The RENO experiment reports more precisely measured values of θ_{13} and |Δm_{ee}^{2}| using ∼2200 live days of data. The amplitude and frequency of reactor electron antineutrino (νover ¯_{e}) ...oscillation are measured by comparing the prompt signal spectra obtained from two identical near and far detectors. In the period between August 2011 and February 2018, the far (near) detector observed 103 212 (850 666) νover ¯_{e} candidate events with a background fraction of 4.8% (2.0%). A clear energy and baseline dependent disappearance of reactor νover ¯_{e} is observed in the deficit of the measured number of νover ¯_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.0896±0.0048(stat)±0.0047(syst) and |Δm_{ee}^{2}|=2.68±0.12(stat)±0.07(syst)×10^{-3} eV^{2}.
TMPRSS4 is a novel type II transmembrane serine protease found at the cell surface that is highly expressed in pancreatic, colon and gastric cancer tissues. However, the biological functions of ...TMPRSS4 in cancer are unknown. Here we show, using reverse transcription-PCR, that TMPRSS4 is highly elevated in lung cancer tissues compared with normal tissues and is also broadly expressed in a variety of human cancer cell lines. Knockdown of TMPRSS4 by small interfering RNA treatment in lung and colon cancer cell lines was associated with reduction of cell invasion and cell-matrix adhesion as well as modulation of cell proliferation. Conversely, the invasiveness, motility and adhesiveness of SW480 colon carcinoma cells were significantly enhanced by TMPRSS4 overexpression. Furthermore, overexpression of TMPRSS4 induced loss of E-cadherin-mediated cell-cell adhesion, concomitant with the induction of SIP1/ZEB2, an E-cadherin transcriptional repressor, and led to epithelial-mesenchymal transition events, including morphological changes, actin reorganization and upregulation of mesenchymal markers. TMPRSS4-overexpressing cells also displayed markedly increased metastasis to the liver in nude mice upon intrasplenic injection. Taken together, these studies suggest that TMPRSS4 controls the invasive and metastatic potential of human cancer cells by facilitating an epithelial-mesenchymal transition; TMPRSS4 may be a potential therapeutic target for cancer treatment.
Although anthropogenic climate change is expected to have caused large shifts in temperature and rainfall, the detection of human influence on global drought has been complicated by large internal ...variability and the brevity of observational records. Here we address these challenges using reconstructions of the Palmer drought severity index obtained with data from tree rings that span the past millennium. We show that three distinct periods are identifiable in climate models, observations and reconstructions during the twentieth century. In recent decades (1981 to present), the signal of greenhouse gas forcing is present but not yet detectable at high confidence. Observations and reconstructions differ significantly from an expected pattern of greenhouse gas forcing around mid-century (1950-1975), coinciding with a global increase in aerosol forcing. In the first half of the century (1900-1949), however, a signal of greenhouse-gas-forced change is robustly detectable. Multiple observational datasets and reconstructions using data from tree rings confirm that human activities were probably affecting the worldwide risk of droughts as early as the beginning of the twentieth century.
Novel therapeutic strategies are needed to overcome cancer recurrence, metastasis, and resistance to chemo- and radiotherapy. Cancer stem cells (CSCs) are major contributors to the malignant ...transformation of cells due to their capacity for self-renewal. Although various CSC markers have been identified in several types of tumors, they are primarily used as cancer-prediction markers and for the isolation of CSC populations. CD133, one of the best-characterized CSC markers in distinct solid tumor types, was shown to be correlated with CSC tumor-initiating capacity; however, the regulation of CD133 expression and its function in cancer are poorly understood. Here, we show that CD133 expression is negatively regulated by direct binding of the p53 tumor suppressor protein to a noncanonical p53-binding sequence in the CD133 promoter. Binding of p53 recruits Histone Deacetylase 1 (HDAC1) to the CD133 promoter and subsequently suppresses CD133 expression by reducing histone H3 acetylation. Furthermore, CD133 depletion suppresses tumor cell proliferation, colony formation, and the expression of core stemness transcription factors including NANOG, octamer-binding transcription factor 4 (OCT4), SOX2, and c-MYC. Critically, the anti-proliferative effects of p53 are antagonized by rescue of CD133 expression in a p53 overexpressing cell line, indicating that the tumor suppressive activity of p53 might be mediated by CD133 suppression. Taken together, our results suggest that p53-mediated transcriptional regulation of CD133 is a key underlying mechanism for controlling the growth and tumor-initiating capacity of CSCs and provide a novel perspective on targeting CSCs for cancer therapy.
