Correlations between non-identical particles at small relative velocity probe asymmetries in the average space-time emission points at freezeout 1. Such asymmetries may arise from long-lived ...resonances, bulk collective effects, or differences in the freezeout scenario for the different particle species. STAR has extracted pion-proton correlation functions from a high-statistics dataset of Au+Au collisions at
= 200 GeV. We present a femtoscopic analysis of this data for all combinations of charged pions and (anti-) protons, for collisions of different centrality. The measurements are compared with calculations of a simple Blast-wave model, in which asymmetries are driven only by collective flow, as well as with Therminator 2, which also accounts fully for resonance effects.
Correlations between non-identical particles at small relative velocity probe asymmetries in the average space-time emission points at freeze-out. The origin of such asymmetries may be from ...long-lived resonances, bulk collective effects, or differences in the freeze-out scenario for the different particle species. STAR has extracted pion-proton correlation functions from a dataset of Au+Au collisions at √
s
NN
= 200 GeV. We present correlation functions in the spherical harmonic decomposition representation, for different centralities and for different combinations of pions and (anti-)protons.
Cladocera (Crustacea: Branchiopoda) quickly respond to changes in environmental conditions and their remains are usually found in large amounts in lacustrine sediments, which make them an important ...biological proxy in paleolimnological studies. Variations in species composition have been used to infer paleo-climate and paleo-environmental variables including lake depth, eutrophication, and deforestation. However, despite their advantages as bioindicators in the study of past conditions, they are underutilized in paleolimnological research in Central America due to limited knowledge about their diversity and the morphological differences between the subfossil remains of different taxa. In order to address this issue, we described and analyzed cladoceran remains from 56 waterbodies located in Mexico, Guatemala, El Salvador, and Honduras. Here, we provide a description of the remains from 10 different taxa that belong to the Sididae, Bosminidae, Daphniidae, Macrothricidae, and Ilyocryptidae families.
Elevated iron in the SNpc may play a key role in Parkinson's disease (PD) neurodegeneration since drug candidates with high iron affinity rescue PD animal models, and one candidate, deferirpone, has ...shown efficacy recently in a phase two clinical trial. However, strong iron chelators may perturb essential iron metabolism, and it is not yet known whether the damage associated with iron is mediated by a tightly bound (eg ferritin) or lower-affinity, labile, iron pool. Here we report the preclinical characterization of PBT434, a novel quinazolinone compound bearing a moderate affinity metal-binding motif, which is in development for Parkinsonian conditions. In vitro, PBT434 was far less potent than deferiprone or deferoxamine at lowering cellular iron levels, yet was found to inhibit iron-mediated redox activity and iron-mediated aggregation of α-synuclein, a protein that aggregates in the neuropathology. In vivo, PBT434 did not deplete tissue iron stores in normal rodents, yet prevented loss of substantia nigra pars compacta neurons (SNpc), lowered nigral α-synuclein accumulation, and rescued motor performance in mice exposed to the Parkinsonian toxins 6-OHDA and MPTP, and in a transgenic animal model (hA53T α-synuclein) of PD. These improvements were associated with reduced markers of oxidative damage, and increased levels of ferroportin (an iron exporter) and DJ-1. We conclude that compounds designed to target a pool of pathological iron that is not held in high-affinity complexes in the tissue can maintain the survival of SNpc neurons and could be disease-modifying in PD.
The feature of self-cleansing in sewer pipes is a standard requirement in the design of drainage systems, as sediments deposited on the channel bottom cause changes in channel geometric properties ...and in hydrodynamic parameters, including the friction caused by the cohesive forces of sediment fractions. Here, it is shown that the content of cohesive fractions significantly inhibits the transport of non-cohesive sediments. This paper presents an advanced calculation procedure for estimating flushing flows in channels. This procedure is based on innovative predictive models developed for non-cohesive and granulometrically heterogeneous sediment transport with additional cohesive fraction content to estimate the magnitude of increased flow necessary to ensure self-cleansing of channels. The computations according to the proposed procedure were carried out for a wide range of hydrodynamic conditions, two grain diameters, six cohesive (clay) fraction additive contents and two critical stress values. The trend lines of calculations were composed with the results of experimental studies in hydraulic flumes.
Use of subfossil cladoceran remains for paleolimnological studies in Mesoamerica, especially in Central America, is constrained by the poorly known composition of cladoceran communities. We examined ...sediments from 56 waterbodies in Central America (Guatemala, El Salvador, Honduras) and the Yucatan Peninsula (Mexico), and provide illustrations and descriptions of the remains of Chydoridae from the region, emphasizing their diagnostic traits. In total, 36 Chydoridae taxa, representing 24 genera, were recognized. The illustrations and descriptions of chydorid subfossils included here will enable paleolimnologists to recognize and identify such remains in lake sediment cores, thereby facilitating paleoenvironmental inferences from lake sites in Mesoamerica. Furthermore, data included here expand knowledge about the geographic distributions of Neotropical chydorids.
•Recommended phase II dose is binimetinib 30 mg BID with carboplatin/pemetrexed in non-squamous NSCLC.•Manageable toxicities observed with the combination of carboplatin, pemetrexed and ...binimetinib.•Objective response rate 50 % and disease control rate 83.3 % with chemotherapy plus binimetinib.
MEK inhibition is a potential therapeutic strategy in non-small cell lung cancer (NSCLC). This phase I study evaluates the MEK inhibitor binimetinib plus carboplatin and pemetrexed in stage IV non-squamous NSCLC patients (NCT02185690).
A standard 3 + 3 dose-escalation design was used. Binimetinib 30 mg BID (dose level 1 DL1) or 45 mg BID (dose level 2 DL2) was given with standard doses of carboplatin and pemetrexed using an intermittent dosing schedule. The primary outcome was determination of the recommended phase II dose (RP2D) and safety of binimetinib. Secondary outcomes included efficacy, pharmacokinetics, and an exploratory analysis of response based on mutation subtype.
Thirteen patients (6 DL1, 7 DL2) were enrolled: 7 KRAS, 5 EGFR, and 1 NRAS mutation. The RP2D was binimetinib 30 mg BID. Eight patients (61.5%) had grade 3/4 adverse events, with dose limiting toxicities in 2 patients at DL2. Twelve patients were evaluated for response, with an investigator-assessed objective response rate (ORR) of 50% (95% CI 21.1%-78.9%; ORR 33.3% by independent-review, IR), and disease control rate 83.3% (95% CI 51.6%-97.9%). Median progression free survival (PFS) was 4.5 months (95% CI 2.6 months–NA), with a 6-month and 12-month PFS rate of 38.5% (95% CI 19.3%-76.5%) and 25.6% (95% CI 8.9%-73.6%), respectively. In an exploratory analysis, KRAS/NRAS-mutated patients had an ORR of 62.5% (ORR 37.5% by IR) vs. 25% in KRAS/NRAS wild-type patients. In MAP2K1–mutated patients, the ORR was 42.8%.
The addition of binimetinib to carboplatin and pemetrexed appears to have manageable toxicity with evidence of activity in advanced non-squamous NSCLC.
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