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Triploid and pentaploid breeding is of great importance in agricultural production, but it is not always easy to obtain double ploidy parents. However, in fishes, chromosome ploidy is diversiform, which may provide natural parental resources for triploid and pentaploid breeding. Both tetraploid and hexaploid exist in Schizothorax fishes, which were thought to belong to different subfamilies with tetraploid Percocypris fishes in morphology, but they are sister genera in molecule. Fortunately, the pentaploid hybrid fishes have been successfully obtained by hybridization of Schizothorax wangchiachii (♀, 2n = 6X = 148) × Percocypris pingi (♂, 2n = 4X = 98). To understand the genetic and morphological difference among the hybrid fishes and their parents, four methods were used in this study: morphology, karyotype, red blood cell (RBC) DNA content determination and inter-simple sequence repeat (ISSR). In morphology, the hybrid fishes were steady, and between their parents with no obvious preference. The chromosome numbers of P. pingi have been reported as 2n = 4X = 98. In this study, the karyotype of S. wangchiachii was 2n = 6X = 148 = 36m + 34sm + 12st + 66t, while that the hybrid fishes was 2n = 5X = 123 = 39m + 28sm + 5st + 51t. Similarly, the RBC DNA content of the hybrid fishes was intermediate among their parents. In ISSR, the within-group genetic diversity of hybrid fishes was higher than that of their parents. Moreover, the genetic distance of hybrid fishes between P. pingi and S.wangchiachii was closely related to that of their parental ploidy, suggesting that parental genetic material stably coexisted in the hybrid fishes. This is the first report to show a stable pentaploid F1 hybrids produced by hybridization of a hexaploid and a tetraploid in aquaculture.
The aim of the study was to investigate any association between extrauterine growth restriction (EUGR) and intestinal flora of <30-week-old preterm infants. A total of 59 preterm infants were assigned to EUGR (n=23) and non-EUGR (n=36) groups. Intestinal bacteria were compared by using high-throughput sequencing of bacterial rRNA. The total abundance of bacteria in 344 genera (7568 v. 13,760; P<0.0001) and 456 species (10,032 v. 18,240; P<0.0001) was significantly decreased in the EUGR group compared with the non-EUGR group. After application of a multivariate logistic model and adjusting for potential confounding factors, as well as false-discovery rate corrections, we found four bacterial genera with higher and one bacterial genus with lower abundance in the EUGR group compared with the control group. In addition, the EUGR group showed significantly increased abundances of six species (Streptococcus parasanguinis, Bacterium RB5FF6, two Klebsiella species and Microbacterium), but decreased frequencies of three species (one Acinetobacter species, Endosymbiont_of_Sphenophorus_lev and one Enterobacter_species) compared with the non-EUGR group. Taken together, there were significant changes in the intestinal microflora of preterm infants with EUGR compared to preterm infants without EUGR.
OBJECTIVES/SPECIFIC AIMS: Prostate cancer is the second leading cause of cancer-related death among men in the U.S. and over half of all prostate cancer patients receive radiation therapy (RT). RT induces double-strand breaks (DSBs) in DNA which are lethal to cells if not repaired. While potentially curative, 10% of low-risk patients and 50% of high-risk patients treated with RT still experience tumor recurrence. Thus, identification of novel therapeutic targets to enhance RT will likely reduce prostate cancer mortality. The only clinical approach to enhance RT is androgen deprivation therapy, which targets androgen receptor (AR) signaling; however, its use is limited due to systemic side effects. We recently reported that PRMT5 epigenetically activates AR which led us to investigate if targeting PRMT5 sensitizes prostate cancer to RT. The goal of this project is to determine if PRMT5 is a therapeutic target for prostate cancer radiosensitization and analyze its mechanistic role in response to radiation. METHODS/STUDY POPULATION: To evaluate if targeting PRMT5 may sensitize prostate cancer cells to radiation, we performed a clonogenic assay of irradiated cells. To determine if PRMT5 is required for repair of radiation-induced DSBs, we performed foci analysis via immunocytochemistry. We then used RNA-seq, qPCR, western blot, and ChIP to evaluate a potential epigenetic role of PRMT5 in activating the expression of genes critical to DSB repair. To extend our findings, we analyzed clinical data from around 18,000 of cancer patients encompassing 43 cancer types to