Non-contact Set Research Articles

Culturally Specific Messaging and the Explanation of Contact in Impacted Bilinguals

A sketch is offered of a framework that would abandon the familiar notion of a language and the accompanying question of whether it has changed under contact. The framework would focus instead on speakers and on the linguistic consequences of people contact. Speakers in contact settings are not failing or deviating from a language’s norm while attempting to say the same things that are said in non-contact settings; rather, they are succeeding at saying different things. New arrivals face vast differences in the conceptualization of referents between their home precursor setting and the new encounter setting. These differences in conceptualization give rise to large numbers of changes in what speakers say. In most cases, these new things they say are just that, new speech or new messaging with no change in the grammar. But in a minority of cases, the new messaging does have linguistic, that is, grammatical consequences. Changes in the grammars of people in contact thus result not only, and perhaps not primarily, from formal copying or modeling but are responses to new conceptualizations prevailing in the new environment. The distinction between expressions reflecting only new conceptualizations, and those reflecting new conceptualizations and new grammar carries theoretical implications for the way linguists think about the grammars of bilinguals. And it carries applied implications for the way educators think about the linguistic performance of bilingual students, especially in social settings where they are minoritized. Data are drawn from the speech of Latin Americans and their descendants in New York City and other U.S. locales.

Two-scale methods for convex envelopes

We develop two-scale methods for computing the convex envelope of a continuous function over a convex domain in any dimension. This hinges on a fully nonlinear obstacle formulation (see A. M. Oberman [Proc. Amer. Math. Soc. 135 (2007), pp. 1689–1694]). We prove convergence and error estimates in the max norm. The proof utilizes a discrete comparison principle, a discrete barrier argument to deal with Dirichlet boundary values, and the property of flatness in one direction within the non-contact set. Our error analysis extends to a modified version of the finite difference wide stencil method provided by Oberman [Math. Models Methods Appl. Sci. 18 (2008), pp. 759–780].

Acoustic Levitation: A Novel Approach to Study the Physical Properties of Blood in Normal Subjects and in Patients with Sickle Cell Disease

Acoustic levitation is a novel technique which we have developed for the purpose of measuring physical properties of blood, plasma and red cells in a non-contact setting, which eliminates issues and concerns related to the interaction of blood with non-physiological surfaces. Figure 1 shows a levitated blood drop between the ultrasound transducer and reflector. By exciting drop shape oscillation, we can study its vibrational behavior and infer its viscoelastic properties.Whole blood samples were collected from volunteers in tubes containing Ethylenediaminetetraacetic acid (EDTA) as anticoagulant. Patients' samples were studied using left-over material after a clinically-ordered CBC had been performed. Samples with different hematocrit (Hct) were obtained in the same subject, by removing or adding autologous plasma after centrifugation.To calibrate the device, we compared the results obtained by our instrument with the blood viscosity determination provided by a cone-plate rotational rheometer (HR-2, Hybrid rheometer - TA Instrument). Figure 2 (Left) shows the results from levitator and rotational rheometer.We also compared normal samples with samples of patients with sickle cell disease (SCD) over a wide range of Hct values, obtained by addition or removal of autologous plasma. As shown in Figure 2 (Right), for any given Hct the viscosity measurements obtained by the levitation device were greater in blood of patients with sickle cell disease compared with normal controls.For each sample of blood from patients with sickle cell disease, we assessed viscosity with the levitation device at different values of Hct (autologous plasma addition or removal) and were able to determine the slope of this regression line. We also compared the viscosity value determined at an arbitrary Hct value of 55% among all the clinical samples collected from patients with SCD. As shown in Figure 3, when these data were analyzed as a function of the fetal Hb content of each blood sample (obtained from the total Hb value of the unmodified clinical sample and the % of Hb F determined by HPLC), a clear negative correlation emerged between total Hb F values (in g/dl) and viscosity, measured as either the slope of the regression line or the value at a fixed Hct of 55%. The clinical samples included several patients treated with hydroxycarbamide, showing an important correlation between higher values of Hb F and lower blood viscosity.These studies demonstrate that acoustic levitation is a non-contact technique which can be successfully used to measure physical properties of human blood. We show that viscosity measurements obtained with this new device compare very favorably with traditional rotational viscometer. Furthermore, this new technology can reproducibly measure viscosity over a wide range of Hct values and for any given Hct, it shows that the viscosity of samples from patients with SCD is greater than normal controls. We also show that our measurement is sensitive enough to detect variation in viscosity associated with different absolute values of fetal Hb in blood, and more specifically showing lower viscosity with higher Hb F values, opening the possibility that this technique could be used to determine changes in viscosity associated with hydroxycarbamide therapy in patients with sickle cell disease. [Display omitted] DisclosuresAnsari Hosseinzadeh:National Science Foundation: Research Funding. Brugnara:National Science Foundation: Research Funding. Holt:National Science Foundation: Research Funding.

