Search

Thin-film transistor (TFT) applications of GeSn have attracted attention as a means of improving the performance of electronic devices. Based on our advanced solid-phase crystallization and TFT process technologies, we comprehensively studied the relationship between the film properties and TFT characteristics of polycrystalline GeSn. The initial Sn concentration ${x}_{\mathrm {i}}$ significantly changed the crystal and electrical properties of the GeSn layer. Excess Sn ( ${x}_{\mathrm {i}} \ge 4.5$ %) precipitated in GeSn and degraded its properties, whereas the appropriate amount of Sn effectively passivated defects in Ge and reduced the density of defect-induced acceptors and grain boundary traps while maintaining a high Hall hole mobility (>200 cm 2 V −1 s −1 ). The performance of the accumulation-mode TFTs fabricated under 400 °C also strongly depended on $\boldsymbol {x}_{\mathrm {i}}$ , achieving both a high field-effect mobility (170 cm 2 V −1 s −1 ) and on/off ratio (10 3 ) at ${x}_{\mathrm {i}} = 1.6$ %. This performance was shown to be the highest among Ge-based TFTs with grain boundaries in the channel.

The molecular subtypes of pancreatic cancer (PC), either classical/progenitor-like or basal/squamous-like, are currently a major topic of research because of their direct association with clinical outcomes. Some transcription factors (TFs) have been reported to be associated with these subtypes. However, the mechanisms by which these molecular signatures of PCs are established remain unknown. Epigenetic regulatory processes, supported by dynamic changes in the chromatin structure, are essential for transcriptional profiles. Previously, we reported the importance of open chromatin profiles in the biological features and transcriptional status of PCs. Here, we aimed to analyze the relationships between three-dimensional (3D) genome structures and the molecular subtypes of human PCs using Hi-C analysis. We observed a correlation of the specific elements of 3D genome modules, including compartments, topologically associating domains, and enhancer-promoter loops, with the expression of related genes. We focused on HNF1B, a TF that is implicated in the progenitor subtype. Forced expression of HNF1B in squamous-type PC organoids induced the upregulation and downregulation of genes associated with progenitor and squamous subtypes, respectively. Long-range genomic interactions induced by HNF1B were accompanied by compartment modulation and H3K27ac redistribution. We also found that these HNF1B-induced changes in subtype-related gene expression required an intrinsically disordered region, suggesting a possible involvement of phase separation in compartment modulation. Thus, mapping of 3D structural changes induced by TFs, such as HNF1B, may become a useful resource for further understanding the molecular features of PCs.

Of the schwannomas that arise from the parapharyngeal space, those in the high cervical region are particularly invasive, requiring mandibular dissection. Because these tumors are benign, however, excessive surgical invasion and postoperative neurological complications should be avoided. Postoperative dropout symptoms may be avoided by intracapsular extraction, including nerve integrity monitoring (NIM) and narrow-band imaging (NBI). Video laryngoscopy surgery is reported to be useful for transoral resection of pharyngeal and laryngeal tumors. This report describes the transoral removal of a giant schwannoma located in the high cervical region from a 74-years-old man using a surgical support device without mandibular dissection. The tumor was located on the right lateral pharyngeal wall and extended from the upper oropharynx to the hypopharynx while compressing the epiglottis to the skull base. No separation was observed between the internal jugular vein and the internal carotid artery. The tumor was diagnosed as a schwannoma with no malignancy on the basis of the histology of a core needle biopsy (CNB), and was completely and safely removed endoscopically using NIM and NBI, with no need for an external incision or mandibular dissection. This case illustrates that even a huge sympathetic schwannoma located in the parapharyngeal space at a high cervical position can be excised transorally using video-laryngoscopic surgery (TOVS) without mandibular dissection.

