106GBaud (200G PAM4) CWDM EML for 800G/1.6T Optical Networks and AI Applications

We report ultrahigh speed 106GBaud (200G PAM4) electro-absorption modulated laser (EML) for 800G and 1.6T optical transmission. Four CWDM EMLs of 1271, 1291, 1311 and 1331nm in 800G FR4 optical transceivers show clear eye diagram after 2km. Our 106GBaud EMLs show high bandwidth, high extinction ratio, low threshold current and high power, making it a suitable source laser for 800G/1.6T and AI applications.&nbsp

Phosphorylation at Ser473 regulates heterochromatin protein 1 binding and corepressor function of TIF1beta/KAP1

<p>Abstract</p> <p>Background</p> <p>As an epigenetic regulator, the transcriptional intermediary factor 1β (TIF1β)/KAP1/TRIM28) has been linked to gene expression and chromatin remodeling at specific loci by association with members of the heterochromatin protein 1 (HP1) family and various other chromatin factors. The interaction between TIF1β and HP1 is crucial for heterochromatin formation and maintenance. The HP1-box, PXVXL, of TIF1β is responsible for its interaction with HP1. However, the underlying mechanism of how the interaction is regulated remains poorly understood.</p> <p>Results</p> <p>This work demonstrates that TIF1β is phosphorylated on Ser473, the alteration of which is dynamically associated with cell cycle progression and functionally linked to transcriptional regulation. Phosphorylation of TIF1β/Ser473 coincides with the induction of cell cycle gene <it>cyclin A2 </it>at the S-phase. Interestingly, chromatin immunoprecipitation demonstrated that the promoter of <it>cyclin A2 </it>gene is occupied by TIF1β and that such occupancy is inversely correlated with Ser473 phosphorylation. Additionally, when HP1β was co-expressed with TIF1β/S473A, but not TIF1β/S473E, the colocalization of TIF1β/S473A and HP1β to the promoters of <it>Cdc2 </it>and <it>Cdc25A </it>was enhanced. Non-phosphorylated TIF1β/Ser473 allowed greater TIF1β association with the regulatory regions and the consequent repression of these genes. Consistent with possible inhibition of TIF1β's corepressor function, the phosphorylation of the Ser473 residue, which is located near the HP1-interacting PXVXL motif, compromised the formation of TIF1β-HP1 complex. Finally, we found that the phosphorylation of TIF1β/Ser473 is mediated by the PKCδ pathway and is closely linked to cell proliferation.</p> <p>Conclusion</p> <p>The modulation of HP1β-TIF1β interaction through the phosphorylation/de-phosphorylation of TIF1β/Ser473 may constitute a molecular switch that regulates the expression of particular genes. Higher levels of phosphorylated TIF1β/Ser473 may be associated with the expression of key regulatory genes for cell cycle progression and the proliferation of cells.</p

Flux tunable graphene-based superconducting quantum circuits coupled to 3D cavity

Correlation between transmon and its composite Josephson junctions (JJ) plays an important role in designing new types of superconducting qubits based on quantum materials. It is desirable to have a type of device that not only allows exploration for use in quantum information processing but also probing intrinsic properties in the composite JJs. Here, we construct a flux-tunable 3D transmon-type superconducting quantum circuit made of graphene as a proof-of-concept prototype device. This 3D transmon-type device not only enables coupling to 3D cavities for microwave probes but also permits DC transport measurements on the same device, providing useful connections between transmon properties and critical currents associated with JJ's properties. We have demonstrated how flux-modulation in cavity frequency and DC critical current can be correlated under the influence of Fraunhofer pattern of JJs in an asymmetric SQUID. The correlation analysis was further extended to link the flux-modulated transmon properties, such as flux-tunability in qubit and cavity frequencies, with SQUID symmetry analysis based on DC measurements. Our study paves the way towards integrating novel materials for exploration of new types of quantum devices for future technology while probing underlying physics in the composite materials

Various criteria in the evaluation of biomedical named entity recognition

BACKGROUND: Text mining in the biomedical domain is receiving increasing attention. A key component of this process is named entity recognition (NER). Generally speaking, two annotated corpora, GENIA and GENETAG, are most frequently used for training and testing biomedical named entity recognition (Bio-NER) systems. JNLPBA and BioCreAtIvE are two major Bio-NER tasks using these corpora. Both tasks take different approaches to corpus annotation and use different matching criteria to evaluate system performance. This paper details these differences and describes alternative criteria. We then examine the impact of different criteria and annotation schemes on system performance by retesting systems participated in the above two tasks. RESULTS: To analyze the difference between JNLPBA's and BioCreAtIvE's evaluation, we conduct Experiment 1 to evaluate the top four JNLPBA systems using BioCreAtIvE's classification scheme. We then compare them with the top four BioCreAtIvE systems. Among them, three systems participated in both tasks, and each has an F-score lower on JNLPBA than on BioCreAtIvE. In Experiment 2, we apply hypothesis testing and correlation coefficient to find alternatives to BioCreAtIvE's evaluation scheme. It shows that right-match and left-match criteria have no significant difference with BioCreAtIvE. In Experiment 3, we propose a customized relaxed-match criterion that uses right match and merges JNLPBA's five NE classes into two, which achieves an F-score of 81.5%. In Experiment 4, we evaluate a range of five matching criteria from loose to strict on the top JNLPBA system and examine the percentage of false negatives. Our experiment gives the relative change in precision, recall and F-score as matching criteria are relaxed. CONCLUSION: In many applications, biomedical NEs could have several acceptable tags, which might just differ in their left or right boundaries. However, most corpora annotate only one of them. In our experiment, we found that right match and left match can be appropriate alternatives to JNLPBA and BioCreAtIvE's matching criteria. In addition, our relaxed-match criterion demonstrates that users can define their own relaxed criteria that correspond more realistically to their application requirements

