We present a generalized contact computation model for arbitrarily shaped polyhedra to simplify the contact analysis in discontinuous deformation analysis. A list of generalized contact constraints can be established for contacting polyhedra during contact detection. Each contact constraint contains information for 2 contact points, unique contact plane, and related contact modes (open, locked, or sliding). Computational aspects of the generalized contact model include identification of contact positions and contact modes, uniform penalty formulation of generalized contact constraint, and uniform updating of contact modes and contact planes in the open-close iteration. Compared with previous strategies, the generalized contact computation model has a simpler data structure and fewer memory requirements. Meanwhile, it simplifies the penalty formulation and facilitates the open-close iteration check while producing enough accuracy. Illustrative examples show the ability of the method to handle the full range of polyhedral shapes.

A fast direct search (FDS) algorithm is presented to increase the efficiency of contact detection for convex polygonal and polyhedral particles. All contact types are detected using only a small subset of these contact types: vertex-to-edge for polygons while vertex-to-face and edge-to-edge for polyhedra. First, an initial contact list is generated. Then in subsequent steps the contact list is updated by checking only local boundaries of the blocks and their separation. An exclusion algorithm is applied to avoid unnecessary examination for particles that are near but not-in-contact. The benchmark tests show that the FDS produces significant speed-up in various cases.

Precise control of alloying sites has long been a challenging pursuit, yet little has been achieved for the atomic-level manipulation of metallic nanomaterials. Here we describe utilization of a surface motif exchange (SME) reaction to selectively replace the surface motifs of parent [Ag₄₄(SR)₃₀]^4- (SR = thiolate) nanoparticles (NPs), leading to bimetallic NPs with well-defined molecular formula and atomically-controlled alloying sites in protecting shell. A systematic mass (and tandem mass) spectrometry analysis suggests that the SME reaction is an atomically precise displacement of SR-Ag(I)-SR-protecting modules of Ag NPs by the incoming SR-Au(I)-SR modules, giving rise to a core-shell [Ag₃₂@Au₁₂(SR)₃₀]^4-. Theoretical calculation suggests that the thermodynamically less favorable core-shell Ag@Au nanostructure is kinetically stabilized by the intermediate Ag₂₀ shell, preventing inward diffusion of the surface Au atoms. The delicate SME reaction opens a door to precisely control the alloying sites in the protecting shell of bimetallic NPs with broad utility.

As a new anticancer treatment option, vaccinia virus (VACV) has shown remarkable antitumor activities (oncolysis) in preclinical studies, but potential infection of other organs remains a safety concern. We present here genome comparisons between the de novo sequence of GLV-1h68, a recombinant VACV, and other VACVs. The identified differences in open reading frames (ORFs) include genes encoding host-range selection, virulence and immune modulation proteins, e.g., ankyrin-like proteins, serine proteinase inhibitor SPI-2/CrmA, tumor necrosis factor (TNF) receptor homolog CrmC, semaphorin-like and interleukin-1 receptor homolog proteins. Phylogenetic analyses indicate that GLV-1h68 is closest to Lister strains but has lost several ORFs present in its parental LIVP strain, including genes encoding CrmE and a viral Golgi anti-apoptotic protein, v-GAAP. The reduced pathogenicity of GLV-1h68 is confirmed in male mice bearing C6 rat glioma and in immunocompetent mice bearing B16-F10 murine melanoma. The contribution of foreign gene expression cassettes in the F14.5L, J2R and A56R loci is analyzed, in particular the contribution of F14.5L inactivation to the reduced virulence is demonstrated by comparing the virulence of GLV-1h68 with its F14.5L-null and revertant viruses. GLV-1h68 is a promising engineered VACV variant for anticancer therapy with tumor-specific replication, reduced pathogenicity and benign tissue tropism.

Barley stripe mosaic virus (BSMV) induces massive actin filament thickening at the infection front of infected Nicotiana benthamiana leaves. To determine the mechanisms leading to actin remodeling, fluorescent protein fusions of the BSMV triple gene block (TGB) proteins were coexpressed in cells with the actin marker DsRed: Talin. TGB ectopic expression experiments revealed that TGB3 is a major elicitor of filament thickening, that TGB2 resulted in formation of intermediate DsRed:Talin filaments, and that TGB1 alone had no obvious effects on actin filament structure. Latrunculin B (LatB) treatments retarded BSMV cell-to-cell movement, disrupted actin filament organization, and dramatically decreased the proportion of paired TGB3 foci appearing at the cell wall (CW). BSMV infection of transgenic plants tagged with GFP-KDEL exhibited membrane proliferation and vesicle formation that were especially evident around the nucleus. Similar membrane proliferation occurred in plants expressing TGB2 and/or TGB3, and DsRed: Talin fluorescence in these plants colocalized with the ER vesicles. TGB3 also associated with the Golgi apparatus and overlapped with cortical vesicles appearing at the cell periphery. Brefeldin A treatments disrupted Golgi and also altered vesicles at the CW, but failed to interfere with TGB CW localization. Our results indicate that actin cytoskeleton interactions are important in BSMV cell-to-cell movement and for CW localization of TGB3.