assess if PRMT5 expression correlates with the expression of its putative target genes. RESULTS/ANTICIPATED RESULTS: Targeting PRMT5 sensitizes prostate cancer cells to radiation independently of AR status. RNA-seq analysis revealed putative PRMT5 target genes including several involved in DSB repair and G2 arrest. Mechanistically, PRMT5 functions as a master epigenetic activator of DNA damage response (DDR) genes: PRMT5 maintains the basal expression of several DDR genes including BRCA1, BRCA2, and RAD51 and is recruited upon radiation to DDR gene promoters to activate their expression via histone methylation. Targeting PRMT5 decreases expression of these genes at the protein level and hinders repair of radiation-induced DSBs in multiple cancer and non-cancer cell types. Clinically, PRMT5 expression positively correlates with the expression of these DDR genes across all 43 cancer types analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: PRMT5 acts as a master epigenetic activator of genes involved in DDR and is critical for cells to survive radiation treatment. Importantly, PRMT5 epigenetically activates multiple genes that encode for well-characterized core repair proteins involved in HR (RAD51, RAD51AP1, RAD51D, BRCA1 and BRCA2) and NHEJ (NHEJ1, Ku80, XRCC4, and DNAPKcs), which may explain why PRMT5 is essential to repair IR-induced DSBs in several cell lines. As PRMT5 is overexpressed in many human cancers and its overexpression correlates with poor prognosis, our findings suggest that more efficient DSB repair via PRMT5 overexpression in these cancers may confer survival advantages particularly following DNA damaging treatments. Lastly, because targeting DSB repair is a clinically validated therapeutic approach for cancer treatment, our findings also suggest that PRMT5 targeting may be explored as a monotherapy or in combination therapy with radiation therapy or chemotherapy for cancer treatment.
Alanyl-glutamine (Ala-Gln), a highly soluble and stable glutamine dipeptide, is known to improve gut integrity and function. The aim of this study was to evaluate whether dietary Ala-Gln supplementation could improve growth performance, intestinal development and digestive-absorption function in weaned piglets. A total of 100 purebred Yorkshire piglets weaned at 21 days of age were assigned randomly to four dietary treatment groups and fed a basal diet (control group) or a basal diet containing 0.15%, 0.30% and 0.45% Ala-Gln, respectively. Compared with the control group, piglets fed the Ala-Gln diets had higher average daily gain and lower feed : gain and diarrhea rate (P < 0.05). Moreover, dietary Ala-Gln supplementation increased villous height and villous height : crypt depth ratio in duodenum and jejunum (P < 0.05), as well as the activities of maltase and lysozyme in jejunum mucosa (P < 0.05). In addition, a decrease in serum diamine oxidase activity and crypt depth in duodenum and jejunum was observed in piglets fed the Ala-Gln diets (P < 0.05). Serum cytosolic phospholipase A2 (cPLA2) concentration and gene expression of cPLA2, Na+-dependent glucose transporter 1, glucose transporter 2 and peptide transporter 1 in jejunum were increased by feeding Ala-Gln diets relative to control diet (P < 0.05). These results indicated that feeding Ala-Gln diet has beneficial effects on the growth performance of weaned piglets, which associated with maintaining intestinal morphology and digestive-absorption function.
Adults with congenital heart disease face psychological challenges although an understanding of depression vs. anxiety symptoms is unclear. We analyzed the prevalence of elevated symptoms of anxiety and depression and explored associations with demographic and medical factors as well as quality of life.
Adults with congenital heart disease enrolled from an outpatient clinic completed the Hospital Anxiety and Depression Scale and two measures of quality of life: the Linear Analogue Scale and the Satisfaction with Life Scale. Medical data were obtained by chart review.
Of 130 patients (median age = 32 years; 55% female), 55 (42%) had elevated anxiety symptoms and 16 (12%) had elevated depression symptoms on subscales of the Hospital Anxiety and Depression Scale. Most patients with elevated depression symptoms also had elevated anxiety symptoms (15/16; 94%). Of 56 patients with at least one elevated subscale, 37 (66%) were not receiving mental health treatment. Compared to patients with 0 or 1 elevated subscales, patients with elevations in both (n=15) were less likely to be studying or working (47% vs. 81%; p=0.016) and reported lower scores on the Linear Analogue Scale (60 vs. 81, p<0.001) and the Satisfaction with Life Scale (14 vs. 28, p<0.001).
