We describe the performance of high bandwidth-density silicon photonic based integrated circuits (SiPh ICs) that enable the first fully functional photonic engine (PE) module co-packaged with an ...Ethernet switch. We demonstrate the 1.6 Tbps SiPh transmitter (Tx) IC that integrates on-die all the lasers, micro ring modulators, monitor photodetectors, spot size converters, and V-grooves that are needed to support sixteen 106.25 Gbps PAM4 optical transmit channels. This SiPh Tx, together with discrete receiver (Rx) SiPh ICs, enabled an 800 Gbps PE. The PE is designed to allow up to sixteen modules to be co-packaged around a high-bandwidth switch ASIC. The PE test results described in this article were obtained using sixteen 53.125 Gbps electrical channels that were multiplexed to drive eight simultaneously operating 106.25 Gbps optical channels. We report DR4 IEEE standards compliant high-speed optical eye performance as well as full link operation. Post-FEC error-free operation over temperature and over extended time duration is demonstrated on all channels.
We report the observation of photoluminescence (PL) and electroluminescence (EL) from a-SiN x :H/SiO 2 multilayer structures. The luminescence intensity is improved by a thermal annealing process. A ...new method of effective current injection has been implemented for electrical excitation of these structures whereby the electric field is applied parallel to the plane of the multilayers. Such structures are promising as Si based light sources for Si optoelectronics technology.
A homemade spectral shift fluorescence microscope (SSFM) is coupled with a spectrometer to record the spectral images of specimens based on the emission wavelength. Here a reliable diagnosis of ...neoplasia is achieved according to the spectral fluorescence properties of ex-vivo skin tissues after rhodamine6G (Rd6G) staining. It is shown that certain spectral shifts occur for nonmelanoma/melanoma lesions against normal/benign nevus, leading to spectral micrographs. In fact, there is a strong correlation between the emission wavelength and the sort of skin lesions, mainly due to the Rd6G interaction with the mitochondria of cancerous cells. The normal tissues generally enjoy a significant red shift regarding the laser line (37 nm). Conversely, plenty of fluorophores are conjugated to unhealthy cells giving rise to a relative blue shift i.e., typically SCC (6 nm), BCC (14 nm), and melanoma (19 nm) against healthy tissues. In other words, the redshift takes place with respect to the excitation wavelength i.e., melanoma (18 nm), BCC (23 nm), and SCC (31 nm) with respect to the laser line. Consequently, three data sets are available in the form of micrographs, addressing pixel-by-pixel signal intensity, emission wavelength, and fluorophore concentration of specimens for prompt diagnosis.
CRISPR-Cas systems protect bacteria and archaea from phages and other mobile genetic elements, which use small anti-CRISPR (Acr) proteins to overcome CRISPR-Cas immunity. Because Acrs are challenging ...to identify, their natural diversity and impact on microbial ecosystems are underappreciated. To overcome this discovery bottleneck, we developed a high-throughput functional selection to isolate ten DNA fragments from human oral and fecal metagenomes that inhibit
Cas9 (SpyCas9) in
. The most potent Acr from this set, AcrIIA11, was recovered from a
phage. We found that AcrIIA11 inhibits SpyCas9 in bacteria and in human cells. AcrIIA11 homologs are distributed across diverse bacteria; many distantly-related homologs inhibit both SpyCas9 and a divergent Cas9 from
. We find that AcrIIA11 antagonizes SpyCas9 using a different mechanism than other previously characterized Type II-A Acrs. Our study highlights the power of functional selection to uncover widespread Cas9 inhibitors within diverse microbiomes.
Background
Germline autosomal dominant and autosomal recessive mutations in PERP, encoding p53 effector related to PMP‐22 (PERP), a component of epidermal desmosomes, have been associated with a ...spectrum of keratodermas. Monoallelic nonsense mutations cause Olmsted syndrome with severe periorificial keratoderma and palmoplantar keratoderma (PPK). Biallelic recessive frameshift and missense mutations are associated with milder forms of the disease, including generalised erythrokeratoderma and PPK.
