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Background and Objectives: Endoscopic ultrasound (EUS) is an imaging modality that can be applied to predict preoperative T staging. It is important for the patient to decide whether to receive endoscopic therapy, surgical intervention, or neoadjuvant therapy. The objectives of our study were to (1) identify if EUS could precisely predict T1-stage tumor, which is suitable for endoscopic treatment and (2) identify if EUS could precisely predict tumors more advanced than T3, which would mandate neoadjuvant therapy., Methods: A retrospective study of patients who received gastrectomy was conducted from March 2017 to December 2021 at Taichung Veterans General Hospital. Those who received preoperative EUS, with final pathology showing gastric adenocarcinoma were included. Consistency of EUS prediction and pathology, accuracy, and parameters impacting accuracy were analyzed., Results: The κ value was 0.6 if the T stage was not grouped, indicating moderate agreement. Overall accuracy was 52.8%. Overestimation and underestimation rates were 17.6% and 29.5%, respectively. The accuracy of T stages is highest in T1 (85.23%). The κ value of T1-stage was 0.67, and those of T2, T3, and T4 were below 0.5. Regarding parameters affecting accuracy, we found longitudinal portion, Borrmann type, ulcer presentation, early gastric cancer, and size of tumor could influence the accuracy., Conclusions: Our study showed that EUS was a good tool for precisely predicting T1-stage of gastric adenocarcinoma preoperatively. For this situation, endoscopic treatment would be enough. However, for predicting more advanced gastric adenocarcinoma, EUS should be combined with other modalities to achieve better accuracy., (© 2024 Wiley Periodicals LLC.)

Background: Gastric cancer (GC) is a leading malignant disease in numerous countries, including Taiwan with limited therapeutic options. Animal viruses including oncolytic avian reovirus (ARV) have the possibility to avoid pre-existing immunity in humans, while being safe and immunostimulatory. Here, we provide a novel insight into oncolytic ARV and UV-ARV-sensitized patient's peripheral blood mononuclear cells (P-PBMCs) and tumor infiltrating lymphocytes (TILs) killing primary GC (PGC) cells through the surface TLR3 and TRAIL/DR4/DR5 immunogenic apoptosis pathway., Methods: We conducted a comprehensive study to reveal whether ARV- or UV-inactivated ARV (UV-ARV)-modulated P-PBMCs or TILs killing ARV- and UV-ARV-sensitized AGS cells and PGC cells derived from clinical patients and to investigate the regulation of surface TLR3 receptor and upstream signaling pathways. Apoptosis analysis by flow cytometry and Western blot, suppression of signal pathway by specific inhibitors, in situ proximity ligation assay (PLA), time-resolved flurometry and lactate dehydrogenase (LDH) cytotoxicity assays, and an in vitro co-culture model were established to study the interplay between ARV- and UV-ARV-sensitized P-PBMCs and TILs to kill PGC cells and their upstream pathways., Results: Our results reveal that increased levels of DR4 and DR5 were observed in ARV and UV-ARV sensitized PGC cells through the TLR3/p38/p53 signaling pathway. Importantly, we found that the σC protein of ARV or UV-ARV interacted with surface TLR3 of CD8 + TILs, thereby triggering the TLR3/NF-κB/IFN-γ/TRAIL signaling pathway which induces immunogenic apoptosis of PGC cells. This study sheds further light on the molecular basis behind ARV oncolysis and facilitates the ARV or UV-ARV as a cancer therapeutic., Conclusions: The study provides novel insights into ARV- or UV-ARV-sensitized P-PBMCs and CD8 + TILs to kill PGC cells through the immunogenic apoptosis pathway. We conclude that P-PBMCs can easily be obtained from GC patients and provide a rich source as TILs to kill PGC cells., (© 2024. The Author(s).)

Mass spectrometry (MS) using an electron multiplier for intact protein analysis remains limited. Because of the massive size and complex structure of proteins, the slow flight speed of their ions results in few secondary electrons and thus low detection sensitivity and poor spectral resolution. Thus, we present a compact ion trap-mass spectrometry approach to directly detect ion packets and obtain the high-resolution molecular signature of proteins. The disturbances causing deviations of ion motion and mass conversion have been clarified in advance. The radio frequency waveform used to manipulate ions is proposed to be a sequence of constant-frequency steps, interconnected by short time-outs, resulting in least dispersive distortion. Furthermore, more such constant-phase conjunctions are arranged in each step to compensate for fluctuations resulting from defects in the system and operation. In addition, two auxiliary pulses are generated in the right phase of each step to select ions of a specific secular state to detect one clean and sharp spectral line.This study demonstrates a top-down approach for the MS measurement of cytochrome C molecules, resulting in a spectral profile of the protein in its natural state at a resolution of 20 Da. Additionally, quick MS scans of other proteins were performed.

The articular cartilage has poor intrinsic healing potential, hence, imposing a great challenge for articular cartilage regeneration in osteoarthritis. Tissue regeneration by scaffolds and bioactive materials has provided a healing potential for degenerated cartilage. In this study, decellularized cartilage powder (DCP) and hyaluronic acid hydrogel modified by aldehyde groups and methacrylate (AHAMA) were fabricated and evaluated in vitro for efficacy in articular cartilage regeneration. In vitro tests such as cell proliferation, cell viability, and cell migration showed that DCP/AHAMA has negligible cytotoxic effects. Furthermore, it could provide an enhanced microenvironment for infrapatellar fat pad stem cells (IFPSCs). Mechanical property tests of DCP/AHAMA showed suitable adhesive and compressive strength. IFPSCs under three-dimensional (3D) culture in DCP/AMAHA were used to assess their ability to proliferate and differentiate into chondrocytes using normal and chondroinductive media. Results exhibited increased gene expression of COL2 and ACN and decreased COL1 expression. DCP/AHAMA provides a microenvironment that recapitulates the biomechanical properties of the native cartilage, promotes chondrogenic differentiation, blocks hypertrophy, and demonstrates applicability for cartilage tissue engineering and the potential for clinical biomedical applications., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Adjuvant chemotherapy is recommended as the standard treatment for patients with stage II/III resected gastric cancer. However, it is unclear whether older patients also benefit from an adjuvant chemotherapy strategy. This study aimed to investigate the clinical impact of adjuvant chemotherapy in older patients with stage II/III gastric cancer., Methods: This retrospective, real-world study analyzed 404 patients with stage II/III gastric cancer visited at our institute between January 2009 and December 2019. The clinical characteristics and outcomes of patients aged 70 years or older who received adjuvant chemotherapy were compared with those who did not receive this type of treatment. Propensity score analysis was performed to mitigate selection bias., Results: Of the 404 patients analyzed, 179 were aged 70 years or older. Fewer older patients received adjuvant chemotherapy than did younger patients (60.9% vs. 94.7%, respectively; P < 0.001). Among patients aged 70 years or older, those who received adjuvant chemotherapy had improved disease-free survival (DFS) (5-year DFS rate, 53.1% vs. 30.4%; P < 0.001) and overall survival (OS) (5-year OS rate, 68.7% vs. 52.1%; P = 0.002) compared to those who did not receive adjuvant chemotherapy. A similar survival benefit was observed in the propensity-matched cohort. Multivariate analysis showed that more advanced stage was associated with poorer OS. Receipt of adjuvant chemotherapy was independently associated with a decreased hazard of death (hazard ratio (HR), 0.37; 95% confidence intervals (CI), 0.20-0.68; P = 0.002)., Conclusions: Adjuvant chemotherapy may benefit older stage II/III gastric cancer patients aged ≥ 70 years. Further prospective studies are needed to confirm these findings., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Suitable biomechanical properties, good biocompatibility, and osteoconductivity of a degradable magnesium (Mg) alloy make it a potential material for orthopedic implants. The main limitation of Mg is its high corrosion rate in the human body. Surface modification is necessary to improve the Mg corrosion resistance. In this work, a polymeric layer of gelatin/nanohydroxyapatite (Gel/nHA) was coated on a ZK60 Mg alloy by dip coating and spin coating to test the corrosion resistance and biocompatibility in vitro and in vivo. The results from the in vitro test revealed that the coated groups reduced the corrosion rate with the corrosion current density by 59 and 81%, from 31.22 to 12.83 μA/cm 2 and 5.83 μA/cm 2 in the spin coating and dip coating groups, respectively. The dip coating group showed better corrosion resistance than the spin coating group with the lowest released hydrogen content (17.5 mL) and lowest pH value (8.23) and reducing the current density by 45%. In vitro, the relative growth rate was over 75% in all groups tested with MG63, demonstrating that the Mg substrate and coating materials were within the safety range. The dip coating and spin coating groups enhanced the cell proliferation with significantly higher OD values (3.3, 3.0, and 2.5, respectively) and had better antihemolysis and antiplatelet adhesion abilities than the uncoated group. The two coating methods showed no difference in the cellular response, cell migration, hemolysis, and platelet adhesion test. In in vivo tests in rats, the dip coating group also showed a higher corrosion resistance with a lower corrosion rate and mass loss than the spin coating group. In addition, the blood biochemistry and histopathology results indicated that all materials used in this study were biocompatible with living subjects. The present research confirmed that the two methods have no noticeable difference in cell and organ response but the corrosion resistance of dip coating was higher than that of spin coating either in vitro or in vivo.

