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β decay of proton-rich nuclei plays an important role in exploring isospin mixing. The β decay of ^{26}P at the proton drip line is studied using double-sided silicon strip detectors operating in conjunction with high-purity germanium detectors. The T=2 isobaric analog state (IAS) at 13 055 keV and two new high-lying states at 13 380 and 11 912 keV in ^{26}Si are unambiguously identified through β-delayed two-proton emission (β2p). Angular correlations of two protons emitted from ^{26}Si excited states populated by ^{26}P β decay are measured, which suggests that the two protons are emitted mainly sequentially. We report the first observation of a strongly isospin-mixed doublet that deexcites mainly via two-proton decay. The isospin mixing matrix element between the ^{26}Si IAS and the nearby 13 380-keV state is determined to be 130(21) keV, and this result represents the strongest mixing, highest excitation energy, and largest level spacing of a doublet ever observed in β-decay experiments.

The 3 August 2014 Ludian, China, Ms = 6.5 earthquake caused many large landslides. The biggest occurred at Hongshiyan near the epicenter, had a volume of 1.0 × 107 m3 and dammed the Niulanjiang River, creating a large lake. Post-event field investigations yielded detailed data on the following aspects: rock structure of the landslide, the local lithology and geometry of the area around the landslide dam and composition and grain sizes of the debris avalanche. Based on these data, this work analyzes the geology and topography of the Hongshiyan area, and explores reasons for the occurrence of an unusually large landslide at this location. Our analysis suggests the following conditions are responsible for this catastrophic event. (1) Due to recent crustal deformation, intense incision on the river increased topographic relief with steep slopes and scarps. (2) Combined structures, including unloading fissures, high-angle joints and low-angle beds along the river, as well as an upper-strong and lower-weak interlayer structure on the slope, especially the existence of weak layers in the slope, are important factors that contribute to this large failure. (3) Hongshiyan lies near an active fault, where intense crustal deformation has resulted in rock fractures and weathering, and frequent earthquakes may progressively reduce the strength of the slope. (4) During the Ms = 6.5 earthquake, the terrain and site conditions led to abnormally strong ground shaking. The combined impacts of these factors triggered a very large landslide during a moderate-sized earthquake.

The 3 August 2014 Ludian, China, Ms = 6.5 earthquake caused many large landslides. The biggest occurred at Hongshiyan near the epicenter, had a volume of 1.0 × 107 m3 and dammed the Niulanjiang River, creating a large lake. Post-event field investigations yielded detailed data on the following aspects: rock structure of the landslide, the local lithology and geometry of the area around the landslide dam and composition and grain sizes of the debris avalanche. Based on these data, this work analyzes the geology and topography of the Hongshiyan area, and explores reasons for the occurrence of an unusually large landslide at this location. Our analysis suggests the following conditions are responsible for this catastrophic event. (1) Due to recent crustal deformation, intense incision on the river increased topographic relief with steep slopes and scarps. (2) Combined structures, including unloading fissures, high-angle joints and low-angle beds along the river, as well as an upper-strong and lower-weak interlayer structure on the slope, especially the existence of weak layers in the slope, are important factors that contribute to this large failure. (3) Hongshiyan lies near an active fault, where intense crustal deformation has resulted in rock fractures and weathering, and frequent earthquakes may progressively reduce the strength of the slope. (4) During the Ms = 6.5 earthquake, the terrain and site conditions led to abnormally strong ground shaking. The combined impacts of these factors triggered a very large landslide during a moderate-sized earthquake.

To construct sphingosine 1-phosphate receptor-1 (S1P1)-small interfering RNA (siRNA) lentiviral vectors and infect human salivary gland cells (HSG), and to investigate its possible therapy on Sjogren's syndrome.HSG cells were divided into blank group, empty vector group, scramble-siRNA group and S1P1-siRNA group. The lentiviral vectors expressing siRNA against S1P1 and the pLL3.7 were respectively transfected into 293T cells with pMD2.G, pMDL g/p RRE, pRSV-REV to produce virus, and then infect HSG cells. The efficiency was observed by flow cytometry after the transfection for 48 h. The expression levels of S1P1 mRNA of HSG were detected by real-time RT-PCR and the expression of S1P1 protein was detected by immunohistochemistry method. The expression levels of interferon-γ (IFN-γ) and interleukin (IL)-17 in the supernatant of the cells were detected by ELISA method.(1) The scramble-siRNA, S1P1-siRNA lentiviral vector was successfully constructed, and the lentivirus titer was about 3.5×10The lentiviral vector targeting S1P1 was successfully constructed. S1P1 siRNA could suppress the levels of S1P1 mRNA and protein, and decrease the expression of IL-17 and IFN-γ. S1P1 siRNA could infect HSG cells stably and inhibit the expression of S1P1 gene specifically and efficiently, and reduce the levels of inflammatory cytokines.

