Role of phase change materials in backfilling of flat-panels ground heat exchanger

The behaviour of a multi-source heat pump system coupled with phase change materials (PCMs) is discussed in this manuscript, as based on selected data collected during one-year testing at the TekneHub Laboratory of the University of Ferrara (Italy), as a synergic prototype setup of two European projects: IDEAS, an H2020 project, and CLIWAX, an EFDR project. Three geothermal loops of novel shallow FlatPanels ground heat exchangers (GHX) provide the coupling of a water-to-water heat pump with the ground, as backfilled with sand, a mixture of sand and granules with paraffins and containers filled in with hydrated salts. Furthermore, two hybrid photovoltaic panels and a dry-cooler complete the exploitable thermal sources landscape. Finally, a control unit manages all the elements for the exploitation of the different thermal sources. How the increased underground thermal energy storage is driven by PCMs has been investigated by means of specific tests, and compared with the standard case of backfilling sand. Results confirm that PCMs can compensate peak loads occurring during hard weather conditions. Good performances of the multi-source heat pump were found, with a winter coefficient of performance always higher than 5. Finally, the application of PCM in summer should be preferred in climatic zones with hot summers and cold winters, With evidence, latent heat, thermal conductivity and melting point of PCMs should be tuned accordingly to the energy requirements and the local ground thermal conditions. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

CDK12/13 promote splicing of proximal introns by enhancing the interaction between RNA polymerase II and the splicing factor SF3B1

Transcription-associated cyclin-dependent kinases (CDKs) regulate the transcription cycle through sequential phosphorylation of RNA polymerase II (RNAPII). Herein, we report that dual inhibition of the highly homologous CDK12 and CDK13 impairs splicing of a subset of promoter-proximal introns characterized by weak 3 ' splice sites located at larger distance from the branchpoint. Nascent transcript analysis indicated that these introns are selectively retained upon pharmacological inhibition of CDK12/13 with respect to downstream introns of the same pre-mRNAs. Retention of these introns was also triggered by pladienolide B (PdB), an inhibitor of the U2 small nucelar ribonucleoprotein (snRNP) factor SF3B1 that recognizes the branchpoint. CDK12/13 activity promotes the interaction of SF3B1 with RNAPII phosphorylated on Ser2, and disruption of this interaction by treatment with the CDK12/13 inhibitor THZ531 impairs the association of SF3B1 with chromatin and its recruitment to the 3 ' splice site of these introns. Furthermore, by using suboptimal doses of THZ531 and PdB, we describe a synergic effect of these inhibitors on intron retention, cell cycle progression and cancer cell survival. These findings uncover a mechanism by which CDK12/13 couple RNA transcription and processing, and suggest that combined inhibition of these kinases and the spliceosome represents an exploitable anticancer approach

Highly bactericidal Ag nanoparticle films obtained by cluster beam deposition

Abstract The recent emergence of bacterial pathogens resistant to most or all available antibiotics is among the major global public health problems. As indirect transmission through contaminated surfaces is a main route of dissemination for most of such pathogens, the implementation of effective antimicrobial surfaces has been advocated as a promising approach for their containment, especially in the hospital settings. However, traditional wet synthesis methods of nanoparticle-based antimicrobial materials leave a number of key points open for metal surfaces: such as adhesion to the surface and nanoparticle coalescence. Here we demonstrate an alternative route, i.e. supersonic cluster beam deposition, to obtain antimicrobial Ag nanoparticle films deposited directly on surfaces. The synthesized films are simple to produce with controlled density and thickness, are stable over time, and are shown to be highly bactericidal against major Gram positive and Gram negative bacterial pathogens, including extensively drug-resistant strains. From the Clinical Editor The use of silver nanoparticle in health care is getting more widespread. The authors here describe the technique of cluster beam deposition for spraying silver on surfaces used in health care sectors. This may open a new avenue for future anti-bacterial coatings

Spontaneous Reversion of Clinical Conditions Measuring the Risk Profile of the Individual : from Frailty to Mild Cognitive Impairment

The number of people living with disabilities worldwide is rapidly growing due to a longer life expectancy and the subsequent increasing burden of chronic diseases. The need of developing and implementing effective strategies aimed at delaying or preventing disability has been repeatedly underlined and is currently the main focus of several health-care policies. In this scenario, a special attention is addressed to the identification of specific clinical conditions measuring the risk profile of the individual of developing an overt disability and other negative outcomes. These risk profiles can indeed become promising targets for developing and implementing preventive interventions. When the disabling cascade is fully established, in fact, the reversing/attenuating the process becomes more challenging. However, the exact nature of these relatively new constructs is not yet sufficiently clear, and several related issues remain poorly explored. In particular, these entities tend to be considered as unequivocally prodromal stages of a future disease, neglecting and underestimating their fluctuations/transitions over time and their potential to clinically improve/revert. This unbalanced judgment did probably contribute to an ambiguous and biased use of these conditions. Considering them as an early stage of an unavoidable future disease, in fact, determined a tendency to start a targeted intervention as if in presence of the disease itself, with the subsequent risk of over-diagnosis and over-treatment. In the present article, we discuss the dynamics underlying the reversion from a clinical at-risk condition to normality and its implications, specifically focusing on the examples of frailty and mild cognitive impairment