Background: Anaemia has a deleterious effect on surgical patients, but the long-term impact of anaemia in critically ill surgical patients remains unclear., Methods: We enrolled consecutive patients who were admitted to surgical intensive care units (ICUs) at a tertiary referral centre in central Taiwan between 2015 and 2020. We used both Cox proportional hazards analysis and propensity score-based analyses, including propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and covariate balancing propensity score (CBPS) to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for one-year mortality., Results: A total of 7,623 critically ill surgical patients were enrolled, and 29.9% (2,280/7,623) of them had week-one anaemia (haemoglobin <10 g/dL). We found that anaemia was independently associated with an increased risk of one-year mortality after adjustment for relevant covariates (aHR, 1.170; 95% CI, 1.045-1.310). We further identified a consistent strength of association between anaemia and one-year mortality in propensity score-based analyses, with the adjusted HRs in the PSM, IPTW, and CBPS were 1.164 (95% CI 1.025-1.322), 1.179 (95% CI 1.030-1.348), and 1.181 (1.034-1.349), respectively., Conclusions: We identified the impact on one-year mortality of anaemia in critically ill surgical patients, and more studies are needed to validate our findings., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Feng-Hsu Wu et al.)

To characterize the correlation of the crystal structure and Al-ion storage behavior, we prepared various crystal structures of MoO 3 (α-MoO 3 , β-MoO 3 and h -MoO 3 ) electrode materials and studied them via in situ X-ray absorption spectroscopy (XAS) and X-ray diffraction (XRD) techniques. The α-MoO 3 electrode material possesses a specific capacitance of 575.4 F g -1 and a gravimetric capacity of 207.8 mA h g -1 at a current density of 1 A g -1 . From the in situ XRD results, the crystal structures of α-MoO 3 and β-MoO 3 show a significant distortion, whereas that of h -MoO 3 is minorly affected during the insertion or extraction of Al 3+ ions. Based on the in situ XAS results, the MoO 6 octahedral structure and Mo ion valence of α-MoO 3 and β-MoO 3 also exhibit a strong variation, whereas those of h -MoO 3 are nearly unchanged during the insertion or extraction of Al 3+ ions. Notably, in situ XRD and XAS also clearly show a possible phase of Al x MoO 3 during the Al 3+ insertion and extraction cycles in the α-MoO 3 and β-MoO 3 electrode materials, which may play a crucial role in the behavior of the residue of Al 3+ ions and poor cycling stability. We provide clear evidence that the Al-ion energy storage performance of various MoO 3 electrode materials is strongly associated with the corresponding tunnel space and the stability of their crystal structures. This work also provides new insight into a strong correlation between ion-storage efficiency and the corresponding crystal structure, which is greatly helpful for the development and improvement of new electrode materials for Al-ion energy storage.

(1) Background: Hepatocellular carcinoma (HCC) with a large right atrium tumor thrombus (RATT) is a rare and critical presentation. Emergency hepatectomy and thrombectomy under cardiopulmonary bypass (CPB) is life-saving and potentially curative. The aim of this study is to propose an appropriate approach for this condition. (2) Methods: In period A (1998 to 2010, n = 7), hepatectomy and thrombectomy were concomitantly performed, and staged hepatectomy was performed in period B (2011 to 2018, n = 17). (3) Results: The median overall survival time (MOST) in the published studies was 14 months. Moreover, the blood loss, blood transfusion rate, length of ICU stays, and hospital costs were significantly reduced in period B. The MOSTs of patients in period A ( n = 6) and period B ( n = 17) were 14 vs. 18 months ( p = 0.099). The median disease-free survival times (MDFTs) in period A ( n = 6) and period B ( n = 15) were 8 vs. 14 months ( p = 0.073), while the MOSTs in period A and period B were 14 vs. 24 months ( p = 0.040). (4) Conclusions: Emergency thrombectomy under CPB and staged hepatectomy 4-6 weeks later may be an appropriate approach for HCC with large RATT. However, the optimal waiting interval requires further investigation.

The use of conventional fabrication methods rapidly developed the performance and notable enhancements of optoelectronic devices. However, it proved challenging to develop and demonstrate stable optoelectronic devices with biodegradability and biocompatibility properties towards sustainable development and extensive applications. This study incorporates a water-soluble Cr-phycoerythrin (Cr-PE) biomaterial to observe its optical and electronic properties effects on the pristine indium gallium zinc oxide (IGZO)-based photodetector. The fabricated photodetector demonstrates an extended absorption detection region, enhanced optoelectronic performance, and switchable function properties. The resulting photocurrent and responsivity of the IGZO/Cr-PE structure have increased by 5.7 and 7.1 times as compared to the pristine IGZO photodetector. It was also observed that the photodetector could operate in UV and UV-visible with enhanced optical properties by effectively adding the water-soluble Cr-PE. Also, the sensing region of IGZO photodetector becomes changeable. It exhibits switchable dual detection by alternatively dripping and removing the Cr-PE on the IGZO layer. Different measurement parameters such as detectivity, repeatability, and sensitivity are highlighted to effectively prove the advantage of including Cr-PE on the photodetector structure. This study contributes to understanding the potential functions in improving optoelectronic devices through an environmental-friendly method., (© 2022 IOP Publishing Ltd.)

