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Abstract Background The distribution of anti‐factor Xa activity (AXA) in patients with nonvalvular atrial fibrillation (NVAF) taking edoxaban 15 mg has not been fully elucidated. Methods and Results The trough and peak AXA were measured in 19 NVAF patients taking edoxaban 15 mg. We compared these results with those in patients taking edoxaban 30 mg. The peak AXA differed significantly between the 15 mg and the 30 mg groups (0.74 ± 0.40 IU/mL vs. 1.25 ± 0.48 IU/mL, respectively; p

Abstract Adipocyte-cancer cell interactions promote tumor development and progression. Previously, we identified adipsin (CFD) and its downstream effector, hepatocyte growth factor (HGF), as adipokines that enhance adipocyte-breast cancer stem cell interactions. Here, we show that adipsin-dependent adipocyte maturation and the subsequent upregulation of HGF promote tumor invasion in breast cancers. Mature adipocytes, but not their precursors, significantly induced breast tumor cell migration and invasion in an adipsin expression-dependent manner. Promoters of tumor invasion, galectin 7 and matrix metalloproteinases, were significantly upregulated in cancer cells cocultured with mature adipocytes; meanwhile, their expression levels in cancer cells cocultured with adipocytes were reduced by adipsin knockout (Cfd KO) or a competitive inhibitor of CFD. Tumor growth and distant metastasis of mammary cancer cells were significantly suppressed when syngeneic mammary cancer cells were transplanted into Cfd KO mice. Histological analyses revealed reductions in capsular formation and tumor invasion at the cancer-adipocyte interface in the mammary tumors formed in Cfd KO mice. These findings indicate that adipsin-dependent adipocyte maturation may play an important role in adipocyte-cancer cell interaction and breast cancer progression.

Abstract Background Polypharmacy is an escalating public health concern across various healthcare settings worldwide. We aimed to comprehensively investigate postoperative complications after laparoscopic surgery for colorectal cancer and explore their association with polypharmacy. As laparoscopic surgery is widespread, clarifying the association between polypharmacy and postoperative complications is clinically important. Methods We retrospectively surveyed the medical charts of adult inpatients who underwent laparoscopic surgery for colorectal cancer at Tohoku Medical and Pharmaceutical University Hospital between April 2019 and March 2023. Postoperative complications were determined using the Clavien–Dindo classification. We explored the factors related to postoperative complications and calculated the cut-off values for the number of medication ingredients. Results Among the 236 patients, 32 (13.6%) developed postoperative complications. On multivariable logistic regression analysis, the number of regularly used medication ingredients (odds ratio = 1.160, 95% confidence interval 1.050–1.270, p = 0.002) was identified as a factor related to postoperative complications. The identified cut-off value for complications was 10 ingredients. Patients using 10 or more ingredients had approximately 3.5 times higher occurrence of postoperative complications than those using fewer than 10 ingredients (33.3% vs. 9.3%, p

Antibodies are powerful tools for the therapy and diagnosis of various diseases. In addition to conventional hybridoma-based screening, recombinant antibody-based screening has become a common choice; however, its application is hampered by two factors: (1) screening starts after Ig gene cloning and recombinant antibody production only, and (2) the antibody is composed of paired chains, heavy and light, commonly expressed by two independent expression vectors. Here, we introduce a method for the rapid screening of recombinant monoclonal antibodies by establishing a Golden Gate-based dual-expression vector and in-vivo expression of membrane-bound antibodies. Using this system, we demonstrate the rapid isolation of influenza cross-reactive antibodies with high affinity from immunized mice within 7 days. This system is particularly useful for isolating therapeutic or diagnostic antibodies, for example during foreseen pandemics.

Leea asiatica (L.) Ridsdale has been used by different ethnic communities to manage diseased conditions that can be traced to oxidative stress and cellular inflammations but scientific evidences to support the claim are scanty. The objective of this study was to isolate and identify the antioxidants present in the aerial parts of Leea asiatica, perform their molecular docking against proteins to inspect whether the traditional uses of the plant can be validated by an in-silico approach. Quercetin (1), gallic acid (2), kaempferol (3), methyl gallate (4), myricetin 3-O-α-L-rhamnopyranoside (5), (−)-epicatechin-3-O-gallate (6) and (−)-epigallocatechin-3-O-gallate (7) were isolated from the 70 % methanolic extract of the aerial parts. Compounds 2, 4, 6, and 7 are reported for the first time from Leea asiatica. Quercetin (1), gallic acid (2), (−)-epicatechin-3-O-gallate (6) and (−)-epigallocatechin-3-O-gallate (7) showed potent antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. Molecular docking with NADPH oxidase and TNF-α revealed that epicatechin-3-O-gallate, epigallocatechin-3-O-gallate and quercetin bound with the least binding energy amongst the isolated compounds as well as standard (Trolox and Prednisolone). By molecular dynamics analysis, epicatechin-3-O-gallate maintained stable conformation with NADPH oxidase and TNF-α and was found to possess good ADMET profile thereby validating the ethnic use of the plant as a medicine in the management of inflammatory conditions by an in vitro and in silico approach.

Background Appropriate prognostic indicators are required for patients with stage IV colorectal cancer (CRC). Lymph node metastasis mainly involves four histological types of CRC. Some metastatic lymph nodes (mLNs) showing cribriform carcinoma are associated with distant metastasis in patients with node-positive CRC and are correlated with recurrence and survival in stage III disease. However, the significance of mLN histology in the prognosis of patients with node-positive stage IV disease remains unclear. Methods We enrolled 449 consecutive patients with CRC who underwent primary tumor resection with lymph node dissection between January 2011 and November 2018. This study included 88 patients with node-positive stage IV CRC and synchronous or metachronous distant metastases. We retrospectively investigated the association between cancer histology in the mLNs based on our classification and cancer-specific survival (CSS) in patients with node-positive stage IV CRC. Results Kaplan-Meier analysis showed that CSS was better in patients with CRC and all the mLNs showing tubular-type carcinoma. In contrast, patients with at least some mLNs showing poorly differentiated-type carcinoma had poor prognosis. Multivariate analysis showed that “all mLNs showing tubular-type carcinoma” was an independent good prognostic factor for CSS in patients with node-positive stage IV CRC. In addition, “at least some mLNs showing poorly differentiated-type carcinoma” was an independent poor prognostic factor for CSS in patients with node-positive stage IV disease. Conclusions The histological type of the mLN may indicate a better or poor prognosis for patients with stage IV CRC.

