Fluorination on cyclopentadithiophene-based hole-transport materials for high-performance perovskite solar cells.

A new class of fluorinated cyclopenta[2,1-b:3,4-b']dithiophene (CPDT)-based small molecules, namely YC-oF, YC-mF, and YC-H, are demonstrated as hole-transporting materials (HTMs) for high-performance perovskite solar cells (PSCs). PSCs employing YC-oF as the HTM delivered an excellent efficiency of 22.41% with encouraging long-term stability.

Characterization of molecular mechanisms driving Merkel cell polyomavirus oncogene transcription and tumorigenic potential.

Merkel cell polyomavirus (MCPyV) is associated with approximately 80% of cases of Merkel cell carcinoma (MCC), an aggressive type of skin cancer. The incidence of MCC has tripled over the past twenty years, but there are currently very few effective targeted treatments. A better understanding of the MCPyV life cycle and its oncogenic mechanisms is needed to unveil novel strategies for the prevention and treatment of MCC. MCPyV infection and oncogenesis are reliant on the expression of the early viral oncoproteins, which drive the viral life cycle and MCPyV+ MCC tumor cell growth. To date, the molecular mechanisms regulating the transcription of the MCPyV oncogenes remain largely uncharacterized. In this study, we investigated how MCPyV early transcription is regulated to support viral infection and MCC tumorigenesis. Our studies established the roles of multiple cellular factors in the control of MCPyV gene expression. Inhibitor screening experiments revealed that the histone acetyltransferases p300 and CBP positively regulate MCPyV transcription. Their regulation of viral gene expression occurs through coactivation of the transcription factor NF-κB, which binds to the viral genome to drive MCPyV oncogene expression in a manner that is tightly controlled through a negative feedback loop. Furthermore, we discovered that small molecule inhibitors specifically targeting p300/CBP histone acetyltransferase activity are effective at blocking MCPyV tumor antigen expression and MCPyV+ MCC cell proliferation. Together, our work establishes key cellular factors regulating MCPyV transcription, providing the basis for understanding the largely unknown mechanisms governing MCPyV transcription that defines its infectious host cell tropism, viral life cycle, and oncogenic potential. Our studies also identify a novel therapeutic strategy against MCPyV+ MCC through specific blockage of MCPyV oncogene expression and MCC tumor growth.

Characterization of the Impact of Merkel Cell Polyomavirus-Induced Interferon Signaling on Viral Infection.

Merkel cell polyomavirus (MCPyV) has been associated with approximately 80% of Merkel cell carcinoma (MCC), an aggressive and increasingly incident skin cancer. The link between host innate immunity, viral load control, and carcinogenesis has been established but poorly characterized. We previously established the importance of the STING and NF-κB pathways in the host innate immune response to viral infection. In this study, we further discovered that MCPyV infection of human dermal fibroblasts (HDFs) induces the expression of type I and III interferons (IFNs), which in turn stimulate robust expression of IFN-stimulated genes (ISGs). Blocking type I IFN downstream signaling using an IFN-ß antibody, JAK inhibitors, and CRISPR knockout of the receptor dramatically repressed MCPyV infection-induced ISG expression but did not significantly restore viral replication activities. These findings suggest that IFN-mediated induction of ISGs in response to MCPyV infection is not crucial to viral control. Instead, we found that type I IFN exerts a more direct effect on MCPyV infection postentry by repressing early viral transcription. We further demonstrated that growth factors normally upregulated in wounded or UV-irradiated human skin can significantly stimulate MCPyV gene expression and replication. Together, these data suggest that in healthy individuals, host antiviral responses, such as IFN production induced by viral activity, may restrict viral propagation to reduce MCPyV burden. Meanwhile, growth factors induced by skin abrasion or UV irradiation may stimulate infected dermal fibroblasts to promote MCPyV propagation. A delicate balance of these mutually antagonizing factors provides a mechanism to support persistent MCPyV infection. IMPORTANCE Merkel cell carcinoma is an aggressive skin cancer that is particularly lethal to immunocompromised individuals. Though rare, MCC incidence has increased significantly in recent years. There are no lasting and effective treatments for metastatic disease, highlighting the need for additional treatment and prevention strategies. By investigating how the host innate immune system interfaces with Merkel cell polyomavirus, the etiological agent of most of these cancers, our studies identified key factors necessary for viral control, as well as conditions that support viral propagation. These studies provide new insights for understanding how the virus balances the effects of the host immune defenses and of growth factor stimulation to achieve persistent infection. Since virus-positive MCC requires the expression of viral oncogenes to survive, our observation that type I IFN can repress viral oncogene transcription indicates that these cytokines could be explored as a viable therapeutic option for treating patients with virus-positive MCC.

