The MRE11 complex (MRE11, RAD50 and NBS1) and the ataxia-telangiectasia mutated (ATM) kinase function in the same DNA damage response pathway to effect cell cycle checkpoint activation and apoptosis. The functional interaction between the MRE11 complex and ATM has been proposed to require a conserved C-terminal domain of NBS1 for recruitment of ATM to sites of DNA damage. Human Nijmegen breakage syndrome (NBS) cells and those derived from multiple mouse models of NBS express a hypomorphic NBS1 allele that exhibits impaired ATM activity despite having an intact C-terminal domain. This indicates that the NBS1 C terminus is not sufficient for ATM function. We derived Nbs1(DeltaC/DeltaC) mice in which the C-terminal ATM interaction domain is deleted. Nbs1(DeltaC/DeltaC) cells exhibit intra-S-phase checkpoint defects, but are otherwise indistinguishable from wild-type cells with respect to other checkpoint functions, ionizing radiation sensitivity and chromosome stability. However, multiple tissues of Nbs1(DeltaC/DeltaC) mice showed a severe apoptotic defect, comparable to that of ATM- or CHK2-deficient animals. Analysis of p53 transcriptional targets and ATM substrates showed that, in contrast to the phenotype of Chk2(-/-) mice, NBS1(DeltaC) does not impair the induction of proapoptotic genes. Instead, the defects observed in Nbs1(DeltaC/DeltaC) result from impaired phosphorylation of ATM targets including SMC1 and the proapoptotic factor, BID.

In this paper, we investigate the effect of high modes of buckling on the mechanical behavior of a pre-shaped curved beam. In a first stage, the presented modeling develops further the snapping forces solution and bistability conditions in order to include high modes of buckling. In a second stage, we develop the analytical solution of the stresses inside the beam during deflection between the two sides of buckling. The buckling with or without mechanical conditions on antisymmetric modes, the force characteristics, bistability conditions and stresses are described in this paper based on mathematical approach in order to provide a clear physical understanding of the curved beam behavior and its design parameters. The accurate knowledge of the design parameters is important in order to achieve the best integration of the curved beam in a complete microstructure. The analytical results are compared with and without considering high modes of buckling and have shown to be in excellent agreement with FEM simulations. The results show the importance of the high modes in calculating stresses and snapping forces.

This paper presents a compliant monolithic multistable actuator which is able to switch its moving part between several stable positions linearly in one dimensional direction. The number of stable positions can be increased by extending the range of displacement of the moving part. The transition in each step of displacement is made to the nearest stable position in the direction of motion. Upward and downward steps are made by a specific sequence of moving, using a bistable module, opening and closing two internal clamps which are actuated by U-shaped electrothermal actuator using three subsystems. The principle and the design of each subsystem in the discrete acruator, fabrication process and experimental results are presented. The fabricated prototypes of the discrete actuator showed a proper functioning. The mean achieved displacement is 120.67±0.08 µm over 12 upward steps with a mean step of 10.06 µm, which is very close to the designed performance.

The maximal duration of cardiopulmonary resuscitation (CPR) is unknown. We report a case of prolonged CPR. We have then reviewed all published cases with CPR duration equal to or more than 20 minutes. The objective was to determine the survival rate, the neurological outcome, and the characteristics of the survivors. Measurements and Main Results. The CPR data for 82 patients was reviewed. The median duration of CPR was 75 minutes. Patients mean age was 43 ± 21 years with no significant comorbidities. The main causes of the cardiac arrests were myocardial infarction (29%), hypothermia (21%), and pulmonary emboli (12%). 74% of the arrests were witnessed, with a mean latency to CPR of 2 ± 6 minutes and good quality chest compression provided in 96% of the cases. Adjunct therapy included extracorporeal membrane oxygenation (18%), thrombolysis (15.8%), and rewarming for hypothermia (19.5%). 83% were alive at 1 year, with full neurological recovery reported in 63 patients. Conclusion. Patients undergoing prolonged CPR can survive with good outcome. Young age, myocardial infarction, and potentially reversible causes of cardiac arrest such as hypothermia and pulmonary emboli predict a favorable result, especially when the arrest is witnessed and followed by prompt and good resuscitative efforts.

We derive the snap-through solution and the governing snapping force equations for an arbitrarily pre-shaped beam deflected under a mid-length lateral point force. The exact solution is obtained based on the classical theory of elastic beams as a superposition of the initial shape and the modes of buckling. Two kinds of solution are identified depending on the axial force level. The two solutions, bifurcation conditions, bistability conditions, and the snapping force equations are derived and discussed. The snap-through and snapping force solutions are then calculated for two common beam initial shapes, the curved (first buckling shape) and the inclined one (V-shape). In both cases, explicit expressions are obtained describing the snap-through behavior. The analytical modeling results show excellent agreement with the finite element simulations. The comparison between the two cases shows a similar snap-through behavior qualitatively, while several differences and similarities are noticed quantitatively.

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This article deals with the optimization of the main element of a digital microrobot, which is a bistable module. the bistable module consists of curved beams and electrothermal actuators. A design study of the curved beam and the electrothermal actuator is presented in order to achieve the limits in line with miniaturization. Finally, An optimization for the dimensions is proposed respect to microfabrication and elastic limits.