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An 8-week feeding trial was conducted to evaluate the effects of dietary n-3 LC-PUFA levels on growth performance, tissue fatty acid profiles and relative expression of genes involved in the lipid metabolism of mud crab (Scylla paramamosain). Ten isonitrogenous diets were formulated to contain five n-3 LC-PUFA levels at 7 and 12 % dietary lipid levels. The highest weight gain and specific growth rate were observed in crabs fed the diets with 19·8 and 13·2 mg/g n-3 LC-PUFA at 7 and 12 % lipid, respectively. Moisture and lipid contents in hepatopancreas and muscle were significantly influenced by dietary n-3 LC-PUFA at the two lipid levels. The DHA, EPA, n-3 LC-PUFA contents and n-3:n-6 PUFA ratio in hepatopancreas and muscle significantly increased as dietary n-3 LC-PUFA levels increased at both lipid levels. The expression levels of Δ-6 fatty acyl desaturase and acyl-CoA oxidase in hepatopancreas increased significantly, and expression levels of fatty acid synthase, carnitine palmitoyltransferase I and hormone-sensitive TAG lipase were down-regulated, with increased dietary n-3 LC-PUFA regardless of lipid level. Based on weight gain, n-3 LC-PUFA requirements of S. paramamosain were estimated to be 20·1 and 12·7 mg/g of diet at 7 and 12 % dietary lipid, respectively. Overall, dietary lipid level influenced lipid metabolism, and purified, high-lipid diets rich in palmitic acid reduced the n-3 LC-PUFA requirement of juvenile mud crab.
An artificial intelligence (AI) control system is developed to maximize the mixing rate of a turbulent jet. This system comprises of six independently operated unsteady minijet actuators, two hot-wire sensors placed in the jet and genetic programming for the unsupervised learning of a near-optimal control law. The ansatz of this law includes multi-frequency open-loop forcing, sensor feedback and nonlinear combinations thereof. Mixing performance is quantified by the decay rate of the centreline mean velocity of the jet. Intriguingly, the learning process of AI control discovers the classical forcings, i.e. axisymmetric, helical and flapping achievable from conventional control techniques, one by one in the order of increased performance, and finally converges to a hitherto unexplored forcing. Careful examination of the control landscape unveils typical control laws, generated in the learning process, and their evolutions. The best AI forcing produces a complex turbulent flow structure that is characterized by periodically generated mushroom structures, helical motion and an oscillating jet column, all enhancing the mixing rate and vastly outperforming others. Being never reported before, this flow structure is examined in various aspects, including the velocity spectra, mean and fluctuating velocity fields and their downstream evolution, and flow visualization images in three orthogonal planes, all compared with other classical flow structures. Along with the knowledge of the minijet-produced flow and its effect on the initial condition of the main jet, these aspects cast valuable insight into the physics behind the highly effective mixing of this newly found flow structure. The results point to the great potential of AI in conquering the vast opportunity space of control laws for many actuators and sensors and in optimizing turbulence.
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.
The present study evaluated the effects of dietary Zn level on growth performance, serum and hepatopancreas metabolites, expression of genes involved in lipid and energy metabolism, and the signalling pathway of dietary Zn-induced lipolysis. Five isonitrogenous and isolipidic diets were formulated to contain different Zn levels: 46·4 (basal diet), 77·2, 87·0, 117·1 and 136·8 mg/kg, respectively. The results indicated that shrimp fed the diet containing Zn at 117·1 mg/kg had higher weight gain and specific growth rate, and the lowest feed intake and feed conversion rate, than shrimp fed the other diets. The deposition rate of Zn in whole body significantly decreased with increasing dietary Zn level. Dietary Zn prevented the accumulation of free radicals and improved antioxidant activities by increasing Cu/Zn superoxide dismutase and reducing malondialdehyde in hepatopancreas. Dietary Zn supplementation enhanced lipase activity and adiponectin, which could promote TAG breakdown and fatty acid oxidation and lead to reduced lipid in hepatopancreas. The mRNA expressions of ob-rb, adipor, camkkβ, ampk, cd36, mcd and cpt1 involved in Zn-induced lipid catabolism were up-regulated, and the expressions of srebp, acc, fas and scd1 were down-regulated. The mRNA levels of SLC39 family genes (zip3, zip9, zip11 and zip14) in hepatopancreas were up-regulated with increasing dietary Zn level. The results demonstrated that dietary Zn level could significantly affect growth performance, tissue deposition of Zn, lipid metabolites and expression of genes involved in lipogenesis and lipolysis in Litopenaeus vannamei.
