Respiratory disease and breathing abnormalities worsen with dehydration of the upper airways. We find that humidification of inhaled air occurs by evaporation of water over mucus lining the upper airways in such a way as to deliver an osmotic force on mucus, displacing it towards the epithelium. This displacement thins the periciliary layer of water beneath mucus while thickening topical water that is partially condensed from humid air on exhalation. With the rapid mouth breathing of dry air, this condensation layer, not previously reported while common to transpiring hydrogels in nature, can deliver an osmotic compressive force of up to around 100 cm H2O on underlying cilia, promoting adenosine triphosphate secretion and activating neural pathways. We derive expressions for the evolution of the thickness of the condensation layer, and its impact on cough frequency, inflammatory marker secretion, cilia beat frequency and respiratory droplet generation. We compare our predictions with human clinical data from multiple published sources and highlight the damaging impact of mouth breathing, dry, dirty air and high minute volume on upper airway function. We predict the hypertonic (or hypotonic) saline mass required to reduce (or amplify) dysfunction by restoration (or deterioration) of the structure of ciliated and condensation water layers in the upper airways and compare these predictions with published human clinical data. Preserving water balance in the upper airways appears critical in light of contemporary respiratory health challenges posed by the breathing of dirty and dry air.

The application of drag-control strategies on canonical wall-bounded turbulence, such as periodic channel and zero- or adverse-pressure-gradient boundary layers, raises the question on how to distinguish consistently the origin of control effects under different reference conditions. We employ the RD identity (Renard & Deck, J. Fluid Mech., vol. 790, 2016, pp. 339–367) to decompose the mean friction drag and investigate the control effects of uniform blowing and suction applied to an NACA4412 airfoil at chord Reynolds numbers $Re_c=200\,000$ and $400\,000$. The connection of the drag reduction/increase by using blowing/suction with the turbulence statistics (including viscous dissipation, turbulence kinetic energy production and spatial growth of the flow) across the boundary layer, subjected to adverse or favourable pressure gradients, is examined. We found that the inner and outer peaks of the contributions associated with the friction-drag generation show good scaling with either inner or outer units, respectively. They are also independent of the Reynolds number, control scheme and intensity of the blowing/suction. The small- and large-scale structures are separated with an adaptive scale-decomposition method, namely the empirical mode decomposition (EMD), which aims to analyse the scale-specific contribution of turbulent motions to friction-drag generation. Results unveil that blowing on the suction side of the airfoil is able to enhance the contribution of large-scale motions and to suppress that of small scales; however, suction behaves contrarily. The contributions related to cross-scale interactions remain almost unchanged with different control strategies.

Patients with liver cancer or space-occupying cysts suffer from malnutrition due to compression of gastric and digestive structures, liver and cancer-mediated dysmetabolism, and impaired nutrient absorption. As proportion of these patients requires removal of lesions through hepatic resection, it is important to evaluate the effects of malnutrition on post-hepatectomy outcomes. In our study approach, 2011–2017 National Inpatient Sample was used to isolate in-hospital hepatectomy cases, which were stratified using malnutrition (composite of malnutrition, sarcopenia and weight loss/cachexia). The malnutrition-absent controls were matched to cases using nearest neighbour propensity score matching method and compared with the following endpoints: mortality, length of stay, hospitalisation costs and postoperative complications. There were 2531 patients in total who underwent hepatectomy with matched number of controls from the database; following the match, malnutrition cohort (compared with controls) was more likely to experience in-hospital death (6·60 % v. 5·25 % P < 0·049, OR 1·27, 95 % CI 1·01, 1·61) and was more likely to have higher length of stay (18·10 d v. 9·32 d, P < 0·001) and hospitalisation costs ($278 780 v. $150 812, P < 0·001). In terms of postoperative complications, malnutrition cohort was more likely to experience bleeding (6·52 % v. 3·87 %, P < 0·001, OR 1·73, 95 % CI 1·34, 2·24), infection (6·64 % v. 2·49 %, P < 0·001, OR 2·79, 95 % CI 2·07, 3·74), wound complications (4·5 % v. 1·38 %, P < 0·001, OR 3·36, 95 % CI 2·29, 4·93) and respiratory failure (9·40 % v. 4·11 %, P < 0·001, OR 2·42, 95 % CI 1·91, 3·07). In multivariate analysis, malnutrition was associated with higher mortality (P < 0·028, adjusted OR 1·3, 95 % CI 1·03, 1·65). Thus, we conclude that malnutrition is a risk factor of postoperative mortality in patients undergoing hepatectomy.