The specific energy of an aqueous carbon supercapacitor is generally small, resulting mainly from a narrow potential window of aqueous electrolytes. Here, we introduced agarose, an ecologically compatible polymer, as a novel binder to fabricate an activated carbon supercapacitor, enabling a wider potential window attributed to a high overpotential of the hydrogen-evolution reaction (HER) of agarose-bound activated carbons in sulfuric acid. Assembled symmetric aqueous cells can be galvanostatically cycled up to 1.8 V, attaining an enhanced energy density of 13.5 W h/kg (9.5 µW h/cm 2 ) at 450 W/kg (315 µW/cm 2 ). Furthermore, a great cycling behavior was obtained, with a 94.2% retention of capacitance after 10,000 cycles at 2 A/g. This work might guide the design of an alternative material for high-energy aqueous supercapacitors.

The dorsomedial hypothalamus (DMH) receives dense orexinergic innervation. Intra-DMH application of orexins increases arterial pressure and heart rate in rats. We studied the effects of orexin-A on DMH neurons, including those innervating the medullary cardiovascular center, the rostral ventrolateral medulla (RVLM), by using whole-cell recordings in brain slices. In the presence of tetrodotoxin, orexin-A (30-1000 nM) depolarized 56% of DMH neurons (EC 50 82.4 ± 4.4 nM). Under voltage-clamp recording, orexin-A (300 nM) induced three types of responses characterized by different current-voltage relationships, namely unchanged, increased, and decreased slope conductance in 68%, 14%, and 18% of orexin-A-responsive neurons, respectively. The reversal potential of the decreased-conductance response was near the equilibrium potential of K + and became more positive in a high-K + solution, suggesting that K + conductance blockade is the underlying mechanism. In a low-Na + solution, unchanged-, increased-, and decreased-conductance responses were observed in 56%, 11%, and 33% of orexin-A-responsive neurons, respectively, implying that a non-selective cation current (NSCC) underlies orexin-A-induced responses in a small population of DMH neurons. KBR-7943 (70 μM), an inhibitor of Na + -Ca 2+ exchanger (NCX), suppressed orexin-A-induced depolarization in 7 of 10 neurons. In the presence of KBR-7943, the majority of orexin-A-responsive neurons exhibited decreased-conductance responses. These findings suggest that NCX activation may underlie orexin-A-induced depolarization in the majority of orexin-responsive DMH neurons. Of 19 RVLM-projecting DMH neurons identified by retrograde labeling, 17 (90%) were orexin-A responsive. In conclusion, orexin-A directly excited over half of DMH neurons, including those innervating the RVLM, through decreasing K + conductance, activating NCX, and/or increasing NSCC., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this paper, we aim to detect distributed denial of service (DDoS) attacks, and receive a notification of destination service, changing immediately, without the additional efforts of other modules. We designed a kernel-based mechanism to build a new Transmission Control Protocol/Internet Protocol (TCP/IP) connection smartly by the host while the users or clients not knowing the location of the next host. Moreover, we built a lightweight flooding attack detection mechanism in the user mode of an operating system. Given that reinstalling a modified operating system on each client is not realistic, we managed to replace the entry of the system call table with a customized sys&#95;connect. An effective defense depends on fine detection and defensive procedures. In according with our experiments, this novel mechanism can detect flooding DDoS successfully, including SYN flood and ICMP flood. Furthermore, through cooperating with a specific low cost network architecture, the mechanism can help to defend DDoS attacks effectively.

This study investigated the diagnostic accuracy of using an artificial neural network (ANN) for the prediction of metabolic syndrome (MetS) based on socioeconomic status and lifestyle factors. The data of 27,415 subjects who went through examinations and answered questionnaires during three stages from 2006 to 2014 at a health institute in Taiwan were collected and analyzed. The repeated measurements over time were set as predictive factors and used to train and test an ANN for MetS prediction. Among the subjects, 18.3%, 24.6%, and 30.1% were diagnosed with MetS during the respective three stages. ANN analysis applied with an over-sampling technique performed with an area under the curve (AUC) of up to 0.93 based on different models. The over-sampling technique helped improve prediction performance in terms of sensitivity and F 2 measures. The results indicated that waist circumference, socioeconomic status (SES), and lifestyle factors can be utilized in a non-invasive screening tool to assist health workers in making primary care decisions when MetS is suspected. By predicting the occurrence of MetS, individuals or healthcare professionals can then develop preventive strategies in time, thus enhancing the effectiveness of health promotion.

Binary transition metal oxide CoMoO4@NiWO4 core-shell nanoplates grown directly on a Ni foam substrate were synthesized via a facile two-step hydrothermal process. The core-shell nanoplates with high electrochemical surface area (2933 cm2) demonstrated excellent electrochemical properties (areal capacity as high as 0.464 mA h cm-2 at a current density of 5 mA cm-2) and great cycle stability (92.5% retention after 3000 cycles with a high current density of 40 mA cm-2). The mechanism of the electrochemical reactions based on the in situ X-ray absorption spectroscopy technique clearly shows that the Co and Ni elements simultaneously participate in the faradaic reactions with the electrolyte. These results indicate that the excellent electrochemical performance of CoMoO4@NiWO4 compared to that of CoMoO4 nanoplates is attributed to a large electrochemical surface area and synergistic effect between NiWO4 and CoMoO4. This combination of two binary transition metal oxides can hence provide an excellent route to develop a high-performance electrode material for supercapacitor applications.

Adipocyte-macrophage crosstalk plays a critical role to regulate adipose tissue microenvironment and cause chronic inflammation in the pathogenesis of obesity. Interleukin-29 (IL-29), a member of type 3 interferon family, plays a role in host defenses against microbes, however, little is known about its role in metabolic disorders. We explored the function of IL-29 in the pathogenesis of obesity-induced inflammation and insulin resistance. We found that serum IL-29 level was significantly higher in obese patients. IL-29 upregulated IL-1β, IL-8, and monocyte chemoattractant protein-1 (MCP-1) expression and decreased glucose uptake and insulin sensitivity in human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes through reducing glucose transporter 4 (GLUT4) and AKT signals. In addition, IL-29 promoted monocyte/macrophage migration. Inhibition of IL-29 could reduce inflammatory cytokine production in macrophage-adipocyte coculture system, which mimic an obese microenvironment. In vivo, IL-29 reduced insulin sensitivity and increased the number of peritoneal macrophages in high-fat diet (HFD)-induced obese mice. IL-29 increased M1/M2 macrophage ratio and enhanced MCP-1 expression in adipose tissues of HFD mice. Therefore, we have identified a critical role of IL-29 in obesity-induced inflammation and insulin resistance, and we conclude that IL-29 may be a novel candidate target for treating obesity and insulin resistance in patients with metabolic disorders.

The era of flexible optoelectronics demands development of wearable and bendable structures, foldable touch screens, paper-like displays, and curved and flexible solid-state lighting devices. Here, we demonstrate the fabrication of highly flexible light valves using polymer-dispersed liquid crystal (PDLC) and TiO 2 /Ag/TiO 2 transparent conductive films. TiO 2 /Ag/TiO 2 multilayers were prepared by magnetron sputtering technique on polyethylene terephthalate (PET) substrates at room temperature. By keeping the equivalent TiO 2 layers and varying the deposition time of the Ag layer, proper metal nanograins on TiO 2 planar plane were formed, providing the best tradeoff between the transmittance, sheet resistance and bending ability. The results are validated by numerical simulations that suggest the best match between the deposition time and individual layer thickness. Based on the performed characteristics of TiO 2 /Ag/TiO 2 /PET structures, several flexible light valves are fabricated and characterized. The sheet resistance values of TiO 2 /Ag/TiO 2 /PET remain unchanged over 1000 bending cycles. The measured driving voltage and response time values open great potential of TiO 2 /Ag/TiO 2 /PET for integration into next-generation ITO-free flexible and stretchable devices.

