Fischer–Tropsch Synthesis Over Zr-Promoted Co/γ-Al2O3 Catalysts

Two Zr-modified alumina supports were synthetized containing the same amount of Zr but a different distribution of this modifier over the alumina surface. These supports, together with the unmodified alumina carrier, were used to prepare three cobalt-based catalysts which were characterized and tested under relevant Fischer–Tropsch conditions. The three catalysts presented very similar porosity and cobalt dispersion. The addition of Zr nor its distribution enhanced the catalyst reducibility. The catalyst activity was superior when using a carrier consisting of large ZrO2 islands over the alumina surface. The use of a carrier with a homogeneous Zr distribution had however, a detrimental effect. Moreover, a faster initial deactivation rate was observed for the Zr-promoted catalysts, fact that may explain this contradictory effect of Zr on activity. Finally, the addition of Zr showed a clear enhancement of the selectivity to long chain hydrocarbons and ethylene, especially when Zr was well dispersed

Bird collisions in a railway crossing a wetland of international importance (Sado estuary, Portugal)

L. Borda-de-Água et al. (eds.), Railway Ecology, chapter 7, p. 103-115Many studies have evaluated bird mortality in relation to roads and other human structures, but little is known about the potential impacts of railways. In particular, it is uncertain whether railways are an important mortality source when crossing wetlands heavily used by aquatic birds. Here we analyze bird collisions in a railway that crosses the Nature Reserve of the Sado Estuary (Portugal) over an annual cycle, documenting bird mortality and the flight behaviour of aquatic birds in relation to a bowstring bridge. During monthly surveys conducted on 16.3 km of railway, we found 5.8 dead birds/km/10 survey days in the section crossing wetland habitats (6.3 km), while <0.5 dead birds/km/10 survey days were found in two sections crossing only forested habitats. Most birds recorded were small songbirds (Passeriformes), while there was only a small number of aquatic birds (common moorhen, mallard, flamingo, great cormorant, gulls) and other non-passerines associated with wetlands (white stork). During nearly 400 h of observations, we recorded 27,000 movements of aquatic birds across the Sado bridge, particularly in autumn and winter. However, only <1% of movements were within the area of collision risk with trains, while about 91% were above the collision risk area, and 8% were below the bridge. Overall, our case study suggests that bird collisions may be far more numerous in railways crossing wetland habitats than elsewhere, although the risk to aquatic birds may be relatively low. Information from additional study systems would be required to evaluate whether our conclusions apply to other wetlands and railway linesinfo:eu-repo/semantics/publishedVersio

Phenotypic heterogeneity in IGHV-mutated CLL patients has prognostic impact and identifies a subset with increased sensitivity to BTK and PI3Kδ inhibition

The majority of chronic lymphocytic leukemia (CLL) patients are diagnosed with early-stage disease but the currently used prognostic tools appear to be less informative in this group of patients.1 This is especially problematic for patients with mutated immunoglobulin genes (M-CLL) as they have a more diverse clinical course when compared with patients with unmutated immunoglobulin genes (U-CLL).1, 2, 3, 4 Given the emergence of promising targeted, less toxic, therapeutics in CLL,5, 6 there is an increased need to identify patients who might benefit from early treatment with these new agents

Outcomes with ibrutinib by line of therapy and post‐ibrutinib discontinuation in patients with chronic lymphocytic leukemia: Phase 3 analysis

The efficacy of ibrutinib has been demonstrated in patients with chronic lymphocytic leukemia (CLL), including as first‐line therapy. However, outcomes after ibrutinib discontinuation have previously been limited to higher‐risk populations with relapsed/refractory (R/R) disease. The objective of this study was to evaluate outcomes of ibrutinib‐treated patients based on prior lines of therapy, including after ibrutinib discontinuation. Data were analyzed from two multicenter phase 3 studies of single‐agent ibrutinib: RESONATE (PCYC‐1112) in patients with R/R CLL and RESONATE‐2 (PCYC‐1115) in patients with treatment‐naive (TN) CLL without del(17p). This integrated analysis included 271 ibrutinib‐treated non‐del(17p) patients with CLL (136 TN and 135 R/R). Median progression‐free survival (PFS) was not reached for subgroups with 0 and 1/2 prior therapies but was 40.6 months for patients with ≥3 therapies (median follow‐up: TN, 36 months; R/R, 44 months). Median overall survival (OS) was not reached in any subgroup. Overall response rate (ORR) was 92% in TN and 92% in R/R, with depth of response increasing over time. Adverse events (AEs) and ibrutinib discontinuation due to AEs were similar between patient groups. Most patients (64%) remain on treatment. OS following discontinuation was 9.3 months in R/R patients (median follow‐up 18 months, n = 51) and was not reached in TN patients (median follow‐up 10 months, n = 30). In this integrated analysis, ibrutinib was associated with favorable PFS and OS, and high ORR regardless of prior therapies in patients with CLL. The best outcomes following ibrutinib discontinuation were for patients receiving ibrutinib in earlier lines of therapy