The incidence of central nervous system (CNS) metastases in patients with anaplastic lymphoma kinase (ALK) fusion gene-positive (ALK+) non-small cell lung cancer (NSCLC) is high, ranging from approximately 20%-70%. Although ALK inhibitors (ALKis) are generally effective for CNS metastases in patients with ALK+ NSCLC, relapse with CNS metastases is frequently observed. A 37-year-old woman with a high level of carcinoembryonic antigen was diagnosed with right lung adenocarcinoma (pathological stage IIIA) and underwent right lower lobectomy. Despite the administration of postoperative chemotherapy, her carcinoembryonic antigen (CEA) level remained elevated. Although crizotinib was administered due to the positivity for ALK fusion, brain metastases appeared at 19.0 months after the start of treatment. Treatment with alectinib following crizotinib resulted in the complete disappearance of brain metastases. However, brain metastases relapsed, and meningeal dissemination appeared at 38.3 months after the start of treatment with alectinib. Although ceritinib, brigatinib, and alectinib rechallenge were attempted, the CNS lesions worsened. Lorlatinib was then administered, resulting in the normalization of the CEA level (4.5 ng/ml) 4.1 months after the start of lorlatinib. The brain metastases and meningeal dissemination almost disappeared. The overall time from the start of crizotinib to lorlatinib is 89.5 months at present, and the patient continues to be treated with lorlatinib without relapse. Lorlatinib was effective in this case with brain metastases and meningeal dissemination after resistance to first- and second-generation ALKis. Appropriate sequential treatment with first-, second- and third-generation ALKis can lead to a long-term survival in ALK+ patients with brain metastases and meningeal dissemination.

The conventional picking robots suffered from low picking throughput due to a large amount of computation of the object-pose-estimation algorithm which is called iterative-closest-point (ICP) algorithm. This article presents an field-programmable gate array (FPGA)-based ICP accelerator, which achieves 11.7-times-faster object-pose estimation by a picking robot compared with the state-of-the-art technique based on K-D-tree k -nearest neighbor (NN) search and four-core CPU. To accelerate the ICP, both algorithm-level and hardware-level techniques have been proposed and developed. The former is a hierarchical-graph-based k -NN search enabling simultaneous acquisition of plural neighboring points. The latter is a sorting-network-based circuit implemented on an system on a chip (SoC)-FPGA. In addition, dynamic structural reconfiguration between the two key functionalities (graph generation and nearest neighbor search) is explored by utilizing the partial reconfiguration capability of FPGA to save the required hardware resource. Experiments of the proposed FPGA-based ICP accelerator using Amazon Picking Challenge data sets have confirmed that the object-pose estimation by ICP takes only 0.72 s at the power consumption of 4.2 W.

Accurate diagnosis of the disease extension of cholangiocarcinoma (CCA) is often difficult in clinical practice. The diagnostic yield of conventional pre-operative imaging or endoscopic procedures is sometimes insufficient for the evaluation of longitudinal spreading of CCA. Here we investigated the usefulness of 5-aminolevulinic acid (5-ALA) for the pre- or intra-operative diagnosis of CCA, using patient-derived organoids.Four CCA- and two adjacent tissue-derived organoids were established. After 5-ALA treatment, we assessed their photodynamic activity using fluorescence microscopy.CCA organoids established from different patients showed diverse morphology in contrast to monolayer structures of non-tumor organoids, and had the ability to form subcutaneous tumors in immunodeficient mice. CCA organoids demonstrated remarkably high photodynamic activity based on higher accumulation of protoporphyrin IX as a metabolite of 5-ALA compared to non-tumor organoids (40-71% vs. 4%, respectively). Importantly, cancer cell-specific high photodynamic activity distinguished the organoids originated from biliary stenotic lesions from those of non-stenotic lesions in a CCA patient. The high photodynamic activity did not depend on the expression profile of heme biosynthesis genes.Distinct 5-ALA-based photodynamic activity could have diagnostic potential for the discrimination of CCA from non-tumor tissues.

