The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy has been ...previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival. Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR. A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease, and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment. In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept.
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•Predict response to treatment is a challenge when using antiangiogenic therapies.•Aflibercept is an antiangiogenic VEGF-targeted agent for colorectal cancer.•Circulating miRNAs discerned responder from non-responder patients.•Combining VEGF-A and miR-33b-5p improves patient selection for aflibercept therapy.
ABSTRACT We compute upper limits on the nanohertz-frequency isotropic stochastic gravitational wave background (GWB) using the 9 year data set from the North American Nanohertz Observatory for ...Gravitational Waves (NANOGrav) collaboration. Well-tested Bayesian techniques are used to set upper limits on the dimensionless strain amplitude (at a frequency of 1 yr−1) for a GWB from supermassive black hole binaries of A gw < 1.5 × 10 − 15 . We also parameterize the GWB spectrum with a broken power-law model by placing priors on the strain amplitude derived from simulations of Sesana and McWilliams et al. Using Bayesian model selection we find that the data favor a broken power law to a pure power law with odds ratios of 2.2 and 22 to one for the Sesana and McWilliams prior models, respectively. Using the broken power-law analysis we construct posterior distributions on environmental factors that drive the binary to the GW-driven regime including the stellar mass density for stellar-scattering, mass accretion rate for circumbinary disk interaction, and orbital eccentricity for eccentric binaries, marking the first time that the shape of the GWB spectrum has been used to make astrophysical inferences. Returning to a power-law model, we place stringent limits on the energy density of relic GWs, gw ( f ) h 2 < 4.2 × 10 − 10 . Our limit on the cosmic string GWB, gw ( f ) h 2 < 2.2 × 10 − 10 , translates to a conservative limit on the cosmic string tension with G < 3.3 × 10 − 8 , a factor of four better than the joint Planck and high-l cosmic microwave background data from other experiments.
In the agriculture sector, livestock are considered extremely resilient to climate change and are tipped to play a significant role in ensuring food security to meet the increased demands of growing ...human population by 2050. Compared to other domestic species, goats are considered the ideal animal model for climate change due to its high thermal and drought resilience, ability to survive on limited pastures, and high disease resistance. This review is therefore a revisit to the advantages of rearing goats over other livestock species under current and future trends of changes in climate, particularly to cope with recurrent multiple stressors such as heat load, and lack of water and feed. In summary, goats, also called as poor man’s cow, are preferred by the small-scale landless farmers due to their low input and assured higher output system, as they require low initial investment, with minimum specialized facilities and labors. Furthermore, they perceive goats as better resilient animal to cope with multiple stressors such as heat load, and water and feed scarcity, and possess better skills to cope with bush, when compared with sheep and cattle. The unique capacity for employing behavioral plasticity and morphological features of goats gives them clear advantage over sheep and cattle, when coping with seasonal biotopes, and experiences of water and feed shortage. When facing with low-quality feed, they also are superior to cattle and sheep to digest dry matter and to recycle nitrogen. Additionally, goats have superior ability to desiccate feces and concentrate urine, when compared with sheep and cattle. These advantages make goat the go-to species for efficiently countering the adversities associated with climate change and to optimize appropriate economic return through sustained production. Therefore, goats are tipped to be the future animals with extreme potential to counter the projected alarming climate change impacts and expected to play a significant role in ensuring food security to meet the demands of the growing human population by the end of this century.
species are medically important fungi that are present in soil and human impacted areas and capable of causing a wide spectrum of diseases in humans. Although little is known about their ...pathogenesis, their growth process and infection routes are very similar to those of
species, which grow as biofilms in invasive infections. All nine strains tested here displayed the ability to grow as biofilms
and to produce a dense network of interconnected hyphae on both polystyrene and the surfaces of central venous catheters, but with different characteristics.
and
clinical isolates were able to form biofilms faster than the corresponding environmental strains, as evidenced in kinetic assays for
and CLSM for
. Biofilms formed by
species had significantly higher resistance to the class of antifungal azole than was observed in planktonic cells, indicating a protective role for this structure. In addition, the clinical
isolate that formed the most robust biofilms was also more virulent in a larvae
infection model, suggesting that the ability to form biofilms enhances virulence in
species.
The present study aimed to evaluate the effect of crude protein degradability and corn processing on lactation performance, milk protein composition, milk ethanol stability (MES), heat coagulation ...time (HCT) at 140°C, and the efficiency of N utilization for dairy cows. Twenty Holstein cows with an average of 162 ± 70 d in milk, 666 ± 7 kg of body weight, and 36 ± 7.8 kg/d of milk yield (MY) were distributed in a Latin square design with 5 contemporaneous balanced squares, 4 periods of 21 d, and 4 treatments (factorial arrangement 2 × 2). Treatment factor 1 was corn processing ground (GC) or steam-flaked corn (SFC) and factor 2 was crude protein (CP) degradability (high = 10.7% rumen-degradable protein and 5.1% rumen-undegradable protein; low = 9.5% rumen-degradable protein and 6.3% rumen-undegradable protein; dry matter basis). A significant interaction was observed between CP degradability and corn processing on dry matter intake (DMI). When cows were fed GC with low CP degradability, DMI increased by 1.24 kg/d compared with cows fed GC with high CP degradability; however, CP degradability did not change DMI when cows were fed SFC. Similar interactions were observed for MY, HCT, and lactose content. When cows were fed GC diets, high CP degradability reduced MY by 2.3 kg/d, as well as HCT and lactose content, compared with low CP degradability. However, no effect of CP degradability was observed on those variables when cows were fed SFC diets. The SFC diets increased dry matter and starch total-tract digestibility and reduced β-casein (CN) content (% total milk protein) compared with GC diets. Cows fed low-CP degradability diets had higher glycosylated κ-CN content (% total κ-CN) and MES, as well as milk protein content, 3.5% fat-corrected milk, and efficiency of N for milk production, than cows fed high-CP degradability diets. Therefore, GC and high-CP degradability diets reduced milk production and protein stability. Overall, low CP degradability increased the efficiency of dietary N utilization and MES, probably due to changes in casein micelle composition, as CP degradability or corn processing did not change the milk concentration of ionic calcium. The GC diets increased β-CN content, which could contribute to reducing HTC when cows were fed GC and high-CP degradability diets.