Objectives
To add new insights into the genotype‐phenotype correlations as a consequence of PERP mutations and to provide a comprehensive review of the literature.
Methods
Among 26 previously unresolved families within a cohort of 180 extended Iranian families with syndromic or non‐syndromic ichthyosis, two families with shared clinical features were examined by whole‐exome sequencing and genome‐wide homozygosity mapping. Mycological and dermatopathological studies were performed to further characterise their atypical phenotypic presentations.
Results
In two unrelated multiplex consanguineous families affected by ichthyosis, two novel biallelic PERP variants, NM_022121.5, c.89T > C, p.Leu30Pro and c.466G > C, p.Gly156Arg, located inside of genomic homozygosity regions of the probands were detected. Interestingly, some patients had areas of scaly psoriasiform plaques on the background of generalised ichthyosis that appeared during active cutaneous fungal infections. Mycological examinations of these lesions revealed infections caused by Candida albicans, Epidermophyton floccosum, or Trichophyton rubrum. Histopathology of the psoriasiform lesions shared some features with psoriasis, which when combined with clinical presentation, led to incorrect diagnosis of guttate psoriasis or pustular psoriasis.
Conclusions
PERP variants in ichthyosis patients can confer susceptibility to recalcitrant cutaneous fungal infections. Additionally, patients with episodic psoriasiform dermatitis in the setting of keratoderma should be considered for PERP genotyping and cutaneous fungal examinations.
Aims Our primary aim was to establish the proportion of female orthopaedic consultants who perform arthroplasty via cases submitted to the National Joint Registry (NJR), which covers England, Wales, ...Northern Ireland, the Isle of Man, and Guernsey. Secondary aims included comparing time since specialist registration, private practice participation, and number of hospitals worked in between male and female surgeons. Methods Publicly available data from the NJR was extracted on the types of arthroplasty performed by each surgeon, and the number of procedures of each type undertaken. Each surgeon was cross-referenced with the General Medical Council (GMC) website, using GMC number to extract surgeon demographic data. These included sex, region of practice, and dates of full and specialist registration. Results Of 2,895 surgeons contributing to the NJR in 2023, 102 (4%) were female. The highest proportions of female surgeons were among those who performed elbow (n = 25; 5%), shoulder (n = 24; 4%), and ankle (n = 8; 4%) arthroplasty. Hip (n = 66; 3%) and knee arthroplasty (n = 39; 2%) had the lowest female representation. Female surgeons had been practising for a median of 10.4 years since specialist registration compared to 13.7 years for males (p < 0.001). Northern Ireland was the region with the highest proportion of female arthroplasty surgeons (8%). A greater proportion of male surgeons worked in private practice (63% vs 24%; p < 0.001) and in multiple hospitals (74% vs 40%; p < 0.001). Conclusion Only 4% of surgeons currently contributing cases to the NJR are female, with the highest proportion performing elbow arthroplasty (5%). Female orthopaedic surgeons in the NJR are earlier in their careers than male surgeons, and are less involved in private practice. There is a wide geographical variation in the proportion of female arthroplasty surgeons. Cite this article: Bone Jt Open 2024;5(8):637–643.
A chronic low-grade inflammation, originating in the adipose tissue, is considered a driver of obesity-associated insulin resistance. Macrophage composition in white adipose tissue is believed to ...contribute to the pathogenesis of metabolic diseases, but a detailed characterization of pro- and anti-inflammatory adipose tissue macrophages (ATMs) in human obesity and how they are distributed in visceral- and subcutaneous adipose depots is lacking. In this study, we performed a surface proteome screening of pro- and anti-inflammatory ATMs in both subcutaneous- (SAT) and visceral adipose tissue (VAT) and evaluated their relationship with systemic insulin resistance. From the proteomics screen we found novel surface proteins specific to M1-like- and M2-like macrophages, and we identified depot-specific immunophenotypes in SAT and VAT. Furthermore, we found that insulin resistance, assessed by HOMA-IR, was positively associated with a relative increase in pro-inflammatory M1-like macrophages in both SAT and VAT.