Lipid Nanoparticles Delivering Constitutively Active STING mRNA to Stimulate Antitumor Immunity.

Treating immunosuppressive tumors represents a major challenge in cancer therapies. Activation of STING signaling has shown remarkable potential to invigorate the immunologically "cold" tumor microenvironment (TME). However, we have shown that STING is silenced in many human cancers, including pancreatic ductal adenocarcinoma (PDAC) and Merkel cell carcinoma (MCC). In this study, we demonstrated that mRNA-lipid nanoparticle (LNP) technology could be used to efficiently deliver naturally occurring constitutively active STING mutant STINGR284S into these cancer cells to reactivate STING antitumor immunity and trigger robust killing of tumor cells. STING agonists are being actively pursued as cancer immunotherapies. However, traditional STING agonists can induce T cell cytotoxicity, counteracting the desired antitumor immune response. In addition, the antitumor efficacy of traditional STING agonists obligatorily depends on STING expression and does not work in STING-silenced cancers. Importantly, we found that STINGR284S mRNA-LNP does not introduce T cell cytotoxicity. Our studies demonstrated that mRNA-LNP delivery of STINGR284S can reactivate the antitumor response without introducing antiproliferative effects in lymphocytic immune cells, overcoming the toxicity and limitations of conventional STING agonists. Our work therefore identifies a novel therapeutic tool for reactivating antitumor immunity in an array of STING-silenced immunologically "cold" tumors that are refractory to current therapies.

Mixed-Dimensional Formamidinium Bismuth Iodides Featuring In-Situ Formed Type-I Band Structure for Convolution Neural Networks.

For valence change memory (VCM)-type synapses, a large number of vacancies help to achieve very linearly changed dynamic range, and also, the low activation energy of vacancies enables low-voltage operation. However, a large number of vacancies increases the current of artificial synapses by acting like dopants, which aggravates low-energy operation and device scalability. Here, mixed-dimensional formamidinium bismuth iodides featuring in-situ formed type-I band structure are reported for the VCM-type synapse. As compared to the pure 2D and 0D phases, the mixed phase increases defect density, which induces a better dynamic range and higher linearity. In addition, the mixed phase decreases conductivity for non-paths despite a large number of defects providing lots of conducting paths. Thus, the mixed phase-based memristor devices exhibit excellent potentiation/depression characteristics with asymmetricity of 3.15, 500 conductance states, a dynamic range of 15, pico ampere-scale current level, and energy consumption per spike of 61.08 aJ. A convolutional neural network (CNN) simulation with the Canadian Institute for Advanced Research-10 (CIFAR-10) dataset is also performed, confirming a maximum recognition rate of approximately 87%. This study is expected to lay the groundwork for future research on organic bismuth halide-based memristor synapses usable for a neuromorphic computing system.

Merkel cell polyomavirus and associated Merkel cell carcinoma.

Merkel cell polyomavirus (MCPyV) is a ubiquitous skin infection that can cause Merkel cell carcinoma (MCC), a highly lethal form of skin cancer with a nearly 50% mortality rate. Since the discovery of MCPyV in 2008, great advances have been made to improve our understanding of how the viral encoded oncoproteins contribute to MCC oncogenesis. However, our knowledge of the MCPyV infectious life cycle and its oncogenic mechanisms are still incomplete. The incidence of MCC has tripled over the past two decades, but effective treatments are lacking. Only recently have there been major victories in combatting metastatic MCC with the application of PD-1 immune checkpoint blockade. Still, these immune-based therapies are not ideal for patients with a medical need to maintain systemic immune suppression. As such, a better understanding of MCPyV's oncogenic mechanisms is needed in order to develop more effective and targeted therapies against virus-associated MCC. In this review, we discuss current areas of interest for MCPyV and MCC research and the progress made in elucidating both the natural host of MCPyV infection and the cell of origin for MCC. We also highlight the remaining gaps in our knowledge on the transcriptional regulation of MCPyV, which may be key to understanding and targeting viral oncogenesis for developing future therapies.

