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The current study investigated associations between variation in the bovine perilipin-2 gene (PLIN2) and milk traits (milk fat content, milk protein content, milk yield and milk fatty acid (FA) component levels) in 409 New Zealand pasture-grazed Holstein-Friesian × Jersey-cross (HF × J-cross or Kiwicross™) cows. Five nucleotide sequence variants were found in three regions of the gene, including c.17C>T in exon 2, c.53A>G in exon 3, c.595+23G>A and c.595+104_595+108del in intron 5, and c.*302T>C in the 3′-untranslated region. The c.*302T>C substitution produces two nucleotide sequence variants (A5 and B5), and this variation was associated with variation in milk protein content and milkfat composition for C10:0, C11:0, C12:0, C13:0 and C16:0 FA and medium-chain fatty acid (MCFA) and long-chain fatty acid (LCFA) groups. After correcting for the effect of variation in the diacylglycerol acyl-CoA acyltransferase 1 gene (DGAT1) that results in the amino acid substitution p.K232A, variation in the FA binding protein 4 gene (FABP4) and variation in the stearoyl-CoA desaturase (Δ-9-desaturase) gene (SCD) that results in the amino acids substitution p.A293V, significant differences between A5A5 and B5B5 cows were found for C10:0, C11:0, C12:0, C13:0, C16:0, and the MCFA, LCFA, total saturated FA and C10:1 index groups. This suggests that nucleotide sequence variation in PLIN2 may be affecting milk FA component levels.
This work investigated the photophysical pathways for light absorption, charge generation, and charge separation in donor–acceptor nanoparticle blends of poly(3-hexylthiophene) and indene-C60-bisadduct. Optical modeling combined with steady-state and time-resolved optoelectronic characterization revealed that the nanoparticle blends experience a photocurrent limited to 60% of a bulk solution mixture. This discrepancy resulted from imperfect free charge generation inside the nanoparticles. High-resolution transmission electron microscopy and chemically resolved X-ray mapping showed that enhanced miscibility of materials did improve the donor–acceptor blending at the center of the nanoparticles; however, a residual shell of almost pure donor still restricted energy generation from these nanoparticles.
In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.
OBJECTIVES/GOALS: Peri-implantitis is the inflammation of peri-implant mucosa and subsequent loss of supporting bone. Its treatment is only <40% successful mainly due to persistent bacterial infection. The goal of this project is to increase success rates by developing a robust antibiofilm multi-biomolecular membrane that can be placed around implant surfaces. METHODS/STUDY POPULATION: A collagen membrane was soaked in the antimicrobial peptide GL13K solution overnight to form an interpenetrating fibrillary network. The nanostructure of the membrane was imaged with scanning electron microscope (SEM). The hydrophobicity of the membrane was analyzed by water contact angle (WCA) measurements. The biodegradability was tested in a 0.01 mg/mL Type I collagenase solution for up to 5 weeks. The antimicrobial activity of the membrane was assessed with Gram-positive oral bacteria Streptococcus gordonii. The cytotoxicity was evaluated by culturing human gingival fibroblasts (HGF), and the osteogenesis was assessed using preosteoblasts MC3T3. Pure collagen membrane was used as the control. Statistical significance (p<0.05) was determined by one-way ANOVA with Tukey’s HSD test. RESULTS/ANTICIPATED RESULTS: The antimicrobial peptide GL13K self-assembled to short fibrils (< 1 µm long), which entangled with the larger collagen fibers (around 200 nm in diameter). The collagen fibers presented characteristic periodic banding structures, which provided biomimetic cues for cell behavior as extracellular matrix. The interpenetrated GL13K fibrils turned the highly hydrophilic collagen membrane to a hydrophobic membrane (WCA = 135 °) and significantly reduced the rate of degradation by collagenases. The developed membrane was efficient in preventing the attachment of S. gordonii. A large portion of the attached bacteria was killed on the surface of the membrane. The incorporation of GL13K did not affect the cytocompatibility of the membrane for HGF. DISCUSSION/SIGNIFICANCE OF IMPACT: We developed an antibiofilm membrane with interpenetrating collagen and antimicrobial peptide fibrils. The strong antimicrobial activity and low cytotoxicity support its further translational evaluation as scaffolds for increasing success rate in treating peri-implantitis.
This report is on the synthesis by electrospinning of multiferroic core-shell nanofibers of strontium hexaferrite and lead zirconate titanate or barium titanate and studies on magneto-electric (ME) coupling. Fibers with well-defined core–shell structures showed the order parameters in agreement with values for nanostructures. The strength of ME coupling measured by the magnetic field-induced polarization showed the fractional change in the remnant polarization as high as 21%. The ME voltage coefficient in H-assembled films showed the strong ME response for the zero magnetic bias field. Follow-up studies and potential avenues for enhancing the strength of ME coupling in the core–shell nanofibers are discussed.
