■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.

Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis

https://digital.csic.es/bitstream/10261/134282/5/ADVANCED%20TARGETED.pdf

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.

Recent advances in nanotechnology and biotechnology have contributed to the development of engineered nanoscale materials as innovative prototypes to be used for biomedical applications and optimized therapy. Due to their unique features, including a large surface area, structural properties, and a long circulation time in blood compared with small molecules, a plethora of nanomaterials has been developed, with the potential to revolutionize the diagnosis and treatment of several diseases, in particular by improving the sensitivity and recognition ability of imaging contrast agents and by selectively directing bioactive agents to biological targets. Focusing on cancer, promising nanoprototypes have been designed to overcome the lack of specificity of conventional chemotherapeutic agents, as well as for early detection of precancerous and malignant lesions. However, several obstacles, including difficulty in achieving the optimal combination of physicochemical parameters for tumor targeting, evading particle clearance mechanisms, and controlling drug release, prevent the translation of nanomedicines into therapy. In spite of this, recent efforts have been focused on developing functionalized nanoparticles for delivery of therapeutic agents to specific molecular targets overexpressed on different cancer cells. In particular, the combination of targeted and controlled-release polymer nanotechnologies has resulted in a new programmable nanotherapeutic formulation of docetaxel, namely BIND-014, which recently entered Phase II clinical testing for patients with solid tumors. BIND-014 has been developed to overcome the limitations facing delivery of nanoparticles to many neoplasms, and represents a validated example of targeted nanosystems with the optimal biophysicochemical properties needed for successful tumor eradication.

/pdf/targeted-therapy-using-nanotechnology-focus-on-cancer-4j28smzyme.pdf

Targeted therapy using nanotechnology: focus on cancer.

Hydrophobic modifications of cationic polymers for gene delivery

Biomimetic scaffolds mimic important features of the extracellular matrix (ECM) architecture and can be finely controlled at the nano- or microscale for tissue engineering. Rational design of biomimetic scaffolds is based on consideration of the ECM as a natural scaffold; the ECM provides cells with a variety of physical, chemical, and biological cues that affect cell growth and function. There are a number of approaches available to create 3D biomimetic scaffolds with control over their physical and mechanical properties, cell adhesion, and the temporal and spatial release of growth factors. Here, an overview of some biological features of the natural ECM is presented and a variety of original engineering methods that are currently used to produce synthetic polymer-based scaffolds in pre-fabricated form before implantation, to modify their surfaces with biochemical ligands, to incorporate growth factors, and to control their nano- and microscale geometry to create biomimetic scaffolds are discussed. Finally, in contrast to pre-fabricated scaffolds composed of synthetic polymers, injectable biomimetic scaffolds based on either genetically engineered- or chemically synthesized-peptides of which sequences are derived from the natural ECM are discussed. The presence of defined peptide sequences can trigger in situ hydrogelation via molecular self-assembly and chemical crosslinking. A basic understanding of the entire spectrum of biomimetic scaffolds provides insight into how they can potentially be used in diverse tissue engineering, regenerative medicine, and drug delivery applications.

Biomimetic Scaffolds for Tissue Engineering

A variety of organic and inorganic nanomaterials with dimensions below several hundred nanometers are recently emerging as promising tools for cancer therapeutic and diagnostic applications due to their unique characteristics of passive tumor targeting. A wide range of nanomedicine platforms such as polymeric micelles, liposomes, dendrimers, and polymeric nanoparticles have been extensively explored for targeted delivery of anti-cancer agents, because they can accumulate in the solid tumor site via leaky tumor vascular structures, thereby selectively delivering therapeutic payloads into the desired tumor tissue. In recent years, nanoscale delivery vehicles for small interfering RNA (siRNA) have been also developed as effective therapeutic approaches to treat cancer. Furthermore, rationally designed multi-functional surface modification of these nanomaterials with cancer targeting moieties, protective polymers, and imaging agents can lead to fabrication versatile theragnostic nanosystems that allow simultaneous cancer therapy and diagnosis. This review highlights the current state and future prospects of diverse biomedical nanomaterials for cancer therapy and imaging.

Nanomaterials for cancer therapy and imaging

Folate receptor-mediated intracellular delivery of recombinant caspase-3 for inducing apoptosis.

Energy efficient path planning for a marine surface vehicle considering heading angle

Fiber-optics gyroscopes (gyros) are gaining importance as a means for improving dead-reckoning accuracy in mobile robots. In the past, the relatively high drift rate of moderately priced gyros presented the foremost technical limitation of these devices. More recently, fiber-optics gyros with very low drift rates have become available and affordable. Because of their low drift rate attention is warranted to sources of errors that were previously considered as of secondary importance. In the KVH E-Core RD2100 gyros that were examined at our lab we found that the nonlinearity of the scale-factor and temperature dependency caused significant errors. A calibration method, described in the paper, reduces the resulting errors by one order of magnitude.

/pdf/precision-calibration-of-fiber-optics-gyroscopes-for-mobile-2vc4zp54zc.pdf

Hyun Chung

Papers

Nanomaterials for cancer therapy and imaging

Folate receptor-mediated intracellular delivery of recombinant caspase-3 for inducing apoptosis.

Energy efficient path planning for a marine surface vehicle considering heading angle

Precision calibration of fiber-optics gyroscopes for mobile robot navigation

Arctic sea route path planning based on an uncertain ice prediction model