Quantum chemical calculations of electron affinities of alkaline earth metal atoms (Ca, Sr, Ba, and Ra).

We performed high-level ab initio quantum chemical calculations, incorporating higher-order excitations, spin-orbit coupling (SOC), and the Gaunt interaction, to calculate the electron affinities (EAs) of alkaline earth (AE) metal atoms (Ca, Sr, Ba, and Ra), which are notably small. The coupled-cluster singles and doubles with perturbative triples [CCSD(T)] method is insufficient to accurately calculate the EAs of AE metal atoms. Higher-order excitations proved crucial, with the coupled-cluster singles, doubles, and triples with perturbative quadruples [CCSDT(2)Q] method effectively capturing dynamic electron correlation effects. The contributions of SOC (ΔESOs) to the EAs calculated using the multireference configuration interaction method with the Davidson correction, including SOC, positively enhance the EAs; however, these contributions are overestimated. The Dirac-Hartree-Fock (DHF)-CCSD(T) method addresses this overestimation and provides reasonable values for ΔESO (ΔESO-D). Employing additional sets of diffuse and core-valence correlation basis sets is critical for accurately calculating the EAs of AE metal atoms. The contributions of the Gaunt interaction (ΔEGaunt) to the EAs of AE metal atoms are negligible. Notably, the CCSDT(2)Q with the complete basis set limit + ΔESO-D + ΔEGaunt produced EA values for Ca, Sr, and Ba that closely aligned with experimental data and achieved accuracy exceeding the chemical accuracy. Based on our findings, the accurately proposed EA for Ra is 9.88 kJ/mol.

Photochemical Reaction Mechanism of Intramolecular H Transfer Reaction of H2 C3 O+ ⋠Radical Cation.

The photochemical reaction mechanism underlying the intramolecular H-transfer of the H2 C3 O+ ⋅ radical cation to the H2 CCCO+ ⋅ methylene ketene cation was elucidated using time-dependent density functional theory and high-level ab initio methods. Once the D1 state of H2 C3 O+ ⋅ is populated, the reaction proceeds to form an intermediate (IM) in the D1 state (IM4D1 ). The molecular structure of the conical intersection (CI) was optimized using a multiconfigurational ab initio method. The CI is readily accessible because it lies slightly above the IM4D1 in energy. In addition, the gradient difference vector of the CI is almost parallel to the intramolecular H-transfer reaction coordinate. Once the vibration mode of IM4D1 which is parallel to the reaction coordinate is populated, the degeneracy of the CI is readily lifted and H2 CCCO+ ⋅ was formed via a relaxation pathway in the D0 state. Our calculated results clearly describe the photochemical intramolecular H transfer reaction reported in a recent study.

Do Planar Tetracoordinate Fluorine Atoms Exist? Revisiting a Theoretical Prediction.

We re-examined the existence of planar tetracoordinate F (ptF) atoms, which was proposed recently by using high-level ab initio methods such as coupled-cluster singles and doubles with perturbative triples (CCSD(T)) with large basis sets. Our calculations indicate that the planar structures of FIn4+ (D4h), FTl4+ (D4h), FGaIn3+ (C2V), FIn2Tl2+ (D2h), FIn3Tl+ (C2V), and FInTl3+ (C2V) are not the minimum energy states; by contrast, they are transition states. Density functional theory calculations overestimate the size of the cavity formed by the four peripheral atoms, leading to erroneous conclusions regarding the existence of ptF atoms. Our analysis suggests that the preference for non-planar structures in the six cations studied is not due to the pseudo Jahn-Teller effect. Additionally, spin-orbit coupling does not alter the main conclusion that the ptF atom does not exist. If sufficiently large cavity formation by group 13 elements to accommodate the central F- ion is guaranteed, then the existence of ptF atoms is plausible.

High level ab initio and density functional study of TeF6+ and TeCl6+: Attainability of +7 oxidation state for tellurium.

