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Monoamine neurotransmitters generated by de novo synthesis are rapidly transported and stored into synaptic vesicles at axon terminals. This transport is essential both for sustaining synaptic transmission and for limiting the toxic effects of monoamines. Here, synthesis of the monoamine histamine by histidine decarboxylase (HDC) and subsequent loading of histamine into synaptic vesicles are shown to be physically and functionally coupled within Drosophila photoreceptor terminals. This process requires HDC anchoring to synaptic vesicles via interactions with N-ethylmaleimide-sensitive fusion protein 1 (NSF1). Disassociating HDC from synaptic vesicles disrupts visual synaptic transmission and causes somatic accumulation of histamine, which leads to retinal degeneration. We further identified a proteasome degradation system mediated by the E3 ubiquitin ligase, purity of essence (POE), which clears mislocalized HDC from the soma, thus eliminating the cytotoxic effects of histamine. Taken together, our results reveal a dual mechanism for translocation and degradation of HDC that ensures restriction of histamine synthesis to axonal terminals and at the same time rapid loading into synaptic vesicles. This is crucial for sustaining neurotransmission and protecting against cytotoxic monoamines., (© 2024. The Author(s).)

The utilization of polyamide 10,12 (PA10,12) composites in various industries has been limited constrained by their inherent low toughness, making it a challenge to achieve a balance between toughness and structural integrity through conventional elastomer addition strategies. Herein, we introduce a straightforward method for the concurrent toughening and reinforcement of PA10,12 composites. This is accomplished by blending polyolefin elastomer (POE) and 3-pentadecylphenol (PDP) with the PA10,12 matrix. The incorporation of 5 wt% PDP effectively blurred the PA10,12/POE interface due to PDP's role as a compatibilizer. This phenomenon is attributed to the formation of intermolecular hydrogen bonds, as evidenced by Fourier Transform Infrared Spectroscopy (FTIR) analysis. Further investigation, using differential scanning calorimetry (DSC), elucidated the crystallization thermodynamics and kinetics of the resulting binary PA10,12/POE and ternary PA10,12/POE/PDP composites. Notably, the crystallization temperature ( T c ) was observed to decrease from 163.1 °C in the binary composite to 161.5 °C upon the addition of PDP. Increasing the PDP content to 10% led to a further reduction in T c to 159.5 °C due to PDP's capacity to slow down crystallization. Consequently, the ternary composite of PA10,12/POE/PDP (92/3/5 wt%) demonstrated a synergistic improvement in mechanical properties, with an elongation at break of 579% and a notch impact strength of 61.54 kJ/m 2 . This represents an approximately eightfold increase over the impact strength of unmodified PA10,12. Therefore, our work provides the potential of PDP as a compatibilizer to develop nylon composites with enhanced stiffness and toughness.

To address the dilemma of the stiffness and toughness properties of high-density polyethylene (HDPE) composites, titanate coupling agent-treated CaCO 3 nanoparticles (nano-CaCO 3 ) and ethylene-octene copolymer (POE) were utilized to blend with HDPE to prepare ternary nanocomposites via a two-sequence-step process. Meanwhile, a one-step process was also studied as a control. The obtained ternary nanocomposites were characterized by scanning electron microscopy (SEM), Advanced Rheometrics Expansion System (ARES), Dynamic Mechanical Analysis (DMA), wide-angle X-ray diffraction analysis (WXRD), and mechanical test. The SEM results showed one or two CaCO 3 nanoparticles were well-encapsulated by POE and were uniformly dispersed into the HDPE matrix to form a core-shell structure of 100-200 nm in size by the two-step process, while CaCO 3 nanoparticles were aggregated in the HDPE matrix by the one-step method. The result of the XRD showed that the nano-CaCO 3 particle played a role in promoting crystallization in HDPE nanocomposites. Mechanical tests showed that the synergistic effect of both the POE elastomer and CaCO 3 nanoparticles should account for the balanced performance of the ternary composites. In comparison with neat HDPE, the notched impact toughness of the ternary nanocomposites of HDPE/POE/nano-CaCO 3 was significantly increased. In addition, the core-shell structure absorbed the fracture impact energy and prevent further propagation of micro-cracks, thus obtaining a higher notched Izod impact strength.

