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Because fixed-wing unmanned aerial vehicles (UAVs) require high-speed taxiing for takeoff and landing, the aircraft's stability during taxiing is critical. However, despite research on the taxiing stability of fixed-wing UAVs conducted in taxiing motion simulations employing various tire models, the applicability of the models to fixed-wing UAV taxiing simulations remains unclear, as does the rationale behind the parameter settings in the models. Therefore, in our study, we measured the forces acting on the tires of a fixed-wing UAV under various conditions, including tire loads of 1.6–3.6 kg and tire slip angles of 0–40 deg. Based on the results, we modified conventional tire models and assessed their applicability in taxiing simulations. Among our findings, the parameter values of the models significantly differed from those used in crewed aircraft taxiing simulations, and the presence or absence of load parameters in the lateral force tire models significantly affected the dynamics. Furthermore, the aerodynamics acting on the aircraft enhanced the straight-line stability during taxiing, resulting in reduced forces on the tires. [ABSTRACT FROM AUTHOR]

Introduction: We report a case of cerebral venous sinus thrombosis (CVST) that presented with bilateral optic disc swelling and diplopia in the absence of headaches. Case Presentation: A 54-year-old woman with no relevant medical history presented with a 2-week history of diplopia and no loss of visual acuity in each eye. Eye movements revealed bilateral abduction deficits, and fundoscopic examination revealed bilateral optic disc swelling. Non-contrast computed tomography of the head showed no abnormalities. Magnetic resonance venography revealed the absence of flow in the superior sagittal and left transverse sinuses as a consequence of thrombosis. The patient was diagnosed with intracranial hypertension associated with abducens nerve palsies secondary to CVST and was initiated on anticoagulant therapy. CVST can lead to stroke even in younger individuals. Conclusion: CVST should be considered in differential diagnosis when bilateral papilledema and abducens nerve palsies are present, even in the absence of headache or other neurological findings. [ABSTRACT FROM AUTHOR]

We report a case of a patient with autism spectrum disorder (ASD) and perforated keratomalacia secondary to vitamin A deficiency. A 6-year-old boy complained of difficulty in opening the eyelids. The ocular conjunctiva was hyperemic and keratinized with purulent ocular (eye) discharge. Both corneas showed epithelial defects with hypopyon. The serum vitamin A level was ≤5 IU/dL (normal 97–316), leading to a diagnosis of xerophthalmia and keratomalacia due to vitamin A deficiency. Intramuscular injection of vitamin A (50,000 IU/day), as well as oral administration of multivitamin (containing 2,500 IU of vitamin A) and zinc supplement at 50 mg/day, allowed him to open both eyes and show interest in tablet devices 14 days after the diagnosis. During the course of the treatment, corneal perforation was observed, but it was closed without contact lens wear or amniotic patch and managed with vitamin A replacement therapy and antimicrobial eye drops. The epithelium extended to the area of the right cornea that had been melted, and although scarring corneal opacity remained, there were no obvious signs of infection. Early diagnosis is difficult because children with ASD do not express complaints, and vitamin A deficiency should be considered in patients with a severely unbalanced diet and complaints of difficulty opening the eyelids. [ABSTRACT FROM AUTHOR]

In the context of the growing prevalence of type 2 diabetes (T2DM), control of postprandial hyperglycemia is crucial for its prevention. Blood glucose levels are determined by various factors including carbohydrate hydrolyzing enzymes, the incretin system and glucose transporters. Furthermore, inflammatory markers are recognized predictors of diabetes outcome. Although there is some evidence that isoflavones may exhibit anti-diabetic properties, little is known about to what extent their corresponding hydroxylated metabolites may affect glucose metabolism. We evaluated the ability of a soy extract before (pre-) and after (post-) fermentation to counteract hyperglycemia in vitro and in Drosophila melanogaster in vivo. Fermentation with Aspergillus sp. JCM22299 led to an enrichment of hydroxy-isoflavones (HI), including 8-hydroxygenistein, 8-hydroxyglycitein and 8-hydroxydaidzein, accompanied by an enhanced free radical scavenging activity. This HI-rich extract demonstrated inhibitory activity towards α-glucosidase and a reduction of dipeptidyl peptidase-4 enzyme activity. Both the pre- and post-fermented extracts significantly inhibited the glucose transport via sodium-dependent glucose transporter 1. Furthermore, the soy extracts reduced c-reactive protein mRNA and secreted protein levels in interleukin-stimulated Hep B3 cells. Finally, supplementation of a high-starch D. melanogaster diet with post-fermented HI-rich extract decreased the triacylglyceride content of female fruit flies, confirming its anti-diabetic properties in an in vivo model. [ABSTRACT FROM AUTHOR]

