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Transporting epithelial cells of the gut and kidney interact with their luminal environment through a densely-packed collection of apical microvilli known as the brush border. Proper brush border assembly depends on the intermicrovillar adhesion complex (IMAC), a protocadherin-based adhesion complex found at the distal tips of microvilli that mediates adhesion between neighboring protrusions to promote their organized packing. Loss of the IMAC adhesion molecule Cadherin-related family member 5 (CDHR5) correlates with poor prognosis of colon cancer patients, though the functional properties of this protocadherin have not been thoroughly explored in relevant cell systems. Here, we show that the two dominant CDHR5 splice isoforms expressed in enterocytes interact to form an apparentcis-oligomer that is competent to target to the apical domain to drive microvillar elongation. The two isoforms exhibited distinct sequence-dependent apical targeting properties, with one isoform requiring its cytoplasmic tail. Library screening identified the Ezrin-associated scaffolds EBP50 and E3KARP as cytoplasmic binding partners for CDHR5. Consistent with this, loss of EBP50 disrupted proper brush border assembly with cells exhibiting markedly reduced apical IMAC levels. Together, our results shed light on the apical targeting determinants of CDHR5 and further define the interactome of the IMAC involved in brush border assembly.

Specialized transporting and sensory epithelial cells employ homologous protocadherin-based adhesion complexes to remodel their apical membrane protrusions into organized functional arrays. Within the intestine, the nutrient-transporting enterocytes utilize the intermicrovillar adhesion complex (IMAC) to assemble their apical microvilli into an ordered brush border. The IMAC bears remarkable homology to the Usher complex, whose disruption results in the sensory disorder type 1 Usher syndrome (USH1). However, the entire complement of proteins that comprise both the IMAC and Usher complex are not yet fully elucidated. Using a protein isolation strategy to recover the IMAC, we have identified the small EF-hand protein calmodulin-like protein 4 (CALML4) as an IMAC component. Consistent with this finding, we show that CALML4 exhibits marked enrichment at the distal tips of enterocyte microvilli, the site of IMAC function, and is a direct binding partner of the IMAC component myosin-7b. Moreover, distal tip enrichment of CALML4 is strictly dependent upon its association with myosin-7b, with CALML4 acting as a light chain for this myosin. We further show that genetic disruption of CALML4 within enterocytes results in brush border assembly defects that mirror the loss of other IMAC components and that CALML4 can also associate with the Usher complex component myosin-7a. Our study further defines the molecular composition and protein-protein interaction network of the IMAC and Usher complex and may also shed light on the etiology of the sensory disorder USH1H.

MyTH4-FERM (MF) myosins evolved to play a role in the creation and function of a variety of actin-based membrane protrusions that extend from cells. Here we performed an analysis of the MF myosins, Myo7A, Myo7B, and Myo10, to gain insight into how they select for their preferred actin networks. Using enterocytes that create spatially separated actin tracks in the form of apical microvilli and basal filopodia, we show that actin track selection is principally guided by the mode of oligomerization of the myosin along with the identity of the motor domain, with little influence from the specific composition of the lever arm. Chimeric variants of Myo7A and Myo7B fused to a leucine zipper parallel dimerization sequence in place of their native tails both selected apical microvilli as their tracks, while a truncated Myo10 used its native antiparallel coiled-coil to traffic to the tips of filopodia. Swapping lever arms between the Class 7 and 10 myosins did not change actin track preference. Surprisingly, fusing the motor-neck region of Myo10 to a leucine zipper or oligomerization sequences derived from the Myo7A and Myo7B cargo proteins USH1G and ANKS4B, respectively, re-encoded the actin track usage of Myo10 to apical microvilli with significant efficiency.

