Over the summer of 2007, we obtained 1191 hr of "drift-scan" pulsar search observations with the Green Bank Telescope at a radio frequency of 350 MHz. Here we describe the survey setup, search ...procedure, and the discovery and follow-up timing of 13 pulsars. Among the new discoveries, one (PSR J1623-0841) was discovered only through its single pulses, two (PSRs J1327-0755 and J1737-0814) are millisecond pulsars, and another (PSR J2222-0137) is a mildly recycled pulsar. PSR J1327-0755 is a 2.7 ms pulsar at a dispersion measure (DM) of 27.9 pc cm super(-3) in an 8.7 day orbit with a minimum companion mass of 0.22 M sub(middot in circle). PSR J1737-0814 is a 4.2 ms pulsar at a DM of 55.3 pc cm super(-3) in a 79.3 day orbit with a minimum companion mass of 0.06 M sub(middot in circle). PSR J2222-0137 is a 32.8 ms pulsar at a very low DM of 3.27 pc cm super(-3) in a 2.4 day orbit with a minimum companion mass of 1.11 Mmiddot in circle. It is most likely a white-dwarf-neutron-star system or an unusual low-eccentricity double neutron star system. Ten other pulsars discovered in this survey are reported in the companion paper Lynch et al.
Iodide chemical ionization mass spectrometry (CIMS) is a common analytical
tool used in both laboratory and field experiments to measure a large suite
of atmospherically relevant compounds. Here, we ...describe a systematic ion
molecule reactor (IMR) temperature dependence of iodide CIMS analyte
sensitivity for a wide range of analytes in laboratory experiments. Weakly
bound iodide clusters, such as HCl, HONO, HCOOH, HCN, phenol, 2-nitrophenol,
and acyl peroxynitrate (PAN) detected via the peroxy radical cluster, all
exhibit strong IMR temperature dependence of sensitivity ranging from −3.4 % ∘C−1
to 5.9 % ∘C−1 (from 37 to 47 ∘C). Strongly
bound iodide clusters, such as Br2, N2O5, ClNO2, and PAN
detected via the carboxylate anion, all exhibit little to no IMR temperature
dependence ranging from 0.2 % ∘C−1 to −0.9 % ∘C−1 (from 37 to 47 ∘C). The IMR temperature relationships of weakly bound clusters
provide an estimate of net reaction enthalpy, and comparison with database
values indicates that these clusters are in thermal equilibrium. Ground site
HCOOH data collected in the summer of 2021 in Pasadena (CA) are corrected
and show a reversal in the diel cycle, emphasizing the importance of this
correction (35±6 % during the day, -26±2 % at night).
Finally, we recommend two approaches to minimize this effect in the field,
namely heating or cooling the IMR; the latter technique has the added benefit of
improving absolute sensitivity.
Recent preclinical studies revealed the efficacy of combined use of PI3K inhibitor BKM120 and PARP inhibitor Olaparib in breast and prostate cancers. The current study investigated the effect of such ...drug combination on ovarian cancer. Here we showed that combined inhibition of PI3K and PARP effectively synergized to inhibit proliferation, survival and invasion in the majority of ovarian cancer cell lines harboring PIK3CA mutations, including SKOV3, HEYA8, and IGROV1. Mechanistically, combined treatment of PARP and PI3K inhibitors resulted in an exacerbated DNA damage response and more substantially reduced AKT/mTOR signaling when compared to single-agent. Notably, ovarian cancer cells responsive to the PI3K/PARP combination displayed decreased BRCA1/2 expression upon drug treatment. Furthermore, the effect of the drug combination was corroborated in an intraperitoneal dissemination xenograft mouse model in which SKOV3 ovarian cancer cells responded with significantly decreased BRCA1 expression, suppressed PI3K/AKT signaling and reduced tumor burden. Collectively, our data suggested that combined inhibition of PI3K and PARP may be an effective therapeutic strategy for ovarian cancers with PIK3CA mutations and that the accompanied BRCA downregulation following PI3K inhibition could serve as a biomarker for the effective response to PARP inhibition.