Current available antidepressants exhibit low remission rate with a long response lag time. Growing evidence has demonstrated acute sub-anesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant effects. However, a long term use of ketamine tends to elicit its adverse reactions. The present study aimed to investigate the antidepressant-like effects of intermittent and consecutive administrations of ketamine on chronic unpredictable mild stress (CUMS) rats, and to determine whether ketamine can redeem the time lag for treatment response of classic antidepressants. The behavioral responses were assessed by the sucrose preference test, forced swimming test, and open field test. In the first stage of experiments, all the four treatment regimens of ketamine (10 mg/kg ip, once daily for 3 or 7 consecutive days, or once every 7 or 3 days, in a total 21 days) showed robust antidepressant-like effects, with no significant influence on locomotor activity and stereotype behavior in the CUMS rats. The intermittent administration regimens produced longer antidepressant-like effects than the consecutive administration regimens and the administration every 7 days presented similar antidepressant-like effects with less administration times compared with the administration every 3 days. In the second stage of experiments, the combination of ketamine (10 mg/kg ip, once every 7 days) and citalopram (20 mg/kg po, once daily) for 21 days caused more rapid and sustained antidepressant-like effects than citalopram administered alone. In summary, repeated sub-anesthestic doses of ketamine can redeem the time lag for the antidepressant-like effects of citalopram, suggesting the combination of ketamine and classic antidepressants is a promising regimen for depression with quick onset time and stable and lasting effects.
Planning ability as a critical component of executive function has been used to investigate prefrontal cortex (PFC) function in Schizophrenia patients by several neuroimaging studies. However, the changes of PFC activation after effective antipsychotic treatment are still unclear.
The aim of this study is to explore whether there is any variation in the prefrontal hemodynamic response during Tower of London test after 6 weeks’ antipsychotic treatment in schizophrenia patients, and the relationship between the changes in PFC activation and some demographic factors as well as the severity of the patients’ psychiatric symptoms.
40 patients with first-episode schizophrenia were recruited for the present study. 28-channel NIRS (near infrared spectroscopy) was used to measure changes in hemoglobin concentration in the prefrontal cortical surface area during Tower of London (TOL) test—a classic neuropsychological test for planning abilities. The patients were examined before treatment and after six weeks’ treatment with second-generation antipsychotic medicines.
After the short-term treatment, the patients’ TOL test performance and the activations in PFC during the task period did not differ from baseline (P>0.05), although the psychiatric symptoms of the patients were improved significantly(positive subscale score 18.25±2.86 & 12.75±2.60; general psychopathology 33.67±3.65 & 27.00±3.67; PANSS total score 72.25±7.07 & 55.42±7.53; P<0.001).
It suggests that the impairment of cognitive function and the function of the PFC of schizophrenia patients would not be improved with the improvement of psychiatric symptoms, as further support the hypothesis that PFC damage is a durable impairment for schizophrenia.
The present study identified the neural mechanism of risky decision-making in Internet gaming disorder (IGD) under a probability discounting task.
Independent component analysis was used on the functional magnetic resonance imaging data from 19 IGD subjects (22.2 ± 3.08 years) and 21 healthy controls (HC, 22.8 ± 3.5 years).
For the behavioral results, IGD subjects prefer the risky to the fixed options and showed shorter reaction time compared to HC. For the imaging results, the IGD subjects showed higher task-related activity in default mode network (DMN) and less engagement in the executive control network (ECN) than HC when making the risky decisions. Also, we found the activities of DMN correlate negatively with the reaction time and the ECN correlate positively with the probability discounting rates.
The results suggest that people with IGD show altered modulation in DMN and deficit in executive control function, which might be the reason for why the IGD subjects continue to play online games despite the potential negative consequences.
The aim of this research was to identify variation in the yak lipin-1 gene (LPIN1) and determine whether this variation affects milk traits. PCR-single stranded conformational polymorphism (PCR-SSCP) analysis was used to detect variation in the 5′ untranslated region of LPIN1 in 500 yaks from four populations: Tianzhu white yaks, Qinghai yaks, wild × domestic-cross yaks and Gannan yaks. Four unique PCR-SSCP patterns, representing four different DNA sequence variants (named A, B, C and D), were observed. These contained six single nucleotide polymorphisms. Female Gannan yaks with BC genotype produced milk with a higher fat content (P < 0.001) and total milk solids (P < 0.001), than those with the AA, AB and BB genotypes. These results would suggest that LPIN1 is having an effect on yak milk fat synthesis.
