Designing Prosthetic Hands With Embodied Intelligence: The KIT Prosthetic Hands.

Hand prostheses should provide functional replacements of lost hands. Yet current prosthetic hands often are not intuitive to control and easy to use by amputees. Commercially available prostheses are usually controlled based on EMG signals triggered by the user to perform grasping tasks. Such EMG-based control requires long training and depends heavily on the robustness of the EMG signals. Our goal is to develop prosthetic hands with semi-autonomous grasping abilities that lead to more intuitive control by the user. In this paper, we present the development of prosthetic hands that enable such abilities as first results toward this goal. The developed prostheses provide intelligent mechatronics including adaptive actuation, multi-modal sensing and on-board computing resources to enable autonomous and intuitive control. The hands are scalable in size and based on an underactuated mechanism which allows the adaptation of grasps to the shape of arbitrary objects. They integrate a multi-modal sensor system including a camera and in the newest version a distance sensor and IMU. A resource-aware embedded system for in-hand processing of sensory data and control is included in the palm of each hand. We describe the design of the new version of the hands, the female hand prosthesis with a weight of 377 g, a grasping force of 40.5 N and closing time of 0.73 s. We evaluate the mechatronics of the hand, its grasping abilities based on the YCB Gripper Assessment Protocol as well as a task-oriented protocol for assessing the hand performance in activities of daily living. Further, we exemplarily show the suitability of the multi-modal sensor system for sensory-based, semi-autonomous grasping in daily life activities. The evaluation demonstrates the merit of the hand concept, its sensor and in-hand computing systems.

Angiopoietin-2-induced blood-brain barrier compromise and increased stroke size are rescued by VE-PTP-dependent restoration of Tie2 signaling.

The homeostasis of the central nervous system is maintained by the blood-brain barrier (BBB). Angiopoietins (Ang-1/Ang-2) act as antagonizing molecules to regulate angiogenesis, vascular stability, vascular permeability and lymphatic integrity. However, the precise role of angiopoietin/Tie2 signaling at the BBB remains unclear. We investigated the influence of Ang-2 on BBB permeability in wild-type and gain-of-function (GOF) mice and demonstrated an increase in permeability by Ang-2, both in vitro and in vivo. Expression analysis of brain endothelial cells from Ang-2 GOF mice showed a downregulation of tight/adherens junction molecules and increased caveolin-1, a vesicular permeability-related molecule. Immunohistochemistry revealed reduced pericyte coverage in Ang-2 GOF mice that was supported by electron microscopy analyses, which demonstrated defective intra-endothelial junctions with increased vesicles and decreased/disrupted glycocalyx. These results demonstrate that Ang-2 mediates permeability via paracellular and transcellular routes. In patients suffering from stroke, a cerebrovascular disorder associated with BBB disruption, Ang-2 levels were upregulated. In mice, Ang-2 GOF resulted in increased infarct sizes and vessel permeability upon experimental stroke, implicating a role of Ang-2 in stroke pathophysiology. Increased permeability and stroke size were rescued by activation of Tie2 signaling using a vascular endothelial protein tyrosine phosphatase inhibitor and were independent of VE-cadherin phosphorylation. We thus identified Ang-2 as an endothelial cell-derived regulator of BBB permeability. We postulate that novel therapeutics targeting Tie2 signaling could be of potential use for opening the BBB for increased CNS drug delivery or tighten it in neurological disorders associated with cerebrovascular leakage and brain edema.

Pentameric CRP attenuates inflammatory effects of mmLDL by inhibiting mmLDL--monocyte interactions.

Previous studies have reported that C-reactive protein (CRP) interacting with low-density lipoproteins (LDL) affects macrophage activation and LDL uptake. However, the physiological relevance of CRP-LDL interaction with circulating monocytes remains elusive. Moreover, recent studies have shown that CRP exists in two isoforms with partly opposing characteristics pentameric (pCRP) and monomeric CRP (mCRP). Here we investigated the effects of CRP interacting with minimally modified low-density lipoprotein (mmLDL) interaction in regard to events involved in formation of atherosclerotic plaque. We analyzed the effect of mmLDL on human monocytes and found a substantial increase in monocyte activation as evaluated by CD11b/CD18 expression and increased monocyte adhesion under static and under shear flow conditions to human endothelial cells. Monocyte adhesion and activation was attenuated by pCRP via the prevention of mmLDL binding to monocytes. These anti-inflammatory properties of pCRP were lost when it dissociates to the monomeric form. Our results elucidate the physiological relevance of the CRP-mmLDL interaction and furthermore confirm the importance of the previously described pCRP dissociation to mCRP as a localized inflammatory "activation" mechanism.

The influence of cardiac preload and positive end-expiratory pressure on the pre-ejection period.

The pre-ejection period (PEP) has recently been described as a potential parameter for monitoring cardiac preload. This study further investigated the influence of changes in intravascular volume status and the application of positive end-expiratory pressure (PEEP) on the pre-ejection period. In ten pigs, ECG, arterial pressure and stroke volume derived from an aortic flowprobe were registered. Global end-diastolic volume (GEDV) was measured by transcardiopulmonary thermodilution. Total blood volume (TBV) and intrathoracic blood volume (ITBV) were measured by the dye-dilution technique. Measurements were performed during normovolaemic conditions, after volume loading with haemodilution blood (20 ml kg(-1)) and following haemorrhage (30 ml kg(-1)) without PEEP and with PEEP (15 cm H(2)O) applied. Volume loading increased GEDV, ITBV, TBV and SV, whereas PEP remained constant. However, the changes were not significant (P > 0.05). Subsequent haemorrhage significantly decreased GEDV (from 436 to 308 ml), ITBV (from 729 to 452 ml), TBV (from 2,131 to 1,488 ml) (all P-values <0.05), and SV (from 20.7 ml to 14.3 ml, P < 0.001). However, PEP did not change significantly (from 73 to 82 ms, P > 0.05). No correlation between the changes in PEP and changes in any other variable was observed. It is concluded that PEP is not sensitive to the changes in intravascular volume status.