A Potent Lead Induces Apoptosis in Pancreatic Cancer Cells

Pancreatic cancer is considered a lethal and treatment-refractory disease. To obtain a potent anticancer drug, the cytotoxic effect of 2-(benzo[d]oxazol-3(2H)-ylmethyl)- 5-((cyclohexylamino)methyl)benzene-1,4-diol, dihydrochloride (NSC48693) on human pancreatic cancer cells CFPAC-1, MiaPaCa-2, and BxPC-3 was assessed in vitro. The proliferation of CFPAC-1, MiaPaCa-2, and BxPC-3 is inhibited with IC50 value of 12.9±0.2, 20.6±0.3, and 6.2±0.6 µM at 48 h, respectively. This discovery is followed with additional analysis to demonstrate that NSC48693 inhibition is due to induction of apoptosis, including Annexin V staining, chromatins staining, and colony forming assays. It is further revealed that NSC48693 induces the release of cytochrome c, reduces mitochondrial membrane potential, generates reactive oxygen species, and activates caspase. These results collectively indicate that NSC48693 mainly induces apoptosis of CFPAC-1, MiaPaCa-2, and BxPC-3 cells by the mitochondrial-mediated apoptotic pathway. Excitingly, the study highlights an encouraging inhibition effect that human embryonic kidney (HEK-293) and liver (HL-7702) cells are more resistant to the antigrowth effect of NSC48693 compared to the three cancer cell lines. From this perspective, NSC48693 should help to open up a new opportunity for the treatment of patients with pancreatic cancer

Mechanical Work as an Indirect Measure of Subjective Costs Influencing Human Movement

To descend a flight of stairs, would you rather walk or fall? Falling seems to have some obvious disadvantages such as the risk of pain or injury. But the preferred strategy of walking also entails a cost for the use of active muscles to perform negative work. The amount and distribution of work a person chooses to perform may, therefore, reflect a subjective valuation of the trade-offs between active muscle effort and other costs, such as pain. Here we use a simple jump landing experiment to quantify the work humans prefer to perform to dissipate the energy of landing. We found that healthy normal subjects (N = 8) preferred a strategy that involved performing 37% more negative work than minimally necessary (P<0.001) across a range of landing heights. This then required additional positive work to return to standing rest posture, highlighting the cost of this preference. Subjects were also able to modulate the amount of landing work, and its distribution between active and passive tissues. When instructed to land softly, they performed 76% more work than necessary (P<0.001), with a higher proportion from active muscles (89% vs. 84%, P<0.001). Stiff-legged landings, performed by one subject for demonstration, exhibited close to the minimum of work, with more of it performed passively through soft tissue deformations (at least 30% in stiff landings vs. 16% preferred). During jump landings, humans appear not to minimize muscle work, but instead choose to perform a consistent amount of extra work, presumably to avoid other subjective costs. The degree to which work is not minimized may indirectly quantify the relative valuation of costs that are otherwise difficult to measure

Role of biomechanics in the understanding of normal, injured, and healing ligaments and tendons

Ligaments and tendons are soft connective tissues which serve essential roles for biomechanical function of the musculoskeletal system by stabilizing and guiding the motion of diarthrodial joints. Nevertheless, these tissues are frequently injured due to repetition and overuse as well as quick cutting motions that involve acceleration and deceleration. These injuries often upset this balance between mobility and stability of the joint which causes damage to other soft tissues manifested as pain and other morbidity, such as osteoarthritis

Measurement of the nuclear modification factor for muons from charm and bottom hadrons in Pb+Pb collisions at 5.02 TeV with the ATLAS detector

Heavy-flavour hadron production provides information about the transport properties and microscopic structure of the quark-gluon plasma created in ultra-relativistic heavy-ion collisions. A measurement of the muons from semileptonic decays of charm and bottom hadrons produced in Pb+Pb and pp collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV with the ATLAS detector at the Large Hadron Collider is presented. The Pb+Pb data were collected in 2015 and 2018 with sampled integrated luminosities of 208 mu b(-1) and 38 mu b(-1), respectively, and pp data with a sampled integrated luminosity of 1.17 pb(-1) were collected in 2017. Muons from heavy-flavour semileptonic decays are separated from the light-flavour hadronic background using the momentum imbalance between the inner detector and muon spectrometer measurements, and muons originating from charm and bottom decays are further separated via the muon track's transverse impact parameter. Differential yields in Pb+Pb collisions and differential cross sections in pp collisions for such muons are measured as a function of muon transverse momentum from 4 GeV to 30 GeV in the absolute pseudorapidity interval vertical bar eta vertical bar &lt; 2. Nuclear modification factors for charm and bottom muons are presented as a function of muon transverse momentum in intervals of Pb+Pb collision centrality. The bottom muon results are the most precise measurement of b quark nuclear modification at low transverse momentum where reconstruction of B hadrons is challenging. The measured nuclear modification factors quantify a significant suppression of the yields of muons from decays of charm and bottom hadrons, with stronger effects for muons from charm hadron decays

A search for an unexpected asymmetry in the production of e+μ− and e−μ+ pairs in proton-proton collisions recorded by the ATLAS detector at root s = 13 TeV

This search, a type not previously performed at ATLAS, uses a comparison of the production cross sections for e(+)mu(-) and e(-)mu(+) pairs to constrain physics processes beyond the Standard Model. It uses 139 fb(-1) of proton-proton collision data recorded at root s = 13 TeV at the LHC. Targeting sources of new physics which prefer final states containing e(+)mu(-) and e(-)mu(+), the search contains two broad signal regions which are used to provide model-independent constraints on the ratio of cross sections at the 2% level. The search also has two special selections targeting supersymmetric models and leptoquark signatures. Observations using one of these selections are able to exclude, at 95% confidence level, singly produced smuons with masses up to 640 GeV in a model in which the only other light sparticle is a neutralino when the R-parity-violating coupling lambda(23)(1)' is close to unity. Observations using the other selection exclude scalar leptoquarks with masses below 1880 GeV when g(1R)(eu) = g(1R)(mu c) = 1, at 95% confidence level. The limit on the coupling reduces to g(1R)(eu) = g(1R)(mu c) = 0.46 for a mass of 1420 GeV

Atributos físicos, químicos e mineralógicos de solos da região das Várzeas de Sousa (PB)

O presente trabalho teve por objetivo caracterizar, física, química e mineralogicamente, os solos localizados nas várzeas de Sousa (Sertão da Paraíba), bem como verificar o efeito dos cátions alcalinos e alcalino-terrosos na estabilidade das substâncias húmicas. Procurou-se, ainda, identificar os critérios de distinção de ambientes utilizados pelos pequenos agricultores e as diferentes formas de uso dos solos da região estudada. Para isso, foram selecionados, amostrados e analisados perfis de solos das classes: Neossolo Flúvico, Luvissolo, Planossolo Nátrico e Vertissolo Cromado. Constatou-se que, além do sódio, o magnésio teve participação efetiva na dispersão de argila, principalmente nos Vertissolos. Os teores de Fe 2 O 3 foram baixos em todos os perfis, com provável predomínio das formas menos cristalinas, identificadas pelas altas relações Feo/Fed. A mineralogia cálcio-sódica da fração silte é condizente com os teores, relativamente elevados, de cálcio, magnésio e sódio, sendo, provavelmente, o principal responsável por esses valores nos solos estudados. Na fração argila de todos os solos, foi observada a presença marcante da vermiculita/esmectita eilita. Nos Vertissolos, o teor expressivo de ferro na fração argila revela, além da presença da hematita, a ocorrência de mineral 2:1 expansivo rico em ferro, sobretudo a nontronita. O pré-tratamento para eliminação de carbonatos (HCl 0,1 mol L -1 ), efetuado durante o fracionamento das substâncias húmicas, resultou em aumentos de 300 e 340 % para as frações ácidos húmicos e fúlvicos, respectivamente, e redução de 60 % na fração humina, evidenciando a participação de humatos e fulvatos de cálcio e de magnésio na estabilização da matéria orgânica.Physical, chemical and mineralogical characteristics of soils from the meadows of Sousa (Paraíba State - Brazil) were studied, as well as the effect of alkaline and alkaline-earthy cations on humic substance stability. Furthermore, criteria of environmental distinction used by the small farmers and different forms of land use in the studied region were identified. Profiles from the classes Ustifluvents (Neossolo Flúvico), Haplustalfs (Luvissolo), Natrustalfs (Planossolo nátrico), and Usterts (Vertissolo crómico) were therefore selected, sampled and analyzed. Besides sodium, magnesium also had an effective participation in clay dispersion, mainly in the Usterts. Fe 2 O 3 contents were low in all profiles, with a probable prevalence of less crystalline forms. The calcium-sodic mineralogy of the silt fraction is in agreement with the relative high content of calcium, magnesium and sodium. The outstanding presence of vermiculite/smectite and ilite was observed in the soil clay fraction of all soils. The high iron content in the clay fraction of Usterts suggests, besides the presence of hematite, the occurrence of 2:1 expansible mineral, rich in iron, possibly nontronita. The pre-treatment for carbonate elimination (HCl 0.1 mol L -1 ), applied during the humic substance fractionation, caused increases of 300 and 340 % for the humic and fulvic acid fractions, respectively, and a reduction of 60 % in the humin fraction, suggesting a participation of calcium and of magnesium humates and fulvates in organic matter stabilization