Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a broad spectrum of clinical presentations that can affect almost all organ systems. Lupus nephritis (LN) is a severe complication that affects approximately half of the systemic erythematosus lupus (SLE) patients, which significantly increases the morbidity and the mortality risk. LN is characterized by the accumulation of immune complexes, ultimately leading to renal failure. Aberrant activation of T cells plays a critical role in the pathogenesis of both SLE and LN and is involved in the production of inflammatory cytokines, the recruitment of inflammatory cells to the affected tissues and the co-stimulation of B cells. Calcineurin is a serine-threonine phosphatase that, as a consequence of the T cell hyperactivation, induces the production of inflammatory mediators. Moreover, calcineurin is also involved in the alterations of the podocyte phenotype, which contribute to proteinuria and kidney damage observed in LN patients. Therefore, calcineurin inhibitors have been postulated as a potential treatment strategy in LN, since they reduce T cell activation and promote podocyte cytoskeleton stabilization, both being key aspects in the development of LN. Here, we review the role of calcineurin in SLE and the latest findings about calcineurin inhibitors and their mechanisms of action in the treatment of LN. Full article

Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY karyotype and functioning testes. CAIS is caused by inactivating mutations in the androgen receptor gene (AR). It is organized in eight exons located on the X chromosome. Hundreds of genetic variants in the AR gene have been reported in CAIS. They are distributed throughout the gene with a preponderance located in the ligand-binding domain. CAIS mainly presents as primary amenorrhea in an adolescent female or as a bilateral inguinal/labial hernia containing testes in prepubertal children. Some issues regarding the management of females with CAIS remain poorly standardized (such as the follow-up of intact testes, the timing of gonadal removal and optimal hormone replacement therapy). Basic research will lead to the consideration of new issues to improve long-term well-being (such as bone health, immune and metabolic aspects and cardiovascular risk). An expert multidisciplinary approach is mandatory to increase the long-term quality of life of women with CAIS. Full article

To ensure the usability of parts made of fiber-reinforced polymers, a lifetime assessment has to be made in an early stage of the development process. To describe the whole life cycle of these parts, continuous simulation chains can be used. From production to the end of the service life, all influences are mapped virtually. The later material strength is already given after the manufacturing process due to the process dependent fiber alignment. To be able to describe this fiber orientation within the lifetime assessment, this paper presents an approach for model calibration and data set determination to consider the local micro-structure. Therefore, quasi-static and cyclic tests were performed on specimens with longitudinal and transversal fiber orientation. A supplementary failure analysis provides additional information about the local micro-structure. The local fiber orientation is determined with µCT (micro computer tomography)-measurements, correlated to the extraction positions of the specimen, and implemented in a dataset. With an attached lifetime calculation on a demonstrator, a major influence of the local micro-structure on the calculation results can be shown. Therefore, it is indispensable to consider the local fiber orientation in the data set determination of short fiber reinforced polymers. Full article

Nitrogen-doped and heteroatom multi-doped carbon materials are considered excellent metal-free catalysts, superior catalyst supports for transition metal particles and single metal atoms (single-atom catalysts), as well as efficient sorbents for gas- and liquid-phase substances. Acid-catalyzed sol–gel polycondensation of hydroxybenzenes with heterocyclic aldehydes yields cross-linked thermosetting resins in the form of porous organic polymers (i.e., organic gels). Depending on the utilized hydroxybenzene (e.g., phenol, resorcinol, phloroglucinol, etc.) and heterocyclic aldehyde variety of heteroatom-doped organic polymers can be produced. Upon pyrolysis, highly porous and heteroatom-doped carbons are obtained. Herein, polycondensation of phloroglucinol with imidazole-2-carboxaldehyde (and other, similar heterocyclic aldehydes with two heteroatoms in the aromatic ring) is utilized to obtain porous, N-doped organic and carbon gels with N-content of up to 16.5 and 12 wt.%, respectively. Utilization of a heterocyclic aldehyde with two different heteroatoms yields dually-doped carbon materials. Upon pyrolysis, the porous polymers yield ultramicroporous N-doped and N,S co-doped carbons with specific surface areas of up to 800 m²g⁻¹. The influence of the initial composition of reactants and the pyrolysis temperature on the structure and chemical composition of the final doped organic and carbon materials is studied in detail. Full article