Among adults with congenital heart disease, elevated anxiety symptoms are common and typically accompany elevated depressive symptoms. The combination is associated with unemployment and lower quality of life. Improved strategies to provide psychosocial care and support appropriate engagement in employment are required.
Muons produced by the Bethe–Heitler process from laser wakefield accelerated electrons interacting with high
materials have velocities close to the laser wakefield. It is possible to accelerate those muons with laser wakefield directly. Therefore for the first time we propose an all-optical ‘Generator and Booster’ scheme to accelerate the produced muons by another laser wakefield to supply a prompt, compact, low cost and controllable muon source in laser laboratories. The trapping and acceleration of muons are analyzed by one-dimensional analytic model and verified by two-dimensional particle-in-cell (PIC) simulation. It is shown that muons can be trapped in a broad energy range and accelerated to higher energy than that of electrons for longer dephasing length. We further extrapolate the dependence of the maximum acceleration energy of muons with the laser wakefield relativistic factor
and the relevant initial energy
. It is shown that a maximum energy up to 15.2 GeV is promising with
on the existing short pulse laser facilities.
Vessel flexure can be triggered naturally by surgical operation, heart pulsation and body movement. It may affect the mechanical behavior of the stent and the existence of a stent may in turn cause vessel injury. In the present study, the finite element method is employed to study the interaction between stent and vessel during vessel flexure. Two- and four-link stents made of stainless steel 316L and magnesium alloy WE43 are considered. Results indicate that longitudinal deformation of the stent can be caused by vessel flexure, and the higher levels of stress exist in the link struts. The existence of the stent could induce significant stress concentration and straightened deformation on vessel wall in the course of vessel flexure. Stents with more links or made of harder materials show greater anti-deformation capability, thus inducing a more severe stress concentration and straightened deformation on the vessel wall. The bending direction also affects the mechanical performance of the vessel-stent system. The results obtained could provide useful information for better stent designs and clinical decisions.
Binge eating disorder (BED) is the most common eating disorder in the US, with a lifetime prevalence of 2.8%. Disturbances in reward circuitry have been implicated in its pathogenesis. Dasotraline is a novel and potent dopamine and norepinephrine reuptake inhibitor with slow absorption and a long half-life resulting in stable plasma concentrations over 24 hours with once-daily dosing. This study evaluated the efficacy and safety of flexibly-dosed dasotraline (4, 6, and 8 mg/day) vs placebo in adults with moderate to severe BED over a 12-week period (NCT02564588).
Key inclusion criteria included moderate to severe BED based on a history of ≥2 binge eating days/week for ≥6 months prior to screening, and ≥3 binge eating days for each of2 weeks prior to randomization, as documented in participant’s binge eating diary. Patients were randomized 1:1 to flexibly-dosed dasotraline (4, 6, 8 mg/day) or placebo. Theprimary endpoint was change from baseline (CFB) in the number of binge eating days per week at Week 12. Key secondary endpoints were: CFB in Clinical Global Impression–Severity (CGI-S) Scale at Week 12; CFB in Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (YBOCS-BE) at Week 12; and the percentage ofsubjects with a 4-week cessation from binge eating prior to Week 12 or end of treatment (EOT). Except for 4-week cessation, the other three variables were analyzed using amixed model for repeated measures (MMRM).
317 subjects (84% female) received ≥1 dose of study medication (mean age was 38.2 years; mean number of binge eating days per week, 4.25; mean CGI-S score, 4.5; mean BMI, 34.7). The MMRM analysis of CFB at Week 12 in the number of binge days/week yielded a significant mean difference of –0.99 (95% CI: –0.65 to –1.33; p<0.001) infavour of dasotraline (–3.74 in the dasotraline group vs –2.75 in the placebo group). All three key secondary endpoints were met at Week 12 or EOT: 46.5% of subjects in thedasotraline group achieved at least 4 consecutive weeks’ cessation from binge eating vs 20.6% in the placebo group (p<0.001); CFB in CGI-S and YBOCS-BE scores were also statistically significant in favour of dasotraline (p<0.001). The treatment-emergent adverse events (TEAEs) that occurred more frequently with dasotraline vs placebo at >2% incidence included: insomnia (44.6% vs 8.1%), dry mouth (27.4% vs 5.0%), decreased appetite (19.7% vs 6.9%), anxiety (17.8% vs 2.5%), nausea (12.7% vs 6.9%) and decreased body weight (12.1% vs 0%). Discontinuation due to AEs occurred in 11.5% of patients taking dasotraline vs 2.5% taking placebo.
