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Elastic binders with supramolecular interactions are widely explored to mitigate the stress caused by the volume expansion of electrode materials, such as Si, S, or Li metals, in next‐generation secondary batteries. Herein, a new class of elastic binders is proposed with an automatic stress‐control mechanism capable of responding in real time to dynamic local stress variations. Specifically, this study focuses on the shear‐thickening behavior, wherein polymers automatically amplify their viscoelasticity in response to local shear‐stress changes. To realize an intelligent stress‐adaptive binder, starch analogs exhibiting shear‐thickening properties and unique crystallinity are employed as binders for highly expandable Si anodes. The shear‐thickening mechanism is comprehensively investigated using deep‐learning‐based molecular dynamics (MD) simulations and in situ transmission electron microscopy (TEM) analysis, which determines the optimal conditions for effectively limiting dynamic local surface expansion. Among the starch analogs, the amylose and long‐chain amylopectin (AMLAP) binder demonstrates improved high‐rate capability (1710 mAh g−1 at 5 C) and superior reversible capacity (2025 and 1493 mAh g−1 after 100 and 500 cycles, respectively, at 1 C) with optimal shear‐thickening properties. Furthermore, AMLAP exhibits favorable characteristics for affordable large‐scale production. Hence, this study clearly demonstrates that the shear‐thickening properties of binders can be considered a new factor in fabricating stable electrodes with extremely expandable materials. [ABSTRACT FROM AUTHOR]

The development of flexible displays and electronics is hindered by the disadvantages of polymeric window films, such as low mechanical strength, poor optical properties, and lack of folding and rolling reliability. To overcome these critical limitations, a novel colorless polyimide window film is prepared in this study using the concept of charge‐transfer complex (CTC) intensification. The resulting window film has a tensile modulus of 8.4 GPa, total transmittance of ≈90%, and yellow index below 3, which is the best recorded balance between mechanical strength and optical properties for a highly flexible optical film. Unlike commercially available optical‐grade engineering plastic films and glass substrates, the prepared window film has both pencil hardness grade over 2H and folding reliability over 200 000 folding/unfolding cycles. These remarkable properties are attributed to the unique supramolecular structure with multiple hydrogen bonding and salt complexation interactions, which exhibits CTC intensification. The CTC intensification mechanism is also proposed in this study. [ABSTRACT FROM AUTHOR]

Background: Next-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform. Methods: The KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50% ± 3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment. Discussion: This pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers. Trial registration: NCT05525858. [ABSTRACT FROM AUTHOR]

Background: Endocrine treatment is recommended by clinical guidelines as the preferred treatment option for premenopausal as well as postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. In real-world clinical practice, however, a substantial number of patients are treated with chemotherapy. We aimed to compare the clinical antitumour activity and safety of palbociclib plus endocrine therapy with that of capecitabine chemotherapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer.Methods: This multicentre, open-label, randomised, phase 2 study was done in 14 academic institutions in South Korea. Premenopausal women aged 19 years or older with hormone receptor-positive, HER2-negative breast cancer that had relapsed or progressed during previous tamoxifen therapy and with an Eastern Cooperative Oncology Group performance status of 0-2 were included. One line of previous chemotherapy for metastatic breast cancer was allowed. Patients were randomly assigned, using a random permuted block design (with a block size of two), to receive palbociclib plus combination endocrine therapy (oral exemestane 25 mg per day for 28 days and oral palbociclib 125 mg per day for 21 days every 4 weeks plus leuprolide 3·75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1250 mg/m2 twice daily for 2 weeks every 3 weeks). Randomisation was stratified by previous chemotherapy for metastatic breast cancer and visceral metastasis. The primary endpoint was progression-free survival. All analyses were done in a modified intention-to-treat population that excluded patients who did not receive study medication. This study is registered with ClinicalTrials.gov, NCT02592746, and is ongoing for follow-up of overall survival.Findings: Between June 15, 2016, and Dec 10, 2018, 189 patients were enrolled, of whom 184 were randomly assigned to the palbociclib plus endocrine therapy group (n=92) or the capecitabine group (n=92). Six patients in the capecitabine group withdrew from the study before drug administration; therefore, 92 patients in the palbociclib plus endocrine therapy group and 86 patients in the capecitabine group were included in the modified intention-to-treat analyses. 46 (50%) of 92 patients in the palbociclib plus endocrine therapy group and 45 (51%) of 92 in the capecitabine group were treatment naive for metastatic breast cancer. During a median follow-up of 17 months (IQR 9-22), median progression-free survival was 20·1 months (95% CI 14·2-21·8) in the palbociclib plus endocrine therapy group versus 14·4 months (12·1-17·0) in the capecitabine group (hazard ratio 0·659 [95% CI 0·437-0·994], one-sided log-rank p=0·0235). Treatment-related grade 3 or worse neutropenia was more common in the palbociclib plus endocrine therapy group than in the capecitabine group (69 [75%] of 92 vs 14 [16%] of 86 patients). 2 (2%) patients in the palbociclib plus endocrine therapy group and 15 (17%) patients in the capecitabine group had treatment-related serious adverse events. No treatment-related deaths occurred.Interpretation: Exemestane plus palbociclib with ovarian function suppression showed clinical benefit compared with capecitabine in terms of improved progression-free survival in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Palbociclib plus exemestane with ovarian suppression is an active treatment option in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer who have been pretreated with tamoxifen.Funding: Pfizer, Shinpoong, and Daewoong Korea and Takeda. [ABSTRACT FROM AUTHOR]

Background: Poziotinib (HM781-36B) is an irreversible pan-HER tyrosine kinase inhibitor which targets EGFR, HER2, and HER4. This prospective, multicenter, open-label, phase I/II study determined the maximum tolerated dose (MTD) and evaluated the safety and efficacy of poziotinib combined with paclitaxel and trastuzumab in patients with HER2-positive advanced gastric cancer (GC). Methods: Patients with HER2-positive GC previously treated with one line of chemotherapy received oral poziotinib (8 mg or 12 mg) once daily for 14 days, followed by 7 days off. Paclitaxel (175 mg/m2 infusion) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg infusion) were administered concomitantly with poziotinib on day 1 every 3 weeks. Results: In the phase I part, 12 patients were enrolled (7 at dose level 1, 5 at dose level 2). One patient receiving poziotinib 8 mg and 2 receiving poziotinib 12 mg had dose-limiting toxicities (DLTs); all DLTs were grade 4 neutropenia, one with fever. The most common poziotinib-related adverse events were diarrhea, rash, stomatitis, pruritus and loss of appetite. The MTD of poziotinib was determined to be 8 mg/day and this was used in the phase II part which enrolled 32 patients. Two patients (6.3%) had complete responses and 5 (15.6%) had partial responses (objective response rate 21.9%). Median progression-free survival and overall survival were 13.0 weeks (95% CI 9.8–21.9) and 29.5 weeks (95% CI 17.9–59.2), respectively. Conclusions: The MTD of poziotinib combined with paclitaxel and trastuzumab was 8 mg/day. This combination yielded promising anti-tumor efficacy with manageable toxicity in previously treated patients with HER2-positive GC. [ABSTRACT FROM AUTHOR]