Discovery of a new oxidation state for an element expands its chemistry. A high oxidation state, such as +7, is rare for sp-block elements except for halogens. In this study, we determined that Te can attain a +7 oxidation state through the existence of a distorted octahedron (DOH) structure of TeCl6+ based on coupled cluster singles and doubles with perturbative triples calculations. We propose a new type of isomerization that resembles pseudorotation. The octahedron structure of TeF6+ bearing one elongated axial bond isomerizes to a DOH via an associated pseudorotation.

Genetic vulnerabilities upon inhibition of DNA damage response.

Because of essential roles of DNA damage response (DDR) in the maintenance of genomic integrity, cellular homeostasis, and tumor suppression, targeting DDR has become a promising therapeutic strategy for cancer treatment. However, the benefits of cancer therapy targeting DDR are limited mainly due to the lack of predictive biomarkers. To address this challenge, we performed CRISPR screens to search for genetic vulnerabilities that affect cells' response to DDR inhibition. By undertaking CRISPR screens with inhibitors targeting key DDR mediators, i.e. ATR, ATM, DNAPK and CHK1, we obtained a global and unbiased view of genetic interactions with DDR inhibition. Specifically, we identified YWHAE loss as a key determinant of sensitivity to CHK1 inhibition. We showed that KLHL15 loss protects cells from DNA damage induced by ATM inhibition. Moreover, we validated that APEX1 loss sensitizes cells to DNAPK inhibition. Additionally, we compared the synergistic effects of combining different DDR inhibitors and found that an ATM inhibitor plus a PARP inhibitor induced dramatic levels of cell death, probably through promoting apoptosis. Our results enhance the understanding of DDR pathways and will facilitate the use of DDR-targeting agents in cancer therapy.

Genome-Wide CRISPR Screens Reveal ZATT as a Synthetic Lethal Target of TOP2-Poison Etoposide That Can Act in a TDP2-Independent Pathway.

Etoposide (ETO) is an anticancer drug that targets topoisomerase II (TOP2). It stabilizes a normally transient TOP2-DNA covalent complex (TOP2cc), thus leading to DNA double-strand breaks (DSBs). Tyrosyl-DNA phosphodiesterases two (TDP2) is directly involved in the repair of TOP2cc by removing phosphotyrosyl peptides from 5'-termini of DSBs. Recent studies suggest that additional factors are required for TOP2cc repair, which include the proteasome and the zinc finger protein associated with TDP2 and TOP2, named ZATT. ZATT may alter the conformation of TOP2cc in a way that renders the accessibility of TDP2 for TOP2cc removal. In this study, our genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screens revealed that ZATT also has a TDP2-independent role in promoting cell survival following ETO treatment. ZATT KO cells showed relatively higher ETO sensitivity than TDP2-KO cells, and ZATT/TDP2 DKO cells displayed additive hypersensitivity to ETO treatment. The study using a series of deletion mutants of ZATT determined that the N-terminal 1-168 residues of ZATT are required for interaction with TOP2 and this interaction is critical to ETO sensitivity. Moreover, depletion of ZATT resulted in accelerated TOP2 degradation after ETO or cycloheximide (CHX) treatment, suggesting that ZATT may increase TOP2 stability and likely participate in TOP2 turnover. Taken together, this study suggests that ZATT is a critical determinant that dictates responses to ETO treatment and targeting. ZATT is a promising strategy to increase ETO efficacy for cancer therapy.

Association between the COVID-19 pandemic, caregiving burden, and quality of life of caregivers of people with dementia: A cross-sectional study.