Background: For hepatocellular carcinoma (HCC), liver resection is a classical curative modality, despite its technical complexity. The incidence of HCC in the oldest old people (aged ≥ 85 years) is rising along with the global increase in life expectancy. Currently, no report has addressed liver resection for HCC in this aged population., Patients and Methods: We conducted a retrospective review of 1889 patients receiving curative liver resection for newly diagnosed HCC from 1992 to 2016. At the time of operation, 1858 of them were aged < 85 years (group A), and 31 were aged ≥ 85 years (group B). Another 18 oldest old patients, whose HCC was considered resectable but were not operated on due to the patient's refusal, served as the control group (group C). The clinicopathological characteristics and early and long-term outcomes were compared between groups A and B. All associated co-morbidities of the patients were well-treated before liver resection. The overall survival (OS) rates were also compared between groups B and C., Result: Group B had a significantly higher incidence of associated co-morbidities and hepatitis C infection. Postoperative complication rates and 90-day mortality rates after liver resection did not differ between groups A and B (p = 0.834 and p = 1.000, respectively), though group B had a longer postoperative stay (p = 0.001). In groups A and B, the 5-year disease-free survival rates were 29.7% and 22.6% (p = 0.163), respectively, and their overall survival rates were 43.5% and 35.5% (p = 0.086). The overall survival rate of group B was significantly different from group C (35.5% vs. 0%, p = 0.001)., Conclusion: Despite a longer postoperative recovery period, liver resection for HCC in the oldest old patients may be justified if co-morbidities are well controlled.

We propose a prism-hologram-prism sandwiched recording method for the fabrication of polarization-selective substrate-mode volume holograms with a large diffraction angle. In fabrication, the C-RT20 photopolymer is sandwiched between two 45°-90°-45° prisms and the interference fringes can be easily recorded in the recording material. The experimental results are in good agreement with the theoretical predictions. The proposed method features of a reflection-type recording setup for a transmission element and belongs to a technique of longer-wavelength construction for shorter-wavelength reconstruction. In addition, the method is much easier than the traditional recording method of two incident beam interference and has application potential in holographic photonics.

Previous raster-scanning with a 1μm X-ray beam of individual, myelinated fibers from glutaraldehyde-fixed rat sciatic nerve revealed a spatially-dependent variation in the diffraction patterns from single fibers. Analysis indicated differences in the myelin periodicity, membrane separations, distribution of proteins, and orientation of membrane lamellae. As chemical fixation is known to produce structural artifacts, we sought to determine in the current study whether the structural heterogeneity is intrinsic to unfixed myelin. Using a 200nm-beam that was about five-fold smaller than before, we raster-scanned individual myelinated fibers from both the peripheral (PNS; mouse and rat sciatic nerves) and central (CNS; rat corpus callosum) nervous systems. As expected, the membrane stacking in the internodal region was nearly parallel to the fiber axis and in the paranodal region it was perpendicular to the axis. A myelin lattice was also frequently observed when the incident beam was injected en face to the sheath. Myelin periodicity and diffracted intensity varied with axial position along the fiber, as did the calculated membrane profiles. Raster-scanning with an X-ray beam at sub-micron resolution revealed for the first time that the individual myelin sheaths in unfixed nerve are heterogeneous in both membrane structure and packing., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A GaN/AlGaN ultraviolet light emitting diode (UV-LED) structure with a porous AlGaN reflector structure has been demonstrated. Inside the UV-LED, the n + -AlGaN/undoped-AlGaN stack structure was transformed into a porous-AlGaN/undoped-AlGaN stack structure through a doping-selective electrochemical etching process. The reflectivity of the porous AlGaN reflector was 93% at 374 nm with a stop-bandwidth of 35 nm. In an angle-dependent reflectance measurement, the central wavelength of the porous AlGaN reflector had blueshift phenomenon by increasing light-incident angle from 10° to 50°. A cut-off wavelength was observed at 349 nm due to the material absorption of the porous-AlGaN/u-AlGaN stack structure. In the treated UV-LED structure, the photoluminescence emission wavelength was measured at 362 nm with a 106° divergent angle covered by the porous-AlGaN reflector. The light output power of the treated UV-LED structure was higher than that of the non-treated UV-LED structure due to the high light reflectance on the embedded porous AlGaN reflector.

The capsular polysaccharides in different serotypes of Klebsiella pneumoniae (KP) coded by the (CPS) gene cluster are characterized by a conserved and a hyper-variable region. We performed a virulence study by switching genes in the highly conserved region of the CPS cluster between strains. Six genes in the CPS conserved region in serotype K20, including galF, acidPPc, wzi, wza, wzb and wzc, were knocked out and replaced by the homologous genes from serotype K1. Compared to the parental K20 strain, the mutants showed a decline in lethality (LD 50 ) in mice from 10-fold to > 10 5 -fold and were categorized in terms of the effect on virulence as low (L) for galF and acidPPC, moderate (M) for wzi, and high (H) for wza, wzb and wzc. Although substituting the acidPPC gene from K1 for acidPPC in the K20 strain fully restored virulence, substitution with the wzi, wza, wzb or wzc homologs from K1 did not. The restoration with wzi from K1 led to a partial restoration of virulence, with the LD 50 in mice changing from 10 4 to 10 3 CFU . For the wza, wzb and wzc genes, Complementation of K20 wza, wzb and wzc from K1 resulted in varied degrees of lethality in mice. Variable improvement in serum killing and phagocytosis was observed when the knockout mutants were compared with the gene-switched strains. In conclusion, homologous genes for capsule synthesis failed to exhibit the same functionality when switched between serotypes and virulence was decreased in different degree in according to the genes' homology.

Introduction: Osteochondral allograft (OCA) transplantation is generally effective for treating large cartilage lesions. Cleansing OCA subchondral bone to remove donor marrow elements is typically performed with pulsed lavage. However, the effects of clinical and experimental parameters on OCA marrow removal by pulsed lavage are unknown. The aim of the current study was to determine the effects on marrow cleansing in human osteochondral cores (OCs) of (1) lavage duration, (2) lavage flow intensity, and (3) OC sample type and storage condition., Methods: OCs were harvested from human femoral condyles and prepared to a clinical geometry (cylinder, diameter = 20 mm). The OCs were from discarded remnants of Allograft tissues (OCA) or osteoarthritis patients undergoing Total Knee Replacement (OCT). The experimental groups subjected to standard flow lavage for 45 seconds (430 mL of fluid) and 120 seconds (1,150 mL) were (1) OCT/FROZEN (stored at -80°C), (2) OCT/FRESH (stored at 4°C), and (3) OCA/FRESH. The OCA/FRESH group was subsequently lavaged at high flow for 45 seconds (660 mL) and 120 seconds (1,750 mL). Marrow cleansing was assessed grossly and by micro-computed tomography (μCT)., Results: Gross and μCT images indicated that marrow cleansing progressed from the OC base toward the cartilage. Empty marrow volume fraction (EMa.V/Ma.V) increased between 0, 45, and 120 seconds of standard flow lavage, and varied between groups, being higher after FROZEN storage (86-92% after 45-120 seconds) than FRESH storage of either OCT or OCA samples (36% and 55% after 45 and 120 seconds, respectively). With a subsequent 120 seconds of high flow lavage, EMa.V/Ma.V of OCA/FRESH samples increased from 61% to 78%., Conclusions: The spatial and temporal pattern of marrow space clearance was consistent with gradual fluid-induced extrusion of marrow components. Pulsed lavage of OCAs with consistent time and flow intensity will help standardize marrow cleansing and may improve clinical outcomes.