Effects of cation-site vacancies on the characteristics of the cubic–tetragonal displacive transitions in La-modified PbTiO[sub 3] (PLT) were studied using in situ XRD measurements and Raman scattering. For this purpose, two distinct types of PLT series having cation-site vacancies either at the A site (PLT-A) or at the B site (PLT-B) were separately prepared. The PLT-A series exhibited normal ferroelectricity and underwent the cubic-to-tetragonal structural transition for La substitution up to 30 at. %. Contrary to this, the PLT-B became a typical relaxor with the absence of the macroscopic cubic–tetragonal transition. However, for both types of PLTs, Raman-forbidden bands appeared in the high-temperature cubic-phase field at 30 at. % La modification. These observations were attributed to the formation of short-ranged clusters with tetragonal symmetry in a globally cubic matrix and to the reduced dipolar interaction between the clusters in the PLT-B, as compared with the PLT-A. © 2002 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Highlights • FKBP5 is involved in human stress responses and regulation of HPA axis. • An interaction effect of FKBP5 genotype and PTSD status on FKBP5 methylation level. • The risk allele of rs1360780 was associated with lower FKBP5 methylation levels. • Genetic and epigenetic modulation of FKBP5 may play a role in PTSD pathophysiology. Abstract Background FK506-binding protein 5 (FKBP5) binds to glucocorticoid receptors and modulates glucocorticoid sensitivity. The FKBP5 gene has been implicated in the dysregulation of human stress responses, contributing to the risk and treatment response of stress-related disorders. The present study examined whether epigenetic changes in FKBP5 are associated with chronic post-traumatic stress disorder (PTSD) status in the context of FKBP5 genetic variation (rs1360780 polymorphism) among male veterans exposed to combat trauma. Methods Korean male veterans who served on active duty during the Vietnam War were categorized into 2 groups: with PTSD (n = 123) and without PTSD (n = 116). The genotype of FKBP5 rs1360780 and DNA methylation levels of two CpG sites at the FKBP5 intron 7 region were assessed in peripheral blood. Analysis of covariance was performed to examine main and interaction effects of PTSD status and FKBP5 genotype on FKBP5 DNA methylation level, with age, trauma levels, and alcohol use as covariates. Results A significant main effect of FKBP5 rs1360780 and PTSD and an interaction effect between genotype and PTSD status were found on mean FKBP5 DNA methylation level. The T allele of rs1360780 was associated with lower FKBP5 methylation level. In addition, the PTSD group showed significantly higher methylation than did the non-PTSD group among veterans carrying the risk T allele (n = 96), while no group difference was observed on methylation levels among veterans with the CC genotype (n = 143). Among veterans carrying the T allele, FKBP5 methylation levels were positively correlated with the severity of PTSD symptoms. Conclusions The present study demonstrated different FKBP5 methylation levels in PTSD depending on FKBP5 genetic variation among veterans exposed to combat trauma. The present finding suggests that the genetic and epigenetic modulation of FKBP5 is involved in the pathophysiology of PTSD. Further longitudinal research involving people exposed to trauma is required to understand causal relationships of FKBP5 in the development and recovery of PTSD. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess radiological changes of the ankle joint, subtalar joint and foot following the correction of varus deformity of the knee with total knee arthroplasty (TKA). It was hypothesized that following the correction of varus deformity by TKA, compensatory reactions would occur at the subtalar joint in accordance with the extent of the correction.Methods: For this prospective study, 375 knees of patients who underwent TKA between 2011 and 2012 were enrolled. The varus angle of the knee, talar tilt of the ankle joint (TT), ground-talar dome angle of the foot (GD), anterior surface angle of the distal tibia and lateral surface angle of the distal tibia, heel alignment ratio (HR), heel alignment angle (HA), and heel alignment distance (HD) were measured on radiographs obtained pre-operatively and at post-operative 6 months.Results: The mean correction angle in varus deformity of the knee was 10.8 ± 4.1°. TT and GD changed significantly from 0.4 ± 1.9° and 6.5 ± 3.1° pre-operatively to 0.1 ± 1.8° and 0.2 ± 2.1°, respectively (p = 0.007, p < 0.001). No correlation was found between the preop-postop variance in mechanical axis of the lower extremity (MA) and TT, but there was a strong correlation between the preop-postop variance in MA and GD (r = 0.701). HR, HA and HD also changed significantly post-operatively, and the preop-postop variance in MA showed correlations with the preop-postop variances in HR, HA and HD (r = 0.206, - 0.348, and - 0.418). TT and the three indicators of hindfoot alignment all shifted to varus whereas GD was oriented in valgus.Conclusion: Following the correction of varus deformity of the knee through TKA, significant compensatory changes occurred not only at the ankle and subtalar joints, but also at the foot. The findings of this study are useful in predicting the orientation of changes in the ankle and subtalar joints and the foot following TKA, and in determining the sequence of surgery when both the ankle and knee have a problem. In other words, changes in the parts of the lower extremity below the ankle joint following the correction of varus deformity of the knee must be considered when TKA is planned and performed. Patients who have problems at the ankle, subtalar, and foot joints in addition to varus deformity of the knee are recommended to undergo knee joint correction first.Level Of Evidence: II. [ABSTRACT FROM AUTHOR]

We investigated the effect of picosecond pulsed laser irradiation on the sheet resistance and microstructure of the silver nanowire films coated on PET substrates. The sheet resistance of the silver nanowire film abruptly increases from ∼102 to ∼108 ohm/square at a certain range of laser power. The sheet resistance of the picosecond laser annealed silver nanowire film strongly depends on the microstructure. The silver nanowires are ablated from the substrate and the surface of the substrate are seriously damaged above certain range of laser power. We analyzed the abrupt increase of sheet resistance and the damage of substrate surface in terms of temperature rising during the laser irradiation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Active site structure of a lithium phosphate is proposed. • The (001) surface of a lithium phosphate is the most plausible active surface. • The under-coordinated Li sites activates the C O bond of an epoxide ring. • The surface P O group receives a proton from the terminal carbon. Basic lithium phosphate (B-LPO) catalyst selectively produces unsaturated alcohols from epoxides. The catalytic activity of B-LPO is known to originate from appropriate acidic-basic properties, but no details were available on the structure of the active site. In this study, experimental methods and DFT calculations were performed in an attempt to identify the active surface structure of B-LPO for the isomerization of 2,3-epoxybutane to 3-buten-2-ol. The experimental results showed that exchanged Na ions in B-LPO suppressed the formation of an acid-catalyzed by-product (methyl ethyl ketone). In addition, H 2 O had a negative effect on the formation of 3-buten-2-ol due to the preoccupation of the active site. DFT calculations in conjunction with these experimental observations showed that the most plausible active surface for the formation of 3-buten-2-ol is the (001) surface of LPO whose acidic proton is exchanged with Na atom. On this surface, the under-coordinated Li atoms and the surface P O groups are exposed, and these play a role in activating the C O bond of an epoxide ring, and in receiving a proton from the terminal carbon, respectively. [ABSTRACT FROM AUTHOR]

