Learning in Hybrid-Project Systems: The Effects of Project Performance on Repeated Collaboration

This study advances contingency theories of performance-outcome learning in hybrid-project systems, in which both project participants and superordinate organizations influence the formation of project ventures. We propose that performance-outcome learning depends on the perceived relevance of prior performance and on organizational control over project participants. We examine this framework using data on 239 U.S. movie projects from the years 1931-40. In keeping with our theory, higher project performance led to future collaborations with the same partners, contingent on prior collaborations, project similarity, and organizational control. Our findings imply distinct patterns of network evolution and unfolding adaptation of hybrid-project systems through slow-moving, local adjustments

Silica Nanowires-Filled Glass Microporous Sensor for the Ultrasensitive Detection of Deoxyribonucleic Acid

DNA carries genetic information and can serve as an important biomarker for the early diagnosis and assessment of the disease prognosis. Here, we propose a bottom-up assembly method for a silica nanowire-filled glass microporous (SiNWs@GMP) sensor and develop a universal sensing platform for the ultrasensitive and specific detection of DNA. The three-dimensional network structure formed by SiNWs provides them with highly abundant and accessible binding sites, allowing for the immobilization of a large amount of capture probe DNA, thereby enabling more target DNA to hybridize with the capture probe DNA to improve detection performance. Therefore, the SiNWs@GMP sensor achieves ultrasensitive detection of target DNA. In the detection range of 1 aM to 100 fM, there is a good linear relationship between the decrease rate of current signal and the concentration of target DNA, and the detection limit is as low as 1 aM. The developed SiNWs@GMP sensor can distinguish target DNA sequences that are 1-, 3-, and 5-mismatched, and specifically recognize target DNA from complex mixed solution. Furthermore, based on this excellent selectivity and specificity, we validate the universality of this sensing strategy by detecting DNA (H1N1 and H5N1) sequences associated with the avian influenza virus. By replacing the types of nucleic acid aptamers, it is expected to achieve a wide range and low detection limit sensitive detection of various biological molecules. The results indicate that the developed universal sensing platform has ultrahigh sensitivity, excellent selectivity, stability, and acceptable reproducibility, demonstrating its potential application in DNA bioanalysis

The peroxidic bridge is essential to the inhibitory activity of artemisinin in both yeast and malaria parasites.

<p>(A) Molecular structures of artemisinin and analogues (artemisinins) used in the study. Deoxyartemisinin contains only one O in the otherwise O-O bridge. (B) Inhibition of yeast growth with artemisinins. Strains of <i>ndi1</i>Δ and <i>nde1</i>Δ, with mutated internal and external NADH dehydrogenase (type II complex I) respectively, exhibit reduced sensitivity to artemisinins. (C) Inhibition of <i>P. falciparum</i> growth by artemisinins in cell culture. Data were shown as mean ± SEM.</p

Artemisinin acts by depolarizing mitochondrial membrane of malaria parasites and yeast cells.

<p>(A,B) Artemisinin treatment resulted in loss of Δψ_m (mitochondrial membrane potential) in <i>P. berghei</i> (A) and yeast (B). The membrane potential could be mostly recovered by washing off artemisinin shortly after treatment. Δψ_m was monitored by the fluorescence intensity of DiOC₆(3) or rhodamine 123 (Rh123). Higher fluorescence intensity of stained cells indicates higher Δψ_m. n = 5. (C) Effect of artemisinin and deoxyartemisinin on the membrane potential of isolated malarial mitochondria. Isolated <i>P. berghei</i> mitochondria were incubated with artemisinin or deoxyartemisinin. Loss of membrane potential was apparent with 100 nM artemisinin treatment but not visible with 8 µM deoxyartemisinin. Δψ_m was assessed by measuring the Δψ_m-dependent uptake of Rh123. n = 3. Art, artemisinin. Deoxy-Art, deoxyartemisinin (D) Effect of artemisinin and deoxyartemisinin on membrane potential of isolated yeast mitochondria. Isolated yeast mitochondria were incubated with 1 µM artemisinin or 8 µM deoxyartemisinin. Δψ_m was assessed by measuring the Δψ_m-dependent uptake of Rh123. n = 3. Art, artemisinin. Deoxy-Art, deoxyartemisinin (E) Artemisinin selectively depolarizes malarial mitochondria but not CHO mitochondria. Mitochondria isolated from <i>P. berghei</i> and CHO cells were mixed and treated with 100 nM artemisinin. Artemisinin is not effective on the mammalian mitochondria. n = 3. Data were shown as mean ± SEM. * <i>p</i><0.05 versus control; ** <i>p</i><0.01 versus control.</p

Interference of the electron transport chain affects the artemisinin's action.

<p>(A) An isobologram for DPI and artemisinin. Data points above the line indicate antagonism between DPI and artemisinin. FIC: fractional inhibitory concentration. DPI: diphenylene iodonium chloride. (B) An isobologram for DPI and chloroquine (CQ). (C) Effect of DPI on the ROS promoting ability of artemisinin. ROS was monitored using the DCFH-DA assay. (D) Effect of DPI on the depolarizing ability of artemisinin. Δψ of isolated <i>P. berghei</i> mitochondria was assessed by measuring the Δψ-dependent uptake of Rh123. (E) Iron chelator DFO inhibits ETC activity. (F) Iron chelator DFO reduces artemisinin-induced ROS production in isolated malarial mitochondria. n = 3. Data were shown as mean ± SEM. ** <i>p</i><0.01 versus conrol; *** <i>p</i><0.001 versus control; ^##<i>p</i><0.01 versus Art.</p

Artemisinins are distributed to the mitochondria.