SETTING: Multicentre study.OBJECTIVE: To define the clinical characteristics of patients with tuberculosis (TB) destroyed lung due to past TB.DESIGN: We reviewed patients with TB-destroyed lung ...between May 2005 and June 2011.RESULTS: A total of 595 patients from 21 hospitals
were enrolled. The mean age was 65.63 ± 0.47 (mean ± standard error); 60.5% were male. The mean number of lobes involved was 2.59 ± 0.05. Pleural thickening was observed in 54.1% of the patients. Mean forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1),
FEV1/FVC, bronchodilator response and number of exacerbations per year were respectively 2.06 ± 0.03 l (61.26% ± 0.79), 1.16 ± 0.02 l (49.05% ± 0.84), 58.03% ± 0.70, 5.70% ± 0.34, and 0.40 ± 0.04. The number of lobes involved was
significantly correlated with FVC and FEV1, and with the number of exacerbations per year. Use of long-acting muscarinic antagonists or long-acting beta-2 agonists plus inhaled corticosteroids resulted in bronchodilatory effects. Multivariable regression analysis showed that age,
initial FEV1 (%) and number of exacerbations during follow-up were independent factors affecting change in FEV1.CONCLUSION: Decreased lung function with exacerbation, and progressive decline of FEV1 were observed in patients with TB-destroyed lung.
This study examined how patients with cancer estimate caregiver burden (CB) and the association between their underestimation of CB and their caregivers' self‐ratings of their quality of life ...(CQOLC‐K; Korean version of the Caregiver Quality of Life Index‐Cancer), depression and anxiety (Korean version of the Hospital Anxiety and Depression Scale). Participants consisted of 990 patient‐caregiver dyads recruited from a nationwide cross‐sectional survey conducted in South Korea. Medical baseline data were retrieved from the hospital information systems of the participating centres. The patients with cancer who underestimated CB ranged from 18.62% (for physical CB) to 23.33% (for social CB). They had less advanced cancer, a lower income, were the caregiver's spouse, reported higher levels of family avoidance of communication about cancer, and had female caregivers. The patients' underestimation of CB was significantly related to lower CQoL and higher levels of caregiver depression and anxiety. The current study provides empirical evidence for the link between the underestimation of CB by patients with cancer and compromised caregiving experiences of cancer caregivers. Open family communication about cancer was discussed as one of several practical strategies for decreasing patients' underestimation of CB.
Objectives: Histone deacetylase (HDAC) is an important therapeutic target in cancer. Two of the main anticancer mechanisms of HDAC inhibitors are induction of terminal differentiation and inhibition ...of cell proliferation. To investigate the role of HDAC in maintenance of self‐renewal and cell proliferation, we treated mesenchymal stem cells (MSCs) that originated from adipose tissue or umbilical cord blood with valproic acid (VPA) and sodium butyrate (NaBu).
Materials and methods: Human MSCs were isolated from mammary fat tissue and cord blood. We performed MTT assay and flow cytometry‐based cell cycle analysis to assess self‐renewal of MSCs. In vitro differentiation assays into osteogenic, adipogenic, neurogenic and chondrogenic lineages were conducted to investigate MSC multipotency. Immunocytochemistry, Western blot and reverse transcription‐polymerase chain reaction were used to interrogate molecular pathways.