We developed highly efficient solution-processed phosphorescent organic light-emitting device by annealing of hole transporting polymer layer at about glass transition temperature. Poly( N,N '-bis(4-butylphenyl)- N,N '-bis(phenyl)benzidine) (poly-TPD) was used as a hole transporting polymer layer and tris(2-phenylpyridine)iridium(III) [Ir(ppy) 3 ] doped N,N '-dicarbazolyl-3,5-benzene (mCP) was used as a solution-processed emission layer. The annealing temperature was critical to the well-defined interface between the poly-TPD and mCP:Ir(ppy) 3 layers. In addition, the carrier recombination was significantly enhanced by high temperature annealing of poly-TPD layer. A current efficiency of 61.5 cd/A and an external quantum efficiency of 17.5% were achieved by annealing of poly-TPD layer at about glass transition temperature. [ABSTRACT FROM AUTHOR]

Drug discovery aims to select proper targets and drug candidates to address unmet clinical needs. The end-to-end drug discovery process includes all stages of drug discovery from target identification to drug candidate selection. Recently, several artificial intelligence and machine learning (AI/ML)-based drug discovery companies have attempted to build data-driven platforms spanning the end-to-end drug discovery process. The ability to identify elusive targets essentially leads to the diversification of discovery pipelines, thereby increasing the ability to address unmet needs. Modern ML technologies are complementing traditional computer-aided drug discovery by accelerating candidate optimization in innovative ways. This review summarizes recent developments in AI/ML methods from target identification to molecule optimization, and concludes with an overview of current industrial trends in end-to-end AI/ML platforms. [ABSTRACT FROM AUTHOR]

This paper describes an assessment of vulnerability to global damage of a dry storage structure subjected to postulated commercial aircraft crashes. The vulnerability from plausible collisions of an aircraft is expressed by failed volume fraction in distribution curves obtained from an integrated deterministic and probabilistic approach. Nonlinear dynamic analyses are performed using smoothed particle hydrodynamics and finite element method to simulate the aircraft impact and the subsequent reinforced concrete damage. The response surface method, polynomial regressions and Monte Carlo simulation are employed for the probabilistic assessment. Failure probabilities of damage for three predefined response modes are estimated at side and upper impact locations. Resultant probabilities under these scenarios were relatively high and, thus, global resistance of the structure to withstand aircraft crashes is generally low. The outcomes of this study can be incorporated into quantitative evaluation within a probabilistic risk assessment framework and associated with further numerical analysis methodologies. [Display omitted] • Integrated deterministic and probabilistic approach is proposed to evaluate structural damage induced by aircraft impacts. • SPH-FE coupling method is applied to simulate postulated aircraft crashes on a dry storage facility. • Response surface, polynomial regression, and Monte Carlo simulation methods are employed to quantify the structural damage. • The probability of damage is estimated at two impact locations according to variations in impact velocity and angle. [ABSTRACT FROM AUTHOR]

N2O activation of Cu-MOR enhanced methanol production at elevated temperatures, to a greater extent than activation by O2 under optimal conditions. The increase in methanol production by N2O activation was attributed to the facile formation of an active copper center with no formation of inactive intermediate species. [ABSTRACT FROM AUTHOR]

A total of 19 bacteriophages were isolated from seawater, wet sand, sea rocks, and suspended solids collected from 10 different sites in Busan, Republic of Korea. Among them, the best-performed novel phage was designated as BPVP-3325 that demonstrated the highest lytic activity in 76% of the total studied strains of Vibrio parahaemolyticus. The complete genome of the novel phage was 222,634 bp with 42% G + C content; electron microscopy showed that the total length and head length were 411.66 ± 6.69 and 129.87 ± 5.10 nm, respectively. In vitro characterization, V. parahaemolyticus ATCC 17802 was used as a standard pathogenic strain of BPVP-3325 host. The latent period was approximately 40 min, and the burst size was 6.76 PFU/infected cell. BPVP-3325 demonstrated excellent efficacy in a relatively wide pH range of up to 5–10 and temperature of <50 °C. When ATCC 17802 was treated with BPVP-3325 in a liquid medium for 6 h, OD 600 in the phage-treated group was significantly lower (~50%) than that in the host. The application of BPVP-3325 to oyster meat effectively inhibited the growth and activity of the standard strain (P < 0.05). Therefore, this study described the potential of novel BPVP-3325 therapy for natural oyster culture and food industry for the biocontrol of V. parahaemolyticus disease in aquaculture and human food. • Novel BPVP-3325 phage was isolated from seawater. • BPVP-3325 inhibited the growth of Vibrio parahaemolyticus. • Complete genome of the BPVP-3325 phage was 222,634 bp with 42% G + C content. • BPVP-3325 showed excellent efficacy in a relatively wide pH range and temperature. [ABSTRACT FROM AUTHOR]

Postulated high energy line breaks have been considered as a part of design of nuclear safety-related structures, systems and components for a long time. However, recently, technical controversy was raised over the adequacy in assumption of complex phenomena and assessment of dynamic loads. This study is to address blast wave evaluation under a typical main steam line break condition of 1,400MWe power plant. At first, a mock-up facility was developed and six tests were performed by changing rupture pressures and target distances. Corresponding computational fluid dynamics analyses were also carried out after optimization of numerical model. Finally, pressure – time histories caused by plant specific blast wave were generated in use of a theoretical correlation, which were applied to finite element analyses of neighboring steam generator and containment wall. Integrity assessment results as well as the details of tests and analyses data were provided, and their applicability was discussed. • Pipe break tests were performed to examine HELB-induced blast wave. • Test results were supplemented by optimized CFD analyses. • Dynamic loads were determined through a theoretical correlation. • Integrity of typical SSCs was assessed for a 1400MWe plant. [ABSTRACT FROM AUTHOR]

