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Purpose: Understanding the configuration and characteristics of the comminuted fifth metacarpal neck fractures is essential for successful operative treatment, especially for antegrade intramedullary Kirchner wire (K-wire) fixation. This study aimed to investigate the characteristics and shape of comminuted fragments in fifth metacarpal neck fractures and suggest the appropriate K-wire position. Methods: Forty-one cases of fifth metacarpal neck fractures operated from January 2010 to April 2022 were enrolled in this study. The length and width of the comminuted fragments were measured, as well as the distance from the articular surface of the fifth metacarpal head to the comminuted fragment (Da-c) and the distance from the articular surface to the proximal end of the metacarpal head (Da-h). The location of the comminuted fragments was categorized in terms of four quadrants: dorsal-ulnar (DU), dorsal-radial (DR), palmar-radial, and palmar-ulnar.Results: Among 41 patients with fifth metacarpal neck fractures, comminuted fracture fragments were observed in 35 cases (85.4%). The mean length and width of the comminuted fragments were 7.5±2.3 mm and 3.2±0.8 mm, respectively. The comminuted fragments were on the dorsal aspect of the fracture in all cases; 27 (77.1%) in the DU quadrant and 8 (22.9%) in the DR quadrant. The mean Da-c and Da-h were 5.3±1.6 mm and 10.9±1.5 mm, respectively.Conclusion: To ensure stable K-wire fixation, it is essential to identify the location and characteristics of the comminuted fracture fragments before surgery and subsequently choose an appropriate K-wire position.

KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer. However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.

Alzheimer’s Disease (AD) is a global healthcare crisis. The TgF344-AD rat is an AD model exhibiting age-dependent AD pathological hallmarks. We confirmed that AD rats developed cognitive deficits at 6 months without alteration of any other major biophysical parameters. We longitudinally characterized cerebral hemodynamics in AD rats at 3, 4, 6, and 14 months. The myogenic responses of the cerebral arteries and arterioles were impaired at 4 months of age in the AD rats. Consistent with theex vivoresults, the AD rat exhibited poor autoregulation of surface and deep cortical cerebral blood flow two months preceding cognitive decline. The dysfunction of cerebral hemodynamics in AD is exacerbated with age associated with reduced cerebral perfusion. Further, abolished cell contractility contributes to cerebral hemodynamics imbalance in AD. This may be attributed to enhanced ROS production, reduced mitochondrial respiration and ATP production, and disrupted actin cytoskeleton in cerebral vascular contractile cells.

Piezo2 mechanotransduction channel is a crucial mediator of sensory neurons for sensing and transducing touch, vibration, and proprioception. We here characterized Piezo2 expression and cell specificity in rat peripheral sensory pathway using a validated Piezo2 antibody. Immunohistochemistry using this antibody revealed Piezo2 expression in pan primary sensory neurons of dorsal root ganglia in naive rats, which was actively transported along afferent axons to both central presynaptic terminals innervating the spinal dorsal horn (DH) and peripheral afferent terminals in the skin. Piezo2 immunoreactivity (IR) was also detected in the postsynaptic neurons of the DH and in the motor neurons of the ventral horn, but not in spinal glial fibrillary acidic protein-positive and Iba1-positive glia. Notably, Piezo2-IR was clearly identified in peripheral nonneuronal cells, including perineuronal glia, Schwann cells in the sciatic nerve and surrounding cutaneous afferent endings, as well as in skin epidermal Merkel cells and melanocytes. Immunoblots showed increased Piezo2 in dorsal root ganglia ipsilateral to plantar injection of complete Freund's adjuvant, and immunostaining revealed increased Piezo2-IR intensity in the DH ipsilateral to complete Freund's adjuvant injection. This elevation of DH Piezo2-IR was also evident in various neuropathic pain models and monosodium iodoacetate knee osteoarthritis pain model, compared with controls. We conclude that (1) the pan neuronal profile of Piezo2 expression suggests that Piezo2 may function extend beyond simply touch or proprioception mediated by large-sized low-threshold mechanosensitive primary sensory neurons; (2) Piezo2 may have functional roles involving sensory processing in the spinal cord, Schwann cells, and skin melanocytes; and (3) aberrant Piezo2 expression may contribute pain pathogenesis.

Background Peripheral and central nociceptive sensitization is a critical pathogenetic component in osteoarthritis (OA) chronic pain. T-type calcium channel 3.2 (CaV3.2) regulates neuronal excitability and plays important roles in pain processing. We previously identified that enhanced T-type/CaV3.2 activity in the primary sensory neurons (PSNs) of dorsal root ganglia (DRG) is associated with neuropathic pain behavior in a rat model of monosodium iodoacetate (MIA)-induced knee OA. PSN-specific T-type/CaV3.2 may therefore represent an important mediator in OA painful neuropathy. Here, we test the hypothesis that the T-type/CaV3.2 channels in PSNs can be rationally targeted for pain relief in MIA-OA. Methods MIA model of knee OA was induced in male and female rats by a single injection of 2 mg MIA into intra-knee articular cavity. Two weeks after induction of knee MIA-OA pain, recombinant adeno-associated viruses (AAV)-encoding potent CaV3.2 inhibitory peptide aptamer 2 (CaV3.2iPA2) that have been characterized in our previous study were delivered into the ipsilateral lumbar 4/5 DRG. Effectiveness of DRG-CaV3.2iPA2 treatment on evoked (mechanical and thermal) and spontaneous (conditioned place preference) pain behavior, as well as weight-bearing asymmetry measured by Incapacitance tester, in the arthritic limbs of MIA rats were evaluated. AAV-mediated transgene expression in DRG was determined by immunohistochemistry. Results AAV-mediated expression of CaV3.2iPA2 selective in the DRG-PSNs produced significant and comparable mitigations of evoked and spontaneous pain behavior, as well as normalization of weight-bearing asymmetry in both male and female MIA-OA rats. Analgesia of DRG-AAV-CaV3.2iPA1, another potent CaV3.2 inhibitory peptide, was also observed. Whole-cell current-clamp recordings showed that AAV-mediated CaV3.2iPA2 expression normalized hyperexcitability of the PSNs dissociated from the DRG of MIA animals, suggesting that CaV3.2iPA2 attenuated pain behavior by reversing MIA-induced neuronal hyperexcitability. Conclusions Together, our results add therapeutic support that T-type/CaV3.2 in primary sensory pathways contributes to MIA-OA pain pathogenesis and that CaV3.2iPAs are promising analgesic leads that, combined with AAV-targeted delivery in anatomically segmental sensory ganglia, have the potential for further development as a peripheral selective T-type/CaV3.2-targeting strategy in mitigating chronic MIA-OA pain behavior. Validation of the therapeutic potential of this strategy in other OA models may be valuable in future study.

