Genipin,an Inhibitor of UCP2 as a Promising New Anticancer Agent: A Review of the Literature

Genipin is a protein cross-linking agent extracted from Gardenia (Gardenia jasminoides Ellis) fruits. This fruit has conventionally been used as a Chinese herbal medicine for the treatment of inflammation and jaundice and as an edible colorant in oriental countries. Uncoupling protein (UCP)-2 is a member of the family of uncoupling proteins, which are anion transporters positioned in the mitochondrial inner membrane. Genipin has been shown to have hepatoprotective activity, acting as an effective antioxidant and inhibitor of mitochondrial UCP2, and is also reported to exert significant anticancer effects. In this review, the author presents the latest progress of genipin as an anticancer agent and concisely describes its various mechanisms of action. In brief, genipin inhibits UCP2 to attenuate generation of reactive oxygen species (ROS), leading to ROS/c-Jun N-terminal kinase-dependent apoptosis of cancer cells. Genipin also increases the tissue inhibitors of matrix metalloproteases (MMP)-2, a kind of tumor promoter in a variety of cancers, as well as induces caspase-dependent apoptosis in in vitro and in vivo models. These findings suggest that genipin can serve as a promising novel antitumor agent that could be applicable for chemotherapy and/or chemoprevention for cancers.     

Advanced Code-Division Multiplexers for Superconducting Detector Arrays

Multiplexers based on the modulation of superconducting quantum interference devices are now regularly used in multi-kilopixel arrays of superconducting detectors for astrophysics, cosmology, and materials analysis. Over the next decade, much larger arrays will be needed. These larger arrays require new modulation techniques and compact multiplexer elements that fit within each pixel. We present a new in-focal-plane code-division multiplexer that provides multiplexing elements with the required scalability. This code-division multiplexer uses compact lithographic modulation elements that simultaneously multiplex both signal outputs and superconducting transition-edge sensor (TES) detector bias voltages. It eliminates the shunt resistor used to voltage bias TES detectors, greatly reduces power dissipation, allows different dc bias voltages for each TES, and makes all elements sufficiently compact to fit inside the detector pixel area. These in-focal plane code-division multiplexers can be combined with multi-GHz readout based on superconducting microresonators to scale to even larger arrays.     

Characterization of Inhibitory Capability on Hyperpolarization-Activated Cation Current Caused by Lutein (β,ε-Carotene-3,3′-Diol), a Dietary Xanthophyll Carotenoid

Lutein (β,ε-carotene-3,3′-diol), a xanthophyll carotenoid, is found in high concentrations in the macula of the human retina. It has been recognized to exert potential effectiveness in antioxidative and anti-inflammatory properties. However, whether and how its modifications on varying types of plasmalemmal ionic currents occur in electrically excitable cells remain incompletely answered. The current hypothesis is that lutein produces any direct adjustments on ionic currents (e.g., hyperpolarization-activated cation current, I_h [or funny current, I_f]). In the present study, GH₃-cell exposure to lutein resulted in a time-, state- and concentration-dependent reduction in I_h amplitude with an IC₅₀ value of 4.1 μM. There was a hyperpolarizing shift along the voltage axis in the steady-state activation curve of I_h in the presence of this compound, despite being void of changes in the gating charge of the curve. Under continued exposure to lutein (3 μM), further addition of oxaliplatin (10 μM) or ivabradine (3 μM) could be effective at either reversing or further decreasing lutein-induced suppression of hyperpolarization-evoked I_h, respectively. The voltage-dependent anti-clockwise hysteresis of I_h responding to long-lasting inverted isosceles-triangular ramp concentration-dependently became diminished by adding this compound. However, the addition of 10 μM lutein caused a mild but significant suppression in the amplitude of erg-mediated or A-type K⁺ currents. Under current-clamp potential recordings, the sag potential evoked by long-lasting hyperpolarizing current stimulus was reduced under cell exposure to lutein. Altogether, findings from the current observations enabled us to reflect that during cell exposure to lutein used at pharmacologically achievable concentrations, lutein-perturbed inhibition of I_h would be an ionic mechanism underlying its changes in membrane excitability.     