Background: In advanced gastric cancer (AGC), HER2 is a validated therapeutic target. However, the metabolic landscape of AGC based on HER2 status has not been reported. Furthermore, the prognostic value of HER2 in AGC is under debate. The purpose of this study was to determine the metabolic landscape and prognosis on the basis of HER2 status in AGC. Methods: We analyzed 866 AGC patients treated with palliative chemotherapy and whose HER2 status was evaluated. HER2 positivity was defined as HER2 IHC 3+ or HER2/CEP17 ratio ≥2. Among them, 363 patients were evaluated with F FDG-PET before chemotherapy. We analyzed mSUV (maximal standardized uptake value) according to HER2 status and clinical outcomes. Results: Among 866 patients, 225 (26.0 %) had HER2+ GC. The mSUV of HER2+ GC was significantly higher than that of HER2− GC (12.6 vs. 8.7, p < 0.001). Increased HER2 IHC positivity was correlated with increased mSUV (IHC−: 8.1, IHC 1+: 8.2, 2+: 11.4, 3+: 13.2, p < 0.001). Excluding HER2+ patients who received HER2-targeting agents, OS of patients was not different by HER2 status (12.5 vs. 11.9 months, p = 0.688). However, according to tumor metabolism, patients with higher mSUV showed worse OS regardless of HER2 positivity (mSUV < 12.8:14.8, ≥12.8:8.6 months, p < 0.001). Conclusion: Tumor metabolism of AGC adversely influenced OS under treatment with cytotoxic chemotherapy. Tumor metabolism was higher in HER2+ AGC than HER2−. However, HER2 was not a prognostic factor in patients who received chemotherapy without HER2-targeting agents. [ABSTRACT FROM AUTHOR]

Keywords: charge-transfer complex; flexible displays; folding reliability; mechanical bulk and surface strength; optical film EN charge-transfer complex flexible displays folding reliability mechanical bulk and surface strength optical film 1 1 1 05/17/22 20220513 NES 220513 B Flexible Displays b In article number 2111040, Haksoo Han, Sung Woo Hong, and co-workers show that the outstanding optical and mechanical properties of the flexible transparent window film, as well as its folding reliability over 200,000 folding/unfolding cycles, are attributed to a unique supramolecular structure with multiple hydrogen bonding and salt complexation interactions, which exhibits charge transfer complex intensification. Charge-transfer complex, flexible displays, folding reliability, mechanical bulk and surface strength, optical film Highly Transparent, Colorless Optical Film with Outstanding Mechanical Strength and Folding Reliability Using Mismatched Charge-Transfer Complex Intensification (Adv. Funct. [Extracted from the article]

A novel type of dehydration reaction that produces epoxides from vicinal diols (dehydrative epoxidation) using a basic catalyst is reported. Epoxyethane, 1,2-epoxypropane, and 2,3-epoxybutane were produced from the dehydrative epoxidation of ethylene glycol, 1,2-propanediol, and 2,3-butanediol, respectively. Among a number of tested basic catalysts, the Cs/SiO 2 catalyst showed outstanding performance for the dehydrative epoxidation of 2,3-butanediol and is considered to be the most promising catalyst for this type of reaction. In order to identify the superiority of the Cs/SiO 2 catalyst and a mechanism of the reaction, structure–activity relationships were studied along with density functional theory (DFT) calculations. The following features are found to be responsible for the excellent activity of the Cs/SiO 2 catalyst: i) strong basic sites formed by Cs + , ii) low penetration of Cs + into SiO 2 which permits basic sites to be accessible to the reactant, iii) stable basic sites due to the strong interactions between Cs + and SiO 2 surface, and iv) mildly acidic surface of SiO 2 which is advantageous for the elimination to H 2 O. In addition, the dehydrative epoxidation involves an inversion of chirality (e.g. meso -2,3-butanediol ( R,S ) to trans -2,3-epoxybutane ( R,R or S,S )), which is in agreement with DFT results that the reaction follows a stereospecific S N 2-like mechanism. [ABSTRACT FROM AUTHOR]

Tin oxide coating by employing electron cyclotron resonance metal–organic chemical vapor deposition was performed on 5 V-class spinel LiNi 0.5 Mn 1.5 O 4 cathode electrodes prepared by a conventional tape-casting method. The pristine and SnO 2 -deposited LiNi 0.5 Mn 1.5 O 4 electrodes were characterized by X-ray diffraction, field-emission electron probe microanalyzer, field-emission scanning electron microscopy, Auger electron spectroscopy, charge–discharge measurements, and electrochemical impedance spectroscopy were evaluated in lithium cells using the fabricated electrodes. The SnO 2 -deposited LiNi 0.5 Mn 1.5 O 4 electrodes exhibited better rate capability at room temperature and superior electrochemical performance during the storage test evaluated at 60 °C in a fully charged state than the pristine LiNi 0.5 Mn 1.5 O 4 electrode. Also, surface modification of the LiNi 0.5 Mn 1.5 O 4 electrode was found by impedance analyses to be effective for suppressing the increase of the charge transfer resistance during the storage test at elevated temperatures. [ABSTRACT FROM AUTHOR]

Objective A larger primary tumour size, greater numbers of cervical lymph node ( LN) metastasis are associated with a higher risk of distant metastases in papillary thyroid carcinoma ( PTC). However, the impact of the location of cervical LN metastasis on distant metastasis is controversial. The aim of this study was to evaluate the risk of distant metastases according to the tumour size and LN status in PTC patients, with special consideration of the LN metastasis pattern. Patients This retrospective cohort study reviewed 1700 classical PTC patients who underwent initial thyroid surgery at Asan Medical Center between 2000 and 2004. Results The cumulative risk of distant metastases was increased with the increase in tumour size and was significantly different according to the location of involved LNs by the tumour node metastasis (TNM) staging. The cumulative risk in pN1b group showed the steepest increasing pattern with the increase in tumour size compared with pN1a and pN0/Nx group. When we analysed the cumulative risk of distant metastases according to the number of involved LNs, patients with more than 20 involved LNs also had the steepest increase in the risk of distant metastases with the increase in tumour size. However, only the location of involved LNs, not the number of involved LNs, was associated with distant metastases in multivariate analysis. Conclusions We confirm that the location of involved LNs categories based on the TNM staging system is more useful than the number of involved LNs categories for estimating the risk of distant metastasis in PTC. Differentiating N1a disease from N1b disease is important for the follow-up and management of patients with PTC. [ABSTRACT FROM AUTHOR]

Highlights: [•] The electrode is prepared by electrodeposition and then heat-treatment of iridium oxide. [•] The electrode exhibits the near-Nernstian pH response of 59.5 (±1) mV/pH. [•] Hysteresis of the electrode is negligible in the reversibility test. [•] The potential deviation is less than 10mV between the electrodes. [ABSTRACT FROM AUTHOR]

