Photodisintegration of 4^4He into p+t

The two-body photodisintegration of $^4$He into a proton and a triton has been studied using the CEBAF Large-Acceptance Spectrometer (CLAS) at Jefferson Laboratory. Real photons produced with the Hall-B bremsstrahlung-tagging system in the energy range from 0.35 to 1.55 GeV were incident on a liquid $^4$He target. This is the first measurement of the photodisintegration of $^4$He above 0.4 GeV. The differential cross sections for the $\gamma$$^4$He$\to pt$ reaction have been measured as a function of photon-beam energy and proton-scattering angle, and are compared with the latest model calculations by J.-M. Laget. At 0.6-1.2 GeV, our data are in good agreement only with the calculations that include three-body mechanisms, thus confirming their importance. These results reinforce the conclusion of our previous study of the three-body breakup of $^3$He that demonstrated the great importance of three-body mechanisms in the energy region 0.5-0.8 GeV .Comment: 13 pages submitted in one tgz file containing 2 tex file and 22 postscrip figure

The pharmacological regulation of cellular mitophagy

Small molecules are pharmacological tools of considerable value for dissecting complex biological processes and identifying potential therapeutic interventions. Recently, the cellular quality-control process of mitophagy has attracted considerable research interest; however, the limited availability of suitable chemical probes has restricted our understanding of the molecular mechanisms involved. Current approaches to initiate mitophagy include acute dissipation of the mitochondrial membrane potential (ΔΨm) by mitochondrial uncouplers (for example, FCCP/CCCP) and the use of antimycin A and oligomycin to impair respiration. Both approaches impair mitochondrial homeostasis and therefore limit the scope for dissection of subtle, bioenergy-related regulatory phenomena. Recently, novel mitophagy activators acting independently of the respiration collapse have been reported, offering new opportunities to understand the process and potential for therapeutic exploitation. We have summarized the current status of mitophagy modulators and analyzed the available chemical tools, commenting on their advantages, limitations and current applications

ELASTISITAS HASIL TANGKAPAN UDANG MANTIS (Harpiosquilla raphidea) DENGAN MESH SIZE DAN PANJANG JARING INSANG DI KELURAHAN KAMPUNG NELAYAN KUALA TUNGKAL

The fishing gear used by fishermen in catching mantis shrimp is a gillnet. The purpose of the study was to determine the elasticity of mesh size and net length to the production of mantis shrimp catch. The gillnet used in this study has a mesh size of 3.5 inches and 4 inches and a net length of 900 m, 1050 m and 1200 m. The method used in this study is a survey, and the data analysis used is the Cobb Douglas production function using SPSS version 26 and subsequently in the elasticity analysis. The results of the descriptive study both in number and composition show that the production of mantis shrimp catch based on mesh size in Kuala Tungkal waters is the most using a size of 4 inches, which is as many as 480 fish or 50.57%, while based on the length of the net, the most is using a size of 1,200 m, which is 419 fish or 45.15%. Simultaneous analysis of the signification obtained was 0.00 < 0.05, meaning that the mesh size and net length together had a significant influence on the production of mantis shrimp catch, while partially the significance value for the mesh size was 0.00 < 0.05 and the net length also had a significance of 0.00 < 0.05 which means that the mesh size and net length had an effect on the production of mantis shrimp catch. Based on the elasticity analysis, the value of the parameter coefficient of the cobb douglas regression equation is 1.229 or greater than 1, which means that the production of mantis shrimp catch is included in the category of increasing return to scale or the change in output obtained will be greater than the input usedAlat tangkap yang digunakan oleh nelayan dalam penangkapan udang mantis adalah gillnet. Tujuan dari penelitian adalah untuk mengetahui elastisitas mesh size dan panjang jaring terhadap produksi tangkapan udang mantis. Gillnet yang digunakan pada penelitian ini adalah yang memiliki mesh size 3,5 inchi dan 4 inchi dan panjang jaring 900 m, 1050 m dan 1200 m. Metode yang digunakan pada penelitian ini adalah survey, dan analisis data yang digunakan adalah fungsi produksi Cobb Douglas menggunakan SPSS versi 26 dan selanjutnya di analisis elastisitasnya. Hasil penelitian secara deskriptif baik jumlah maupun komposisi menunjukkan bahwa produksi tangkapan udang mantis berdasarkan mesh size di perairan kuala tungkal yang terbanyak adalah menggunakan ukuran 4 inci yaitu sebanyak 480 ekor atau sebesar 50,57 % sedangkan berdasarkan panjang jaring yang terbanyak adalah menggunakan ukuran 1.200 m yaitu sebanyak 419 ekor atau sebesar 45,15%. Analisis secara simultan siginifikasi yang didapatkan adalah sebesar 0,00 < 0,05 artinya mesh size dan panjang jaring secara bersama sama memiliki pengaruh yang signifikan terhadap produksi hasil tangkapan udang mantis, sedangkan secara parsial didapatkan nilai signifikasi untuk mesh size sebesar 0,00 < 0,05 dan panjang jaring juga memiliki signifikasi sebesar 0,00 < 0,05 yang artinya mesh size dan panjang jaring berpengaruh terhadap produksi hasil tangkapan udang mantis. Berdasarkan analsisis elastisitas didapatkan nilai koefisien parameter dari persamaan regresi cobb douglas sebesar 1,229 atau lebih besar dari 1 yang artinya produksi hasil tangkapan udang mantis termasuk kedalam katagori increasing return to scale atau perubahan output yang didapatkan akan lebih besar dari input yang digunaka

Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c

Cortico-basal ganglia circuits are critical for speech and language and are implicated in autism spectrum disorder, in which language function can be severely affected. We demonstrate that in the mouse striatum, the gene Foxp2 negatively interacts with the synapse suppressor gene Mef2c. We present causal evidence that Mef2c inhibition by Foxp2 in neonatal mouse striatum controls synaptogenesis of corticostriatal inputs and vocalization in neonates. Mef2c suppresses corticostriatal synapse formation and striatal spinogenesis, but can itself be repressed by Foxp2 through direct DNA binding. Foxp2 deletion de-represses Mef2c, and both intrastriatal and global decrease of Mef2c rescue vocalization and striatal spinogenesis defects of Foxp2-deletion mutants. These findings suggest that Foxp2-Mef2C signaling is critical to corticostriatal circuit formation. If found in humans, such signaling defects could contribute to a range of neurologic and neuropsychiatric disorders.National Institutes of Health (U.S.) (Grant R37 HD028341)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Award R37 HD028341

π0\pi^0 photoproduction on the proton for photon energies from 0.675 to 2.875 GeV

Differential cross sections for the reaction $\gamma p \to p \pi^0$ have been measured with the CEBAF Large Acceptance Spectrometer (CLAS) and a tagged photon beam with energies from 0.675 to 2.875 GeV. The results reported here possess greater accuracy in the absolute normalization than previous measurements. They disagree with recent CB-ELSA measurements for the process at forward scattering angles. Agreement with the SAID and MAID fits is found below 1 GeV. The present set of cross sections has been incorporated into the SAID database, and exploratory fits have been extended to 3 GeV. Resonance couplings have been extracted and compared to previous determinations.Comment: 18 pages, 48 figure

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells

First Measurement of Beam-Recoil Observables Cx and Cz in Hyperon Photoproduction

Spin transfer from circularly polarized real photons to recoiling hyperons has been measured for the reactions $\vec\gamma + p \to K^+ + \vec\Lambda$ and $\vec\gamma + p \to K^+ + \vec\Sigma^0$. The data were obtained using the CLAS detector at Jefferson Lab for center-of-mass energies $W$ between 1.6 and 2.53 GeV, and for $-0.85<\cos\theta_{K^+}^{c.m.}< +0.95$. For the $\Lambda$, the polarization transfer coefficient along the photon momentum axis, $C_z$, was found to be near unity for a wide range of energy and kaon production angles. The associated transverse polarization coefficient, $C_x$, is smaller than $C_z$ by a roughly constant difference of unity. Most significantly, the {\it total} $\Lambda$ polarization vector, including the induced polarization $P$, has magnitude consistent with unity at all measured energies and production angles when the beam is fully polarized. For the $\Sigma^0$ this simple phenomenology does not hold. All existing hadrodynamic models are in poor agreement with these results.Comment: 28 pages, 18 figures, Submitted to Physical Review

Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness

Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide and lead to more than 50,000 deaths annually. The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp., respectively. These parasites have similar biology and genomic sequence, suggesting that all three diseases could be cured with drugs that modulate the activity of a conserved parasite target. However, no such molecular targets or broad spectrum drugs have been identified to date. Here we describe a selective inhibitor of the kinetoplastid proteasome (GNF6702) with unprecedented in vivo efficacy, which cleared parasites from mice in all three models of infection. GNF6702 inhibits the kinetoplastid proteasome through a non-competitive mechanism, does not inhibit the mammalian proteasome or growth of mammalian cells, and is well-tolerated in mice. Our data provide genetic and chemical validation of the parasite proteasome as a promising therapeutic target for treatment of kinetoplastid infections, and underscore the possibility of developing a single class of drugs for these neglected diseases

Spirulina (Arthrospira) industry in Inner Mongolia of China: current status and prospects

This paper outlines an investigation on current situation of Spirulina (Arthrospira) industry in Inner Mongolia, an internal region of China with temperate continental climate. More than 20 Spirulina plants have been established in Inner Mongolia since 2001, most of which are located at Wulan Town in the Ordos Plateau. By the end of 2009, the total annual production of Spirulina in the Ordos Plateau surpassed 700 t (dw), which account for ca. 80% of the total productivity of Inner Mongolia, and ca. 20% of China. Besides abundant solar radiation and enough freshwater favorable for Spirulina production, the three technical strategies contribute to the prosperity and success of Spirulina industry in the region: (1) reducing the cost or investment by overall advantages of rich local natural resources with low cost for Spirulina production, such as alkaline lakes, coal, electricity, and sandy land; (2) controlling the culture temperature and to avoid contamination by building plastic greenhouses on raceway ponds, (3) reducing investment by simplifying the construction of the ponds and the greenhouses. As the result, the growth period of Spirulina has been prolonged from about 120 to about 165 days, the cost of Spirulina has decreased by 25–30%, and the quality of products has been enhanced substantially. Inner Mongolia is expected to become the largest base for Spirulina production not only in China, but also in the world in the near future

MET overexpression in ovarian cancer via CD24-induced downregulation of miR-181a: A signalling for cellular quiescence-like state and chemoresistance in ovarian CSCs

Increased expression of CD24 and MET, markers for cancer stem-like cells (CSCs), are each associated with ovarian cancer severity. However, whether CD24 and MET are co-expressed in ovarian CSCs and, if so, how they are related to CSC phenotype manifestation remains unknown. Our immunohistochemistry analysis showed that the co-expression of CD24 and MET was associated with poorer patient survival in ovarian cancer than those without. In addition, analyses using KM plotter and ROC plotter presented that the overexpression of CD24 or MET in ovarian cancer patients was associated with resistance to platinum-based chemotherapy. In our miRNA transcriptome and putative target genes analyses, miR-181a was downregulated in CD24-high ovarian cancer cells compared to CD24-low and predicted to bind to CD24 and MET 3'UTRs. In OV90 and SK-OV-3 cells, CD24 downregulated miR-181a expression by Src-mediated YY1 activation, leading to increased expression of MET. And, CD24 or MET knockdown or miR-181a overexpression inhibited the manifestation of CSC phenotypes, cellular quiescence-like state and chemoresistance, in OV90 and SK-OV-3 cells: increased colony formation, decreased G0/G1 phase cell population and increased sensitivity to Cisplatin and Carboplatin. Our findings suggest that CD24-miR-181a-MET may consist of a signalling route for ovarian CSCs, therefore being a combinatory set of markers and therapeutic targets for ovarian CSCs