InGaN light emitting diodes (LED) structure with an embedded 1/4λ-stack nanoporous-GaN/undoped-GaN distributed Bragg reflectors (DBR) structure have been demonstrated. Si-heavily doped GaN epitaxial layers (n(+)-GaN) in the 12-period n(+)-GaN/u-GaN stack structure are transformed into low refractive index nanoporous GaN structure through the doping-selective electrochemical wet etching process. The central wavelength of the nanoporous DBR structure was located at 442.3 nm with a 57 nm linewidth and a 97.1% peak reflectivity. The effective cavity length (6.0λ), the effective penetration depth (278 nm) in the nanoporous DBR structure, and InGaN active layer matching to Fabry-Pérot mode order 12 were observed in the far-field photoluminescence radiative spectra. High electroluminescence emission intensity and line-width narrowing effect were measured in the DBR-LED compared with the non-treated LED structure. Non-linear emission intensity and line-width reducing effect, from 11.8 nm to 0.73 nm, were observed by increasing the laser excited power. Resonant cavity effect was observed in the InGaN LED with bottom nanoporous-DBR and top GaN/air interface.

Targeting Bruton's tyrosine kinase (BTK) with the small molecule BTK inhibitor ibrutinib has significantly improved patient outcomes in several B-cell malignancies, with minimal toxicity. Given the reported expression and constitutive activation of BTK in acute myeloid leukemia (AML) cells, there has been recent interest in investigating the anti-AML activity of ibrutinib. We noted that ibrutinib had limited single-agent toxicity in a panel of AML cell lines and primary AML samples, and therefore sought to identify ibrutinib-sensitizing drugs. Using a high-throughput combination chemical screen, we identified that the poly(ADP-ribose) glycohydrolase (PARG) inhibitor ethacridine lactate synergized with ibrutinib in TEX and OCI-AML2 leukemia cell lines. The combination of ibrutinib and ethacridine induced a synergistic increase in reactive oxygen species that was functionally important to explain the observed cell death. Interestingly, synergistic cytotoxicity of ibrutinib and ethacridine was independent of the inhibitory effect of ibrutinib against BTK, as knockdown of BTK did not sensitize TEX and OCI-AML2 cells to ethacridine treatment. Thus, our findings indicate that ibrutinib may have a BTK-independent role in AML and that PARG inhibitors may have utility as part of a combination therapy for this disease.

Mitochondrial respiration is a crucial component of cellular metabolism that can become dysregulated in cancer. Compared with normal hematopoietic cells, acute myeloid leukemia (AML) cells and patient samples have higher mitochondrial mass, without a concomitant increase in respiratory chain complex activity. Hence these cells have a lower spare reserve capacity in the respiratory chain and are more susceptible to oxidative stress. We therefore tested the effects of increasing the electron flux through the respiratory chain as a strategy to induce oxidative stress and cell death preferentially in AML cells. Treatment with the fatty acid palmitate induced oxidative stress and cell death in AML cells, and it suppressed tumor burden in leukemic cell lines and primary patient sample xenografts in the absence of overt toxicity to normal cells and organs. These data highlight a unique metabolic vulnerability in AML, and identify a new therapeutic strategy that targets abnormal oxidative metabolism in this malignancy., (© 2015 by The American Society of Hematology.)

The high oxidation activity of coinage metals (Cu, Ag and Au) has been widely applied in various important reactions, such as oxidation of carbon monoxide, alkenes or alcohols. The catalytic behavior of those inert metals has mostly been attributable to their size effect, the physical effect. In the present study, the chemical effects on their high oxidation activity have been investigated. We mechanistically examine the direct and oxidative dehydrogenation (partial oxidation) reactions of ethanol to acetaldehyde on a series of transition metals (groups 9, 10 and 11) with identical physical characteristics and varied chemical origins using density functional theory (DFT) calculations and electronic structure analyses at the GGA-PW91 level. The energetic results show that coinage metals have much lower activation energies and higher exothermicities for the oxidative dehydrogenation steps although they have higher energy for the direct dehydrogenation reaction. In the electronic structure analyses, coinage metals with saturated d bands can efficiently donate electrons to O* and OH*, or other electronegative adspecies, and better promote their p bands to higher energy levels. The negatively charged O* and OH* with high-lying p bands are responsible for lowering the energies in oxidative steps. The mechanistic understanding well explains the better oxidation activity of coinage metals and provides valuable information on their utilization in other useful applications, for example, the dehydrogenation process.

When polypeptide chains fold into a protein, hydrophobic groups are compacted in the center with exclusion of water. We report the crystal structure of an alanine-rich antifreeze protein that retains ~400 waters in its core. The putative ice-binding residues of this dimeric, four-helix bundle protein point inwards and coordinate the interior waters into two intersecting polypentagonal networks. The bundle makes minimal protein contacts between helices, but is stabilized by anchoring to the semi-clathrate water monolayers through backbone carbonyl groups in the protein interior. The ordered waters extend outwards to the protein surface and likely are involved in ice binding. This protein fold supports both the anchored-clathrate water mechanism of antifreeze protein adsorption to ice and the water-expulsion mechanism of protein folding.

In this study, a novel moiré fringe analysis technique is proposed for measuring the surface profile of an object. After applying a relative displacement between two gratings at a constant velocity, every pixel of CMOS camera can capture a heterodyne moiré signal. The precise phase distribution of the moiré fringes can be extracted using a one-dimensional fast Fourier transform (FFT) analysis on every pixel, simultaneously filtering the harmonic noise of the moiré fringes. Finally, the surface profile of the tested objected can be generated by substituting the phase distribution into the relevant equation. The findings demonstrate the feasibility of this measuring method, and the measurement error was approximately 4.3 μm. The proposed method exhibits the merits of the Talbot effect, projection moiré method, FFT analysis, and heterodyne interferometry.

Emerging targeted therapies have shown benefits such as less toxicity and higher effectiveness in specific types of cancer treatment; however, the accessibility of these advantages may rely on correct identification of suitable patients, which remains highly immature. We assume that copy number profiles, being accessible genomic data via microarray techniques, can provide useful information regarding drug response and shed light on personalized therapy. Based on the mechanism of action (MOA) of trastuzumab in the HER2 signaling pathway, a Bayesian network model in which copy number alterations (CNAs) serve as latent parents modifying signal transduction is applied. Two model parameters M-score and R -value which stand for the qualitative and quantitative effects of CNAs on drug effectiveness and are functions of conditional probabilities (CPs), are defined. An expectation-maximization (EM) algorithm is developed for estimating CPs, M-scores, and R-values from continuous measures, such as microarray data. We show through simulations that the EM algorithm can outperform classical threshold-based methods in the estimation of CPs and thereby provide improved performance for the detection of unfavorable CNAs. Several candidates of unfavorable CNAs to the trastuzumab therapy in breast cancer are provided in a real data example.