Lysosomes are crucial cellular organelles for human health that function in digestion and recycling of extracellular and intracellular macromolecules. We describe a signaling role for lysosomes that affects aging. In the worm Caenorhabditis elegans, the lysosomal acid lipase LIPL-4 triggered nuclear translocalization of a lysosomal lipid chaperone LBP-8, which promoted longevity by activating the nuclear hormone receptors NHR-49 and NHR-80. We used high-throughput metabolomic analysis to identify several lipids in which abundance was increased in worms constitutively overexpressing LIPL-4. Among them, oleoylethanolamide directly bound to LBP-8 and NHR-80 proteins, activated transcription of target genes of NHR-49 and NHR-80, and promoted longevity in C. elegans. These findings reveal a lysosome-to-nucleus signaling pathway that promotes longevity and suggest a function of lysosomes as signaling organelles in metazoans.

Background

Strict medication guidance and lifestyle interventions to manage blood pressure (BP) in hypertensive patients are typically difficult to follow.

Objective

To evaluate the 1-year effectiveness of lifestyle and drug intervention in the management of rural hypertensive patients.

Design

Randomized community intervention trial.

Participants

The control group comprised 967 patients who received standard antihypertensive drug intervention therapy from two communities, whereas the intervention group comprised 1945 patients who received antihypertensive drug and lifestyle intervention therapies from four communities in rural China.

Main measures

Data on lifestyle behaviors and BP measurements at baseline and 1-year follow-up were collected. A difference-in-difference logistic regression model was used to assess the effect of the intervention.

Key results

BP control after the 1-year intervention was better than that at baseline in both groups. The within-group change in BP control of 59.3% in the intervention group was much higher than the 25.2% change in the control group (P < 0.001). Along with the duration of the follow-up period, systolic and diastolic BP decreased rapidly in the early stages and then gradually after 6 months in the intervention group (P < 0.001). In the intervention group, drug therapy adherence was increased by 39.5% (from 48.1% at 1 month to 87.6% at 1 year) (P < 0.001), more in women (45.6%) than in men (31.2%; P < 0.001). The net effect of the lifestyle intervention improved the rate of BP control by 56.1% (70.8% for men and 44.7% for women). For all physiological and biochemical factors, such as body mass index, waist circumference, lipid metabolism, and glucose control, improvements were more significant in the behavioral intervention group than those in the control group (all P < 0.001).

Conclusion

The addition of lifestyle intervention by physicians or nurses helps control BP effectively and lowers BP better than usual care with antihypertensive drug therapy alone.

Airborne particles play critical roles in air quality, health effects, visibility, and climate. Secondary organic aerosols (SOA) formed from oxidation of organic gases such as α-pinene account for a significant portion of total airborne particle mass. Current atmospheric models typically incorporate the assumption that SOA mass is a liquid into which semivolatile organic compounds undergo instantaneous equilibrium partitioning to grow the particles into the size range important for light scattering and cloud condensation nuclei activity. We report studies of particles from the oxidation of α-pinene by ozone and NO₃ radicals at room temperature. SOA is primarily formed from low-volatility ozonolysis products, with a small contribution from higher volatility organic nitrates from the NO₃ reaction. Contrary to expectations, the particulate nitrate concentration is not consistent with equilibrium partitioning between the gas phase and a liquid particle. Rather the fraction of organic nitrates in the particles is only explained by irreversible, kinetically determined uptake of the nitrates on existing particles, with an uptake coefficient that is 1.6% of that for the ozonolysis products. If the nonequilibrium particle formation and growth observed in this atmospherically important system is a general phenomenon in the atmosphere, aerosol models may need to be reformulated. The reformulation of aerosol models could impact the predicted evolution of SOA in the atmosphere both outdoors and indoors, its role in heterogeneous chemistry, its projected impacts on air quality, visibility, and climate, and hence the development of reliable control strategies.

BAF complexes are composed of different subunits with varying functional and developmental roles, although many subunits have not been examined in depth. Here we show that the Baf45 subunit Dpf2 maintains pluripotency and ESC differentiation potential. Dpf2 co-occupies enhancers with Oct4, Sox2, p300, and the BAF subunit Brg1, and deleting Dpf2 perturbs ESC self-renewal, induces repression of Tbx3, and impairs mesendodermal differentiation without dramatically altering Brg1 localization. Mesendodermal differentiation can be rescued by restoring Tbx3 expression, whose distal enhancer is positively regulated by Dpf2-dependent H3K27ac maintenance and recruitment of pluripotency TFs and Brg1. In contrast, the PRC2 subunit Eed binds an intragenic Tbx3 enhancer to oppose Dpf2-dependent Tbx3 expression and mesendodermal differentiation. The PRC2 subunit Ezh2 likewise opposes Dpf2-dependent differentiation through a distinct mechanism involving Nanog repression. Together, these findings delineate distinct mechanistic roles for specific BAF and PRC2 subunits during ESC differentiation.