Ontological dependence in a spacetime-world

Priority Monism (hereafter, ‘Monism’), as defined by Jonathan Schaffer (Philos Rev 119:131–176, 2010), has a number of components. It is the view that: the cosmos exists; the cosmos is a maximal actual concrete object, of which all actual concrete objects are parts; the cosmos is basic—there is no object upon which the cosmos depends, ontologically; ontological dependence is a primitive and unanalysable relation. In a recent attack, Lowe (Spinoza on monism. Palgave Macmillan, London, pp 92–122, 2012) has offered a series of arguments to show that Monism fails. He offers up four tranches of argument, with different focuses. These focal points are: (1) being a concrete object; (2) aggregation and dependence; (3) analyses of ontological dependence; (4) Schaffer’s no-overlap principle. These are all technical notions, but each figures at the heart of a cluster of arguments that Lowe puts forward. To respond, I work through each tranche of argument in turn. Before that, in the first section, I offer a cursory statement of Monism, as Schaffer presents it in his 2010 paper, Monism: The Priority of the Whole. I then respond to each of Lowe’s criticisms in turn, deploying material from Schaffer’s 2009 paper Spacetime: the One Substance, as well as various pieces of conceptual machinery from Lowe’s own works (The possibility of metaphysics. Clarendon, Oxford, 1998, 2010) to deflect Lowe’s (Spinoza on monism. Palgave Macmillan, London, pp 92–122, 2012) attacks. In the process of defending Monism from Lowe (Spinoza on monism. Palgave Macmillan, London, pp 92–122, 2012), I end up offering some subtle refinements to Schaffer’s (Philos Rev 119:131–176, 2010) view and explain how the resulting ‘hybrid’ view fares in the wider dialectic

Development and Validation of a 28-gene Hypoxia-related Prognostic Signature for Localized Prostate Cancer.

BACKGROUND: Hypoxia is associated with a poor prognosis in prostate cancer. This work aimed to derive and validate a hypoxia-related mRNA signature for localized prostate cancer. METHOD: Hypoxia genes were identified in vitro via RNA-sequencing and combined with in vivo gene co-expression analysis to generate a signature. The signature was independently validated in eleven prostate cancer cohorts and a bladder cancer phase III randomized trial of radiotherapy alone or with carbogen and nicotinamide (CON). RESULTS: A 28-gene signature was derived. Patients with high signature scores had poorer biochemical recurrence free survivals in six of eight independent cohorts of prostatectomy-treated patients (Log rank test P \u3c .05), with borderline significances achieved in the other two (P \u3c .1). The signature also predicted biochemical recurrence in patients receiving post-prostatectomy radiotherapy (n = 130, P = .007) or definitive radiotherapy alone (n = 248, P = .035). Lastly, the signature predicted metastasis events in a pooled cohort (n = 631, P = .002). Prognostic significance remained after adjusting for clinic-pathological factors and commercially available prognostic signatures. The signature predicted benefit from hypoxia-modifying therapy in bladder cancer patients (intervention-by-signature interaction test P = .0026), where carbogen and nicotinamide was associated with improved survival only in hypoxic tumours. CONCLUSION: A 28-gene hypoxia signature has strong and independent prognostic value for prostate cancer patients

Co-ordination of early and late ripening events in apples is regulated through differential sensitivities to ethylene

In this study, it is shown that anti-sense suppression of Malus domestica 1-AMINO-CYCLOPROPANE-CARBOXYLASE OXIDASE (MdACO1) resulted in fruit with an ethylene production sufficiently low to be able to assess ripening in the absence of ethylene. Exposure of these fruit to different concentrations of exogenous ethylene showed that flesh softening, volatile biosynthesis, and starch degradation, had differing ethylene sensitivity and dependency. Early ripening events such as the conversion of starch to sugars showed a low dependency for ethylene, but a high sensitivity to low concentrations of ethylene (0.01 μl l−1). By contrast, later ripening events such as flesh softening and ester volatile production showed a high dependency for ethylene but were less sensitive to low concentrations (needing 0.1 μl l−1 for a response). A sustained exposure to ethylene was required to maintain ripening, indicating that the role of ethylene may go beyond that of ripening initiation. These results suggest a conceptual model for the control of individual ripening characters in apple, based on both ethylene dependency and sensitivity

Superconducting density of states and band structure at the surface of the candidate topological superconductor Au2 Pb

The electronic band structure of Au2Pb has a Dirac cone which gaps when undergoing a structural transition into a low temperature superconducting phase. This suggests that the superconducting phase (Tc = 1.1 K) might hold topological properties at the surface. Here we make Scanning Tunneling Microscopy experiments on the surface of superconducting Au2Pb. We measure the superconducting gap and find a sizable superconducting density of states at the Fermi level. We discuss possible origins for this finding in terms of superconductivity induced into surface state

Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family.

By consensus, the acyl-CoA synthetase (ACS) community, with the advice of the human and mouse genome nomenclature committees, has revised the nomenclature for the mammalian long-chain acyl-CoA synthetases. ACS is the family root name, and the human and mouse genes for the long-chain ACSs are termed ACSL1,3-6 and Acsl1,3-6, respectively. Splice variants of ACSL3, -4, -5, and -6 are cataloged. Suggestions for naming other family members and for the nonmammalian acyl-CoA synthetases are made

Effect of oxygen on the expression of renin-angiotensin system components in a human trophoblast cell line

During the first trimester, normal placental development occurs in a low oxygen environment that is known to stimulate angiogenesis via upregulation of vascular endothelial growth factor (VEGF). Expression of the placental renin-angiotensin system (RAS) is highest in early pregnancy. While the RAS and oxygen both stimulate angiogenesis, how they interact within the placenta is unknown. We postulated that low oxygen increases expression of the proangiogenic RAS pathway and that this is associated with increased VEGF in a first trimester human trophoblast cell line (HTR-8/SVneo). HTR-8/SVneo cells were cultured in one of three oxygen tensions (1%, 5% and 20%). RAS and VEGF mRNA expression were determined by qPCR. Prorenin, angiotensin converting enzyme (ACE) and VEGF protein levels in the supernatant, as well as prorenin and ACE in cell lysates, were measured using ELISAs. Low oxygen significantly increased the expression of both angiotensin II type 1 receptor (AGTR1) and VEGF (both P < 0.05). There was a positive correlation between AGTR1 and VEGF expression at low oxygen (r = 0.64, P < 0.005). Corresponding increases in VEGF protein were observed with low oxygen (P < 0.05). Despite no change in ACE1 mRNA expression, ACE levels in the supernatant increased with low oxygen (1% and 5%, P < 0.05). Expression of other RAS components did not change. Low oxygen increased AGTR1 and VEGF expression, as well as ACE and VEGF protein levels, suggesting that the proangiogenic RAS pathway is activated. This highlights a potential role for the placental RAS in mediating the proangiogenic effects of low oxygen in placental development

Identification and Quantification of Proteoforms by Mass Spectrometry

A proteoform is a defined form of a protein derived from a given gene with a specific amino acid sequence and localized post-translational modifications. In top-down proteomic analyses, proteoforms are identified and quantified through mass spectrometric analysis of intact proteins. Recent technological developments have enabled comprehensive proteoform analyses in complex samples, and an increasing number of laboratories are adopting top-down proteomic workflows. In this review, we outline some recent advances and discuss current challenges and future directions for the field

Superconducting density of states and band structure at the surface of the candidate topological superconductor Au2Pb

[EN] The electronic band structure of Au2Pb has a Dirac cone which gaps when undergoing a structural transition into a low temperature superconducting phase. This suggests that the superconducting phase (Tc = 1.1 K) might hold topological properties at the surface. Here we make Scanning Tunneling Microscopy experiments on the surface of superconducting Au2Pb. We measure the superconducting gap and find a sizable superconducting density of states at the Fermi level. We discuss possible origins for this finding in terms of superconductivity induced into surface states.This work was supported by the Spanish Research State Agency (Grants No. PID2020-114071RB-I00, No. FIS2017-84330-R, No. CEX2018-000805-M, No. RYC-2014-15093, and No. MAT2017-87134-C2-2-R), by the Comunidad de Madrid through program NANOFRONTMAG-CM (Grant No. S2013/MIT-2850), by the European Research Council PNICTEYES Grant Agreement No. 679080 and by the Swedish Research Council (Vetenskapsrådet Grant No. 2018-03488). F.M. and M.G.H. acknowledge European Union’s Horizon 2020 research and innovation program Grant Agreement No. 881603 Graphene Core3-Graphene-based disruptive technologies, EU FLAG-ERA through the project To2Dox, JTC-2019-009 and the Comunidad de Madrid through the project CAIRO-CM project, Y2020/NMT-6661.We acknowledge collaborations through EU program Cost CA16218 (Nanocohybri). J.J.B. acknowledges the Marie Curie Fellowship program (H2020 MSCA-IF2016-751047) and the Generalitat Valenciana (CDEIGENT/2019/022). Ames Laboratory is operated for the U.S. Department of Energy by Iowa State University under Contract No. DE-AC02-07CH11358. We acknowledge SEGAINVEX at UAM for design and construction of cryogenic equipment.Peer reviewe