Jet pumps for thermoacoustic applications: design guidelines based on a numerical parameter study

The oscillatory flow through tapered cylindrical tube sections (jet pumps) is characterized by a numerical parameter study. The shape of a jet pump results in asymmetric hydrodynamic end effects which cause a time-averaged pressure drop to occur under oscillatory flow conditions. Hence, jet pumps are used as streaming suppressors in closed-loop thermoacoustic devices. A two-dimensional axisymmetric computational fluid dynamics model is used to calculate the performance of a large number of conical jet pump geometries in terms of time-averaged pressure drop and acoustic power dissipation. The investigated geometrical parameters include the jet pump length, taper angle, waist diameter and waist curvature. In correspondence with previous work, four flow regimes are observed which characterize the jet pump performance and dimensionless parameters are introduced to scale the performance of the various jet pump geometries. The simulation results are compared to an existing quasi-steady theory and it is shown that this theory is only applicable in a small operation region. Based on the scaling parameters, an optimum operation region is defined and design guidelines are proposed which can be directly used for future jet pump design.Comment: The following article has been accepted by the Journal of the Acoustical Society of America. After it is published, it will be found at http://scitation.aip.org/JAS

Computational analysis of surface-tension-driven coating-defect flow

Bondline readout (BLRO) is a coating defect frequently exhibited on adhesively-bonded, polymeric automotive body panels painted with high-glamor/flow clearcoats. BLRO or telegraphing results from Marangoni-type, surface-tension-driven flows. An efficient numerical code was developed to predict temperature- and concentration-induced BLRO flows to use it as an effective tool for screening and developing potential clearcoat systems. Two numerical codes were developed: a 1-D code based on the lubrication approximation; a 2-D code based on the SIMPLER (Semiimplicit method for pressure-linked equations revised) algorithm. The 1-D code produced BLRO profiles in agreement with those predicted from the 2-D code and those measured from BLRO flow experiments, thus confirming a proposed BLRO mechanism. Moreover, the 1-D code was vastly more time-efficient than the 2-D code due to a severe time-step stability limitation found with the latter.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49314/1/690470404_ftp.pd

Element redistribution along hydraulic and redox gradients of low-centered polygons, Lena Delta, northern Siberia

Wetland soils affected by permafrost are extensive in subarctic and arctic tundra. However, this fact does not imply these soils have been sufficiently investigated. In particular, studies of element translocation processes are scarce. This study was conducted (i) to determine the relationship between water and redox regimes in wetland soils in the Siberian tundra, and (ii) to investigate their influence on the distribution of redox sensitive and associate elements (Mn, Fe, P). Major geomorphic units were chosen (microhigh, polygon rim and slope; microlow, polygon center) from two low-centered polygons in the Lena Delta. Within polygons, redox potential, permafrost, and water level were measured during summer in 1999 and 2000 and (related) compared with element distribution. Manganese, Fe, and P accumulations were preferentially observed in aerobic microhighs. Anaerobic conditions in the microlows lead to a mobilization of Mn, Fe, and P. The elements migrate via water and are immobilized at the microhigh, which acts as an oxidative barrier. The element pattern, indicating an upward flux via water along redox gradients, is explained by higher evapotranspiration from soils and vegetation of the microhighs (Typic Aquiturbel) compared with soils and vegetation of the microlows (Typic Historthel). However, in further research this upward transport should be validated using labeled elements

Mechanism of baricitinib supports artificial intelligence-predicted testing in COVID-19 patients