ABSTRACT IMPACT: Plasma and CSF are not reliable estimates of drug exposure in tissue compartments relevant for treatment and prevention of infectious diseases. OBJECTIVES/GOALS: Globally, high dose fluconazole is widely used in the management of cryptococcal meningitis. While it is known to readily penetrate into cerebrospinal (CSF), less is known about drug concentrations in brain parenchymal tissues. Similarly, distribution of fluconazole into gynecological tissues has not been robustly characterized. METHODS/STUDY POPULATION: With informed consent from next-of-kin, we conducted autopsies within 24h of death for hospitalized Ugandans receiving fluconazole for treatment or secondary prophylaxis of cryptococcal meningitis. Dosing history was abstracted from medical chart and caregiver interviews. Fluconazole concentrations were determined using high-performance liquid chromatography- tandem mass spectrometry (LC-MS/MS) in plasma, CSF, 10 brain compartments (frontal, parietal, and occipital lobes, corpus callosum, globus pallidus, hippocampus, midbrain, medulla oblongata, spinal cord, and choroid plexus) and 4 female genital compartments (cervix, vagina, ovary, and uterus), depending on tissue availability. Descriptive statistics of tissue to plasma ratios were used to describe concentrations relative to plasma. RESULTS/ANTICIPATED RESULTS: Fluconazole concentrations were measured in available tissues of 21 individuals with detectable fluconazole in plasma. Daily doses of fluconazole were 200 mg (n=4), 400 mg (n=1), 800 mg (n=4), 1200 mg (n=9) or unknown (n=3). CSF concentrations (n=10) ranged from 93-1380% (median 100%) of plasma while brain concentrations (n=3) across all 10 compartments ranged from 45% to 89% (median 69%) of plasma. In the female genital tract, cervical concentrations (n=10) were 9-78% (median 65%) of plasma and in the 2 individuals with available tissue, concentrations in vaginal, ovarian, and uterine tissues were similar to cervix, ranging from 63-105% of plasma. DISCUSSION/SIGNIFICANCE OF FINDINGS: Measuring drug concentrations directly in tissues, the presumed site of action, improves estimates of drug efficacy. While fluconazole concentrations in CSF were similar to plasma, actual brain tissues were consistently lower. Concentrations were similar between upper and lower female genital tracts, but were consistently lower than plasma.

ABSTRACT IMPACT: The knowledge acquired from my research can inform the development of early diagnostic methods for HIV-associated neurocognitive disorders. OBJECTIVES/GOALS: In the era of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains high but the neural mechanisms are unclear. We examined whether older people with HIV (PWH) with minimal cognitive impairment have reduced functional connectivity in frontostriatal circuits compared to controls. METHODS/STUDY POPULATION: 99 PWH (mean age 56.6 years, 75% male, 62% Black, mean duration of HIV-infection 26.2 years ±9.3, 90% viral load <50 copies, 98% on stable cART) and 38 demographically-comparable controls (mean age 54.5 years, 71% male, 58% Black) participated in a cross-sectional study. A 7-domain neuropsychological battery and an Activities of Daily Living index were used to determine HAND diagnoses: 32 PWH met criteria for asymptomatic to mild HAND. Motor skill was assessed using the Grooved Pegboard Test by measuring performance speed. Structural MRI and resting-state functional MRI were collected. Seed-to-voxel analyses were conducted using 4 distinct regions in the striatum as seed regions. We used a voxel threshold of p<0.001 and cluster threshold of p<0.05 (FDR-corrected) after controlling for demographic variables. RESULTS/ANTICIPATED RESULTS: Compared to controls, PWH had lower resting state functional connectivity between the default mode region of the striatum (i.e., medial caudate) and bilateral superior frontal gyrus, supplementary motor cortex and paracingulate gyrus (p<0.05; cluster size: 567 voxels). Also, compared to controls, PWH had reduced resting state functional connectivity between the motor division of the striatum (i.e., posterior putamen) and anterior cingulate cortex and left supplementary motor cortex (p<0.05, cluster size: 405 voxels). Performance speed on the Grooved Pegboard motor test negatively correlated with functional connectivity between the motor region of the striatum and supplementary motor frontal regions in all participants (Spearman’s rho=-0.18, p=0.04). DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results support the hypothesis that frontostriatal abnormalities are widely present in PWH and might play a key role in HAND development. Our data suggest that dysfunction within the frontostriatal circuits may be involved in motor impairment in PWH, and ongoing inflammation may contribute to motor impairment and frontostriatal injury.