Enhancing the supply of arginine (Arg), a semi-essential amino acid, has positive effects on immune function in dairy cattle experiencing metabolic stress during early lactation. Our objective was to determine the effects of Arg supplementation on biomarkers of liver damage and inflammation in cows during early lactation. Six Chinese Holstein lactating cows with similar BW (508 ± 14 kg), body condition score (3.0), parity (4.0 ± 0), milk yield (30.6 ± 1.8 kg) and days in milk (20 ± days) were randomly assigned to three treatments in a replicated 3 × 3 Latin square design balanced for carryover effects. Each period was 21 days with 7 days for infusion and 14 days for washout. Treatments were (1) Control: saline; (2) Arg group: saline + 0.216 mol/day l-Arg; and (3) Alanine (Ala) group: saline + 0.868 mol/day l-Ala (iso-nitrogenous to the Arg group). Blood and milk samples from the experimental cows were collected on the last day of each infusion period and analyzed for indices of liver damage and inflammation, and the count and composition of somatic cells in milk. Compared with the Control, the infusion of Arg led to greater concentrations of total protein, immunoglobulin M and high density lipoprotein cholesterol coupled with lower concentrations of haptoglobin and tumor necrosis factor-α, and activity of aspartate aminotransferase in serum. Infusion of Ala had no effect on those biomarkers compared with the Control. Although milk somatic cell count was not affected, the concentration of granulocytes was lower in response to Arg infusion compared with the Control or Ala group. Overall, the biomarker analyses indicated that the supplementation of Arg via the jugular vein during early lactation alleviated inflammation and metabolic stress.
Drug Safety Communications (DSCs) are used by the Food and Drug Administration (FDA) to inform health care providers, patients, caregivers, and the general public about safety issues related to FDA-approved drugs. To assess patient knowledge of the messaging contained in DSCs related to the sleep aids zolpidem and eszopiclone, we conducted a large, cross-sectional patient survey of 1,982 commercially insured patients selected by stratified random sampling from the Optum Research Database who had filled at least two prescriptions for either zolpidem or eszopiclone between July 1, 2012 and June 30, 2013. Among the 594 respondents (32.7% response rate), two-thirds reported hearing generally about drug safety information prior to starting a new drug, with the remaining one-third “rarely” or “never” hearing such information. Providers and pharmacists were primary sources of drug safety information. Two-thirds of zolpidem users and half of eszopiclone users reported having heard about the related DSC messages, ability to accurately identify the major factual messages was limited (overall median 2 correct out of 5, with men and those reporting higher educational level scoring higher [2/5 vs. 1/5, p=0.001]). Respondents reacted to new drug safety information about their sleep aids by reporting that they would want to learn about alternative ways to help them sleep (70%) and seek out more information about the safety of their specific sleeping pill (59-78%). Opportunities may exist for the FDA to work with providers and pharmacies to help ensure the DSC information is more widely received and is more fully understood by those taking the affected medications.
The present study aimed to evaluate the effect of mandatory iodine fortification of bread on the iodine status of South Australian populations using newborn thyroid-stimulating hormone (TSH) concentration as a marker.
The study used an interrupted time-series design.
TSH data collected between 2005 and 2016 (n 211 033) were extracted from the routine newborn screening programme in South Australia for analysis. Iodine deficiency is indicated when more than 3 % of newborns have TSH > 5 mIU/l.
Newborns were classified into three groups: the pre-fortification group (those born before October 2009); the transition group (born between October 2009 and June 2010); and the post-fortification group (born after June 2010).
The percentage of newborns with TSH > 5 mIU/l was 5·1, 6·2 and 4·6 % in the pre-fortification, transition and post-fortification groups, respectively. Based on a segmented regression model, newborns in the post-fortification period had a 10 % lower risk of having TSH > 5 mIU/l than newborns in the pre-fortification group (incidence rate ratio (IRR) = 0·90; 95 % CI 0·87, 0·94), while newborns in the transitional period had a 22 % higher risk of having TSH > 5 mIU/l compared with newborns in the pre-fortification period (IRR = 1·22; 95 % CI 1·13, 1·31).
Using TSH as a marker, South Australia would be classified as mild iodine deficiency post-fortification in contrast to iodine sufficiency using median urinary iodine concentration as a population marker. Re-evaluation of the current TSH criteria to define iodine status in populations is warranted in this context.
KRTAP8-1 was the initial high-glycine-tyrosine keratin-associated protein gene recognized in sheep, but little is known about the functional influence of this gene. The current study used polymerase chain reaction-single stranded conformational polymorphism analysis to genotype KRTAP8-1 in 391 Southdown × Merino-cross sheep from six sire-lines. Five previously described variants (named A to E) of KRTAP8-1 were identified with frequencies of 67.0, 14.2, 7.0, 10.7 and 1.0%, respectively. Of the four variants (A, B, C and D) that occurred at a frequency greater than 5%, the presence of C was found to be associated with a reduction in mean fibre curvature (MFC) and the presence of D was associated with an increase in mean staple strength (MSS), whereas the presence of A had a trend of association with reduced MSS. Associations were not identified with other wool traits. These results suggest that variation in KRTAP8-1 affects MSS and MFC, and that KRTAP8-1 has the potential to be used as a genetic marker for improving these traits.