This study aimed to examine the association of COVID-19-related stress, anxiety, access to public healthcare services, and the presence of secondary caregivers (CGs) on the burden of caregiving and health-related quality of life (HRQoL) for CGs of people with dementia (PwD). A cross-sectional survey with 218 family CGs for PwD was completed in various settings between August and September 2021. The CGs had moderate and severe stress (42.7%) and reported having difficulty accessing public healthcare services (51.8%) and receiving help from secondary CGs (42.7%). In the multivariable linear regression, the stress and anxiety levels related to COVID-19 had a positive association with caregiver burden (ß = 4.25, p < 0.001, and ß = 5.73, p = 0.032, respectively), with no statistically significant association to HRQoL. Unexpectedly, accessing public healthcare services and supporting the secondary CGs were unrelated to the caregiving burden and HRQoL. Therefore, interventions aiming to alleviate family CGs' stress and anxiety levels should be provided to ensure PwD live in their homes in terms of continuity of public health service delivery.

Association between coffee consumption and periodontal diseases: a systematic review and meta-analysis.

BACKGROUND: Several studies have demonstrated association between coffee consumption and periodontal diseases. However, no systematic review and meta-analysis was performed. Therefore, we performed a systematic review and meta-analysis to evaluate the association between coffee intake and periodontitis. METHODS: We defined PICO statement as "Do coffee drinkers have a higher association of periodontitis or tooth loss than non-coffee drinkers?". We searched for articles using the Embase and Medline databases. The odds ratio was used as an effect measure to evaluate the association between coffee and periodontitis We divided coffee intake doses into three groups: no intake (≤ 0.03 cups/day), low intake (0.03 < x < 1 cups/day), and high intake (≥ 1 cup/day). Cohort and cross-sectional studies were eligible for inclusion in this study. The Newcastle-Ottawa scale was used to qualitatively assess the risk of bias. The degree of heterogeneity between studies was quantified using I2 statistics. RESULTS: Six articles were analysed, including two cohort studies and four cross-sectional studies. The pooled unadjusted odds ratios of periodontitis were 1.14 (0.93-1.39), 1.05 (0.73-1.52), 1.03 (0.91-1.16) and 1.10 (0.84-1.45) in the 4 meta-analyses (coffee drinker vs. non-coffee drinker, high intake vs. low intake, low intake vs. no intake, high intake vs. no intake), respectively. CONCLUSION: This is the first meta-analysis to investigate the relationship between coffee consumption and periodontitis. There was no relationship between coffee consumption and periodontitis. Further studies are required to assess whether a relationship between coffee consumption and periodontitis exists or not. PROSPERO registration number: CRD42022301341.

Aspects of Psychiatric Comorbidities in Breast Cancer Patients in Tertiary Hospitals Due to COVID-19 Outbreak in South Korea: A Single Center Longitudinal Cohort Study.

Background and Objectives: This study aimed to analyze the prevalence of mental disorders in patients with breast cancer at Ajou University Hospital. In addition, the patterns and prevalence of mental disorders according to the occurrence of coronavirus disease (COVID-19) were analyzed. Materials and Methods: From 1 January 2008 to 30 June 2021, psychiatric disorders were identified in 5174 female patients diagnosed with breast cancer at Ajou University Hospital. Based on the time when COVID-19 occurred, the pattern of onset of mental disorders in patients with breast cancer was analyzed. In addition, the prevalence of mental disorders according to the time of breast cancer diagnosis and age was evaluated. Results: A year before the diagnosis of breast cancer, 371 patients were diagnosed with a mental disorder. Of these, 201 patients were diagnosed with stress and adjustment disorders, and 97 patients had anxiety disorders. The overall frequency of psychiatric disorders after breast cancer diagnosis peaked two months later. Among psychiatric disorders reported before the COVID-19 pandemic, the proportion of stress/adaptation disorders was 52%, and among psychiatric disorders reported after the pandemic, it was significantly higher at 94.7%. Anxiety was found to be high in the elderly group aged ≥ 60 years, and the prevalence of stress and adjustment disorders tended to increase in the non-elderly group. Conclusions: Breast cancer patients showed different patterns of psychiatric disorders according to age, time of breast cancer diagnosis, and the occurrence of COVID-19. Owing to the COVID-19 pandemic, delays in treatment and anxiety about infection have increased the rate of stress and adjustment disorders in cancer patients. Mental health management during the pandemic and after cancer diagnosis can improve the quality of life of patients with cancer.