Countermeasures against Zika virus (ZIKV), including vaccines, are frequently tested in nonhuman primates (NHP). Macaque models are important for understanding how ZIKV infections impact human pregnancy due to similarities in placental development. The lack of consistent adverse pregnancy outcomes in ZIKV-affected pregnancies poses a challenge in macaque studies where group sizes are often small (4–8 animals). Studies in small animal models suggest that African-lineage Zika viruses can cause more frequent and severe fetal outcomes. No adverse outcomes were observed in macaques exposed to 1x104 PFU (low dose) of African-lineage ZIKV at gestational day (GD) 45. Here, we exposed eight pregnant rhesus macaques to 1x108 PFU (high dose) of African-lineage ZIKV at GD 45 to test the hypothesis that adverse pregnancy outcomes are dose-dependent. Three of eight pregnancies ended prematurely with fetal death. ZIKV was detected in both fetal and placental tissues from all cases of early fetal loss. Further refinements of this exposure system (e.g., varying the dose and timing of infection) could lead to an even more consistent, unambiguous fetal loss phenotype for assessing ZIKV countermeasures in pregnancy. These data demonstrate that high-dose exposure to African-lineage ZIKV causes pregnancy loss in macaques and also suggest that ZIKV-induced first trimester pregnancy loss could be strain-specific.

There are currently no approved drugs to treat Zika virus (ZIKV) infection during pregnancy. Hyperimmune globulin products such as VARIZIG and WinRho are FDA-approved to treat conditions during pregnancy such as Varicella Zoster virus infection and Rh-incompatibility. We administered ZIKV-specific human immune globulin as a treatment in pregnant rhesus macaques one day after subcutaneous ZIKV infection. All animals controlled ZIKV viremia following the treatment and generated robust levels of anti-Zika virus antibodies in their blood. No adverse fetal or infant outcomes were identified in the treated animals, yet the placebo control treated animals also did not have signs related to congenital Zika syndrome (CZS). Human immune globulin may be a viable prophylaxis and treatment option for ZIKV infection during pregnancy, however, more studies are required to fully assess the impact of this treatment to prevent CZS.

Pancreatic ductal adenocarcinoma (PDAC) evolves a complex microenvironment comprised of multiple cell types, including pancreatic stellate cells (PSC). Previous studies have demonstrated that stromal supply of alanine, lipids, and nucleotides supports the metabolism, growth, and therapeutic resistance of PDAC. Here we demonstrate that alanine cross-talk between PSCs and PDAC is orchestrated by the utilization of specific transporters. PSCs utilize SLC1A4 and other transporters to rapidly exchange and maintain environmental alanine concentrations. Moreover, PDAC cells upregulate SLC38A2 to supply their increased alanine demand. Cells lacking SLC38A2 fail to concentrate intracellular alanine and undergo a profound metabolic crisis resulting in markedly impaired tumor growth. Our results demonstrate that stromal–cancer metabolic niches can form through differential transporter expression, creating unique therapeutic opportunities to target metabolic demands of cancer. Significance: This work identifies critical neutral amino acid transporters involved in channeling alanine between pancreatic stellate and PDAC cells. Targeting PDAC-specific alanine uptake results in a metabolic crisis impairing metabolism, proliferation, and tumor growth. PDAC cells specifically activate and require SLC38A2 to fuel their alanine demands that may be exploited therapeutically. This article is highlighted in the In This Issue feature, p. 890

Controlling the stacking order in bilayer graphene (BLG) allows realizing interesting physical properties. In particular, the possibility of tuning the band gap in Bernal-stacked (AB) BLG (AB-BLG) has a great technological importance for electronic and optoelectronic applications. Most of the current methods to produce AB-BLG suffer from inhomogeneous layer thickness and/or coexistence with twisted BLG. Here, we demonstrate a method to synthesize highly pure large-area AB-BLG by chemical vapor deposition using Cu-Ni films. Increasing the reaction time resulted in a gradual increase of the AB stacking, with the BLG eventually free from twist regions for the longer growth times (99.4% of BLG has AB stacking), due to catalyst-assisted continuous BLG reconstruction driven by carbon dissolution-segregation processes. The band gap opening was confirmed by the electrical measurements on field-effect transistors using two different device configurations. The concept of the continuous reconstruction to achieve highly pure AB-BLG offers a way to control the stacking order of catalytically grown two-dimensional materials.

