevTeX), 3 Postscript figures (uuencoded

Characteristics of interactive communication between Pepper robot, patients with schizophrenia, and healthy persons

Background: Expressing enjoyment when conversing with healthcare robots is an opportunity to enhance the value of human robots with interactive capabilities. In clinical practice, it is common to find verbal dysfunctions in patients with schizophrenia. Thus, interactive communication characteristics may vary between Pepper robot, persons with schizophrenia, and healthy persons. Objective: Two case studies aimed to describe the characteristics of interactive communications, 1) between Pepper as a healthcare robot and two patients with schizophrenia, and 2) between Pepper as a healthcare robot and two healthy persons. Case Report: The “Intentional Observational Clinical Research Design” was used to collect data. Using audio-video technology, the conversational interactions between the four participants with the Pepper healthcare robot were recorded. Their interactions were observed, with significant events noted. After their interactions, the four participants were interviewed regarding their experience and impressions of interacting with the Pepper healthcare robot. Audio-video recordings were analyzed following the analysis and interpretation protocol, and the interview data were transcribed, analyzed, and interpreted. Discussion: There were similarities and differences in the interactive communication characteristics between the Pepper robot and the two participants with schizophrenia and between Pepper and the two healthy participants. The similarities were experiences of human enjoyment while interacting with the Pepper robot. This enjoyment was enhanced with the expectancy of the Pepper robot as able to entertain, and possessing interactive capabilities, indicating two-way conversational abilities. However, different communicating characteristics were found between the healthy participants’ impressions of the Pepper robot and the participants with schizophrenia. Healthy participants understood Pepper to be an automaton, with responses to questions often constrained and, on many occasions, displaying inaccurate gaze. Conclusion: Pepper robot showed capabilities for effective communication pertaining to expressing enjoyment. The accuracy and appropriateness of gaze remained a critical characteristic regardless of the situation or occasion with interactions between persons with schizophrenia, and between healthy persons. It is important to consider that in the future, for effective use of healthcare robots with multiple users, improvements in the areas of the appropriateness of gaze, response time during the conversation, and entertaining functions are critically observed

Capillary electrophoresis as a tool for genotyping SH3 mediated coffee leaf rust resistance

Coffee is an important agricultural commodity in the world. However, it is susceptible to Hemileia vastatrix (Hv), an obligatory biotrophic fungus that causes coffee leaf rust (CLR). Natural resistance to rust has been identified in the wild species Coffea canephora and Coffea liberica. These species have been used in breeding programs where interspecific resistant hybrids have been generated. The SH3 gene, derived from C. liberica, has been shown to confer extreme and long-lasting resistance to Hv. A total of 167 accessions of the INIA’s Coffee Germplasm Collection of Peru (INIA-CGC) were screened with 4 markers linked to the SH3 gene. As positive controls, EA67 (C. liberica) and the hybrid S.288 (C. arabica x C. liberica) were used. Separation of PCR products was done by capillary electrophoresis, which allow to discriminate the alleles of each marker. For three markers, specific alleles for either C. arabica or C. liberica species were found. In all cases, S.288 exhibited specific alleles for both species; whereas the INIA-CGC accessions had exclusively C. arabica alleles and EA67 had C. liberica alleles. The BA-48-21O-f marker did not produce PCR fragments for any of the positive controls, suggesting that this marker is not as predictive as the other three to determine the presence of SH3. This work reports the existence of multiple alleles for the Sat244 marker; however, the collection does not have the SH3 mediated-resistance gene. Finally, the utility of capillary electrophoresis as a tool to identify alleles linked to SH3 was demonstrated

Spacial and temporal dynamics of the volume fraction of the colloidal particles inside a drying sessile drop

Using lubrication theory, drying processes of sessile colloidal droplets on a solid substrate are studied. A simple model is proposed to describe temporal dynamics both the shape of the drop and the volume fraction of the colloidal particles inside the drop. The concentration dependence of the viscosity is taken into account. It is shown that the final shapes of the drops depend on both the initial volume fraction of the colloidal particles and the capillary number. The results of our simulations are in a reasonable agreement with the published experimental data. The computations for the drops of aqueous solution of human serum albumin (HSA) are presented.Comment: Submitted to EPJE, 7 pages, 8 figure