Asymmetric carrier transport in flexible interface-type memristor enables artificial synapses with sub-femtojoule energy consumption.

Flexible and transparent artificial synapses with extremely low energy consumption have potential for use in brain-like neuromorphic electronics. However, most of the transparent materials for flexible memristive artificial synapses were reported to show picojoule-scale high energy consumption with kiloohm-scale low resistance, which limits the scalability for parallel operation. Here, we report on a flexible memristive artificial synapse based on Cs3Cu2I5 with energy consumption as low as 10.48 aJ (= 10.48 × 10-18 J) µm-2 and resistance as high as 243 MΩ for writing pulses. Interface-type resistive switching at the Schottky junction between p-type Cu3Cs2I5 and Au is verified, where migration of iodide vacancies and asymmetric carrier transport owing to the effective hole mass is three times heavier than effective electron mass are found to play critical roles in controlling the conductance, leading to high resistance. There was little difference in synaptic weight updates with high linearity and 250 states before and after bending the flexible device. Moreover, the MNIST-based recognition rate of over 90% is maintained upon bending, indicative of a promising candidate for highly efficient flexible artificial synapses.

A layered (n-C4H9NH3)2CsAgBiBr7 perovskite for bipolar resistive switching memory with a high ON/OFF ratio.

Lead-based halide perovskites have been proposed as potential candidates for resistive switching memristors due to the high ON/OFF ratio along with millivolt-level low operational voltage. However, lead-free perovskites with 3-dimensional structures, such as Cs2AgBiBr6, were reported to suffer from low ON/OFF ratios. We report here that reduction of dimensionality is an effective method to improve remarkably the ON/OFF ratio in lead-free perovskites. Introduction of butylammonium (BA) into the double perovskite Cs2AgBiBr6 forms 2-dimensional BA2CsAgBiBr7, which is confirmed by the well-developed (00l) peaks from powder X-ray diffraction. A 230 nm thick BA2CsAgBiBr7 film is sandwiched in between Ag and Pt electrodes, which demonstrates bipolar resistive switching behavior with a potential ON/OFF ratio up to 107. Reliable and reproducible SET and RESET processes occur at +0.13 V and -0.20 V, respectively. Endurance of 1000 cycles and a retention time of 2 × 104 s are measured. Multi-level storage capability is confirmed by controlling the compliance current. Schottky conduction at the high resistance state (HRS) and ohmic conduction at the low resistance state (LRS) are found to be responsible for resistive switching. The stability test at 85 °C or for 22 days under ambient conditions indicates that BA2CsAgBiBr7 is durably operable.

Activation of STING Signaling Pathway Effectively Blocks Human Coronavirus Infection.

The COVID-19 pandemic poses a serious global health threat. The rapid global spread of SARS-CoV-2 highlights an urgent need to develop effective therapeutics for blocking SARS-CoV-2 infection and spread. Stimulator of Interferon Genes (STING) is a chief element in host antiviral defense pathways. In this study, we examined the impact of the STING signaling pathway on coronavirus infection using the human coronavirus OC43 (HCoV-OC43) model. We found that HCoV-OC43 infection did not stimulate the STING signaling pathway, but the activation of STING signaling effectively inhibits HCoV-OC43 infection to a much greater extent than that of type I interferons (IFNs). We also discovered that IRF3, the key STING downstream innate immune effector, is essential for this anticoronavirus activity. In addition, we found that the amidobenzimidazole (ABZI)-based human STING agonist diABZI robustly blocks the infection of not only HCoV-OC43 but also SARS-CoV-2. Therefore, our study identifies the STING signaling pathway as a potential therapeutic target that could be exploited for developing broad-spectrum antiviral therapeutics against multiple coronavirus strains in order to face the challenge of future coronavirus outbreaks.IMPORTANCE The highly infectious and lethal SARS-CoV-2 is posing an unprecedented threat to public health. Other coronaviruses are likely to jump from a nonhuman animal to humans in the future. Novel broad-spectrum antiviral therapeutics are therefore needed to control known pathogenic coronaviruses such as SARS-CoV-2 and its newly mutated variants, as well as future coronavirus outbreaks. STING signaling is a well-established host defense pathway, but its role in coronavirus infection remains unclear. In the present study, we found that activation of the STING signaling pathway robustly inhibits infection of HCoV-OC43 and SARS-CoV-2. These results identified the STING pathway as a novel target for controlling the spread of known pathogenic coronaviruses, as well as emerging coronavirus outbreaks.