Background/Aim: The entire mechanisms by which epigenetic modifiers contribute to the development of pancreatic cancer remain unknown. Although the histone methyltransferase G9a is a promising target in human cancers, its role in pancreatic carcinogenesis has been under-studied. The aim of the study was to examine the role of G9a in pancreatic carcinogenesis by a gene-targeting mouse model. Materials and Methods: We established pancreas-specific G9a(flox/flox )mice and crossed them with Ptf1a(Cre/); Kras(G12D/+ )(KC) mice, which spontaneously develop pancreatic cancer. The phenotypes of the resulting KC mice with G9a deletion were examined. We analyzed transcriptomic data by microarray and genome-wide chromatin accessibility by transposase-accessible chromatin using sequencing. We established pancreatic organoids from KC mice. Results: G9a deficiency impaired the progression of pancreatic intraepithelial neoplasia (PanIN) and prolonged the survival of KC mice. The number of phosphorylated Erk-positive cells and Dclk1-positive cells, which are reported to be essential for the progression of PanIN, were decreased by G9a deletion. UNC0638, an inhibitor of G9a, suppressed the growth of organoids and increased global chromatin accessibility, especially around the regions including the protein phosphatase 2A genes. Conclusion: Thus, our study suggested the functional interaction of G9a, Dclk1 and Mapk pathway in the Kras-driven pancreatic carcinogenesis. The inhibition of G9a may suppress the initiation of oncogenic Kras-driven pancreatic carcinogenesis.

Background/aim Tracheostomy performed on patients with Coronavirus disease 2019 (COVID-19) may lead to the infection of operators and medical staff. To date, there are no established methods of infection control. The aim of this study was to provide helpful and useful information regarding tracheostomy during the COVID-19 pandemic. Patients and methods We performed a retrospective analysis on 12 patients with severe COVID-19 who were intubated and underwent tracheostomy in our hospital. Results Percutaneous tracheostomy was performed in eight cases, and open tracheostomy was performed in four cases. Open tracheostomy in the operating room was performed under a negative pressure closed-space system using a surgical drape to prevent aerosolization. Conclusion Our experience suggests that bedside percutaneous tracheostomy may be a useful option in patients with COVID-19. In cases where percutaneous tracheostomy is anticipated to be difficult, open tracheostomy using a negative pressure closure may be useful in preventing aerosolization and reducing the risk of infection of healthcare workers.

Metabolism is a critical regulator of cell fate determination. Recently, the significance of metabolic reprogramming in environmental adaptation during tumorigenesis has attracted much attention in cancer research. Recurrent mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes have been identified in several cancers, including intrahepatic cholangiocarcinoma (ICC). Mutant IDHs convert α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG), which affects the activity of multiple α-KG-dependent dioxygenases including histone lysine demethylases. Although mutant IDH can be detected even in the early stages of neoplasia, how IDH mutations function as oncogenic drivers remains unclear. In this study, we aimed to address the biological effects of IDH1 mutation using intrahepatic biliary organoids (IBOs). We demonstrated that mutant IDH1 increased the formation of IBOs as well as accelerated glucose metabolism. Gene expression analysis and ChIP results revealed the upregulation of platelet isoform of phosphofructokinase-1 (PFKP), which is a rate-limiting glycolytic enzyme, through the alteration of histone modification. Knockdown of the Pfkp gene alleviated the mutant IDH1-induced increase in IBO formation. Notably, the high expression of PFKP was observed more frequently in patients with IDH-mutant ICC compared to in those with wild-type IDH (p