In this review, we focus on prenatal opioid exposure (POE) given the significant concern for the mental health outcomes of children with parents affected by opioid use disorder (OUD) in the view of the current opioid crisis. We highlight some of the less explored interactions between developmental age and sex on synaptic plasticity and associated behavioral outcomes in preclinical POE research. We begin with an overview of the rich literature on hippocampal related behaviors and plasticity across POE exposure paradigms. We then discuss recent work on reward circuit dysregulation following POE. Additional risk factors such as early life stress (ELS) could further influence synaptic and behavioral outcomes of POE. Therefore, we include an overview on the use of preclinical ELS models where ELS exposure during key critical developmental periods confers considerable vulnerability to addiction and stress psychopathology. Here, we hope to highlight the similarity between POE and ELS on development and maintenance of opioid-induced plasticity and altered opioid-related behaviors where similar enduring plasticity in reward circuits may occur. We conclude the review with some of the limitations that should be considered in future investigations. This article is part of the Special Issue on 'Opioid-induced addiction'., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Published by Elsevier Ltd.)

Glass/glass (G/G) photovoltaic modules are quickly rising in popularity, but the durability of modern G/G packaging has not yet been established. In this work, we examine the interfacial degradation modes in G/G and glass/transparent backsheet modules under damp heat (DH) with and without system bias voltage, comparing emerging polyolefin elastomer (POE) and industry-standard poly(ethylene-co-vinyl acetate) (EVA) encapsulants. We investigate the transport of ionic species at cell/encapsulant interfaces, demonstrating that POE limits both sodium and silver ion migration compared with EVA. Changes to the chemical structures of the encapsulants at the cell/encapsulant interfaces demonstrate that both POE and EVA are more susceptible to degradation in modules with a transparent backsheet than in the G/G configuration. Adhesion testing reveals that POE and EVA have comparable critical debond energies after the DH exposures regardless of system bias polarity. The results of this study indicate that the interfacial degradation mechanisms of G/G appear to be similar to those of conventional glass/backsheet modules. For emerging materials, our results demonstrate that POE offers advantages over EVA but that transparent backsheets may accelerate encapsulant degradation due to increased moisture ingress when compared with the G/G structure., (© 2022 The Authors. Progress in Photovoltaics: Research and Applications published by John Wiley & Sons Ltd.)

Encapsulants based on ethylene-vinyl acetate copolymers (EVA) or polyolefin elastomers (POE) are essential for glass or photovoltaic module laminates. To improve their multi-functional property profile and their durability, the encapsulants are frequently peroxide crosslinked. The crosslinking kinetics are affected by the macromolecular structure and the formulation with stabilizers such as phenolic antioxidants, hindered amine light stabilizers or aromatic ultraviolet (UV) absorbers. The main objective of this study was to implement temperature-rise and isothermal dynamic mechanical analysis (DMA) approaches in torsional mode and to assess and compare the crosslinking kinetics of novel UV-transparent encapsulants based on EVA and POE. The gelation time was evaluated from the crossover of the storage and loss shear modulus. While the investigated EVA and POE encapsulants revealed quite similar activation energy values of 155 kJ/moles, the storage modulus and complex viscosity in the rubbery state were significantly higher for EVA. Moreover, the gelation of the polar EVA grade was about four times faster than for the less polar POE encapsulant. Accordingly, the curing reaction of POE was retarded up to a factor of 1.6 to achieve a progress of crosslinking of 95%. Hence, distinct differences in the crosslinking kinetics of the UV-transparent EVA and POE grades were ascertained, which is highly relevant for the lamination of modules.