Purpose. We report a case of neuroretinitis associated with cat scratch disease (CSD) in young children. Method. Case report. Results. A 16-month-old boy was admitted for a detailed examination and treatment of a fever of unknown origin. Blood tests revealed no significant findings other than a white blood cell count of 16,100/mm3 and C-reactive protein level of 9.89 mg/dL. Computed tomography revealed no relevant findings to determine the causative disease. Antibiotic therapy with cefotaxime was initiated; however, the fever did not resolve. The patient was referred to our department for further examination to detect the cause of the fever. Fundoscopy revealed neuroretinitis in the right eye. His mother reported a history of breeding cats. Cat scratch disease (CSD) was suspected based on the clinical course and fundus findings. Cefotaxime was discontinued, and azithromycin, rifampicin, and prednisolone were administered, following which the fever disappeared and fundus findings improved. Immunoglobulin G (IgG) and IgM antibodies against Bartonella henselae was positive, leading to a definitive diagnosis of CSD. Conclusion. Infants cannot complain of decreased visual acuity; therefore, these findings may be overlooked unless a fundus examination is performed. As in this case, the early detection of neuroretinitis by an ophthalmologist may help in the diagnosis of CSD. It is extremely difficult to capture a photograph of the fundus of an infant, and recording with a smartphone is relatively simple and useful for monitoring continuous changes. Summary. We describe a case of neuroretinitis associated with cat scratch disease (CSD) that was diagnosed on the basis of fundus findings. The findings suggest the importance of an aggressive ophthalmologic examination when CSD is suspected in young children who are unable to describe their symptoms. [ABSTRACT FROM AUTHOR]

We report a case of Fabry disease diagnosed after recurrent cerebral infarction in a patient with central retinal artery occlusion (CRAO). A 23-year-old man presented with vision loss in his right eye (20/2000), showing CRAO. There was no identified cause for the loss of vision; however, corneal verticillata was detected in both eyes on the recurrence of the cerebral infarction. The α-galactosidase activity in leukocytes was significantly reduced to <0.3 nmol/mg of protein/hour, leading to a definitive diagnosis of Fabry disease. Enzyme replacement therapy was commenced concomitant to rehabilitation. It is necessary to identify Fabry disease as a cause of CRAO in young individuals, and the detection of cornea verticillata, used frequently as an ocular finding, is helpful. [ABSTRACT FROM AUTHOR]

In this study, a novel single-piece thin multi-layer tungsten resistive heater was successfully fabricated using additive manufacturing and tested as an electrothermal thruster. The heater has 12 resistive layers, with each layer having a thickness and height of 0.15 and 81 mm, respectively, and can provide high heating efficiency. A single-piece or monolithic heater was manufactured via additive manufacturing technique, which drastically improved its reliability and decreased its manufacturing cost. In the heating and thrust measurement tests that used nitrogen gas as a propellant, the heater reached a gas temperature of ∼2000 K at a 140-A heater current without experiencing any failure. The tungsten-heater resistance linearly increased with an increase in temperature due to the temperature dependence of tungsten's resistivity. The specific impulse and thrust increased with the heater temperature in accordance with the theoretical prediction. Even including a voltage drop due to a contact resistance, the achieved heater efficiency reached 63% at a 100-A heater current even without a thermal insulation around the thruster. The heater efficiency decreased with an increase in the heater temperature due to heat loss to the surroundings. The heat-loss analysis indicated that both thermal conduction and radiation heat losses were crucial for improving the heater performance at a high-temperature operation of over 2000 K. [ABSTRACT FROM AUTHOR]

Abstract: The modulation of pre‐mRNA splicing is proposed as an attractive anti‐neoplastic strategy, especially for the cancers that exhibit aberrant pre‐mRNA splicing. Here, we discovered that T‐025 functions as an orally available and potent inhibitor of Cdc2‐like kinases (CLKs), evolutionally conserved kinases that facilitate exon recognition in the splicing machinery. Treatment with T‐025 reduced CLK‐dependent phosphorylation, resulting in the induction of skipped exons, cell death, and growth suppression in vitro and in vivo. Further, through growth inhibitory characterization, we identified high CLK2 expression or MYC amplification as a sensitive‐associated biomarker of T‐025. Mechanistically, the level of CLK2 expression correlated with the magnitude of global skipped exons in response to T‐025 treatment. MYC activation, which altered pre‐mRNA splicing without the transcriptional regulation of CLKs, rendered cancer cells vulnerable to CLK inhibitors with synergistic cell death. Finally, we demonstrated in vivo anti‐tumor efficacy of T‐025 in an allograft model of spontaneous, MYC‐driven breast cancer, at well‐tolerated dosage. Collectively, our results suggest that the novel CLK inhibitor could have therapeutic benefits, especially for MYC‐driven cancer patients. [ABSTRACT FROM AUTHOR]