Here, we present evidence showing Piezo1 protein expression in the primary sensory neurons (PSNs) and non-neuronal cells of rat peripheral nervous system. Using a knockdown/knockout validated antibody, we detected Piezo1 immunoreactivity (IR) in ∼60% of PSNs of rat dorsal root ganglia (DRG) with higher IR density in the small- and medium-sized neurons. Piezo1-IR was clearly identified in DRG perineuronal glia, including satellite glial cells (SGCs) and Schwann cells; in sciatic nerve Schwann cells surrounding the axons and cutaneous afferent endings; and in skin epidermal Merkel cells and melanocytes. Neuronal and non-neuronal Piezo1 channels were functional since various cells (dissociated PSNs and SGCs from DRGs, isolated Schwann cells, and primary human melanocytes) exhibited a robust response to Piezo1 agonist Yoda1 by an increase of intracellular Ca2+ concentration ([Ca2+]i). These responses were abolished by non-specific Piezo1 antagonist GsMTx4. Immunoblots showed elevated Piezo1 protein in DRG proximal to peripheral nerve injury-induced painful neuropathy, while PSNs and SGCs from rats with neuropathic pain showed greater Yoda1-evoked elevation of [Ca2+]i and an increased frequency of cells responding to Yoda1, compared to controls. Sciatic nerve application of GsMTx4 alleviated mechanical hypersensitivity induced by Yoda1. Overall, our data show that Piezo1 is widely expressed by the neuronal and non-neuronal cells in the peripheral sensory pathways and that painful nerve injury appeared associated with activation of Piezo1 in PSNs and peripheral glial cells.

Ample data support a prominent role of peripheral T-type calcium channels 3.2 (Ca V 3.2) in generating pain states. Development of primary sensory neuron-specific inhibitors of Ca V 3.2 channels is an opportunity for achieving effective analgesic therapeutics, but success has been elusive. Small peptides, especially those derived from natural proteins as inhibitory peptide aptamers (iPAs), can produce highly effective and selective blockade of specific nociceptive molecular pathways to reduce pain with minimal off-target effects. In this study, we report the engineering of the potent and selective iPAs of Ca V 3.2 from the intrinsically disordered regions (IDRs) of Ca V 3.2 intracellular segments. Using established prediction algorithms, we localized the IDRs in Ca V 3.2 protein and identified several Ca V 3.2iPA candidates that significantly reduced Ca V 3.2 current in HEK293 cells stably expressing human wide-type Ca V 3.2. Two prototype Ca V 3.2iPAs (iPA1 and iPA2) derived from the IDRs of Ca V 3.2 intracellular loops 2 and 3, respectively, were expressed selectively in the primary sensory neurons of dorsal root ganglia in vivo using recombinant adeno-associated virus (AAV), which produced sustained inhibition of calcium current conducted by Ca V 3.2/T-type channels and significantly attenuated both evoked and spontaneous pain behavior in rats with neuropathic pain after tibial nerve injury. Recordings from dissociated sensory neurons showed that AAV-mediated Ca V 3.2iPA expression suppressed neuronal excitability, suggesting that Ca V 3.2iPA treatment attenuated pain by reversal of injury-induced neuronal hypersensitivity. Collectively, our results indicate that Ca V 3.2iPAs are promising analgesic leads that, combined with AAV-mediated delivery in anatomically targeted sensory ganglia, have the potential to be a selective peripheral Ca V 3.2-targeting strategy for clinical treatment of pain.

This study reports that targeting intrinsically disordered regions (IDRs) of NaV1.7 protein facilitated discovery of sodium channel inhibitory peptide aptamers (NaviPA) for adeno-associated virus (AAV)-mediated, sensory neuron-specific analgesia. A multipronged inhibition of INa1.7, INa1.6, and INa1.3, but not INa1.5and INa1.8was found for a prototype, named NaviPA1, which was derived from the NaV1.7 intracellular loop 1 and is conserved among the TTXs NaVsubtypes. NaviPA1 expression in primary sensory neurons (PSNs) of dorsal root ganglia (DRG) produced significant inhibition of TTXs INabut not TTXr INa. DRG injection of AAV6-encoded NaviPA1 significantly attenuated evoked and spontaneous pain behaviors in both male and female rats with neuropathic pain induced by tibial nerve injury (TNI). Whole-cell current-clamp of the PSNs showed that NaviPA1 expression normalized PSN excitability in TNI rats, suggesting that NaviPA1 attenuated pain by reversal of injury-induced neuronal hypersensitivity. Immunohistochemistry revealed efficient NaviPA1 expression restricted in PSNs and their central and peripheral terminals, indicating PSN-restricted AAV biodistribution. Inhibition of sodium channels by NaviPA1 was replicated in the human iPSC-derived sensory neurons. These results summate that NaviPA1 is a promising analgesic lead that, combined with AAV-mediated PSN-specific block of multiple TTXs NaVs has potential as peripheral nerve-restricted analgesic therapeutics.

S-SCAM/MAGI-2 gene duplication is associated with schizophrenia (SCZ). S-SCAM overexpression in the forebrain induces SCZ-like phenotypes in a transgenic (Tg) mouse model. Interestingly, S-SCAM Tg mice show male-specific impairments in synaptic plasticity and working memory. However, mechanisms underlying the sex-specific deficits remain unknown. Here we report that S-SCAM Tg mice have male-specific deficits in synaptic GSK3β functions, as shown by reduced synaptic protein levels and increased inhibitory phosphorylation of GSK3β. This GSK3β hyper-phosphorylation was associated with increased CaMKII activities. Notably, synaptic levels of Axin1, to which GSK3β binds in competition with S-SCAM, were also reduced in male S-SCAM Tg mice. We demonstrated that Axin-binding is required for the S-SCAM overexpression-induced synaptic GSK3β reduction. Axin stabilization using XAV939 rescued the GSK3β deficits and restored the temporal activation of GSK3β during long-term depression in S-SCAM overexpressing neurons. Interestingly, synaptic Axin2 levels were increased in female S-SCAM Tg mice. Female sex hormone 17β-estradiol increased Axin2 expression and increased synaptic GSK3β levels in S-SCAM overexpressing neurons. These results reveal the role of S-SCAM in controlling Axin-dependent synaptic localization of GSK3β. Moreover, our studies point out the pathological relevance of GSK3β hypofunction found in humans and contribute to understanding the molecular underpinnings of sex differences in SCZ.