For processes such as water injection in deep geothermal production, heat transfer and fluid flow are coupled and affect one another, which leads to numerous challenges in wellbore structure safety. Due to complicated wellbore structures, consisting of casing, cement sheaths, and formations under high temperature, pressure, and in situ stress, the effects of thermo-hydro-mechanical (THM) coupling are crucial for the instability control of geothermal wellbores. A THM-coupled model was developed to describe the thermal, fluid, and mechanical behavior of the casing, cement sheath, and geological environment around the geothermal wellbore. The results show that a significant disturbance of effective stress occurred mainly due to the excess pore pressure and temperature changes during cold water injection. The effective stress gradually propagated to the far-field and disrupted the integrity of the wellbore structure. A serious thermal stress concentration occurred at the junction of the cased-hole and open-hole section. When the temperature difference between the injected water and the formation was up to 160 °C, the maximum hoop tensile stress in the granite formation reached up to 43.7 MPa, as high as twice the tensile strength, which may increase the risk of collapse or rupture of the wellbore structure. The tensile radial stress, with a maximum of 31.9 MPa concentrated at the interface between the casing and cement sheath, can cause the debonding of the cementing sheath. This study provides a reference for both the prediction of THM responses and the design of drilling fluid density in geothermal development. Full article

2D WS₂ is a promising candidate for the next generation nanoelectronics, spintronics, valleytronics, and optoelectronics. However, the uncontrollably large-area growth of WS₂ nanosheets and their unsatisfactory performance of the photodetectors based on WS₂ hindered its applications. Here, we proposed a CVD method using tungstic acid as the precursors to grow WS₂ flakes. After being characterized by AFM, Raman, PL, and TEM, we found the as-grown WS₂ flakes were high-quality structures. Then the photodetectors based on the as-grown WS₂ were fabricated, which exhibited high responsivity (7.3 A W⁻¹), a fast response rate (a response time of 5 ms and a recovery time of 7 ms), prefect external quantum efficiency (EQE) (1814%), and remarkable detectivity (D*) (3.4 × 10¹² Jones). Our works provided a new CVD method to grow some high-quality WS₂ nanosheets. Full article

Dementia is characterized by a range of cognitive defects with impaired activities of daily living that have implications for patient oral health. Objectives. A case-control study was made of the impact of dementia upon oral health. A total of 152 patients were included: 69 with dementia and 83 controls from the region of Murcia (Spain). The Global Deterioration Scale (GDS) was used to classify the patients and an oral exploration was carried out. Odds ratios (ORs) and confidence intervals (CIs) were estimated using regression models. The patients with more severe disease were significantly more likely to have fewer natural teeth (OR 11.00, 95%CI 1.28–23.22; p = 0.001), a higher plaque index (p = 0.001), and a greater bleeding index (p = 0.001) than the control group. These findings suggest that older adults with dementia have deficient oral health. A higher bleeding index increases the risk of deterioration of cognitive function. The oral hygiene and health of older people with dementia need to be improved. Full article

Voltage control of standalone converters with LC filter is usually based on proportional-resonant or proportional-integral controllers, which often require further active damping methods to achieve stability. These solutions place design constraints in the selection of the closed-loop pole locations which limit the achievable bandwidth and increase the design complexity. In contrast, in state-space based controllers, the closed-loop poles can be placed freely through state feedback, which makes them particularly suitable for high order plants and/or low sampling frequencies. Among the modern control methods, direct pole placement is a simple technique that enables the establishment of a straightforward relationship between outcome and design, as opposed to more advanced approaches. This paper presents a discrete state-space voltage controller for standalone converters with LC output filter. The proposed method combines the direct pole placement technique with a virtual disturbance observer in order to compensate the effects produced by the load and model mismatches. The design process takes into account both the filter parameters and the sampling frequency, rendering the performance of the obtained controller independent of both. The result is a streamlined design procedure that leads to consistent outcomes for a wide range of plant parameter variations, requiring only one input: the desired closed-loop bandwidth. Full article