Advances in cancer treatment have improved the survival of patients with cancer, with a concomitant increase in the proportion of patients with metastatic brain tumors (MBTs). In this study, we used cancer registries established in Japan after 2016 and available patient data by organ in order to conduct an accurate epidemiological study. To the best of our knowledge, this is the first study to report on the detailed epidemiological data on MBT at the prefectural level in Japan using the Miyazaki Brain Tumor Database and Miyazaki Cancer Registry. This study included 425 new cases of MBTs diagnosed in Miyazaki Prefecture from 2007 to 2016. As per our findings, the most frequent primary tumor in Miyazaki Prefecture was found to be in the lung (49.4%), followed by colon/rectum/anus (9.4%) and breast (8.5%). Among patients with MBTs, 59.1% were males, a number closely similar to that of Japan, as shown in the Japanese Brain Tumor Registry (55.5%). The median age at diagnosis was 68 and 63 years in Miyazaki Prefecture and Japan, respectively. Although more patients were symptomatic in Miyazaki Prefecture than in Japan (88.5% vs. 15.5%), fewer patients opted for surgery (33.6% vs. 61.9%), probably because of their advanced age at diagnosis. As per the findings of this study, the annual incidence rate of new MBTs (i.e., ratio of the number of new cancer registrations to that of new MBT patients in Miyazaki Prefecture) was at 0.41%. The number of tumor sites in MBTs was independent of the total number of cancers per organ. Considering the expansion of cancer registries worldwide, including those on brain tumors, further epidemiological analysis of MBTs is deemed warranted.

Abstract Background Schizophrenia is a psychiatric disorder characterized by hallucinations, delusions, and other symptoms. Although treatment guidelines for schizophrenia have been established in Japan, drugs are not recommended for pediatric schizophrenia. Additionally, the temporal trends in prescribing antipsychotics for pediatric patients with schizophrenia are unclear. Therefore, we aimed to clarify the trends in antipsychotic prescriptions for Japanese pediatric outpatients from 2015 to 2022. Methods Administrative data (as of November 2023) of Japanese pediatric outpatients with schizophrenia aged 0–18 years who visited acute-care diagnosis procedure combination hospitals between January 1, 2015, and December 31, 2022, were included in this study. The target drugs for schizophrenia were all indicated for treating schizophrenia and marketed in Japan as of December 2022. Annual prescription trends for antipsychotics during this period were calculated based on their proportions. The Cochran–Armitage trend test was used to evaluate the proportion of prescriptions for each antipsychotic. Results The main drugs prescribed for these patients were aripiprazole and risperidone. Among male patients, the proportion of prescriptions for aripiprazole increased significantly from 21.2% in 2015 to 35.9% in 2022, whereas that for risperidone decreased significantly from 47.9% in 2015 to 36.7% in 2022 (both P

Abstract Background As methadone can prevent the development of opioid resistance, it has application in alleviating cancer-related pain that proves challenging to manage with other opioids. QT interval prolongation is a serious side effect of methadone treatment, with some reported deaths. In particular, owing to the increased risk of QT interval prolongation, caution should be exercised when using it in combination with drugs that also prolong the QT interval. Case presentation This study presents a case in which methadone was introduced to a patient (a man in his 60s) already using levofloxacin, which could prolong the QT interval—a serious side effect of methadone treatment—and whose QTc value tended to increase. Given that levofloxacin can increase the risk of QT interval prolongation, we considered switching to other antibacterial agents before introducing methadone. However, because the neurosurgeon judged that controlling a brain abscess was a priority, low-dose methadone was introduced with continuing levofloxacin. Owing to the risks, we performed frequent electrocardiograms. Consequently, we responded before the QTc increased enough to meet the diagnostic criteria for QT interval prolongation. Consequently, we prevented the occurrence of drug-induced long QT syndrome. Conclusions When considering the use of methadone for intractable cancer pain, it is important to eliminate possible risk factors for QT interval prolongation. However, as it may be difficult to discontinue concomitant drugs owing to comorbidities, there could be cases in which the risk of QT interval prolongation could increase, even with the introduction of low-dose methadone. In such cases, frequent monitoring, even with simple measurements such as those used in this case, is likely to prevent progression to more serious conditions.

Viewport-based 360-degree video delivery is a typical method to reduce video traffic for virtual reality (VR) applications. However, viewport-based solutions cause key issues in multi-user VR applications, including high video traffic due to redundant video transmission across multiple headset users and quality degradation due to viewport transitions. These problems occur in both camera-to-server and server-to-user video transmissions. In this study, we propose a 360-degree video delivery scheme for multi-user VR applications. To overcome the above issues, the proposed approach includes appropriate quality and transmission control for camera-to-server and server-to-user video transmissions. The camera extracts the estimated potential region from the dual fisheye video. The server controls recompression at the server to follow the viewport transition and hybrid unicast and multicast tile delivery to avoid redundant transmissions. Evaluations using 360-degree video and corresponding fixation points from multiple users show that the proposed scheme prevents redundant transmissions across multiple headset users and provides better viewport quality for each user under the same video traffic. For example, the proposed scheme reduces video traffic by up to 36.4% compared to the existing viewport-based 360-degree video delivery scheme for ten headset users.

Cloud gaming allows users to play high-quality games on low-end devices by offloading game processing to the cloud. However, network latency remains a significant issue affecting the gaming experience. Speculative execution is a promising approach to hide network latency by predicting and transmitting future frames early. However, existing methods generate excessive compute load and network traffic due to many potential input patterns. This paper introduces a pattern reduction method that uses a bit field representation of the input and facilitates efficient speculative execution in cloud games. There are two pattern reduction techniques: analyzing temporal patterns to detect frequent transitions and using LSTM-based predictions to estimate input probabilities. Experiments using actual gaming data show that the proposed methods significantly reduce rendered frames and network traffic versus prior speculative execution methods. The results demonstrate the method’s effectiveness and scalability across diverse game genres.

Abstract After activation, some invariant natural killer T (iNKT) cells are differentiated into Klrg1+ long-lived effector NKT1 cells. However, the regulation from the effector phase to the memory phase has not been elucidated. Zeb2 is a zinc finger E homeobox-binding transcription factor and is expressed in a variety of immune cells, but its function in iNKT cell differentiation remains also unknown. Here, we show that Zeb2 is dispensable for development of iNKT cells in the thymus and their maintenance in steady state peripheral tissues. After ligand stimulation, Zeb2 plays essential roles in the differentiation to and maintenance of Klrg1+ Cx3cr1+GzmA+ iNKT cell population derived from the NKT1 subset. Our results including single-cell-RNA-seq analysis indicate that Zeb2 regulates Klrg1+ long-lived iNKT cell differentiation by preventing apoptosis. Collectively, this study reveals the crucial transcriptional regulation by Zeb2 in establishment of the memory iNKT phase through driving differentiation of Klrg1+ Cx3cr1+GzmA+ iNKT population.