Baricitinib, is an oral Janus kinase (JAK)1/JAK2 inhibitor approved for the treatment of rheumatoid arthritis (RA) that was independently predicted, using artificial intelligence (AI)-algorithms, to be useful for COVID-19 infection via a proposed anti-cytokine effects and as an inhibitor of host cell viral propagation. We evaluated the in vitro pharmacology of baricitinib across relevant leukocyte subpopulations coupled to its in vivo pharmacokinetics and showed it inhibited signaling of cytokines implicated in COVID-19 infection. We validated the AI-predicted biochemical inhibitory effects of baricitinib on human numb-associated kinase (hNAK) members measuring nanomolar affinities for AAK1, BIKE, and GAK. Inhibition of NAKs led to reduced viral infectivity with baricitinib using human primary liver spheroids. These effects occurred at exposure levels seen clinically. In a case series of patients with bilateral COVID-19 pneumonia, baricitinib treatment was associated with clinical and radiologic recovery, a rapid decline in SARS-CoV-2 viral load, inflammatory markers, and IL-6 levels. Collectively, these data support further evaluation of the anti-cytokine and anti-viral activity of baricitinib and supports its assessment in randomized trials in hospitalized COVID-19 patients

Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: Results from the RA-BUILD study

Background Baricitinib is an oral, reversible, selective Janus kinase 1 and 2 inhibitor. Methods In this phase III, double-blind 24-week study, 684 biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with rheumatoid arthritis and inadequate response or intolerance to ≥1 conventional synthetic DMARDs were randomly assigned 1:1:1 to placebo or baricitinib (2 or 4 mg) once daily, stratified by region and the presence of joint erosions. Endpoint measures included American College of Rheumatology 20% response (ACR20, primary endpoint), Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) score ≤3.3. Results More patients achieved ACR20 response at week 12 with baricitinib 4 mg than with placebo (62% vs 39%, p≤0.001). Compared with placebo, statistically significant improvements in DAS28, SDAI remission, Health Assessment Questionnaire-Disability Index, morning joint stiffness, worst joint pain and worst tiredness were observed. In a supportive analysis, radiographic progression of structural joint damage at week 24 was reduced with baricitinib versus placebo. Rates of adverse events during the treatment period and serious adverse events (SAEs), including serious infections, were similar among groups (SAEs: 5% for baricitinib 4 mg and placebo). One patient had an adverse event of tuberculosis (baricitinib 4 mg); one patient had an adverse event of non-melanoma skin cancer (baricitinib 4 mg). Two deaths and three major adverse cardiovascular events occurred (placebo). Baricitinib was associated with a decrease in neutrophils and increases in low-density and high-density lipoprotein. Conclusions In patients with rheumatoid arthritis and an inadequate response or intolerance to conventional synthetic DMARDs, baricitinib was associated with clinical improvement and inhibition of progression of radiographic joint damage

A Coin Vibrational Motor Swimming at Low Reynolds Number

Low-cost coin vibrational motors, used in haptic feedback, exhibit rotational internal motion inside a rigid case. Because the motor case motion exhibits rotational symmetry, when placed into a fluid such as glycerin, the motor does not swim even though its oscillatory motions induce steady streaming in the fluid. However, a piece of rubber foam stuck to the curved case and giving the motor neutral buoyancy also breaks the rotational symmetry allowing it to swim. We measured a 1 cm diameter coin vibrational motor swimming in glycerin at a speed of a body length in 3 seconds or at 3 mm/s. The swim speed puts the vibrational motor in a low Reynolds number regime similar to bacterial motility, but because of the oscillations of the motor it is not analogous to biological organisms. Rather the swimming vibrational motor may inspire small inexpensive robotic swimmers that are robust as they contain no external moving parts. A time dependent Stokes equation planar sheet model suggests that the swim speed depends on a steady streaming velocity V stream ~ Re 1/2s U 0 where U 0 is the velocity of surface oscillations, and streaming Reynolds number Re s = U 20/(ων) for motor angular frequency ω and fluid kinematic viscosity ν

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). BCAC is funded by Cancer Research UK [C1287/A10118, C1287/A12014] and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 16 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defense (W81XWH-10-1- 0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Project established by the National Cancer Institute and National Human Genome Research Institute.This is the author accepted manuscript. The final version is available from BMJ Group at http://dx.doi.org/10.1136/jmedgenet-2015-103529

Oral Abstracts 7: RA ClinicalO37. Long-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach

Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naïve early (<1 year) RA patients. Therapy was adjusted at week 26: ADA + MTX-responders (R) who achieved DAS28 (CRP) <3.2 at weeks 22 and 26 (Period 1, P1) were re-randomized to withdraw or continue ADA and PBO + MTX-R continued randomized therapy for 52 weeks (P2); IR-patients received open-label (OL) ADA + MTX during P2. This post hoc analysis evaluated the proportion of patients at week 78 with DAS28 (CRP) <3.2, HAQ-DI <0.5, and/or ΔmTSS ≤0.5 by initial treatment. To account for patients who withdrew ADA during P2, an equivalent proportion of R was imputed from ADA + MTX-R patients. Results: At week 26, significantly more patients had low disease activity, normal function, and/or no radiographic progression with ADA + MTX vs PBO + MTX (Table 1). Differences in clinical and functional outcomes disappeared following additional treatment, when PBO + MTX-IR (n = 348/460) switched to OL ADA + MTX. Addition of OL ADA slowed radiographic progression, but more patients who received ADA + MTX from baseline had no radiographic progression at week 78 than patients who received initial PBO + MTX. Conclusions: Early RA patients treated with PBO + MTX achieved comparable long-term clinical and functional outcomes on a group level as those who began ADA + MTX, but only when therapy was optimized by the addition of ADA in PBO + MTX-IR. Still, ADA + MTX therapy conferred a radiographic benefit although the difference did not appear to translate to an additional functional benefit. Disclosures: P.E., AbbVie, Merck, Pfizer, UCB, Roche, BMS—Provided Expert Advice, Undertaken Trials, AbbVie—AbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. R.F., AbbVie, Pfizer, Merck, Roche, UCB, Celgene, Amgen, AstraZeneca, BMS, Janssen, Lilly, Novartis—Research Grants, Consultation Fees. S.F., AbbVie—Employee, Stocks. A.K., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, UCB—Research Grants, Consultation Fees. H.K., AbbVie—Employee, Stocks. S.R., AbbVie—Employee, Stocks. J.S., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, GlaxoSmithKline, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB—Research Grants, Consultation Fees. R.V., AbbVie, BMS, GlaxoSmithKline, Human Genome Sciences, Merck, Pfizer, Roche, UCB Pharma—Consultation Fees, Research Support. Table 1.Week 78 clinical, functional, and radiographic outcomes in patients who received continued ADA + MTX vs those who continued PBO + MTX or added open-label ADA following an inadequate response ADA + MTX, n/N (%)a PBO + MTX, n/N (%)b Outcome Week 26 Week 52 Week 78 Week 26 Week 52 Week 78 DAS28 (CRP) <3.2 246/466 (53) 304/465 (65) 303/465 (65) 139/460 (30)*** 284/460 (62) 300/460 (65) HAQ-DI <0.5 211/466 (45) 220/466 (47) 224/466 (48) 150/460 (33)*** 203/460 (44) 208/460 (45) ΔmTSS ≤0.5 402/462 (87) 379/445 (86) 382/443 (86) 330/459 (72)*** 318/440 (72)*** 318/440 (72)*** DAS28 (CRP) <3.2 + ΔmTSS ≤0.5 216/462 (47) 260/443 (59) 266/443 (60) 112/459 (24)*** 196/440 (45) 211/440 (48)*** DAS28 (CRP) <3.2 + HAQ-DI <0.5 + ΔmTSS ≤0.5 146/462 (32) 168/443 (38) 174/443 (39) 82/459 (18)*** 120/440 (27)*** 135/440 (31)** aIncludes patients from the ADA Continuation (n = 105) and OL ADA Carry On (n = 259) arms, as well as the proportional equivalent number of responders from the ADA Withdrawal arm (n = 102). bIncludes patients from the MTX Continuation (n = 112) and Rescue ADA (n = 348) arms. Last observation carried forward: DAS28 (CRP) and HAQ-DI; Multiple imputations: ΔmTSS. ***P < 0.001 and **iP < 0.01, respectively, for differences between initial treatments from chi-squar