Nutrient-transporting enterocytes interact with their luminal environment using a densely packed collection of apical microvilli known as the brush border. Assembly of the brush border is controlled by the intermicrovillar adhesion complex (IMAC), a protocadherin-based complex found at the tips of brush border microvilli that mediates adhesion between neighboring protrusions. ANKS4B is known to be an essential scaffold within the IMAC, although its functional properties have not been thoroughly characterized. We report here that ANKS4B is directed to the brush border using a noncanonical apical targeting sequence that maps to a previously unannotated region of the scaffold. When expressed on its own, this sequence targeted to microvilli in the absence of any direct interaction with the other IMAC components. Sequence analysis revealed a coiled-coil motif and a putative membrane-binding basic-hydrophobic repeat sequence within this targeting region, both of which were required for the scaffold to target and mediate brush border assembly. Size-exclusion chromatography of the isolated targeting sequence coupled with in vitro brush border binding assays suggests that it functions as an oligomer. We further show that the corresponding sequence found in the closest homolog of ANKS4B, the scaffold USH1G that operates in sensory epithelia as part of the Usher complex, lacks the inherent ability to target to microvilli. This study further defines the underlying mechanism of how ANKS4B targets to the apical domain of enterocytes to drive brush border assembly and identifies a point of functional divergence between the ankyrin repeat–based scaffolds found in the IMAC and Usher complex.

The purpose of this paper is to solve the social pathological problems through the application of scientific and systematic training methods in response to the demand for improvement of muscular strength of elderly people. It is expected that it will be used as the evaluation, strengthening of muscular function, and rehabilitation exercise program through the provision of exercise information and training program. This paper introduces exercise equipment for the muscular strength of elderly, which provides measurement data and training programs. Though control module and training information module, training load is controlled for safety and effective exercise.

Novel design of integrated power—LED module (IPLM) driving system for RGB-LED backlight in LCD has been developed. The DC-DC converters in driver have been integrated into main power and the constant current circuits have been merged into LED modules so that we have accomplished driver board eliminations from backlight.

Aluminum oxide provides high impedance insulation layer on the surface of the aluminum (alloy) body and many 1-dimensional PCBs or module arrays based upon aluminum anodization have been proposed. However 3-dimensional packages or modules can hardly be found. This mismatch is because reliable vertical interconnection through aluminum i.e. ‘through aluminum via’ (TVA) has not been established. Due to the volumetric expansion during the oxidation of Al to Al 2 O 3 , it has been believed preventing cracks in the vicinity of sharp edges is hardly possible. In this paper, we will introduce a vertically conductive ‘through aluminum via’ (TAV) that can be made by aluminum anodization and industry standard PCB manufacturing process. With this structure, we succeeded in constructing an ‘anodized metal substrate’ (AMS) that has supremacy in thermal conductivity, long term reliability and cost effectiveness. The manufacturing process of the substrate was almost identical to that of standard PCB except anodizing process; Mechanical drilling or etching to make the vias, anodizing to form an electrical insulation layer on the whole surface of aluminum plate including the inside wall of the vias, metal layer deposition on the anodized surface by sputtering and electro plating, and patterning by chemical etching. The two key processes are the anodization and metallization of the anodized surface. The electrolytes for anodization contained complex acidic solutions. Industry-standard soft anodizing procedure at room temperature was used and the thickness of the oxidation layer was about 30∼40 um. Adhesion metal and copper directly on the anodized surface were deposed by inline sputter. Average electrical resistance between the pads that include the vias was over 100 mega ohm at 250 V and the yield rate was over 90 %. AMS is thermally ideal for its high thermal conductivity of aluminum and aluminum oxide and the cost effectiveness is very high for its material cost and process cost.

New design of integrated power and integrated driver with LED module (IP-IDLM) driving system with microcontroller for RGB-LED backlight in LCD has been proposed. The DC-DC converters in the conventional driver have been integrated into the main set power and the constant current control circuits in the conventional driver have been merged into the LED modules composed of LED arrays on the substrate so that we have accomplished the driver board eliminations from the LED backlight. In the system aspect, the system power efficiency could be increased and it's capable of achieving a perfect linearity characteristic of driver so that a stable constant current source is entirely maintained.

Novel RGB-LED driving system for LED backlight in LCD display have been developed and demonstrated. The driving system consists of the non-isolation type high efficiency constant current DC-DC converter and the dynamic controller with microcontroller. The efficiency of driver is up to 94.4% and the maximum color deviation, Δu'v', from the target is 0.002.

Novel non-isolation type high efficiency constant current DC-DC converters and color control system with microcontroller for RGB-LED backlight in LCD TV display have been developed and demonstrated. The efficiency of driver board is up to 94.4% and The maximum color deviation, Δu‘v’, from the target is 0.002.