Four hexachlorosubphthalocyanines SubPcCl6‐X bearing different axial substituents (X) have been synthesized for use as novel electron acceptors in solution‐processed bulk‐heterojunction organic solar ...cells. Subphthalocyanines are aromatic chromophoric molecules with cone‐shaped structure, good solution processability, intense optical absorption in the visible spectral region, appropriate electron mobilities, and tunable energy levels. Solar cells with subphthalocyanines as the electron acceptor and PTB7‐Th as the electron donor exhibit a power conversion efficiency up to 4 % and an external quantum efficiency approaching 60 % due to significant contributions from both the electron donor and the electron acceptor to the photocurrent, indicating a promising prospect of non‐fullerene acceptors based on subphthalocyanines and structurally related systems.
A promising prospect: Subphthalocyanines SubPcCl6‐X bearing different axial substituents (X) are presented as novel electron acceptors in bulk‐heterojunction organic solar cells. Power conversion efficiencies up to 4 % were achieved due to photocurrent contribution from both electron donor and electron acceptor, which makes non‐fullerene acceptors based on SubPcs and structurally related systems a promising synthesis goal.
Fault slip rate is one of the most crucial parameters to characterize earthquake occurrence in fault‐based seismic hazard assessments (SHA). Accordingly, paleoseismic studies have increasingly ...focused on constraining this parameter in active faults worldwide. We present a comprehensive paleoseismic study in the Alhama de Murcia Fault (AMF), one of the most active faults in SE Spain and source of destructing earthquakes such as the 2011 Mw 5.2 Lorca event. Contrasting with previous studies, we integrate paleoseismic data from four fault strands in the AMF and, based on trench slip analysis and numerical dates, we derive slip rate estimates of each strand over the whole transect and assess their time variability. The AMF has a minimum net slip rate between 1.35+0.16/−0.10 and 1.64+0.16/−0.11 mm/yr for the past 18 ± 1 to 15.2 ± 1.1 ka. These results prove the importance of accounting for the complete sections of a geological structure as they are almost twice the previous estimates for a single fault branch. Slip rate variability is identified in the AMF, with cyclic acceleration‐quiescence patterns that could be related to stress field changes driven by fault interaction or synchronicity with neighboring faults (e.g., Carrascoy). We hope that the data presented here motivates their inclusion into forthcoming fault‐based SHAs. In this regard, limitations related to the lack of paleoseismic data for one fault strand, along with poor characterization of the strike component of slip and insufficient age control of the units for another strand are highlighted and need to be accounted for by modelers.
Key Points
Multi‐site paleoseismic surveys allow to improve the estimations of the geological slip rates in the Alhama de Murcia Fault (AMF)
The AMF shows a geological slip rate between 1.35 and 1.64 mm/yr for the past 18–15 ka
Late Quaternary slip rate fluctuations suggest strain rate variations and highlight possible synchronicities with neighboring faults
Summary
Background
Reprogramming of energy metabolism to enhanced aerobic glycolysis has been defined as a hallmark of cancer.
Objectives
To investigate the role of the mitochondrial proteins, ...β‐subunit of the H+‐ATP synthase (β‐F1‐ATPase), and heat‐shock protein 60 (HSP60), and the glycolytic markers, glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) and pyruvate kinase M2 (PKM2), as well as the bioenergetic cellular (BEC) index, in melanoma progression.
Materials and methods
The expression of energy metabolism proteins was assessed on a set of different melanoma cells representing the natural biological history of the disease: primary cultures of melanocytes, radial (WM35) and vertical (WM278) growth phases, and poorly (C81‐61‐PA) and highly (C8161‐HA) aggressive melanoma cells. Cohorts of 63 melanocytic naevi, 55 primary melanomas and 35 metastases were used; and 113 primary melanoma and 33 metastases were used for validation.
Results
The BEC index was significantly reduced in melanoma cells and correlated with their aggressive characteristics. Overexpression of HSP60, GAPDH and PKM2 was detected in melanoma human samples compared with naevi, showing a gradient of increased expression from radial growth phase to metastatic melanoma. The BEC index was also significantly reduced in melanoma samples and correlated with worse overall and disease‐free survival; the multivariate Cox analysis showed that the BEC index (hazard ratio 0·64; 95% confidence interval 0·4–1·2) is an independent predictor for overall survival.
Conclusions
A profound alteration in the mitochondrial and glycolytic proteins and in the BEC index occurs in the progression of melanoma, which correlates with worse outcome, supporting that the alteration of the metabolic phenotype is crucial in melanoma transformation.
What's already known about this topic?
Aerobic glycolysis is a hallmark in the malignant phenotype. The characterization of mitochondrial and glycolytic proteins (β‐subunit of the H+‐ATP synthase, heat‐shock protein 60, glyceraldehyde‐3‐phosphate dehydrogenase and pyruvate kinase M2), and the bioenergetic cellular (BEC) index in melanoma has not been previously reported.
What does this study add?
The mitochondrial and glycolytic proteins are dysregulated and the BEC index reduced in tumour cells in the malignant transformation of melanocytes. The alteration of their expression is associated with the clinical outcome in cutaneous malignant melanoma.
A BEC index reduction correlates with tumour aggressiveness and worse overall and disease‐free survival in patients with melanoma.
What is the translational message?
The understanding of energetic dysregulation in melanoma from in vitro and in vivo models might help to predict the evolution of this tumour in patients.
Linked Comment: Armstrong. Br J Dermatol 2019; 181:15–16.
