Investigations of lubricant rheology as applied to elastohydrodynamic lubrication

Traction prediction in sliding elastohydrodynamic (EHD) contacts was examined along with an elastohydrodynamic lubrication simulation of the effects of load and speed on temperatures in the EHD contact. An existing shear stress theory and lubricant rheological model were studied and evaluated by applying them to traction prediction. Results obtained using measured film thickness and surface temperature data, were compared with measured traction values. The infrared technique for measuring temperatures in an EHD contact was further developed and ball surface and fluid temperatures are reported for sliding speeds of 0.35 to 5.08 m/s at 0.52 to 2.03 GN/sq m maximum pressure and surface roughnesses of .011 to .381 micrometers c.1.a. The relationship between asperity interaction, as measured by relocation surface profilimetry and high frequency temperature measurements, and the ratio of film thickness to surface roughness was also studied

Principles of meiotic chromosome assembly revealed in S. cerevisiae

During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we use Saccharomyces cerevisiae to explore how this elaborate three-dimensional chromosome organisation is linked to genomic sequence. As cells enter meiosis, we observe that strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion with growth limited by barriers, in which a heterogeneous population of expanding loops develop along the chromosome. Importantly, CTCF, the factor that imposes similar features in mammalian interphase, is absent in S. cerevisiae, suggesting alternative mechanisms of barrier formation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process

Pesticide use and opportunities of exposure among farmers and their families: cross-sectional studies 1998-2006 from Hebron governorate, occupied Palestinian territory

<p>Abstract</p> <p>Background</p> <p>Adverse health effects caused by pesticide exposure have been reported in occupied Palestinian territory and the world at large. The objective of this paper is to compare patterns of pesticide use in Beit-U'mmar village, West Bank, between 1998 and 2006.</p> <p>Methods</p> <p>We studied two populations in Beit-U'mmar village, comprised of: 1) 61 male farmers and their wives in 1998 and 2) 250 male farmers in 2006. Both populations completed a structured interview, which included questions about socio-demographic factors, types of farming tasks, as well as compounds, quantities, and handling of pesticides. Using the 1998 population as a reference, we applied generalized linear regression models (GLM) and 95% confidence intervals (CI) in order to estimate prevalence differences (PD) between the two populations.</p> <p>Results</p> <p>In 1998, farmers used 47 formulated pesticides on their crops. In 2006, 16 of these pesticides were still in use, including five internationally banned compounds. There were positive changes with less use of large quantities of pesticides (>40 units/year) (PD -51; CI -0.60, -0.43), in applying the recommended dosage of pesticides (PD +0.57; CI +0.48, +0.68) and complying with the safety period (PD +0.89; CI+0.83, +0.95). Changes also included farmers' habits while applying pesticides, such as less smoking (PD -0.20; CI-0.34, -0.07) and eating at the work place (PD -0.33; CI-0.47, -0.19). No significant changes were found from 1998 to 2006 regarding use of personal protective equipment, pesticide storage, farmers' habits after applying pesticides, and in using some highly hazardous pesticides.</p> <p>Conclusions</p> <p>The results were based on two cross-sectional surveys and should be interpreted with caution due to potential validity problems. The results of the study suggest some positive changes in the handling of pesticides amongst participants in 2006, which could be due to different policy interventions and regulations that were implemented after 1998. However, farm workers in Beit -U'mmar village are still at risk of health effects because of ongoing exposure to pesticides. To the best of our knowledge, no studies on long-term changes in pesticide use have been reported from developing countries.</p

Quercetin Suppresses Cyclooxygenase-2 Expression and Angiogenesis through Inactivation of P300 Signaling

Quercetin, a polyphenolic bioflavonoid, possesses multiple pharmacological actions including anti-inflammatory and antitumor properties. However, the precise action mechanisms of quercetin remain unclear. Here, we reported the regulatory actions of quercetin on cyclooxygenase-2 (COX-2), an important mediator in inflammation and tumor promotion, and revealed the underlying mechanisms. Quercetin significantly suppressed COX-2 mRNA and protein expression and prostaglandin (PG) E(2) production, as well as COX-2 promoter activation in breast cancer cells. Quercetin also significantly inhibited COX-2-mediated angiogenesis in human endothelial cells in a dose-dependent manner. The in vitro streptavidin-agarose pulldown assay and in vivo chromatin immunoprecipitation assay showed that quercetin considerably inhibited the binding of the transactivators CREB2, C-Jun, C/EBPβ and NF-κB and blocked the recruitment of the coactivator p300 to COX-2 promoter. Moreover, quercetin effectively inhibited p300 histone acetyltransferase (HAT) activity, thereby attenuating the p300-mediated acetylation of NF-κB. Treatment of cells with p300 HAT inhibitor roscovitine was as effective as quercetin at inhibiting p300 HAT activity. Addition of quercetin to roscovitine-treated cells did not change the roscovitine-induced inhibition of p300 HAT activity. Conversely, gene delivery of constitutively active p300 significantly reversed the quercetin-mediated inhibition of endogenous HAT activity. These results indicate that quercetin suppresses COX-2 expression by inhibiting the p300 signaling and blocking the binding of multiple transactivators to COX-2 promoter. Our findings therefore reveal a novel mechanism of action of quercetin and suggest a potential use for quercetin in the treatment of COX-2-mediated diseases such as breast cancers

MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors

There is increasing evidence that oncogenic transformation modifies the metabolic program of cells. A common alteration is the upregulation of glycolysis, and efforts to target glycolytic enzymes for anticancer therapy are under way. Here, we performed a genome-wide haploid genetic screen to identify resistance mechanisms to 3-bromopyruvate (3-BrPA), a drug candidate that inhibits glycolysis in a poorly understood fashion. We identified the SLC16A1 gene product, MCT1, as the main determinant of 3-BrPA sensitivity. MCT1 is necessary and sufficient for 3-BrPA uptake by cancer cells. Additionally, SLC16A1 mRNA levels are the best predictor of 3-BrPA sensitivity and are most elevated in glycolytic cancer cells. Furthermore, forced MCT1 expression in 3-BrPA–resistant cancer cells sensitizes tumor xenografts to 3-BrPA treatment in vivo. Our results identify a potential biomarker for 3-BrPA sensitivity and provide proof of concept that the selectivity of cancer-expressed transporters can be exploited for delivering toxic molecules to tumors.National Institutes of Health (U.S.) (NIH CA103866)Jane Coffin Childs Memorial Fund for Medical Research (Fellowship)National Science Foundation (U.S.) (Fellowship)Howard Hughes Medical Institute (Investigator

SMC complexes differentially compact mitotic chromosomes according to genomic context

Structural maintenance of chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modelling, we study how cohesin and condensin, two deeply conserved SMC complexes, organize chromosomes in the budding yeast Saccharomyces cerevisiae. The canonical role of cohesin is to co-align sister chromatids, while condensin generally compacts mitotic chromosomes. We find strikingly different roles for the two complexes in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosome arms, independently of sister chromatid cohesion. Polymer simulations demonstrate that this role can be fully accounted for through cis-looping of chromatin. Second, condensin is generally dispensable for compaction along chromosome arms. Instead, it plays a targeted role compacting the rDNA proximal regions and promoting resolution of peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that distinct SMC-dependent looping activities are selectively deployed to appropriately compact chromosomes

The Sariçiçek Howardite Fall in Turkey: Source Crater of HED Meteorites on Vesta and İmpact Risk of Vestoids

The Sariçiçek howardite meteorite shower consisting of 343 documented stones occurred on 2 September 2015 in Turkey and is the first documented howardite fall. Cosmogenic isotopes show that Sariçiçek experienced a complex cosmic ray exposure history, exposed during ~12–14 Ma in a regolith near the surface of a parent asteroid, and that an ~1 m sized meteoroid was launched by an impact 22 ± 2 Ma ago to Earth (as did one third of all HED meteorites). SIMS dating of zircon and baddeleyite yielded 4550.4 ± 2.5 Ma and 4553 ± 8.8 Ma crystallization ages for the basaltic magma clasts. The apatite U-Pb age of 4525 ± 17 Ma, K-Ar age of ~3.9 Ga, and the U,Th-He ages of 1.8 ± 0.7 and 2.6 ± 0.3 Ga are interpreted to represent thermal metamorphic and impact-related resetting ages, respectively. Petrographic, geochemical and O-, Cr- and Tiisotopic studies confirm that Sariçiçek belongs to the normal clan of HED meteorites. Petrographic observations and analysis of organic material indicate a small portion of carbonaceous chondrite material in the Sariçiçek regolith and organic contamination of the meteorite after a few days on soil. Video observations of the fall show an atmospheric entry at 17.3 ± 0.8 kms-1 from NW, fragmentations at 37, 33, 31 and 27 km altitude, and provide a pre-atmospheric orbit that is the first dynamical link between the normal HED meteorite clan and the inner Main Belt. Spectral data indicate the similarity of Sariçiçek with the Vesta asteroid family (V-class) spectra, a group of asteroids stretching to delivery resonances, which includes (4) Vesta. Dynamical modeling of meteoroid delivery to Earth shows that the complete disruption of a ~1 km sized Vesta family asteroid or a ~10 km sized impact crater on Vesta is required to provide sufficient meteoroids ≤4 m in size to account for the influx of meteorites from this HED clan. The 16.7 km diameter Antonia impact crater on Vesta was formed on terrain of the same age as given by the 4He retention age of Sariçiçek. Lunar scaling for crater production to crater counts of its ejecta blanket show it was formed ~22 Ma ago

Optimization of Non-Coding Regions for a Non-Modified mRNA COVID-19 Vaccine

The CVnCoV (CureVac) mRNA vaccine for SARS-CoV-2 has recently been evaluated in a phase 2b/3 efficacy trial in humans1. CV2CoV is a second-generation mRNA vaccine with non-modified nucleosides but optimized non-coding regions and enhanced antigen expression. Here we report a head-to-head study of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in nonhuman primates. We immunized 18 cynomolgus macaques with two doses of 12 ug of lipid nanoparticle formulated CVnCoV, CV2CoV, or sham (N=6/group). CV2CoV induced substantially higher binding and neutralizing antibodies, memory B cell responses, and T cell responses as compared with CVnCoV. CV2CoV also induced more potent neutralizing antibody responses against SARS-CoV-2 variants, including the delta variant. Moreover, CV2CoV proved comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. While CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tract. Binding and neutralizing antibody titers correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in nonhuman primates