There is an active technological development effort into the fuel efficiency enhancement of the existing internal combustion engine vehicles. As part of this technological development effort, researches are being conducted on the use of lithium batteries as the starter battery for internal combustion engine vehicles, in place of lead–acid batteries. While the use of lithium starter battery is expected to result in various advantages and disadvantages, there is a lack of specific research on this area. Therefore, in this paper, we present a quantitative analysis of the characteristics and performance of internal combustion engine vehicles with different types of starter batteries. For this purpose, we simulate the power-net system of a vehicle, including charging control, through a test bench based on actual vehicle data, and develop an automotive power-net hardware-in-the-loop simulation (HILS) by combining the test bench with a powertrain model. HILS-based test and evaluation were performed for vehicles equipped with absorbent glass mat (AGM) battery and those with lithium battery, using an actual road evaluation pattern to compare their characteristics and performance with impedance measurements for each type of battery.

Pancreatic cancer exhibits an oncogenic KRAS mutation rate of ∼90%. Despite research and drug development efforts focused on KRAS, no targeted therapy has been clinically approved for the treatment of pancreatic cancer with KRAS mutation. Also, the efficacy of gemcitabine is poor due to rapidly acquired resistance. We developed RT11-i antibody, which directly targets the intracellularly activated GTP-bound form of oncogenic RAS mutants. Here, we investigated the combined effects of RT11-i and gemcitabine in vitro and in vivo, and the mechanism involved. RT11-i significantly sensitized pancreatic cancer cells to gemcitabine. Also, the co-treatment synergistically inhibited angiogenesis, migration, and invasion, and showed synergistic anticancer activity by inhibiting the RAF/MEK/ERK or PI3K/AKT pathways. Furthermore, co-treatment inhibited endothelial barrier disruption in tumor vessels, which is a critical step in vascular leakiness of metastasis, and improved vessel structural stability. Importantly, co-treatment significantly suppressed tumor growth in an orthotopic tumor model. Taken together, our findings show that RT11-i synergistically increased the antitumor activity of gemcitabine by inhibiting RAS downstream signaling, which suggests RT11-i and gemcitabine be viewed a potential combination treatment option for pancreatic cancer patients with KRAS mutation.

KRAS mutation is associated with the progression and growth of pancreatic cancer and contributes to chemo-resistance, which poses a significant clinical challenge in pancreatic cancer. Here, we developed a RT22-ep59 antibody (Ab) that directly targets the intracellularly activated GTP-bound form of oncogenic KRAS mutants after it is internalized into cytosol by endocytosis through tumor-associated receptor of extracellular epithelial cell adhesion molecule (EpCAM) and investigated its synergistic anticancer effects in the presence of gemcitabine in pancreatic cancer. We first observed that RT22-ep59 specifically recognized tumor-associated EpCAM and reached the cytosol by endosomal escape. In addition, the anticancer effect of RT22-ep59 was observed in the high-EpCAM-expressing pancreatic cancer cells and gemcitabine-resistant pancreatic cancer cells, but it had little effect on the low-EpCAM-expressing pancreatic cancer cells. Additionally, co-treatment with RT22-ep59 and gemcitabine synergistically inhibited cell viability, migration, and invasion in 3D-cultures and exhibited synergistic anticancer activity by inhibiting the RAF/ERK or PI3K/AKT pathways in cells with high-EpCAM expression. In an orthotopic mouse model, combined administration of RT22-ep59 and gemcitabine significantly inhibited tumor growth. Furthermore, the co-treatment suppressed cancer metastasis by blocking EMT signaling in vitro and in vivo. Our results demonstrated that RT22-ep59 synergistically increased the antitumor activity of gemcitabine by inhibiting RAS signaling by specifically targeting KRAS. This indicates that co-treatment with RT22-ep59 and gemcitabine might be considered a potential therapeutic strategy for pancreatic cancer patients harboring KRAS mutation.

The Sigma-1 receptor (σ(1)R) is highly expressed in the primary sensory neurons (PSNs) that are the critical site of initiation and maintenance of pain following peripheral nerve injury. By immunoblot and immunohistochemistry, we observed increased expression of both σ(1)R and σ1R-binding immunoglobulin protein (BiP) in the lumbar (L) dorsal root ganglia (DRG) ipsilateral to painful neuropathy induced by spared nerve injury (SNI). To evaluate the therapeutic potential of PSN-targeted σ(1)R inhibition at a selected segmental level, we designed a recombinant adeno-associated viral (AAV) vector expressing a small hairpin RNA (shRNA) against rat σ(1)R. Injection of this vector into the L4/L5 DRGs induced downregulation of σ(1)R in DRG neurons of all size groups, while expression of BiP was not affected. This was accompanied by attenuation of SNI-induced cutaneous mechanical and thermal hypersensitivity. Whole-cell current-clamp recordings of dissociated neurons showed that knockdown of σ(1)R suppressed neuronal excitability, suggesting that σ(1)R silencing attenuates pain by reversal of injury-induced neuronal hyperexcitability. These findings support a critical role of σ(1)R in modulating PSN nociceptive functions, and that the nerve injury-induced elevated σ(1)R activity in the PSNs can be a significant driver of neuropathic pain. Further understanding the role of PSN-σ(1)R in pain pathology may open routes to exploit this system for DRG-targeted pain therapy.

The duplication and deletion mutations of the S-SCAM/MAGI-2 gene are associated with schizophrenia and infantile spasms, respectively. S-SCAM is a unique synaptic scaffolding protein that localizes to both excitatory and GABAergic synapses. However, consequences of aberrant S-SCAM expression on GABAergic synapses is little studied. Here we report the effect of S-SCAM knockdown and overexpression on GABAergic synapses. S-SCAM knockdown in cultured hippocampal neurons caused a drastic loss of both pre- and post-synaptic components of GABAergic synapses, indicating its essential role in GABAergic synapse formation and maintenance. Surprisingly, S-SCAM overexpression also attenuated GABAergic synapses, but the effect is mediated by the loss of postsynaptic GABAA receptors, gephyrin, and neuroligin 2 and does not involve presynaptic component vesicular GABA transporters. Overexpression studies using S-SCAM mutants with various domain deletions indicated that GABAergic synapse loss correlates with their ability to increase excitatory synaptic function. Consistently, AMPA receptor antagonist CNQX or calcineurin inhibitor FK506 abolished the S-SCAM overexpression-induced loss of GABAA receptors, supporting that GABAergic synapse loss by S-SCAM overexpression is due to the activity-induced dispersal of synaptic GABAA receptors. These results suggest that abnormal S-SCAM protein levels disrupt excitation/inhibition balance in neurons, which may explain the pathogenic nature of S-SCAM copy number variations.