Introduction: The efficacy of catheter ablation in patients with low cardiac function has been previously reported; however, only a few studies have included mid-range ejection fraction (mrEF). This study aimed to evaluate the efficacy and safety of atrial fibrillation (AF) ablation in patients with left ventricular ejection fraction (LVEF)

Even with advanced plasmid and viral vectors, attaining copy numbers of multiple genes among different transfected cells is challenging. We achieved one gene expression from a single-copy gene in one cell using a transgene competition system, a combination of the Kazusa cDNA clones and our dual recombinase-mediated cassette exchange system. All 48 nuclear receptors were simultaneously expressed in one dish at the same expression level in HEK293 using this system, and the cell proliferation rate was compared. Significant differences were observed between cells transfected with CMV- or EF1 promoter-driven expression of the 48 nuclear receptors after 8 weeks. The EF1-NR1I2 cell line, which exhibited the highest increase from 2 to 8 weeks, showed 1.13-fold higher proliferation than the EF1-DsRed line. On the other hand, the EF1-NR4A1 cell line, which showed the maximum decrease at 8 weeks, showed 0.88-fold lower proliferation than the EF1-DsRed line. The results were confirmed in both our transgene competition system and long-term growth experiments. Our transgene competition system offers a wide-range, simple, and accurate cell competition method.

Abstract Background Sugarcane trash (SCT) represents up to 18% of the aboveground biomass of sugarcane, surpassing 28 million tons globally per year. The majority of SCT is burning in the fields. Hence, efficient use of SCT is necessary to reduce carbon dioxide emissions and global warming and establish agro-industrial biorefineries. Apart from its low costs, conversion of whole biomass with high production efficiency and titer yield is mandatory for effective biorefinery systems. Therefore, in this study, we developed a simple, integrated method involving a single step of glycerolysis pretreatment to produce antiviral glycerolysis lignin (AGL). Subsequently, we co-fermented glycerol with hydrolyzed glucose and xylose to yield high titers of bioethanol. Results SCT was subjected to pretreatment with microwave acidic glycerolysis with 50% aqueous (aq.) glycerol (MAG50); this pretreatment was optimized across different temperature ranges, acid concentrations, and reaction times. The optimized MAG50 (opMAG50) of SCT at 1:15 (w/v) in 1% H2SO4, 360 µM AlK(SO4)2 at 140 °C for 30 min (opMAG50) recovered the highest amount of total sugars and the lowest amount of furfural byproducts. Following opMAG50, the soluble fraction, i.e., glycerol xylose-rich solution (GXRS), was separated by filtration. A residual pulp was then washed with acetone, recovering 7.9% of the dry weight (27% of lignin) as an AGL. AGL strongly inhibited the replication of encephalomyocarditis virus (EMCV) in L929 cells without cytotoxicity. The pulp was then saccharified in yeast peptone medium by cellulase to produce a glucose concentration similar to the theoretical yield. The total xylose and arabinose recoveries were 69% and 93%, respectively. GXRS and saccharified sugars were combined and co-fermented through mixed cultures of two metabolically engineered Saccharomyces cerevisiae strains: glycerol-fermenting yeast (SK-FGG4) and xylose-fermenting yeast (SK-N2). By co-fermenting glycerol and xylose with glucose, the ethanol titer yield increased to 78.7 g/L (10% v/v ethanol), with a 96% conversion efficiency. Conclusion The integration of AGL production with the co-fermentation of glycerol, hydrolyzed glucose, and xylose to produce a high titer of bioethanol paves an avenue for the use of surplus glycerol from the biodiesel industry for the efficient utilization of SCT and other lignocellulosic biomasses.

Abstract Biodegradable plastics can solve the problem of unwanted plastics accumulating in the environment if they can be given the contradictory properties of durability in use and rapid degradation after use. Commercially available agricultural biodegradable mulch films are made from formulations containing polybutylene adipate-co-terephthalate (PBAT) to provide mechanical and UV resistance during the growing season. Although used films are ploughed into the soil using a tiller to promote decomposition, it is difficult if they remain durable. We showed that an enzyme produced by the leaf surface yeast Pseudozyma antarctica (PaE) degrades PBAT-containing films. In laboratory studies, PaE randomly cleaved the PBAT polymer chain and induced erosion of the film surface. In the field, commercial biodegradable films containing PBAT placed on ridges were weakened in both the warm and cold seasons by spraying the culture filtrate of P. antarctica. After the field was ploughed the next day, the size and total weight of residual film fragments decreased significantly (p

The demand for wireless communication capacity continues to increase with the extensive usage of smartphones, tablets, and devices that are related to the Internet of Things (IoT). However, devices and base stations are diversified, and base stations of various sizes are mixed. In existing cellular networks, the transmission powers of the base stations are different. If the downlink received power from the base station that belongs to the device is maximum, the uplink received power from the device at the base station is not always the maximum. This study maximizes the power that is received from the device through downlink-uplink decoupling (DUDe). DUDe can improve the spectral efficiency by selecting the downlink base station and the uplink base station independently in a network with base stations with different transmission powers. This study focuses on two technologies, DUDe and the dynamic channel assignment (DCA). It proposes an association algorithm to solve the dynamic combinational optimization problem for uplink and downlink cellular networks separately using DUDe. When a user device arrives, it first connects to the base station that has the maximum capacity at that time. Subsequently, by using the base station assignment at that time as an individual, the proposed method performs a more optimal base station assignment with DCA by using a genetic algorithm. The computer simulations demonstrate that the proposed method can achieve up to a 140 % higher spectral efficiency than the existing DUDe in the fixed channel assignment (FCA).

Abstract Background Glioma-initiating cells (GICs) are the source of glioma cells that can self-renew, have pluripotency, and are treatment-resistant, so are the starting point for relapse and eventual death despite multimodality therapy. L-[methyl-11C] methionine PET has observed high accumulation at the time of recurrence, it is important to understand the mechanism of tumor cell activation caused by the reorganization of methionine metabolism. Methods We cultured cells in methionine-deprived culture medium for comprehensive analysis. Based on the obtained results, the possible target molecules were chemically inhibited and the respective markers were analyzed. Results Methionine depletion markedly decreased proliferation and increased cell death of GICs. Decreased S-adenosyl-methionine, which is synthesized intracellularly by catalyzed by methionine adenosyltransferase using methionine, triggered the following: (i) global DNA demethylation, (ii) hyper-methylation of signaling pathways regulating pluripotency of stem cells, (iii) decreased expression of the core-genes and pluripotent markers of stem cells including FOXM1, SOX2, SOX4, PROM1, and OLIG2, (iv) decreased cholesterol synthesis and increased excretion mainly through decreased SREBF2, and (v) down-regulation of the large subunit of ribosomal protein configured 28S and ACA43, small nucleolar RNA guiding the pseudouridylation of 28S rRNA, which is essential for translation. In addition, inhibition of cholesterol synthesis with statin resulted in a phenotype similar to that of methionine depletion and decreases in stem cell markers and small nucleolar RNA ACA43. Moreover, suppression of FOXM1 decreased stem cell markers such as SOX4 and PROM1. The gene expression profile for cholesterol production was obtained from the Ivy Glioblastoma Atlas Project database and compared between tumor cells with relatively low methionine levels in areas of pseudopalisading arrangement around necrosis and tumor cells in the infiltrating region, showing that cells in the infiltrating region have higher capacity to produce cholesterol. Conclusions Methionine metabolism is closely related with self-renewal, pluripotency, and cell death in GICs through modification of cholesterol biosynthesis, especially in the SREBF2-FOXM1 and ACA43 axis with modification of rRNA.

