Comparison of Code-Pass-Skipping Strategies for Accelerating a JPEG 2000 Decoder

Code-Pass-Skipping allows a JPEG 2000 decoder to be accelerated by sacrificing the output precision. This paper presents an evaluation on how the speed gain can be maximized and the quality loss minimized. In particular, the scenario of rendering a 24-bit preview of a Digital Cinema Package (DCP) with the maximum permitted bitrate is examined. A comparison shows, that a new proposed strategy outperforms the reference implementation from Kakadu Software v6 by up to 1 dB. Furthermore, it is shown what speed gain can be achieved for a given acceptable quality loss

Evaluation of GPU/CPU Co-Processing Models for JPEG 2000 Packetization

With the bottom-line goal of increasing the throughput of a GPU-accelerated JPEG 2000 encoder, this paper evaluates whether the post-compression rate control and packetization routines should be carried out on the CPU or on the GPU. Three co-processing models that differ in how the workload is split among the CPU and GPU are introduced. Both routines are discussed and algorithms for executing them in parallel are presented. Experimental results for compressing a detail-rich UHD sequence to 4 bits/sample indicate speed-ups of 200x for the rate control and 100x for the packetization compared to the single-threaded implementation in the commercial Kakadu library. These two routines executed on the CPU take 4x as long as all remaining coding steps on the GPU and therefore present a bottleneck. Even if the CPU bottleneck could be avoided with multi-threading, it is still beneficial to execute all coding steps on the GPU as this minimizes the required device-to-host transfer and thereby speeds up the critical path from 17.2 fps to 19.5 fps for 4 bits/sample and to 22.4 fps for 0.16 bits/sample

Regulation of the Immune Balance During Allogeneic Hematopoietic Stem Cell Transplantation by Vitamin D

One of the most promising therapeutic approaches for numerous hematological malignancies represents the allogeneic hematopoietic stem cell transplantation (allo-HSCT). One major complication is the development of the life-threatening graft-vs.-host disease (GvHD) which limits beneficial effects of graft-vs.-leukemia (GvL) responses during allo-HSCT. Strengthening GvL effects without induction of severe GvHD is essential to decrease the relapse rate after allo-HSCT. An interesting player in this context is vitamin D3 since it has modulatory capacity in both preventing GvHD and boosting GvL responses. Current studies claim that vitamin D3 induces an immunosuppressive environment by dendritic cell (DC)-dependent generation of regulatory T cells (Tregs). Since vitamin D3 is known to support the antimicrobial defense by re-establishing the physical barrier as well as releasing defensins and antimicrobial peptides, it might also improve graft-vs.-infection (GvI) effects in patients. Beyond that, alloreactive T cells might be attenuated by vitamin D3-mediated inhibition of proliferation and activation. Despite the inhibitory effects of vitamin D3 on T cells, anti-tumor responses of GvL might be reinforced by vitamin D3-triggered phagocytic activity and antibody-based immunotherapy. Therefore, vitamin D3 treatment does not only lead to a shift from a pro-inflammatory toward a tolerogenic state but also promotes tumoricidal activity of immune cells. In this review we focus on vitamin D3 and its immunomodulatory effects by enhancing anti-tumor activity while alleviating harmful allogeneic responses in order to restore the immune balance

Human Double-Negative Regulatory T-Cells Induce a Metabolic and Functional Switch in Effector T-Cells by Suppressing mTOR Activity

The recently discovered population of TCRαβ+ CD4–/CD8– (double-negative, DN) T-cells are highly potent suppressor cells in mice and humans. In preclinical transplantation models, adoptive transfer of DN T-cells specifically inhibits alloreactive T-cells and prevents transplant rejection or graft-vs.-host disease (GvHD). Interestingly, clinical studies in patients who underwent allogeneic stem cell transplantation reveal an inverse correlation between the frequency of circulating DN T-cells and the severity of GvHD, suggesting a therapeutic potential of human DN T-cells. However, their exact mode of action has not been elucidated yet. Investigating the impact of DN T-cells on conventional T-cells, we found that human DN T-cells selectively inhibit mTOR signaling in CD4 T-cells. Given that mTOR is a critical regulator of cellular metabolism, we further determined the impact of DN T-cells on the metabolic framework of T-cells. Intriguingly, DN T-cells diminished expression of glucose transporters and glucose uptake, whereas fatty acid uptake was not modified, indicating that DN T-cells prevent metabolic adaptation of CD4 T-cells upon activation (i.e., glycolytic switch) thereby contributing to their suppression. Further analyses demonstrated that CD4 T-cells also do not upregulate homing receptors associated with inflammatory processes. In contrast, expression of central memory-cell associated cell surface markers and transcription factors were increased by DN T-cells. Moreover, CD4 T-cells failed to produce inflammatory cytokines after co-culture with DN T-cells, whereas IL-2 secretion was enhanced. Taken together DN T-cells impair metabolic reprogramming of conventional CD4 T-cells by abrogating mTOR signaling, thereby modulating CD4 T-cell functionality. These results uncover a new mechanism of DN T-cell-mediated suppression, pointing out that DN T-cells could serve as cell-based therapy to limit alloreactive immune response

Two distinct secretory vesicle–priming steps in adrenal chromaffin cells

The calcium-dependent activator proteins for secretion, CAPS1 and CAPS2, facilitate syntaxin opening during synaptic vesicle priming

Dual checkpoint blockade of CD47 and LILRB1 enhances CD20 antibody-dependent phagocytosis of lymphoma cells by macrophages

Antibody-dependent cellular phagocytosis (ADCP) by macrophages, an important effector function of tumor targeting antibodies, is hampered by ‘Don´t Eat Me!’ signals such as CD47 expressed by cancer cells. Yet, human leukocyte antigen (HLA) class I expression may also impair ADCP by engaging leukocyte immunoglobulin-like receptor subfamily B (LILRB) member 1 (LILRB1) or LILRB2. Analysis of different lymphoma cell lines revealed that the ratio of CD20 to HLA class I cell surface molecules determined the sensitivity to ADCP by the combination of rituximab and an Fc-silent variant of the CD47 antibody magrolimab (CD47-IgGσ). To boost ADCP, Fc-silent antibodies against LILRB1 and LILRB2 were generated (LILRB1-IgGσ and LILRB2-IgGσ, respectively). While LILRB2-IgGσ was not effective, LILRB1-IgGσ significantly enhanced ADCP of lymphoma cell lines when combined with both rituximab and CD47-IgGσ. LILRB1-IgGσ promoted serial engulfment of lymphoma cells and potentiated ADCP by non-polarized M0 as well as polarized M1 and M2 macrophages, but required CD47 co-blockade and the presence of the CD20 antibody. Importantly, complementing rituximab and CD47-IgGσ, LILRB1-IgGσ increased ADCP of chronic lymphocytic leukemia (CLL) or lymphoma cells isolated from patients. Thus, dual checkpoint blockade of CD47 and LILRB1 may be promising to improve antibody therapy of CLL and lymphomas through enhancing ADCP by macrophages

Physiological levels of 25‐hydroxyvitamin D₃ induce a suppressive CD4⁺ T cell phenotype not reflected in the epigenetic landscape

1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D3 has a strong impact on the differentiation and function of immune cells. Here we analysed the influence of its precursor 25-hydroxyvitamin D3 (25(OH)D3) on the differentiation of human CD4+ T cells applying physiological concentrations in vitro. Our data show that 25(OH)D3 is converted to its active form 1,25(OH)2D3 by T cells, which in turn supports FOXP3, CD25 and CTLA-4 expression and inhibits IFN-γ production. These changes were not reflected in the demethylation of the respective promoters. Furthermore, we investigated the impact of vitamin D3 metabolites under induced Treg (iTreg) polarization conditions using TGF-β. Surprisingly, no additive effect but a decreased percentage of FOXP3 expressing cells was observed. However, the combination of 25(OH)D3 or 1,25(OH)2D3 together with TGF-β further upregulated CD25 and CTLA-4 and significantly increased soluble CTLA-4 and IL-10 secretion whereas IFN-γ expression of iTreg was decreased. Our data suggest that physiological levels of 25(OH)D3 act as potent modulator of human CD4+ T cells and autocrine or paracrine production of 1,25(OH)2D3 by T cells might be crucial for the local regulation of an adaptive immune response. However, since no epigenetic changes are detected by 25(OH)D3 a rather transient phenotype is induced

Strain specific differences in vitamin D3 response: impact on gut homeostasis

Vitamin D3 regulates a variety of biological processes irrespective of its well-known importance for calcium metabolism. Epidemiological and animal studies indicate a role in immune regulation, intestinal barrier function and microbiome diversity. Here, we analyzed the impact of different vitamin D3- containing diets on C57BL/6 and BALB/c mice, with a particular focus on gut homeostasis and also investigated effects on immune cells in vitro. Weak regulatory effects were detected on murine T cells. By trend, the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 suppressed IFN, GM-CSF and IL-10 cytokine secretion in T cells of C57BL/6 but not BALB/c mice, respectively. Using different vitamin D3-fortified diets, we found a tissue–specific enrichment of mainly CD11b+ myeloid cells but not T cells in both mouse strains e.g. in spleen and Peyer’s Patches. Mucin Reg3γ and Batf expression, as well as important proteins for gut homeostasis, were significantly suppressed in the small intestine of C57BL76 but not BALB/c mice fed with a high-vitamin D3 containing diet. Differences between both mouse stains were not completely explained by differences in vitamin D3 receptor expression which was strongly expressed in epithelial cells of both strains. Finally, we analyzed gut microbiome and again an impact of vitamin D3 was detected in C57BL76 but not BALB/c. Our data suggest strain-specific differences in vitamin D3 responsiveness under steady state conditions which may have important implications when choosing a murine disease model to study vitamin D3 effects

Fluid venting in the eastern Aleutian subduction zone

Fluid venting has been observed along 800 km of the Alaska convergent margin. The fluid venting sites are located near the deformation front, are controlled by subsurface structures, and exhibit the characteristics of cold seeps seen in other convergent margins. The more important characteristics include (1) methane plumes in the lower water column with maxima above the seafloor which are traceable to the initial deformation ridges; (2) prolific colonies of vent biota aligned and distributed in patches controlled by fault scarps, over‐steepened folds or outcrops of bedding planes; (3) calcium carbonate and barite precipitates at the surface and subsurface of vents; and (4) carbon isotope evidence from tissue and skeletal hard parts of biota, as well as from carbonate precipitates, that vents expel either methane‐ or sulfide‐dominated fluids. A biogeochemical approach toward estimating fluid flow rates from individual vents based on oxygen flux measurements and vent fluid analysis indicates a mean value of 5.5±0.7 L m−2 d−1 for tectonics‐induced water flow [Wallmann et al., 1997b]. A geophysical estimate of dewatering from the same area [von Huene et al., 1997] based on sediment porosity reduction shows a fluid loss of 0.02 L m−2 d−1 for a 5.5 km wide converged segment near the deformation front. Our video‐guided surveys have documented vent biota across a minimum of 0.1% of the area of the convergent segment off Kodiak Island; hence an average rate of 0.006 L m−2 d−1 is estimated from the biogeochemical approach. The two estimates for tectonics‐induced water flow from the accretionary prism are in surprisingly good agreement