The Neuroprotective Effects of 17β-Estradiol Pretreatment in a Model of Neonatal Hippocampal Injury Induced by Trimethyltin

Hippocampal dysfunction plays a central role in neurodevelopmental disorders, resulting in severe impairment of cognitive abilities, including memory and learning. On this basis, developmental studies represent an important tool both to understanding the cellular and molecular phenomena underlying early hippocampal damage and to study possible therapeutic interventions, that may modify the progression of neuronal death. Given the modulatory role played by 17β-estradiol (E2) on hippocampal functions and its neuroprotective properties, the present study investigates the effects of pretreatment with E2 in a model of neonatal hippocampal injury obtained by trimethyltin (TMT) administration, characterized by neuronal loss in CA1 and CA3 subfields and astroglial and microglial activation. At post-natal days (P)5 and P6 animals received E2 administration (0.2 mg/kg/die i.p.) or vehicle. At P7 they received a single dose of TMT (6.5 mg/kg i.p.) and were sacrificed 72 h (P10) or 7 days after TMT treatment (P14). Our findings indicate that pretreatment with E2 exerts a protective effect against hippocampal damage induced by TMT administration early in development, reducing the extent of neuronal death in the CA1 subfield, inducing the activation of genes involved in neuroprotection, lowering the neuroinflammatory response and restoring neuropeptide Y- and parvalbumin- expression, which is impaired in the early phases of TMT-induced damage. Our data support the efficacy of estrogen-based neuroprotective approaches to counteract early occurring hippocampal damage in the developing hippocampus

A Heat Pump-Based Multi-source Renewable Energy System for the Building Air Conditioning: The IDEAS Project Experience

The current paper presents the state-of-the-art of the ongoing IDEAS research project, funded under the Horizon 2020 EU framework programme. The project involves fourteen partners from six European countries and proposes a multi-source cost-effective renewable energy system for the decarbonisation of the building envelope. The system features a radiant floor fed by a heat pump for the building thermal management. The heat pump can exploit sun, air, and/or ground as thermal sources through the use of photovoltaic/thermal solar panels, air heat exchangers, and shallow ground flat-panel heat exchangers. Thermal energy storage is achieved by means of phase change materials spread along several system components, such as: radiant floor to increase its thermal inertia, solar panels for cooling purposes, ground to enhance soil thermal capacity. Within the project framework, a small- scale building, featuring a plethora of sensors for test purposes, and two large-scale buildings are meant to be equipped with the renewable energy system proposed. The small- scale building is currently in operation, and the first results are discussed in the present work. Preliminary data suggest that while multi-source systems coupled with heat pumps are particularly effective, it is complex to obtain suitable thermal energy storages on urban scale

EWS splicing regulation contributes to balancing Foxp1 isoforms required for neuronal differentiation

Alternative splicing is a key regulatory process underlying the amplification of genomic information and the expansion of proteomic diversity, particularly in brain. Here, we identify the Ewing sarcoma protein (EWS) as a new player of alternative splicing regulation during neuronal differentiation. Knockdown of EWS in neuronal progenitor cells leads to premature differentiation. Transcriptome profiling of EWS-depleted cells revealed global changes in splicing regulation. Bioinformatic analyses and biochemical experiments demonstrated that EWS regulates alternative exons in a position-dependent fashion. Notably, several EWS-regulated splicing events are physiologically modulated during neuronal differentiation and EWS depletion in neuronal precursors anticipates the splicing-pattern of mature neurons. Among other targets, we found that EWS controls the alternative splicing of the forkhead family transcription factor FOXP1, a pivotal transcriptional regulator of neuronal differentiation, possibly contributing to the switch of gene expression underlying the neuronal differentiation program

Pleiotropic effects of anti-thrombotic therapies: have direct oral anticoagulants any anti-inflammatory effect?

Direct oral anticoagulants (DOACs) are currently recommended by European guidelines as the first line therapy for both stroke prevention in patients with atrial fibrillation (AF) and the prevention and the treatment of venous thromboembolism (VTE). Recently, it has been speculated that DOACs have anti-inflammatory capabilities in reducing the abnormal release of pro-inflammatory factors in addition to inhibiting the activation of factor X or factor II of the coagulation cascade. However, this hypothesis is based on limited pathophysiological data with small sample size, often on in vitro studies. Real-world, in vivo, and large clinical data are scarce. The aim of the present study was the evaluation of the possible anti-inflammatory and anti-proliferative effects of DOACs treatment in a cohort of patients affected by AF or VTE, by analyzing an extensive panel of cytokines and molecules involved in the process of vascular and tissue remodeling. Our data evidenced that DOACs treatment is associated with variations in systemic inflammation markers and in metalloproteinases. Further studies with larger number of patients are required to confirm these data