Bone Marrow Stromal Cell Mediated Drug Resistance in AML Cells: Role of Extracellular Vesicles and AKT Signaling

Accumulating evidence suggests that bone marrow stromal micro-environment act as sanctuary site for acute myeloid leukemia (AML) cells and affords protection from conventional chemotherapy agents. Recently, there has been considerable interest in extracellular vesicles (EVs) and their role in intercellular communication. We had previously reported that there is significant stromal cell mediated drug resistance in acute promyelocytic leukemia (APL) which was predominantly driven by up-regulation of the NF-kB pathway in the malignant cells (Ganesan S et al, Leukemia 2016). Though there are reports of similar stromal cell mediated protection against chemotherapy in non-M3 AML cells, there is limited data on the role EVs play, if any, in inducing such chemotherapy resistance. We undertook a preliminary study to evaluate the role of EVs in inducing resistance to chemotherapeutic agents in AML.We demonstrated that direct stromal co-culture experiments with AML cell lines as well as primary AML cells showed a significant stromal mediated protective effect against both cytosine arabinoside (AraC) and daunorubicin (DNR) [U937: AraC p < 0.01, DNR p < 0.001 (n=5); primary AML cells: AraC p < 0.01, DNR p < 0.001 (n=26)]. Gene expression profiling (GEP) analysis of AML cell line U937 co-cultured with HS-5 revealed a significant enrichment of genes involved in PI3K-AKT signaling pathway (p < 0.0001) followed by NF-kB pathway genes. It has been previously reported that on direct co-culture with stromal cells there is activation of the PI3K-AKT pathway in AML cells leading to drug resistance (Tabe Y et al. Cancer Res 2007). It is also well recognized that PI3K-AKT pathway can drive NF-kB signaling, which is consistent with our earlier reported observation in APL. We hypothesize that this effect of PI3K-AKT activation could be mediated by EVs without direct malignant and stromal cell interaction as well. Towards this, we isolated stromal EVs as previously described (Suzanne M et al, Blood 2016). The size and concentration of EVs was characterized by NanoSight and flow cytometry (data not shown).We demonstrated an activation of PI3K-AKT signaling by showing phosphorylation of AKT (P-AKTser473) in U937 cells when treated with stromal EVs (figure 1A). We further demonstrated that stromal EVs were able to mediate a protective effect against AraC and DNR similar to that seen on direct co-culture with HS-5 cells [AraC p < 0.01, DNR p < 0.01 (n=3)]. This was further confirmed by looking at the pathway genes using Q-PCR, where an increased expression of PI3K-AKT signaling was observed in AML cells upon treatment with stromal EVs. The activation PI3K signaling was also confirmed by showing down regulation of PTEN [p < 0.01 (n=5)] which is a negative regulator of PI3K-AKT signaling. Further, to demonstrate the role of stromal EVs induced PI3K-AKT signaling in drug resistance, we treated the leukemic cells with a small molecule inhibitor of PI3 kinase (LY294002-10uM) along with AraC and DNR in the presence of stromal EVs. We noted that inhibiting PI3K-AKT signaling along with AraC or DNR was able to overcome the resistance mediated by stromal EVs (figure 1B). The mechanism of inducing apoptosis by LY294002 along with DNR or AraC (in the presence of stroma or stromal EVs) probably involves a TP53 dependent apoptosis pathway as evidenced through upregulation of TP53 and its target apoptotic genes such as BAD, CASP9 and PUMA (AraC- figure 1C, DNR - data not shown).Our study thus illustrates the complexity of cellular crosstalk between leukemic cells and its microenvironment in inducing drug resistance. This resistance can be mediated by non-contact setting via stromal EVs through up regulation of PI3K-AKT signaling in myeloid leukemic cells. Our data highlights the need for additional studies that are required to explore and characterize in detail the cargo of these EVs and the mechanisms by which they mediate drug resistance. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Assessment of the Tribological Contact Between Sliding Surfaces Via an Entropy Approach

