Linear Dependent Types in a Call-by-Value Scenario (Long Version)

Linear dependent types allow to precisely capture both the extensional behaviour and the time complexity of lambda terms, when the latter are evaluated by Krivine's abstract machine. In this work, we show that the same paradigm can be applied to call-by-value evaluation. A system of linear dependent types for Plotkin's PCF is introduced, called dlPCFV, whose types reflect the complexity of evaluating terms in the so-called CEK machine. dlPCFV is proved to be sound, but also relatively complete: every true statement about the extensional and intentional behaviour of terms can be derived, provided all true index term inequalities can be used as assumptions.Comment: 22 page

Endogenous erythropoietin as part of the cytokine network in the pathogenesis of experimental autoimmune encephalomyelitis

Erythropoietin (EPO) is of great interest as a therapy for many of the central nervous system (CNS) diseases and its administration is protective in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Endogenous EPO is induced by hypoxic/ischemic injury, but little is known about its expression in other CNS diseases. We report here that EPO expression in the spinal cord is induced in mouse models of chronic or relapsing-remitting EAE, and is prominently localized to motoneurons. We found a parallel increase of hypoxia-inducible transcription factor (HIF)-1 alpha, but not HIF-2 alpha, at the mRNA level, suggesting a possible role of non-hypoxic factors in EPO induction. EPO mRNA in the spinal cord was co-expressed with interferon (IFN)-gamma and tumor necrosis factor (TNF), and these cytokines inhibited EPO production in vitro in both neuronal and glial cells. Given the known inhibitory effect of EPO on neuroinflammation, our study indicates that EPO should be viewed as part of the inflammatory/anti-inflammatory network in MS

Acrylamide in almond products

Acrylamide was determined in 86 different almond products, such as roasted almonds, almond-containing bakery products, raw almonds, and marzipan. The highest acrylamide concentrations were found in dark roasted almonds, while only moderate acrylamide contents were determined in bakery products. Roasting experiments under different process conditions showed that acrylamide increases with time and that temperature has a much stronger effect on acrylamide formation than time. During roasting reducing sugars are consumed faster and to a larger extent than free asparagine, suggesting that the content of reducing sugars may be a critical factor for acrylamide formation in roasted almonds. Acrylamide was found to decrease in roasted almonds during storage at room temperatur

In vitro degradation of 3D-printed polycaprolactone\biomimetic hydroxyapatite scaffolds: Impact of the sterilization method

In the transition from the laboratory to the clinic, the sterilization of medical devices becomes a fundamental and mandatory step to ensure patient safety. This work evaluates the impact of three different sterilization methods - autoclave, ethylene oxide and gamma irradiation - on the physicochemical properties and degradation kinetics of 3D-printed polycaprolactone\calcium deficient hydroxyapatite (PCL\CDHA) scaffolds for bone regeneration. The in vitro degradation test was performed in phosphate buffer saline solution at 47 °C for 18 weeks by recording the evolution of pH, scaffold morphology, swelling degree, mass loss as well as polymer content, molecular weight and crystallinity. The results showed that under thermally accelerated degradation, the scaffolds underwent hydrolytic bulk degradation without altering the pH of the soaking medium nor compromising the morphology and integrity of the constructs. Although the structural integrity of the scaffolds was maintained, autoclaving severely deteriorated the properties of the polymer, resulting in a faster degradation pattern, confirming that it is not an appropriate sterilization method for PCL\CDHA scaffolds. While ethylene oxide had no significant effect on degradation, gamma irradiation slightly accelerated hydrolysis by chain scission. However, due to the porous nature of the scaffolds, the use of ethylene oxide is inadvisable due to the risk of gas trapping in the pores. Therefore, gamma irradiation, a non-toxic, effective, predictable and reproducible sterilization method, is considered the most appropriate.Peer ReviewedPostprint (published version

A major glacial-interglacial change in aeolian dust composition inferred from Rare Earth Elements in Antarctic ice

