Genetic heterogeneity of pseudoxanthoma elasticum: the Chinese signature profile of ABCC6 and ENPP1 mutations.

Pseudoxanthoma elasticum (PXE), an autosomal recessive disorder characterized by ectopic mineralization, is caused by mutations in the ABCC6 gene. We examined clinically 29 Chinese PXE patients from unrelated families, so far the largest cohort of Asian PXE patients. In a subset of 22 patients, we sequenced ABCC6 and another candidate gene, ENPP1, and conducted pathogenicity analyses for each variant. We identified a total of 17 distinct mutations in ABCC6, 15 of them being, to our knowledge, previously unreported, including 5 frameshift and 10 missense variants. In addition, a missense mutation in combination with a recurrent nonsense mutation in ENPP1 was discovered in a pediatric PXE case. No cases with p.R1141X or del23-29 mutations, common in Caucasian patient populations, were identified. The 10 missense mutations in ABCC6 were expressed in the mouse liver via hydrodynamic tail-vein injections. One mutant protein showed cytoplasmic accumulation indicating abnormal subcellular trafficking, while the other nine mutants showed correct plasma membrane location. These nine mutations were further investigated for their pathogenicity using a recently developed zebrafish mRNA rescue assay. Minimal rescue of the morpholino-induced phenotype was achieved with eight of the nine mutant human ABCC6 mRNAs tested, implying pathogenicity. This study demonstrates that the Chinese PXE population harbors unique ABCC6 mutations. These genetic data have implications for allele-specific therapy currently being developed for PXE

Probing the non-Abelian fusion of a pair of Majorana zero modes

In this work, we perform real time simulations for probing the non-Abelian fusion of a pair of Majorana zero modes (MZMs). The nontrivial fusion outcomes can be either a vacuum, or an unpaired fermion, which reflect the underlying non-Abelian statistics. The two possible outcomes can cause different charge variations in the nearby probing quantum dot (QD), while the charge occupation in the dot is detected by a quantum point contact. In particular, we find that gradual fusion and gradual coupling of the MZMs to the QD (in nearly adiabatic switching-on limit) provide a simpler detection scheme than sudden coupling after fusion to infer the coexistence of two fusion outcomes, by measuring the occupation probability of the QD. For the scheme of sudden coupling (after fusion), we propose and analyze continuous weak measurement for the quantum oscillations of the QD occupancy. From the power spectrum of the measurement currents, one can identify the characteristic frequencies and infer thus the coexistence of the fusion outcomes.Comment: 7 pages, 5 figure

HEAD: HEtero-Assists Distillation for Heterogeneous Object Detectors

Conventional knowledge distillation (KD) methods for object detection mainly concentrate on homogeneous teacher-student detectors. However, the design of a lightweight detector for deployment is often significantly different from a high-capacity detector. Thus, we investigate KD among heterogeneous teacher-student pairs for a wide application. We observe that the core difficulty for heterogeneous KD (hetero-KD) is the significant semantic gap between the backbone features of heterogeneous detectors due to the different optimization manners. Conventional homogeneous KD (homo-KD) methods suffer from such a gap and are hard to directly obtain satisfactory performance for hetero-KD. In this paper, we propose the HEtero-Assists Distillation (HEAD) framework, leveraging heterogeneous detection heads as assistants to guide the optimization of the student detector to reduce this gap. In HEAD, the assistant is an additional detection head with the architecture homogeneous to the teacher head attached to the student backbone. Thus, a hetero-KD is transformed into a homo-KD, allowing efficient knowledge transfer from the teacher to the student. Moreover, we extend HEAD into a Teacher-Free HEAD (TF-HEAD) framework when a well-trained teacher detector is unavailable. Our method has achieved significant improvement compared to current detection KD methods. For example, on the MS-COCO dataset, TF-HEAD helps R18 RetinaNet achieve 33.9 mAP (+2.2), while HEAD further pushes the limit to 36.2 mAP (+4.5).Comment: ECCV 2022, Code: https://github.com/LutingWang/HEA

ZnO Tetrapods: Synthesis and Applications in Solar Cells

Zinc oxide (ZnO) tetrapods have received much interest due to their unique morphology, that is, four arms connected to one centre. Tetrapod networks possess the excellent electronic properties of the ZnO semiconductor, which is attractive for photoelectrode materials in energy-conversion devices because of their advantages in electron extraction and transportation. In this review, we have discussed recent advancements in the field of ZnO tetrapod synthesis, including vapour transport synthesis and the wet chemical method, together with their advantages and disadvantages in terms of morphology control and yield regulation. The developments and improvements in the applications of ZnO nanotetrapods in photovoltaics, including dye-sensitized solar cells and polymer solar cells, are also described. Our aim is to give readers a comprehensive and critical overview of this unique morphology of ZnO, including synthesis control and growth mechanism, and to understand the role of this particular morphology in the development of solar cells. The future research directions in ZnO tetrapods-based solar cell are also discussed

The Neurobase of ambiguity loss aversion about decision making

In our daily decision-making, there are two confusing problems: risk and ambiguity. Many psychological studies and neuroscience studies have shown that the prefrontal cortex (PFC) is an important neural mechanism for modulating the human brain in risk and ambiguity decision-making, especially the dorsolateral prefrontal cortex (DLPFC). We used transcranial direct current stimulation (tDCS) to reveal the causal relationship between the DLPFC and ambiguity decision-making. We design two experimental tasks involving ambiguity to gain and ambiguity to loss. The results of our study show that there is a significant effect on left DLPFC stimulation about ambiguity to loss, there is an insignificant effect on left DLPFC stimulation about ambiguity to gain, and there is an insignificant effect on right DLPFC stimulation about ambiguity to gain and ambiguity to loss. This result indicates that people are more sensitive to ambiguity loss than ambiguity gain. Further analysis found that the degree of participants’ attitudes toward ambiguity loss who received anodal simulation was lower than that who received sham stimulation across the left DLPFC, which means that the subjects had a strong ambiguity loss aversion after the participants received the anodal simulation of the left DLPFC

Youth online and their community's preparedness to protect them : mapping youth online social norms and community risk preparedness for online sexual exploitation and abuse of children (OSEAC) cases in the Philippines

Youth are increasingly online and so are those who seek to exploit and abuse them. This study explores the social norms of youth online and the risk awareness and preparedness of the Sorsogon City commu-nity for cases of Online Sexual Exploitation and Abuse of Children (OSEAC). A complementary mixed-methods approach was applied. A survey was distributed among students at the local national high school and received 407 responses. Two focus groups were conducted with a total of 49 youth. In-terviews were then conducted among a few selected key members in the community. The results re-vealed that the social norm for youth online includes befriending people online and meeting them in person. Youth are likely to be exposed to inappropriate content online. Youth have also become better at securing their privacy online. The community's risk awareness for OSEAC is low. Though the per-ceived harm of OSEAC is high, the community does not believe it is at-risk for OSEAC cases. Key ac-tors are recommended to develop comprehensive sexuality education modules and internet safety mod-els alongside targeted media interventions that can educate both the youth and the community based on current data and trends of youth online

Generating and stabilizing the GHZ state in circuit QED: Joint measurement, Zeno effect and feedback

In solid-state circuit QED system, we extend the previous study of generating and stabilizing two-qubit Bell state [Phys. Rev. A 82, 032335 (2010)], to three-qubit GHZ state. In dispersive regime, we employ the homodyne joint readout for multiple qubits to infer the state for further processing, and in particular use it to stabilize the state directly by means of an alternate-flip-interrupted Zeno (AFIZ) scheme. Moreover, the state-of-the-art feedback action based on the filtered current enables not only a deterministic generation of the pre-GHZ state in the initial stage, but also a fast recovery from the environment-caused degradation in the later stabilization process. We show that the proposed scheme can maintain the state with high fidelity if the efficient quantum measurement and rapid single-qubit rotations are available.Comment: 6 pages, 5 figure

Acquired cystic disease-associated renal cell carcinoma with PTCH1 mutation: a case report

Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is an extremely rare kidney tumor seen mainly in patients with end-stage renal disease. Currently, there are few reports on this type of tumor. We describe the case of a 58-year-old man who had been receiving peritoneal dialysis for more than nine years due to chronic renal insufficiency and uremia. One year after undergoing left renal clear cell renal cell carcinoma resection, a space-occupying lesion was found in the right kidney for which he underwent right nephrectomy. The histopathology of this tumor showed solid or tubular cell arrangements, with some areas of cyst formation. Vacuoles of varying sizes were present in the cytoplasm, and varying amounts of calcium oxalate crystals were found in the tumor cells or interstitium. The pathological diagnosis was ACD-RCC. Next-generation sequencing detected mutations in the PTCH1, MTOR, FAT1, SOS1, RECQL4, and CDC73 genes in the right renal tumor. This is a rare case of a patient with ACD-RCC in the right kidney and clear cell renal cell carcinoma in the left kidney. The findings suggest that mutations in PTCH1 associated with ACD-RCC may have acted as oncogenic drivers for the development of ACKD-RCC, together with providing insight into mechanisms underlying ACD-RCC development, as well as diagnostic and treatment options