Energy recovery from renewable sources is a very attractive, and sometimes, challenging issue. To recover solar energy, the production of photovoltaic (PV) modules becomes a prosperous industrial certainty. An important material in PV modules production and correct functioning is the encapsulant material and it must have a good performance and durability. In this work, accurate characterizations of performance and durability, in terms of photo- and thermo-oxidation resistance, of encapsulants based on PolyEthylene Vinyl Acetate (EVA) and PolyOlefin Elastomer (POE), containing appropriate additives, before (pre-) and after (post-) lamination process have been carried out. To simulate industrial lamination processing conditions, both EVApre-lam and POEpre-lam sheets have been subjected to prolonged thermal treatment upon high pressure. To carry out an accurate characterization, differential scanning calorimetry, rheological and mechanical analysis, FTIR and UV-visible spectroscopy analyses have been performed on pre- and post-laminated EVA and POE. The durability, in terms of photo- and thermo-oxidation resistance, of pre-laminated and post-laminated EVA and POE sheets has been evaluated upon UVB exposure and prolonged thermal treatment, and the progress of degradation has been monitored by spectroscopy analysis. All obtained results agree that the lamination process has a beneficial effect on 3D-structuration of both EVA and POE sheets, and after lamination, the POE shows enhanced rigidity and appropriate ductility. Finally, although both EVA and POE can be considered good candidates as encapsulants for bifacial PV modules, it seems that the POE sheets show a better resistance to oxidation than the EVA sheets.

Student housing significantly influences the quality and competitiveness of the university education environment. Whereas the traditional post-occupancy evaluations (POEs) of buildings have typically focussed on investigating users' satisfaction, an earlier study developed the gap theory based post-occupancy evaluation (GTbPOE) method, by which both the users' expectation and satisfaction (viz. performance gap) of a university dormitory were investigated. To validate the applicability of the GTbPOE method, further research was undertaken to evaluate the building performance of another dormitory. Using face-to-face interviews, responses of 104 dormitory users were collected, of which the relative importance ratings of six essential aspects (namely: visual comfort, thermal comfort, aural comfort, fire safety, hygiene, and communication via information technology) were analyzed via the Analytic Hierarchy Process (AHP). A series of gap analyses on the users' expectation and satisfaction levels corroborated the existence of the adaptation effect on the users' perception: that is, the longer the stay, the smaller the performance gap. A comparative analysis on the findings between the two dormitories - one from the earlier study and the other from the present study - further demonstrated the usefulness of the GTbPOE method in benchmarking building performance. Adoption of this method in future POE studies will enable reliable identification of any shortcoming in building performance and hence, can form the basis for improvement measures to augment the performance of buildings within the built environment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Elsevier Ltd. All rights reserved.)

Background: Understanding the outcomes associated with both receiving and providing support to people with intellectual disability in specific settings can facilitate the alignment of health providers, community care providers, architects, and urban planners to strengthen levels of autonomy and community participation of people with intellectual disability living in the community. This study explores the impact of providing support (available 24 hours a day) for people with intellectual disability in a high-density apartment. It seeks the perspectives of people with intellectual disability who have moved into an apartment from a group home (where 4-6 people with disability live), their families, and support staff. It will enable comparison between two models of supported accommodation, group homes and individualized apartments, in a community setting., Objective: The aims of this study are to explore the impact of an individualized apartment model of supported accommodation in a high-density setting on the well-being, autonomy, and participation of people with intellectual disability living and receiving support; the experience of providing care or support; and how this setting impacts the logistics of how quality support is provided., Methods: Qualitative research methods were employed as the primary means of collecting and analyzing data. There are two main sources of data in this study: (1) semistructured interviews with participants in up to 3 waves (pre, post 1, and post 2) and (2) pre- and postoccupancy evaluation data on the design, layout, and location details of the built environments. Coded interview data will be paired with pre- and postoccupancy evaluations of the two accommodation settings., Results: As of May 2020, we have recruited 55 participants. There have been 96 interviews conducted in 2 waves with people who have moved into supported accommodation, families, and staff. Collected data are currently being analyzed. We expect the results of the trial to be published in a peer-reviewed journal in late 2020., Conclusions: This paper sets out a study of an alternative housing and support model for people with intellectual disability. It will capture personal experiences of people with intellectual disability receiving support in an apartment compared to their experiences in a group home. It will also capture the experiences of support staff working in the new setting and reveal how this differs from a group home setting. The inclusion of pre (group home) and post (apartment integrated into a community setting) measures addresses evaluative and comparative questions around the nature and impacts of the small-scale apartment and support model for both those who live and receive support, and those who support them., International Registered Report Identifier (irrid): DERR1-10.2196/18248., (©Phillippa Carnemolla. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 07.08.2020.)

