Dexterous Miniature in Vivo Surgical Robot for Long Duration Space Flight

2008 ◽  
Author(s):  
Nathan Wood ◽  
Amy Lehman ◽  
Jason Dumpert ◽  
Shane Farritor ◽  
Dmitry Oleynikov
Keyword(s):  
Space Flight ◽  
Surgical Robot ◽  
Long Duration

scholarly journals Measurement of the dynamics of stimulation and inhibition of steroidogenesis in isolated rat adrenal cells by using column perfusion

1974 ◽  
Vol 142 (2) ◽  
pp. 287-294 ◽  
Author(s):  
P. J. Lowry ◽  
Colin McMartin
Keyword(s):  
Cyclic Amp ◽  
Time Course ◽  
Acth Stimulation ◽  
Duration Of Action ◽  
Adrenal Cells ◽  
Small Column ◽  
Long Duration ◽  
Full Effect ◽  
Rapid Fall

Isolated adrenal cells were perfused in a small column by using Bio-Gel polyacrylamide beads as an inert supporting matrix, and the time-course of the response to various stimuli was observed by measuring fluorogenic 11-hydroxycorticosteroids in the effluent. A small but significant response was observed 1 min after stimulation with physiological concentrations of ACTH (adrenocorticotrophin), but the response did not start to build up rapidly for 3–4min and eventually reached a plateau after 9–10min. A similar pattern of events was observed for the decay of the steroid output on removal of ACTH. ACTH analogues, including one with a long duration of action in vivo, were found to produce responses with similar kinetics. However, cyclic AMP caused a more rapid increase in steroidogenesis and its effects were more short-lived after withdrawal. If, as present evidence suggests, cyclic AMP is produced rapidly after ACTH stimulation the delayed build-up of the steroidogenic response to ACTH would indicate that cyclic AMP may not be the intracellular mediator. When inhibitors were applied during ACTH stimulation, aminoglutethimide, which blocks mitochondrial conversion of cholesterol into pregnenolone (3β-hydroxypregn-5-en-20-one), caused a rapid fall in steroid output (1 min), whereas cycloheximide took longer to achieve its full effect. Nevertheless, the response had fallen by 50% in 2 min, indicating a much shorter half-life than that previously reported for the labile protein implicated in steroidogenesis. In addition the rapid response to cyclic AMP makes it unlikely that steroid production is induced as a result of initiation of protein synthesis. This suggests that the labile protein plays an obligatory but permissive role in the development of the response. Column perfusion has proved to be a simple technique which can readily yield accurate data on responses of cells to stimulants and inhibitors.

scholarly journals Induction of Heat Shock Protein 70 in Mouse RPE as an In Vivo Model of Transpupillary Thermal Stimulation

2020 ◽  
Vol 21 (6) ◽  
pp. 2063
Author(s):  
Mooud Amirkavei ◽  
Marja Pitkänen ◽  
Ossi Kaikkonen ◽  
Kai Kaarniranta ◽  
Helder André ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
In Vivo Model ◽  
Tunel Staining ◽  
Long Duration ◽  
Shock Response

The induction of heat shock response in the macula has been proposed as a useful therapeutic strategy for retinal neurodegenerative diseases by promoting proteostasis and enhancing protective chaperone mechanisms. We applied transpupillary 1064 nm long-duration laser heating to the mouse (C57Bl/6J) fundus to examine the heat shock response in vivo. The intensity and spatial distribution of heat shock protein (HSP) 70 expression along with the concomitant probability for damage were measured 24 h after laser irradiation in the mouse retinal pigment epithelium (RPE) as a function of laser power. Our results show that the range of heating powers for producing heat shock response while avoiding damage in the mouse RPE is narrow. At powers of 64 and 70 mW, HSP70 immunostaining indicates 90 and 100% probability for clearly elevated HSP expression while the corresponding probability for damage is 20 and 33%, respectively. Tunel staining identified the apoptotic regions, and the estimated 50% damaging threshold probability for the heating (ED50) was ~72 mW. The staining with Bestrophin1 (BEST1) demonstrated RPE cell atrophy with the most intense powers. Consequently, fundus heating with a long-duration laser provides an approachable method to develop heat shock-based therapies for the RPE of retinal disease model mice.

scholarly journals New emerging targets in cancer immunotherapy: the role of LAG3

ESMO Open ◽  
2019 ◽  
Vol 4 (2) ◽  
pp. e000482 ◽  
Author(s):  
Hannah Christina Puhr ◽  
Aysegül Ilhan-Mutlu
Keyword(s):  
Cytotoxic T Lymphocyte ◽  
Single Agent ◽  
Death Receptor ◽  
Treatment Resistance ◽  
Alternative Pathways ◽  
Long Duration ◽  
Duration Of Response ◽  
Death Receptor Ligand ◽  
Dual Blockade

The success of immunotherapy in many disease entities is limited to a specific subpopulation of patients. To overcome this problem, dual blockade treatments mainly against cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and programmed cell death receptor (ligand) 1 (PD-(L)1) axis were developed. However, due to high toxicity rates and treatment resistance, alternative pathways and novel strategies were desperately needed. Lymphocyte-associated gene 3 (LAG3) represents an inhibitory receptor, which is mainly found on activated immune cells and involved in the exhaustion of T cells in malignant diseases. Its co-expression with other inhibitory receptors, particularly with PD-1 leads to an extensive research on the blockade of LAG3 and PD-1 in preclinical settings. Interestingly, several in-vivo approaches demonstrated a highly significant clinical benefit under dual blockade, whereas the efficacy was very low in case of single agent targeting. Moreover, human tumour tissues showed co-expression of LAG3 and PD-1 in infiltrated lymphocytes, which again generated a rationale for blocking these both molecules in clinical settings. The ongoing clinical studies mainly use dual blockage of LAG3/PD-1, which demonstrated promising survival benefits and long duration of response rates. The following review focuses on the biological background and rationale of combining LAG3 with other agents and serves as an update on the state of clinical research on LAG3 targeting.

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