In the elevation of the muco-perichondrium flap during septoplasty and septorhinoplasty, it is important to elevate the subperichondrial layer. When performing subperichondrial elevation of the flap, the surgeon uses differences in color tone to distinguish the perichondrium from cartilage; however, it is relatively difficult to understand these differences and to share them with assistants. Furthermore, the perichondrium at the caudal end adheres tightly to the cartilage, making it difficult to detach accurately the subperichondrial layer. Narrow band imaging (NBI) is an optical technology that facilitates detailed observation of microvessels in the mucosal surface layer. In this study, we investigated whether NBI is better than white light (WL) in accentuating differences in contrast between cartilage and perichondrium in the elevation of the muco-perichondrium flap during septoplasty and septorhinoplasty.Twenty-six sides of 15 patients (the modified Killian approach was used in two patients, the hemitransfixion approach was used in seven patients, and open septorhinoplasty was used in six patients) with elevated muco-perichondrium flaps were studied under WL endoscopy and NBI. The brightness of the perichondrium and cartilage and the differences between the two tissues were compared between WL and NBI using ImageJ 1.53a. Next, the WL and NBI endoscopic images used for cartilage identification were divided into the three separate primary color channels of red, green, and blue, and the brightness of the perichondrium and cartilage were measured separately for each channel.Under WL, the perichondrium appeared reddish-white and the cartilage appeared white, whereas under NBI the perichondrium appeared greenish-gray, differentiating it from the white cartilage. The difference in brightness between the cartilage and perichondrium was significantly higher on NBI (grayscale difference 80.8 (SD 42.4)) than on WL imaging (grayscale difference 35.6 (SD 31.1)) (p0.001). In the red channel, the difference in image intensity between cartilage and perichondrium was significantly higher on NBI than on WL imaging (Red WL grayscale difference -1.5 (SD 33.7), Red NBI grayscale difference 90.0 (SD 56.7); p0.001).NBI is better than WL at accentuating the difference in contrast between cartilage and the perichondrium during the elevation of the muco-perichondrium flap during septoplasty and septorhinoplasty. The difference in the processing of red light between WL and NBI provides the largest contribution to the differentiation of cartilage from the perichondrium under WL and NBI. We believe that NBI can be usefully applied during septoplasty and septorhinoplasty to distinguish cartilage from the perichondrium with precision.

An 18-year-old man presented with sudden vision loss in his left eye. Magnetic resonance imaging revealed a tumor that had invaded the left optic nerve, originating from the left posterior ethmoid sinus. Immunohistochemical analyses identified positive staining for NUT protein in the nuclei of tumor cells. We diagnosed locally advanced NUT carcinoma (NC) and initiated concurrent chemoradiotherapy (CCRT), consisting of chemotherapy with vincristine, doxorubicin, and cyclophosphamide, alternating with ifosphamide and etoposide, plus radiation therapy. The patient achieved a complete response. CCRT can be a useful treatment option for adolescent and young-adult patients with locally advanced unresectable NC.

Three-dimensional (3D) chromatin structures connect genes to regulatory elements, thereby contributing to cell-type-specific gene regulation. However, its role in pancreatic cancer remains unclear. Inspired by our previous finding that open chromatin profiles analyzed by ATAC-seq well characterize the biological features and transcriptional status of pancreatic neoplasms, we hereby demonstrate the previously overlooked impact of 3D epigenetic regulation in pancreatic cancers. Through integrative analysis of Hi-C, ChIP-seq, and RNA-seq using patient-derived organoids, 3D genome modules, including compartments, topologically associating domains, and enhancer-promoter loops were found to play important roles in characterizing pancreatic tumors. Interestingly, intraductal papillary mucinous neoplasm (IPMN) lineages tended to have unique 3D chromatin structure profiles. We further found that transcriptional subtypes in pancreatic cancer, either classical/progenitor-like or basal/squamous-like, were largely underpinned by 3D structures. Compartment was responsible for supporting many subtype-specific genes, by synchronously activating genes that were in the vicinity, as represented by CYP2C family genes. Meanwhile, enhancer-promoter loop fine-tuned some key subtype genes, such as GATA6. By exploring the driving forces behind these 3D structures, we found that HNF1B, a transcription factor implicated in the progenitor subtype, was sufficient to induce subtype switch, together with their underlying 3D genome structure alterations. We demonstrate that HNF1B overexpression in squamous-type pancreatic cancer organoids induced the upregulation and downregulation of genes associated with the progenitor and squamous subtype, respectively. Mechanistically, these dynamic transcriptional and 3D structural modulation were accompanied by HNF1B-induced long-range genomic interactions and H3K27ac modification at HNF1B bound sites, implying HNF1B as a driving force. We also provide evidence suggesting that this HNF1B-induced subtype switch was mediated through the phase-separating property of HNF1B, which was enabled by its intrinsically disordered region (IDR). Induction of mutant HNF1B, whose IDR was either deleted (HNF1B-dIDR) or substituted by transcriptional phase-separation forming IDR from another peptide AKAP95 (HNF1B-AKAP95), showed that subtype switching effects of HNF1B were diminished by HNF1B-dIDR or recapitulated by HNF1B-AKAP95. Thus, HNF1B contributes to the transcriptional subtype formation in pancreatic cancers through its phase-separating structural ability. Collectively, the mapping of 3D structural changes induced by transcription factors, such as HNF1B, is useful for further understanding the features of pancreatic cancers. Our study may imply the potential of 3D structures to effectively suppress or unwind the malignant transformation process and to discover subtype-specific therapeutic targets. Citation Format: Hiroyuki Kato, Dosuke Iwadate, Keisuke Yamamoto, Hiroaki Fujiwara, Hideaki Ijichi, Mitsuhiro Fujishiro, Keisuke Tateishi. Hi-C analysis in patient-derived organoids reveals the impact of three-dimensional chromatin structures on pancreatic cancer transcriptional subtypes [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A069.