The aim of the present study was to investigate the effects of dietary Zn level on growth performance, Zn bioaccumulation, antioxidant capacity and innate immunity in juvenile mud crabs (Scylla paramamosain). Six semi-purified diets were formulated to contain dietary Zn levels of 44·5, 56·9, 68·5, 97·3, 155·6 or 254·7 mg/kg. Dietary Zn level significantly influenced percentage weight gain (PWG), with the highest observed in crabs fed the diet containing 97·3 mg/kg Zn. Tissue Zn concentrations significantly increased as dietary Zn levels increased from 44·5 to 254·7 mg/kg. Retention of Zn in hepatopancreas increased with dietary Zn levels up to 68·5 mg/kg and then significantly decreased. Moreover, inadequate dietary Zn (44·5 and 56·9 mg/kg) reduced antioxidation markers including total superoxide dismutase (SOD) and Cu/Zn SOD activities and total antioxidant level. Crabs fed the diet with 44·5 mg/kg Zn also showed significantly lower expression of genes involved in antioxidant status, such as Cu/Zn SOD, glutathione peroxidase, catalase and thioredoxin than those fed diets containing 68·5 and 97·3 mg/kg Zn. The highest activities of phenoloxidase and alkaline phosphatase were recorded in crabs fed the diets containing 68·5 and 97·3 mg/kg Zn. Expression levels of prophenoloxidase and toll-like receptor 2 were higher in crabs fed the 97·3 mg/kg Zn diet compared with crabs fed the other diets. Based on PWG alone, the optimal dietary Zn level was estimated to be 82·9 mg/kg, with 68·5 to 97·3 mg/kg recommended for maintaining optimal Zn bioaccumulation, oxidation resistance and innate immune response of juvenile mud crabs.
Most previous researches indicated that impaired inhibition to emotional stimuli could be one of the important cognitive characteristics of depression individuals. The antisaccade tasks which composed of prosaccade task (PS) and antisaccade task (AS) were often used to investigate response inhibition.
This study aimed to investigate the volition inhibition toward emotional stimuli in depressed mood undergraduates (DM).
Subjects were grouped as 21 DM and 25 non-depressed undergraduates (ND) on the Beck Depression Inventory and Self-rating Depression Scale. The antisaccade tasks were conducted to examine the inhibition abilities by varying the arousal level of volition (low and high) of the tasks, with happy, neutral and sad facial expressions as stimuli.
The results showed that at the low volition level in the AS condition, the correct saccade latency in the DM were significant slower than the ND; The DM had reliable higher direction error rates in response to emotional facial expressions, especially for sad expressions. However, all of the differences disappeared in the high volition level antisaccade tasks. The amplitude errors data were not influenced by emotional facial expressions, and there were no group differences across tasks.
These results indicated the DM showed slower speed of cognitive processing and impaired inhibition abilities toward emotional faces than the ND, particularly for sad faces, but these abilities will be repaired in the high arousal level of volition, which enlighten us that training the DM's volition level of inhibition could prove to be an effective strategy to alleviate depression.
We examine the scaling of the two-point correlation function for
, the energy dissipation rate, over a range of values of the separation
between the two points and the Taylor microscale Reynolds number
. The correlation function is estimated from hot-wire measurements in grid turbulence, along the axes of wakes and jets, and along the centreline of a fully developed channel flow. When
exceeds a value of approximately 300, a condition which is achieved for both plane and circular jets, the correlation function collapses over nearly all values of
when the normalization uses Kolmogorov scales. However, there is no collapse in either the power-law range or dissipative range when the normalization is on the integral (or external) length scale, which indicates that there is no self-similarity based on external scales. Although the maximum value of
is not much larger than
, the behaviour of the energy dissipation correlation function on the axes of plane and circular jets seems consistent with the first similarity hypothesis of Kolmogorov (Dokl. Akad. Nauk SSSR, vol. 30, 1941, pp. 299–303) but not with the revised phenomenology of Kolmogorov (J. Fluid Mech., vol. 13, 1962, pp. 82–85).
Silicon carbide (SiC) is ideally suitable as a sensor material in harsh environments. Despite the brittleness in the macroscopic scale, plasticity in SiC is observed at small component length-scales. Previous nanoindentation based study combining experiment and numerical approaches of single-crystal 6H-SiC has shown that slip activation is rather complex, and that non-basal slip could potentially dominate the plastic deformation behaviour. In this study, we investigated the local deformation response evolution of shear strain directly under and in the vicinity of the indenter tip. The results show the pyramidal slip families contribute significantly to the deformation process.
