Biomechanical study comparing the energy cost of human bipedalism versus zenkutsu-dachi stepping of a karateka.

Traditional stepping in the zenkutsu-dachi stance of the Shotokan style of karate is very physically demanding. It requires considerably more effort than what is expended during conventional human bipedalism. We performed a biomechanical study to analyze and compare these two types of gaits when performed by a highly experienced karateka. The study involved a three-dimensional motion analysis system (digital cameras and optical reflectors) and a force platform to analyze the ground reaction forces in all three planes. The study had both kinematic and kinetic components. We found that zenkutsu-dachi stepping is much more costly from an energetics point of view because the properties of the biarticular muscles are not used, the muscular moments of force are higher, and the body's potential energy is not converted into kinetic energy, contrary to the more economical model of human bipedalism that involves an inverted pendulum pattern.

Automated linkage of proteins and payloads producing monodisperse conjugates.

Controlled protein functionalization holds great promise for a wide variety of applications. However, despite intensive research, the stoichiometry of the functionalization reaction remains difficult to control due to the inherent stochasticity of the conjugation process. Classical approaches that exploit peculiar structural features of specific protein substrates, or introduce reactive handles via mutagenesis, are by essence limited in scope or require substantial protein reengineering. We herein present equimolar native chemical tagging (ENACT), which precisely controls the stoichiometry of inherently random conjugation reactions by combining iterative low-conversion chemical modification, process automation, and bioorthogonal trans-tagging. We discuss the broad applicability of this conjugation process to a variety of protein substrates and payloads.

Development and evaluation of ß-galactosidase-sensitive antibody-drug conjugates.

The selective destruction of tumour cells while sparing healthy tissues is one of the main challenges in cancer therapy. Antibody-drug conjugates (ADCs) are arguably the most rapidly expanding class of targeted cancer therapies. Efficient drug conjugation and release technologies are essential for the development of these new therapeutic agents. In response to the ever-increasing demand for efficient drug release systems, we have developed a new class of ß-galactosidase-cleavable linkers for ADCs. Within this framework, novel payloads comprising a galactoside linker, the monomethyl auristatin E (MMAE) and cysteine-reactive groups were synthesized, conjugated with trastuzumab and evaluated both in vitro and in vivo. The ADCs with galactoside linkers demonstrated superior therapeutic efficacy in mice compared to the marketed trastuzumab emtansine used for the treatment of breast cancer.

Palladium-Catalyzed Chemoselective and Biocompatible Functionalization of Cysteine-Containing Molecules at Room Temperature.

The third generation of aminobiphenyl palladacycle pre-catalyst "G3-Xantphos" enables functionalization of peptides containing cysteine in high yields. The conjugation (bioconjugation) occurs chemoselectively at room temperature under biocompatible conditions. Extension of the method to protein functionalization allows selective bioconjugation of the trastuzumab antibody.

Glycosylation mediated-BAIL in aqueous solution.

The use of Brønsted acid ionic liquid (BAIL) as a catalyst for the activation of unreactive and unprotected glycosyl donors has been demonstrated for the first time in aqueous solution.

Kinetic strategies of patients with shoulder impingement syndrome.

Our aim was to determine whether subjects with shoulder impingement syndrome (SIS) have abnormal multijoint torque patterns compared to healthy subjects during normalized isometric force along specific directions. Subjects had to generate an isometric force corresponding to 40% of the maximal pain-free force. Eight targets were displayed on a monitor (0, 45, 90, 135, 180, 225, 270, and 315 degrees ). We calculated shoulder and elbow torques (kinetic strategies) using a biomechanical model. Regardless of the target location, the SIS group succeeded in reaching the target; however, when compared to the healthy subjects, they needed more time to do so, suggesting that SIS may slow down the execution of the kinetic strategies. Moreover, the SIS group produced lower shoulder external/internal torque to reach the targets located at 0 degrees and 225 degrees, and they generated greater abduction/adduction torque for targets located at 0, 135, and 180 degrees. In addition, they had lower elbow extension/flexion torque for the target located at 315 degrees. The investigation of atypical kinetic strategies is essential to provide an understanding of the pathomechanics of the SIS and to develop more effective treatment strategies.