In adults with moderate to severe BED, there were highly significant and clinically meaningful reductions with dasotraline vs placebo in the frequency of binge eating, global severity of illness, and obsessive-compulsive symptoms related to binge eating. These results suggest dasotraline may offer a novel, well-tolerated and efficacious treatmentfor BED.
We present first results from pilot observations using a phased array feed (PAF) mounted on the Parkes 64-m radio telescope. The observations presented here cover a frequency range from 1 150 to 1 480 MHz and are used to show the ability of PAFs to suppress standing wave problems by a factor of ~10, which afflict normal feeds. We also compare our results with previous HIPASS observations and with previous H i images of the Large Magellanic Cloud. Drift scan observations of the GAMA G23 field resulted in direct H i detections at z = 0.0043 and z = 0.0055 of HIPASS galaxies J2242-30 and J2309-30. Our new measurements generally agree with archival data in spectral shape and flux density, with small differences being due to differing beam patterns. We also detect signal in the stacked H i data of 1 094 individually undetected galaxies in the GAMA G23 field in the redshift range 0.05 ⩽ z ⩽ 0.075. Finally, we use the low standing wave ripple and wide bandwidth of the PAF to set a 3σ upper limit to any positronium recombination line emission from the Galactic Centre of <0.09 K, corresponding to a recombination rate of <3.0 × 1045 s−1.
We present a scenario for the evolution of massive stars in which a new mixing mechanism (named global diffusion) is taken into account. This type of mixing stands on the critical Reynolds number and radiative viscosity (Schatzman 1977) and allows mixing of material to take place between the core and the surface during the whole evolution on a very slow time scale. The physical processes triggering global diffusion deserve further study. We find that stellar models of massive stars calculated with global diffusion offer interesting clues to understanding the properties of Wolf-Rayet stars and their location in the HRD.
During 2016 February, CSIRO Astronomy and Space Science and the Max-Planck-Institute for Radio Astronomy installed, commissioned, and carried out science observations with a phased array feed receiver system on the 64-m diameter Parkes radio telescope. Here, we demonstrate that the phased array feed can be used for pulsar observations and we highlight some unique capabilities. We demonstrate that the pulse profiles obtained using the phased array feed can be calibrated and that multiple pulsars can be simultaneously observed. Significantly, we find that an intrinsic polarisation leakage of −31 dB can be achieved with a phased array feed beam offset from the centre of the field of view. We discuss the possibilities for using a phased array feed for future pulsar observations and for searching for fast radio bursts with the Parkes and Effelsberg telescopes.
This paper reports an investigation of the relationship between spray characteristics and a nozzles’ internal structure to reveal the working mechanism of anti-drift spray nozzles. Three important structural factors were taken into account, the diameter of the inner chamber, the angle of V-shaped slot and the relative kerf depth. Three-dimensional models of the fan nozzles were set up using Solidworks software and the corresponding real nozzles were produced using high-precision 3-D printer. The flow fields inside the nozzles were simulated using the software FLUENT. By comparing the flow fields inside and outside the nozzles under the conditions of the same inner structural parameter, the relationships between spraying flow characteristics and different structural parameters was made clear, and provides a reference for optimal design of anti-drift spray nozzles.
We are interested in the rate of convergence of a subordinate Markov process to its invariant measure. Given a subordinator and the corresponding Bernstein function (Laplace exponent), we characterize the convergence rate of the subordinate Markov process; the key ingredients are the rate of convergence of the original process and the (inverse of the) Bernstein function. At a technical level, the crucial point is to bound three types of moment (subexponential, algebraic, and logarithmic) for subordinators as time t tends to ∞. We also discuss some concrete models and we show that subordination can dramatically change the speed of convergence to equilibrium.