Objective: This study investigates how patients and medical staff assess the physical environments of two recently built hospitals in Sulaimani City to understand the extent to which indoor environmental factors influence the creation of an optimal healing environment., Background: A contemporary healing environment may be recognized by the quality of an indoor environment in positively influencing patients' psychological comfort and supporting their recovery., Method: Post-occupancy evaluations were conducted in Shar General Hospital and Faruk Medical City wards. A 43-item questionnaire was distributed to 312 patients, doctors, and nurses to gather their perspectives. In total, 175 valid questionnaires were retrieved., Results: The results show that the quality of the indoor environments met patients' psychological needs and expectations, and as a result, they were generally satisfied with the indoor healing environments. The findings from the patient and medical staff surveys suggest three essential factors in creating a healing environment, which are (1) Interior appearance , (2) Privacy , and (3) Comfort and control . Significant negative correlations of some demographic characteristics, such as educational attainment and age, with patient satisfaction were observed., Conclusions: This study shows that exploring patients' and medical staff's experiences can reveal factors that positively influence patients' satisfaction levels, which may vary depending on their sociocultural perspectives and personal characteristics. Additionally, the findings emphasize the role of the tested factors in increasing patients' satisfaction levels, optimizing healing environments, and informing design decisions.

Background: The influences of genetic variants on functional clinical outcomes following stroke are unclear. In order to reliably quantify these influences, we undertook a comprehensive meta-analysis of outcomes after acute intracerebral haemorrhage (ICH) or ischaemic stroke (AIS) in relation to different genetic variants., Methods: PubMed, PsycInfo, Embase and Medline electronic databases were searched up to January 2019. Outcomes, defined as favourable or poor, were assessed by validated scales (Barthel index, modified Rankin scale, Glasgow outcome scale and National Institutes of Health stroke scale)., Results: Ninety-two publications comprising 31,895 cases met our inclusion criteria. Poor outcome was observed in patients with ICH who possessed the APOE4 allele: OR =2.60 (95% CI = 1.25-5.41, p = 0.01) and in AIS patients with the GA or AA variant at the BDNF-196 locus: OR = 2.60 (95% CI = 1.25-5.41, p = 0.01) or a loss of function allele of CYP2C19: OR = 2.36 (95% CI = 1.56-3.55, p < 0.0001). Poor outcome was not associated with APOE4: OR = 1.02 (95% CI = 0.81-1.27, p = 0.90) or IL6-174 G/C: OR = 2.21 (95% CI = 0.55-8.86, p = 0.26) in patients with AIS., Conclusions: We demonstrate that recovery of AIS was unfavourably associated with variants of BDNF and CYP2C19 genes whilst recovery of ICH was unfavourably associated with APOE4 gene.

Novel nanocomposites for dielectric applications-based polypropylene/poly(ethylene-co-octene) (PP/POE) blends filled with nano silica are developed in the framework of the European 'GRIDABLE' project. A tailor-made low-pressure-plasma reactor was applied in this study for an organic surface modification of silica. Acetylene gas was used as the monomer for plasma polymerization in order to deposit a hydrocarbon layer onto the silica surface. The aim of this modification is to increase the compatibility between silica and the PP/POE blends matrix in order to improve the dispersion of the filler in the polymer matrix and to suppress the space charge accumulation by altering the charge trapping properties of these silica/PP/POE blends composites. The conditions for the deposition of the acetylene plasma-polymer onto the silica surface were optimized by analyzing the modification in terms of weight loss by thermogravimetry (TGA). X-ray photoelectron spectroscopy (XPS) and energy-dispersive X-ray fluorescence spectroscopy (EDX) measurements confirmed the presence of hydrocarbon compounds on the silica surface after plasma modification. The acetylene plasma modified silica with the highest deposition level was selected to be incorporated into the PP/POE blends matrix. X-ray diffraction (XRD) showed that there is no new crystal phase formation in the PP/POE blends nanocomposites after addition of the acetylene plasma modified silica. Differential scanning calorimetry results (DSC) show two melting peaks and two crystallization peaks of the PP/POE blends nanocomposites corresponding to the PP and POE domains. The improved dispersion of the silica after acetylene plasma modification in the PP/POE blends matrix was shown by means of SEM-EDX mapping. Thermally stimulated depolarization current (TSDC) measurements confirm that addition of the acetylene plasma modified silica affects the charge trapping density and decreases the amount of injected charges into PP/POE blends nanocomposites. This work shows that acetylene plasma modification of the silica surface is a promising route to tune charge trapping properties of PP/POE blend-based nanocomposites.