The interaction observed between two surfaces in contact with one another is part of a number of physical processes, such as wear. In this paper, we present a numerical study of the asperities between two surfaces in contact with each other. The real contact area between two surfaces varies due to the multiple roughness scales caused by the stochastic nature of asperities. In our research, we employ a tribological system comprising two partitions: C1 is the contact set (CS), where the two surfaces are in direct contact with each other, and C2 is the noncontact set, where the two surfaces are not in contact with each other. Here, we have developed a new numerical model to describe the CS using ε-entropy to prove the existence of a minimum value for entropy in sliding contact scenarios. In this system, the lower and upper bounds of entropy are determined through the Kolmogorov approach using the aforementioned model. Using this model, we conclude that the ε-entropy value is bound between ln 2 and 2·ln 2 for a tribological system comprising two partitions. Additionally, we conclude that a correlation between the stochastic tribological contact behavior and the rate of entropy change is the key parameter in thermal nonequilibrium scenarios.

Kiselman's principle, the Dirichlet problem for the Monge–Ampère equation, and rooftop obstacle problems

First, we obtain a new formula for Bremermann type upper envelopes, that arise frequently in convex analysis and pluripotential theory, in terms of the Legendre transform of the convex- or plurisubharmonic-envelope of the boundary data. This yields a new relation between solutions of the Dirichlet problem for the homogeneous real and complex Monge-Ampere equations and Kiselman's minimum principle. More generally, it establishes partial regularity for a Bremermann envelope whether or not it solves the Monge-Ampere equation. Second, we prove the second order regularity of the solution of the free-boundary problem for the Laplace equation with a rooftop obstacle, based on a new a priori estimate on the size of balls that lie above the non-contact set. As an application, we prove that convex- and plurisubharmonic-envelopes of rooftop obstacles have bounded second derivatives.

Millisecond direct measurement of the magnetocaloric effect of a Fe2P-based compound by the mirage effect

We present direct measurements of the magnetocaloric effect on a Fe2P-based compound induced by a milliseconds pulsed magnetic field of 1 T to test their possible use in high frequency (up to 100 Hz) thermomagnetic cycles. The reported measurements were performed with an innovative and versatile non-contact set up based on the mirage effect. The adiabatic temperature change of a MnFeP0.45As0.55 sample is presented and compared with measurements performed varying the same magnetic field in a time interval of 1 s and 100 ms. These results demonstrate the absence of kinetic constraints in the first-order phase transition of this sample induced on the milliseconds time scale. The study of the materials' response to millisecond magnetic field pulses represents a fundamental test for the development of more powerful and efficient magnetic refrigerators.

The Effect of Carbon Dioxide (CO2) Laser on Sandblasting with Large Grit and Acid Etching (SLA) Surface.

The purpose of this study was to investigate the effect of 6W power Carbon Dioxide Laser (CO2) on the biologic compatibility of the Sandblasting with large grit and acid etching (SLA) titanium discs through studying of the Sarcoma Osteogenic (SaOS-2) human osteoblast-like cells viability. Sterilized titanium discs were used together with SaOS-2 human osteoblast-like cells. 6 sterilized SLA titanium discs of the experimental group were exposed to irradiation by CO2 laser with a power of 6W and 10.600nm wavelength, at fixed frequency of 80Hz during 45 seconds in both pulse and non-contact settings. SaOS-2 human osteoblast-like cells were incubated under 37°C in humid atmosphere (95% weather, 5% CO2) for 72 hours. MTT test was performed to measure the ratio level of cellular proliferation. The results indicated that at 570nm wavelength, the 6W CO2 laser power have not affected the cellular viability. CO2 laser in 6w power has had no effect on the biologic compatibility of the SLA titanium surface.