This paper describes the issues relating to the measurement of nanoparticle size, shape and dispersion when evaluating the toxicity of nanoparticles. Complete characterization of these materials ...includes much more than size, size distribution and shape; nonetheless, these attributes are usually the essential foundation. The measurement of particle size, particularly at scales of 100 nm or less, can be challenging under the best of conditions. Measurements that are routine in the laboratory setting become even more difficult when made under the physiological conditions relevant to toxicity studies, where the environment of the particles can be quite complex. Passive and active cellular responses, as well as the presence of a variety of nano-scale biological structures, often complicate the collection and interpretation of size and shape data. In this paper, we highlight several of the common issues faced when characterizing nanoparticles for toxicity testing and suggest general protocols to address these problems.
Multispecies host-parasite evolution is common, but how parasites evolve after speciating remains poorly understood. Shared evolutionary history and physiology may propel species along similar ...evolutionary trajectories whereas pursuing different strategies can reduce competition. We test these scenarios in the economically important association between honey bees and ectoparasitic mites by sequencing the genomes of the sister mite species
and
. These genomes were closely related, with 99.7% sequence identity. Among the 9,628 orthologous genes, 4.8% showed signs of positive selection in at least one species. Divergent selective trajectories were discovered in conserved chemosensory gene families (IGR, SNMP), and Halloween genes (CYP) involved in moulting and reproduction. However, there was little overlap in these gene sets and associated GO terms, indicating different selective regimes operating on each of the parasites. Based on our findings, we suggest that species-specific strategies may be needed to combat evolving parasite communities.
Genes encoding subunits of the SWI/SNF chromatin-remodeling complex constitute, collectively, one of the most frequently mutated targets in cancer. Although mutations in SWI/SNF genes are uncommon in ...prostate cancer, a new study shows that SChLAP1, a long noncoding RNA frequently expressed in aggressive prostate tumors, drives cancer by directly disrupting SNF5, a core subunit of the SWI/SNF complex.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
There is a need to develop new ways of protecting plants against aphid attack. Here, we investigated the effect of a plant defence activator,
cis
-jasmone (CJ), in a range of cultivars of
Brassica ...napus, Brassica rapa
and
Brassica oleracea
. Plants were sprayed with
cis
-jasmone or blank formulation and then tested with peach potato aphids (
Myzus persicae
Sulzer) (Hemiptera: Aphididae) and their parasitoid
Diaeretiella rapae
(M'Intosh) (Hymenoptera: Braconidae). CJ treated plants had significantly lower aphid settlement than control plants in a settlement bioassay. Conversely, in a foraging bioassay,
D. rapae
parasitoids spent a significantly longer time foraging on CJ treated plants. Our results reveal that CJ treatment makes plants less attractive to and less suitable for
M. persicae
but more attractive to
D. rapae
in a range of brassica cultivars. It is likely that these effects are due to changes in volatile emission indicating activation of defence and presence of conspecific competitors to aphids but presence of prey to parasitoids. Increases in volatile emission were found in CJ induced plants but varied with genotype. Among the synthetic volatile compounds that were induced in the headspace of CJ treated brassica cultivars, methyl isothiocyanate, methyl salicylate and
cis
-jasmone were most repellent to aphids. These results build on earlier studies in
Arabidopsis
and show that tritrophic interactions are influenced by CJ in a wide range of brassica germplasm. The implication is that CJ is a promising treatment that could be used in brassica crops as part of an integrated pest management system.
We propose a new threshold quantity for the analysis of the epidemiology of infectious diseases. The quantity is similar in concept to the familiar basic reproduction ratio, R0, but it singles out ...particular host types instead of providing a criterion that is uniform for all host types. Using this methodology we are able to identify the long-term effects of disease-control strategies for particular subgroups of the population, to estimate the level of control necessary when targeting control effort at a subset of host types, and to identify host types that constitute a reservoir of infection. These insights cannot be obtained by using R0 alone.
Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included ...supportive care, correction of acid-base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong ("we recommend") or weak/conditional ("we suggest"), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration ≤ 12 mmol/L (or anion gap ≤ 28 mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50 mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50 mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L; or iv) Suggest ECTR if glycolate concentration 8-12 mmol/L or anion gap 23-27 mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is < 18 mmol/L or suggested if EG concentration is < 4 mmol/L. The dosage of antidotes (fomepizole or ethanol) needs to be adjusted during ECTR.
PDF