The mean skin-friction drag in a wall-bounded turbulent flow can be decomposed into different physics-informed contributions based on the mean and statistical turbulence quantities across the wall layer. Following Renard & Deck’s study (J. Fluid Mech., vol. 790, 2016, pp. 339–367) on the skin-friction drag decomposition of incompressible wall-bounded turbulence, we extend their method to a compressible form and use it to investigate the effect of density and viscosity variations on skin-friction drag generation, using direct numerical simulation data of compressible turbulent channel flows. We use this novel decomposition to study the skin-friction contributions associated with the molecular viscous dissipation and the turbulent kinetic energy production and we investigate their dependence on Reynolds and Mach number. We show that, upon application of the compressibility transformation of Trettel & Larsson (Phys. Fluids, vol. 28, 2016, 026102), the skin-friction drag contributions can be only partially transformed into the equivalent incompressible ones, as additional terms appear representing deviations from the incompressible counterpart. Nevertheless, these additional contributions are found to be negligible at sufficiently large equivalent Reynolds number and low Mach number. Moreover, we derive an exact relationship between the wall heat flux coefficient and the skin-friction drag coefficient, which allows us to relate the wall heat flux to the skin-friction generation process.

In this work, we investigate misfit dislocations in PbTe/PbSe heteroepitaxial systems using the concurrent atomistic–continuum (CAC) method. A potential model containing the long-range Coulombic interaction and short-range Buckingham potential is developed for the system. By considering the minimum potential energy of relaxed interface structures for various initial conditions and PbTe layer thicknesses, the equilibrium structure of misfit dislocations and the dislocation spacings in PbTe/PbSe(001) heteroepitaxial thin films are obtained as a function of the PbTe layer thicknesses grown on a PbSe substrate. The critical layer thickness above which misfit dislocations inevitably form, the structure of the misfit dislocations at the interfaces, and the dependence of average dislocation spacing on PbTe layer thickness are obtained and discussed. The simulation results provide an explanation for the narrowing of the spread of the distribution of misfit dislocation spacing as layer thickness increases in PbTe/PbSe(001) heteroepitaxy.

Controlling microscopic morphology of energetic materials is of significant interest for the improvement of their performance and production consistency. As an important insensitive high explosive material, triaminotrinitrobenzene (TATB) has attracted tremendous research effort for military grade explosives and propellants. In this study, a new, rapid and inexpensive synthesis method for monodispersed TATB microparticles based on micelle-confined precipitation was developed. Surfactant with proper hydrophilic-lipophilic balance value was found to be critical to the success of this synthesis. The morphology of the TATB microparticles can be tuned between quasi-spherical and faceted by controlling the speed of recrystallization.

Morphological control of energetic materials (EM) is highly desired because ill-defined morphology arising from variations in processing method and supplier make it impossible to reproducibly engineer their physicochemical properties. As the most powerful, non nuclear energetic material to date, 2,4,6,8,10,12-hexanitro -2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) has been the subject of significant interest for improved applications in military grade explosives. Here we report a new method for recrystallization of CL-20 from irregular bulk EMs using a surfactant assisted self-assembly process to produce uniform spherical micron-sized particles. Detailed electron microscopy studies indicate that surfactant plays a critical role in controlling CL-20 morphology. Combined X-ray diffraction and Raman spectroscopy results reveal that the resultant spherical CL-20 particles exhibit an orthorhombic β-phase crystal structure. This material is expected to display enhanced functional reproducibility due to its monodisperse nature as well as decreased shock sensitivity due to their sub-micron particle size.