This work was supported by the Industrial technology Innovation Program (No. 10063421, 'Development of the in-line welds quality estimation system and network-based quality control technology in arc and spot welds of ultra high strength steels for automotive parts assembly') funded By the Ministry of Trade, industry & Energy(MI, Korea).This research was respectfully supported by Engineering Development Research Center (EDRC) funded by the Ministry of Trade, Industry & Energy (MOTIE). (No. N0000990)

Oncogenic Ras mutants, and most frequently KRas mutants (86% of Ras-driven cancers), are found in approximately 25% of human cancers and are high-priority anticancer drug targets. Despite 30 years of effort to develop drugs that directly target oncogenic Ras mutants, no effective pharmacologic inhibitors for these mutants are clinically available, mainly because of the lack of suitable surface binding pockets for small molecules. More than 50 therapeutic antibodies have been clinically approved against many extracellular proteins. However, such antibodies do not have the capacity to localize in intracellular cytosolic regions after receptor-mediated endocytosis, restricting their therapeutic application for targeting cytosolic proteins. Our group recently developed a platform technology of cytosol-penetrating antibody, which in the IgG format can reach the cytosolic space of living cells owing to its endosomal escaping ability after receptor-mediated endocytosis. Exploiting the cytosol-penetrating antibody technology, we have engineered a human IgG1 format antibody, named iMab (internalizing and protein-protein interaction [PPI] interfering monoclonal antibody), which internalizes into the cytosol of living cells and selectively binds to the activated GTP-bound form of oncogenic Ras mutants. iMab specifically binds to the PPI interfaces of activated Ras with effector proteins to block the associations, thereby inhibiting the Ras downstream oncogenic signaling and exerting antiproliferation effects on oncogenic Ras mutant tumor cells. For in vivo antitumor efficacy assessment, we further engineer iMab to have tumor tissue-homing ability by fusion of tumor-associated integrin αvβ3/αvβ5 binding cyclic peptide to the N-terminus of light chain. When systemically administered, the iMab variant significantly inhibited the in vivo growth of oncogenic Ras-mutated tumor xenografts in mice, but not wild-type Ras-harboring tumors. Our results demonstrate the feasibility of developing antibody therapeutics that directly target cytosolic proteins involved in disease-associated PPIs, such as oncogenic Ras mutants, by systemic administration, similar to conventional therapeutic antibody regimens. Because the oncogenic Ras targeting antibody holds many desirable features of the conventional IgG antibody, it shows great potential for development as a first-in-class anticancer antibody. Citation Format: Seung-Min Shin, Ji-Sun Kim, Jin-Sun Hong, Seong-wook Park, Sei-Yong Jun, Hye-Jin Kweon, Dong-Ki Choi, Yong-Sung Kim. Direct targeting oncogenic Ras mutants by IgG-format cytosol-penetrating antibody [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr B28.

Secreted Wnts play crucial roles in synaptogenesis and synapse maintenance, but endogenous factors promoting synapse elimination in central neurons remain unknown. Here we show that proline-rich 7 (PRR7) induces specific removal of excitatory synapses and acts as a Wnt inhibitor. Remarkably, transmembrane protein PRR7 is activity-dependently released by neurons via exosomes. Exosomal PRR7 is uptaken by neurons through membrane fusion and eliminates excitatory synapses in neighboring neurons. Conversely, PRR7 knockdown in sparse neurons greatly increases excitatory synapse numbers in all surrounding neurons. These non-cell autonomous effects of PRR7 are effectively negated by augmentation or blockade of Wnt signaling. PRR7 exerts its effect by blocking the exosomal secretion of Wnts, activation of GSK3β, and promoting proteasomal degradation of PSD proteins. These data uncover a proximity-dependent, reciprocal mechanism for the regulation of excitatory synapse numbers in local neurons and demonstrate the significance of exosomes in inter-neuronal signaling in the vertebrate brain., Wnts are important for synapse formation and maintenance. Here, the authors show that proline-rich 7 (PRR7) is a Wnt inhibitor that is secreted via exosomes to regulate excitatory synapse numbers.

The main obstacles for practical uses of cytosol-penetrating peptides and proteins include their lack of cell- or tissue-specific targeting and limited cytosolic access owing to the poor endosomal escape ability. We have previously reported a cytosol-penetrating, human IgG1 antibody TMab4-WYW, generally referred to as a cytotransmab (CT), which reaches the cytosol of living cells but nonspecifically because it is endocytosed via a ubiquitously expressed receptor called heparan sulfate proteoglycan (HSPG). Here, our aim was to construct a next-generation CT with tumor cell specificity and improved endosomal escape efficiency. We first substantially reduced the HSPG-binding activity of TMab4-WYW and then fused a cyclic peptide specifically recognizing tumor-associated epithelial cell adhesion molecule (EpCAM) to the N terminus of the light chain for EpCAM-mediated endocytosis, while maintaining the endosomal escape ability in the light chain variable domain (VL), thus generating epCT05. Then, we separately engineered another CT, dubbed epCT65-AAA, with an endosomal escape ability only in the heavy chain variable domain (VH) but not in VL, by functional grafting of the endosomal escape motif of epCT05 VL to the VH. We finally combined the heavy chain of epCT65-AAA and the light chain of epCT05 to create epCT65 with endosomal escape capacity in both the VH and VL. epCT65 effectively localized to the cytosol of only EpCAM-expressing tumor cells and showed approximately twofold improved endosomal escape efficiency, as compared with CTs with endosomal escape motifs in either VH or VL. The full-IgG format CT, epCT65, with a tumor cell-specific cytosol-penetrating activity, has a great potential for practical medical applications, e.g., as a carrier for cytosolic delivery of payloads.

Considering the number of cytosolic proteins associated with many diseases, development of cytosol-penetrating molecules from outside of living cells is highly in demand. To gain access to the cytosol after cellular uptake, cell-penetrating molecules should be released from intermediate endosomes prior to the lysosomal degradation. However, it is very challenging to distinguish the pool of cytosolic-released molecules from those trapped in the endocytic vesicles. Here we describe a method to directly demonstrate the cytosolic localization and quantification of cytosolic amount of a cytosol-penetrating IgG antibody, TMab4, based on enhanced split GFP complementation system. We generated TMab4 genetically fused with one GFP fragment and separately established HeLa cells expressing the other GFP fragment in the cytosol such that the complemented GFP fluorescence is observed only when extracellular-treated TMab4 reaches the cytosol after cellular internalization. The high affinity interactions between streptavidin-binding peptide 2 and streptavidin was employed as respective fusion partners of GFP fragments to enhance the sensitivity of GFP complementation. With this method, cytosolic concentration of TMab4 was estimated to be about 170 nM after extracellular treatment of HeLa cells with 1 μM TMab4 for 6 h. We also found that after cellular internalization into living cells, nearly 1.3-4.3% of the internalized TMab4 molecules escaped into the cytosol from the endocytic vesicles. Our enhanced split GFP complementation assay provides a useful tool to directly quantify cytosolic amount of cytosol-penetrating agents and allows cell-based high-throughput screening for cytosol-penetrating agents with increased endosomal-escaping activity.