Mounting evidence suggests that constitutively active androgen receptor (AR) splice variants, typified by AR-V7, are associated with poor prognosis and resistance to androgen deprivation therapy in prostate cancer patients. However, mechanisms governing the generation of AR splice variants are not fully understood. In this study, we aimed to investigate the dynamics of AR splice variant generation using the JDCaP prostate cancer model that expresses AR splice variants under androgen depletion. Microarray analysis of JDCaP xenografts before and after expression of AR splice variants suggested that dysregulation of RNA processing pathways is likely involved in AR splice variant generation. To explore factors contributing to generation of AR-V7 mRNA, we conducted a focused RNA interference screen in AR-V7-positive JDCaP-hr cells using an shRNA library targeting spliceosome-related genes. This screen identified DDX39B as a regulator of AR-V7 mRNA expression. Simultaneous knockdown of DDX39B and its paralog DDX39A drastically and selectively downregulated AR-V7 mRNA expression in multiple AR-V7-positive prostate cancer cell lines. DDX39B was upregulated in relapsed JDCaP xenografts expressing AR splice variants, suggesting its role in expression of AR splice variants. Taken together, our findings offer insight into the mechanisms of AR splice variant generation and identify DDX39 as a potential drug target for the treatment of AR splice variant-positive prostate cancer. [ABSTRACT FROM AUTHOR]

Alterations of carbohydrate structures in cancer cells are the most promising targets for developing clinical diagnostic reagents. Pancreatic cancer is one of the most difficult cancers to diagnose because it lacks definitive symptoms. Two antibodies were raised against human pancreatic ribonuclease 1 that bind to the enzyme containing unglycosylated Asn88, but not when its Asn88 isN-glycosylated. Differential studies using these antibodies in immunoassays and Western blot analyses showed a significant increase in the serum levels of pancreatic ribonuclease 1 containingN-glycosylated Asn88 in pancreatic cancer patients compared with normal human subjects. Focusing on the increase in anN-glycosylated Asn residue of serum pancreatic ribonuclease 1, specifically Asn88, affords a new diagnostic marker for pancreatic cancer. This is the first report of a diagnostic cancer marker that takes advantage of the presence or absence ofN-glycosylation at a specific Asn residue of a glycoprotein. [ABSTRACT FROM AUTHOR]

R(+)-alpha lipoic acid (RALA) is one of the cofactors for mitochondrial enzymes and, therefore, plays a central role in energy metabolism. RALA is unstable when exposed to low pH or heat, and therefore, it is difficult to use enantiopure RALA as a pharma- and nutra-ceutical. In this study, we have aimed to stabilize RALA through complex formation with cyclodextrins (CDs). α-CD, β-CD and γ-CD were used for the formation of these RALA-CD complexes. We confirmed the complex formation using differential scanning calorimetry and showed by using HPLC analysis that complexed RALA is more stable than free RALA when subjected to humidity and high temperature or acidic pH conditions. Scanning electron microscopy studies showed that the particle size and shape differed depending on the cyclodextrin used for complexation. Further, the complexes of CD and RALA showed a different particle size distribution pattern compared with that of CD itself or that of the physical mixture of RALA and CD. [ABSTRACT FROM AUTHOR]

Abstract: We previously reported the bioavailability enhancement of lipophilic Coenzyme Q10 (CoQ10) by complexing with γ- Cyclodextrin (γCD). Here, we report on its mechanism. Hydrophobic CoQ10 generally agglutinates but the dissociated CoQ10 from γCD was captured by bile acid to form nanometer molecular micelle without aggregation and therefore both solubility and bioavailability could be enhanced. Furthermore, we succeeded in the expansion of this finding to personal care field by the use of Dipotassium glycyrrhizate (GZK2) instead of bile acid. The skin absorptions of actives could be significantly enhanced by the combination of cosme-ceutical-γCD complexes with GZK2. [Copyright &y& Elsevier]

The article presents a study to determine the bioavailability of tocotrienol complex with y-cyclodextrin and its effects on tocotrienol concentration in rat plasma and tissues. The study used male Wistar rats and tocotrienol mixture extracted from rice bran for complexation with y-cyclodextrin. The result showed that by enhancing intestinal absoprtion, complexation of tocotrienol with y-cyclodextrin elevates plasma and tissue tocotrienol concentrations.