Carbon monoxide ameliorates acetaminophen-induced liver injury by increasing hepatic HO-1 and Parkin expression.

Acetaminophen (APAP) is widely used as an antifebrile and analgesic drug at recommended doses, whereas an overdose of APAP can cause severe liver damage. The molecular mechanisms underlying APAP-induced liver damage remain incompletely understood. Carbon monoxide (CO), an end-product of heme oxygenase (HO)-1 activity, can confer anti-inflammatory and antiapoptotic properties in cellular models of toxicity via regulation of mitochondrial function. The objective of this study was to evaluate the effects of CO on APAP-induced hepatotoxicity and CO's relationship to regulation of endoplasmic reticulum (ER) stress and mitochondrial signaling using CO-releasing molecules or low concentrations of CO applied as pretreatment or posttreatment. Using genetic deletion or knockdown approaches in alpha mouse liver cells or primary hepatocytes, respectively, we investigated the role of HO-1 and the mitophagy regulator protein Parkin on APAP-induced expression of the ER stress-associated apoptosis regulator cytosine-cytosine-adenosine-adenosine-thymidine (CCAAT)/enhancer-binding protein homologous protein (CHOP). We found that CO induced Parkin expression in hepatocytes via the protein kinase RNA-like ER kinase/eukaryotic translation initiation factor 2-α/activating transcription factor-4 signaling pathway. Additionally, CO gas inhalation significantly alleviated APAP-induced liver damage in vivo and correspondingly reduced serum alanine aminotransferase and aspartate aminotransferase levels as well as proinflammatory cytokines and reduced the expression of CHOP in liver tissues while dramatically increasing hepatic HO-1 and Parkin expression. We found that the protective effects of CO on APAP-induced liver damage were mediated by down-regulation of CHOP at a transcriptional and post-translational level via induction of HO-1 and Parkin, respectively, and associated with decreases in reactive oxygen species production and JNK phosphorylation. We conclude that CO may represent a promising therapeutic agent for APAP-induced liver injury.-Chen, Y., Park, H.-J., Park, J., Song, H.-C., Ryter, S. W., Surh, Y.-J., Kim, U.-H., Joe, Y., Chung, H. T. Carbon monoxide ameliorates acetaminophen-induced liver injury by increasing hepatic HO-1 and Parkin expression.

Carbon monoxide induces the assembly of stress granule through the integrated stress response.

Stress granules (SGs) are membraneless and phase-dense organelles that form transiently in response to a variety of harmful stimuli, including oxidative, heat, osmotic, ultraviolet light and chemotoxic stresses, and thus providing protective effects, allowing survivals. Carbon monoxide (CO), a gaseous second messenger, is synthesized by heme-oxygenases, and exerts anti-inflammatory, anti-proliferative and anti-apoptotic effects in a variety of cellular- and tissue-injury models. Several reports indicate that low levels of mitochondrial reactive oxygen species (mtROS) generated by CO can selectively activate PERK-eIF2α integrated stress response (ISR) to preserve the cellular homeostasis. Hence, CO can confer protection against cellular stresses. However, the mechanisms underlying the cyto-protective effects of CO against various harmful stimuli remain to be elucidated. Here, we sought to examine whether CO induces the SG assembly, and uncover its molecular mechanisms. We treated WI-38 cells and primary mouse embryonic fibroblasts (MEFs) with CO-releasing molecule 2 (CORM2) or CO gas, and found the SG assemblies were gradually increased in time and dose dependent manners. Next, we used Mito-TEMPO, an mtROS scavenger, to explore if mtROS might be involved in the CO-induced SG assembly. Furthermore, we confirmed the involvement of ISR consisted of PERK-eIF2α signaling pathway induced by CO for the SGs assembly. Finally, the inhibition of SG assembly by ISR inhibitor further verified CO-induced ISR might be responsible for SG. Taken together, in this study, we first demonstrated that CO is a novel SG inducer by activating ISR. Moreover, mtROS might be an initiator for the CO-induced ISR responsible for SG assembly.