This paper presents the results of an investigation into the effect of forced temperature change cycles on physical and mechanical properties of sand and weathered granite soil. The effect of forced temperature change cylecs on the particle arrangement and the thermal conductivity was first investigated. A series of triaxial compression tests on the soils were also performed to look into the effect of temperature change cycles on the stress-strain-strength behavior. The results indicated that the forced temperature change cycle does not significantly affect the particle arrangement and thermal conductivity. It is shown however that the heating duration showed some effect on the deviatoric stress at failure while no significant effect due to the number of heating-cooling cycle was observed.

In this study, the authors propose a signal detection technique of successive interference cancellation to reduce the effect of inter-symbol interference (ISI), which is caused by the time difference of arrivals among distributed nodes in an asynchronous wireless mesh network based on filtered multi-tone modulation. The proposed signal detection technique uses partial matrices of a transmission gain matrix to mitigate the ISI effect from the adjacent symbols. Under the assumption of perfect symbol time offset and channel estimation at each node, it is shown by simulation that the proposed technique can improve the bit error rate performance with lower complexity compared with the conventional technique.

This paper proposes a maximum efficiency operation strategy for three-level T-type inverter in entire operation areas. The three-level T-type inverter has higher and lower efficiency areas compared with two-level inverter. The proposed strategy aims to operate in the maximum efficiency point for the low-voltage and low-power home appliances. The three-level T-type inverter is analyzed in detail, and the two operation mode selection strategy is developed. The proposed algorithm is verified by theoretical analysis and experimental results.

Accumulating genetic evidence suggests that schizophrenia (SZ) is associated with individually rare copy number variations (CNVs) of diverse genes, often specific to single cases. However, the causality of these rare mutations remains unknown. One of the rare CNVs found in SZ cohorts is the duplication ofSynaptic Scaffolding Molecule(S-SCAM, also calledMAGI-2), which encodes a postsynaptic scaffolding protein controlling synaptic AMPA receptor levels, and thus the strength of excitatory synaptic transmission. Here we report that, in a transgenic mouse model simulating the duplication conditions, elevation of S-SCAM levels in excitatory neurons of the forebrain was sufficient to induce multiple SZ-related endophenotypes. S-SCAM transgenic mice showed an increased number of lateral ventricles and a reduced number of parvalbumin-stained neurons. In addition, the mice exhibited SZ-like behavioral abnormalities, including hyperlocomotor activity, deficits in prepulse inhibition, increased anxiety, impaired social interaction, and working memory deficit. Notably, the S-SCAM transgenic mice showed a unique sex difference in showing these behavioral symptoms, which is reminiscent of human conditions. These behavioral abnormalities were accompanied by hyperglutamatergic function associated with increased synaptic AMPA receptor levels and impaired long-term potentiation. Importantly, reducing glutamate release by the group 2 metabotropic glutamate receptor agonist LY379268 ameliorated the working memory deficits in the transgenic mice, suggesting that hyperglutamatergic function underlies the cognitive functional deficits. Together, these results contribute to validate a causal relationship of the rare S-SCAM CNV and provide supporting evidence for the rare CNV hypothesis in SZ pathogenesis. Furthermore, the S-SCAM transgenic mice provide a valuable new animal model for studying SZ pathogenesis.

Purpose: To establish management protocol for mandibular angle fracture, we describe pertinent factors including cause, impacted third molar and recent treatment tendency. Methods: We examined the records of 62 patients who had unilateral mandibular angle fracture. Sixty patients who had open reduction surgery were examined at postoperative weeks 1, 4, 8, 12, and 28. Results: Left mandibular angle fracture is frequent in younger males. Presence of the mandibular third molar can increase fracture risk. Because of attached muscle, favorable fractures occurred primarily in the mandibular angle area. Conclusion: Extracting the mandibular third molar can prevent angle fractures, and open reduction with only one plate adaptation is generally the proper treatment method for mandibular angle fracture.

This paper proposes a compensation PWM technique for the extension of output voltage ranges in three-phase VSI applications using three shunt resistors. The proposed technique aims to solve the dead zone, which occurs in high modulation indexes. In the dead zone, two phase currents cannot be sampled correctly, so that the three-phase VSI cannot be operated up to the maximum output voltage. The dead zone is analyzed in detail, and the compensation PWM algorithm is developed. The proposed algorithm is verified by numerical analysis and experimental results.

Supplemental Digital Content is Available in the Text., Introduction: Tmem100 modulates interactions between TRPA1 and TRPV1. The cell specificity of Tmem100 expression in dorsal root ganglia (DRGs) is not well defined, nor is the effect of peripheral nerve injury on Tmem100 expression. Objective: This study was designed to determine the cell specificity of Tmem100 expression in DRG and its subcellular localization, and to examine how Tmem100 expression may be altered in painful conditions. Methods: Dorsal root ganglion Tmem100 expression was determined by immunohistochemistry, immunoblot, and quantitative real-time PCR, and compared between various experimental rat pain models and controls. Results: Tmem100 is expressed in both neurons and perineuronal glial cells in the rat DRG. The plasma membrane and intracellular localization of Tmem100 are identified in 83% ± 6% of IB4-positive and 48% ± 6% of calcitonin gene-related peptide–positive neurons, as well as in medium- and large-sized neurons, with its immunopositivity colocalized to TRPV1 (94% ± 5%) and TRPA1 (96% ± 3%). Tmem100 is also detected in the perineuronal satellite glial cells and in some microglia. Tmem100 protein is significantly increased in the lumbar DRGs in the complete Freund adjuvant inflammatory pain. By contrast, peripheral nerve injury by spinal nerve ligation diminishes Tmem100 expression in the injured DRG, with immunoblot and immunohistochemistry experiments showing reduced Tmem100 protein levels in both neurons and satellite glial cells of DRGs proximal to injury, whereas Tmem100 is unchanged in adjacent DRGs. The spared nerve injury model also reduces Tmem100 protein in the injured DRGs. Conclusion: Our data demonstrate a pain pathology–dependent alteration of DRG Tmem100 protein expression, upregulated during CFA inflammatory pain but downregulated during neuropathic pain.

