Metal–organic frameworks in proton-exchange membrane for intermediate-to-high-temperature fuel-cell applications: a review

A proton-exchange membrane (PEM) is a vital component in fuel cells as a solid electrolyte that conducts ions. The high cost and degradation of Nafion® membrane in low-temperature fuel cells limits the technology’s commercialization. The development of intermediate (IT-PEMFCs) to high-temperature (HT-PEMFCs) fuel cells operating within the range of 80–200 °C has made progress over the last few decades, and improvements in water management addressing the issues of low-temperature PEMFCs have been observed. However, these types of PEM fuel cells (IT-PEMFCs and HT-PEMFCs) still face considerable challenges, such as unsatisfactory performance stability at high temperatures. Particularly, in HT-PEMFC, despite the high acid doping level (ADL) in membranes as a potential means to improve proton conductivity, high ADL decreases the membrane’s mechanical stability. Recently, metal–organic frameworks (MOFs) have achieved satisfactory results in applications of PEM modification. This manuscript reviews the development in applying MOFs in improving the properties of composite membranes in IT- and HT-PEMFCs by using SPEEK and PBI, respectively. The synthesis strategies using MOFs in the PEM are discussed together with the electrochemical properties obtained. The success of incorporating of MOFs into PEMs could shed light on the synthesis of new-generation IT- and HT-PEMFCs, which could improve several properties such as mechanical and thermal stability, oxidative stability, and acid-retention capacity

Fabrication of light-weighted acoustic absorbers made of natural fiber composites via additive manufacturing

Synthetic fiber is still considered the best sound absorptive material. However, due to the health concern of synthetic fiber usage, researchers are trying to find another viable alternative. A microperforated panel (MPP) is a promising alternative that relies on the concept of a Helmholtz resonator for sound absorption. MPP possessed excellent acoustic resistance and a considerable range of absorption bandwidth. In this paper, MPP made of natural fiber composite was fabricated and its acoustic absorption was measured using a two-microphone impedance tube method as per ISO 10534-2 standard. Later, the tensile strength of the fabricated acoustic absorbers was measured using an Instron Universal Testing Machine as per ASTM D638. The idea of employing additive manufacturing, better known as the 3D printing technique, is proposed to produce lightweight MPP. The 3D printing technique provides design freedom and is less tedious in creating complex and light structures. The 3D printing technique has various important parameters, and infill density is one of the parameters. It was found that the reduction of infill density leads to a decrease of the MPP’s mass and thus, slightly affects the resonance frequency of the MPP, still within the mid-frequency spectrum. It was also noted that the increment of air gap thickness leads to the shifting of MPP’s resonance frequency to a lower frequency range. The tensile strength of the 3D printed samples decreases with a decrease in infill density. A sample with an infill density of 100% has the highest tensile strength of 22 MPa, and a sample with an infill density of 20% has the lowest tensile strength of 12 MPa

Performance analysis of photovoltaic passive heat storage system with microencapsulated paraffin wax for thermoelectric generation

The depletion of non-renewable energy sources and negative effects towards the environment push research towards the widespread adoption of renewable energy sources such as solar energy. The main drawback of solar panels is that temperatures above 27°C will result in an efficiency drop of 0.1-0.5%/°C. In previous studies, usage of photovoltaic thermal (PVT) systems was mainly for the purpose of heating water, warming buildings, and drying crops. This research will focus on the usage of a standalone PVT and thermoelectric generator (TEG) system whereby it uses heat extracted from the PVT system for thermoelectric generation. A passive standalone PVT-TEG system design with microencapsulated paraffin wax as a phase change material (PCM) as a heat storage medium was created. The heat stored in the PCM is used as a heat source for thermoelectric generation. To extract the heat from the PV panel, an aluminum heatsink underneath the PV panel is used as a heat absorber to passively extract heat without external power sources. This setup reduces the surface temperature by 22.7°C. Transient thermal analysis and thermoelectric simulation of the system was conducted through Computational Fluid Dynamics (CFD) using ANSYS 2019 software. The error recorded between the experimental and simulation results was 4.2%. This proposed system panel successfully increased the electrical efficiency of the PV panel by approximately 12.8%, where the overall electrical power produced shows a significant increase from 7.7W to 17.7W

Adjunctive mood stabilizer treatment for hospitalized schizophrenia patients: Asia psychotropic prescripton study (2001-2008)