In order to effectively control and monitor schistosomiasis, new diagnostic methods are essential. Taking advantage of computational approaches provided by immunoinformatics and considering the ...availability of Schistosoma mansoni predicted proteome information, candidate antigens of schistosomiasis were selected and used in immunodiagnosis tests based on Enzime-linked Immunosorbent Assay (ELISA). The computational selection strategy was based on signal peptide prediction; low similarity to human proteins; B- and T-cell epitope prediction; location and expression in different parasite life stages within definitive host. Results of the above-mentioned analysis were parsed to extract meaningful biological information and loaded into a relational database developed to integrate them. In the end, seven proteins were selected and one B-cell linear epitope from each one of them was selected using B-cell epitope score and the presence of intrinsically disordered regions (IDRs). These predicted epitopes generated synthetic peptides that were used in ELISA assays to validate the rational strategy of in silico selection. ELISA was performed using sera from residents of areas of low endemicity for S. mansoni infection and also from healthy donors (HD), not living in an endemic area for schistosomiasis. Discrimination of negative (NEG) and positive (INF) individuals from endemic areas was performed using parasitological and molecular methods. All infected individuals were treated with praziquantel, and serum samples were obtained from them 30 and 180 days post-treatment (30DPT and 180DPT). Results revealed higher IgG levels in INF group than in HD and NEG groups when peptides 1, 3, 4, 5 and 7 were used. Moreover, using peptide 5, ELISA achieved the best performance, since it could discriminate between individuals living in an endemic area that were actively infected from those that were not (NEG, 30DPT, 180DPT groups). Our experimental results also indicate that the computational prediction approach developed is feasible for identifying promising candidates for the diagnosis of schistosomiasis and other diseases.
ABSTRACT
Using commissioning data from the first year of operation of the Canadian Hydrogen Intensity Mapping Experiment’s (CHIME) Pulsar backend system, we conduct a systematic analysis of the ...Faraday Rotation Measure (RM) of the Northern hemisphere pulsars detected by CHIME. We present 55 new RMs as well as obtain improved RM uncertainties for 25 further pulsars. CHIME’s low observing frequency and wide bandwidth between 400 and 800 MHz contribute to the precision of our measurements, whereas the high cadence observation provides extremely high signal-to-noise co-added data. Our results represent a significant increase of the pulsar RM census, particularly regarding the Northern hemisphere. These new RMs are for sources that are located in the Galactic plane out to 10 kpc, as well as off the plane to a scale height of ∼16 kpc. This improved knowledge of the Faraday sky will contribute to future Galactic large-scale magnetic structure and ionosphere modelling.
An electrolyte supported solid oxide fuel cell (SOFC) using standard electrodes, doped-lanthanum manganite cathode and Ni-cermet anode, was operated with direct (anhydrous) ethanol for more than ...100h, delivering essentially the same power output as running on hydrogen. A ceria-based layer provides the catalytic activity for the gradual internal reforming, which uses the steam formed by the electrochemical oxidation of hydrogen for the decomposition of ethanol. Such a concept opens up the way for multi-fuel SOFCs using standard components and a catalytic layer.
► A solid oxide fuel cell was operated under anhydrous ethanol for more than 100h. ► The same power output was observed for both fuels, hydrogen and ethanol. ► A ceria-based layer provided the catalytic activity for ethanol decomposition. ► Anhydrous ethanol was decomposed by the gradual internal reforming. ► Such a concept opens up the way for multi-fuel SOFCs.
Abstract
We present new discoveries and results from long-term timing of 72 pulsars discovered in the Pulsar Arecibo
L
-band Feed Array (PALFA) survey, including precise determination of astrometric ...and spin parameters, and flux density and scatter broadening measurements at 1.4 GHz. Notable discoveries include two young pulsars (characteristic ages ∼30 kyr) with no apparent supernova remnant associations, three mode-changing, 12 nulling and two intermittent pulsars. We detected eight glitches in five pulsars. Among them is PSR J1939+2609, an apparently old pulsar (characteristic age ∼1 Gy), and PSR J1954+2529, which likely belongs to a newly emerging class of binary pulsars. The latter is the only pulsar among the 72 that is clearly not isolated: a nonrecycled neutron star with a 931 ms spin period in an eccentric (
e
= 0.114) wide (
P
b
= 82.7 days) orbit with a companion of undetermined nature having a minimum mass of ∼0.6
M
⊙
. Since operations at Arecibo ceased in 2020 August, we give a final tally of PALFA sky coverage, and compare its 207 pulsar discoveries to the known population. On average, they are 50% more distant than other Galactic plane radio pulsars; PALFA millisecond pulsars (MSPs) have twice the dispersion measure per unit spin period than the known population of MSP in the plane. The four intermittent pulsars discovered by PALFA more than double the population of such objects, which should help to improve our understanding of pulsar magnetosphere physics. The statistics for these, rotating radio transients, and nulling pulsars suggest that there are many more of these objects in the Galaxy than was previously thought.
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