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The collection and dissemination of vertebrate ichnological data is struggling to keep up with techniques that are becoming commonplace in the wider palaeontological field. A standard protocol is ...required to ensure that data is recorded, presented and archived in a manner that will be useful both to contemporary researchers, and to future generations. Primarily, our aim is to make the 3D capture of ichnological data standard practice, and to provide guidance on how such 3D data can be communicated effectively (both via the literature and other means) and archived openly and in perpetuity. We recommend capture of 3D data, and the presentation of said data in the form of photographs, false‐colour images, and interpretive drawings. Raw data (3D models of traces) should always be provided in a form usable by other researchers (i.e. in an open format). If adopted by the field as a whole, the result will be a more robust and uniform literature, supplemented by unparalleled availability of datasets for future workers.
Cataclastic rocks, as clay-rich fault gouges, are commonly present in brittle rock masses when fault zones appear during geological engineering projects. Highly deformed rocks that are of poor ...mechanical quality can lead to technical, safety, and economic problems in rock engineering. The aim of this study is to characterise the resistant behaviour of a highly deformed clay-rich gouge >40 m wide with a marked tectonic fabric that indicates strength anisotropy. We present the results of consolidated-undrained (CU) triaxial tests that were performed at low confining pressures (50, 150, and 300 kPa) on several sets of foliated gouge specimens with four different orientations in the tectonic fabric. Specimens were collected from the encapsulated rock cores of two research boreholes drilled through the Alhama de Murcia Fault (AMF), a main regional fault located in SE Spain. The strain–stress relationships and failure modes were established, indicating that the gouge behaves as hard soil or very soft rock. The test results were adjusted at each orientation using the non-linear Hoek and Brown criteria by considering the fault gouge as an intact material or as a tectonised rockmass. Here, we use the Geological Strength Index (GSI) as an indicator of the rockmass strength that depends on the direction of the tectonic fabric. However, the results from specimens with tectonic fabric that is oriented most favourably for failure were not the weakest in terms of rock strength. Such an anomalous result could be the result of asymmetry in the roughness of the weakness planes that is related to the original gouge microstructure characterised by the strong reorientation of clays in an S-C′ like tectonic fabric.
Our results will be useful for practical applications that are related to the stability of slopes and/or shallow underground excavations in brittle fault zones, and provide an inexpensive and easy way to preliminarily evaluate the anisotropic behaviour of this type of brittle fault zones for future engineering projects.
•Strength of a foliated clay-rich fault gouge is controlled by roughness within the weak planes.•Gouge microstructure defined by strong reorientation of clays in a S-C’ fabric controls the roughness of the weakness planes•Strength of clay gouges shows a medium to low anisotropy.•GSI is a sensitive index with which the strength anisotropy of tectonised rocks can be investigated.
Footprints represent a relevant vestige providing direct information on the biology, locomotion, and behaviour of the individuals who left them. However, the spatiotemporal distribution of hominin ...footprints is heterogeneous, particularly in North Africa, where no footprint sites were known before the Holocene. This region is important in the evolution of hominins. It notably includes the earliest currently known Homo sapiens (Jebel Irhoud) and the oldest and richest African Middle Stone Age hominin sites. In this fragmented ichnological record, we report the discovery of 85 human footprints on a Late Pleistocene now indurated beach surface of about 2800 m
at Larache (Northwest coast of Morocco). The wide range of sizes of the footprints suggests that several individuals from different age groups made the tracks while moving landward and seaward across a semi-dissipative bar-trough sandy beach foreshore. A geological investigation and an optically stimulated luminescence dating of a rock sample extracted from the tracksite places this hominin footprint surface at 90.3 ± 7.6 ka (MIS 5, Late Pleistocene). The Larache footprints are, therefore, the oldest attributed to Homo sapiens in Northern Africa and the Southern Mediterranean.
Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been linked to poor health outcomes, including diminished quality and length of life. This condition is characterized by high phosphate ...levels and requires phosphate-lowering agents-phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on patient-important outcomes in patients with CKD-MBD.
Data sources included MEDLINE and EMBASE Trials from 1996 to February 2016. We also searched the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD, randomized them to receive calcium (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet, placebo or no treatment, and reported effects on all-cause mortality, cardiovascular mortality or hospitalization at ≥4 weeks follow-up. We performed network meta-analyses (NMA) for all cause-mortality for individual agents (seven-node analysis) and conventional meta-analysis of calcium vs. NCBPBs for all-cause mortality, cardiovascular mortality and hospitalization. In the NMAs, we calculated the effect estimates for direct, indirect and network meta-analysis estimates; for both NMA and conventional meta-analysis, we pooled treatment effects as risk ratios (RR) and calculated 95% confidence intervals (CIs) using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each paired comparison.
Our search yielded 1190 citations, of which 71 RCTs were retrieved for full review and 15 proved eligible. With 13 eligible studies from a prior review, we included 28 studies with 8335 participants; 25 trials provided data for our quantitative synthesis. Results suggest higher mortality with calcium than either sevelamer (NMA RR, 1.89 95% CI, 1.02 to 3.50, moderate quality evidence) or NCBPBs (conventional meta-analysis RR, 1.76 95% CI, 1.21 to 2.56, moderate quality evidence). Conventional meta-analysis suggested no difference in cardiovascular mortality between calcium and NCBPBs (RR, 2.54 95% CI, 0.67 to 9.62 low quality evidence). Our results suggest higher hospitalization, although non-significant, with calcium than NCBPBs (RR, 1.293 95% CI, 0.94 to 1.74, moderate quality evidence).
Use of calcium results in higher mortality than either sevelamer in particular and NCBPBs in general (moderate quality evidence). Our results raise questions about whether administration of calcium as an intervention for CKD- MBD remains ethical. Further research is needed to explore the effects of different types of phosphate binders, including novel agents such as iron, on quality and quantity of life.
PROSPERO CRD-42016032945.
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