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.

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.

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.

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.

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, $u_{i}$ and $\unicode[STIX]{x1D714}_{i}$ ( $i=1,2,3$ ), are simultaneously measured, along with the fluctuating temperature $\unicode[STIX]{x1D703}$ and the temperature gradient vector, at nominally the same spatial point in the plane of mean shear at $x/d=10$ , where $x$ is the streamwise distance from the cylinder axis and $d$ 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 $d$ and the free-stream velocity is $2.5\times 10^{3}$ . The phase-averaged distributions of $\unicode[STIX]{x1D703}$ and $u_{i}$ follow closely the Gaussian distribution for $r/d\leqslant 0.2$ ( $r$ is the distance from the vortex centre), but not for $r/d>0.2$ . 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.

OBJECTIVES/SPECIFIC AIMS: The objective of this project is to determine whether HRV, collected peri-operatively, is predictive of cognitive decline among older adults who undergo elective surgery/anesthesia. METHODS/STUDY POPULATION: This project is a part of the ongoing INTUIT/PRIME study, which is collecting pre- and post-operative cognitive testing, fMRI imaging, CSF samples, and EEG recordings from 200 older adults (age ≥ 60) undergoing elective non-cardiac/non-neurologic surgery scheduled to last > 2 hours at Duke University Medical Center and Duke Regional Hospital. This project utilizes data from the first 60 INTUIT participants who contributed continuous heart rate data before and during surgery. Participants undergo cognitive testing prior to surgery (baseline) and at 6 weeks after surgery. Our primary dependent variable is the change in the composite score from baseline to 6-weeks. Delirium is assessed in the hospital with the twice daily 3D-CAM tool, so we will report the proportion of individuals with 6-week cognitive decline who exhibited delirium in the days following surgery. Participants’ echocardiogram (ECG) recordings are extracted pre- and intraoperatively from B650/B850 patient monitors with VSCapture software. HRV is defined as the variability between successive R-spikes or inter-beat-intervals on ECG. RESULTS/ANTICIPATED RESULTS: We anticipate that lower intraoperative HRV is associated with worse cognitive decline at 6 weeks after surgery. As secondary objectives, we will determine whether pre-operative HRV or change in HRV (from pre-operative to intra-operative measures) are predictive of cognitive decline after surgery. We expect that in-hospital delirium will be detected in a higher proportion of those with 6-week cognitive decline, compared to those with stable or improved cognition at 6 weeks. DISCUSSION/SIGNIFICANCE OF IMPACT: HRV may address the present need for pre- and intra-operative cognitive risk stratification in the elderly. Physiological indices like HRV have the potential to dramatically change our understanding of CI in older adults undergoing surgery, as they offer an accessible, cost-effective, and non-invasive means whereby clinicians, particularly those unfamiliar with the nuances of geriatric and CI/dementia-related care, can monitor patients and refer those at high-risk of CI after surgery for early intervention.

Keratins are the main structural proteins of wool fibres, and it is thought that variation in the keratins may affect wool fibre characteristics. Polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) analyses were used to investigate four regions of the ovine keratin gene KRT31 including a portion of the promoter, the exon 1, exon 3 and exon 7 regions. Initially, in a screening panel of 300 New Zealand Romney, Merino and White Dorper sheep obtained from 26 farms, three, two, two and two PCR-SSCP banding patterns were observed for these four regions, respectively. The promoter region, the exon 1 and exon 3 regions contained two single nucleotide polymorphisms (SNPs) and the exon 7 region contained one SNP. The effect of the variation found in the promoter region on wool traits was subsequently investigated in 485 Southdown × Merino-cross lambs from seven sire-lines. The three variants identified in the original 300 sheep (named A, B and C) were observed with frequencies of 56, 29 and 15%, respectively. The presence of A and B had no significant effect on wool traits, but the presence of C was found to be associated with an increase in greasy fleece weight (GFW), clean fleece weight (CFW) and mean staple length (MSL). There was an effect of genotype on CFW and MSL, with BC sheep producing wool of higher CFW and MSL than AA, AB, AC and BB sheep. These results suggest that ovine KRT31 might be a useful candidate gene for improving wool traits.

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.