To determine why certain desert plants form nebkhas whereas others do not, we investigated common sand-fixing plants of the Minqin desert region, with 108 plants and nebkha samples set up at the edge of the above region. Measurement and comparative analysis of markers such as silhouette layer width, area, and center height revealed the following trends: (i) The silhouettes of nebkha-forming plants are triangular or cylindrical, i.e., the width of these silhouettes decreases with increasing height, and the silhouette centers are positioned 30 cm above the ground. Thus, these plants are shrubs. Plants that do not accumulate sand to form nebkhas are rhombus-shaped, and their silhouette centers are located more than 30 cm above the ground. (ii) Drifting sand flux and sandstorm particles are mainly concentrated in the region between 0 and 30 cm above the ground, explaining why plants with lower silhouettes can easily accumulate sand to form nebkhas. (iii) After being buried in sand, plants whose stems are capable of producing adventitious roots can form nebkhas/sand dunes dozens of times higher than the plant. Although other plants can still form nebkhas, the height of the produced dunes does not exceed the height of the plant. (iv) Silhouette area size is an important marker reflecting wind-breaking and sand-fixing ability, i.e., the ability of a plant to accumulate sand and form nebkhas. However, plants that cannot accumulate sand to form nebkhas, e.g., Haloxylon ammodendron, Calligonum mongolicum, and Artemisia desertorum also exhibit wind-breaking and sand-fixing abilities.

To evaluate the prognostic significance of serum GGT in patients with hepatitis C virus-related hepatocellular carcinoma (HCV-HCC) treated with transcatheeter arterial chemoembolization (TACE).The clinicopathological data of 110 patients with hepatitis C virus-related stage B hepatocellular carcinoma, who received TACE treatment from January 2008 to May 2011, were retrospectively analyzed. The patients were divided into two groups: the normal GCT group (GGT50 U/L, 41 cases) and high GCT group (GGT≥50 U/L, 69 cases). The Kaplan-Meier method was used to analyze the survival rates, log-rank test was used for univariate analysis, and Cox regression model was used for multivariate analysis. The factors affecting survival and prognosis of the patients were analyzed.The pretreatment GGT level was (160.0±120.2) U/L in the high GGT group and (40.1±8.5) U/L in the normal GGT group (P0.001). After TACE treatment, the 1-, 2- and 3-year survival rates were 90.2%, 45.9% and 24.6% in the high GGT group, and 90.2%, 75.6% and 58.5%, respectively, in the normal GGT group (P=0.002). The univariate analysis showed that the pretreatment GGT level, ECOG score, α-fetoprotein, tumor size, tumor number, and Child grade are factors affecting the prognosis of HCV-related hepatocellular carcinoma patients (P0.05 for all). The Cox multivariate survival analysis revealed that the tumor size, tumor number, Child grade, and serum GGT level are independent prognostic factors for patients with stage B HCV-related hepatocellular carcinoma.The level of serum GGT before TACE is an independent prognostic factor for patients with stage B HCV-related hepatocellular carcinoma.

The 3 August 2014 Ludian, China Ms 6.5 earthquake has spawned a mass of severe landslides. Of them the biggest occurred at Hongshiyan near the epicenter, which has 1200 × 104 m3, clogging the Niulanjiang River, and creating a large dammed lake. Post-event field investigations yield detailed data on following aspects: rock structure of landslides, lithology, and geometry of the dam, composition and grain sizes of debris avalanches. Based on these data, this work further analyzes the geology and topography of the Hongshiyan area, and explores the mechanism for occurrence of such an unusual big landslide at this place. Our analysis suggests the following conditions are responsible for this catastrophic event: (1) during the Ms 6.5 earthquake, the special terrain and site conditions led to abnormally strong ground shake. (2) Hongshiyan lies nearby an active fault, where intense crustal deformation resulted in rock fractures and weathering. (3) Intense incision on the river increased topographic relief with steep slopes and scarps. (4) Combined structures, including unloading fissures, high-angle joints and low-angle beds along the river as well as upper-tough and lower-soft structure on the slopes. It is the joint functions of these conditions that triggered such seldom seen landslides during a moderated-sized earthquake.

