STNet: Selective Tuning of Convolutional Networks for Object Localization

Visual attention modeling has recently gained momentum in developing visual hierarchies provided by Convolutional Neural Networks. Despite recent successes of feedforward processing on the abstraction of concepts form raw images, the inherent nature of feedback processing has remained computationally controversial. Inspired by the computational models of covert visual attention, we propose the Selective Tuning of Convolutional Networks (STNet). It is composed of both streams of Bottom-Up and Top-Down information processing to selectively tune the visual representation of Convolutional networks. We experimentally evaluate the performance of STNet for the weakly-supervised localization task on the ImageNet benchmark dataset. We demonstrate that STNet not only successfully surpasses the state-of-the-art results but also generates attention-driven class hypothesis maps

Cladribine Exposure Results in a Sustained Modulation of the Cytokine Response in Human Peripheral Blood Mononuclear Cells

<div><p>Background and Objectives</p><p>Cladribine is a cytotoxic drug which ameliorates the clinical course of relapsing-remitting multiple sclerosis. In addition to cytotoxicity, the mode of action may include immunomodulatory mechanisms. This <i>in vitro</i> study was designed to investigate cladribine’s effects on cell function after the removal of cladribine to distinguish cytotoxic versus immunomodulatory effects.</p><p>Methods</p><p>Cells were incubated in the absence or presence of cladribine (1×10^-8 M to 1×10^-5 M) for 72 h. Cladribine was removed from the cell culture and surviving peripheral blood mononuclear cells were cultured up to 58 days to determine the immunomodulatory effects of cladribine on cell function (e.g., proliferation and cytokine release).</p><p>Results</p><p>In the long-term, brief cladribine exposure did not impair the proliferation of surviving peripheral blood mononuclear cells. However, it induced an anti-inflammatory shift in the cytokine milieu with significantly enhanced release of IL-4 (Days 9 and 44, p<0.01; Day 58, p<0.05) and IL-5 (Day 9, p<0.01), resulting in an increased IL-4/INF-gamma ratio (Days 9 and 44, p<0.01; Day 58, p<0.05). Additionally, a trend towards an increased IL-10 production was observed. No changes were found in the production of IFN-gamma, TNF-alpha, IL-6, IL-8, IL-17A, IL-23 or NGF-beta.</p><p>Conclusions</p><p><i>In vitro</i> cladribine exposure induces a sustained anti-inflammatory shift in the cytokine profile of surviving peripheral blood mononuclear cells. This immunomodulatory action might contribute to cladribine’s beneficial effects in the treatment of multiple sclerosis.</p></div

<i>In vitro</i> effects of cladribine on cell survival of PBMCs and proliferation of PBMCs, CD4⁺ cells and CD8⁺ cells Human immune cells were stimulated with anti-CD3/anti-CD28 antibodies (a, n = 4; c, n = 6) or PHA (b, n = 4; d, n = 3) in the absence or presence of cladribine (1×10⁻⁸ M to 1×10⁻⁵ M) for 72 h.

<p>Determination of cell survival in PBMCs (a, b) was performed by standard trypan blue exclusion method. Proliferation was determined separately in PBMC, CD4⁺ cells and CD8⁺ cells (c, d) by the incorporation of tritiated thymidine. Stimulation indices were calculated as the ratios of the counts per minute of stimulated samples to unstimulated and untreated samples. Data are depicted as mean + standard deviation (SD).</p

<i>In vitro</i> effects of initial cladribine treatment on the proliferation of PBMCs stimulated at Days 9, 16, 23, 30, 44 and 58 after transfer into cladribine-free medium PBMCs were initially incubated in the absence or presence of cladribine (1×10⁻⁸ M to 5×10⁻⁷ M) for 72 h.

<p>Cells were washed three times and then transferred into cladribine-free medium. Cells were restimulated with anti-CD3/anti-CD28 antibodies (a, n = 5) or PHA (b, n = 4) for 48h at Days 9, 16, 23, 30, 44 and 58; proliferation was determined by the incorporation of tritiated thymidine. Stimulation indices were defined as the ratios of the counts per minute of stimulated samples to unstimulated and untreated samples. Data are depicted as mean + standard deviation (SD).</p

<i>In vitro</i> effects of initial cladribine treatment on cytokine secretion of PBMCs restimulated at Days 9, 16, 23 and 30 after transfer into cladribine-free medium.