We measure current spikes superimposed on dc conduction currents through a LDPE sheet with charge injection from corona discharges in air or N2. The ions or electrons produced by the dc corona at the needle electrode pass through a screen mesh electrode and they are artificially injected into the LDPE. Negative corona discharges in N2 increase the mean repetition frequency of spikes. However, it decreases the mean repetition frequency of spikes in air. Positive corona discharge decreases the mean repetition frequency of spikes regardless of the gas components. These results suggest that the electron component in the injected charges acts as an important role for the spike current. Space charge distributions in the LDPE with the artificial charge injection are also measured.

Concerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that macaques with a prior DENV-2 exposure had a higher burden of ZIKV vRNA in maternal-fetal interface tissues as compared to DENV-naive macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate., Author summary Zika virus (ZIKV) gained global attention during an explosive outbreak in the Americas in 2015–16 when it was causally associated with the constellation of birth defects now termed congenital Zika syndrome (CZS). However, a substantial proportion of gestational ZIKV infections result in babies without apparent birth defects. Could there be other factors that influence ZIKV pathogenicity? For example, it is well-established that pre-existing immunity to one dengue virus (DENV) serotype can enhance the severity of a secondary DENV infection. ZIKV is antigenically closely related to DENV, but whether DENV-specific antibodies enhance the severity of ZIKV infection is unclear. To answer this question, we used our non-human primate model of ZIKV to assess the impact of pre-existing immunity to DENV on ZIKV pathogenesis during pregnancy. We did not observe any difference in ZIKV replication in plasma between macaques that were immune to DENV and those that were not. However, there was more ZIKV vRNA detected in the placenta of macaques immune to DENV, suggesting DENV immunity could enhance ZIKV infection of the placenta. As vaccines to both DENV and ZIKV are developed, it remains critical to understand the risks of DENV immunity for pregnant women exposed to ZIKV.