Here, we present the draft genome sequence of Pseudomonas sp. GC01, a cadmium-resistant Antarctic bacterium capable of biosynthesizing CdS fluorescent nanoparticles (quantum dots, QDs) employing a unique mechanism involving the production of methanethiol (MeSH) from methionine (Met). To explore the molecular/metabolic components involved in QDs biosynthesis, we conducted a comparative genomic analysis, searching for the genes related to cadmium resistance and sulfur metabolic pathways. The genome of Pseudomonas sp. GC01 has a 4,706,645 bp size with a 58.61% G+C content. Pseudomonas sp. GC01 possesses five genes related to cadmium transport/resistance, with three P-type ATPases (cadA, zntA, and pbrA) involved in Cd-secretion that could contribute to the extracellular biosynthesis of CdS QDs. Furthermore, it exhibits genes involved in sulfate assimilation, cysteine/methionine synthesis, and volatile sulfur compounds catabolic pathways. Regarding MeSH production from Met, Pseudomonas sp. GC01 lacks the genes E4.4.1.11 and megL for MeSH generation. Interestingly, despite the absence of these genes, Pseudomonas sp. GC01 produces high levels of MeSH. This is probably associated with the metC gene that also produces MeSH from Met in bacteria. This work is the first report of the potential genes involved in Cd resistance, sulfur metabolism, and the process of MeSH-dependent CdS QDs bioproduction in Pseudomonas spp. strains. Full article

Objective: To determine blood transfusion practices, risk factors, and outcomes associated with the use of blood products in the setting of the acute management of burn patients at the Victorian Adult Burn Service. Background: Patients with burn injuries have variable transfusion requirements, based on a multitude of factors. We reviewed all acute admissions to the Victorian Adult Burns Service (VABS) between 2011 and 2017: 1636 patients in total, of whom 948 had surgery and were the focus of our analysis. Method and results: Patient demographics, surgical management, transfusion details, and outcome parameters were collected and analyzed. A total of 175 patients out of the 948 who had surgery also had a blood transfusion, while 52% of transfusions occurred in the perioperative period. The median trigger haemoglobin in perioperative was 80mg/dl (IQR = 76–84.9 mg/dl), and in the non-perioperative setting was 77 mg/dl (IQR = 71.61–80.84 mg/dl). Age, gender, % total body surface area (TBSA) burn, number of surgeries, and intensive care unit and hospital length of stay were associated with transfusion. Conclusions: The use of blood transfusions is an essential component of the surgical management of major burns. As observed in our study, half of these transfusions are related to surgical procedures and may be influenced by the employment of blood conserving strategies. Furthermore, transfusion trigger levels in stable patients may be amenable to review and reduction. Risk adjusted analysis can support the implementation of blood transfusion as a useful quality indicator in burn care. Full article

In addition to formalized leadership roles within organizations, leadership can also influence members through informal channels. This work argues that multifamily residential buildings can be viewed as organizations and, as such, explores the influence that informal leaders can wield in shaping culture around the motivation for conserving energy. This work draws on qualitative fieldwork conducted in a Brooklyn cooperative building. Findings indicate that the study building benefitted from the leadership of a long-standing board member, which contributed to the implementation of a number of energy efficiency initiatives. Interestingly, this leadership also led to a culture of cost efficiency over environmental concern as the motivating force behind these initiatives. This narrative was well disseminated, with most residents reporting that the building does not have a culture of conservation, despite a strong energy efficiency leaning. Thus, this work posits that leadership can greatly shape perception and culture around energy but can also be leveraged to craft a more environmentally-motivated conservation culture. It also argues that leadership can be complementary to decentralized organizational structures, and that creative mechanisms in residential buildings can capitalize on both, allowing members at all levels of the organization more influence in shaping the building’s culture. Full article

Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii, strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn²⁺) ions, a decapeptide, and orthophosphate. Mn²⁺ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 10⁷ irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80–100% protection. Full article

Embracing sustainability in the 21st century entails developing environmental identity, so that attitudes towards energy sustainability result from the core values of one’s individual and social identity. This study aims to explore the shift in the formation of environmental identity and attitudes towards energy sustainability throughout the course of the two-year study period (2018–2020). A dataset of 8,677,961 tweets, Facebook posts and comments and 325,228 news articles was collected to carry out quantitative analysis of the distribution of the posts, likes, and comments. A correlation with media coverage of energy and green topics was sought to establish the impact of the media on public debate. A qualitative analysis of posts and tweets was carried out to establish dominant themes. The findings of the study reveal that both positive attitudes towards energy sustainability and environmental identity have been consolidated throughout the two-year study period. Social media users are not only increasingly interested in green issues but also produce more reactions towards posts related to sustainability topics. The results also suggest that sustainable values and green behavior are independent from the media coverage of current events and the perceived threat to one’s health from COVID-19. Social networking sites provide a context in which users not only reinforce their beliefs and values, but also mimic the behavior of other users, which leads to the formation of a social media identity bubble that reinforces shared identity—in this case, environmental identity. This study offers a multidisciplinary perspective on sustainable development that will be able to drive equitable energy security and environmental security. Full article

