This manuscript describes a unique class of locomotive robot: A soft robot, composed exclusively of soft materials (elastomeric polymers), which is inspired by animals (e.g., squid, starfish, worms) that do not have hard internal skeletons. Soft lithography was used to fabricate a pneumatically actuated robot capable of sophisticated locomotion (e.g., fluid movement of limbs and multiple gaits). This robot is quadrupedal; it uses no sensors, only five actuators, and a simple pneumatic valving system that operates at low pressures (<10 psi). A combination of crawling and undulation gaits allowed this robot to navigate a difficult obstacle. This demonstration illustrates an advantage of soft robotics: They are systems in which simple types of actuation produce complex motion.biomimetic | mobile R obotics developed to increase the range of motions and functions open to machines, and to build into them some of the characteristics [including autonomous motion (1-3), adaptability to the environment (4-7), and capability of decision making (8, 9)] of animals, particularly animals with skeletons. Most mobile robots are built with hard materials (hard robots), either by adding treads or wheels (10, 11) to conventional machines to increase their mobility, or by starting with conceptual models based on animals [e.g., Big Dog (12) and many others (13-15)], and replicating some of their features in hard structures. Although robotics has made enormous progress in the last 50 years, hard robots still have many limitations. Some of these limitations are mechanical, and include instability when moving in difficult terrain; some have to do with the ranges of motions afforded by actuators and structures (e.g., metal rods, mechanical joints, and electric motors); some stem from the complexity in control (especially when handling materials and structures that are soft, delicate, and complex in shape). Hard robots fabricated from metals are also often heavy and expensive, and thus are not suitable for some applications.New classes of robots may thus find uses in applications where conventional hard robots are unsuitable. We are interested in a unique class of robots: That is, soft robots fabricated in materials (predominantly elastomeric polymers) that do not use a rigid skeleton to provide mechanical strength. The objective of this work is to demonstrate a soft robot that requires only simple design and control to generate mobility. In this demonstration, we begin to address some of the issues that have limited the development of soft robots. Instead of basing this and other designs on highly evolved animals as models, we are using simpler organisms [e.g., worms (16) and starfish (17)] for inspiration. These organisms, ones without internal skeletons, suggest designs that are simpler to make and are less expensive than conventional hard robots, and that may, in some respects, be more capable of complex motions and functions. Simple, inexpensive systems will probably not replace more complex and expensive ones, but may have different...

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Lenalidomide plus dexamethasone is superior to placebo plus dexamethasone in patients with relapsed or refractory multiple myeloma. (ClinicalTrials.gov number, NCT00056160 [ClinicalTrials.gov].).

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In addition to the previously characterized viruses BK and JC, three new human polyomaviruses (Pys) have been recently identified: KIV, WUV, and Merkel Cell Py (MCV). Using an ELISA employing recombinant VP1 capsid proteins, we have determined the seroprevalence of KIV, WUV, and MCV, along with BKV and JCV, and the monkey viruses SV40 and LPV. Soluble VP1 proteins were used to assess crossreactivity between viruses. We found the seroprevalence (+/− 1%) in healthy adult blood donors (1501) was SV40 (9%), BKV (82%), JCV (39%), LPV (15%), KIV (55%), WUV (69%), MCV strain 350 (25%), and MCV strain 339 (42%). Competition assays detected no sero-crossreactivity between the VP1 proteins of LPV or MCV or between WUV and KIV. There was considerable sero-crossreactivity between SV40 and BKV, and to a lesser extent, between SV40 and JCV VP1 proteins. After correcting for crossreactivity, the SV40 seroprevalence was ∼2%. The seroprevalence in children under 21 years of age (n = 721) for all Pys was similar to that of the adult population, suggesting that primary exposure to these viruses likely occurs in childhood.

Purpose Therapies with novel mechanisms of action are needed for multiple myeloma (MM). T cells can be genetically modified to express chimeric antigen receptors (CARs), which are artificial proteins that target T cells to antigens. B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells but not normal essential cells. We conducted the first-in-humans clinical trial, to our knowledge, of T cells expressing a CAR targeting BCMA (CAR-BCMA). Patients and Methods Sixteen patients received 9 × 10 CAR-BCMA T cells/kg at the highest dose level of the trial; we are reporting results of these 16 patients. The patients had a median of 9.5 prior lines of MM therapy. Sixty-three percent of patients had MM refractory to the last treatment regimen before protocol enrollment. T cells were transduced with a γ-retroviral vector encoding CAR-BCMA. Patients received CAR-BCMA T cells after a conditioning chemotherapy regimen of cyclophosphamide and fludarabine. Results The overall response rate was 81%, with 63% very good partial response or complete response. Median event-free survival was 31 weeks. Responses included eradication of extensive bone marrow myeloma and resolution of soft-tissue plasmacytomas. All 11 patients who obtained an anti-MM response of partial response or better and had MM evaluable for minimal residual disease obtained bone marrow minimal residual disease-negative status. High peak blood CAR cell levels were associated with anti-MM responses. Cytokine-release syndrome toxicities were severe in some cases but were reversible. Blood CAR-BCMA T cells were predominantly highly differentiated CD8 T cells 6 to 9 days after infusion. BCMA antigen loss from MM was observed. Conclusion CAR-BCMA T cells had substantial activity against heavily treated relapsed/refractory MM. Our results should encourage additional development of CAR T-cell therapies for MM.