In order to map quantitative trait loci (QTLs) for allometries of body compositions and metabolic traits in chicken, we phenotypically characterize the allometric growths of multiple body components and metabolic traits relative to BWs using joint allometric scaling models and then establish random regression models (RRMs) to fit genetic effects of markers and minor polygenes derived from the pedigree on the allometric scalings. Prior to statistically inferring the QTLs for the allometric scalings by solving the RRMs, the LASSO technique is adopted to rapidly shrink most of marker genetic effects to zero. Computer simulation analysis confirms the reliability and adaptability of the so-called LASSO-RRM mapping method. In the F2 population constructed by multiple families, we formulate two joint allometric scaling models of body compositions and metabolic traits, in which six of nine body compositions are tested as significant, while six of eight metabolic traits are as significant. For body compositions, a total of 14 QTLs, of which 9 dominant, were detected to be associated with the allometric scalings of drumstick, fat, heart, shank, liver and spleen to BWs; while for metabolic traits, a total of 19 QTLs also including 9 dominant be responsible for the allometries of T4, IGFI, IGFII, GLC, INS, IGR to BWs. The detectable QTLs or highly linked markers can be used to regulate relative growths of the body components and metabolic traits to BWs in marker-assisted breeding of chickens.
Besnoitia besnoiti is an obligate intracellular apicomplexan protozoan parasite, which causes bovine besnoitiosis. Recently increased emergence within Europe was responsible for significant economic losses in the cattle industry due to the significant reduction of productivity. However, still limited knowledge exists on interactions between B. besnoiti and host innate immune system. Here, B. besnoiti bradyzoites were successfully isolated from tissue cysts located in skin biopsies of a naturally infected animal, and we aimed to investigate for the first time reactions of polymorphonuclear neutrophils (PMN) exposed to these vital bradyzoites. Freshly isolated bovine PMN were confronted to B. besnoiti bradyzoites. Scanning electron microscopy (s.e.m.)- and immunofluorescence microscopy-analyses demonstrated fine extracellular networks released by exposed bovine PMN resembling suicidal NETosis. Classical NETosis components were confirmed via co-localization of extracellular DNA decorated with histone 3 (H3) and neutrophil elastase (NE). Live cell imaging by 3D holotomographic microscopy (Nanolive®) unveiled rapid vital NETosis against this parasite. A significant increase of autophagosomes visualized by specific-LC3B antibodies and confocal microscopy was observed in B. besnoiti-stimulated bovine PMN when compared to non-stimulated group. As such, a significant positive correlation (r = 0.37; P = 0.042) was found between B. besnoiti-triggered suicidal NETosis and autophagy. These findings suggest that vital- as well as suicidal-NETosis might play a role in early innate host defence mechanisms against released B. besnoiti bradyzoites from tissue cysts, and possibly hampering further parasitic replication. Our data generate first hints on autophagy being associated with B. besnoiti bradyzoite-induced suicidal NETosis and highlighting for first time occurrence of parasite-mediated vital NETosis.
The present study aimed to investigate whether dietary choline can regulate lipid metabolism and suppress NFκB activation and, consequently, attenuate inflammation induced by a high-fat diet in black sea bream (Acanthopagrus schlegelii). An 8-week feeding trial was conducted on fish with an initial weight of 8·16 ± 0·01 g. Five diets were formulated: control, low-fat diet (11 %); HFD, high-fat diet (17 %); and HFD supplemented with graded levels of choline (3, 6 or 12 g/kg) termed HFD + C1, HFD + C2 and HFD + C3, respectively. Dietary choline decreased lipid content in whole body and tissues. Highest TAG and cholesterol concentrations in serum and liver were recorded in fish fed the HFD. Similarly, compared with fish fed the HFD, dietary choline reduced vacuolar fat drops and ameliorated HFD-induced pathological changes in liver. Expression of genes of lipolysis pathways were up-regulated, and genes of lipogenesis down-regulated, by dietary choline compared with fish fed the HFD. Expression of nfκb and pro-inflammatory cytokines in liver and intestine was suppressed by choline supplementation, whereas expression of anti-inflammatory cytokines was promoted in fish fed choline-supplemented diets. In fish that received lipopolysaccharide to stimulate inflammatory responses, the expression of nfκb and pro-inflammatory cytokines in liver, intestine and kidney were all down-regulated by dietary choline compared with the HFD. Overall, the present study indicated that dietary choline had a lipid-lowering effect, which could protect the liver by regulating intrahepatic lipid metabolism, reducing lipid droplet accumulation and suppressing NFκB activation, consequently attenuating HFD-induced inflammation in A. schlegelii.