Time-course expression profiles and methods for spectrum analysis have been applied for detecting transcriptional periodicities, which are valuable patterns to unravel genes associated with cell cycle and circadian rhythm regulation. However, most of the proposed methods suffer from restrictions and large false positives to a certain extent. Additionally, in some experiments, arbitrarily irregular sampling times as well as the presence of high noise and small sample sizes make accurate detection a challenging task. A novel scheme for detecting periodicities in time-course expression data is proposed, in which a real-valued iterative adaptive approach (RIAA), originally proposed for signal processing, is applied for periodogram estimation. The inferred spectrum is then analyzed using Fisher's hypothesis test. With a proper p-value threshold, periodic genes can be detected. A periodic signal, two nonperiodic signals, and four sampling strategies were considered in the simulations, including both bursts and drops. In addition, two yeast real datasets were applied for validation. The simulations and real data analysis reveal that RIAA can perform competitively with the existing algorithms. The advantage of RIAA is manifested when the expression data are highly irregularly sampled, and when the number of cycles covered by the sampling time points is very reduced.

DNA copy number alterations (CNAs) are known to be related to genetic diseases, including cancer. The unlimited transcription (UT) model, in which transcription occurs permissively with a simple activation probability, has been proposed to investigate long-term effects of CNAs on gene expression values. Queueing theory was applied, and the copy-number-gene-expression relationship has been shown to be generally nonlinear in the UT model. However, the dynamic effects of CNAs on transcription and the underlying disorders related to diseases remain greatly unknown. Since most genes in a single cell are permissively transcribed in short periods of time interspersed by long periods of limited transcription, an alternative model for transcription in the restrictive state is needed for unraveling the effects of CNAs on gene expression levels with time. To address these issues, herein a single transcription (ST) model is proposed, in which bound TFs are assumed to be unloaded immediately after stimulating a transcription. Using the Laplace-Stieltjes transform and numerical analysis, the relationship between DNA copy number and gene expression level is evaluated. Dynamic modeling reveals that CNAs would potentially alter, or even reverse, the burst-like gene expression modifications while shifting from the ST model to the UT model. Moreover, functional disorders in transcriptional oscillation due to CNAs are shown via simulation. This paper demonstrates how mathematical theories could be helpful to interpret statistical findings from real data and achieve a better understanding of cancer biology.

The only hyperactive antifreeze protein (AFP) found to date in fishes is an extreme variant of the 3-kDa, alpha-helical, alanine-rich type I AFP, which is referred to here as type Ih. Purification of the 33-kDa homodimeric AFP Ih from a natural source was hampered by its low levels in fish plasma; by the need to remove the more abundant smaller isoforms; and by its extreme thermolability. Moreover, ice affinity as a purification tool was spoiled by the tendency of fish IgM antibodies to bind to ice in the presence of AFPs. In order to produce enough protein for crystallography we expressed AFP Ih as a recombinant protein in the Arctic Express® strain of Escherichia coli at 12 °C, just below the thermal denaturation temperature of 16-18 °C. His-tags were not useful because they compromised the activity and yield of AFP Ih. But in the absence of fish antibodies we were able to recover 10-mg quantities of the antifreeze protein using two cycles of ice affinity purification followed by anion-exchange chromatography to remove contaminating chaperones. The purified recombinant AFP Ih yielded diffraction-quality crystals with an extremely asymmetrical unit cell. By transferring the genes of the chaperones into a methionine auxotroph we were able to grow this host at low temperatures and produce sufficient selenomethionine-labeled AFP Ih for crystallography., (Copyright © 2011 Elsevier Inc. All rights reserved.)

DNA copy number alterations (CNAs) can cause genetic diseases, and studies have revealed a relationship between CNAs and gene expression; however, the manner in which CNAs relate to gene expression and what regulatory mechanisms underlying the relationship remain unclear. In many instances, real data have revealed a nonlinear relationship between copy number and gene expression. In this paper, queueing theory is used to model this relationship, with the basic structural parameters involving transcription factor (TF) arrival and departure rates. A key finding is that the ratio of TF arrival rate to TF departure rate is critical: small and large ratios corresponding to nonlinear and linear relationships, respectively. Indeed, copy number amplifications do not necessarily lead to expression increases: when one of the regulatory TFs exists in a small amount, copy number gains can cause a down regulation. Using the concept of mutual information, we show that the TF with minimum activation probability can have maximum dependence in regulation: a TF in small amount could result in a nonlinear copy-number-gene-expression relationship and play a major role in regulation. The expectation-maximization algorithm is used to estimate the ratio of TF arrival rate to TF departure rate. The theoretical results are illustrated via simulations., (© 2011 IEEE)

Background: Despite initial response in adjuvant chemotherapy, ovarian cancer patients treated with the combination of paclitaxel and carboplatin frequently suffer from recurrence after few cycles of treatment, and the underlying mechanisms causing the chemoresistance remain unclear. Recently, The Cancer Genome Atlas (TCGA) research network concluded an ovarian cancer study and released the dataset to the public. The TCGA dataset possesses large sample size, comprehensive molecular profiles, and clinical outcome information; however, because of the unknown molecular subtypes in ovarian cancer and the great diversity of adjuvant treatments TCGA patients went through, studying chemotherapeutic response using the TCGA data is difficult. Additionally, factors such as sample batches, patient ages, and tumor stages further confound or suppress the identification of relevant genes, and thus the biological functions and disease mechanisms., Results: To address these issues, herein we propose an analysis procedure designed to reduce suppression effect by focusing on a specific chemotherapeutic treatment, and to remove confounding effects such as batch effect, patient's age, and tumor stages. The proposed procedure starts with a batch effect adjustment, followed by a rigorous sample selection process. Then, the gene expression, copy number, and methylation profiles from the TCGA ovarian cancer dataset are analyzed using a semi-supervised clustering method combined with a novel scoring function. As a result, two molecular classifications, one with poor copy number profiles and one with poor methylation profiles, enriched with unfavorable scores are identified. Compared with the samples enriched with favorable scores, these two classifications exhibit poor progression-free survival (PFS) and might be associated with poor chemotherapy response specifically to the combination of paclitaxel and carboplatin. Significant genes and biological processes are detected subsequently using classical statistical approaches and enrichment analysis., Conclusions: The proposed procedure for the reduction of confounding and suppression effects and the semi-supervised clustering method are essential steps to identify genes associated with the chemotherapeutic response.

Background: Circular Binary Segmentation (CBS) is a permutation-based algorithm for array Comparative Genomic Hybridization (aCGH) data analysis. CBS accurately segments data by detecting change-points using a maximal-t test; but extensive computational burden is involved for evaluating the significance of change-points using permutations. A recent implementation utilizing a hybrid method and early stopping rules (hybrid CBS) to improve the performance in speed was subsequently proposed. However, a time analysis revealed that a major portion of computation time of the hybrid CBS was still spent on permutation. In addition, what the hybrid method provides is an approximation of the significance upper bound or lower bound, not an approximation of the significance of change-points itself., Results: We developed a novel model-based algorithm, extreme-value based CBS (eCBS), which limits permutations and provides robust results without loss of accuracy. Thousands of aCGH data under null hypothesis were simulated in advance based on a variety of non-normal assumptions, and the corresponding maximal-t distribution was modeled by the Generalized Extreme Value (GEV) distribution. The modeling results, which associate characteristics of aCGH data to the GEV parameters, constitute lookup tables (eXtreme model). Using the eXtreme model, the significance of change-points could be evaluated in a constant time complexity through a table lookup process., Conclusions: A novel algorithm, eCBS, was developed in this study. The current implementation of eCBS consistently outperforms the hybrid CBS 4× to 20× in computation time without loss of accuracy. Source codes, supplementary materials, supplementary figures, and supplementary tables can be found at http://ntumaps.cgm.ntu.edu.tw/eCBSsupplementary.