The leaves of Chrysanthemum indicum L. are known to have various bioactive compounds; however, industrial use is extremely limited. To overcome this situation by producing high-quality leaves with high bioactive content, this study examined the environmental factors affecting the phytochemical content and antioxidant activity using C. indicum leaves collected from 22 sites in Kochi Prefecture, Japan. Total phenolic and flavonoid content in the dry leaves ranged between 15.0 and 64.1 (mg gallic acid g−1) and 2.3 and 11.4 (mg quercetin g−1), while the antioxidant activity (EC50) of the 50% ethanol extracts ranged between 28.0 and 123.2 (µg mL−1) in 1,1-Diphenyl-2-picrylhydrazyl radical scavenging assay. Among the identified compounds, chlorogenic acid and 1,5-dicaffeoylquinic acid were the main constituents in C. indicum leaves. The antioxidant activity demonstrated a positive correlation with 1,5-dicaffeoylquinic acid (R2 = 0.62) and 3,5-dicaffeoylquinic acid (R2 = 0.77). The content of chlorogenic acid and dicaffeoylquinic acid isomers varied significantly according to the effects of exchangeable magnesium, cation exchange capacity, annual temperature, and precipitation, based on analysis of variance. The habitat suitability map using the geographical information system and the MaxEnt model predicted very high and high regions, comprising 3.2% and 10.1% of the total area, respectively. These findings could be used in future cultivation to produce high-quality leaves of C. indicum.

Podosomes are actin structures important in multiple cell functions. Here, the authors use iPALM microscopy to reveal an “hourglass” shape of the podosome actin core, a protruding “knob” at the bottom of the core, and two actin networks extending from it.

Introduction The sequelae of COVID-19 have been described as a multisystemic condition, with a great impact on the cardiovascular and pulmonary systems with abnormalities in pulmonary function tests, such as lower diffusing capacity of the lung for carbon monoxide (DLco) levels and pathological patterns in spirometry; persistence of radiological lesions; cardiac involvement such as myocarditis and pericarditis; and an increase in mental disorders such as anxiety and depression. Several factors, such as infection severity during the acute phase as well as vaccination status, have shown some variable effects on these post-COVID-19 conditions, mainly at a clinical level such as symptoms persistence. Longitudinal assessments and reversibility of changes across the spectrum of disease severity are required to understand the long-term impact of COVID-19.Methods and analysis A prospective cohort study aims to assess the impact of SARS-CoV-2 infection on cardiopulmonary function and quality of life after the acute phase of the disease over a 6-month follow-up period. Sample size was calculated to recruit 200 participants with confirmatory COVID-19 tests who will be subsequently classified according to infection severity. Four follow-up visits at baseline, month 1, month 3 and month 6 after discharge from the acute phase of the infection will be scheduled as well as procedures such as spirometry, DLco test, 6-minute walk test, chest CT scan, echocardiogram, ECG, N-terminal pro-B-type natriuretic peptide measurement and RAND-36 scale. Primary outcomes are defined as abnormal pulmonary function test considered as DLco

Article highlights The critical value in which Taylor flow with a small aspect ratio bifurcated into the wavy Taylor flow was clarified by a numerical analysis. The analytical results were in agreements with the experimental results, while there were quantitative differences in some areas. This numerical analysis was confirmed that the bifurcation phenomenon from the Taylor flow into the wavy Taylor flow can be clarified.

Abstract Background The inappropriate use of antibiotics significantly contributes to the development of antibiotic resistance. There is limited information about the use of antibiotics among parents from rural areas in Peru. This study aimed to describe the knowledge, attitudes and practices towards antibiotics among parents of children 40 years. Parents who had self-medicated his/her child with antibiotics (n = 120, 52%) were more likely to have purchased antibiotics without prescription (aPR 2.70, 95% CI 1.74–4.19) and to have received antibiotics after the recommendation of a pharmacist (aPR 1.79, 95% CI 1.13–2.82). Conclusions Knowledge about antibiotics among parents from rural settings in Peru is limited and highlights the need for educational interventions. Public health policies to limit the acquisition of antibiotics without prescription should be implemented.

Abstract Central diabetes insipidus (CDI) is a rare condition caused by various underlying diseases including inflammatory and autoimmune diseases, and neoplasms. Obtaining an accurate definitive diagnosis of the underlying cause of CDI is difficult. Recently, anti-rabphilin-3A antibodies were demonstrated to be a highly sensitive and specific marker of lymphocytic infundibuloneurohypophysitis (LINH). Here, we report a detailed case series, and evaluated the significance of anti-rabphilin-3A antibodies in differentiating the etiologies of CDI. A prospective analysis was conducted in 15 consecutive patients with CDI from 2013 to 2020 at a single referral center. Anti-rabphilin-3A antibodies were measured and the relationship between antibody positivity and the clinical/histopathological diagnoses was evaluated. Among 15 CDI patients, the positive anti-rabphilin-3A antibodies were found in 4 of 5 LINH cases, 3 of 4 lymphocytic panhypophysitis (LPH) cases, one of 2 sarcoidosis cases, and one intracranial germinoma case, respectively. Two Rathke cleft cyst cases and one craniopharyngioma case were negative. This is the first report of anti-rabphilin-3A antibodies positivity in CDI patients with biopsy-proven LPH. Measurement of anti-rabphilin-3A antibodies may be valuable for differentiating CDI etiologies.

Collaborative learning is an educational approach to teaching and learning that involves groups of learners collaborating to solve a problem, complete a task, or create a product. To enhance the performance of collaborative learning, the studies in Yamaguchi et al. (2021, 2021, 2021, and 2022) develop an IoT system and quantitatively extract collaboration between learners. The studies acquire sensor data from IoT badges on learners and analyze learning activities with the acquired sensor data on a computer. However, existing studies are not user-friendly for learning analysts who are unfamiliar with information technology owing to complex software installation and command line interface (CLI) operation. Such drawbacks hinder the wide expansion of technology and the exploration of new learning patterns in learning science. Considering high usability for analysts, this paper proposes novel web services named Sensor-based Regulation Profiler Web Services (SRP Web Services) for collaboration analysis with IoT badges. The proposed web application consists of front-end on Next.js and back-end on FastAPI, SQLite, and Python and extracts key points in learning activities for the analysts from the acquired sensor data on a web browser. Experimental evaluations showed that the proposed web services support learning analysts in quantitative analysis of learning activities with high usability. In addition, SRP Web Services are scalable with hundreds of users.