The regulation of lipogenesis and lipolysis mechanisms related to consumption of lipid has not been studied in swimming crab. The aims of the present study were to evaluate the effects of dietary lipid levels on growth, enzymes activities and expression of genes of lipid metabolism in hepatopancreas of juvenile swimming crab. Three isonitrogenous diets were formulated to contain crude lipid levels at 5·8, 9·9 and 15·1 %. Crabs fed the diet containing 15·1 % lipid had significantly lower growth performance and feed utilisation than those fed the 5·8 and 9·9 % lipid diets. Crabs fed 5·8 % lipid had lower malondialdehyde concentrations in the haemolymph and hepatopancreas than those fed the other diets. Highest glutathione peroxidase in haemolymph and superoxide dismutase in hepatopancreas were observed in crabs fed 5·8 % lipid. The lowest fatty acid synthase and glucose 6-phosphate dehydrogenase activities in hepatopancreas were observed in crabs fed 15·1 % lipid, whereas crabs fed 5·8 % lipid had lower carnitine palmitoyltransferase-1 activity than those fed the other diets. Crabs fed 15·1 % lipid showed lower hepatopancreas expression of genes involved in long-chain-PUFA biosynthesis, lipoprotein clearance, fatty acid uptake, fatty acid oxidation, lipid anabolism and lipid catabolism than those fed the other diets, whereas expression of some genes of lipoprotein assembly and fatty acid oxidation was up-regulated compared with crabs fed 5·8 % lipid. Overall, high dietary lipid level can inhibit growth, reduce antioxidant enzyme activities and influence lipid metabolic pathways to regulate lipid deposition in crab.
In vivo positron emission tomography (PET) using [C11]-labeled Pittsburgh Compound B ([C11]PiB) has previously been shown to detect amyloid-β (Aβ) in late-onset Alzheimer disease (LOAD) brain; however, the sensitivity of this technique for detecting β-amyloidosis in autosomal dominant Alzheimer disease (ADAD) has not been systematically investigated. To validate [C11]PiB PET as a useful biomarker of β-amyloidosis, we measured the cortical and regional standardized uptake value ratios (SUVRs) in 16 ADAD and 15 LOAD cases and compared them with histopathologic measures of β-amyloidosis in postmortem brain. The PiB-PET data were obtained between 40–70 min after bolus injection of ∼15 mCi of [11C]PiB. MRI and PiB-PET images were co-registered and SUVRs were generated for several brain regions. Using Aβ immunohistochemistry (10D5, Eli Lilly), the burden of Aβ plaques was quantified in 16 regions of interest using an area fraction fractionator probe (Stereo Investigator, MicroBrightfield, VT). There were regional variations in Aβ plaque burden with highest densities observed in the neocortical areas and the striatum. On spearman correlations, in vivo PiB-PET correlated with postmortem Aβ plaque burden in both LOAD and ADAD, with strongest correlations seen in neocortical areas. In summary, [C11]PiB-PET has utility as a biomarker in both ADAD and LOAD.
This presentation will enable the learner to:
1.Discuss how PET-PiB beta-amyloid imaging is used as a potential biomarker of Alzheimer disease (AD)
2.Correlate postmortem neuropathologic evidence of beta-amyloidosis with PET-PiB data, and learn that PET-PiB is a potentially useful tool to detect beta-amyloidosis in presymptomatic and symptomatic individuals
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.
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.
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.
High-energy electron radiography (HEER) has been proposed for time-resolved imaging of materials, high-energy density matter, and for inertial confinement fusion. The areal-density resolution, determined by the image intensity information is critical for these types of diagnostics. Preliminary experimental studies for different materials with the same thickness and the same areal-density target have been imaged and analyzed. Although there are some discrepancies between experimental and theory analysis, the results show that the density distribution can indeed be attained from HEER. The reason for the discrepancies has been investigated and indicates the importance of the uniformity in the transverse distribution beam illuminating the target. Furthermore, the method for generating a uniform transverse distribution beam using octupole magnets was studied and verified by simulations. The simulations also confirm that the octupole field does not affect the angle-position correlation in the center part beam, a critical requirement for the imaging lens. A more practical method for HEER using collimators and octupoles for generating more uniform beams is also described. Detailed experimental results and simulation studies are presented in this paper.