Inchworm larvae of the pale beauty geometer moth, Campaea perlata, exhibit strong (6.4 °C) freezing point depression activity, indicating the presence of hyperactive antifreeze proteins (AFPs). We have purified two novel Thr- and Ala-rich AFPs from the larvae as small (∼3.5 kDa) and large (∼8.3 kDa) variants and have cloned the cDNA sequences encoding both. They have no homology to known sequences in current BLAST databases. However, these proteins and the newly characterized AFP from the Rhagium inquisitor beetle both contain stretches rich in alternating Thr and Ala residues. On the basis of these repeats, as well as the discontinuities between them, a detailed structural model is proposed for the 8.3 kDa variant. This 88-residue protein is organized into an extended parallel-stranded β-helix with seven strands connected by classic β-turns. The alternating β-strands form two β-sheets with a thin core composed of interdigitating Ala and Ser residues, similar to the thin hydrophobic core proposed for some silks. The putative ice-binding face of the protein has a 4 × 5 regular array of Thr residues and is remarkably flat. In this regard, it resembles the nonhomologous Thr-rich AFPs from other moths and some beetles, which contain two longer rows of Thr in contrast to the five shorter rows in the inchworm protein. Like that of some other hyperactive AFPs, the spacing between these ice-binding Thr residues is a close match to the spacing of oxygen atoms on several planes of ice.

A comprehensive study of the alkaloids presentin the leaves of Crinum asiaticum var. sinicum, assisted by HPLC-SPE-NMR, led to the characterization of 21 compounds of similar polarity on an analytical scale. Thirteen of these were isolated for further structural confirmation. Seven are proved to be new, namely, (+)-siculine (4), 1-epijosephinine (11), 7-methoxycrinamabine (10), 2-O-acetylcrinamabine (16), 3-O-acetyl-8-O-demethylmaritidine (17), 2-O-acetylbulbisine (18), and 1-O-acetylbulbisine (19). In addition, dihydrovittatine (6) and 8-O-demethyloxomaritidine (21) were isolated for the first time from Nature, although they have been prepared previously as synthetic products. Their structures were established by spectroscopic analysis.

The snow flea (Hypogastrum harveyi) is protected from freezing at sub-zero temperatures by a glycine-rich antifreeze protein (AFP) that binds to seed ice crystals and prevents them from growing larger. This AFP is hyperactive and comprises two isoforms [Graham, L. A., and Davies, P. L. (2005) Science 310, 461]. The larger isoform (15.7 kDa) exhibits several-fold higher activity than the smaller isoform (6.5 kDa), although it is considerably less abundant. To establish the molecular basis for this difference in activity, we determined the sequence of the large isoform. The primary sequences of these two isoforms are surprisingly divergent. However, both contain tripeptide repeats and turn motifs that enabled us to build a three-dimensional model of the large isoform based upon the six-polyproline helix structure of the small isoform. Our model contains 13 polyproline type II helices connected by proline-containing loops stacked into two flat sheets oriented antiparallel to one another. The structure is strictly amphipathic, with a hydrophilic surface on one side and a hydrophobic, putative ice-binding surface on the other. The putative ice-binding site is approximately twice as large in area as that of the small isoform, providing an explanation for the difference in activity that is consistent with other examples noted. By tagging the recombinant AFP with green fluorescent protein, we observed its binding to multiple planes of ice, especially the basal plane. This finding supports the correlation between AFP hyperactivity and basal plane binding first observed with spruce budworm AFP.

Background: The subtropical island of Taiwan is an area of high endemism and a complex topographic environment. Phylogeographic studies indicate that vicariance caused by Taiwan's mountains has subdivided many taxa into genetic phylogroups. We used mitochondrial DNA sequences and nuclear microsatellites to test whether the evolutionary history of an endemic montane bird, Steere's Liocichla (Liocichla steerii), fit the general vicariant paradigm for a montane organism., Results: We found that while mountains appear to channel gene flow they are not a significant barrier for Steere's Liocichla. Recent demographic expansion was evident, and genetic diversity was relatively high across the island, suggesting expansion from multiple areas rather than a few isolated refugia. Ecological niche modeling corroborated the molecular results and suggested that populations of Steere's Liocichla are connected by climatically suitable habitat and that there was less suitable habitat during the Last Glacial Maximum., Conclusions: Genetic and ecological niche modeling data corroborate a single history--Steere's Liocichla was at lower density during the Last Glacial Maximum and has subsequently expanded in population density. We suggest that such a range-wide density expansion might be an overlooked cause for the genetic patterns of demographic expansion that are regularly reported. We find significant differences among some populations in FST indices and an admixture analysis. Though both of these results are often used to suggest conservation action, we affirm that statistically significant results are not necessarily biologically meaningful and we urge caution when interpreting highly polymorphic data such as microsatellites.

Local nasal immunotherapy (LNIT) has been reported to be effective for mite-induced allergic rhinitis. However, its compliance is poor due to persistent nasal reactions and difficult application. The main objective of this study was to develop a Dermatophagoides pteronyssinus (Der p)-coated strip for self-application and to evaluate its clinical efficacy. Randomized, double-blind, placebo-controlled trials were carried out to evaluate the efficacy and compliance of LNIT. A total of 35 patients with allergic rhinitis from the allergy clinic were recruited to receive four months of LNIT. Clinical efficacy was evaluated by the symptoms of sneezing, rhinorrhea and nasal stuffiness. Local and systemic effects were evaluated by measuring histamine and eosinophil cationic protein (ECP) in nasal discharge and allergen-specific IgG1, IgG4 and IgE in sera. LNIT with Der p-coated strips could reduce nasal symptoms and modulate the serum levels of Der p-specific IgG1, IgG4 and IgE. The secretion of both histamine and ECP was reduced within four months after treatment. When the symptomatic and immunological changes were compared between active treatment and placebo groups, the improvements were greater in the active treatment groups for all three symptom scores. There were no severe adverse events except nasal response persisting within the first month in some cases. LNIT with a steady dose of Der p-coated strips can be self-administered at home without any systemic reactions. Both local and systemic immune responses were observed after LNIT. This therapeutic modality may serve as a good alternative treatment for allergic rhinitis.