Therapeutic Effects of Insulin-Producing Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Type 1 Diabetes Mouse Model

In patients with type 1 diabetes (T1D), compromised pancreatic β-cell functions are compensated through daily insulin injections or the transplantation of pancreatic tissue or islet cells. However, both approaches are associated with specific challenges. The transplantation of mesenchymal stem cells (MSCs) represents a potential alternative, as MSCs have tissue-forming capacity and can be isolated from various tissues. The human umbilical cord (hUC) is a good source of freely available MSCs, which can be collected through pain-free, non-invasive methods subject to minimal ethical concerns. We sought to develop a method for the in vitro generation of insulin-producing cells (IPCs) using MSCs. We examined the potential therapeutic uses and efficacy of IPCs generated from hUC-derived MSCs (hUC-IPCs) and human adipose tissue (hAD)-derived MSCs (hAD-IPCs) through in vitro experiments and streptozotocin (STZ)-induced C57BL/6 T1D mouse models. We discovered that compared to hAD-IPCs, hUC-IPCs exhibited a superior insulin secretion capacity. Therefore, hUC-IPCs were selected as candidates for T1D cell therapy in mice. Fasting glucose and intraperitoneal glucose tolerance test levels were lower in hUC-IPC-transplanted mice than in T1D control mice and hAD-IPC-transplanted mice. Our findings support the potential use of MSCs for the treatment of T1D.     

A new methodology for identification of critical lines using damping sensitivity analysis

When an inter-area mode dominates a low-frequency oscillation in a stressed condition, control of the active power flow of interface lines, with compensating devices, can effectively reduce the electromechanical power oscillations. In general, interface lines in which inter-area oscillations are large are considered to be good locations for installation of compensating devices. A sensitivity analysis with respect to change in active power flow can provide an important factor in electric power system operation. This paper proposes a new methodology to calculate the damping sensitivity with respect to change in active power flow, which can be useful for accurate selection of critical lines from the viewpoint of small-signal stability. In the proposed methodology, a damping sensitivity index is used to select the critical lines to damp power system oscillations. This paper describes how to derive the damping sensitivity for the selected mode and illustrates an example applying the proposed algorithm to a simple two-area system and the New England 39-bus test system.     

Morphology-based approaches for detecting stream channels from ALSM data

To map the Earth's surface at remarkable resolution, Airborne Laser Swath Mapping (ALSM) instrument technology and subsequent algorithms have been used over the last several years. Since forested watersheds have commonly been problematic to study with remote sensing techniques, the ability of ALSM technology to densely sample ground elevations beneath forest canopies is especially considerable. Stream network detection from digital elevation models (DEMs) is a key role in modelling spatially distributed hydrological processes. To detect stream channels, we have developed two approaches. The first approach is based on an encoding of mathematical morphological operators. In the second approach, a composition of geodesic top-hat and bot-hat operations of different sizes is used in order to build a morphological profile (P _M) that records the image structural information. The two proposed methods perform well in terms of detection results and classification accuracies. The second approach is more general than the first, but it also requires training and more computation.     

Motivations for Open Source Project Participation and Decisions of Software Developers

We provide a rationale for open source project participation by studying the decision problems of the software programmers, whose types are different in terms of ability and intrinsic motivation. We find that motivations, both intrinsic and extrinsic, and the ability level positively affect the optimal level of effort exerted by the programmers in the open source project. In the commercial project, the programmers with higher ability exert much effort although their high level of effort is not compensated properly. Thus, the open source project might be more likely to attract capable and motivated programmers than the commercial project.     

A study on the optimization of KCI-based index (Kor-Factor) in evaluating Korean journals

This study describes the development process of Kor-Factor, which is a novel composite evaluation index that was developed to promote Korean domestic academic journals. As more data accumulate, the Kor-Factor’s optimization process was modified in an attempt to address possible drawbacks of the original form; the result is presented in this study. This study compares Kor-Factor with the Impact Factor, which is the most well-known single element evaluation index. We found that Kor-Factor demonstrates a better power of differentiation and a greater capacity to reflect the reputability of key journals. The modified Kor-Factor, which has been developed through an optimization process, reveals a greater power of differentiation than the original Kor-Factor; however, the modified version has less capacity to reflect reputability. The evaluation elements of the modified Kor-Factor are better and are more evenly reflected on the index value than those of the original version. Finally, we propose the establishment of an appropriate data measurement period for the actual application of the index.