Along with the recent developments of environmentally friendly vehicles, there is an active technological development effort into the fuel efficiency enhancement of the existing internal combustion engine vehicles. As part of such technological development effort, researches are being conducted on the use of lithium batteries as the starter battery for internal combustion engine vehicles in place of lead-acid batteries, which have already been released as a test product for high-end vehicles. While the use of lithium starter battery as a replacement is expected to lead to various advantages and disadvantages at the same time, there is a lack of specific research on this area. Therefore, in this paper, we present a quantitative analysis of characteristics and performance in internal combustion engine vehicles with different battery types. For this purpose, we simulate a power-net system of a vehicle including charging control through a test bench based on actual vehicle data, and develop automotive power-net HILS by combining the test bench with a powertrain model. Based on HILS, we conduct tests of vehicles with AGM battery and lithium battery under various test scenarios, in order to comparatively analyze the characteristics and performance of the vehicle.

How does chronic activity modulation lead to global remodeling of proteins at synapses and synaptic scaling? Here we report a role of guanylate-kinase-associated-protein (GKAP; also known as SAPAP), a scaffolding molecule linking NMDA receptor-PSD-95 to Shank-Homer complexes, in these processes. Over-excitation removes GKAP from synapses via ubiquitin-proteasome system, while inactivity induces synaptic accumulation of GKAP in rat hippocampal neurons. The bi-directional changes of synaptic GKAP levels are controlled by specific CaMKII isoforms coupled to different Ca2+ channels. α-CaMKII activated by NMDA receptor phosphorylates Serine-54 of GKAP to induce poly-ubiquitination of GKAP. In contrast, β-CaMKII activation via L-type voltage-dependent calcium channel promotes GKAP recruitment by phosphorylating Serine-340 and Serine-384 residues, which uncouples GKAP from MyoVa motor complex. Remarkably, overexpressing GKAP turnover mutants not only hampers activity-dependent remodeling of PSD-95 and Shank but also blocks bi-directional synaptic scaling. Therefore, activity-dependent turnover of PSD proteins orchestrated by GKAP is critical for homeostatic plasticity.

Human cervical cancer oncogene 1, HCCR-1, is over-expressed in various human tumors and appears to serve as a negative regulator of the p53 gene. HCCR-1 transgenic mice developed breast cancers but it is unknown how HCCR-1 contributes to tumorigenesis. We identified the HCCR-1 binding protein 3 (HCCRBP-3) as a binding partner for HCCR-1. These two proteins co-localized to the mitochondria. HCCRBP-3 over-expressed in various human tumors converted normal cells into tumor cells in vitro. Nude mice injected with NIH/3T3 cells stably transfected with HCCRBP-3 also induced the tumor formation. In addition, p53 showed the functional impairment in HCCRBP-3-transfected cells as accompanied with defective induction of p21 and bax. In support of this, p21 promoter activities containing p53 responsive elements were inhibited by HCCRBP-3 in a dose-dependent manner. Therefore, our study suggests that HCCRBP-3 contributes to the HCCR-1 induced tumorigenesis by interrupting the p53 function.

Synaptic plasticity, the cellular basis of learning and memory, involves the dynamic trafficking of AMPA receptors (AMPARs) into and out of synapses. One of the remaining key unanswered aspects of AMPAR trafficking is the mechanism by which synaptic strength is preserved despite protein turnover. In particular, the identity of AMPAR scaffolding molecule(s) involved in the maintenance of GluA2-containing AMPARs is completely unknown. Here we report that the synaptic scaffolding molecule (S-SCAM; also called membrane-associated guanylate kinase inverted-2 and atrophin interacting protein-1) plays the critical role of maintaining synaptic strength. Increasing S-SCAM levels in rat hippocampal neurons led to specific increases in the surface AMPAR levels, enhanced AMPAR-mediated synaptic transmission, and enlargement of dendritic spines, without significantly effecting GluN levels or NMDA receptor (NMDAR) EPSC. Conversely, decreasing S-SCAM levels by RNA interference-mediated knockdown caused the loss of synaptic AMPARs, which was followed by a severe reduction in the dendritic spine density. Importantly, S-SCAM regulated synaptic AMPAR levels in a manner, dependent on GluA2 not GluA1, sensitive toN-ethylmaleimide-sensitive fusion protein interaction, and independent of activity. Further, S-SCAM increased surface AMPAR levels in the absence of PSD-95, while PSD-95 was dependent on S-SCAM to increase surface AMPAR levels. Finally, S-SCAM overexpression hampered NMDA-induced internalization of AMPARs and prevented the induction of long term-depression, while S-SCAM knockdown did not. Together, these results suggest that S-SCAM is an essential AMPAR scaffolding molecule for the GluA2-containing pool of AMPARs, which are involved in the constitutive pathway of maintaining synaptic strength.

This paper presents a design and topology selection of bi-direcional buck converter based on PV PCS for managing the electric power. Futhermore, Current Ringing on DCM bi-directional buck converter for soft switching is analyzed in detail. PSIM Simulation and Experiments at the various operating points show the propriety of this paper. Building on the result of simulation and experiment, a comparative analysis is performed with the approximate estimate. By use of a study, the selecion of switch and diode which improve efficiency of the overall system is appiled to DCM bi-directional buck converter based on PV PCS.

In this paper, an effective method has been proposed for selection of white Gaussian noise(WGN) band for radio background noise measurement system under broad band noise environment. MMN which comes from industrial devices and equipment mostly happens in the shape of broad band noise mostly like impulsive noise and this is the main reason for increasing level in the present radio noise measurements. The existing method based on singular value decomposition has weak point that it cannot give good performance for the broad band signal because it uses signal`s white property. The proposed method overcomes such a weakness of singular value decomposition based method by using signal`s Gaussian property based method in parallel. Moreover, this proposed method hires a modelling based method which uses parameter estimation algorithm like maximum likelihood estimation(MLE) and gives more accurate result than the method using amplitude probability distribution(APD) graph. Experiment results under the natural environment has done to verify feasibility of the proposed method.