The late Miocene is a time of strong environmental change in SW Asia. Himalayan foreland stable isotope data show a shift in the dominant vegetation of the flood plains away from trees and shrubs towards more C4 grasslands at a time when oceanic upwelling increased along the Oman margin. We present integrated geochemical and colour spectral records from International Ocean Discovery Program Site U1456 in the eastern Arabian Sea to reconstruct changing chemical weathering and erosion, as well as relative humidity during this climatic transition. Increasing hematite/goethite ratios derived from spectral data are consistent with long-term drying after c. 7.7 Ma. Times of dry conditions are largely associated with weaker chemical alteration measured by K/Rb and reduced coarse clastic flux, constrained by Si/Al and Zr/Al. A temporary phase of increased humidity from 6.3 to 5.95 Ma shows a reversal to stronger weathering and erosion. Wetter conditions can result in both more and less alteration due to the nonlinear relationship between weathering rates, precipitation and sediment transport times. Trends in relative aridity do not follow existing palaeoceanographic records and are not apparently linked to changes in Tibetan or Himalayan elevation, but more closely correlate with global cooling. An apparent opposing trend in the humidity evolution in the Indus compared to southern China, as tracked by spectrally estimated hematite/goethite, likely reflects differences in the topography in the Indus compared to the Pearl River drainage basins, as well as the generally wetter climate in southern China.
This work focuses on the temperature (passive scalar) and velocity characteristics within a turbulent Kármán vortex using a phase-averaging technique. The vortices are generated by a circular cylinder, and the three components of the fluctuating velocity and vorticity vectors,
), are simultaneously measured, along with the fluctuating temperature
and the temperature gradient vector, at nominally the same spatial point in the plane of mean shear at
is the streamwise distance from the cylinder axis and
is the cylinder diameter. We believe this is the first time the properties of fluctuating velocity, temperature, vorticity and temperature gradient vectors have been explored simultaneously within the Kármán vortex in detail. The Reynolds number based on
and the free-stream velocity is
. The phase-averaged distributions of
follow closely the Gaussian distribution for
is the distance from the vortex centre), but not for
. The collapse of the distributions of the mean-square streamwise derivative of the velocity fluctuations within the Kármán vortex implies that the velocity field within the vortex tends to be more locally isotropic than the flow field outside the vortex. A possible physical explanation is that the large and small scales of velocity and temperature fields are statistically independent of each other near the Kármán vortex centre, but interact vigorously outside the vortex, especially in the saddle region, due to the action of coherent strain rate.
Employing atomic-scale simulations, the response of a high-angle grain boundary (GB), the soft/hard GB, against external loading was systematically investigated. Under tensile loading close to the hard orientation, strain-induced dynamic recrystallization was observed to initiate through direct soft-to-hard grain reorientation, which was triggered by stress mismatch, inhibited by surface tension from the soft-hard GB, and proceeded by interface ledges. Such grain reorientation corresponds with expansion and contraction of the hard grain along and perpendicular to the loading direction, respectively, accompanied by local atomic shuffling, providing relatively large normal strain of 8.3% with activation energy of 0.04 eV per atom. Tensile strain and residual dislocations on the hard/soft GB facilitate the initiation of dynamic recrystallization by lowering the energy barrier and the critical stress for grain reorientation, respectively.
Guangxi, a province in southwestern China, has the second highest reported number of HIV/AIDS cases in China. This study aimed to develop an accurate and effective model to describe the tendency of HIV and to predict its incidence in Guangxi. HIV incidence data of Guangxi from 2005 to 2016 were obtained from the database of the Chinese Center for Disease Control and Prevention. Long short-term memory (LSTM) neural network models, autoregressive integrated moving average (ARIMA) models, generalised regression neural network (GRNN) models and exponential smoothing (ES) were used to fit the incidence data. Data from 2015 and 2016 were used to validate the most suitable models. The model performances were evaluated by evaluating metrics, including mean square error (MSE), root mean square error, mean absolute error and mean absolute percentage error. The LSTM model had the lowest MSE when the N value (time step) was 12. The most appropriate ARIMA models for incidence in 2015 and 2016 were ARIMA (1, 1, 2) (0, 1, 2)12 and ARIMA (2, 1, 0) (1, 1, 2)12, respectively. The accuracy of GRNN and ES models in forecasting HIV incidence in Guangxi was relatively poor. Four performance metrics of the LSTM model were all lower than the ARIMA, GRNN and ES models. The LSTM model was more effective than other time-series models and is important for the monitoring and control of local HIV epidemics.