Sum-rates of asynchronous GFDMA and SC-FDMA for 5G uplink

The fifth generation (5G) of mobile communication envisions ultralow latency less than 1 ms for radio interface. To this end, frameless asynchronous multiple access may be needed to allow users to transmit instantly without waiting for the next frame start. In this paper, generalized frequency division multiple-access (GFDMA), one of the promising multiple-access candidates for 5G mobile, is compared with the conventional single-carrier FDMA (SC-FDMA) in terms of the uplink sum rate when both techniques are adapted for the asynchronous scenario. In particular, a waveform windowing technique is applied to both schemes to mitigate the inter-user interference due to non-zero out-of-band emission.ope

Enzymatic synthesis of defined-length poly(ADP-ribose) and the investigation of cell-permeable poly(ADP-ribose) glycohydrolase inhibitors

Poly(ADP-ribosylation) (PARylation) is an important post-translational modification that maintains genomic stability in a cell. Engaging in important cellular processes such as DNA repair and cell death signaling, PARylation has gathered considerable interest as a target for genotoxic chemotherapy against cancer cells. To this end, various Poly(ADP-ribose) Polymerase (PARP) inhibitors have been developed to induce sensitivity to genotoxic stress in BRCA-mutated cancer cells, and Poly(ADP-ribose) Glycohydrolase (PARG) inhibition is investigated as an alternate pathway to PARP inhibition in genotoxic chemotherapy. However, little is known about the exact mode of interaction between PAR and different proteins mainly due to the fact that PARP produces polydisperse mixtures of PAR through a heterogeneous modification process. To tackle these problems, a controlled enzymatic synthesis pathway of PAR has been investigated through the use of masked β-NAD+ derivatives that can homogenously and monomerically modify PARP. In order to verify its ability to modify PARP, a sample of proparagyl-β-NAD+ derivative was used in an automodification assay with hTNKS-1. In addition, a PARG inhibitor prodrug in the form of an alanine-ester-masked ADP-HPM was developed as a cell-permeable PARG inhibitor to investigate its effect in a whole cell. In order to verify its activity, an in vitro experiment of the enzymatic cleavage of its masking group with HINT-1 was performed and the results were analyzed via LC/MS

Predicting neurodegeneration from sleep related biofluid changes

Sleep-wake disturbances are common in neurodegenerative diseases and may occur years before the clinical diagnosis, potentially either representing an early stage of the disease itself or acting as a pathophysiological driver. Therefore, discovering biomarkers that identify individuals with sleep-wake disturbances who are at risk of developing neurodegenerative diseases will allow early diagnosis and intervention. Given the association between sleep and neurodegeneration, the most frequently analyzed fluid biomarkers in people with sleep-wake disturbances to date include those directly associated with neurodegeneration itself, such as neurofilament light chain, phosphorylated tau, amyloid-beta and alpha-synuclein. Abnormalities in these biomarkers in patients with sleep-wake disturbances are considered as evidence of an underlying neurodegenerative process. Levels of hormonal sleep-related biomarkers such as melatonin, cortisol and orexin are often abnormal in patients with clinical neurodegenerative diseases, but their relationships with the more standard neurodegenerative biomarkers remain unclear. Similarly, it is unclear whether other chronobiological/circadian biomarkers, such as disrupted clock gene expression, are causal factors or a consequence of neurodegeneration. Current data would suggest that a combination of fluid biomarkers may identify sleep-wake disturbances that are most predictive for the risk of developing neurodegenerative disease with more optimal sensitivity and specificity

Reduced radiation exposure to circulating blood cells in proton therapy compared with X-ray therapy in locally advanced lung cancer: Computational simulation based on circulating blood cells

BackgroundWe estimated the dose of circulating blood cells (CBCs) in patients with locally advanced non-small cell lung cancer for predicting severe radiation-induced lymphopenia (SRIL) and compared pencil-beam scanning proton therapy (PBSPT) and intensity-modulated (photon) radiotherapy (IMRT).Materials and methodsAfter reviewing 325 patients who received definitive chemoradiotherapy with PBSPT (n = 37) or IMRT (n = 164). SRIL was diagnosed when two or more events of an absolute lymphocyte count < 200 µL occurred during the treatment course. Dose information for the heart and lungs was utilized for the time-dependent computational dose calculation of CBCs.ResultsThe dose distribution of CBCs was significantly lesser in the PBSPT group than that in the IMRT group. Overall, 75 (37.3%) patients experienced SRIL during the treatment course; 72 and 3 patients were treated with IMRT and PBSPT, respectively. SRIL was associated with poor progression-free and overall survival outcomes. Upon incorporating the dose information of CBCs for predicting SRIL, CBC D90% > 2.6 GyE was associated with the development of SRIL with the baseline lymphocyte count and target volume. Furthermore, PBSPT significantly reduced the dose of CBC D90% (odds ratio = 0.11; p = 0.004) compared with IMRT.ConclusionThe results of this study demonstrate the significance of the dose distribution of CBCs in predicting SRIL. Furthermore, reducing the dose of CBCs after PBSPT minimized the risk of SRIL. Lymphocyte-sparing radiotherapy in PBSPT could improve outcomes, particularly in the setting of maintenance immunotherapy