A lipoprotein-like antifreeze protein (type IV AFP) has previously been isolated only from the blood plasma of the longhorn sculpin. However, the plasma antifreeze activity in all individuals of this species tested from Newfoundland and New Brunswick waters ranges from low to undetectable. A close relative of the longhorn sculpin, the shorthorn sculpin, does have appreciable antifreeze activity in its blood but this is virtually all accounted for by the alpha-helical, alanine-rich type I AFP, other isoforms of which are also present in the skin of both fishes. We have characterized a putative ortholog of type IV AFP in shorthorn sculpin by cDNA cloning. This 12.2-kDa Gln-rich protein is 87% identical to the longhorn sculpin's type IV AFP. Recombinant versions of both orthologs were produced in bacteria and shown to have antifreeze activity. Immunoblotting with antibodies raised to type IV AFP shows this protein present in longhorn sculpin plasma at levels of less than 100 microg/mL, which are far too low to protect the blood from freezing at the temperature of icy seawater. This confirms the results of direct antifreeze assays on the plasmas. It appears that type IV AFP has the potential to develop as a functional antifreeze in these fishes but may not have been selected for this role because of the presence of type I AFP. Consistent with this hypothesis is the observation that the type IV AFP gene has not been amplified the way functional antifreeze protein genes have in all other species examined.

Motivation: Genomic instability is one of the fundamental factors in tumorigenesis and tumor progression. Many studies have shown that copy-number abnormalities at the DNA level are important in the pathogenesis of cancer. Array comparative genomic hybridization (aCGH), developed based on expression microarray technology, can reveal the chromosomal aberrations in segmental copies at a high resolution. However, due to the nature of aCGH, many standard expression data processing tools, such as data normalization, often fail to yield satisfactory results., Results: We demonstrated a novel aCGH normalization algorithm, which provides an accurate aCGH data normalization by utilizing the dependency of neighboring probe measurements in aCGH experiments. To facilitate the study, we have developed a hidden Markov model (HMM) to simulate a series of aCGH experiments with random DNA copy number alterations that are used to validate the performance of our normalization. In addition, we applied the proposed normalization algorithm to an aCGH study of lung cancer cell lines. By using the proposed algorithm, data quality and the reliability of experimental results are significantly improved, and the distinct patterns of DNA copy number alternations are observed among those lung cancer cell lines., Supplementary Information: Source codes and.gures may be found at http://ntumaps.cgm.ntu.edu.tw/aCGH&#95;supplementary.

The nano grade hollow silica sphere (HSS) was synthesized by a novel soft template method. We found that the precipitate of aluminate had a porous structure that could be the soft template for HSS. After mixing the colloidal silica with the aluminate precipitate, the bubble trapped in this porous structure could form the nano grade HSS. The aluminate precipitate was removed by adjusting the pH of the slurry to approximately 1. The outside diameter, the specific surface, and the mean pore size diameter of the forming HSS were 60-90 nm, 571 m2/g, and 3 nm, respectively. The formed HSS was collected by modifying the surface with Si(OCH3)3CHCH2 (VTMO) and then filtrating the precipitated gel in the n-butanol and ethanol solvent system.

Antifreeze proteins (AFPs) are produced to prevent freezing in many fish species that are exposed to icy seawater. There are a number of nonhomologous types of AFPs, diverse in both sequence and structure, which share the function of binding to ice and inhibiting its growth. We recently discovered a hyperactive AFP in the winter flounder and related species that is many-fold more active than other fish AFPs. Like the 3-4-kDa type I AFPs, it is alanine-rich and highly helical, but this 17-kDa protein is considerably larger and forms a dimer. We have sequenced the cDNA encoding this new AFP to gain insight into its structure and evolutionary relationship to the type I AFP family. The gene is clearly homologous to the righteye flounder type I AFP genes. Thus we have designated this protein "hyperactive type I AFP" (hyp-type I). The sequence of hyp-type I AFP supports a structural model in which two extended 195-amino acid alpha-helices form an amphipathic homodimer with a series of linked Ala- and Thr-rich patches on the surface of the dimer, each of which resembles ice-binding sites of type I AFPs. The superior activity of hyp-type I AFP may derive from the large combined surface area of the ice-binding sites, recognition of multiple planes of ice, and protection of the basal plane from ice growth.

The objectives of this paper are to determine effects of different grass species and their harvests on pollutant removal, elucidate impacts on soil characteristics and grass constituents, observe grass yield and quantify nutrient uptake by vegetation in an overland flow system (OLFS). Polluted creek water was applied to eight channels in the OLFS, which were planted with Paragrass, Nilegrass, Cattail, and Vetiver, with each two channels being randomly planted with a given grass species. The grass in one channel was harvested while that in the other channel was not. At a high rate of 27.8 m d(-1) hydraulic loading, the removal efficiencies of conventional pollutants such as BOD, COD, suspended solids (SS), and total coliforms in wastewater are not affected by the type of the grasses species, but those of nitrogen and phosphorus are affected by different species. Overall average removal efficiencies of BOD, COD, SS, ammonia, total nitrogen, total phosphorus and total coliforms through the OLFS are 42%, 48%, 78%, 47%, 40%, 33% and 89%, respectively. The concentration of nitrate, however, increases due to nitrification. Soil characteristics in OLFS have been changed significantly; specific conductivity, organic matter, exchangeable magnesium, extractable copper and zinc in soils all increase with time while pHs decrease. During the winter season, there is a significant accumulation of nitrate in grass with the subsequent reduction during the active growing season (Spring). The contents of nitrate and phosphorus in grass tissue are higher than those of grass in general pastureland, probably due to nutrient luxury uptake by grass. The overall grass yield, growth rate and nutrient uptake are quantified and implication of such high rate OLFS discussed.

The glycine-rich antifreeze protein recently discovered in snow fleas exhibits strong freezing point depression activity without significantly changing the melting point of its solution (thermal hysteresis). BLAST searches did not detect any protein with significant similarity in current databases. Based on its circular dichroism spectrum, discontinuities in its tripeptide repeat pattern, and intramolecular disulfide bonding, a detailed theoretical model is proposed for the 6.5-kDa isoform. In the model, the 81-residue protein is organized into a bundle of six short polyproline type II helices connected (with one exception) by proline-containing turns. This structure forms two sheets of three parallel helices, oriented antiparallel to each other. The central helices are particularly rich in glycines that facilitate backbone carbonyl-amide hydrogen bonding to four neighboring helices. The modeled structure has similarities to polyglycine II proposed by Crick and Rich in 1955 and is a close match to the polyproline type II antiparallel sheet structure determined by Traub in 1969 for (Pro-Gly-Gly)(n). Whereas the latter two structures are formed by intermolecular interactions, the snow flea antifreeze is stabilized by intramolecular interactions between the helices facilitated by the regularly spaced turns and disulfide bonds. Like several other antifreeze proteins, this modeled protein is amphipathic with a putative hydrophobic ice-binding face.

In nucleic acids the N-glycosyl bonds between purines and their ribose sugar moities are broken under acid conditions. If one strand of a duplex DNA segment were more vulnerable to mutation than the other, then the archaeon Picrophilus torridus, with an optimum growth pH near zero, could have adapted by decreasing the purine content of that strand. Yet, P. torridus has an optimum growth temperature near 60 degrees C, and thermophiles prefer purine-rich codons. We found that, as in other thermophiles, high growth temperature correlates with the use of purine-rich codons. The extra purines are often in third, non-amino acid determining, codon positions. However, as in other acidophiles, as open reading frame lengths increase, there is increased use of purine-poor codons, particularly those without purines in second, amino acid-determining, codon positions. Thus, P. torridus can be seen as adapting (a) to temperature by increasing its purines in all open reading frames without greatly impacting protein amino acid compositions, and (b) to pH by decreasing purines in longer open reading frames, thereby potentially impacting protein amino acid compositions. It is proposed that longer open reading frames, being larger mutational targets, have become less vulnerable to depurination by virtue of pyrimidine for purine substitutions.