Joint localization of pursuit quadcopters and target using monocular cues

Pursuit robots (autonomous robots tasked with tracking and pursuing a moving target) require accurate tracking of the target's position over time. One possibly effective pursuit platform is a quadcopter equipped with basic sensors and a monocular camera. However, combined noise of the quadcopter's sensors causes large disturbances of target's 3D position estimate. To solve this problem, in this paper, we propose a novel method for joint localization of a quadcopter pursuer with a monocular camera and an arbitrary target. Our method localizes both the pursuer and target with respect to a common reference frame. The joint localization method fuses the quadcopter's kinematics and the target's dynamics in a joint state space model. We show that predicting and correcting pursuer and target trajectories simultaneously produces better results than standard approaches to estimating relative target trajectories in a 3D coordinate system. Our method also comprises a computationally efficient visual tracking method capable of redetecting a temporarily lost target. The efficiency of the proposed method is demonstrated by a series of experiments with a real quadcopter pursuing a human. The results show that the visual tracker can deal effectively with target occlusions and that joint localization outperforms standard localization methods

Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin

There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters

Genetic Architecture of a Reinforced, Postmating, Reproductive Isolation Barrier between Neurospora Species Indicates Evolution via Natural Selection

A role for natural selection in reinforcing premating barriers is recognized, but selection for reinforcement of postmating barriers remains controversial. Organisms lacking evolvable premating barriers can theoretically reinforce postmating isolation, but only under restrictive conditions: parental investment in hybrid progeny must inhibit subsequent reproduction, and selected postmating barriers must restore parents' capacity to reproduce successfully. We show that reinforced postmating isolation markedly increases maternal fitness in the fungus Neurospora crassa, and we detect the evolutionary genetic signature of natural selection by quantitative trait locus (QTL) analysis of the reinforced barrier. Hybrid progeny of N. crassa and N. intermedia are highly inviable. Fertilization by local N. intermedia results in early abortion of hybrid fruitbodies, and we show that abortion is adaptive because only aborted maternal colonies remain fully receptive to future reproduction. In the first QTL analysis of postmating reinforcement in microbial eukaryotes, we identify 11 loci for abortive hybrid fruitbody development, including three major QTLs that together explain 30% of trait variance. One of the major QTLs and six QTLs of lesser effect are found on the mating-type determining chromosome of Neurospora. Several reinforcement QTLs are flanked by genetic markers showing either segregation distortion or non-random associations with alleles at other loci in a cross between N. crassa of different clades, suggesting that the loci also are associated with local effects on same-species reproduction. Statistical analysis of the allelic effects distribution for abortive hybrid fruitbody development indicates its evolution occurred under positive selection. Our results strongly support a role for natural selection in the evolution of reinforced postmating isolation in N. crassa

Time in a Bottle: The Evolutionary Fate of Species Discrimination in Sibling Drosophila Species

Disadvantageous hybridization favors the evolution of prezygotic isolating behaviors, generating a geographic pattern of interspecific mate discrimination where members of different species drawn from sympatric populations exhibit stronger preference for members of their own species than do individuals drawn from allopatric populations. Geographic shifts in species' boundaries can relax local selection against hybridization; under such scenarios the fate of enhanced species preference is unknown. Lineages established from populations in the region of sympatry that have been maintained as single-species laboratory cultures represent cases where allopatry has been produced experimentally. Using such cultures dating from the 1950s, we assess how Drosophila pseudoobscura and D. persimilis mate preferences respond to relaxed natural selection against hybridization. We found that the propensity to hybridize generally declines with increasing time in experimental allopatry, suggesting that maintaining enhanced preference for conspecifics may be costly. However, our data also suggest a strong role for drift in determining mating preferences once secondary allopatry has been established. Finally, we discuss the interplay between populations in establishing the presence or absence of patterns consistent with reinforcement

Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE(TM) study in patients with previously treated CLL/SLL.

In the phase 3 RESONATE(TM) study, ibrutinib demonstrated superior progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) compared with ofatumumab in relapsed/refractory CLL patients with high-risk prognostic factors. We report updated results from RESONATE in these traditionally chemotherapy resistant high-risk genomic subgroups at a median follow-up of 19 months. Mutations were detected by Foundation One Heme Panel. Baseline mutations in the ibrutinib arm included TP53 (51%), SF3B1 (31%), NOTCH1 (28%), ATM (19%), and BIRC3 (14%). Median PFS was not reached, with 74% of patients randomized to ibrutinib alive and progression-free at 24 months. The improved efficacy of ibrutinib vs. ofatumumab continues in all prognostic subgroups including del17p and del11q. No significant difference within the ibrutinib arm was observed for PFS across most genomic subtypes, although a subset carrying both TP53 mutation and del17p had reduced PFS compared to patients with neither abnormality. Reduced PFS or OS was not evident in patients with only del17p. PFS was significantly better for ibrutinib-treated patients in second-line vs. later lines of therapy. The robust clinical activity of ibrutinib continues to show ongoing efficacy and acceptable safety consistent with prior reports, independent of various known high-risk mutations

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches