Visualization of the flow distribution inside the piston displacement of a gamma-type stirling engine

The dynamics of the confined flow inside the piston displacement of a Gamma-type Stirling engine operating as a heat pump is experimentally analyzed. The diameter of the piston is 30 mm; 2 mm smaller than the internal diameter of the cold cylinder. As the piston performs its reciprocating motion, the gas leaks around the gap between the piston and the cylinder wall, generating a continuous pulsating motion. In the first part of the cycle air is introduced and compressed by the piston motion, and then the second part of the cycle starts by expanding the air and ejecting it from the assembly chamber. Experimental observations were carried out at frequencies in the range 100 to 300 rpm. The flow was visualized using a vertical laser beam plane oriented in the same axial direction of the piston’s motion. The particles used as trackers are water drops condensed on carbon dioxide microcrystals. Images were taken with a high speed video camera with a frame rate of 1000 fps. PIV techniques were implemented to identify the flow main structures. For analysis purposes, fixed phase averages of the velocity fields are required, due to the turbulent regime observed in this phenomena and its oscillatory nature. Based on experimental measurements it can be demonstrated that the average flow involved is not axisymmetric, although very interestingly, specific inlet and exit regions of the piston-cylinder gap were identified.Papers presented to the 12th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Costa de Sol, Spain on 11-13 July 2016

Workshop on reconstruction schemes for magnetic resonance data: summary of findings and recommendations

[EN] The high fidelity reconstruction of compressed and low-resolution magnetic resonance (MR) data is essential for simultaneously improving patient care, accuracy in diagnosis and quality in clinical research. Sponsored by the Royal Society through the Newton Mobility Grant Scheme, we held a half-day workshop on reconstruction schemes for MR data on the 17 of August 2016 to discuss new ideas from related research fields that could be useful to overcome the shortcomings of the conventional reconstruction methods that have been evaluated up to date. Participants were 21 university students, computer scientists, image analysts, engineers and physicists from institutions from 6 different countries. The discussion evolved around exploring new avenues to achieve high resolution, high quality and fast acquisition of MR imaging. In this article, we summarise the topics covered throughout the workshop and make recommendations for ongoing and future works.The workshop was sponsored by the Royal Society through the Newton Mobility Grant NI150340 to E.O.-I. and M.C.V.H. M.C.V.H. is funded by Row Fogo Charitable Trust; R.O.R. is funded by the Ministry of Education, Research, Culture and Sports of Valencia (Spain) under the programme VALi+d 2015; E.O.-I. is funded by Bogazici University, and the research presented at the workshop was supported by TUBITAK Career Development Grant 112E036, EU Marie Curie IRG Grant FP7-PEOPLE-RG-2009 256528, Tubitak 1001 Research Grant 115S219, and Bogazici University BAP Grant 10844SUP; I.M. is funded by core funds from the University of Edinburgh, including the Scottish Funding Council; A.J.V.B. is funded by the Marie Sklodowska Curie scholarship which is part of the European Union's H2020 Framework Programme (H2020-MSCA-ITN-2014) under the grant agreement number 642685 MacSeNet; and V.G.O. and P.F. are privately funded.Ozturk-Isik, E.; Marshall, I.; Filipiak, P.; Benjamin, AJV.; Ones, VG.; Ortiz-Ramón, R.; Valdes Hernandez, MDC. (2017). Workshop on reconstruction schemes for magnetic resonance data: summary of findings and recommendations. Royal Society Open Science. 4(2):1-4. https://doi.org/10.1098/rsos.160731144

Expanded NK cells from umbilical cord blood and adult peripheral blood combined with daratumumab are effective against tumor cells from multiple myeloma patients

In this study we evaluated the potential of expanded NK cells (eNKs) from two sources combined with the mAbs daratumumab and pembrolizumab to target primary multiple myeloma (MM) cells ex vivo. In order to ascertain the best source of NK cells, we expanded and activated NK cells from peripheral blood (PB) of healthy adult donors and from umbilical cord blood (UCB). The resulting expanded NK (eNK) cells express CD16, necessary for carrying out antibody-dependent cellular cytotoxicity (ADCC). Cytotoxicity assays were performed on bone marrow aspirates of 18 MM patients and 4 patients with monoclonal gammopathy of undetermined significance (MGUS). Expression levels of PD-1 on eNKs and PD-L1 on MM and MGUS cells were also quantified. Results indicate that most eNKs obtained using our expansion protocol express a low percentage of PD-1+ cells. UCB eNKs were highly cytotoxic against MM cells and addition of daratumumab or pembrolizumab did not further increase their cytotoxicity. PB eNKs, while effective against MM cells, were significantly more cytotoxic when combined with daratumumab. In a minority of cases, eNK cells showed a detectable population of PD1+ cells. This correlated with low cytotoxic activity, particularly in UCB eNKs. Addition of pembrolizumab did not restore their activity. Results indicate that UCB eNKs are to be preferentially used against MM in the absence of daratumumab while PB eNKs have significant cytotoxic advantage when combined with this mAb

Hydrodynamic Synchronisation of Model Microswimmers

We define a model microswimmer with a variable cycle time, thus allowing the possibility of phase locking driven by hydrodynamic interactions between swimmers. We find that, for extensile or contractile swimmers, phase locking does occur, with the relative phase of the two swimmers being, in general, close to 0 or pi, depending on their relative position and orientation. We show that, as expected on grounds of symmetry, self T-dual swimmers, which are time-reversal covariant, do not phase-lock. We also discuss the phase behaviour of a line of tethered swimmers, or pumps. These show oscillations in their relative phases reminiscent of the metachronal waves of cilia.Comment: 17 pages, 8 figure

Evaluation of monocytes as carriers for armed oncolytic adenoviruses in murine and Syrian hamster models of cancer

Replication-competent (oncolytic) adenoviruses (OAV) can be adapted as vectors for the delivery of therapeutic genes, with the aim of extending the antitumor effect beyond direct cytolysis. Transgene expression using these vectors is usually intense but short-lived, and repeated administrations are hampered by the rapid appearance of neutralizing antibodies (NAbs). We have studied the performance of monocytes as cell carriers to improve transgene expression in cancer models established in athymic mice and immunocompetent Syrian hamsters. Human and hamster monocytic cell lines (MonoMac6 and HM-1, respectively) were loaded with replication-competent adenovirus-expressing luciferase. Intravenous administration of these cells caused a modest increase in transgene expression in tumor xenografts, but this effect was virtually lost in hamsters. In contrast, intratumoral administration of HM-1 cells allowed repeated cycles of expression and achieved partial protection from NAbs in preimmunized hamsters bearing pancreatic tumors. To explore the therapeutic potential of this approach, HM-1 cells were loaded with a hypoxia-inducible OAV expressing the immunostimulatory cytokine interleukin-12 (IL-12). Three cycles of treatment achieved a significant antitumor effect in the hamster model, and transgene expression was detected following each administration, in contrast with the rapid neutralization of the free virus. We propose monocytes as carriers for multiple intratumoral administrations of armed OAVs

Association of VAV2 and VAV3 polymorphisms with cardiovascular risk factors

Hypertension, diabetes and obesity are cardiovascular risk factors closely associated to the development of renal and cardiovascular target organ damage. VAV2 and VAV3, members of the VAV family proto-oncogenes, are guanosine nucleotide exchange factors for the Rho and Rac GTPase family, which is related with cardiovascular homeostasis. We have analyzed the relationship between the presence of VAV2 rs602990 and VAV3 rs7528153 polymorphisms with cardiovascular risk factors and target organ damage (heart, vessels and kidney) in 411 subjects. Our results show that being carrier of the T allele in VAV2 rs602990 polymorphism is associated with an increased risk of obesity, reduced levels of ankle-brachial index and diastolic blood pressure and reduced retinal artery caliber. In addition, being carrier of T allele is associated with increased risk of target organ damage in males. On the other hand, being carrier of the T allele in VAV3 rs7528153 polymorphism is associated with a decreased susceptibility of developing a pathologic state composed by the presence of hypertension, diabetes, obesity or cardiovascular damage, and with an increased risk of developing altered basal glycaemia. This is the first report showing an association between VAV2 and VAV3 polymorphisms with cardiovascular risk factors and target organ damage

The long-time dynamics of two hydrodynamically-coupled swimming cells

Swimming micro-organisms such as bacteria or spermatozoa are typically found in dense suspensions, and exhibit collective modes of locomotion qualitatively different from that displayed by isolated cells. In the dilute limit where fluid-mediated interactions can be treated rigorously, the long-time hydrodynamics of a collection of cells result from interactions with many other cells, and as such typically eludes an analytical approach. Here we consider the only case where such problem can be treated rigorously analytically, namely when the cells have spatially confined trajectories, such as the spermatozoa of some marine invertebrates. We consider two spherical cells swimming, when isolated, with arbitrary circular trajectories, and derive the long-time kinematics of their relative locomotion. We show that in the dilute limit where the cells are much further away than their size, and the size of their circular motion, a separation of time scale occurs between a fast (intrinsic) swimming time, and a slow time where hydrodynamic interactions lead to change in the relative position and orientation of the swimmers. We perform a multiple-scale analysis and derive the effective dynamical system - of dimension two - describing the long-time behavior of the pair of cells. We show that the system displays one type of equilibrium, and two types of rotational equilibrium, all of which are found to be unstable. A detailed mathematical analysis of the dynamical systems further allows us to show that only two cell-cell behaviors are possible in the limit of $t\to\infty$, either the cells are attracted to each other (possibly monotonically), or they are repelled (possibly monotonically as well), which we confirm with numerical computations

Periodic and Quasiperiodic Motion of an Elongated Microswimmer in Poiseuille Flow

We study the dynamics of a prolate spheroidal microswimmer in Poiseuille flow for different flow geometries. When moving between two parallel plates or in a cylindrical microchannel, the swimmer performs either periodic swinging or periodic tumbling motion. Although the trajectories of spherical and elongated swimmers are qualitatively similar, the swinging and tumbling frequency strongly depends on the aspect ratio of the swimmer. In channels with reduced symmetry the swimmers perform quasiperiodic motion which we demonstrate explicitely for swimming in a channel with elliptical cross section

Ectopic T Cell Receptor-α Locus Control Region Activity in B Cells Is Suppressed by Direct Linkage to Two Flanking Genes at Once

The molecular mechanisms regulating the activity of the TCRα gene are required for the production of the circulating T cell repertoire. Elements of the mouse TCRα locus control region (LCR) play a role in these processes. We previously reported that TCRα LCR DNA supports a gene expression pattern that mimics proper thymus-stage, TCRα gene-like developmental regulation. It also produces transcription of linked reporter genes in peripheral T cells. However, TCRα LCR-driven transgenes display ectopic transcription in B cells in multiple reporter gene systems. The reasons for this important deviation from the normal TCRα gene regulation pattern are unclear. In its natural locus, two genes flank the TCRα LCR, TCRα (upstream) and Dad1 (downstream). We investigated the significance of this gene arrangement to TCRα LCR activity by examining transgenic mice bearing a construct where the LCR was flanked by two separate reporter genes. Surprisingly, the presence of a second, distinct, reporter gene downstream of the LCR virtually eliminated the ectopic B cell expression of the upstream reporter observed in earlier studies. Downstream reporter gene activity was unaffected by the presence of a second gene upstream of the LCR. Our findings indicate that a gene arrangement in which the TCRα LCR is flanked by two distinct transcription units helps to restrict its activity, selectively, on its 5′-flanking gene, the natural TCRα gene position with respect to the LCR. Consistent with these findings, a TCRα/Dad1 locus bacterial artificial chromosome dual-reporter construct did not display the ectopic upstream (TCRα) reporter expression in B cells previously reported for single TCRα transgenes