In this work, an isotactic polypropylene (PP) and a polyethylene-octene copolymer (POE) have been blended and injection-molded, obtaining solids and foamed samples with a relative density of 0.76. Different mold temperature and injection temperature were used. The Izod impact strength was measured. For solids, higher mold temperature increased the impact resistance, whereas in foams, the opposite trend was observed. In order to understand the reasons of this behavior, the morphology of the elastomeric phase, the crystalline morphology and the cellular structure have been studied. The presence of the elastomer near the skin in the case of high mold temperature can explain the improvement produced with a high mold temperature in solids. For foams, aspects as the elastomer coarsening in the core of the sample or the presence of a thicker solid skin are the critical parameters that justify the improved behavior of the materials produced with a lower mold temperature.

Conventional NMR pulse sequences record one spectrum per experiment, while spending most of the time waiting for the spin system to return to the equilibrium. As a result, a full set of multidimensional NMR experiments for biological macromolecules may take up to several months to complete. Here, we present a practical guide for setting up a new class of MAS solid-state NMR experiments (POE or polarization optimized experiments) that enable the simultaneous acquisition of multiple spectra of proteins, accelerating data acquisition. POE exploit the long-lived 15 N polarization of isotopically labeled proteins and enable one to obtain up to eight spectra, by concatenating classical NMR pulse sequences. This new strategy propels data throughput of solid-state NMR spectroscopy of fibers, microcrystalline preparations, as well as membrane proteins.

This work reports the first pure hydrocarbon thermoplastic polyolefin material with reversible shape memory effect under stress-free or very small external loading condition. A thermoplastic ethylene/1-octene diblock copolymer with designed chain microstructure was synthesized. The polyolefin material performed not only the conventional one-way multishape memory effects, but also a two-way reversible shape memory effect (RSME). The elongation and contraction induced by oriented crystallization with heating was confirmed as the mechanism of RSME without chemical cross-linking. This work demonstrated that the thermoplastic reversible shape memory could be achieved through careful design of chain microstructure, based on sole hydrocarbon materials such as ethylene-1-octene copolymer.

Objective: Conducting high-quality design research in a mental health setting presents significant challenges, limiting the availability of high-quality evidence to support design decisions for built environments. Here, we outline key approaches to overcoming these challenges., Background: In conducting a rigorous post-occupancy evaluation of a newly built mental health and addictions facility, St. Joseph's Healthcare, Hamilton, we identified a number of systematic barriers associated with conducting design research in mental health settings., Methods: Our approach to overcoming these barriers relied heavily upon (i) selecting established measures and methods with demonstrated efficacy in a mental health context, (ii) navigating institutional protocols designed to protect vulnerable members of this population, and (iii) designing innovative data collection strategies to increase participation in research by individuals with mental illness. Each of these approaches drew heavily on the expert knowledge of mental health settings and the experiences with mental health, facilities management, and research of a research team that was well integrated within the parent institution., Conclusions: Engaging multiple stakeholders (e.g., care providers, patients, ethics board, and hospital administrators) contributed their trust and support of the research. Traditionally, post-occupancy evaluation researchers are independent of the facilities they research, yet this is not an effective approach in mental health settings. We found that, in working toward solutions to the three obstacles we described, having team members who were well "networked" within the parent institution was necessary. This approach can turn "gatekeepers" into champions for patients' engagement in the research, which is essential in generating high-quality evidence., (© The Author(s) 2015.)