<p><b>PBMCs from healthy blood donors (n = 4) were incubated in the absence or presence of cladribine</b>. (1×10⁻⁸ M to 5×10⁻⁷ M) for 72 h. Then cells were washed three times and transferred into cladribine-free medium. Cells were restimulated with PHA for 48 h at days 9, 16, 23 and 30; supernatants were collected and cytokine were determined. Data are depicted as box plot diagrams. Whiskers represent maximum and minimum values. The IL-4/IFN-γ ratio was defined as the ratio of IL-4 (pg/ml) to IFN-γ (pg/ml). *: p<0.05; **: p<0.01.</p

<i>In vitro</i> effects of initial cladribine treatment on cytokine secretion of PBMCs restimulated at Days 9, 16, 23, 30, 44 and 58 after transfer into cladribine-free medium.

<p>PBMCs from healthy blood donors (n = 5) were incubated in the absence or presence of cladribine. (1×10⁻⁸ M to 5×10⁻⁷ M) for 72 h. Then cells were washed three times and transferred into cladribine-free medium. Cells were restimulated with anti-CD3/anti-CD28 antibodies for 48 h at days 9, 16, 23, 30, 44 and 58; supernatants were collected and cytokine concentrations were determined. Data are depicted as box plot diagrams. Whiskers represent maximum and minimum values. The IL-4/IFN-γ ratio was defined as the ratio of IL-4 (pg/ml) to IFN-γ (pg/ml). *: p<0.05; **: p<0.01.</p

Additional file 3: of Ischaemic stroke and the recanalization drug tissue plasminogen activator interfere with antibacterial phagocyte function

Influence of adrenaline, noradrenaline, dexamethasone and acetylcholine on intracellular NE and MPO in vitro. A: Intracellular MPO of granulocytes and monocytes of healthy donors treated with adrenaline, noradrenaline, dexamethasone or acetylcholine (n = 10). The mean and SD ranges are given. B: Intracellular NE of granulocytes and monocytes treated with adrenaline, noradrenaline, dexamethasone or acetylcholine (n = 10). The mean and SD ranges are given. (PDF 2057 kb

Increased metanephrine and cortisol serum levels in patients with subsequent infection.

<p>Metanephrine and cortisol serum levels are increased in serum of stroke patients with subsequent infection (grey bars) compared to stroke patients without subsequent infection (white bars) within 24h following stroke. * p<0.05; ** p<0.01. Means±SEM. n_{(Metanephrine)} = 8; 8; 8; 7; n_(Cortisol) = 10; 8; 9; 9; (no infection day 0; subsequent infection day 0; no infection day 1; subsequent infection day 1).</p

Relative proportion of activated T cells were undistinguishable between patient subgroups.

<p>Activation markers on lymphocytes from stroke patients without subsequent infection (white bars) remained undistinguishable from those of stroke patients with subsequent infection (grey bars) within the relative proportion of lymphocytes in the first two weeks following stroke. * p<0.05; ** p<0.01. Medians and interquartile ranges. . n_(CD4⁺_CD25⁺_{, CD25}⁺_%CD4⁺₎ = 5; 7; 7; 7; 7; 6; 6; 3; n_(CD4⁺_HLA-DR⁺_{, HLA-DR}⁺_%CD4⁺₎ = 14; 12; 16; 11; 12; 9; 8; 5 (no infection day 0; subsequent infection day 0; no infection day 1; subsequent infection day 1; no infection day 7; subsequent infection day 7; no infection day 14; subsequent infection day 14).</p

Lack of CTLA-4 expression and inhibition by catecholamines.

<p>A) The percentage of PBMC expressing CTLA-4 is undistinguishable between healthy controls (white bars) and stroke patients (grey bars) in the first two weeks following stroke. Medians and interquartile ranges. n = 9; 31; 33; 27; 20; (control; day 0; day 1; day 7; day14). B) Percentage of CTLA-4 expression on PBMC decreases after <i>in vitro</i> treatment with PHA+epinephrine or PHA+norepinephrine compared to treatment with PHA alone. *** p<0.001. Medians and interquartile ranges. .n = 13; 6; 9; (PHA; PHA+Epi; PHA+Norepi).</p