Electrophysiological catheters are used for both diagnostics and clinical intervention. To facilitate more accurate and precise catheter navigation, robotic cardiac catheter navigation systems have been developed and commercialized. The authors have developed a novel force-reflecting robotic catheter navigation system. The system is a network-based master-slave configuration having a 3-degree of freedom robotic manipulator for operation with a conventional cardiac ablation catheter. The master manipulator implements a haptic user interface device with force feedback using a force or torque signal either measured with a sensor or estimated from the motor current signal in the slave manipulator. The slave manipulator is a robotic motion control platform on which the cardiac ablation catheter is mounted. The catheter motions-forward and backward movements, rolling, and catheter tip bending-are controlled by electromechanical actuators located in the slave manipulator. The control software runs on a real-time operating system-based workstation and implements the master/slave motion synchronization control of the robot system. The master/slave motion synchronization response was assessed with step, sinusoidal, and arbitrarily varying motion commands, and showed satisfactory performance with insignificant steady-state motion error. The current system successfully implemented the motion control function and will undergo safety and performance evaluation by means of animal experiments. Further studies on the force feedback control algorithm and on an active motion catheter with an embedded actuation mechanism are underway.

Obese women have an increased risk for post-menopausal breast cancer. The physiological mechanism by which obesity contributes to breast tumourigenesis is not understood. We previously showed that HCCR-1 oncogene contributes to breast tumourigenesis as a negative regulator of p53 and detection of HCCR-1 serological level was useful for the diagnosis of breast cancer(.) In this study, we found that the HCCR-1 level is elevated in breast cancer tissues and cell lines compared to normal breast tissues. We identified apolipoprotein E (ApoE) interacting with HCCR-1. Our data show that HCCR-1 inhibits anti-proliferative effect of ApoE, which was mediated by diminishing ApoE secretion of breast cancer cells. Finally, HCCR-1 induced the severe obesity in transgenic mice. Those obese mice showed severe hyperlipidaemia. In conclusion, our results suggest that HCCR-1 might play a role in the breast tumourigenesis while the overexpression of HCCR-1 induces the obesity probably by inhibiting the cholesterol-lowering effect of ApoE. Therefore, HCCR-1 seems to provide the molecular link between the obesity and the breast cancer risk.

The human cervical cancer oncogene HCCR-1 is overexpressed in various human cancers, and might function as a negative regulator of the p53 tumor suppressor. To determine the regulatory pathway involved in the HCCR-1 gene expression, we searched the 5' flanking region of HCCR-1 and identified HCCR-1 promoter including putative homeodomain protein binding sites. The level of HCCR-1 expression was increased during the mouse embryogenesis. Expression of phosphatidylinositol 3-kinase (PI3K) in NIH/3T3 cells activated the HCCR-1 promoter. This promoter was also activated by wild type Akt but not by dominant negative Akt in K562 cells. In addition, the level of HCCR-1 was decreased by PI3K inhibitor, LY-294002, in a dose dependent manner. Northern blot analysis revealed that the HCCR-1 gene expression was down-regulated by LY-294002. These results suggest that the HCCR-1 oncogene expression was regulated by the PI3K/Akt signaling pathway.

Full-length IgG antibodies cannot cross cell membranes of living cells; this limits their use for direct targeting of cytosolic proteins. Here, we describe a general strategy for the generation of intact, full-length IgG antibodies, herein called cytotransmabs, which internalize into living cells and localize in the cytosol. We first generated a humanized light chain variable domain (VL) that could penetrate into the cytosol of living cells and was engineered for association with various subtypes of human heavy chain variable domains (VHs). When light chains with humanized VL were co-expressed with 3 heavy chains (HCs), including 2 HCs of the clinically approved adalimumab (Humira®) and bevacizumab (Avastin®), all 3 purified IgG antibodies were internalized into the cytoplasm of living cells. Cytotransmabs primarily internalized into living cells by the clathrin-mediated endocytic pathway through interactions with heparin sulfate proteoglycan that was expressed on the cell surface. The cytotransmabs escaped into the cytosol from early endosomes without being further transported into other cellular compartments, like the lysosomes, endoplasmic reticulum, Golgi apparatus, and nucleus. Furthermore, we generated a cytotransmab that co-localized with the targeted cytosolic protein when it was incubated with living cells, demonstrating that the cytotransmab can directly target cytosolic proteins. Internalized cytotransmabs did not show any noticeable cytotoxicity and remained in the cytosol for more than 6 h before being degraded by proteosomes. These results suggest that cytotransmabs, which efficiently enter living cells and reach the cytosolic space, will find widespread uses as research, diagnostic, and therapeutic agents.

Purpose: The purpose of our study was to identify an unique gene that shows cancer-associated expression, evaluates its potential usefulness in cancer diagnosis, and characterizes its function related to human carcinogenesis. Experimental Design: We used the differential display reverse transcription-PCR method with normal cervical, cervical cancer and metastatic tissues, and cervical cancer cell line to identify genes overexpressed in cancers. Results: We identified a minichromosome maintenance 3 (MCM3) gene that was overexpressed in various human cancers, including leukemia, lymphoma, and carcinomas of the uterine cervix, colon, lung, stomach, kidney and breast, and malignant melanoma. Western blot and immunohistochemical analyses also revealed that MCM3 protein was elevated in most of human cancer tissues tested. We compared the MCM3 protein expression levels in human cancers with conventional proliferation markers, Ki-67 and proliferating cell nuclear antigen. MCM3 antibody was the most specific for multiple human cancers, whereas proliferating cell nuclear antigen was relatively less effective in specificity, and Ki-67 failed to detect several human cancers. The down-regulation of MCM3 protein level was examined under serum starvation in both normal and cancer cells. Interestingly, MCM3 protein was stable in MCF-7 breast cancer cells even up to 96 hours after serum starvation, whereas it was gradually degraded in normal BJ fibroblast cells. Nude mice who received injections of HEK 293 cells stably transfected with MCM3 formed tumors in 6 weeks. Conclusions: Our study indicates that determination of MCM3 expression level will facilitate the assessment of many different human malignancies in tumor diagnosis, and MCM3 is involved in multiple types of human carcino-genesis.

Basic studies of oncogenesis have demonstrated that either the elevated production of particular oncogene proteins or the occurrence of qualitative abnormalities in oncogenes can contribute to neoplastic cellular transformation. The purpose of this study was to identify unique oncogenes that are differentially expressed in human cancers and characterize their functions in tumorigenesis. To discover new putative oncogenes, the differential display RT-PCR method was applied using normal cervical tissues, cervical cancer cell lines, cervical cancer tissues, and metastatic tissues. We identified a new human cervical cancer oncogene HCCR-2 that was overexpressed in various human tumors including leukemia, lymphoma, and carcinomas of the breast, kidney, ovary, stomach, colon, and uterine cervix. Ectopic expression of HCCR-2 resulted in direct tumorigenic conversions of NIH/3T3 and Rat1 fibroblasts. Nude mice injected with NIH/3T3 cells stably transfected with HCCR-2 formed tumors in 4 weeks. The resultant tumors display characteristics of an epithelial carcinoma. In HCCR-2 transfected NCI-H460 cells and RKO cells, stabilization of the p53 tumor suppressor occurred without genetic mutation and correlated with functional impairment, as indicated by the defective induction of p53-induced p21(WAF1), MDM2, and bax. These results indicate that HCCR-2 probably represents a new oncogene that is related to tumorigenesis, functioning as a negative regulator of the p53 tumor suppressor.

