The emergence of rapidly expanding infectious diseases such as coronavirus (COVID-19) demands effective biosensors that can promptly detect and recognize the pathogens. Field-effect transistors based ...on semiconducting two-dimensional (2D) materials (2D-FETs) have been identified as potential candidates for rapid and label-free sensing applications. This is because any perturbation of such atomically thin 2D channels can significantly impact their electronic transport properties. Here, we report the use of FET based on semiconducting transition metal dichalcogenide (TMDC) WSe2 as a promising biosensor for the rapid and sensitive detection of SARS-CoV-2 in vitro. The sensor is created by functionalizing the WSe2 monolayers with a monoclonal antibody against the SARS-CoV-2 spike protein and exhibits a detection limit of down to 25 fg/μL in 0.01X phosphate-buffered saline (PBS). Comprehensive theoretical and experimental studies, including density functional theory, atomic force microscopy, Raman and photoluminescence spectroscopies, and electronic transport properties, were performed to characterize and explain the device performance. The results demonstrate that TMDC-based 2D-FETs can potentially serve as sensitive and selective biosensors for the rapid detection of infectious diseases.
Low-temperature Ag sintering provides a lead-free die attachment method that is compatible with high-temperature (300 °C) power electronics applications. The reliability of sintered Ag die attach for ...Si and SiC die has been studied on both thick film substrates for lower current power applications and direct bond copper (DBC) substrates for higher current power applications. Pressureless and low-pressure sintering were evaluated. Sintering with low pressure yielded lower porosity (15-17%) versus pressureless sintering (~30%). Reliability was evaluated with thermal aging (300 °C) and thermal cycling (-55 °C to + 300 °C) tests. Reliable Ag sintered die attach was achieved with assemblies having Ag-bearing surface finishes on both the die and the substrate. In contrast, the shear strength after 300 °C aging was greatly reduced when Au metallization was used either on the die or on substrate surface. In some cases, low-pressure sintering delayed the failure of the sintered Ag die attach to Au surfaces when aged at 300 °C compared to the pressureless sintering. The reliability with Pd-containing substrate metallizations was intermediate between Ag and Au metallizations. The thermal cycle reliability on DBC substrates was limited by failure at the Cu-to-alumina interface over the wide temperature range, while on the thick film substrates high adhesion was maintained after 1000 thermal cycles.
This article distinguishes the obligation of States to 'facilitate' and 'protect' the right of peaceful assembly under Article 21 of the International Covenant on Civil and Political Rights (iccpr) ...from State practices that rather seek to 'manage' or 'control' its exercise. Focusing on the protection of public assemblies in the Asia-Pacific region and drawing principally on the UN Human Rights Committee's assembly jurisprudence and its Concluding Observations on State reports, it emphasises the critical importance of the language in which State obligations are framed and understood. Many domestic laws over-regulate the right of assembly by creating broad discretionary powers, impermissible grounds of restriction, bureaucratic procedures and onerous liabilities. Such laws reinforce a police ego-image premised on the pernicious logic of 'management' and encourage preventive policing tactics that fundamentally undermine the right of peaceful assembly.
We have designed a traveling-wave parametric amplifier based on quantum phase-slip junctions. This amplifier has a LC-ladder nonlinear transmission line structure, and acts as a dual to the Josephson ...traveling-wave parametric amplifier. We use WRspice simulations to design and analyze the quantum phase-slip junction-based traveling-wave parametric amplifier. Our simulations capture parametric amplification by demonstrating frequency mixing, signal gain, and generation of an idler tone. In additional simulations, we control various circuit parameters: the quantum phase-slip junctions, critical voltage, quantum phase-slip junction count, and bias voltage. We report and discuss these parameters' effects on the amplifier's signal gain. We compare these performance metrics with those from simulations of a typical Josephson traveling-wave parametric amplifier.
Alternative splicing and alternative polyadenylation (APA) of pre-mRNAs greatly contribute to transcriptome diversity, coding capacity of a genome and gene regulatory mechanisms in eukaryotes. ...Second-generation sequencing technologies have been extensively used to analyse transcriptomes. However, a major limitation of short-read data is that it is difficult to accurately predict full-length splice isoforms. Here we sequenced the sorghum transcriptome using Pacific Biosciences single-molecule real-time long-read isoform sequencing and developed a pipeline called TAPIS (Transcriptome Analysis Pipeline for Isoform Sequencing) to identify full-length splice isoforms and APA sites. Our analysis reveals transcriptome-wide full-length isoforms at an unprecedented scale with over 11,000 novel splice isoforms. Additionally, we uncover APA of ∼11,000 expressed genes and more than 2,100 novel genes. These results greatly enhance sorghum gene annotations and aid in studying gene regulation in this important bioenergy crop. The TAPIS pipeline will serve as a useful tool to analyse Iso-Seq data from any organism.
