Radiative Boundary Layer Flow in Porous Medium due to Exponentially Shrinking Permeable Sheet

This communication pertains to the study of radiative heat transfer in boundary layer flow over an exponentially shrinking permeable sheet placed at the bottom of fluid saturated porous medium. The porous medium has permeability of specified form. The fluid considered here is Newtonian, without phase change, optically dense, absorbing-emitting radiation but a nonscattering medium. The setup is subjected to suction to contain the vorticity in the boundary layer. The radiative heat flux in the energy equation is accounted by Rosseland approximation. The thermal conductivity is presumed to vary with temperature in a linear fashion. The governing partial differential equations are reduced to ordinary differential equations by similarity transformations. The resulting system of nonlinear ordinary differential equations is solved numerically by fourth-order Runge-Kutta scheme together with shooting method. The pertinent findings displayed through figures and tables are discussed.</jats:p

The inflammasome: more than a protective innate immune mechanism: Preview

Little is known about the inflammasome beyond its function in innate immune response. In this issue of Immunity, Tyrkalska et al. report that the inflammasome regulates the balance between erythroid and myeloid differentiation in model systems, providing insights into hematopoietic lineage bias associated with inflammatory conditions

GATA1 and cooperating mutations in myeloid leukaemia of Down syndrome

Myeloid leukaemia of Down syndrome (ML‐DS) is an acute megakaryoblastic/erythroid leukaemia uniquely found in children with Down syndrome (constitutive trisomy 21). It has a unique clinical course, being preceded by a pre‐leukaemic condition known as transient abnormal myelopoiesis (TAM), and provides an excellent model to study multistep leukaemogenesis. Both TAM and ML‐DS blasts carry acquired N‐terminal truncating mutations in the erythro‐megakaryocytic transcription factor GATA1. These result in exclusive production of a shorter isoform (GATA1s). The majority of TAM cases resolve spontaneously without the need for treatment; however, around 10% acquire additional cooperating mutations and transform to leukaemia, with differentiation block and clinically significant cytopenias. Transformation is driven by the acquisition of additional mutation(s), which cooperate with GATA1s to perturb normal haematopoiesis

On Dissipative Radiative MHD Boundary Layer Flow in a Porous Medium Over a Non Isothermal Stretching Sheet

The paper aims at investigating the effects of Ohmic and viscous dissipations on the steady two-dimensional radiative boundary-layer flow of an incompressible, viscous, electrically conducting fluid caused by a linearly stretching sheet placed at the bottom of fluid saturated porous medium in the presence of uniform transverse magnetic field. The radiative heat flux is assumed to follow Rosseland approximation. The governing system of partial differential equations are converted to ordinary differential equations by using the similarity transformations, which are then solved numerically using shooting method with fourth order Runge-Kutta scheme. The dimensionless temperature distribution is computed for different thermo-physical parameters and presented graphically. The temperature gradient at the sheet and skin friction coefficient are derived numerically and presented through graph

The impact of trisomy 21 on foetal haematopoiesis

The high frequency of a unique neonatal preleukaemic syndrome, transient abnormal myelopoiesis (TAM), and subsequent acute myeloid leukaemia in early childhood in patients with trisomy 21 (Down syndrome) points to a specific role for trisomy 21 in transforming foetal haematopoietic cells. N-terminal truncating mutations in the key haematopoietic transcription factor GATA1 are acquired during foetal life in virtually every case. These mutations are not leukaemogenic in the absence of trisomy 21. In mouse models, deregulated expression of chromosome 21-encoded genes is implicated in leukaemic transformation, but does not recapitulate the effects of trisomy 21 in a human context. Recent work using primary human foetal liver and bone marrow cells, human embryonic stem cells and iPS cells shows that prior to acquisition of GATA1 mutations, trisomy 21 itself alters human foetal haematopoietic stem cell and progenitor cell biology causing multiple abnormalities in myelopoiesis and B-lymphopoiesis. The molecular basis by which trisomy 21 exerts these effects is likely to be extremely complex, to be tissue-specific and lineage-specific and to be dependent on ontogeny-related characteristics of the foetal microenvironment

A protocol for simultaneous high-sensitivity genotyping and chromatin accessibility profiling in single cells.

Single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq) resolves the heterogeneity of epigenetic states across cells but does not typically capture exonic mutations, which limits our knowledge of how somatic mutations alter chromatin landscapes. Here, we present a plate-based approach coupling high-sensitivity genotyping of genomic loci with high-content scATAC-seq libraries from the same single cells. We first describe steps for optimization of genotyping primers, followed by detailed guidance on the preparation of both scATAC-seq and single-cell genotyping libraries, fully automated on high-throughput liquid handling platforms. For complete details on the use and execution of this protocol, please refer to Turkalj, Jakobsen et al.