We recently developed a vacuum assisted micelle confinement synthesis for spherical microparticles of CL-20 with outstanding monodispersity. These microparticles are promising energetic material for explosive devices with enhanced and predictable performances. In this work, to facilitate further development and application of this synthesis, the particle growth process was monitored by in-situ dynamic light scattering measurements. The result was interpreted by a finite element model to obtain critical parameters. These parameters were then used to predict the behavior and product quality of batch synthesis under various operation conditions.

Cell membrane fatty acids influence fundamental properties of the plasma membrane, including membrane fluidity, protein functionality, and lipid raft signalling. Evidence suggests that dietary n-3 PUFA may target the plasma membrane of immune cells by altering plasma membrane lipid dynamics, thereby regulating the attenuation of immune cell activation and suppression of inflammation. As lipid-based immunotherapy might be a promising new clinical strategy for the treatment of inflammatory disorders, we conducted in vitro and in vivo experiments to examine the effects of n-3 PUFA on CD4+ T cell membrane order, mitochondrial bioenergetics and lymphoproliferation. n-3 PUFA were incorporated into human primary CD4+ T cells phospholipids in vitro in a dose-dependent manner, resulting in a reduction in whole cell membrane order, oxidative phosphorylation and proliferation. At higher doses, n-3 PUFA induced unique phase separation in T cell-derived giant plasma membrane vesicles. Similarly, in a short-term human pilot study, supplementation of fish oil (4 g n-3 PUFA/d) for 6 weeks in healthy subjects significantly elevated EPA (20 : 5n-3) levels in CD4+ T cell membrane phospholipids, and reduced membrane lipid order. These results demonstrate that the dynamic reshaping of human CD4+ T cell plasma membrane organisation by n-3 PUFA may modulate down-stream clonal expansion.

The evolution of arid environments in northern China was a major environmental change during the Quaternary. Here we present the dating and environmental proxy results from a 35 m long core (A-WL10ZK-1) collected from the Ulan Buh Desert (UBD), along with supplemental data from four other cores. The UBD is one of the main desert dune fields in China and our results indicate the UBD has undergone complex evolution during the late Quaternary. Most of the present UBD was covered by a Jilantai-Hetao Mega-paleolake lasting until ~ 90 ka ago. A sandy desert environment prevailed throughout the UBD during the last glacial period and early Holocene. A wetland environment characterized by the formation of numerous interdunal ponds in the northern UBD occurred at ~ 8–7 ka, although a dune field persisted in the southern UBD. The modern UBD landscape formed after these wetlands dried up. During the last 2000 years, eolian sand from the Badain Jaran Desert has invaded the northern UBD, while farming and overgrazing resulted in the formation of the eastern UBD. We suggest that the formation of UBD landforms is related to the disintegration of the megalake Jilantai-Hetao and to summer monsoon changes during the last glaciation and Holocene.

This paper uses the ideodynamic model to assess the impact of persuasive messages on candidate preference in the 1992 presidential election. The methodology is based on approaches common to the natural sciences. These approaches suggested that opinion predictions are most robust when they explicitly omit such factors as opinion poli values, incumbency, and economic performance. Instead, the only persuasive messages used to predict opinion came from 3,394 stories from the Major Paper library of the NEXIS electronic data base scored by computer for news favorable and unfavorable to George Bush, Bill Clinton, and Ross Perot. The scores were used in the equations of ideodynamics to compute media share time trends that predicted 55 public opinion polls with R2 of 0.84 and 0.79 for Clinton and Perot, respectively. These high R2 values together with the significance of the model's parameters suggested that the news media comprised the dominant influence on candidate preference. Campaign stories were also scored for coverage of different issues, and this coverage was related to good and bad news for the candidates.