CO ameliorates endothelial senescence induced by 5-fluorouracil through SIRT1 activation.

Endothelial senescence is the main risk factor that contributes to vascular dysfunction and the progression of vascular disease. Carbon monoxide (CO) plays an important role in preventing vascular dysfunction and in maintaining vascular physiology or homeostasis. The application of exogenous CO has been shown to confer protection in several models of cardiovascular injury or disease, including hypertension, atherosclerosis, balloon-catheter injury, and graft rejection. However, the mechanism by which CO prevents endothelial senescence has been largely unexplored. The aim of this study was to evaluate the effects of CO on endothelial senescence and to investigate the possible mechanisms underlying this process. We measured the levels of senescence-associated-ß-galactosidase activity, senescence-associated secretory phenotype, reactive oxygen species (ROS) production, and stress granule in human umbilical vein endothelial cells and the WI-38 human diploid fibroblast cell line. We found that 5-fluorouracil (5FU)-induced ROS generation was inhibited by CO-releasing molecules (CORM)-A1 treatment, and endothelial senescence induced by 5FU was attenuated by CORM-A1 treatment. The SIRT1 inhibitor EX527 reversed the inhibitory effect of CO on the 5FU-induced endothelial senescence. Furthermore, SIRT1 deficiency abolished the stress granule formation by CO. Our results suggest that CO alleviates the endothelial senescence induced by 5FU through SIRT1 activation and may hence have therapeutic potential for the treatment of vascular diseases.

FGF21 induced by carbon monoxide mediates metabolic homeostasis via the PERK/ATF4 pathway.

The prevalence of metabolic diseases, including type 2 diabetes, obesity, and cardiovascular disease, has rapidly increased, yet the molecular mechanisms underlying the metabolic syndrome, a primary risk factor, remain incompletely understood. The small, gaseous molecule carbon monoxide (CO) has well-known anti-inflammatory, antiproliferative, and antiapoptotic effects in a variety of cellular- and tissue-injury models, whereas its potential effects on the complex pathways of metabolic disease remain unknown. We demonstrate here that CO can alleviate metabolic dysfunction in vivo and in vitro. We show that CO increased the expression and section of the fibroblast growth factor 21 (FGF21) in hepatocytes and liver. CO-stimulated PERK activation and enhanced the levels of FGF21 via the eIF2α-ATF4 signaling pathway. The induction of FGF21 by CO attenuated endoreticulum stress- or diet-induced, obesity-dependent hepatic steatosis. Moreover, CO inhalation lowered blood glucose levels, enhanced insulin sensitivity, and promoted energy expenditure by stimulating the emergence of beige adipose cells from white adipose cells. In conclusion, we suggest that CO acts as a potent inducer of FGF21 expression and that CO critically depends on FGF21 to regulate metabolic homeostasis.-Joe, Y., Kim, S., Kim, H. J., Park, J., Chen, Y., Park, H.-J., Jekal, S.-J., Ryter, S. W., Kim, U. H., Chung, H. T. FGF21 induced by carbon monoxide mediates metabolic homeostasis via the PERK/ATF4 pathway.

Roles of Tristetraprolin in Tumorigenesis.

Genetic loss or mutations in tumor suppressor genes promote tumorigenesis. The prospective tumor suppressor tristetraprolin (TTP) has been shown to negatively regulate tumorigenesis through destabilizing the messenger RNAs of critical genes implicated in both tumor onset and tumor progression. Regulation of TTP has therefore emerged as an important issue in tumorigenesis. Similar to other tumor suppressors, TTP expression is frequently downregualted in various human cancers, and its low expression is correlated with poor prognosis. Additionally, disruption in the regulation of TTP by various mechanisms results in the inactivation of TTP protein or altered TTP expression. A recent study showing alleviation of Myc-driven lymphomagenesis by the forced expression of TTP has shed light on new therapeutic avenues for cancer prevention and treatment through the restoration of TTP expression. In this review, we summarize key oncogenes subjected to the TTP-mediated mRNA degradation, and discuss how dysregulation of TTP can contribute to tumorigenesis. In addition, the control mechanism underlying TTP expression at the posttranscriptional and posttranslational levels will be discussed.