Background Cells of the innate immune system that are implicated in allergy and immunity bind to chitin during tissue infiltration in a process negatively regulated by vertebrate chitinases. Both acidic mammalian chitinase (AMCase) and chitotriosidase (ChT) exert chitinolytic activity. The levels of activities of these enzymes in nasal polyps (NPs) of subjects who smoke or who suffer from allergies are unknown. In the present work, we measured the activities of AMCase and ChT in NPs of smokers and allergic subjects. Methods We report a prospective cohort study in a tertiary care facility. AMCase and ChT activities of NPs were measured in buffers of several pH values using the fluorogenic substrate 4-methylumbelliferyl-β- d- N,N′ ,N″-triacetyl-chitotriose. Results The activities of AMCase and ChT in NPs did not differ significantly among smokers, nonsmokers, and ex-smokers. AMCase and ChT activities were significantly higher in NPs of allergic subjects than in NPs of those who did not suffer from allergy. Conclusion Increased levels of chitinolytic activities in NPs were associated with the allergic rhinitis. We suggest that control of such rhinitis may help to prevent the development and growth of NPs. [ABSTRACT FROM AUTHOR]

Background The symptomatology of posttraumatic stress disorder (PTSD) is related not only to the intensity of the causative trauma, but also to alcohol use and genetic factors. Among the many candidate genes, the apolipoprotein E gene ( APOE) is thought to be associated with stress reactivity. Methods Korean veterans of the Vietnam War with ( n = 128) or without ( n = 128) PTSD participated in this study. The Clinician-Administered PTSD Scale and Combat Exposure Scale were administered, and the severity of alcohol use was assessed among these veterans. The APOE polymorphism and clinical variables of the subjects were compared, and associations between PTSD and potential explanatory variables were tested using logistic regression analysis. Results Higher frequencies of APOE ε2 alleles and a greater number of individuals with the ε2 allele were found in the PTSD group. Among patients with PTSD, ε2-allele noncarriers consumed alcohol in greater amounts and more frequently than did ε2-allele carriers. Regression analysis revealed a significant interactional effect between harmful drinking and the absence of the ε2 allele associated with PTSD risk. Conclusions These results suggest that the APOE ε2 allele operates as a susceptibility gene for combat-related PTSD, with the relationship between alcohol use and PTSD differing according to the ε2-allele status. Future studies should determine the role of the APOE in adaptation to extreme stress, the development of PTSD, and comorbid alcohol-related disorders. [ABSTRACT FROM AUTHOR]

• A commercial aircraft model was developed and validated through FTHA and MTIA. • Postulated aircraft crash to tokamak building was evaluated by SPH-FE coupling method. • Damage of concrete and embedded rebar was quantified under comprehensive conditions. • Sensitivity analyses were performed to rank significance of four independent variables. Nuclear structures, systems and components important to safety should be adequately protected against diverse internal and external hazards. As part of the effort, a few comprehensive guidelines to deal with human-induced events were established and individual researches to assess fissile plant containment buildings under plausible aircraft colliding conditions were carried out. In relation to developing fusion plants, soundness of major structures as a barrier should also be ensured to prevent disaster due to potential external hazards as well as internal hazards like the leakage of radioactive material and electromagnetic waves. The objective of this study is to examine structural integrity of postulated tokamak building taking into account dynamic loading derived from aircraft collision process. The numerical models of aircraft and reinforced concrete structure were made in use of smoothed-particle hydrodynamics and finite element methods. Appropriateness of time-dependent impact force and impulse histories was verified through comparison between preliminary analysis data for a rigid wall and those obtained from Riera method. Systematic analyses of aircraft crash onto the tokamak building were performed under hypothetical scenarios with different variables such as impact velocities, angles and rebar diameters. As results, basic engineering parameters such as stresses and strains of the rebar were calculated, and damage of the concrete was estimated. Further sensitivity analyses were performed and effects of each numerical input were discussed in terms of the significant. [ABSTRACT FROM AUTHOR]

Abstract: Nickel supported γ-alumina (Ni/γ-Al2O3) catalysts are well-known to be highly active on the autothermal reforming of methane, but to be unstable due to coke deposition. Cerium oxide (CeO2) is one of promising promoter to overcome the fast deactivation of nickel-based catalysts by coke formation. Herein, catalytic behavior of CeO2 over Ni/γ-Al2O3 catalysts on the autothermal reforming of methane was investigated. The catalytic activity was maintained for 100 h with H2/CO molar ratio of 1.9. The formation of CeAlO3 is observed at the reduction and reaction conditions. In this work, it was found that the formation of CeAlO3 promoted the catalytic oxidation toward CO2 and prevented the formation of α-Al2O3 and nickel-aluminate, resulting in stable activity for autothermal reforming of methane. [Copyright &y& Elsevier]

The communication between cell phones and sensor networks involves strong user authentication protocols to ensure the data and network security. Generally, in order to obtain the relevant information, cell phones interact with sensor networks via gateways. In 2009, according to Arjan Durresi and Vamsi Paruchuri scheme, this unique ability is used to provide better authentication and security protocols that can be used to establish secure communications among cell phones and sensor networks. In this paper, we show that their scheme is vulnerable to known attacks such as man-in-the-middle attack and reply attack, and it does not provide mutual authentication between gateway node and cell phone. In addition, it does not establish session key after the authentication phase. To fill this security gap, we proposed security patches and improvements, which overcome the weak features in the scheme of Arjan Durresi and Vamsi Paruchuri. Finally, we came out with results which show that our improved security patch establishes trust between the cell phone and gateway in the form of mutual authentication and provides the session key establishment after the authentication phase. [ABSTRACT FROM AUTHOR]

An effective strategy comprising two phases is proposedto determinethe thermodynamically dominant pathways in a metabolic network ofa given phenotype, involving several metabolic reactions. In the firstphase, stoichiometrically feasible metabolic pathways are exhaustivelyidentified through the flux balance analysis and the graph-theoreticmethod based on P-graphs. In the second phase, thermodynamically dominantpathways are selected from these stoichiometrically feasible metabolicpathways on the basis of the Gibbs free energy change of reaction.The proposed strategy’s efficacy is demonstrated by applyingit to two E. colimodels: one is for maximal acetateand ethanol production, and the other is for maximalpoly(3-hydroxybutyrate)production. [ABSTRACT FROM AUTHOR]