Microwave power transfer provides power wirelessly by converting electromagnetic waves emitted by an antenna to DC power using a rectifying antenna (rectenna). We are developing a distributed cooperative power transfer system that intentionally generates constructive interference on a device by applying appropriate phase control to microwaves emitted from each antenna to improve the efficiency of the power supply. This paper proposes a novel phase optimization method to find the optimal phase that maximizes the received power of the device. The proposed method obtains the optimal phase by performing nonlinear curve regression based on the received signal strength indication (RSSI) feedback of the device. Experimental evaluations showed that the proposed method improved the stability of the supplied power and reduced the time of phase optimization in both feedback models.

Wireless local area network (WLAN)-based localization is key for advanced indoor Internet-of-Things and embedded sensor applications. To further improve the accuracy of indoor localization, attention has been focused on WLAN-based indoor localization using channel-state information (CSI) in addition to the existing information provided by received signal strength (RSS). For easy and low cost installation of wireless sensing, wireless sensing based on standardized protocols and commercial WLAN devices, such as IEEE 802.11ac and IEEE 802.11ax, is necessary. There are few papers demonstrating AoA estimation results by using commercial WLAN devices based on CSI. Therefore, we propose a practical method for estimating the AoA to solve four problems: 1) compressed CSI, which cannot be used for AoA estimation directly, 2) the antenna wireline, in which the phase changes depending on the length of the wireline, 3) the antenna spacing, in which the distance between antennas places a restriction on AoA estimation, and 4) antenna individuality, in which the antennas used in actual MIMO communication have different characteristics. We implemented the proposed method on IEEE 802.11ac devices and evaluated it in a lecture room and shield tent. The results indicate that the proposed method can estimate AoA with an average error of 9.1° and reduce the estimation error by 85.4 % compared with a straightforward approach.

The round robin test (the simultaneous analysis of the same problem) is a method to investigate the variance and sensitivity of results provided by different analysts for a given problem and the reliability of the particular software used by each group participating in the test. A round robin test has been conducted for the traditional numerical method (e.g., finite difference method), but not yet for the discrete element method (DEM). This paper presents the results of the first ever round robin test on the DEM simulation for the angle of repose, involving 16 groups from around the world using different softwares. Within the scope of this round robin test, most groups reported similar simulation results for the angle of repose that differed only by a few degrees from the average of the experimental values, which was initially concealed from participants. There was also good agreement on the degree of variance of the angle of repose. In addition, this paper revealed the recent trends on the interparticle constitutive models and DEM softwares by considering the reports obtained from the participants.

The MRE11A-RAD50-NBS1 complex activates the ataxia-telangiectasia mutated (ATM) pathway and plays a central role in genome homeostasis. The association of RAD50 mutations with disease remains unclear; hence, we adopted a medaka rad50 mutant to demonstrate the significance of RAD50 mutation in pathogenesis using the medaka as an experimental animal. A 2-base pair deletion in the rad50 gene was introduced into transparent STIII medaka using the CRISPR/Cas9 system. The mutant was analyzed histologically for tumorigenicity and hindbrain quality, as well as for swimming behavior, to compare with existing ATM-, MRE11A-, and NBS1-mutation-related pathology. Our results revealed that the medaka rad50 mutation concurrently reproduced tumorigenesis (8 out of 10 rad50Δ2/+ medaka), had a decrease in median survival time (65.7 ± 1.1 weeks in control vs. 54.2 ± 2.6 weeks in rad50Δ2/+ medaka, p = 0.001, Welch’s t-test), exhibited semi-lethality in rad50Δ2/Δ2 medaka and most of the major ataxia-telangiectasia phenotypes, including ataxia (rheotaxis ability was lower in rad50Δ2/+ medaka than in the control, Mann–Whitney U test, p < 0.05), and telangiectasia (6 out of 10 rad50Δ2/+ medaka). The fish model may aid in further understanding the tumorigenesis and phenotype of ataxia-telangiectasia-related RAD50 germline mutations and in developing novel therapeutic strategies against RAD50 molecular disorders.

BackgroundA primary colorectal cancer (CRC) tumor can contain heterogeneous cancer cells. As clones of cells with different properties metastasize to lymph nodes (LNs), they could show different morphologies. Cancer histologies in LNs of CRC remains to be described.MethodsOur study enrolled 318 consecutive patients with CRC who underwent primary tumor resection with lymph node dissection between January 2011 and June 2016. 119 (37.4%) patients who had metastatic LNs (mLNs) were finally included in this study. Cancer histologies in LNs were classified and compared with pathologically diagnosed differentiation in the primary lesion. The association between histologies in lymph node metastasis (LNM) and prognosis in patients with CRC was investigated.ResultsThe histologies of the cancer cells in the mLNs were classified into four types: tubular, cribriform, poorly differentiated, and mucinous. Same degree of pathologically diagnosed differentiation in the primary tumor produced various histological types in LNM. In Kaplan-Meier analysis, prognosis was worse in CRC patients with moderately differentiated adenocarcinoma who had at least some mLN also showing cribriform carcinoma than for those whose mLNs all showed tubular carcinoma.ConclusionsHistology in LNM from CRC might indicate the heterogeneity and malignant phenotype of the disease.

Glycosphingolipids (GSLs) are composed of a polar glycan chain and a hydrophobic tail known as ceramide. Together with variation in the glycan chain, ceramides exhibit tissue-specific structural variation in the long-chain base (LCB) and N-acyl chain moieties in terms of carbon chain length, degree of desaturation, and hydroxylation. Here, we report the structural variation in GSLs in the urinary bladders of mice and humans. Using TLC, we showed that the major GSLs are hexosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide, Neu5Ac-Gal-Glc-Ceramide, and Neu5Ac-Neu5Ac-Gal-Glc-Ceramide. Our LC-MS analysis indicated that phytoceramide structures with a 20-carbon LCB (4-hydroxyeicosasphinganine) and 2-hydroxy fatty acids are abundant in hexosylceramide and Neu5Ac-Gal-Glc-Ceramide in mice and humans. In addition, quantitative PCR demonstrated that DES2 and FA2H, which are responsible for the generation of 4-hydroxysphinganine and 2-hydroxy fatty acid, respectively, and SPTLC3 and SPTSSB, which are responsible for the generation of 20-carbon LCBs, showed significant expressions in the epithelial layer than in the subepithelial layer. Immunohistochemically, dihydroceramide:sphinganine C4-hydroxylase (DES2) was expressed exclusively in urothelial cells of the urinary bladder. Our findings suggest that these ceramide structures have an impact on membrane properties of the stretching and shrinking in transitional urothelial cells.