Voltage Scaling of Graphene Device on SrTiO3 Epitaxial Thin Film.

Electrical transport in monolayer graphene on SrTiO3 (STO) thin film is examined in order to promote gate-voltage scaling using a high-k dielectric material. The atomically flat surface of thin STO layer epitaxially grown on Nb-doped STO single-crystal substrate offers good adhesion between the high-k film and graphene, resulting in nonhysteretic conductance as a function of gate voltage at all temperatures down to 2 K. The two-terminal conductance quantization under magnetic fields corresponding to quantum Hall states survives up to 200 K at a magnetic field of 14 T. In addition, the substantial shift of charge neutrality point in graphene seems to correlate with the temperature-dependent dielectric constant of the STO thin film, and its effective dielectric properties could be deduced from the universality of quantum phenomena in graphene. Our experimental data prove that the operating voltage reduction can be successfully realized due to the underlying high-k STO thin film, without any noticeable degradation of graphene device performance.

Tristetraprolin mediates the anti-proliferative effects of metformin in breast cancer cells.

Metformin, which is a drug commonly prescribed to treat type 2 diabetes, has anti-proliferative effects in cancer cells; however, the molecular mechanisms underlying this effect remain largely unknown. The aim is to investigate the role of tristetraprolin (TTP), an AU-rich element-binding protein, in anti-proliferative effects of metformin in cancer cells. p53 wild-type and p53 mutant breast cancer cells were treated with metformin, and expression of TTP and c-Myc was analyzed by semi-quantitative RT-PCR, Western blots, and promoter activity assay. Breast cancer cells were transfected with siRNA against TTP to inhibit TTP expression or c-Myc and, after metformin treatment, analyzed for cell proliferation by MTS assay. Metformin induces the expression of tristetraprolin (TTP) in breast cancer cells in a p53-independent manner. Importantly, inhibition of TTP abrogated the anti-proliferation effect of metformin. We observed that metformin decreased c-Myc levels, and ectopic expression of c-Myc blocked the effect of metformin on TTP expression and cell proliferation. Our data indicate that metformin induces TTP expression by reducing the expression of c-Myc, suggesting a new model whereby TTP acts as a mediator of metformin's anti-proliferative activity in cancer cells.

Transcriptional and Posttranslational Regulation of Nucleotide Excision Repair: The Guardian of the Genome against Ultraviolet Radiation.

Ultraviolet (UV) radiation from sunlight represents a constant threat to genome stability by generating modified DNA bases such as cyclobutane pyrimidine dimers (CPD) and pyrimidine-pyrimidone (6-4) photoproducts (6-4PP). If unrepaired, these lesions can have deleterious effects, including skin cancer. Mammalian cells are able to neutralize UV-induced photolesions through nucleotide excision repair (NER). The NER pathway has multiple components including seven xeroderma pigmentosum (XP) proteins (XPA to XPG) and numerous auxiliary factors, including ataxia telangiectasia and Rad3-related (ATR) protein kinase and RCC1 like domain (RLD) and homologous to the E6-AP carboxyl terminus (HECT) domain containing E3 ubiquitin protein ligase 2 (HERC2). In this review we highlight recent data on the transcriptional and posttranslational regulation of NER activity.

Cilostazol attenuates murine hepatic ischemia and reperfusion injury via heme oxygenase-dependent activation of mitochondrial biogenesis.

