A method is proposed to generate femtosecond, ultra-low emittance (∼10 −8 m rad), electron beams in a laser-plasma accelerator using two lasers of different colors. A long-wavelength pump pulse, with large ponderomotive force and small peak electric field, excites a wake without fully ionizing a high-Z gas. A short-wavelength injection pulse, with small ponderomotive force and large peak electric field, co-propagating and delayed with respect to the pump laser, ionizes a fraction of the remaining bound electrons at a trapping wake phase, generating an electron beam that is accelerated in the wake.

No abstract

The results indicated that WHtR might be an optimal anthropometric predictor of metabolic syndrome risk factors and the cut-point of WHtR was approximately 0.50 in both genders of Chinese adults.

Coumarin (1,2-benzopyrone), an aromatic oxygen-containing heterocyclic compound, has various biological functions. Previous studies have demonstrated that coumarin and its derivatives exhibit antifungal activity against Candida albicans. In this study, we investigated the exact mechanism by which coumarin works against this fungus using Annexin V-FITC/PI double staining, TUNEL assay, and DAPI staining, and found that it induced a series of apoptotic features, including phosphatidylserine (PS) externalization, DNA fragmentation, and nuclear condensation. Moreover, it also induced cytochrome c release from the mitochondria to the cytoplasm and metacaspase activation. Further study revealed that intracellular reactive oxygen species (ROS) levels were increased and mitochondrial functions, such as mitochondrial membrane potential and mitochondrial morphology, were altered after treatment with coumarin. Cytosolic and mitochondrial Ca2+ levels were also found to be elevated. However, pretreatment with ruthenium red (RR), a known mitochondrial Ca2+ channel inhibitor, attenuated coumarin-mediated DNA fragmentation and metacaspase activity, indicating that the coumarin-induced C. albicans apoptosis is associated with mitochondrial Ca2+ influx. Finally, coumarin was found to be low-toxic and effective in prolonging the survival of C. albicans-infected mice. This study highlights the antifungal activity and mechanism of coumarin against C. albicans and provides a potential treatment strategy for C. albicans infection.

Computing protein-protein association affinities is one of the fundamental challenges in computational biophysics/biochemistry. The overwhelming amount of statistics in the phase space of very high dimensions cannot be sufficiently sampled even with today's high-performance computing power. In this paper, we extend a potential of mean force (PMF)-based approach, the hybrid steered molecular dynamics (hSMD) approach we developed for ligand-protein binding, to protein-protein association problems. For a protein complex consisting of two protomers, P1 and P2, we choose m (≥3) segments of P1 whose m centers of mass are to be steered in a chosen direction and n (≥3) segments of P2 whose n centers of mass steered in the opposite direction. The coordinates of these m+n centers constitute a phase space of 3(m+n) dimensions (3(m+n)-D). All the other degrees of freedom of the proteins, ligands, solvents, and solutes are freely subject to the stochastic dynamics of the all-atom model system. Conducting SMD along a line in this phase space, we obtain the 3(m+n)-D PMF difference between two chosen states, one single state in the associated state ensemble and one single state in the dissociated state ensemble. This PMF difference is the first of four contributors to the protein-protein association energy. The second contributor is the 3(m+n−1)-D partial partition in the associated state counting for the rotations and fluctuations of the (m+n−1) centers while fixing one of the m+n centers of the P1-P2 complex. The two other contributors are the 3(m−1)-D partial partition of P1 and the 3(n−1)-D partial partition of P2 counting for the rotations and fluctuations of their m−1 or n−1 centers while fixing one of the m/n centers of P1/P2 in the dissociated state. Each of these three partial partitions can be factored exactly into a 6-D partial partition multiplying a remaining factor counting for the small fluctuations while fixing three of the centers of P1, P2, or the P1-P2 complex, respectively. These small fluctuations can be well approximated as Gaussian. And every 6-D partition can be reduced in an exact manner to three problems of “1-D sampling”, counting the rotations and fluctuations around one of the centers being fixed. We implement this hSMD approach to the Ras-RalGDS complex, choosing three centers on RalGDS and three on Ras (m=n=3). At a computing cost of about 71.6 wall-clock hours using 400 computing cores in parallel, we obtained the association energy, - 9.2±1.9 kcal/mol on the basis of CHARMM 36 parameters, which well agrees with the experimental data, - 8.4±0.2 kcal/mol.

No abstract

No abstract

No abstract