Introduction Adoptive cell transfer of genetically engineered T cells is a promising treatment for malignancies; however, there are few ideal cancer antigens expressed on the cell surface, and the development of chimeric antigen receptor T cells (CAR-T cells) for solid tumour treatment has been slow. CAR-T cells, which recognise major histocompatibility complex and peptide complexes presented on the cell surface, can be used to target not only cell surface antigens but also intracellular antigens. We have developed a CAR-T-cell product that recognises the complex of HLA-A*02:01 and an epitope of the MAGE-A4 antigen equipped with a novel signalling domain of human GITR (investigational product code: MU-MA402C) based on preclinical studies.Methods and analysis This is a dose-escalation, multi-institutional, phase 1 study to evaluate the tolerability and safety of MU-MA402C for patients with MAGE A4-positive and HLA-A*02:01-positive unresectable advanced or recurrent solid cancer. Two dose cohorts are planned: cohort 1, MU-MA402C 2×108/person; cohort 2, MU-MA402C 2×109/person. Prior to CAR-T-cell infusion, cyclophosphamide (CPA) and fludarabine (FLU) will be administered as preconditioning chemotherapy. Three evaluable subjects per cohort, for a total of 6 subjects (maximum of 12 subjects), will be recruited for this clinical trial. The primary endpoints are safety and tolerability. The severity of each adverse event will be evaluated in accordance with Common Terminology Criteria for Adverse Events V.5.0. The secondary endpoint is efficacy. Antitumour response will be evaluated according to Response Evaluation Criteria in Solid Tumours V.1.1.Ethics and dissemination This clinical trial will be conducted in accordance with the current version of Good Clinical Practice. The protocol was approved by the Clinical Research Ethics Review Committee of Mie University Hospital (approval number F-2021-017). The trial results will be published in peer-reviewed journals and/or disseminated through international conferences.Trial registration number jRCT2043210077.

Phagocytosis, the biological process in which cells ingest large particles such as bacteria, is a key component of the innate immune response. Fcγ receptor (FcγR)-mediated phagocytosis is initiated when these receptors are activated after binding immunoglobulin G (IgG). Receptor activation initiates a signaling cascade that leads to the formation of the phagocytic cup and culminates with ingestion of the foreign particle. In the experimental system termed "frustrated phagocytosis", cells attempt to internalize micropatterned disks of IgG. Cells that engage in frustrated phagocytosis form "rosettes" of actin-enriched structures called podosomes around the IgG disk. The mechanism that generates the rosette pattern is unknown. We present data that supports the involvement of Cdc42, a member of the Rho family of GTPases, in pattern formation. Cdc42 acts downstream of receptor activation, upstream of actin polymerization, and is known to play a role in polarity establishment. Reaction-diffusion models for GTPase spatiotemporal dynamics exist. We demonstrate how the addition of negative feedback and minor changes to these models can generate the experimentally observed rosette pattern of podosomes. We show that this pattern formation can occur through two general mechanisms. In the first mechanism, an intermediate species forms a ring of high activity around the IgG disk, which then promotes rosette organization. The second mechanism does not require initial ring formation but relies on spatial gradients of intermediate chemical species that are selectively activated over the IgG patch. Finally, we analyze the models to suggest experiments to test their validity.

Abstract Background Enterococcus casseliflavus is rarely isolated from human specimens. To the best of our knowledge, there are no reports on its detailed treatment course and prognosis. Here, we present the first known case of E. casseliflavus endocarditis with a detailed treatment course. Case presentation An 86-year-old Japanese woman was transferred to the emergency department with dyspnoea, wheezing, and lumbago. Her medical history included hypertension, chronic kidney disease, idiopathic interstitial pneumonia, and rectal carcinoma. Physical examination revealed expiratory wheezes and a diastolic murmur (Levine 2/6) at the 4th right sternal border. Chest radiography revealed bilateral interstitial opacities and slight cardiac dilatation. Transthoracic echocardiography demonstrated the presence of mobile vegetation with perforation, prolapse, and regurgitation of the aortic valve. With a suspicion of infective endocarditis, we started administering intravenous ampicillin/sulbactam. Thereafter, blood cultures identified E. casseliflavus through matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. The antimicrobial treatment was then switched to ampicillin plus gentamicin. The patient underwent aortic valve replacement on the thirteenth hospital day. She was administered intravenous ampicillin and gentamicin for 6 weeks. The patient was discharged 8 weeks after admission. Conclusions Our case demonstrated that E. casseliflavus could cause infective endocarditis, which can be successfully treated with a 6-week regimen of ampicillin and gentamicin in combination with proper surgical treatment.

Introduction: Sacroiliac joint (SIJ) arthrodesis is the last resort for patients with severe SIJ pain. However, this technique does not always provide good outcomes regarding activities of daily living (ADL). This study aims to reveal the preoperative clinical features associated with poor outcomes of SIJ arthrodesis. Methods: Twenty-six consecutive patients who underwent SIJ arthrodesis between 2009 and 2018 were evaluated. Good-outcome was defined as 30% improvement in ADL, quantified by the Roland-Morris Disability Questionnaire (RDQ). The good-outcome group (17 patients; 10 men and 7 women, 42.5±8.4 years old) and the poor-outcome group (9 patients; 1 man and 8 women, 47.0±17.9 years old) were compared to identify the preoperative clinical features of poor surgical outcomes. Results: No significant differences were observed between the two groups regarding age, preoperative RDQ score, time between onset and the confirmed diagnosis of SIJ pain, and the time between diagnosis and surgical treatment. The following preoperative clinical features associated with poor surgical outcomes were identified: female sex, pain in multiple regions, walking with a cane, and the use of a wheelchair before surgery (P

This study aims to determine the upper limit of the wireless sensing capability of acquiring physical space information. This is a challenging objective because, at present, wireless sensing studies continue to succeed in acquiring novel phenomena. Thus, although we have still not obtained a complete answer, a step is taken toward it herein. To achieve this, CSI2Image, a novel channel state information (CSI)-to-image conversion method based on generative adversarial networks (GANs), is proposed. The type of physical information acquired using wireless sensing can be estimated by checking whether the reconstructed image captures the desired physical space information. We demonstrate three types of learning methods: generator-only learning, GAN-only learning, and hybrid learning. Evaluating the performance of CSI2Image is difficult because both the clarity of the image and the presence of the desired physical space information must be evaluated. To solve this problem, we propose a quantitative evaluation methodology using an image-based object detection system. CSI2Image was implemented using IEEE 802.11ac compressed CSI, and the evaluation results show that CSI2Image successfully reconstructs images. The results demonstrate that generator-only learning is sufficient for simple wireless sensing problems; however, in complex wireless sensing problems, GANs are essential for reconstructing generalized images with more accurate physical space information.