Recent studies indicate relatively high international rates of adjunctive psychotropic medication, including mood stabilizers, for patients with schizophrenia. Since such treatments are little studied in Asia, we examined the frequency of mood-stabilizer use and its clinical correlates among hospitalized Asian patients diagnosed with schizophrenia in 2001-2008. We evaluated usage rates of mood stabilizers with antipsychotic drugs, and associated factors, for in-patients diagnosed with DSM-IV schizophrenia in 2001, 2004 and 2008 in nine Asian regions: China, Hong Kong, India, Korea, Japan, Malaysia, Taiwan, Thailand, and Singapore. Overall, mood stabilizers were given to 20.4% (n=1377/6761) of hospitalized schizophrenia patients, with increased usage over time. Mood-stabilizer use was significantly and independently associated in multivariate logistic modeling with: aggressive behaviour, disorganized speech, year sampled (2008 vs. earlier), multiple hospitalizations, less negative symptoms, younger age, with regional variation (Japan, Hong Kong, Singapore>Taiwan or China). Co-prescription of adjunctive mood stabilizers with antipsychotics for hospitalized Asian schizophrenia patients increased over the past decade, and was associated with specific clinical characteristics. This practice parallels findings in other countries and illustrates ongoing tension between evidence-based practice vs. individualized, empirical treatment of psychotic disorders.published_or_final_versio

Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.

One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Upfront autologous haematopoietic stem-cell transplantation versus carfilzomib–cyclophosphamide–dexamethasone consolidation with carfilzomib maintenance in patients with newly diagnosed multiple myeloma in England and Wales (CARDAMON): a randomised, phase 2, non-inferiority trial

Background: Standard-of-care treatment for patients with newly diagnosed multiple myeloma is bortezomib-based induction followed by high-dose melphalan and autologous haematopoietic stem-cell transplantation (HSCT) and lenalidomide maintenance. We aimed to evaluate whether an immunomodulatory-free carfilzomib-based induction, consolidation, and maintenance protocol without autologous HSCT was non-inferior to the same induction regimen followed by autologous HSCT and maintenance. Methods: CARDAMON is a randomised, open-label, phase 2 trial in 19 hospitals in England and Wales, UK. Newly diagnosed, transplantation-eligible patients with multiple myeloma aged 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2 received four 28-day cycles of carfilzomib (56 mg/m2 intravenously on days 1, 2, 8, 9, 15, and 16), cyclophosphamide (500 mg orally on days 1, 8, and 15), and dexamethasone (40 mg orally on days 1, 8, 15, and 22; KCd), followed by peripheral blood stem cell mobilisation. Patients with at least a partial response were randomly assigned (1:1) to either high-dose melphalan and autologous HSCT or four cycles of KCd. All randomised patients received 18 cycles of carfilzomib maintenance (56 mg/m2 intravenously on days 1, 8, and 15). The primary outcomes were the proportion of patients with at least a very good partial response after induction and difference in progression-free survival rate at 2 years from randomisation (non-inferiority margin 10%), both assessed by intention to treat. Safety was assessed in all patients who started treatment. The trial is registered with ClinicalTrials.gov (NCT02315716); recruitment is complete and all patients are in follow-up. Findings: Between June 16, 2015, and July 8, 2019, 281 patients were enrolled, with 218 proceeding to randomisation (109 assigned to the KCd consolidation group [99 of whom completed consolidation] and 109 to the HSCT group [104 of whom underwent transplantation]). A further seven patients withdrew before initiation of carfilzomib maintenance (two in the KCd consolidation group vs five in the HSCT group). Median age was 59 years (IQR 52 to 64); 166 (59%) of 281 patients were male and 115 (41%) were female. 152 (71%) of 214 patients with known ethnicity were White, 37 (17%) were Black, 18 (8%) were Asian, 5 (2%) identified as Mixed, and 2 (1%) identified as other. Median follow-up from randomisation was 40·2 months (IQR 32·7 to 51·8). After induction, 162 (57·7%; 95% CI 51·6 to 63·5) of 281 patients had at least a very good partial response. The 2-year progression-free survival was 75% (95% CI 65 to 82) in the HSCT group versus 68% (95% CI 58 to 76) in the KCd group (difference –7·2%, 70% CI –11·1 to –2·8), exceeding the non-inferiority margin. The most common grade 3–4 events during KCd induction and consolidation were lymphocytopenia (72 [26%] of 278 patients who started induction; 15 [14%] of 109 patients who started consolidation) and infection (50 [18%] of 278 for induction; 15 [14%] of 109 for consolidation), and during carfilzomib maintenance were hypertension (20 [21%] of 97 patients in the KCd consolidation group vs 23 [23%] of 99 patients in the HSCT group) and infection (16 [16%] of 97 patients vs 25 [25%] of 99). Treatment-related serious adverse events at any point during the trial were reported in 109 (39%) of 278 patients who started induction, with infections (80 [29%]) being the most common. Treatment-emergent deaths were reported in five (2%) of 278 patients during induction (three from infection, one from cardiac event, and one from renal failure) and one of 99 patients during maintenance after autologous HSCT (oesophageal carcinoma). Interpretation: KCd did not meet the criteria for non-inferiority compared with autologous HSCT, but the marginal difference in progression-free survival suggests that further studies are warranted to explore deferred autologous HSCT in some subgroups, such as individuals who are MRD negative after induction. Funding: Cancer Research UK and Amgen