As the hosts of lentiviruses, almost 40 species of felids (family Felidae) are distributed around the world, and more than 20 feline species test positive for feline immunodeficiency virus (FIV), a lineage of lentiviruses. These observations suggest that FIVs globally infected a variety of feline species through multiple cross-species transmission events during a million-year history. Cellular restriction factors potentially inhibit lentiviral replication and limit cross-species lentiviral transmission, and cellular APOBEC3 deaminases are known as a potent restriction factor. In contrast, lentiviruses have evolutionary-acquired viral infectivity factor (Vif) to neutralize the APOBEC3-mediated antiviral effect. Because the APOBEC3-Vif interaction is strictly specific for viruses and their hosts, a comprehensive investigation focusing on Vif-APOBEC3 interplay can provide clues that will elucidate the roles of this virus-host interplay on cross-species transmission of lentiviruses. Here, we performed a comprehensive investigation with 144 patterns of a round robin test using 18 feline APOBEC3Z3 genes, an antiviral APOBEC3 gene in felid, and 8 FIV Vifs and derived a matrix showing the interplay between feline APOBEC3Z3 and FIV Vif. We particularly focused on the interplay between the APOBEC3Z3 of three felids (domestic cat, ocelot, and Asian golden cat) and an FIV Vif (strain Petaluma), and revealed that residues 65 and 66 of the APOBEC3Z3 protein of multiple felids are responsible for the counteraction triggered by FIV Petaluma Vif. Altogether, our findings can be a clue to elucidate not only the scenarios of the cross-species transmissions of FIVs in felids but also the evolutionary interaction between mammals and lentiviruses. IMPORTANCE Most of the emergences of new virus infections originate from the cross-species transmission of viruses. The fact that some virus infections are strictly specific for the host species indicates that certain “species barriers” in the hosts restrict cross-species jump of viruses, while viruses have evolutionary acquired their own “arms” to overcome/antagonize/neutralize these hurdles. Therefore, understanding of the molecular mechanism leading to successful cross-species viral transmission is crucial for considering the menus of the emergence of novel pathogenic viruses. In the field of retrovirology, APOBEC3-Vif interaction is a well-studied example of the battles between hosts and viruses. Here, we determined the sequences of 11 novel feline APOBEC3Z3 genes and demonstrated that all 18 different feline APOBEC3Z3 proteins tested exhibit anti-feline immunodeficiency virus (FIV) activity. Our comprehensive investigation focusing on the interplay between feline APOBEC3 and FIV Vif can be a clue to elucidate the scenarios of the cross-species transmissions of FIVs in felids.

A border trap (BT) evaluation method was established for SiO2/GeO2/Ge gate stacks by using deep-level transient spectroscopy with a lock-in integrator. Ge metal-oxide-semiconductor capacitors (MOSCAPs) with SiO2/GeO2/Ge gate stacks were fabricated by post-passivation thermal oxidation. The interface trap (IT) and BT signals were successfully separated based on their different dependences on the intensity of injection pulses. By using p-type MOSCAPs, BTs at the position of 0.4 nm from GeO2/Ge interface were measured. The energy of these BTs was centralized at the position near to the valence band edge of Ge, and the density (Nbt) was in the range of 1017-1018 cm−3. For n-type MOSCAPs, BTs at the position range of 2.8-3.4 nm from the GeO2/Ge interface were measured. The energy of these BTs were distributed in a relatively wide range near to the conduction band edge of Ge, and the Nbt was approximately one order of magnitude higher than those for p-MOSCAPs. We also found that Al post metallization annealing can passivate both ITs and BTs near to the valence band edge of Ge but not those near to the conduction band edge.

Silicosis is an occupational lung disorder caused by inhalation of silica dust. It not only causes respiratory disorders but also affects other organs. We report an extremely rare case of silicosis complicated by pericarditis in an 83-year-old male. He had been working as a coal miner and was diagnosed with silicosis at the age of 63. Because he had experienced repeated pericardial effusions, he was referred for a surgical pericardial biopsy to elucidate the cause of his repeated pericardial effusion and to perform pericardial fenestration. Thoracoscopic surgery was performed. The pericardium was resected, and a drain was placed in the left thoracic cavity. Histopathological examination revealed the pericardial degeneration due to silicosis, suggesting that pericarditis and pericardial effusion are related to silicosis. The operation was successful, and he experienced no recurrence of pericardial effusion at the 7-month follow-up.