The existing viewport-adaptive 360-degree video streaming schemes encode tiled 360-degree videos with digital-based compression. However, these schemes cause a cliff effect wherein the headset video quality drops when the channel signal-to-noise ratio (SNR) falls below a certain threshold. To realize high-quality wireless 360-degree video streaming, we propose a novel viewport-adaptive soft delivery scheme for 360-degree videos, called 360Cast+. 360Cast+ skips the non-linear operations in digital-based streaming and adopts power allocation and analog modulation to achieve graceful video quality improvement in unstable wireless links. In particular, 360Cast+ integrates the human vision system (HVS) and projection distortion as a perceptual weight in power allocation operations. A near-optimal low-complexity subcarrier matching algorithm was also adopted to extend 360Cast+ to fading channel environments. To reduce the effect of the prediction error, 360Cast+ uses dynamic linear regression (DLR) to predict the future orientation and future prediction error to extract the extension area around a viewport. The evaluation results demonstrated that the proposed 360Cast+ provides sophisticated video quality irrespective of the prediction error and channel conditions in orthogonal frequency-division multiplexing (OFDM)-based systems.

Human collaboration has a great impact on the performance of multi-person activities. The analysis of speaker information and speech timing can be used to extract human collaboration data in detail. Some studies have extracted human collaboration data by identifying a speaker with business-card-type sensors. However, it is difficult to realize speaker identification for business-card-type sensors at low cost and high accuracy because of spikes in the measured sound pressure data, ambient noise in the non-speaker sensor, and synchronization errors across each sensor. This study proposes a novel sound pressure sensor and speaker identification algorithm to realize speaker identification for business-card-type sensors. The sensor extracts the user's speech at low cost and high accuracy by employing a peak hold circuit and time synchronization module for spike mitigation and precise time synchronization. The algorithm identifies a speaker with high accuracy by removing ambient noise. The evaluations show that the algorithm accurately identifies a speaker in a multi-person activity considering varying numbers of users, environmental noises, and reverberation conditions as well as long or short utterances. In addition, the peak hold circuit enables accurate extraction of speech and the synchronization error between the sensors is always within $\pm$30 $\boldsymbol\mu$s, that is, negligible error.

Future networks require a high degree of flexibility over wide areas to enable many services that require higher quality wireless networks such as remote control of cars and remote surgery. Therefore, the network technology must combine high capacity, low latency, and flexibility. To deal with these requirements, we developed Software-Defined Radio over Fiber (SD-RoF), which is an architecture that tightly couples light and radio at a low cost. SD-RoF offers the following two key features: elastic wireless service and elastic bidirectional passthrough. The elastic wireless service provides users with access to wireless services that they need at any time in any place. The elastic bidirectional passthrough connects two remotely located points via RoF through radio waves and enables allowing for bidirectional radio communication between devices at each location. In this study, we design and prototype implementation of SD-RoF, and conduct a basic evaluation of the implemented circuit and demonstration experiments on elastic bidirectional passthrough. Through demonstration experiments, we found the feasibility and the challenges of SD-RoF. In addition, the deployment of SD-RoF, application scenarios, and operational issues are discussed.

Backscatter communication has attracted attention owing to its ultra-low-power consumption ability, which is expected to enhance internet of things (IoT) technology that aims to enable many novel applications for object-to-object communication. Such a network with a large and continuously increasing number of connected objects will benefit significantly from resource-saving. This work introduces a system named QuadScatter, which is a set of algorithms that select and associate transmitters, tags and readers to enable simultaneous backscatter transmissions and increase network capacity. Consequently, the energy consumption in the network is considerably lessened. Intensive simulations have been conducted to demonstrate the effectiveness of backscatter simultaneous transmissions. QuadScatter shows promising results compared to the exhaustive search algorithm. The simulation results highlight computational time and simultaneous transmission improvements of at least $ 250\rm \times$ and $ 2\rm \times$, respectively. Furthermore, while the exhaustive search is limited to a few nodes ($ < 20$), our proposal uses numerous nodes. Additionally, an implementation of limited simultaneous backscatter transmissions is conducted to show its feasibility in the real world.

In online multiplayer shooting games, a long network delay can adversely impact player performance because it leads to large synchronization errors in the game information, such as location errors, between players. To mitigate synchronization errors between players, we propose a novel client-side delay compensation system for online multiplayer shooting games. The proposed delay compensation system comprises regression-based and reinforcement-based methods, which accurately predict present game information based on past game information from within each player’s device. Specifically, the regression-based method utilizes linear regression to accurately predict a player’s present location based on past location information, whereas the reinforcement-based method utilizes deep reinforcement learning to predict a player’s present commands corresponding to the player’s current location, based on past snapshots of the game fields. The advantage of the proposed system over the existing server-side delay compensation methods, e.g., Lag Compensation, is that they display accurate game information in each player’s device as if the player devices were synchronized with each other; thus, any unfair advantages to the players are prevented. We developed a shooting game simulator to experimentally compare the proposed system with existing ones under constant and fluctuating network delays in loss-free and loss-prone networks. The movement models of different players were considered in the experiments. The results demonstrate that the proposed system simultaneously achieves a lower synchronization error between players and higher shooting accuracy, compared to Lag Compensation. For example, the average decrease in player shooting hit rate under a constant network delay of 100 ms is 0.55, 0.076, and 0.0039 without delay compensation and with the proposed regression-based and reinforcement-based methods, respectively. Under the same network delay, the proposed regression-based and reinforcement-based methods show the improvement of 16 pixels and 14 pixels in terms of the synchronization error compared to Lag Compensation, respectively.

We propose a novel wireless control system architecture that divides the wireless service area into smaller optical cells and centrally controls the user equipment (UE) connections under each optical cell. The proposal transmits via IoT smart lighting an optical identifier (ID) specifying connection information to the UE with illuminance sensor. The received optical ID indicates the optimum connection destination. Two solutions are proposed to overcome the hardware restrictions faced by optical ID transmission/reception. Oversampled edge-excluded receiving scheme (OE) reduces the error rate; the signal is oversampled and each window subjected to majority decision. Optical ID reception with lower error rate than conventional approach is realized with a minimum received illuminance of just 8.5 lx (background illuminance 226.67 lx) and a modulation factor of 7 %. Fast optical ID authentication (FA) reduces the authentication cycle preceding optical ID reception by performing correlation calculation between the cyclic matrix and an optical ID list. FA shortens the authentication cycle by 62.5 % (1200 ms to 450 ms). Furthermore, an optical cell control algorithm (ScanLine-based/MinDist-based) is proposed to offset the deterioration in network quality created by non-uniform UE distribution. ScanLine-based algorithm controls optical cells in scanning line manner, while MinDist-based favors optical cells with the minimum distance from the access point (AP). It is confirmed that with an optical cell radius of 5 m or less, the capacity difference per user is reduced compared to the existing RSSI-based alternative while reducing the deterioration of total capacity in extremely biased user distribution scenarios.