The immunosuppressive effect of Wharton's jelly stromal cells depends on the timing of their licensing and on lymphocyte activation

Mesenchymal stromal cells (MSC) have been proven to have potent immunosuppressive action and hence have been proposed for the treatment of severe Graft Versus Host Disease. However, in most models, MSC were added at the same time of lymphocyte stimulation, which is quite different from what occurs in vivo. To investigate how the timing of lymphocyte activation and the exposure to activation-related cytokines (licensing) can influence the immunosuppressive action of Wharton's jelly stromal cells (WJSC). WJSC, licensed or not with activation-related cytokines, were added lymphocytes the same time or 24 hours after their stimulation with phytohaemoagglutinin. Proliferation of lymphocytes and cytokines production was measured after three days co-culture. Lymphocytes stimulated in the presence of WJSC displayed a dramatic decrease in proliferation and production of cytokines, in spite of normal expression of activation markers. The suppression was weakened when targeted lymphocytes were seperated by a membrane and partially rescued by the addition of exogenous l-tryptophan, suggesting a major role for indoleamine 2,3-dioxigenase with a probable paracrine effect. Licensing of WJSC increased the immunosuppressive effect, in both contact and non-contact settings. The timing of WJSC licensing was crucial for the immunosuppressive action. Lymphocytes pre-stimulated alone for 24 h, and added afterwards to non-licensed WJSC, showed normal or even increased proliferation. On the other hand, their proliferation was strongly inhibited by licensed WJSC. WJSC have a potent immunosuppressive function best realized with direct contact, and increased by licensing signals before and during lymphocyte stimulation. Our results could contribute to the set up of new WJSC-based therapies for severe autoimmuno disorders.

Activation of mesangial cells by platelets in systemic lupus erythematosus via a CD154-dependent induction of CD40

Platelets are potential contributors to glomerular injury via the release of chemotactic and/or mitogenic mediators upon activation or through direct CD154/CD40-dependent interaction with cell components of the glomerulus. We examined whether platelets could activate mesangial cells and the potential role of the platelet-associated CD154. Thrombin-activated platelets from systemic lupus erythematosus (SLE) patients or from disease or healthy controls were grown with human mesangial cells in the presence or not of a neutralizing anti-CD154 antibody either in contact or in a noncontact setting, the platelets and mesangial cells being separated by a pore size semipermeable membrane. The induction of mesangial cell surface antigens was assayed by flow cytometry. The quantification of mesangial cell proliferation was performed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and the production of transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor (PDGF) and soluble CD40 were measured by enzyme-linked immunosorbent assay (ELISA). Activated platelets from patients with SLE could induce an up-regulation of the expression of CD40 on mesangial cells with a concomitant release of soluble CD40. This induction required a direct contact between platelets and mesangial cells and was dependent upon the platelet-associated CD154. Pathologic consequences of the up-regulation of CD40 were a CD40-dependent stimulation of the proliferation of mesangial cells and a CD40-dependent increased production of TGF-beta1 by these cells. Platelets from patients with SLE can activate mesangial cells through CD40/CD154 interactions, leading to an induction of proliferation of the mesangial cells and an enhanced production of TGF-beta1, a profibrotic cytokine.

Pointwise a posteriori error control for elliptic obstacle problems

We consider a finite element method for the elliptic obstacle problem over polyhedral domains in ? d , which enforces the unilateral constraint solely at the nodes. We derive novel optimal upper and lower a posteriori error bounds in the maximum norm irrespective of mesh fineness and the regularity of the obstacle, which is just assumed to be Holder continuous. They exhibit optimal order and localization to the non-contact set. We illustrate these results with simulations in 2d and 3d showing the impact of localization in mesh grading within the contact set along with quasi-optimal meshes.

Culture system for extensive production of CD19+IgM+ cells by human cord blood CD34+ progenitors.

We established a co-culture system with a monolayer of the murine bone marrow (BM) stroma cell line, MS-5, in which human cord blood CD34+ cells differentiated to CD19+ cells. The addition of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) highly enhanced the production of CD19+ cells. The expansion of the cell numbers was over 10(3)-fold. Furthermore, a significant proportion (<45%) of the cells expressed surface IgM (sIgM) after 5 weeks of co-culture. CD34+CD19- cells also showed a similar development of CD19+ cells and CD19+sigM+ cells. Filter separation of MS-5 cells and CD34+ cells did not inhibit the growth of CD19+ cells. However, when further purified CD34+CD19-CD13- CD33- cells were cultured in the presence of MS-5 cells with or without a separation filter, CD19+ cells did not appear in the non-contact setting. This result suggested that the highly purified CD34+CD19-CD13-CD33- progenitors require the cell-cell contact for the development of CD19+ cells, whereas other CD34+ fractions contain progenitors that do not require the contact. This co-culture system should be useful for the study of early human B-lymphopoiesis.