Hepatic ischemia-reperfusion (I/R) can cause hepatocellular injury associated with the inflammatory response and mitochondrial dysfunction. We studied the protective effects of the phosphodiesterase inhibitor cilostazol in hepatic I/R and the roles of mitochondria and the Nrf2/heme oxygenase-1 (HO-1) system. Wild-type, Hmox1(-/-), or Nrf2(-/-) mice were subjected to hepatic I/R in the absence or presence of cilostazol followed by measurements of liver injury. Primary hepatocytes were subjected to cilostazol with the HO-1 inhibitor ZnPP, or Nrf2-specific siRNA, followed by assessment of mitochondrial biogenesis. Preconditioning with cilostazol prior to hepatic I/R protected against hepatocellular injury and mitochondrial dysfunction. Cilostazol reduced the serum levels of alanine aminotransferase, TNF-α, and liver myeloperoxidase content relative to control I/R-treated mice. In primary hepatocytes, cilostazol increased the expression of HO-1, and markers of mitochondrial biogenesis, PGC-1α, NRF-1, and TFAM, induced the mitochondrial proteins COX III and COX IV and increased mtDNA and mitochondria content. Pretreatment of primary hepatocytes with ZnPP inhibited cilostazol-induced PGC-1α, NRF-1, and TFAM mRNA expression and reduced mtDNA and mitochondria content. Genetic silencing of Nrf2 prevented the induction of HO-1 and mitochondrial biogenesis by cilostazol in HepG2 cells. Cilostazol induced hepatic HO-1 production and mitochondrial biogenesis in wild-type mice, but not in Hmox1(-/-) or Nrf2(-/-) mice, and failed to protect against liver injury in Nrf2(-/-) mice. These results suggest that I/R injury can impair hepatic mitochondrial function, which can be reversed by cilostazol treatment. These results also suggest that cilostazol-induced mitochondrial biogenesis was mediated by an Nrf-2- and HO-1-dependent pathway.

NDR1 modulates the UV-induced DNA-damage checkpoint and nucleotide excision repair.

Nucleotide excision repair (NER) is the sole mechanism of UV-induced DNA lesion repair in mammals. A single round of NER requires multiple components including seven core NER factors, xeroderma pigmentosum A-G (XPA-XPG), and many auxiliary effector proteins including ATR serine/threonine kinase. The XPA protein helps to verify DNA damage and thus plays a rate-limiting role in NER. Hence, the regulation of XPA is important for the entire NER kinetic. We found that NDR1, a novel XPA-interacting protein, modulates NER by modulating the UV-induced DNA-damage checkpoint. In quiescent cells, NDR1 localized mainly in the cytoplasm. After UV irradiation, NDR1 accumulated in the nucleus. The siRNA knockdown of NDR1 delayed the repair of UV-induced cyclobutane pyrimidine dimers in both normal cells and cancer cells. It did not, however, alter the expression levels or the chromatin association levels of the core NER factors following UV irradiation. Instead, the NDR1-depleted cells displayed reduced activity of ATR for some set of its substrates including CHK1 and p53, suggesting that NDR1 modulates NER indirectly via the ATR pathway.

Quantum Hall conductance of graphene combined with charge-trap memory operation.

The combination of quantum Hall conductance and charge-trap memory operation was qualitatively examined using a graphene field-effect transistor. The characteristics of two terminal quantum Hall conductance appeared clearly on the background of a huge conductance hysteresis during a gate-voltage sweep for a device using monolayer graphene as a channel,hexagonal boron-nitride flakes as a tunneling dielectric and defective silicon oxide as the charge storage node. Even though there was a giant shift of the charge neutrality point, the deviation of quantized resistance value at the state of filling factor 2 was less than 1.6% from half of the von Klitzing constant. At high Landau level indices, the behaviors of quantum conductance oscillation between the increasing and the decreasing electron densities were identical in spite ofa huge memory window exceeding 100 V. Our results indicate that the two physical phenomena, two-terminal quantum Hall conductance and charge-trap memory operation, can be integrated into one device without affecting each other.