Barchan dunes, an important type of dunes, are distributed on the edge of oases. Research of stability mechanisms of barchan dunes is of great importance to the determination of regulation of aeolian sand movement on the edge of oases. However, the stability of barchan dunes remains an unresolved scientific issue. In this paper, the stability mechanisms of the top of barchan dunes in Hexi desert area of Gansu Province were analyzed. The results showed that: (1) in Hexi desert area of Gansu Province, patches of barchan dunes were distributed downwind on the edge of desert. The distribution areas were flat sandy-clay or sandy-gravel beaches. The lowlands among the dunes were wide and had the prominent prevailing wind. (2) The prevailing northwestern wind caused the highest point and sand ridge line of the dunes to coincide, and the dunes to move forward and become lower. The southeastern wind (opposite to the prevailing wind) caused the highest point and sand ridge line of the dunes to separate, the leeward slope to be eroded by wind and the dunes to rise. (3) The higher the barchan dunes were, the longer the two flanks were, and the smaller the angle was. (4) The wide flat beaches were vital to the formation of barchan dunes and a chain of barchan dunes. The largely prevailing wind was the key factor for the stability of barchan dunes and a chain of barchan dunes. The opposite wind and the corridor effect of the two flanks were key factors for the increase of barchan dunes in size and height. The speed and distribution frequency of the prevailing and opposite winds were factors restraining the height of barchan dunes and a chain of barchan dunes here.

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35). Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case - control studies. Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08-1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95-1.09, P = 0.66; P-heterogeneity (P het) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12-1.34, P = 7 × 10 -6) but not males (OR = 1.02, 95% CI = 0.97-1.08, P = 0.35; P het = 6 × 10-4). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (Phet = 0.86). Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. Impact: Further research is warranted to elucidate the mechanisms underlying these observations.©2011 AACR.

When exposed to PMA, the erythroblastic cell line TF-1 and its cytokine-independent variant D2 cells can be induced to undergo differentiation and apoptosis. In this study we investigated the mechanism responsible for the differential responses to PMA induction and show that serum present in the medium has a major role in promoting PMA-induced apoptosis in TF-1 and D2 cells. Interestingly, lysophosphatidic acid (LPA) could replace serum to co-operate with PMA in inducing apoptosis via the Rho-dependent pathway. The expression of a constitutively active form of RhoA also increased PMA-induced apoptosis. However, by inhibiting adhesion, most cells underwent PMA-induced apoptosis even in the absence of LPA or serum, indicating that adhesion is required for PMA-induced differentiation. Given that LPA could prevent adhesion for cells maintained in the serum-free medium, here we propose that RhoA has a switching role in determining whether TF-1 and D2 cells undergo differentiation or apoptosis in response to PMA, by modulating cell adhesion.

The overexpression of the cyclin-dependent kinase (CDK) inhibitor p21(Waf1) can inhibit cell proliferation, which is mediated by direct binding to CDK and proliferating-cell nuclear antigen. In this study, we demonstrated that human cytosolic thymidine kinase 1 (TK1) polypeptide can form a complex with p21(Waf1). The C-terminal domain of p21(Waf1) appeared to interact with the TK1 polypeptide, but, despite the inhibitory function of p21(Waf1), their association did not alter TK1 functional activity. However, overexpression of TK1 overcame p21(Waf1)-mediated growth suppression and blocked the association of CDK2 with p21(Waf1), suggesting that TK1 interferes with the inhibitory function of p21(Waf1). Based on these results, we here propose that the molecular function of p21(Waf1) in cells can be perturbed through its interaction with another cellular protein, TK1.

As human diploid fibroblasts (HDFs) in culture senesce, the expression of thymidine kinase (TK) and the activity of its promoter become attenuated. Herein we analyze the cis-elements involved in transcriptional activation of the hTK promoter, and show that the Sp1 binding site located at -118/-113 and one CCAAT box located at either -71/-67 or -40/-36 are critical for maximal expression of hTK promoter activity in young IMR-90 HDFs. However, the DNA binding activities to TK-CCAAT and Sp1 were not defective in serum-stimulated senescent HDFs. On the other hand, treatment of young HDFs during the late G1 transition with a specific inhibitor of CDK2, roscovitine, blocked the induction of TK RNA expression. Because CDK2 remained inactive during serum stimulation in senescent HDFs, it is likely that the impairment of TK expression in senescent HDFs during serum stimulation is relevant to the inactivation of CDK2, rather than to the controlling mechanism at the level of NF-Y and Sp1 activity.