Cyclodextrin-based metal–organic frameworks-1 (CD-MOF-1) prepared using potassium hydroxide, ethanol, and γ-cyclodextrin (γ-CD) has been reported as a new type of MOF for the development of pharmaceutical formulations. The present study aimed to investigate the physicochemical properties of ascorbic acid derivatives (L-ascorbyl 6-palmitate (ASCP); L-ascorbyl 2,6-palmitate (ASCDP)) complexed with CD-MOF-1 by a solvent evaporation method. Powder X-ray diffraction revealed that the crystal diffraction pattern of CD-MOF-1 changed from α-type to β-type when prepared by a solvent evaporation method. For ASCP/CD-MOF-1 = 1/2 and ASCDP/CD-MOF-1 = 1/4 evaporated samples, the crystal diffraction peaks derived from ASCP and ASCDP disappeared, indicating a β-like behavior. Differential scanning calorimetry results revealed that the endothermic peaks of evaporated samples (ASCP/CD-MOF-1 = 1/2 and ASCDP/CD-MOF-1 = 1/4) were not detected due to melting. Furthermore, intermolecular interactions were observed in the hydrogen bonds between the CH groups of the side chains of ASCP and ASCDP and the OH group of CD-MOF-1 in (ASCP/CD-MOF-1 = 1/2) and EVP (ASCDP/CD-MOF-1 = 1/4), based on the near-infrared absorption spectroscopy analysis. CD-MOF-1 did not form inclusion complexes with the lactone rings of ASCP and ASCDP, but with the lipophilic side chains. These results suggested that CD-MOF-1 may be useful in preparing novel drug carriers for ASCP and ASCDP. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this study was to determine the effect of molecular encapsulation of coenzyme Q10 (CoQ10) by complexation with γ-cyclodextrin (γ-CD) (CoQ10-γ-CD) compared with a mixture of CoQ10 with microcrystalline cellulose (CoQ10-MCC) on absorption and bioavailability of CoQ10 in supplement form in healthy adults. Twenty-two volunteers received a single dose of a 150-mg capsule containing 30 mg CoQ10 under fasting conditions in an open-label, crossover design with a 2-week washout period. Blood was collected before dosing and after dosing periodically over 48 hours. Plasma levels of CoQ10 were determined by high-performance liquid chromatography using an electrochemical detector and an online reduction system. After 6 and 8 hours of dosing there was a significant increase in mean CoQ10 plasma levels of subjects after a single oral administration of the CoQ10-γ-CD capsule compared with those with the CoQ10-MCC capsule. In addition, the mean plasma levels at 24 and 48 hours tended to be higher after CoQ10-γ-CD administration in comparison with CoQ10-MCC administration. The area under the plasma CoQ10 concentration curve and the maximum plasma concentration (C max) values as well as their corresponding log-transformed values, log area under the plasma CoQ10 concentration curve, and log C max for the CoQ10-γ-CD formulation were significantly higher than those for the CoQ10-MCC formulation. These results indicate that the oral absorption and bioavailability of CoQ10 in healthy adult volunteers could be significantly enhanced by complexation with γ-CD, suggesting the potential use of γ-CD as formulation aid for orally administered CoQ10. [Copyright &y& Elsevier]

α2,8-Linked polysialic acid (polySia) is a structurally unique anti-adhesive glycotope that covalently modifies N-linked glycans on neural cell adhesion molecules (N-CAMs). These sugar chains play a key role in modulating cell-cell interactions, principally during embryonic development, neural plasticity, and tumor metastasis. The degree of polymerization (DP) of polySia chains on N-CAM is postulated to be of critical importance in regulating N-CAM function. There are limitations, however, in the conventional methods to accurately determine the DP of polySia on N-CAM, the most serious being partial acid hydrolysis of internal α2,8-ketosidic linkages that occur during fluorescent derivatization, a step necessary to enhance chromatographic detection. To circumvent this problem, we have developed a facile method that combines the use of Endo-β-galactosidase to first release linear polySia chains from N-CAM, with high resolution high pressure liquid chromatography profiling. This strategy avoids acid hydrolysis prior to chromatographic profiling and thus provides an accurate determination of the DP and distribution of polySia on N-CAM. The potential of this new method was evaluated using a nonpolysialylated construct of N-CAM that was polysialylated in vitro using a soluble construct of ST8Sia II or ST8Sia IV. Whereas most of the oligosialic acid/polySia chains consisted of DPs ∼50–60 or less, a subpopulation of chains with DPs ∼150 to ∼180 and extending to DP ∼400 were detected. The DP of this subpopulation is considerably greater than reported previously for N-CAM. Endo-β-galactosidase can also release poly-Sia chains from polysialylated membranes expressed in the neuroblastoma cell line, Neuro2A, and native N-CAM from embryonic chick brains. [ABSTRACT FROM AUTHOR]