Enzymatic synthesis of chlorogenic acid glucoside using dextransucrase and its physical and functional properties

Chlorogenic acid, a major polyphenol in edible plants, possesses strong antioxidant activity, anti-lipid peroxidation and anticancer effects. It used for industrial applications; however, this is limited by its instability to heat or light. In this study, we, for the first time synthesized chlorogenic acid glucoside (CHG) via transglycosylation using dextransucrase from Leuconostoc mesenteroides and sucrose. CHG was purified and its structure determined by nuclear magnetic resonance and matrix-associated laser desorption ionization–time-of-flight mass spectroscopy. The production yield of CHG was 44.0% or 141 mM, as determined by response surface methodology. CHG possessed a 65% increase in water solubility and a 2-fold browning resistance and it displayed stronger inhibition of lipid peroxidation and of colon cancer cell growth by MTT assay, compared to chlorogenic acid. Therefore, this study may expand the industrial applications of chlorogenic acid as water-soluble or browning resistant compound (CHG) through enzymatic glycosylation

Characteristics of stable chronic obstructive pulmonary disease patients in the pulmonology clinics of seven Asian cities

Background and objectives Chronic obstructive pulmonary disease (COPD) is responsible for significant morbidity and mortality worldwide. We evaluated the characteristics of stable COPD patients in the pulmonology clinics of seven Asian cities and also evaluated whether the exposure to biomass fuels and dusty jobs were related to respiratory symptoms, airflow limitation, and quality of life in the COPD patients. Methods: This cross-sectional observational study recruited 922 COPD patients from seven cities of Asia. The patients underwent spirometry and were administered questionnaires about their exposure to cigarette smoking, biomass fuels, and dusty jobs in addition to respiratory symptoms and health related quality of life. Results: Of the patients, there appeared to be variations from city to city in the history of exposure to biomass fuels and dusty jobs and also in respiratory symptoms of cough, phlegm, wheeze, and dyspnea. These symptoms were more frequent in those COPD patients with a history of exposure to biomass fuels than without and those with a history of exposure to dusty jobs than without (P < 0.01 for all comparisons). Airflow limitation was more severe in those COPD patients with a history of exposure to biomass fuels than without (52.2% predicted versus 55.9% of post-bronchodilator forced expiratory volume in 1 second [FEV1], P = 0.009); quality of life was poorer in those with exposure to biomass fuels than without (40.4 versus 36.2 of the St George’s Respiratory Questionnaire [SGRQ] total score, P = 0.001). Airflow limitation was more severe in those COPD patients with a history of exposure to dusty jobs than without (51.2% predicted versus 57.3% of post-bronchodilator FEV1, P < 0.001); quality of life was poorer in those with dusty jobs than without (41.0 versus 34.6 of SGRQ score, P = 0.006). Conclusion: In Asian cities, the characteristics of COPD patients vary and the history of exposure to biomass fuels or dusty jobs was related to frequency of symptoms, severe airflow limitation, and poor quality of life

Identification of preferential target sites for human DNA methyltransferases

DNA methyltransferases (DNMTs) play an important role in establishing and maintaining DNA methylation. Aberrant expression of DNMTs and their isoforms has been found in many types of cancer, and their contribution to aberrant DNA methylation has been proposed. Here, we generated HEK 293T cells stably transfected with each of 13 different DNMTs (DNMT1, two DNMT3A isoforms, nine DNMT3B isoforms and DNMT3L) and assessed the DNA methylation changes induced by each DNMT. We obtained DNA methylation profiles of DNA repetitive elements and 1505 CpG sites from 808 cancer-related genes. We found that DNMTs have specific and overlapping target sites and their DNA methylation target profiles are a reflection of the DNMT domains. By examining H3K4me3 and H3K27me3 modifications in the 808 gene promoter regions using promoter ChIP-on-chip analysis, we found that specific de novo DNA methylation target sites of DNMT3A1 are associated with H3K4me3 modification that are transcriptionally active, whereas the specific target sites of DNMT3B1 are associated with H3K27me3 modification that are transcriptionally inactive. Our data suggest that different DNMT domains are responsible for targeting DNA methylation to specific regions of the genome, and this targeting might be associated with histone modifications