Merkel Cell Polyomavirus Infection Induces an Antiviral Innate Immune Response in Human Dermal Fibroblasts.

Merkel cell polyomavirus (MCPyV) infects most of the human population asymptomatically, but in rare cases it leads to a highly aggressive skin cancer called Merkel cell carcinoma (MCC). MCC incidence is much higher in aging and immunocompromised populations. The epidemiology of MCC suggests that dysbiosis between the host immune response and the MCPyV infectious cycle could contribute to the development of MCPyV-associated MCC. Insufficient restriction of MCPyV by normal cellular processes, for example, could promote the incidental oncogenic MCPyV integration events and/or entry into the original cell of MCC. Progress toward understanding MCPyV biology has been hindered by its narrow cellular tropism. Our discovery that primary human dermal fibroblasts (HDFs) support MCPyV infection has made it possible to closely model cellular responses to different stages of the infectious cycle. The present study reveals that the onset of MCPyV replication and early gene expression induces an inflammatory cytokine and interferon-stimulated gene (ISG) response. The cGAS-STING pathway, in coordination with NF-κB, mediates induction of this innate immune gene expression program. Further, silencing of cGAS or NF-κB pathway factors led to elevated MCPyV replication. We also discovered that the PYHIN protein IFI16 localizes to MCPyV replication centers but does not contribute to the induction of ISGs. Instead, IFI16 upregulates inflammatory cytokines in response to MCPyV infection by an alternative mechanism. The work described herein establishes a foundation for exploring how changes to the skin microenvironment induced by aging or immunodeficiency might alter the fate of MCPyV and its host cell to encourage carcinogenesis. IMPORTANCE MCC has a high rate of mortality and an increasing incidence. Immune-checkpoint therapies have improved the prognosis of patients with metastatic MCC. Still, a significant proportion of the patients fail to respond to immune-checkpoint therapies or have a medical need for iatrogenic immune-suppression. A greater understanding of MCPyV biology could inform targeted therapies for MCPyV-associated MCC. Moreover, cellular events preceding MCC oncogenesis remain largely unknown. The present study aims to explore how MCPyV interfaces with innate immunity during its infectious cycle. We describe how MCPyV replication and/or transcription elicit an innate immune response via cGAS-STING, NF-κB, and IFI16. We also explore the effects of this response on MCPyV replication. Our findings illustrate how healthy cellular conditions may allow low-level infection that evades immune destruction until highly active replication is restricted by host responses. Conversely, pathological conditions could result in unbridled MCPyV replication that licenses MCC tumorigenesis.

Regulation of Polyomavirus Transcription by Viral and Cellular Factors.

Polyomavirus infection is widespread in the human population. This family of viruses normally maintains latent infection within the host cell but can cause a range of human pathologies, especially in immunocompromised individuals. Among several known pathogenic human polyomaviruses, JC polyomavirus (JCPyV) has the potential to cause the demyelinating disease progressive multifocal leukoencephalopathy (PML); BK polyomavirus (BKPyV) can cause nephropathy in kidney transplant recipients, and Merkel cell polyomavirus (MCPyV) is associated with a highly aggressive form of skin cancer, Merkel cell carcinoma (MCC). While the mechanisms by which these viruses give rise to the relevant diseases are not well understood, it is clear that the control of gene expression in each polyomavirus plays an important role in determining the infectious tropism of the virus as well as their potential to promote disease progression. In this review, we discuss the mechanisms governing the transcriptional regulation of these pathogenic human polyomaviruses in addition to the best-studied simian vacuolating virus 40 (SV40). We highlight the roles of viral cis-acting DNA elements, encoded proteins and miRNAs that control the viral gene expression. We will also underline the cellular transcription factors and epigenetic modifications that regulate the gene expression of these viruses.