2-Keto-3-deoxy-d-glycero-d-galacto-nononic acid (KDN) isa sialic acid (Sia) that is ubiquitously expressed in vertebrates duringnormal development and tumorigenesis. Its expression is thoughtto be regulated by multiple biosynthetic steps catalyzed by severalenzymes, including CMP-Sia synthetase. Using crude enzyme preparations,it was shown that mammalian CMP-Sia synthetases had very low activityto synthesize CMP-KDN from KDN and CTP, and the corresponding enzymefrom rainbow trout testis had high activity to synthesize both CMP-KDNand CMP-N-acetylneuraminic acid (Neu5Ac) (Terada et al. [1993] J.Biol. Chem., 268, 2640–2648). To demonstrate if theunique substrate specificity found in the crude trout enzyme is conveyedby a single enzyme, cDNA cloning of trout CMP-Sia synthetase wascarried out by PCR-based strategy. The trout enzyme was shown toconsist of 432 amino acids with two potential nuclear localizationsignals, and the cDNA sequence displayed 53.8% identityto that of the murine enzyme. Based on the Vmax/Km values, the recombinant trout enzymehad high activity toward both KDN and Neu5Ac (1.1 versus 0.68 min–1).In contrast, the recombinant murine enzyme had 15 times lower activitytoward KDN than Neu5Ac (0.23 versus 3.5 min–1).Northern blot analysis suggested that several sizes of the mRNAare expressed in testis, ovary, and liver in a tissue-specific manner.These results indicate that at least one cloned enzyme has the abilityto utilize both KDN and Neu5Ac as substrates efficiently and isuseful for the production of CMP-KDN. [ABSTRACT FROM PUBLISHER]

The minimal gene set essential for life has long been sought. We report the 860-kb genome of the obligate intracellular plant pathogen phytoplasma (Candidatus Phytoplasma asteris, OY strain). The phytoplasma genome encodes even fewer metabolic functions than do mycoplasma genomes. It lacks the pentose phosphate cycle and, more unexpectedly, ATP-synthase subunits, which are thought to be essential for life. This may be the result of reductive evolution as a consequence of life as an intracellular parasite in a nutrient-rich environment. [ABSTRACT FROM AUTHOR]

Nonlinear voltage transfer characteristics in GaAs-based three-branch nanowire junctions (TBJs) controlled by Schottky wrap gates (WPGs) are investigated by characterization of the gate voltage and size dependences in detail. WPGs squeezed the nanowires only in the node portion and modulated the curve only in the low-input-voltage region. When the entire nanowire was narrowed geometrically, the voltage transfer curve became abrupt in a wide voltage range. On the other hand, the nanowire length affected only the curve in the high-input-voltage region. These results indicate that the voltage transfer characteristics of the WPG-controlled TBJ device in the low- and high-voltage regions are controlled by the junction node with WPGs and the end of the positively biased nanowire, respectively. The observed behaviors can be understood in terms of a surface-potential-induced field domain model. [ABSTRACT FROM AUTHOR]

A GaAs-based three-branch nanowire junction (TBJ) with Schottky wrap gates (WPGs) is investigated to realize novel Boolean logic gates. The WPG-controlled TBJ shows a bell-shaped voltage input–output curve and is controlled by gate voltage on the WPGs. The observed characteristics are explained using a simple equivalent circuit model. AND gate operation is realized in the WPG-controlled TBJ and its output voltage swing is controlled using WPGs. It can also operate as a NOT gate by changing the measurement circuit. A NAND gate is fabricated by integrating two WPG-controlled TBJs, and correct operation with a voltage transfer gain of 2.2 is realized. [ABSTRACT FROM AUTHOR]