A panel of tumor markers, calreticulin, annexin A2, and annexin A3 in upper tract urothelial carcinoma identified by proteomic and immunological analysis

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a tumor with sizable metastases and local recurrence. It has a worse prognosis than bladder cancer. This study was designed to investigate the urinary potential tumor markers of UTUC. METHODS: Between January 2008 and January 2009, urine was sampled from 13 patients with UTUC and 20 healthy adults. The current study identified biomarkers for UTUC using non-fixed volume stepwise weak anion exchange chromatography for fractionation of urine protein prior to two-dimensional gel electrophoresis. RESULTS: Fifty five differential proteins have been determined by comparing with the 2-DE maps of the urine of UTUC patients and those of healthy people. Western blotting analysis and immunohistochemistry of tumor tissues and normal tissues from patients with UTUC were carried out to further verify five possible UTUC biomarkers, including zinc-alpha-2-glycoprotein, calreticulin, annexin A2, annexin A3 and haptoglobin. The data of western blot and immunohistochemical analysis are consistent with the 2-DE data. Combined the experimental data in the urine and in tumor tissues collected from patients with UTUC, the crucial over-expressed proteins are calreticulin, annexin A2, and annexin A3. CONCLUSIONS: Calreticulin, annexin A2, and annexin A3 are very likely a panel of biomarkers with potential value for UTUC diagnosis

FTO Obesity Variant Circuitry and Adipocyte Browning in Humans

Background Genomewide association studies can be used to identify disease-relevant genomic regions, but interpretation of the data is challenging. The FTO region harbors the strongest genetic association with obesity, yet the mechanistic basis of this association remains elusive. Methods We examined epigenomic data, allelic activity, motif conservation, regulator expression, and gene coexpression patterns, with the aim of dissecting the regulatory circuitry and mechanistic basis of the association between the FTO region and obesity. We validated our predictions with the use of directed perturbations in samples from patients and from mice and with endogenous CRISPR–Cas9 genome editing in samples from patients. Results Our data indicate that the FTO allele associated with obesity represses mitochondrial thermogenesis in adipocyte precursor cells in a tissue-autonomous manner. The rs1421085 T-to-C single-nucleotide variant disrupts a conserved motif for the ARID5B repressor, which leads to derepression of a potent preadipocyte enhancer and a doubling of IRX3 and IRX5 expression during early adipocyte differentiation. This results in a cell-autonomous developmental shift from energy-dissipating beige (brite) adipocytes to energy-storing white adipocytes, with a reduction in mitochondrial thermogenesis by a factor of 5, as well as an increase in lipid storage. Inhibition of Irx3 in adipose tissue in mice reduced body weight and increased energy dissipation without a change in physical activity or appetite. Knockdown of IRX3 or IRX5 in primary adipocytes from participants with the risk allele restored thermogenesis, increasing it by a factor of 7, and overexpression of these genes had the opposite effect in adipocytes from nonrisk-allele carriers. Repair of the ARID5B motif by CRISPR–Cas9 editing of rs1421085 in primary adipocytes from a patient with the risk allele restored IRX3 and IRX5 repression, activated browning expression programs, and restored thermogenesis, increasing it by a factor of 7. Conclusions Our results point to a pathway for adipocyte thermogenesis regulation involving ARID5B, rs1421085, IRX3, and IRX5, which, when manipulated, had pronounced pro-obesity and anti-obesity effects. (Funded by the German Research Center for Environmental Health and others.)National Institutes of Health (U.S.) (R01HG004037)National Institutes of Health (U.S.) (R01GM113708)National Institutes of Health (U.S.) (R01HG008155)National Institutes of Health (U.S.) (RC1HG005334

Thrombomodulin Regulates Keratinocyte Differentiation and Promotes Wound Healing

The membrane glycoprotein thrombomodulin (TM) has been implicated in keratinocyte differentiation and wound healing, but its specific function remains undetermined. The epidermis-specific TM knockout mice were generated to investigate the function of TM in these biological processes. Primary cultured keratinocytes obtained from TMlox/lox; K5-Cre mice, in which TM expression was abrogated, underwent abnormal differentiation in response to calcium induction. Poor epidermal differentiation, as evidenced by downregulation of the terminal differentiation markers loricrin and filaggrin, was observed in TMlox/lox; K5-Cre mice. Silencing TM expression in human epithelial cells impaired calcium-induced extracellular signal–regulated kinase pathway activation and subsequent keratinocyte differentiation. Compared with wild-type mice, the cell spreading area and wound closure rate were lower in keratinocytes from TMlox/lox; K5-Cre mice. In addition, the lower density of neovascularization and smaller area of hyperproliferative epithelium contributed to slower wound healing in TMlox/lox; K5-Cre mice than in wild-type mice. Local administration of recombinant TM (rTM) accelerated healing rates in the TM-null skin. These data suggest that TM has a critical role in skin differentiation and wound healing. Furthermore, rTM may hold therapeutic potential for the treatment of nonhealing chronic wounds