Chemotherapy-induced neutropenia (CIN) is an important dose-limiting toxicity of chemotherapy. However, evidence suggests that the occurrence of CIN may be predictive of treatment outcome. Indeed, studies have revealed that the onset of CIN is associated with a good chemotherapeutic response.The purpose of this study was to investigate the association between the onset of CIN and overall survival in patients with unresectable or metastatic urothelial carcinoma (UC) who received a combination regimen of gemcitabine and cisplatin (GC).Medical records from 56 patients with unresectable or metastatic UC who were treated with a combination GC regimen between December 2005 and May 2016 were retrospectively analyzed to investigate the association between CIN development and survival.The median duration of survival was 521 days (95% CI = 147-193 days) for patients with severe CIN and 287 days for patients without CIN. Additional multivariate analysis revealed that both the presence of severe CIN (hazard ratio [HR] = 0.399; 95% CI = 0.180-0.880, P = 0.023) and baseline hemoglobin (HR = 2.167; 95% CI = 1.170-4.014, P = 0.014) represented independent prognostic factors for the survival of patients with unresectable or metastatic UC receiving GC treatment. Conclusion and Relevance: CIN onset was associated with longer survival in patients receiving GC therapy for unresectable or metastatic UC, suggesting that neutropenia monitoring during GC chemotherapy may be predictive of treatment efficacy.

We fabricated n-channel MOSFETs with various gate dielectrics on (111) oriented 3C-SiC/Si. Fabricated MOSFETs operated as inversion mode devices successfully. The MOSFET with sputter-deposited SiO2/plasma oxidized interlayer showed a high peak field-effect mobility of 131 cm2 V−1 s−1. The gate stack can be formed at a low temperature of 400 °C, which means the process is absolved from high-temperature thermal oxidation for a gate stack. The detailed analysis of charges and traps in the gate stacks clarified that Coulomb scattering is well-suppressed in the inversion channel. These results will be the first step for a high-performance 3C-SiC application, including on-chip hetero-integrated electronic devices.

Quantifying proliferative virus particles is one of the most important experimental procedures in virology. Compared with classical overlay materials, newly developed cellulose derivatives enable a plaque-forming assay to produce countable clear plaques easily. HEp-2 cells are widely used in plaque assays for human respiratory syncytial virus (RSV). It is crucial to use an overlay material to keep HEp-2 cell proliferation and prevent RSV particles from spreading over the fluid. Among four cellulose derivatives, carboxymethyl cellulose sodium salt (CMC), hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose (MCC), and hydroxyethyl cellulose (HEC), we found that HPMC was the optimal overlay material because HPMC maintained HEp-2 cell proliferation and RSV infectivity. Although MCC was unsuitable for RSV, it assisted the plaque-forming by human metapneumovirus in TMPRSS2-expressing cells. Therefore, depending on the cells and viruses, it is necessary to use different overlay materials at varying concentrations.

Chromatin architecture governs cell lineages by regulating the specific gene expression; however, its role in the diversity of cancer development remains unknown. Among pancreatic cancers, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMN) with an associated invasive carcinoma (IPMNinv) arise from 2 distinct precursors, and their fundamental differences remain obscure. Here, we aimed to assess the difference of chromatin architecture regulating the transcriptional signatures or biological features in pancreatic cancers.We established 28 human organoids from distinct subtypes of pancreatic tumors, including IPMN, IPMNinv, and PDAC. We performed exome sequencing (seq), RNA-seq, assay for transposase-accessible chromatin-seq, chromatin immunoprecipitation-seq, high-throughput chromosome conformation capture, and phenotypic analyses with short hairpin RNA or clustered regularly interspaced short palindromic repeats interference.Established organoids successfully reproduced the histology of primary tumors. IPMN and IPMNinv organoids harbored GNAS, RNF43, or KLF4 mutations and showed the distinct expression profiles compared with PDAC. Chromatin accessibility profiles revealed the gain of stomach-specific open regions in IPMN and the pattern of diverse gastrointestinal tissues in IPMNinv. In contrast, PDAC presented an impressive loss of accessible regions compared with normal pancreatic ducts. Transcription factor footprint analysis and functional assays identified that MNX1 and HNF1B were biologically indispensable for IPMN lineages. The upregulation of MNX1 was specifically marked in the human IPMN lineage tissues. The MNX1-HNF1B axis governed a set of genes, including MYC, SOX9, and OLFM4, which are known to be essential for gastrointestinal stem cells. High-throughput chromosome conformation capture analysis suggested the HNF1B target genes to be 3-dimensionally connected in the genome of IPMNinv.Our organoid analyses identified the MNX1-HNF1B axis to be biologically significant in IPMN lineages.