Sufficiency criteria for a class of p-valent analytic functions of complex order

In this paper we obtain extensions of sufficient conditions for analytic functions f(z) in the open unit disk \mathcal{U} to be starlike and convex of complex order. Our results unify and extend some starlikeness and convexity conditions for analytic functions discussed by Mocanu [1988], Uyanik et al. [2011], Goyal et al. [2012] and others

South-South Collaboration in CCAFS for developing capacity on weather index insurance

Climate risk management has become a key area for research and policy dialogue due to increasing threats of disasters and climate extremes, which are likely to increase due to climate change. Global south (including Latin America, Africa, South and South-east Asia) is a major hotspot for climatic risk challenges due to high exposure to climate extremes when compared to temperate regions, high incidences of poverty, poor enabling environments and low regulatory support. With this backdrop, the CGIAR Research Program Climate Change, Agriculture and Food Security (CCAFS) has been working in Africa, Latin America and Asia together with its partners on accelerating climatic risk management through a dedicated research flagship to Climate services and safety nets. A workshop was thus organized by CCAFS to mobilize stakeholders in different regions to facilitate the diffusion of learnings and advances in climate risk management from one region to another. This workshop was planned after feedback and follow-up from South: South collaboration on climatic risk management workshop in New York, concurrent with the needs and demands of the stakeholders

The effects of monoclonal anti‐CD47 on RBCs, compatibility testing, and transfusion requirements in refractory acute myeloid leukemia

BACKGROUND CD47 is a novel therapeutic target in the treatment of solid‐organ and hematologic malignancies. CD47 is also expressed on RBCs. Here, we report our experience of the RBC effects and the impact on blood bank testing and transfusion management in a Phase 1 trial of the humanized anti‐CD47 monoclonal antibody Hu5F9‐G4 in relapsed or primary refractory acute myeloid leukemia (AML) (NCT02678338). STUDY DESIGN AND METHODS Nineteen patients with relapsed or primary refractory AML treated across five UK centers were included for analysis. Patients received escalating doses of Hu5F9‐G4. Serial laboratory data were collected to evaluate impact on hemoglobin (Hb), markers of hemolysis (bilirubin, lactate dehydrogenase, reticulocyte count), transfusion requirements, and blood compatibility testing. RESULTS A decline in Hb was observed with drug administration (median Hb change, −1.0 g/dL; range, 0.4–1.6) with associated increase in transfusion requirements. Patients responded to transfusion with a median Hb increment per unit of 1.0 g/dL. RBC agglutination was seen in all cases without associated change in Hb, lactate dehydrogenase, bilirubin, or reticulocyte count. Nine of 19 (47%) patients developed a newly positive antibody screen with a pan‐agglutinin identified in plasma. Invalid ABO blood grouping occurred in 4 of 12 (33%) non–group O patients due to anomalous reactivity in the reverse ABO‐type results. CONCLUSIONS Treatment with Hu5F9‐G4 in patients with AML resulted in an Hb decline and increased transfusion requirements. Problems with ABO blood typing and compatibility testing were widely observed and should be expected by centers treating recipients of Hu5F9‐G4

Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial

Enasidenib; Conventional careEnasidenib; Atenció convencionalEnasidenib; Atención convencionalThis open-label, randomized, phase 3 trial (NCT02577406) compared enasidenib, an oral IDH2 (isocitrate dehydrogenase 2) inhibitor, with conventional care regimens (CCRs) in patients aged ≥60 years with late-stage, mutant-IDH2 acute myeloid leukemia (AML) relapsed/refractory (R/R) to 2 or 3 prior AML-directed therapies. Patients were first preselected to a CCR (azacitidine, intermediate-dose cytarabine, low-dose cytarabine, or supportive care) and then randomized (1:1) to enasidenib 100 mg per day or CCR. The primary endpoint was overall survival (OS). Secondary endpoints included event-free survival (EFS), time to treatment failure (TTF), overall response rate (ORR), hematologic improvement (HI), and transfusion independence (TI). Overall, 319 patients were randomized to enasidenib (n = 158) or CCR (n = 161). The median age was 71 years, median (range) enasidenib exposure was 142 days (3 to 1270), and CCR was 36 days (1 to 1166). One enasidenib (0.6%) and 20 CCR (12%) patients received no randomized treatment, and 30% and 43%, respectively, received subsequent AML-directed therapies during follow-up. The median OS with enasidenib vs CCR was 6.5 vs 6.2 months (HR [hazard ratio], 0.86; P = .23); 1-year survival was 37.5% vs 26.1%. Enasidenib meaningfully improved EFS (median, 4.9 vs 2.6 months with CCR; HR, 0.68; P = .008), TTF (median, 4.9 vs 1.9 months; HR, 0.53; P < .001), ORR (40.5% vs 9.9%; P <.001), HI (42.4% vs 11.2%), and red blood cell (RBC)-TI (31.7% vs 9.3%). Enasidenib safety was consistent with prior reports. The primary study endpoint was not met, but OS was confounded by early dropout and subsequent AML-directed therapies. Enasidenib provided meaningful benefits in EFS, TTF, ORR, HI, and RBC-TI in this heavily pretreated older mutant-IDH2 R/R AML population.This work was supported by Celgene, a Bristol-Myers Squibb Company