Spider silk has been drawing much attention as a great biomaterial having many applications in biotechnology and biomedicine owing to its several desired material characteristics such as outstanding strength, toughness, and elasticity as well as biodegradability and biocompatibility. With various applications foreseeable in industry, there has been much effort to produce recombinant spider silk protein in large amounts. However, owing to the difficulties in its production using spiders, alternative host systems and engineering methods have been investigated to develop suitable production systems that can efficiently produce spider silk protein. Here, we review recent advances in production of spider silk proteins in various heterologous host systems with focus given on the development of metabolic and cellular engineering strategies. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Patients with metastatic thyroid cancers that do not uptake iodine need effective therapeutic option. Differentiation-inducing agents have been tried to restore functional expression of sodium iodide symporter (NIS) without success. Our objective was to assess the effect of alpha-lipoic acid (ALA), known as potential antioxidant, on expression of sodium iodide symporter in thyroid cancer cells. Methods: Human thyroid cancer-derived cell lines, TPC-1, were treated with ALA, and changes in NIS mRNA and protein expression were measured. ALA''s effect on NIS gene promoter was evaluated, and functional NIS expression was assessed by iodide uptake assay. Results: Treatment with ALA increased NIS mRNA expression up to ten folds of control dose-dependently after 24 h of exposure. ALA increased NIS promoter activity, and increased iodide uptake by 1.6 fold. ALA induced expression of NIS protein, but had no significant effect on the plasma membrane trafficking. ALA increased phosphorylation of CREB and nuclear translocation of pCREB, and co-treatment of ALA and trichostatin A increased iodide uptake by three folds in TPC-1 cells. Conclusions: ALA is a potential agent to increase NIS transcription in TPC-1. It could be used as an adjunctive agent to increase efficacy of radioiodine therapy if combined with a strategy to increase NIS protein trafficking to cell membrane. [Copyright &y& Elsevier]

In the last decade, reconstruction and applications of genome-scale metabolic models have greatly influenced the field of systems biology by providing a platform on which high-throughput computational analysis of metabolic networks can be performed. The last two years have seen an increase in volume of more than 33% in the number of published genome-scale metabolic models, signifying a high demand for these metabolic models in studying specific organisms. The diversity in modeling different types of cells, from photosynthetic microorganisms to human cell types, also demonstrates their growing influence in biology. Here we review the recent advances and current state of genome-scale metabolic models, the methods employed towards ensuring high quality models, their biotechnological applications, and the progress towards the automated reconstruction of genome-scale metabolic models. [Copyright &y& Elsevier]

Abstract: Transient receptor potential melastatin 7 (TRPM7) channels are divalent cation-selective ion channels that are permeable to Ca2+ and Mg2+. TRPM7 is ubiquitously expressed in vertebrate cells and contains both an ion channel and a kinase domain. TRPM7 plays an important role in regulating cellular homeostatic levels of Ca2+ and Mg2+ in mammalian cells. Although studies have shown that the kinase domain of TRPM7 is required for channel activation and can phosphorylate other target proteins, a systematic analysis of intact TRPM7 channel phosphorylation sites expressed in mammalian cells is lacking. We applied mass spectrometric proteomic techniques to identify and characterize the key phosphorylation sites in TRPM7 channels. We identified 14 phosphorylation sites in the cytoplasmic domain of TRPM7, eight of which have not been previously reported. The identification of phosphorylation sites using antibody-based immunopurification and mass spectrometry is an effective approach for defining the phosphorylation status of TRPM7 channels. The present results show that TRPM7 channels are phosphorylated at multiple sites, which serves as a mechanism to modulate the dynamic functions of TRPM7 channels in mammalian cells. [Copyright &y& Elsevier]

Purpose: In gemcitabine-pretreated pancreatic cancer, salvage chemotherapy has not been established, and the prognostic factors are not completely known. The purpose of this study was to determine the efficacy and safety of infusional 5-fluorouracil (5-FU), doxorubicin, and mitomycin-C (iFAM) in patients with gemcitabine-pretreated pancreatic cancer and to elucidate the prognostic factors. Methods: Study eligibility was as follows: (1) 18-75 years of age; (2) relapse within 6 months after adjuvant gemcitabine-based chemotherapy (GBC) or previously treated with palliative GBC; and (3) an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2. iFAM consisted of a 5-FU (800 mg/m) infusion over 10 h on days 1-5, doxorubicin (30 mg/m) on day 1, and mitomycin-C (8 mg/m) on day 1 every 4 weeks. Results: Sixty patients were enrolled. The responses to iFAM included a partial response in 6 patients (10.0%) and stable disease in 8 patients (13.3%). The median progression-free survival (PFS) and overall survival (OS) were 2.4 months (95% confidence interval [CI], 2.0-2.8 months) and 6.1 months (95% CI, 4.2-8.0 months), respectively. The 6- and 12-month survival rates were 50.4 and 26.4%, respectively. Grade 3/4 hematologic toxicities included neutropenia (3.3%) and thrombocytopenia (3.3%). The ECOG PS was a significant prognostic factor for PFS ( P < 0.001) and OS ( P = 0.022). An elevated CA 19-9 at the time of initiating iFAM ( P = 0.011) was a poor prognostic factor for OS. Conclusions: iFAM is an effective and well-tolerated in patients with gemcitabine-pretreated pancreatic cancer, even patients with an ECOG PS of 2. ECOG PS and CA 19-9 were shown to be significant prognostic factors in this salvage setting. [ABSTRACT FROM AUTHOR]

Metabolic engineering has contributed significantly to the enhanced production of various value-added and commodity chemicals and materials from renewable resources in the past two decades. Recently, metabolic engineering has been upgraded to the systems level (thus, systems metabolic engineering) by the integrated use of global technologies of systems biology, fine design capabilities of synthetic biology, and rational–random mutagenesis through evolutionary engineering. By systems metabolic engineering, production of natural and unnatural chemicals and materials can be better optimized in a multiplexed way on a genome scale, with reduced time and effort. Here, we review the recent trends in systems metabolic engineering for the production of chemicals and materials by presenting general strategies and showcasing representative examples. [ABSTRACT FROM AUTHOR]

Abstract: We have developed red phosphorescent organic light-emitting devices operating at low voltages by using triphenylphosphine oxide (Ph3PO) and 4,4′-bis(2,2′-diphenylvinyl)-1,1′-biphenyl (DPVBi) electron transport layers. 4,4′-bis(N-carbazolyl)-1,1′-biphenyl (CBP) and tris-(1-phenylisoquinolinolato-C 2,N) iridium(III) [Ir(piq)3] were used as host and guest materials, respectively. Small voltage drops across the electron transport layers and direct injection of holes from 4,4′,4″-tris[N-(2-naphthyl)-N-phenyl-amino]-triphenylamine (2-TNATA) hole transport layer into the Ir(piq)3 guests are responsible for the high current density at low voltage, resulting in a high luminance of 1000cd/m2 at low voltages of 2.8–3.0V in devices with a structure of ITO/2-TNATA/CBP:Ir(piq)3/DPVBi/Ph3PO/LiF/Al. [Copyright &y& Elsevier]