We present the first Rare Earth Elements (REE) concentration record determined in 294 sections of an Antarctic ice core (EPICA Dome C), covering a period from 2.9 to 33.7 kyr BP. REE allow a detailed quantitative evaluation of aeolian dust composition because of the large number of variables (i.e. 14 elements). REE concentrations match the particulate dust concentration profile over this period and show a homogeneous crustal-like composition during the last glacial stage (LGS), with only a slight enrichment in medium REE. This signature is consistent with the persistent fallout of a mixture of dust from heterogeneous sources located in different areas or within the same region (e.g. South America). Starting at ∼15 kyr BP, there was a major change in dust composition, the variable character of which persisted throughout the Holocene. This varying signature may highlight the alternation of single dust contributions from different sources during the Holocene. We observe that the frequent changes in REE composition at the onset of the Holocene (10-13.5 kyr BP) are linked to dust size and in turn to wind strength and/or the path of the atmospheric trajectory. This may indicate that atmospheric circulation dictated the composition of the dust fallout to East Antarctica at that time. Although the dust concentrations remained fairly low, a notable return towards more glacial dust characteristics is recorded between 7.5 and 8.3 kyr BP. This happened concomitantly with a widespread cold event around 8 kyr BP that was 400-600 years long and suggests a moderate reactivation of the dust emission from the same potential source areas of the LGS

Ruminal Prevotella spp. May Play an Important Role in the Conversion of Plant Lignans into Human Health Beneficial Antioxidants

Secoisolariciresinol diglucoside (SDG), the most abundant lignan in flaxseed, is metabolized by the ruminal microbiota into enterolignans, which are strong antioxidants. Enterolactone (EL), the main mammalian enterolignan produced in the rumen, is transferred into physiological fluids, with potentially human health benefits with respect to menopausal symptoms, hormone-dependent cancers, cardiovascular diseases, osteoporosis and diabetes. However, no information exists to our knowledge on bacterial taxa that play a role in converting plant lignans into EL in ruminants. In order to investigate this, eight rumen cannulated cows were used in a double 4×4 Latin square design and fed with four treatments: control with no flax meal (FM), or 5%, 10% and 15% FM (on a dry matter basis). Concentration of EL in the rumen increased linearly with increasing FM inclusion. Total rumen bacterial 16S rRNA concentration obtained using Q-PCR did not differ among treatments. PCR-T-RFLP based dendrograms revealed no global clustering based on diet indicating between animal variation. PCR-DGGE showed a clustering by diet effect within four cows that had similar basal ruminal microbiota. DNA extracted from bands present following feeding 15% FM and absent with no FM supplementation were sequenced and it showed that many genera, in particular Prevotella spp., contributed to the metabolism of lignans. A subsequent in vitro study using selected pure cultures of ruminal bacteria incubated with SDG indicated that 11 ruminal bacteria were able to convert SDG into secoisolariciresinol (SECO), with Prevotella spp. being the main converters. These data suggest that Prevotella spp. is one genus playing an important role in the conversion of plant lignans to human health beneficial antioxidants in the rumen

Lymphoblastic predominance of blastic phase in children with chronic myeloid leukaemia treated with imatinib:A report from the I-CML-Ped Study

Background: Chronic myeloid leukaemia (CML) is a rare disease in children. The frequency and outcome of children evolving to accelerated phase (AP) or blastic phase (BP) under treatment with imatinib is unknown. The aim of the current study is to assess the inci-dence of progression from CML in chronic phase with imatinib frontline in a paediatric setting and describe the management and outcome of these patients. Patients and methods: In the I-CML-Ped Study database (www.clinicaltrials.gov, #NCT01281735), 19 of 339 paediatric patients in chronic phase treated with imatinib in the frontline evolved to CML-AP or CML-BP. Results: With a median follow-up of 38 months (range: 2-190 months), the cumulative inci-dence of progression at 1 and 3 years was 3% (confidence interval [CI] 95%: 1-5%) and 7% (CI 95%: 4-11%), respectively. We observed a large predominance of lymphoid-BP (70%) over myeloid-BP (30%) with imatinib in frontline therapy. Sixteen patients underwent haemato-poietic stem cell transplantation, and eight were treated with a tyrosine kinase inhibitor after transplant. Only the transplanted patients are alive. The 5-year overall survival rate of children with CML-AP/BP is 44%, with no statistical difference between the lymphoid-BP and myeloid-BP outcome. Conclusion: Children evolving to AP or BP under treatment with imatinib have a very poor prognosis with an overall survival under 50%, much worse than children with advanced phase at diagnosis. (c) 2020 Elsevier Ltd. All rights reserved