Comparing the difference of adverse events with HER2 inhibitors: a study of the FDA adverse event reporting system (FAERS)

Aim and background: This study attempted to identify similarities and differences in adverse events (AEs) between human epidermal growth factor receptor 2 (HER2) inhibitors, especially those related to hemorrhagic events and nervous system disorders.Methods: This study summarized the types, frequencies, and system organ classes (SOCs) of AEs of HER2 inhibitors. The US Food and Drug Administration Adverse Event Reporting System (FAERS) data from January 2004 through March 2022 was collected and analyzed. Disproportionality analyses were conducted to detect AEs signals for every HER2 inhibitor. The chi-square test, Wilcoxon test, and descriptive analysis were used to compare the differences of AEs for specific SOCs or drugs.Results: A total of 47,899 AE reports were obtained for eight HER2 inhibitors. Trastuzumab-related AEs were reported in the highest number and combination of regimens. In monotherapy, trastuzumab had the highest reported rate of cardiac disorders-related AEs (24.0%). However, small-molecule drugs exceeded other drugs in the reported rates of AEs related to gastrointestinal disorders, metabolism and nutrition disorders. The highest reported rates of respiratory disorders (47.3%) and hematologic disorders (22.4%) were associated with treatment with trastuzumab deruxtecan (T-DXd). Patients treated with trastuzumab emtansine (TDM-1) had the highest reported rate (7.28%) of hemorrhagic events, especially intracranial haemorrhage events. In addition, patients treated with TDM-1 with concomitant thrombocytopenia were likely to experience hemorrhagic events compared to other HER2 inhibitors (p < 0.001). The median time to onset of intracranial haemorrhage associated with trastuzumab (0.5 months) and TDM-1 (0.75 months) was short. However, there was no significant difference in median time to onset intracranial haemorrhage between patients in different age groups or with different outcomes. Disproportionality analysis results reveal that cerebral haemorrhage is a positive signal associated with T-DXd and TDM-1. In addition, tucatinib was the drug with the highest rate of reported nervous system disorders (31.38%). Memory impairment (83 cases) is a positive signal for tucatinib.Conclusion: The types and reporting rates of AEs associated with different HER2 inhibitors vary across multiple systems. In addition, hemorrhagic events concomitant with TDM-1 treatment and nervous system disorders concomitant with tucatinib treatment may be worthy of attention

Comparison of variations detection between whole-genome amplification methods used in single-cell resequencing

Background: Single-cell resequencing (SCRS) provides many biomedical advances in variations detection at the single-cell level, but it currently relies on whole genome amplification (WGA). Three methods are commonly used for WGA: multiple displacement amplification (MDA), degenerate-oligonucleotide-primed PCR (DOP-PCR) and multiple annealing and looping-based amplification cycles (MALBAC). However, a comprehensive comparison of variations detection performance between these WGA methods has not yet been performed. Results: We systematically compared the advantages and disadvantages of different WGA methods, focusing particularly on variations detection. Low-coverage whole-genome sequencing revealed that DOP-PCR had the highest duplication ratio, but an even read distribution and the best reproducibility and accuracy for detection of copy-number variations (CNVs). However, MDA had significantly higher genome recovery sensitivity (~84 %) than DOP-PCR (~6 %) and MALBAC (~52 %) at high sequencing depth. MALBAC and MDA had comparable single-nucleotide variations detection efficiency, false-positive ratio, and allele drop-out ratio. We further demonstrated that SCRS data amplified by either MDA or MALBAC from a gastric cancer cell line could accurately detect gastric cancer CNVs with comparable sensitivity and specificity, including amplifications of 12p11.22 (KRAS) and 9p24.1 (JAK2, CD274, and PDCD1LG2). Conclusions: Our findings provide a comprehensive comparison of variations detection performance using SCRS amplified by different WGA methods. It will guide researchers to determine which WGA method is best suited to individual experimental needs at single-cell level