Metabolic engineering has enabled us to develop strains suitable for their use as microbial factories of chemicals and materials from renewable sources. It has recently become more powerful with the advanced in synthetic biology, which is allowing us to create novel and fine-controlled metabolic and regulatory circuits maximizing metabolic fluxes to the desired products in the strain being developed. This enables us to engineer host microorganisms to enhance their innate metabolic capabilities or to gain new capabilities in the production of target compounds. Here we review recently constructed synthetic pathways that have been successfully applied for producing non-innate chemicals and also discuss recent approaches developed to increase the efficiency of synthetic pathways for achieving higher productivities of desired bioproducts. [Copyright &y& Elsevier]

Abstract: Development of genome-scale metabolic models and various constraints-based flux analyses have enabled more sophisticated examination of metabolism. Recently reported metabolite essentiality studies are also based on the constraints-based modeling, but approaches metabolism from a metabolite-centric perspective, providing synthetic lethal combination of reactions and clues for the rational discovery of antibacterials. In this study, metabolite essentiality analysis was applied to the genome-scale metabolic models of four microorganisms: Escherichia coli, Helicobacter pylori, Mycobacterium tuberculosis and Staphylococcus aureus. Furthermore, chokepoints, metabolites surrounded by enzymes that uniquely consume and/or produce them, were also calculated based on the network properties of the above organisms. A systematic drug targeting strategy was developed by combining information from these two methods. Final drug target metabolites are presented and examined with knowledge from the literature. [Copyright &y& Elsevier]

During the past decade, bottom-up and top-down approaches of network reconstruction have greatly facilitated integration and analysis of biological networks, including transcriptional, protein interaction, and metabolic networks. As increasing amounts of multidimensional high-throughput data become available, biological networks have also been upgraded, allowing more accurate understanding of whole cellular characteristics. The network size is constantly expanding as larger volume of information and omics data are further integrated into the biological networks previously built upon a single type of data. Such effort more recently led to the modeling of human metabolic network and prediction of its tissue-specific metabolism, reconstruction of consensus yeast metabolic network, and simulation of mutual interactions among multiple microorganisms. It is expected that this trend will continue, the outcomes of which will allow development of more sophisticated networks integrating diverse omics data, and enhance our understanding of biological systems. [Copyright &y& Elsevier]

Abstract: Random mutagenesis and selection approaches used traditionally for the development of industrial strains have largely been complemented by metabolic engineering, which allows purposeful modification of metabolic and cellular characteristics by using recombinant DNA and other molecular biological techniques. As systems biology advances as a new paradigm of research thanks to the development of genome-scale computational tools and high-throughput experimental technologies including omics, systems metabolic engineering allowing modification of metabolic, regulatory and signaling networks of the cell at the systems-level is becoming possible. In silico genome-scale metabolic model and its simulation play increasingly important role in providing systematic strategies for metabolic engineering. The in silico genome-scale metabolic model is developed using genomic annotation, metabolic reactions, literature information, and experimental data. The advent of in silico genome-scale metabolic model brought about the development of various algorithms to simulate the metabolic status of the cell as a whole. In this paper, we review the algorithms developed for the system-wide simulation and perturbation of cellular metabolism, discuss the characteristics of these algorithms, and suggest future research direction. [Copyright &y& Elsevier]

Abstract: This study presents an in-depth study on the physiological behavior of Mannheimia succiniciproducens, a capnophilic bacterium and an efficient succinic acid producer, under varying gas conditions as H2 and CO2 play important roles in the production of succinic acid. Constraints-based flux analysis of the genome-scale metabolic model of M. succiniciproducens was performed to estimate the production patterns of several organic acids in response to varying H2, CO2, and glucose uptake rates. Results from controlled cultivations performed previously and constraints-based flux analyses of M. succiniciproducens in this study revealed that there is an optimal range of CO2 level in the medium for enhancing cell growth and succinic acid production at a given glucose uptake rate. Furthermore, the uptake rates of H2 and CO2 from the medium have a direct relationship with each other, significantly influencing the rates of cell growth and succinic acid production. Predictions made in this study quantitatively describe the physiological changes of the cell in response to varying H2, CO2, and glucose uptake rates, which consequently allow us to identify the feasible physiological states of the cell with respect to cell growth rate and succinic acid production rate. [Copyright &y& Elsevier]

Abstract: One of the well-established approaches for the quantitative characterization of large-scale underdetermined metabolic network is constraint-based flux analysis, which quantifies intracellular metabolic fluxes to characterize the metabolic status. The system is typically underdetermined, and thus usually is solved by linear programming with the measured external fluxes as constraints. Thus, the intracellular flux distribution calculated may not represent the true values. 13C-constrained flux analysis allows more accurate determination of internal fluxes, but is currently limited to relatively small metabolic networks due to the requirement of complicated mathematical formulation and limited parameters available. Here, we report a strategy of employing such partial information obtained from the 13C-labeling experiments as additional constraints during the constraint-based flux analysis. A new methodology employing artificial metabolites and converging ratio determinants (CRDs) was developed for improving constraint-based flux analysis. The CRDs were determined based on the metabolic flux ratios obtained from 13C-labeling experiments, and were incorporated into the mass balance equations for the artificial metabolites. These new mass balance equations were used as additional constraints during the constraint-based flux analysis with genome-scale E. coli metabolic model, which allowed more accurate determination of intracellular metabolic fluxes. [Copyright &y& Elsevier]

Abstract: In this paper, a novel method for accurate subject tracking, by selecting only tracked subject boundary edges in a video stream with a changing background and moving camera, is proposed. This boundary edge selection is achieved in two steps: (1) removing background edges using edge motion, and from the output of the previous step, (2) selecting boundary edges using a normal direction derivative of the tracked contour. Accurate tracking is based on reduction of the effects of irrelevant edges, by only selecting boundary edge pixels. In order to remove background edges using edge motion, the tracked subject motion is computed and edge motions and edges having different motion directions from the subjects are removed. In selecting boundary edges using the normal contour direction, the image gradient values on every edge pixel are computed, and edge pixels with large gradient values are selected. Multi-level Canny edge maps are used to obtain proper details of a scene. Multi-level edge maps allow tracking, even though the tracked object boundary has complex edges, since the detail level of an edge map for the scene can be adjusted. A process of final routing is deployed in order to obtain a detailed contour. The computed contour is improved by checking against a strong Canny edge map and hiring strong Canny edge pixels around the computed contour using Dijkstra''s minimum cost routing. The experimental results demonstrate that the proposed tracking approach is robust enough to handle a complex-textured scene in a mobile camera environment. [Copyright &y& Elsevier]