Results: VPA and NaBu flattened the morphology of MSCs and inhibited their growth. VPA and NaBu activated the transcription of p21CIP1/WAF1 by increasing the acetylation of histone H3 and H4 and eventually blocked the cell cycle at G2/M phase. The expression level of p16INK4A, a cdk inhibitor that is closely related to cellular senescence, was not changed by HDAC inhibitor treatment. We performed controlled differentiation into bone, fat, cartilage and nervous tissue to elucidate the role of HDAC in the pluripotency of MSC to differentiate into functional tissues. VPA and NaBu decreased the efficiency of adipogenic, chondrogenic, and neurogenic differentiation as visualized by specific staining and reverse transcription‐polymerase chain reaction. In contrast, osteogenic differentiation was elevated by HDAC inhibitor treatment.
Conclusion: HDAC activity is essential for maintaining the self‐renewal and pluripotency of MSCs.
Improved understanding is required on how hip fracture risk is influenced by landing configuration. We examined how hip impact dynamics was affected by hip joint kinematics during simulated sideways ...falls. Twelve young adults (7 males, 5 females) of mean age 23.5 (SD = 1.5) years, participated in pelvis release experiments. Trials were acquired with the hip flexed 15° and 30° for each of three hip rotations: +15° ("external rotation"), 0°, and -15° ("internal rotation"). During falls, force-deformation data of the pelvis were recorded. Outcome variables included the peak hip impact force (F
) and effective stiffness of the pelvis (k
, k
, and k
) determined with different methods suggested in literature, and predicted hip impact force during a fall from standing height (F
, F
and F
). The two-way repeated-measures ANOVA was used to test whether these variables were associated with hip joint angles. The F
, k
and F
were associated with hip rotation (F = 5.587, p = 0.005; F = 9.278, p < 0.0005; F = 5.778, p = 0.004, respectively), and 15 %, 31 % and 17 % smaller in 15° external than internal rotation (848 versus 998 N; 24.6 versus 35.6 kN/m; 2,637 versus 3,170 N, respectively). However, none of the outcome variables were associated with hip flexion (p > 0.05). Furthermore, there were no interactions between the hip rotation and flexion for all outcome variables (p > 0.05). Our results provide insights on hip impact dynamics, which may help improve a hip model to assess hip fracture risk during a fall.
ANITA's fourth long-duration balloon flight in 2016 detected 29 cosmic-ray (CR)-like events on a background of 0.37_{-0.17}^{+0.27} anthropogenic events. CRs are mainly seen in reflection off the ...Antarctic ice sheets, creating a phase-inverted waveform polarity. However, four of the below-horizon CR-like events show anomalous noninverted polarity, a p=5.3×10^{-4} chance if due to background. All anomalous events are from locations near the horizon; ANITA-IV observed no steeply upcoming anomalous events similar to the two such events seen in prior flights.
The large volume of adult living donor liver transplantations (ALDLTs) at our center affords a unique opportunity to examine the impact of acute‐on‐chronic liver failure (ACLF) among high–Model for ...End‐Stage Liver Disease MELD score patients. From February 1998 to March 2010, 1958 cirrhotic recipients were analyzed to study the relationship between MELD scores and ALDLT outcomes. A total of 327 high‐MELD score recipients were categorized into ACLF and non‐ACLF groups, and their outcomes were compared. The 5‐year graft and patient survival in the high‐MELD group were 75.2% and 76.4%, respectively, which were significantly worse than the low and intermediate MELD groups. The presence of ACLF associated with higher MELD scores appeared to be the dominant factor responsible for the inferior results of patients with MELD score of 30–34 points. The 5‐year graft survivals in the ACLF group was 70.5% and in the non‐ACLF group it was 81.0% (p = 0.035). Therefore, ALDLT should be performed as soon as possible in high‐MELD score patients prior to ACLF development. Moreover, ACLF patients should be separately categorized when analyzing the outcomes of ALDLT. ALDLT for ACLF patients should not be discouraged because favorable outcomes can be expected through timely ALDLT and comprehensive management.
While adult living donor liver transplantation should be performed as soon as possible before acute‐on‐chronic liver failure develops, it should not be discouraged for patients with acute‐on‐chronic liver failure since timely transplantation and comprehensive management can bring a favorable outcome.
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