<p>Immunofluorescence analysis revealed the subcellular localization of artesunate. Artesunate-treated <i>P. berghei</i> cells were stained with DAPI, Mitotracker Red and monoclonal antibody against artesuate. The top and bottom panels are cells without or with artesuate treatment, respectively. Some of the artesuate immunofluorescence signal is colocalized with mitochondria. Scale bar, 5 µm.</p

Relationships between the <i>Osteocalcin</i> Gene Polymorphisms, Serum Osteocalcin Levels, and Hepatitis B Virus-Related Hepatocellular Carcinoma in a Chinese Population

<div><p>Background</p><p>Available evidence has demonstrated that osteocalcin may play a role in pathogenesis of cancer, and mutation of the <i>osteocalcin</i> gene may be involved in the cancer development. The aim of this study is to determine whether <i>osteocalcin</i> gene polymorphisms are associated with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) among Chinese population.</p><p>Methods</p><p>A total of 515 subjects were divided into four groups: 129 patients with chronic hepatitis B (CHB), 62 patients with HBV-related liver cirrhosis (LC), 154 patients with HBV-related HCC, and 170 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect <i>osteocalcin</i> gene <i>rs1800247</i> and <i>rs1543297</i> polymorphisms.</p><p>Results</p><p>Compared with healthy controls, the <i>rs1800247</i> HH and Hh genotypes were associated with a significantly increased susceptibility to HCC (HH versus hh: OR = 6.828, 95% CI 2.620–17.795, <i>P</i> <0.001; Hh versus hh: OR = 6.306, 95% CI 3.480–11.423, <i>P</i> <0.001, respectively). Similarly, the subjects bearing the H allele of <i>rs1800247</i> had more than a 2.4-fold increased risk for development of HCC (OR = 2.484, 95% CI 1.747–3.532, <i>P</i> <0.001) compared with those bearing the h allele. In addition, we found significant decreased serum osteocalcin levels in HBV-related HCC patients (11.73±8.18 ng/mL) compared with healthy controls (15.3±6.06 ng/mL). Furthermore, the serum osteocalcin levels were significantly lower in HCC patients than healthy controls among the individuals with heterozygous Hh genotype (<i>P</i> = 0.003) and CT genotype (<i>P</i> <0.001). In contrast, there were no significant differences in the genotype and allele of <i>rs1543297</i> polymorphisms between the groups of patients and healthy controls.</p><p>Conclusions</p><p>These findings for the first time suggest that genetic variant in <i>osteocalcin</i> gene <i>rs1800247</i> polymorphisms may be a risk factor for HBV-related HCC. We also find an inverse association of serum osteocalcin levels with HCC.</p></div

Association of <i>osteocalcin</i> polymorphisms with serum osteocalcin levels (median ± IQR, ng/mL) in cases and healthy controls.

<p><i>CHB</i> chronic hepatitis B, <i>HCC</i> hepatocellular carcinoma,<i>LC</i> liver cirrhosis,<i>IQR</i> interquartile range, OC, osteocalcin, <i>N</i> group number</p><p>* Kruskal-Wallis test: comparing the difference of serum osteocalcin levels in the three genotypes among the same group subjects.</p><p>** Kruskal-Wallis test: comparing the difference of serum osteocalcin levels in the four group subjects among the individuals with the same genotype.</p><p>Association of <i>osteocalcin</i> polymorphisms with serum osteocalcin levels (median ± IQR, ng/mL) in cases and healthy controls.</p

Artemisinin results in ROS production in the malaria mitochondria but not in mammalian mitochondria.

<p>(A–C) Artemisinin promotes ROS generation in isolated mitochondria from malaria parasites (A) and yeast (B) but not in mammalian mitochondria (C). ROS production was monitored by measuring DCF fluorescence intensity. (D,E) Comparable amount of ROS generated by X/XO system as artemisinin resulted in similar degree of uncoupling effect on isolated malarial mitochondria. Δψ_m of isolated <i>P. berghei</i> mitochondria was assessed by measuring the Δψ_m-dependent uptake of Rh123. ROS production was monitored using dichlorofluorescin diacetate (DCFH-DA) assay. (F) An isobologram for DPI and artemisinin. Data points above the line indicate antagonism between ROS scavenger DPPD and artemisinin. FIC: fractional inhibitory concentration. (G) ROS scavenger DPPD and its effect on the depolarizing activity of artemisnin. (H) Deoxyartemisinin has no effect on ROS production in isolated malaria mitochondria. n = 3. Data were shown as mean ± SEM. *** <i>p</i><0.0001 versus control, ^###<i>p</i><0.0001 versus Art.</p

Artemisinin and its antimalarial derivatives include various peroxide compounds.

<p>(A) Artemisinin. (B) OZ209 and OZ277. (C–E) Enantiomers (1a, 1b; 2a, 2b and 3a, 3b) that have been synthesized and shown with no stereoselective difference in antimalarial activity. (F) Yingzhaosu A. (G and H) Antimalarial tetraoxanes.</p