OBJECTIVES/SPECIFIC AIMS: Determine if synthetic or endogenously produced butyrate can delay Parkinson’s disease (PD) progression, attenuate PD associated GI dysfunction, and impact the gut-microbiota in mice expressing human mutant aSyn. METHODS/STUDY POPULATION: Two transgenic mouse models expressing human mutant alpha-synuclein (aSyn) will be used. Transgenic mice expressing aSyn A53T display GI dysfunction before motor deficit onset and will be used to investigate treatment impact on PD associated GI dysfunction. Mice expressing aSyn Y39C more accurately recapitulate age-related neuropathology and behavioral deficits and will be used to assess treatment impact on PD-associated neuropathology, motor, and cognitive function. Mice will receive a synthetic sodium butyrate, sodium phenylbutyrate, or a synbiotic treatment regimen for 3 months. Disease progression will be assessed by aSyn brain and gut neuropathology, brain and gut inflammatory status, behavioral deficits, and gastrointestinal function. In addition, fecal and gut-microbiota composition and neuroprotective gene expression in the brain will be investigated. RESULTS/ANTICIPATED RESULTS: Our preliminary data shows that both sodium butyrate and sodium phenylbutyrate delay disease progression in aSyn Y39C mice. Butyrate-treated mice have reduced aSyn oligomerization, reduced Lewy body formation, and improved motor and cognitive function compared to placebo-treated mice. 16S rRNA sequencing did not reveal fecal-microbiota shifts between treatment groups or with age progression. Further analysis assessing expression levels for genes with anti-oxidant and protein degradation roles will be performed to determine if sodium butyrate and sodium phenylbutyrate similarly impact cellular mechanisms to delay neurodegeneration. Our future experiments will focus on comparing sodium butyrate and synbiotic treatment outcomes in aSyn A53T mice. DISCUSSION/SIGNIFICANCE OF IMPACT: Our lab developed a Tg mouse model that more accurately recapitulate age-related symptoms, pathology, and mechanisms observed in PD patients compared with animal models onset by neurotoxins. Our use of an age-dependent model of a severe form of Parkinsonism, DLB, will better predict clinical outcomes in PD populations. We will be the first to assess if elevating select microbial product production enhances neuroprotective brain activity in a PD model. Results obtained will further characterize gut-brain axis communication mechanisms. These proposed experiments will be the first to determine if elevating microbial products improves GI deficits associated with PD and may lead to insight on the gut-brain axis role in PD. Overall, this proposal will be the first to investigate a novel, highly accessible treatment with the potential to delay PD progression and target motor, cognitive, and GI deficits associated with PD. Due to the current FDA approval of probiotics and prebiotics that enhance butyrate production, results obtained may be quickly translated for clinical use.
We first analytically show, starting with the Navier–Stokes equations, that the value of the derivative flatness is controlled by pressure diffusion of energy, viscous destructive effects and large-scale effects (decay and/or production). The latter two terms tend to zero when the Taylor-microscale Reynolds number
is sufficiently large. We argue that the pressure-diffusion term should also tend to a constant at large
. Available data for the velocity derivative flatness,
, in different turbulent flows are re-examined and interpreted in the light of the finite-Reynolds-number effect. It is found that
can differ from flow to flow at moderate
; for a given flow,
may also depend on the initial conditions. The data for
in various flows, e.g. along the axis in the far field of plane and circular jets, and grid turbulence, show that it approaches a constant, with a value slightly larger than 10, when
is sufficiently large. This behaviour for
is supported, at least qualitatively, by our analytical considerations. The constancy of
violates the refined similarity hypothesis introduced by Kolmogorov (J. Fluid Mech., vol. 13, 1962, pp. 82–85) to account for the intermittency of the energy dissipation rate. It is not, however, inconsistent with Kolmogorov’s original similarity hypothesis (Dokl. Akad. Nauk SSSR, vol. 30, 1941, pp. 299–303), although we contend that the power-law relation
(Kolmogorov 1962), which is widely accepted in the literature, has in reality been almost invariably used to ‘model’ the finite-Reynolds-number effect for the laboratory data and has been strongly influenced by the weighting given to the atmospheric surface layer data. The inclusion of the latter data has misled previous investigations of how