Using a nonlocal time-dependent theory of convection, we have calculated the linear non-adiabatic oscillations of the Horizontal Branch (HB) stars, with both the dynamic and thermodynamic coupling between convection and oscillations been carefully treated. Turbulent pressure and turbulent viscosity have been included consistently in our equations of non-adiabatic pulsation. When the coupling between convection and oscillations is ignored, for all models with Te ≤ 7350K, the fundamental through the second overtone are pulsationally unstable; while for Te ≤ 6200K all the models are unstable up to (at least) the 9th overtone. When the coupling between convection and oscillations is included, the RR Lyrae instability strip is very well predicted. Within the strip most models are pulsationally unstable only for the fundamental and the first few overtones. Turbulent viscosity is an important damping mechanism. Being exclusively distinct from the luminous red variables (long period variables), the HB stars to the right of the RR Lyrae strip are pulsationally stable for the fundamental and low-order overtones, but become unstable for some of the high-order overtones. This may provide a valuable clue for the short period, low amplitude red variables found outside the red edge of the RR Lyrae strip on the H-R diagram of globular clusters. Moreover, we present a new radiation modulated excitation mechanism functioning in radiation flux gradient regions. The effects of nonlocal convection and the dynamic coupling between convection and oscillations are discussed. The spatial oscillations of the thermal variables in the pulsational calculations have been effectively suppressed.
We have performed a linear pulsational stability survey of long period variable models. The dynamic and thermodynamic couplings between convection and oscillations are treated by using a statistical theory of nonlocal and time-dependent convection. The results show that the fundamental and all the low overtones are always pulsationally unstable for the low-temperature models when the coupling between convection and oscillations is ignored. When the coupling is considered, there is indeed a “Mira” pulsationally instability region outside of the Cepheid instability strip on the H-R diagram. The coolest models near the Hayashi track are pulsationally stable. Towards high temperature the fundamental mode first becomes unstable, and then the first overtone. Some of the 2nd −4th overtones may become unstable for the hotter models. All the modes higher than 4th (n > 4) are pulsationally stable. The position and the width of such an instability region on the H-R diagram critically depends on the mass, luminosity and metal abundance of the star.
Flour whiteness (FW) is an important factor in assessing flour quality and determining the end product quality. It is an integrated sensory indicator reflecting flour colour and is negatively correlated with protein content. In order to dissect the genetic relationship between FW and its five related traits at the quantitative trait locus (QTL)/gene level, a recombinant inbred line population was evaluated under three environments. Quantitative trait loci for FW were analysed by unconditional and conditional QTL mapping. Four unconditional additive QTLs and 16 conditional additive QTLs were detected across the three environments. Of these QTLs, only one major additive QTL (Qfw1D1-1) was consistently identified using both unconditional and conditional QTL analysis. This QTL was independent of flour colour a* (a function of red-green with a positive a* for redness and negative for greenness) and b* (a green-blue value with positive value for yellowness and negative for blueness) and was only slightly affected by flour protein content. A minor additive QTL (Qfw4A-4) was also detected using these two QTL mapping methods, being independent of flour colour a* and b*. Five unconditional and ten conditional epistatic minor QTLs were detected, from which only one pair (Qfw3A-10/Qfw6B-6) was identified by both unconditional and conditional QTL mapping, also independent of flour colour a* and b*. The major QTL (Qfw1D1-1) identified in the current study for the first time can be used for improving wheat FW in marker-assisted breeding.
This paper focuses on the attitude dynamics and control of liquid filled spacecraft, and the large amplitude fuel slosh dynamics is included by using an improved moving pulsating ball model. The moving pulsating ball model is an equivalent mechanical model that is capable of imitating the whole liquid reorientation process, specifically for the occurrence of large amplitude slosh. This model is improved by incorporating a static capillary force and an effective mass factor. The improvements on this model are validated with previously published experiment results. The spacecraft attitude maneuver is implemented by the momentum transfer technique, and the feedback control strategy is designed based on Lyapunov theory. The effects of liquid viscosity, tank location and desired steady time on sloshing torque and control torque are investigated. The attitude control strategy applied in this paper is proved to be applicable for the coupled liquid filled spacecraft system. The obtained conclusions are useful to aid in liquid filled spacecraft overall design.