The flavoprotein CRYPTOCHROME (CRY) is now generally believed to be a magnetosensor, providing geomagnetic information via a quantum effect on a light-initiated radical pair reaction. Whilst there is considerable physical and behavioural data to support this view, the precise molecular basis of animal magnetosensitivity remains frustratingly unknown. A key reason for this is the difficulty in combining molecular and behavioural biological experiments with the sciences of magnetics and spin chemistry. In this review, we highlight work that has utilised the fruit fly, Drosophila melanogaster, which provides a highly tractable genetic model system that offers many advantages for the study of magnetosensitivity. Using this “living test-tube”, significant progress has been made in elucidating the molecular basis of CRY-dependent magnetosensitivity. Full article

Previous studies of human response to whole-body vibration demonstrated nonlinear softening behaviors with increasing vibration magnitudes. Most of these studies were conducted at relatively low vibration magnitudes of less than 3 m/s² root mean square (RMS), and not much knowledge is available to show if this softening behavior exists when humans are exposed to higher vibration magnitudes. In this work, 26 participants were transported in a supine position inside an army medical vehicle on a road that simulated field scenarios and were exposed to input acceleration magnitudes at 0.60, 0.98, 1.32, 3.25, 5.58, and 5.90 m/s² RMS. Motion response data were collected at the head, torso, and pelvis of the participants using inertial sensors. Transmissibility and coherence graphs were used to investigate the type of nonlinearity induced under these transport conditions. Participant responses showed softening behavior when the vibration magnitude increased from 0.60 to 0.98 to 1.32 m/s² RMS. However, this response behavior changed to stiffening when the vibration magnitude increased to 3.25, 5.58, and 5.90 m/s² RMS. In the stiffening range, the transmissibility of the torso transformed from two dominant peaks to a single peak, which may indicate a tonic muscle behavior. The resulting stiffening behaviors may be considered in the design of transport systems subject to rough terrains. Full article

A frequency-adaptable tuned mass damper (FATMD) using metal cushions as tuneable stiffness components is presented. The dynamic properties of the cushions with respect to stiffness and damping are investigated experimentally in this context. The natural frequency of the experimental FATMD is found to be dependent on the precompression of the metal cushions, which behave like nonlinear springs, yielding an adjustable frequency range from 67 to 826 Hz. As the precompression is increased, the stiffness increases while the damping characteristics decrease, the effect of which was quantified using a viscous mass damper model as a first approximation. Measurements have been carried out under five different excitation amplitudes to investigate the amplitude dependency of the resonance frequency. The FATMD was largely unaffected by changes in input amplitude. It was concluded that metal cushions show great potential for use in FATMDs, surpassing the utility of elastomers, especially with respect to their temperature stability. Full article

Looked-after children are exposed to significant developmental trauma which may impact their identity development. Discourses of vulnerability and maladaptation often surround this group, while care-leavers often self-identify as survivors. The role of culture in identity formation is also well documented, and cultural socialisation is linked to psychological adjustment and wellbeing. Despite this, little research has explored identity development in black and minority ethnic (BAME) care-leavers. Interpretative Phenomenological Analysis is used to analyse eight semi-structured interviews with BAME care-leavers about their experience of identity development. Three superordinate themes were developed: My journey—how I became me; Identity as a process—the processes that support identity development; and who am I—how I see myself now. Participants’ identity development was adaptive in the context of surviving significant disruption and trauma. Findings are discussed with reference to previous research and limitations are considered. Clinical implications include the need to address additional barriers to positive self-identity faced by BAME care leavers, the importance of acknowledging care-leaver identity as adaptive and embodying a trauma-informed approach to working with this group. Further research into how care-leavers experience their cultural identity is needed. Full article