Magic angle spinning solid-state NMR (MAS ssNMR) spectroscopy is a powerful method for structure determination of biomacromolecules that are recalcitrant to crystallization (membrane proteins and fibrils). Conventional multidimensional ssNMR methods acquire one experiment at a time. This approach is time consuming and discards orphan (unused) spin operators. Relatively low sensitivity and poor resolution of protein samples require long acquisition times for multidimensional ssNMR experiments. Here, we describe our recent progress in the development of multiple acquisition solid-state NMR methods for protein structure determination. A family of experiments called Polarization Optimized Experiments (POE) were designed, in which we utilized the orphan spin operators that are discarded in classical multidimensional NMR experiments, recovering them to allow simultaneous acquisition of multiple 2D and 3D experiments, all while using conventional probes with spectrometers equipped with one receiver. Three strategies namely, DUMAS, MEIOSIS, and MAeSTOSO were used for the concatenation of various 2D and 3D experiments. These methods open up new avenues for reducing the acquisition times of multidimensional experiments for biomolecular ssNMR spectroscopy.

This chapter considers a neurological approach to analyzing the decadent and fantastic fictions of the French fin-de-siècle. It focuses on three texts whose depictions of male nervosism were influenced by Charles Baudelaire's biography of Edgar Allan Poe and by contemporary medical discourses, including those of Jean-Martin Charcot and George Miller Beard: Joris-Karl Huysmans' À Rebours (1884), Jules Lermina's Les Fous (1885), and Guy de Maupassant's Le Horlà (1885-1887). Although these authors were philosophically antipositivist and antimaterialist, they used scientific theories of neurasthenia, neurodegeneration, and visual hallucination to probe the frontiers between body and spirit, the known and the unknowable., (© 2013 Elsevier B.V. All rights reserved.)

Background: Laboratory ordering functions within computerized provider order entry (CPOE) systems typically support the display of electronic alert messages to improve test utilization or implement new ordering policies. However, alert strategies have been shown to vary considerably in their success and the characteristics contributing to an alert's success are poorly understood. Improved methodologies are needed to evaluate alerts and their mechanisms of action., Materials and Methods: Clinicians order inpatient and emergency department laboratory tests using our institutional CPOE system. We analyzed user interaction data captured by our CPOE system to evaluate how clinicians responded to an alert. We evaluated an alert designed to implement an institutional policy restricting the indications for ordering creatine kinase-MB (CKMB)., Results: Within 2 months of alert implementation, CKMB-associated searches declined by 79% with a corresponding decline in CKMB orders. Furthermore, while prior to alert implementation, clinicians searching for CKMB ultimately ordered this test 99% of the time, following implementation, only 60% of CKMB searches ultimately led to CKMB test orders. This difference presumably represents clinicians who reconsidered the need for CKMB in response to the alert, demonstrating the alert's just-in-time advisory capability. In addition, as clinicians repeatedly viewed the alert, there was a "dose-dependant" decrease in the fraction of searches without orders. This presumably reflects the alerting strategy's long-term educational component, as clinicians aware of the new policy will not search for CKMB when not indicated., Conclusions: Our analytic approach provides insight into the mechanism of a CPOE alert and demonstrates that alerts may act through a combination of just-in-time advice and longer term education. Use of this approach when implementing alerts may prove useful to improve the success of a given alerting strategy.

High-throughput functional proteomic technologies provide a way to quantify the expression of proteins of interest. Statistical inference centers on identifying the activation state of proteins and their patterns of molecular interaction formalized as dependence structure. Inference on dependence structure is particularly important when proteins are selected because they are part of a common molecular pathway. In that case, inference on dependence structure reveals properties of the underlying pathway. We propose a probability model that represents molecular interactions at the level of hidden binary latent variables that can be interpreted as indicators for active versus inactive states of the proteins. The proposed approach exploits available expert knowledge about the target pathway to define an informative prior on the hidden conditional dependence structure. An important feature of this prior is that it provides an instrument to explicitly anchor the model space to a set of interactions of interest, favoring a local search approach to model determination. We apply our model to reverse-phase protein array data from a study on acute myeloid leukemia. Our inference identifies relevant subpathways in relation to the unfolding of the biological process under study.