1,314 research outputs found
Control of Tip Actuated Steerable Needles
No full textPercutaneous procedures are minimally invasive medical procedures that use needles to locally operate on a target in a patient’s body. The precise placement of the needle in the body is a challenging task that can affect the quality and efficiency of these procedures. Needle insertion accuracy may be improved by robot-assisted control of steerable needles. The type of steerable needles considered in this study are needles that are being developed at the Delft University of Technology (TUD) and are intended to be used in liver biopsy procedures. The goal of this research is to prove that these needles are able to reach a predetermined target accuracy during straight needle insertion. First, the uncontrolled insertion is tested in different tissue stiffness samples and with different insertion speeds. The results show that the target is reached with an accuracy that is smaller than 1 mm only when the insertion speed and the tissue stiffness are low. Other conditions require a control of the needle steering during its insertion, so that its deviations from the straight path can be corrected for. Two controllers are applied and tested. They both use direct position feedback that comes from optical strain sensors in the needle stylet and act on the servomotors with a proportional controller. The first controller only takes into account the end-point of the needle, while the second one takes into account its whole trajectory. Results show that both controllers improve the needle insertion accuracy with respect to the uncontrolled insertion at the tested conditions, allowing to reach the target with a position error that is smaller than 1 mm. The trajectory control gave better performance than the end-point control, which is to be expected, considering that the needle is a nonholonomic system. Overall, this study proved that under specified conditions, the TUD tip actuated steerable needles are able to reach a target on a straight trajectory within a position error that is smaller than 1 mm.BioMechanical EngineeringMechanical, Maritime and Materials Engineerin
Human CD4+ T-Cell Clone Expansion Leads to the Expression of the Cysteine Peptidase Inhibitor Cystatin F
No full textThe existence of CD4+ cytotoxic T cells (CTLs) at relatively high levels under different pathological conditions in vivo suggests their role in protective and/or pathogenic immune functions. CD4+ CTLs utilize the fundamental cytotoxic effector mechanisms also utilized by CD8+ CTLs and natural killer cells. During long-term cultivation, CD4+ T cells were also shown to acquire cytotoxic functions. In this study, CD4+ human T-cell clones derived from activated peripheral blood lymphocytes of healthy young adults were examined for the expression of cytotoxic machinery components. Cystatin F is a protein inhibitor of cysteine cathepsins, synthesized by CD8+ CTLs and natural killer cells. Cystatin F affects the cytotoxic efficacy of these cells by inhibiting the major progranzyme convertases cathepsins C and H as well as cathepsin L, which is involved in perforin activation. Here, we show that human CD4+ T-cell clones express the cysteine cathepsins that are involved in the activation of granzymes and perforin. CD4+ T-cell clones contained both the inactive, dimeric form as well as the active, monomeric form of cystatin F. As in CD8+ CTLs, cysteine cathepsins C and H were the major targets of cystatin F in CD4+ T-cell clones. Furthermore, CD4+ T-cell clones expressed the active forms of perforin and granzymes A and B. The levels of the cystatin F decreased with time in culture concomitantly with an increase in the activities of granzymes A and B. Therefore, our results suggest that cystatin F plays a role in regulating CD4+ T cell cytotoxicity. Since cystatin F can be secreted and taken up by bystander cells, our results suggest that CD4+ CTLs may also be involved in regulating immune responses through cystatin F secretion
Studies of radiative charm decays at Belle
No full textWe report a measurement of the branching fractions of the radiative decays D0 → Vγ, whereV = φ, K∗0 or ρ0. This is the first observation of the decay D0 → ρ0γ. We measure preliminary branching fractions B`D0 → φγ´ = (2.76 ± 0.20 ± 0.08) × 10−5, B`D0 → K∗0γ´ = (4 .66 ± 0.21 ± 0.18) × 10−4 and B`D0 → ρ0γ´= (1 .77±0.30±0.08)×10−5, where the first uncertainty is statistical and the second systematic. We also present the first measurement of CP asymmetry in these decays. The preliminary values are ACP `D0 → φγ´ = −0.094±0.066± 0.001, ACP `D0 → K∗0γ´= −0.003±0.020±0.000 and ACP `D0 → ρ0γ´=0 .056±0 .151±0.006. We also present the results of the search for the rare charm decayD 0 → γγ, resulting in an upper limit on the branching fraction Br(D0 → γγ) <8 .5×10−7 at 90% confidence level, the most restrictive limit to date
Observation of D0→ρ0γ and search for CP violation in radiative charm decays
No full textWe report the first observation of the radiative charm decay D0 → ρ0γ and the first search for CP violation in decays D0 → ρ0γ, ϕγ, and K*0bar(892)γ
Cysteine cathepsins as regulators of the cytotoxicity of NK and T cells
No full textCysteine cathepsins are lysosomal peptidases involved at different levels in the processes of the innate and adaptive immune responses. Some, such as cathepsins B, L and H are expressed constitutively in most immune cells. In cells of innate immunity they play a role in cell adhesion and phagocytosis. Other cysteine cathepsins are expressed more specifically. Cathepsin X promotes dendritic cell maturation, adhesion of macrophages and migration of T cells. Cathepsin S is implicated in major histocompatibility complex class II antigen presentation, whereas cathepsin C, expressed in cytotoxic lymphocytes (CTLs) and natural killer (NK) cells, is involved in processing progranzymes into proteolytically active forms, which trigger cell death in their target cells. The activity of cysteine cathepsins is controlled by endogenous cystatins, cysteine protease inhibitors. Of these, cystatin F is the only cystatin that is localized in endosomal/lysosomal vesicles. After proteolytic removal of its N terminal peptide, cystatin F becomes a potent inhibitor of cathepsin C with the potential to regulate progranzyme processing and cell cytotoxicity. This review is focused on the role of cysteine cathepsins and their inhibitors in the molecular mechanisms leading to the cytotoxic activity of T lymphocytes and NK cells in order to address new possibilities for regulation of their function in pathological processes
Extracellular Cystatin F Is Internalised by Cytotoxic T Lymphocytes and Decreases Their Cytotoxicity
No full textCystatin F is a protein inhibitor of cysteine cathepsins, peptidases involved in the activation of the effector molecules of the perforin/granzyme pathway. Cystatin F was previously shown to regulate natural killer cell cytotoxicity. Here, we show that extracellular cystatin F has a role in regulating the killing efficiency of cytotoxic T lymphocytes (CTLs). Extracellular cystatin F was internalised into TALL-104 cells, a cytotoxic T cell line, and decreased their cathepsin C and H activity. Correspondingly, granzyme A and B activity was also decreased and, most importantly, the killing efficiency of TALL-104 cells as well as primary human CTLs was reduced. The N-terminally truncated form of cystatin F, which can directly inhibit cathepsin C (unlike the full-length form), was more effective than the full-length inhibitor. Furthermore, cystatin F decreased cathepsin L activity, which, however, did not affect perforin processing. Cystatin F derived from K-562 target cells could also decrease the cytotoxicity of TALL-104 cells. These results clearly show that, by inhibiting cysteine cathepsin proteolytic activity, extracellular cystatin F can decrease the cytotoxicity of CTLs and thus compromise their function
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