Bromodomain-Containing Protein BRD4 Is Hyperphosphorylated in Mitosis.

The epigenetic reader BRD4 binds acetylated histones and plays a central role in controlling cellular gene transcription and proliferation. Dysregulation of BRD4's activity has been implicated in the pathogenesis of a wide variety of cancers. While blocking BRD4 interaction with acetylated histones using BET inhibitors (BETis) has been tested in clinical trials, many cancers have acquired BETi resistance. However, the underlying mechanisms are poorly understood and BETi resistance remains a pressing clinical problem. We previously showed that BRD4 phosphorylation supports stronger chromatin binding and target oncogene expression. In this study, we discovered that BRD4 is hyperphosphorylated by CDK1 during mitosis and determined the major CDK1 phosphorylation sites in BRD4. Using CRISPR/Cas9 gene editing, we replaced endogenous BRD4 with a non-phosphorylatable mutant and demonstrated that CDK1-mediated BRD4 phosphorylation contributes to BETi resistance. CDK1 over-activation frequently observed in cancers has the potential to cause aberrant BRD4 hyperphosphorylation persisting outside of mitosis to strengthen its target gene binding and confer BETi resistance. We found that dual CDK1 and BET inhibition generates a synergistic effect in killing BETi-resistant cancer cells. Our study therefore suggests that CDK1 inhibition can be employed to overcome tumor BETi resistance and improve treatments for BRD4-associated cancers.

Roadmap on halide perovskite and related devices.

Since the first report on solid-state perovskite solar cells (PSCs) with ∼10% power conversion efficiency (PCE) and 500 h-stability in 2012, tremendous effort has been being devoted to develop PSCs with higher PCE, longer stability and recycling hazardous lead waste. As a result, PCE over 23% was recorded in 2018 and stability over 10 000 h was reported. Beyond photovoltaics, lead halide perovskite materials demonstrated superb properties when they were applied to flat-panel x-ray detectors and non-volatile resistive switching memory. In this review, the progress of the lead halide perovskite in photovoltaics, x-ray imaging and memristors is investigated. Pb-based PSCs and non-Pb-based PSCs are compared, where technologies of non-Pb-based PSCs are not matured for commercialization. Pb-based PSCs were found to be highly suitable for both terrestrial and space photovoltaics. Higher sensitivity under low dose rate observed from the lead halide perovskite suggests a bright future for perovskite x-ray imaging systems. Moreover, high on/off ratio and low energy consumption observed in resistive switching enables perovskite to be a promising candidate for high density memristors.

Effect of interlayer spacing in layered perovskites on resistive switching memory.

We report here the effect of interlayer spacing in 2-dimensional (2D) perovskites of [C6H5(CH2)nNH3]2PbI4 (anilinium (An) for n = 0, benzylammonium (BzA) for n = 1 and phenylethylammonium (PEA) for n = 2) on resistive switching properties. X-ray diffraction (XRD) reveals that the interlayer spacing of layered PbI2 is increased from 6.98 Å to 13.29 Å for (An)2PbI4, 14.20 Å for (BzA)2PbI4 and 15.92 Å for (PEA)2PbI4, which leads to a monolayer of organic cations with stacked benzene rings between inorganic PbI42- layers. All the samples in the device structure of Ag/PMMA (polymethyl methacrylate)/perovskite/Pt show bipolar switching behavior, where the SET voltage is near +0.2 V and the RESET voltage is less than -0.5 V. The ratio of LRS (low resistance state) to HRS (high resistance state), also called the ON/OFF ratio, is increased from 106 to 108 as interlayer spacing is increased due to the gradual increase in resistance in the HRS. Endurance is slightly improved from 1.3 × 102 for An to 2.2 × 102 for PEA, whereas substantial improvement in retention is observed from 2 × 103 to 5.5 × 103. This indicates that the enhanced 2D structure is beneficial to the kinetics of forming and rupturing the conducting filaments. The ohmic-like conduction mechanism in the LRS and the hopping mechanism in the HRS are observed for all three samples. This work finds that the resistive switching properties and conduction mechanism in the HRS depend on interlayer spacing in 2D perovskites.