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Conductive and electroactive polymers have the potential to enhance engineered cardiac tissue function. In this study, an interpenetrating network of the electrically-conductive ...polymer polypyrrole (PPy) was grown within a matrix of flexible polycaprolactone (PCL) and evaluated as a platform for directing the formation of functional cardiac cell sheets. PCL films were either treated with sodium hydroxide to render them more hydrophilic and enhance cell adhesion or rendered electroactive with PPy grown via chemical polymerization yielding PPy–PCL that had a resistivity of 1.0±0.4kΩcm, which is similar to native cardiac tissue. Both PCL and PPy–PCL films supported cardiomyocyte attachment; increasing the duration of PCL pre-treatment with NaOH resulted in higher numbers of adherent cardiomyocytes per unit area, generating cell densities which were more similar to those on PPy–PCL films (1568±126cellsmm−2, 2880±439cellsmm−2, 3623±456cellsmm−2 for PCL with 0, 24, 48h of NaOH pretreatment, respectively; 2434±166cellsmm−2 for PPy–PCL). When cardiomyocytes were cultured on the electrically-conductive PPy–PCL, more cells were observed to have peripheral localization of the gap junction protein connexin-43 (Cx43) as compared to cells on NaOH-treated PCL (60.3±4.3% vs. 46.6±5.7%). Cx43 gene expression remained unchanged between materials. Importantly, the velocity of calcium wave propagation was faster and calcium transient duration was shorter for cardiomyocyte monolayers on PPy–PCL (1612±143μm/s, 910±63ms) relative to cells on PCL (1129±247μm/s, 1130±20ms). In summary, PPy–PCL has demonstrated suitability as an electrically-conductive substrate for culture of cardiomyocytes, yielding enhanced functional properties; results encourage further development of conductive substrates for use in differentiation of stem cell-derived cardiomyocytes and cardiac tissue engineering applications.
Current conductive materials for use in cardiac regeneration are limited by cytotoxicity or cost in implementation. In this manuscript, we demonstrate for the first time the application of a biocompatible, conductive polypyrrole–polycaprolactone film as a platform for culturing cardiomyocytes for cardiac regeneration. This study shows that the novel conductive film is capable of enhancing cell–cell communication through the formation of connexin-43, leading to higher velocities for calcium wave propagation and reduced calcium transient durations among cultured cardiomyocyte monolayers. Furthermore, it was demonstrated that chemical modification of polycaprolactone through alkaline-mediated hydrolysis increased overall cardiomyocyte adhesion. The results of this study provide insight into how cardiomyocytes interact with conductive substrates and will inform future research efforts to enhance the functional properties of cardiomyocytes, which is critical for their use in pharmaceutical testing and cell therapy.
HOXA Transcript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1) is a conserved long non-coding RNA (lncRNA) involved in myeloid and neural differentiation that is deregulated in acute myeloid leukemia ...and other cancers. Previous studies focused on the nuclear unspliced HOTAIRM1 transcript, however cytoplasmic splice variants exist whose roles have remained unknown. Here, we report novel functions of HOTAIRM1 in the kidney. HOTAIRM1 transcripts are induced during renal lineage differentiation of embryonic stem cells and required for expression of specific renal differentiation genes. We show that the major HOTAIRM1 transcript in differentiated cells is the spliced cytoplasmic HM1-3 isoform and that HM1-3 is downregulated in >90% of clear cell renal cell carcinomas (ccRCCs). Knockdown of HM1-3 in renal cells deregulates hypoxia-responsive and angiogenic genes, including ANGPTL4. Furthermore, HOTAIRM1 transcripts are downregulated by hypoxia-mimetic stress and knockdown of the cytoplasmic HM1-3 isoform in normoxic cells post-transcriptionally induces Hypoxia-Inducible Factor 1α (HIF1α) protein, a key activator of ANGPTL4. Our results demonstrate the pervasive downregulation of the specific HOTAIRM1 cytoplasmic isoform HM1-3 in ccRCC and suggest possible roles of HOTAIRM1 in kidney differentiation and suppression of HIF1-dependent angiogenic pathways.
•New role of HOTAIRM1 in the kidney.•Spliced cytoplasmic isoform of HOTAIRM1 is downregulated in ccRCC.•Expression of HOTAIRM1 is associated with renal lineage differentiation.•HOTAIRM1 expression is inhibited by hypoxic stress signaling.•HOTAIRM1 downregulates Hypoxia-Inducible Factor 1α.
Abstract Objective To report the technique and the outcome for the repair of pelvic fractures in cats using external skeletal fixation (ESF). Study design Retrospective case series. Animals ...Client‐owned cats ( n = 125). Methods Medical records of cats with pelvic fractures, treated with an ESF between June 2001 and June 2009, were reviewed. Preoperative, immediate postoperative, and more than 4 weeks’ postoperative radiographs were compared. Clinical examination was performed 4 to 9 weeks following surgery. Longer term follow up (4 to 80 months) was conducted by client questionnaire. Results No intraoperative complications occurred. There was no change in the pelvic canal width observed on follow‐up radiographs ( p = .16). Implant loosening was noted on follow‐up radiographs in 16/125 (13%) of cases, and 67/803 (8%) pins were palpably loose at the time of frame removal. The mean time to frame removal was 37 ± 9 days. No long‐term complications were reported. Long‐term mean mobility score was 95 ± 5 and median lameness was 0 (range: 0–2). Conclusion An ESF may be successfully applied for the stabilization of various pelvic fractures in cats. Clinical significance The application of an ESF for the management of pelvic fractures in cats provides good outcomes.
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