19F magnetic resonance (MR) based detection coupled with well‐designed inorganic systems shows promise in biological investigations. Two proof‐of‐concept inorganic probes that exploit a novel ...mechanism for 19F MR sensing based on converting from low‐spin (S=0) to high‐spin (S=1) Ni2+ are reported. Activation of diamagnetic NiL1 and NiL2 by light or β‐galactosidase, respectively, converts them into paramagnetic NiL0, which displays a single 19F NMR peak shifted by >35 ppm with accelerated relaxation rates. This spin‐state switch is effective for sensing light or enzyme expression in live cells using 19F MR spectroscopy and imaging that differentiate signals based on chemical shift and relaxation times. This general inorganic scaffold has potential for developing agents that can sense analytes ranging from ions to enzymes, opening up diverse possibilities for 19F MR based biosensing.
Two proof‐of‐concept inorganic probes that exploit a novel mechanism for 19F magnetic resonance sensing based on converting from low‐spin (S=0) to high‐spin (S=1) Ni2+ are reported. Activation of diamagnetic NiL1 and NiL2 by light or β‐galactosidase, respectively, converts them into paramagnetic NiL0, which displays a single 19F NMR peak shifted by >35 ppm. This spin‐state switch is effective for sensing light or enzyme expression in live cells.
Incorporating sustainability into Concrete-Filled Steel Tubular (CFST) columns' optimization can enhance efficiency and sustainability in construction. Discrepancies in international standards for ...ultimate load capacity computation in compact CFST columns under eccentric loading, particularly with lightweight high-strength concrete, pose challenges. This research compile a dataset of compact CFST columns, evaluating design codes (AISC 360-16, Eurocode 4) against experimental results. Besides, a comprehensive finite-element model predicts compact CFST column performance, investigating axial force-moment (P-M) interaction behavior with respect to the material strength ratio (fy/fc′). In the second phase of the study, an ANN model, incorporating input parameters, estimates axial load capacity, facilitating multi-objective optimization for optimal CFST column geometry. The results confirmed that Eurocode 4 outperforms AISC 360-16 in experimental axial capacity predictions (Nuc/Nuc,theoretical) where, the mean and standard deviation for Eurocode 4 were estimated at 1.07 and 0.22, respectively, compared to 1.21 and 0.29 for AISC 360-16. Besides, statistical metrics confirm the precision of the ANN model, particularly with high-strength concrete, promising efficiency in future computational intelligence-based structural design platforms.
Holothuria scabra
is the most valued and cultured tropical sea cucumber, given the great demand of this species for human consumption. However, despite its ecological and economic relevance, little ...is known regarding its immune responses under thermal stress. Here, the main goal was to study the response of sea cucumbers to temperature stress, assessing sub-organismal alterations and acclimation capacities of juveniles to temperature changes. After changing temperature (1 °C/day) for 6 days, organisms were exposed to temperature conditions of 21 °C (cold), 27 °C (control), and 33 °C (warm) over a 30 day period. At each 15-day interval (T0, T15, and T30), six replicates per condition were killed for biochemical analysis. Immune responses were addressed by studying the activity of phenoloxidase (PO) and prophenoloxidase (ProPO) in the coelomic fluid. Antioxidant defence responses—catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GR) enzymatic activities—were measured in the muscle and respiratory tree tissues, whereas oxidative damage was evaluated by measuring levels of superoxide radicals (ROS), DNA-strand breaks and lipid peroxidation (LPO). Juvenile
H. scabra
increased SOD and PO activities when temperature was elevated, and revealed low levels of ROS and damage in both cold and warm treatments throughout the experiment, confirming the organism’s moderate thermal stress. After the short acclimation period, the immune and antioxidant responses prevented damage and maintained homeostasis. This multi-biomarker approach highlights its usefulness to monitor the health of
H. scabra
and to gain insight concerning the use of this high-valued species in global-scale aquaculture from different temperature regions.
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