In this article, we describe several enhancements of a three-phase correlation image sensor (3PCIS) toward its uses for a direct algebraic method of optical flow detection, i.e., determining velocity field of image patterns for detecting, tracking, and three-dimensional recovery of objects in a scene. A recent theoretical study has provided an exact closed-form solution of the velocity from temporal Fourier integral measurements of a time-varying intensity distribution. An accurate analog multiplication and integration of incident light and reference signals required for this type of measurements is the inherent advantage of a 3PCIS. We fabricate and compare several types of correlation detection block. As continuous-value inputs of the algebraic solution, compensation operations of systematic sources of error are so designed to realize a near shot-noise-limited performance. For random telegraph noise and interference reduction, we show that a p-epi channel, deep p-well structure is the best 3P multiplier. Several experimental results of optical flow detection including an accuracy evaluation and the dense motion capture of a traffic scene are given.

Abstract Background Highly efficient enzymatic saccharification of pretreated lignocellulose is a key step in achieving lignocellulosic biorefinery. Cellobiohydrolase I (Cel7A) secreted by Trichoderma reesei is an industrially used cellulase that possesses carbohydrate-binding module 1 (TrCBM1) at the C-terminal domain. The nonproductive binding of TrCBM1 to lignin significantly decreases the enzymatic saccharification efficiency and increases the cost of biomass conversion because of the additionally required enzymes. Understanding the interaction mechanism between lignin and TrCBM1 is essential for realizing a cost-effective biofuel production; however, the binding sites in lignin have not been clearly elucidated. Results Three types of 13C-labeled β-O-4 lignin oligomer models were synthesized and characterized. The 2D 1H–13C heteronuclear single-quantum correlation (HSQC) spectra of the 13C-labeled lignin models confirmed that the three types of the 13C labels were correctly incorporated in the (1) aromatic rings and β positions, (2) α positions, and (3) methoxy groups, respectively. The TrCBM1-binding sites in lignin were analyzed by observing NMR chemical shift perturbations (CSPs) using the synthetic 13C-labeled β-O-4 lignin oligomer models. Obvious CSPs were observed in signals from the aromatic regions in oligomers bound to TrCBM1, whereas perturbations in the signals from aliphatic regions and methoxy groups were insignificant. These findings indicated that hydrophobic interactions and π–π stacking were dominating factors in nonproductive binding. The synthetic lignin models have two configurations whose terminal units were differently aligned and donated C(I) and C(II). The C(I) ring showed remarkable perturbation compared with the C(II), which indicated that the binding of TrCBM1 was markedly affected by the configuration of the lignin models. The long-chain lignin models (degree of polymerization (DP) 4.16–4.70) clearly bound to TrCBM1. The interactions of TrCBM1 with the short-chain lignin models (DP 2.64–3.12) were insignificant, indicating that a DP greater than 4 was necessary for TrCBM1 binding. Conclusion The CSP analysis using 13C-labeled β-O-4 lignin oligomer models enabled the identification of the TrCBM1 binding sites in lignins at the atomic level. This specific interaction analysis will provide insights for new molecular designs of cellulase having a controlled affinity to cellulose and lignin for a cost-effective biorefinery process.

Sugarcane trash contains significant amount of xylan that could be hydrolysed to xylose. The xylose could be further fermented to produce xylitol, a sugar alcohol that has low calories and does not cause carries of teeth. In this study we optimized the production of xylose from sugarcane trash by microwave-assisted maleic acid hydrolysis using response surface methodology (RSM). The factors optimized were acid concentration, time, and temperature. The xylose yield based on the weight of initial biomass was determined and it served as a response variable. Results show that acid concentration and interaction between time and temperature had significant effect on xylose yield. The quadratic regression model generated from the optimization was fit and can be used to predict the xylose yield after hydrolysis with various combinations of acid concentration, time, and temperature. The optimum condition for xylose production from sugarcane trash was using maleic acid of 1.52%, and heating at 176 °C for 6.8 min. At this condition the yield of xylose was 24.3% per initial biomass or 0.243 g/ g biomass. Keywords: maleic acid; microwave heating; response surface methodology; sugarcane trash, xylose

Abstract The accumulation of phosphorylated tau protein (pTau) in the entorhinal cortex (EC) is the earliest tau pathology in Alzheimer’s disease (AD). Tau tubulin kinase-1 (TTBK1) is a neuron-specific tau kinase and expressed in the EC and hippocampal regions in both human and mouse brains. Here we report that collapsin response mediator protein-2 (CRMP2), a critical mediator of growth cone collapse, is a new downstream target of TTBK1 and is accumulated in the EC region of early stage AD brains. TTBK1 transgenic mice show severe axonal degeneration in the perforant path, which is exacerbated by crossing with Tg2576 mice expressing Swedish familial AD mutant of amyloid precursor protein (APP). TTBK1 mice show accumulation of phosphorylated CRMP2 (pCRMP2), in the EC at 10 months of age, whereas age-matched APP/TTBK1 bigenic mice show pCRMP2 accumulation in both the EC and hippocampal regions. Amyloid-β peptide (Aβ) and TTBK1 suppress the kinetics of microtubule polymerization and TTBK1 reduces the neurite length of primary cultured neurons in Rho kinase-dependent manner in vitro. Silencing of TTBK1 or expression of dominant-negative Rho kinase demonstrates that Aβ induces CRMP2 phosphorylation at threonine 514 in a TTBK1-dependent manner, and TTBK1 enhances Aβ-induced CRMP2 phosphorylation in Rho kinase-dependent manner in vitro. Furthermore, TTBK1 expression induces pCRMP2 complex formation with pTau in vitro, which is enhanced upon Aβ stimulation in vitro. Finally, pCRMP2 forms a complex with pTau in the EC tissue of TTBK1 mice in vivo, which is exacerbated in both the EC and hippocampal tissues in APP/TTBK1 mice. These results suggest that TTBK1 and Aβ induce phosphorylation of CRMP2, which may be causative for the neurite degeneration and somal accumulation of pTau in the EC neurons, indicating critical involvement of TTBK1 and pCRMP2 in the early AD pathology.

To control asparagus harvest timing, we investigated the effects of short-term low (5%) oxygen (O2) treatment in the cultivation area on asparagus growth and yield using a closed cultivation system. During 120 days of cultivation, low O2 treatments were initiated at 0 to 4, 20 to 24, and 40 to 44 days after planting (DAP). The sprouting spears and control crown yield gradually decreased with increasing DAP. However, low O2 treatment at 0 to 4 DAP significantly delayed the decrease until 80 DAP, although the total yield did not change during cultivation. In contrast, low O2 treatments at 20 to 24 and 40 to 44 DAP did not affect yield performance. Taken together, short-term low O2 treatment immediately after planting can change the harvest timing of white asparagus and can be used for effective asparagus culturing in a closed system, such as a plant factory.