To identify the genes involved in cervical carcinogenesis, we applied the mRNA differential display method and identified a candidate tumor suppressor gene, HCCS-1, which was present in normal cervical tissue but absent in cervical cancer, metastatic lymph node and CUMC-6 cervical cancer cell line. HCCS-1 transcripts were expressed in many normal tissues including leukocyte, lung, spleen, liver, heart and uterine cervix. Its expression was absent in 8 human cancer cell lines. HCCS-1-transfected HeLa cells exhibited growth inhibition by about 50%. This inhibitory effect of HCCS-1 on cervical cancer cells was associated with apoptotic process including DNA fragmentation. HCCS-1-transfected HeLa cells were shown to release cytochrome c from mitochondria, which activates caspase-9 and -3 and finally results in cleavage of poly(ADP-ribose) polymerase. Apoptosis formation was detected by propidium-iodide/annexin V. HCCS-1-transfected HeLa cells were more sensitive to adriamycin or UVC ray triggered apoptosis. These results suggest that HCCS-1 is downregulated in multiple human tumor types and may serve as a candidate tumor suppressor gene through apoptotic pathway against human cervical cancer. © 2001 Wiley-Liss, Inc.

In this paper, the mode selection algorithm and the control flow chart are proposed for DC-module integrated converter (DC-MIC), which can be operated under mismatch problem of each PV module. In order to operate DC-MIC, a simple configuration control algorithm is proposed. This algorithm includes mode selection method to operate switch of cascaded buck-boost converter simply which has two kind of functioned switches. Based on the control algorithm, a system flowchart is also proposed. The validity of the proposed control algorithm and the flowchart are verified by experimental results based on 250W DC-MIC with grid connection inverter.

This paper carries out feasibility study of DC home appliance in appropriate of DC power supply system. For this purpose, the difference of structure and safety between AC and DC home appliance is comparatively analyzed, and the countermeasures against predicted problems are suggested in advance. The power simulator of general specifications is designed for comprehensive evaluation. Under this experimental test-bed, the possibility of DC home appliance with these countermeasures is verified.

This paper performs analysis and verification of active inrush current limiter (AICL) using the MOSFET for high-voltage DC power supply. To active this, the performance characteristic of AICL is analyzed comparatively with inrush current limiters using inductor, NTC thermistor, and relay, which have been used to protect the devices. And utilized of AICL when is applied to high-voltage DC power supply is considered. In addition, a study on the relationship between the strength of a limited current, settling time and parameter of devices, which are organized AICL is performed. To verify effectiveness of AICL experiment is carried out using actual parameters. Through this study, utilization and reliability of AICL for high-voltage DC power supply is analyzed and evaluated theoretically and experimentally.

To analyze the electrical performance of individual PV modules in the field, I–V curve tracers or micro inverters are typically used with the associated shortcomings. In this study, we used a precision electronic load to analyze the electrical performance of individual PV modules. The electronic loads have been used for empirical field studies on 12 PV modules installed in Hyundai Heavy Industries test site (Eumseong factory). Three sets of the electronic loads and controllers have been installed, with each set capable of handling 4 PV modules in a time-divided manner. The main advantages of the electronic load are its low price, high precision, wide input ranges for voltage, current and power, and easy control by electrical communication. Initially, the biggest drawback of the electronic load was the slow control speed, but we resolved the issue by applying a new tracking algorithm.

We analyzed the cell-to-module power conversion loss (CTM power loss) of industrial monocrystalline- (mono-Si) and multi-crystalline-silicon (multi-Si) solar cells. To reduce the CTM power loss of industrial solar cells by improving the optical losses, we investigated the effect of spacing between cells in a PV module by quantum efficiency measurement.

Human cervical cancer oncogene 1, HCCR-1, is over-expressed in various human tumors and appears to serve as a negative regulator of the p53 gene. HCCR-1 transgenic mice developed breast cancers but it is unknown how HCCR-1 contributes to tumorigenesis. We identified the HCCR-1 binding protein 3 (HCCRBP-3) as a binding partner for HCCR-1. These two proteins co-localized to the mitochondria. HCCRBP-3 over-expressed in various human tumors converted normal cells into tumor cells in vitro. Nude mice injected with NIH/3T3 cells stably transfected with HCCRBP-3 also induced the tumor formation. In addition, p53 showed the functional impairment in HCCRBP-3-transfected cells as accompanied with defective induction of p21 and bax. In support of this, p21 promoter activities containing p53 responsive elements were inhibited by HCCRBP-3 in a dose-dependent manner. Therefore, our study suggests that HCCRBP-3 contributes to the HCCR-1 induced tumorigenesis by interrupting the p53 function.

In this paper, the control performances of the three phase SVPWM inverter according to the phase current measuring method are compared. For this comparison, the current measuring methods using a current transducer (CT) and a shunt resistor are adopted. Furthermore, in the case of three shunt resistors are connected between under the emitter of power switch and the dc-link ground for phase current measuring in the SVPWM inverter, the restriction is analyzed and the output voltage compensation method is proposed to fix these problem. The experimental result using 1.5kW lab-prototype set is presented for the performance verification.

Mesothelioma is a rare aggressive tumor arising from the mesothelial cell and regarded as universally fatal disease with average survival around 1 year. The incidence rate is varied from one to forty per million in different countries and increasing by the year. The most common site of tumor origin is the pleura and only 20% to 33% of mesothelioma arise from the peritoneum. There are increasing reports of malignant mesothelioma with forty to fifty fatal cases per year in Korea. Histological studies with immunohistochemical stain is helpful for the diagnosis of peritoneal mesothelioma and imaging modality alone is not sufficient for diagnosis, so it is difficult to confirm diagnosis. A 64-year-old male patient was admitted to the hospital with a palpable mass on abdomen. The 6x6 cm sized huge mass was seen on the body of stomach adjacent to the peritoneum. We report a case of malignant peritoneal mesothelioma without evident exposure to asbestos, of which direct invasion to the gastric mucosa was confirmed by endoscopic biopsy and immunohistochemical stain.