The effect of compositional engineering of imidazolium lead iodide on the resistive switching properties.

We report here resistive switching memory characteristics of imidazolium lead iodide depending on the molar ratio of PbI2 to imidazolium iodide (ImI), that is, PbI2 : ImI = 1 : 0, 1 : 0.5, 1 : 1, 1 : 2, 1 : 3 and 0 : 1. X-ray diffraction confirms that the stoichiometric composition results in a hexagonal structure of (Im)PbI3, showing a one-dimensional face-sharing [PbI3-] chain. Bipolar resistive switching characteristics are observed regardless of the mixing ratio, where the forming process is required prior to SET and RESET processes at around +0.2 V and -0.2 V, respectively. The ON/OFF ratio is increased from 106 to 109 as the ImI content is increased due to the increased HRS associated with the pronounced insulating characteristics by ImI, whereas, the stoichiometric (Im)PbI3 exhibits 5 times longer endurance (103) and an order of magnitude longer retention time (104 s) as compared to other compositions. Multilevel data storage capability is confirmed by changing the compliance current. The low resistance state (LRS) and the high resistance state (HRS) are associated with Ohmic conduction and Schottky conduction, respectively. Density functional theory (DFT) calculation reveals that the defect formation energy of iodine vacancy is estimated to be low indicating that (Im)PbI3 has a sufficient concentration of iodide vacancy for filament formation. Further energy barrier calculations show that iodide migration preferentially occurs along the 1-dimensional [234] crystallographic direction rather than the interlayer [130] direction. A good performance of the (Im)PbI3-based memristor is thus related to the low defect formation energy of iodide vacancy and the preferential growth of the filament along the 1-dimensional chain.

Perovskite-related (CH3NH3)3Sb2Br9 for forming-free memristor and low-energy-consuming neuromorphic computing.

Organic-inorganic halide perovskite materials exhibit excellent memristive properties, such as a high on/off ratio and low switching voltage. However, most studies have focused on Pb-based perovskites. Here, we report on the resistive switching and neuromorphic computing properties of Pb-free perovskite-related MA3Sb2Br9 (MA = CH3NH3). The Ag/PMMA/MA3Sb2Br9/ITO devices show forming-free characteristics due to a self-formed conducting filament induced by metallic Sb present in the as-prepared MA3Sb2Br9 layer. An MA3Sb2Br9-based memristor exhibits a reliable on/off ratio (∼102), an endurance of 300 cycles, a retention time of ∼104 s and multilevel storage characteristics. Furthermore, synaptic characteristics, such as short-term potentiation, short-term depression and long-term potentiation, are revealed along with a low energy-consumption of 117.9 fJ µm-2, which indicates that MA3Sb2Br9 is a promising material for neuromorphic computing.

All-Inorganic Bismuth Halide Perovskite-Like Materials A3Bi2I9 and A3Bi1.8Na0.2I8.6 (A = Rb and Cs) for Low-Voltage Switching Resistive Memory.

As silicon-based metal oxide semiconductor field effect transistors get closer to their scaling limit, the importance of resistive random-access memory devices increases due to their low power consumption, high endurance and retention performance, scalability, and fast switching speed. In the last couple of years, organic-inorganic lead halide perovskites have been used for resistive switching applications, where they outperformed conventional metal oxides in terms of large on/off ratio and low power consumption. However, there were scarce reports on lead-free perovskites for such applications. In this report, we prepared lead-free Au/A3Bi2I9/Pt/Ti/SiO2/Si (A is either Cs+ or Rb+) devices and tested their resistive switching characteristics. They showed a forming step prior to repeating switching, low operating voltage (0.09 V for Rb3Bi2I9 and 0.1 V for Cs3Bi2I9), large on/off ratio (>107), relatively high endurance (200 cycles for Rb3Bi2I9 and 400 cycles for Cs3Bi2I9 cycles), and high retention (1000 s). Such low voltage could be explained by grain boundary-modulated ion drift. Difference in endurance was speculated to be due to the difference in the surface roughness of films because Cs3Bi2I9 films are smoother. To get rid of the forming step, 10% of the Bi3+ cations were substituted with Na+ cations. However, this method only worked on Rb-based structures. This phenomenon was explained by the defect formation energy, which can only be negative in a corner-sharing Rb3Bi2I9 structure compared to a face-sharing octahedral Cs3Bi2I9 structure. As a result, the forming step was removed, and 100 cycles endurance and 1000 s retention performance were obtained. Similarly, the lower endurance is suspected to be due to the poor surface quality of the film.