Transcriptional activation is important for the elevated expression of human thymidine kinase (hTK) in tumor cells. Here, we used TK(-133/+33)-luciferase reporter gene construct and bandshift assay to study the cis-elements involved in transcriptional activation of the hTK promoter. We found that two CCAAT boxes at -71/-67 and -40/-36 and Sp1 binding site located at -118/-113 were critical for maximal expression of the hTK promoter activity. As Sp1-mediated activation of the hTK promoter was not detectable for the promoter construct with double mutations at two CCAAT boxes, we proposed that NF-Y binding to the hTK promoter sequence is a requisite step for the functional interaction with Sp1. Here, we further showed that the hTK promoter activity was reduced in HeLa cells transfected with p16 or p21, both of which are inhibitors of cyclin-dependent kinases (CDKs). Inhibition of the hTK promoter activity by p16 could be abrogated by overexpression of cyclin A, indicating that the cyclin A activating event is more directly involved in transcriptional activation of the hTK promoter. We thus proposed that NF-Y-mediated activation of the hTK promoter is closely linked to the activation of CDK2/cyclin A pathway.

Normal human diploid fibroblasts cannot divide indefinitely in culture. At the end of their lifespan they withdraw from the cell cycle permanently by a process termed cellular senescence. Recent molecular studies indicate that upregulation of two inhibitors of cyclin-dependent kinases, p16 and p21, is responsible for blocking the G1/S transition in senescent cells. Although the state of senescence resembles terminal differentiation in that both exhibit irreversible growth arrest and resistance to apoptosis, other molecular changes are seen only in senescent cells. This suggests that the signal pathway specific for senescence is present in normal cells. Changes in chromosomes, such as progressive shortening of the telomeres and erosive damage by detrimental by-products in metabolism, may be the signals that trigger senescence, leading to the inactivation of cell cycle progression. On the other hand, it seems that a dominant genetic program is intrinsically preset to ensure a growth limit in the normal cell. This notion is supported by cell fusion and microcell transfer experiments which show that escaping from senescence requires recessive mutations in senescence-specific genes. Identification of these participating genes and clarification of their mode of action will provide the basis for understanding the mechanisms governing the differences between mortality in normal cells and immortality in cancer cells.

The expression of cytosolic human thymidine kinase (TK) occurs in a cell cycle-dependent manner. Here, we show that TK is hyperphosphorylated during the M phase in several human cell lines. Our data from characterizing TK phosphorylation in proliferating and M phase-arrested HeLa cells suggest that the polypeptide of TK is differentially phosphorylated during the progression of the cell cycle. TK in the M phase-arrested HeLa cells was found to have a 10-fold lower affinity for its substrate, thymidine, than in the proliferating cells. We propose that phosphorylation of TK by the mitotic kinase(s) may provide an attenuating mechanism to prevent unnecessary synthesis of dTTP at the time of mitosis.

The nuclear protein interacting with the distal CCAAT box of human thymidine kinase (TK) gene promoter has been suggested to be a specific TK-CCAAT-binding protein, which is responsible for the serum-dependence of TK transactivation in normal human IMR-90 fibroblasts. By biochemical characterization, TK-CCAAT-binding protein was found to be distinct from other known CCAAT-binding proteins (Pang, J. H., and Chen, K. Y. (1993) J. Biol. Chem. 268, 2909-2916). In this study, we identify NF-Y, which is composed of Ya and Yb subunits, to be responsible for the TK-CCAAT binding activity in the crude nuclear extract from HL-60 cells. The interaction of NF-Y with the distal CCAAT box of the TK promoter in the crude extract appeared to be more heat-sensitive than that in the DNA affinity chromatography purified fraction. We have further established that the serum dependence of TK-CCAAT binding activity in normal IMR-90 fibroblasts is due to the decrement of NF-Ya, but not NF-Yb expression following serum-deprivation, and that such serum dependence is absent in HL-60 cells.

We have used the sequence of the cell-cycle regulatory region of human thymidine kinase promoter to study the DNA-protein interaction in human tumor and normal cells. By performing band-shift assays and DNase I footprint analysis, we have demonstrated that human tumor cells exhibited an elevated level of binding activity to the distal CCAAT box of human thymidine kinase promoter. The expression of human thymidine kinase CCAAT-binding activity was serum or independent in human tumor cells but serum dependent in normal human diploid fibroblasts. Our results present the fact that the constitutive interaction of CCAAT-binding factor with the promoter of a cell growth-controlled gene, such as thymidine kinase, is consistent with the loss of stringent cell growth regulation associated with tumorigenic phenotype.

It has been well established that the regulation of thymidine kinase (TK) expression is highly growth-dependent. In this report, we present evidence that TK expression in undifferentiated HL-60 cells is not stringently controlled in a growth-dependent manner, except for a very moderate activation of TK in response to growth stimulation. Moreover, we have demonstrated for the first time that TK becomes phosphorylated, and the fluctuation of TK activity in these cells is related to the extent of phosphorylation of seryl residues of the TK polypeptide. This is further reinforced by the observation that the presence of Ser/Thr phosphatases inhibitor in the crude extract increases TK activity. Our data suggest that post-translational modification by phosphorylation is implicated in TK regulation in HL-60 cells.

Expression of a mRNA cross-hybridized to human cytomegalovirus immediate-early gene promoter-enhancer was detected in the human promyelocytic leukemia cell line HL-60. The 0.6 kilobase of NruI/SacI DNA fragment of eukaryotic expression vector pCDM8 representing human cytomegalovirus immediate-early gene promoter-enhancer was used as the probe to hybridize with polyadenylated RNA by the Northern blot analysis. A 3.7-kilobase strand of polyadenylated RNA was visualized in the cytoplasmic fraction of HL-60 promyelocytes. In contrast, other human hematopoietic cell lines, hepatoma cells, and normal human fibroblasts did not show such a transcript by cross-hybridization. This transcript was called CMVE RNA. The expression of CMVE mRNA was also detectable in the fresh blast cells from patients with acute myeloid leukemia, and particularly from a patient with acute myeloid leukemia of the M3 type. Taken together, these findings suggest that the CMVE RNA-encoded gene plays an important role in the pathogenesis of acute promyelocytic leukemia.

Aging of IMR-90 human diploid fibroblasts in vitro is accompanied by significant changes of polyamine metabolism, most notably, a 5-fold decrease of serum-induced activity of ornithine decarboxylase, the key enzyme in the biosynthesis of polyamines (Chen, K. Y., Chang, Z. F., and Liu, A. Y.-C. (1986) J. Cell. Physiol. 129, 142-146). In this paper, we employed Northern blot hybridization and affinity radiolabeling techniques to investigate the molecular basis of this age-associated change of ornithine decarboxylase activity. Since the induction of ornithine decarboxylase by serum is a mid-G1 event, we also examined expressions of other cell cycle-dependent genes that are induced before and after the mid-G1 phase to determine if their expressions may also be age-dependent. Our results demonstrated a 3-fold decrease of the amount of active ornithine decarboxylase molecules that can be labeled by alpha-difluoromethyl[3H]ornithine in senescent IMR-90 cells (population doubling level (PDL) = 52) as compared to young cells (PDL = 22). However, the levels and kinetics of induction of ornithine decarboxylase mRNA in both young and senescent IMR-90 cells were found to be identical throughout a 24-h time period after serum stimulation. The time course and the magnitude of the expression of c-myc, an early G1 gene, were quite similar in young and senescent IMR-90 cells and appeared to be PDL-independent. In contrast, the expression of thymidine kinase, a late G1/S gene, was significantly reduced in senescent IMR-90 cells. Levels of thymidine kinase mRNA and thymidine kinase activity in senescent IMR-90 cells were 6- and 8-fold less than those in young cells, respectively. Based on these data, we proposed that impairment of cell cycling in senescent IMR-90 cells may occur at the late G1/S phase and that decreases of ornithine decarboxylase activity and putrescine accumulation during cell senescence may contribute to this impairment.

Efficient bulk power conversion from a 140-volt battery source to 48 volts dc can be accomplished by using ASCR's (Asymmetrical Silicon Controlled Rectifiers) in a 70-kHz series resonant circuit that operates at a repetition rate of 40 kHz. This paper describes a dc-to-dc converter that can deliver 2.5 kilowatts output power with an efficiency greater than 80 percent using a pair of S7310M's connected in the push-push configuration. The magnetic portion of the circuit consists of an input charging choke and an output transformer whose windings are connected such that the induced voltages are additive to provide a high charging voltage to the capacitors in the LC resonant circuits. In addition, this new circuit will prevent the ASCR's from latching on when the extreme output condition of either open or short circuit is present.