Conditional knockout mice for the distal appendage protein CEP164 reveal its essential roles in airway multiciliated cell differentiation.

Multiciliated cells of the airways, brain ventricles, and female reproductive tract provide the motive force for mucociliary clearance, cerebrospinal fluid circulation, and ovum transport. Despite their clear importance to human biology and health, the molecular mechanisms underlying multiciliated cell differentiation are poorly understood. Prior studies implicate the distal appendage/transition fiber protein CEP164 as a central regulator of primary ciliogenesis; however, its role in multiciliogenesis remains unknown. In this study, we have generated a novel conditional mouse model that lacks CEP164 in multiciliated tissues and the testis. These mice show a profound loss of airway, ependymal, and oviduct multicilia and develop hydrocephalus and male infertility. Using primary cultures of tracheal multiciliated cells as a model system, we found that CEP164 is critical for multiciliogenesis, at least in part, via its regulation of small vesicle recruitment, ciliary vesicle formation, and basal body docking. In addition, CEP164 is necessary for the proper recruitment of another distal appendage/transition fiber protein Chibby1 (Cby1) and its binding partners FAM92A and FAM92B to the ciliary base in multiciliated cells. In contrast to primary ciliogenesis, CEP164 is dispensable for the recruitment of intraflagellar transport (IFT) components to multicilia. Finally, we provide evidence that CEP164 differentially controls the ciliary targeting of membrane-associated proteins, including the small GTPases Rab8, Rab11, and Arl13b, in multiciliated cells. Altogether, our studies unravel unique requirements for CEP164 in primary versus multiciliogenesis and suggest that CEP164 modulates the selective transport of membrane vesicles and their cargoes into the ciliary compartment in multiciliated cells. Furthermore, our mouse model provides a useful tool to gain physiological insight into diseases associated with defective multicilia.

Correction: Wafer-scale reliable switching memory based on 2-dimensional layered organic-inorganic halide perovskite.

Correction for 'Wafer-scale reliable switching memory based on 2-dimensional layered organic-inorganic halide perovskite' by Ja-Young Seo, et al., Nanoscale, 2017, DOI: 10.1039/c7nr05582j.

Wafer-scale reliable switching memory based on 2-dimensional layered organic-inorganic halide perovskite.

Recently, organic-inorganic halide perovskite (OHP) has been suggested as an alternative to oxides or chalcogenides in resistive switching memory devices due to low operating voltage, high ON/OFF ratio, and flexibility. The most studied OHP is 3-dimensional (3D) MAPbI3. However, MAPbI3 often exhibits less reliable switching behavior probably due to the uncontrollable random formation of conducting filaments. Here, we report the resistive switching property of 2-dimensional (2D) OHP and compare switching characteristics depending on structural dimensionality. The dimensionality is controlled by changing the composition of BA2MAn-1PbnI3n+1 (BA = butylammonium, MA = methylammonium), where 2D is formed from n = 1, and 3D is formed from n = ∞. Quasi 2D compositions with n = 2 and 3 are also compared. Transition from a high resistance state (HRS) to a low resistance state (LRS) occurs at 0.25 × 106 V m-1 for 2D BA2PbI4 film, which is lower than those for quasi 2D and 3D. Upon reducing the dimensionality from 3D to 2D, the ON/OFF ratio significantly increases from 102 to 107, which is mainly due to the decreased HRS current. A higher Schottky barrier and thermal activation energy are responsible for the low HRS current. We demonstrate for the first time reliable resistive switching from 4 inch wafer-scale BA2PbI4 thin film working at both room temperature and a high temperature of 87 °C, which strongly suggests that 2D OHP is a promising candidate for resistive switching memory.