As the ambitions of synthetic biology approach genome-scale engineering, comprehensive characterization of cellular systems is required, as well as a means to accurately model cell-scale molecular interactions. These requirements are coincident with the goals of systems biology and, thus, systems biology will become the foundation for genome-scale synthetic biology. Systems biology will form this foundation through its efforts to reconstruct and integrate cellular systems, develop the mathematics, theory and software tools for the accurate modeling of these integrated systems, and through evolutionary mechanisms. As genome-scale synthetic biology is so enabled, it will prove to be a positive feedback driver of systems biology by exposing and forcing researchers to confront those aspects of systems biology which are inadequately understood. [Copyright &y& Elsevier]

Metastasis to the thyroid is uncommon, but the number of cases seems to have increased in recent years. This increase may be related to more frequent use of fine-needle aspiration biopsy (FNAB) in any suspected case.A retrospective review of patients with thyroid metastasis diagnosed by FNAB at the Asan Medical Centre.Twenty-two patients who were seen at the Asan Medical Centre between 1997 and 2003. Median age was 55 years with range between 34 and 74 years.Fourteen patients presented with a palpable thyroid nodule. Eight patients had an impalpable thyroid nodule that was found incidentally during the various imaging studies. The breast (five patients) was the most common primary site followed by the kidney (three), colon (three) and lung (three). FNAB confirmed metastatic disease in 19 patients and raised suspicion in three patients. The suspicion of metastasis to the thyroid was confirmed by Tru-cut needle core biopsy in one patient and surgery in two patients. Thyroid metastases were found during the initial work-up for primary tumour in eight patients. In the remaining 14 patients, the interval from diagnosis of primary tumour to the detection of thyroid metastasis varied from 8 months to 15 years, with a median of 54 months. Fifteen patients had metastatic disease elsewhere at the time of presentation. Ten patients received chemotherapy. Radiotherapy was used in two patients. Seven patients are still alive, with one patient disease free for 16 months following resection of the thyroid metastasis.Thyroid metastases are uncommon but can be detected more frequently with routine use of FNAB. Breast cancer is the most common tumour that metastasizes to the thyroid. They usually occur when there are metastases elsewhere, sometimes many years after the diagnosis of the original primary tumour and show poor prognosis in general. [ABSTRACT FROM AUTHOR]

The behavior of nanometer-sized polar clusters is considered to be of central importance to the understanding of relaxor ferroelectricity. The size of the polar clusters with tetragonal symmetry in PbTiO3-based relaxors was estimated by analyzing the degree of asymmetric Raman line broadening. It was shown that the mean size (L) of the tetragonal polar clusters remained essentially constant with L approximately 1.2 nm for temperatures above 300 K. The estimated L increases rapidly below a certain critical temperature, suggesting a rapid growth of the frozen polar clusters with the same tetragonal symmetry. [Copyright &y& Elsevier]

FK506 binding protein 5 (FKBP5) is a major regulatory protein of the HPA axis, which binds to the glucocorticoid receptors and modulate glucocorticoid sensitivity. The FKBP5 genes have been implicated in dysregulation of human stress responses, contributing to vulnerable phenotypes such as depression and anxiety. The present study aimed to investigate whether genetic and epigenetic factors of the FKBP5 are a predictive biomarker of Posttraumatic Stress Disorder (PTSD) among veterans exposed to combat. In addition, the influence of potentially associated factors, including combat exposure levels and alcohol problem, was examined in the pathophysiology of PTSD. All subjects were Korean male veterans who served on active duty during the Vietnam War and the Combat Exposure Scale (CES) was used for assessing the level of wartime stressors experienced by combatants. Using the Clinician-Administered PTSD Scale (CAPS), combat veterans were grouped into those with (n=124) and without (n=120) PTSD. Three SNPs of the FKBP5 locus (rs9296158, rs1360780, and rs9470080) were genotyped with single base primer extension assay using the ABI PRISM SNaPShot Multiplex kit. DNA methylation levels at two CpG sites in the FKBP5 intron 7 region were quantified in the peripheral blood using the bisulfite pyrosequencing method. The effects of FKBP5 variants, the DNA methylation levels and clinical factors on the diagnosis of PTSD were tested using binary logistic regression analysis. Since a significant interaction effect between alcohol problem and FKBP5 variants was found for PTSD symptom, logistic regression analyses stratified by presence of alcohol problem were performed. Among combat-exposed individuals without alcohol problem, the risk allele of FKBP5 rs1360780, higher methylation levels at the FKBP5 CpG1 site, high combat exposure significantly predicted PTSD diagnosis in combat-exposed individuals (Model Summary: -2 Log likelihood=144.07, Nagelkerke R2=0.279; Overall percentage of correct classification resulting from the model=72.9%). In the logistic model among subjects with alcohol problem, the combat exposure level was an only significant predictor of PTSD status. The present study demonstrated the involvement of FKBP5 genetic variants and higher DNA methylation of the FKBP5 in PTSD status without alcohol problem. The present findings suggest that the external traumatic events may influence PTSD pathophysiology via genetic and epigenetic modulation of the FKBP5 and alcohol problem may be a moderating factor of PTSD. Further prospective research examining genetic variants and epigenetic changes of FKBP5 locus in people exposed to trauma might shed light on the role and the biological basis of FKBP5 in susceptibility to PTSD. [ABSTRACT FROM AUTHOR]

Background: Intramedullary spinal cord metastasis (ISCM) is an uncommon complication of malignancy. ISCM from thyroid cancer is extremely rare, only a few cases had been reported and most were found at autopsy. Here we report a patient with progressive lower leg weakness due to ISCM from papillary thyroid carcinoma who had a good response to surgery. Patient Findings: A 44-year-old woman presented with bilateral lower leg pain in December 2009. She underwent a total thyroidectomy in 1997 because of large mass in the right neck, which was diagnosed as papillary thyroid carcinoma. She had repeated I-131 therapies, but brain metastasis developed in 2002. When she was admitted, lower leg pain and weakness progressed rapidly. We performed magnetic resonance of the spine and whole-body fluorodeoxyglucose (FDG)-positron emission tomography scan, which demonstrated a 2×6 cm intramedullary mass enhanced by gadolinium with FDG-uptake. She underwent emergency laminotomy with subtotal tumor removal. Pathology revealed metastatic papillary thyroid carcinoma. After the emergent operation she could walk without help. Conclusion: We report a patient with ISCM from papillary thyroid carcinoma. Surgical resection should be considered in patients with ISCM from papillary thyroid carcinoma. Early diagnosis and surgical resection could improve the quality of life and the neurologic deficits. [ABSTRACT FROM AUTHOR]

Abstract: We have developed highly efficient blue phosphorescent organic light-emitting devices comprising of two organic layers. Hole transporting 1,1-bis[(di-4-tolylamino)phenyl]cyclohexane (TAPC) was used as an emitting host for iridium(III)bis[(4,6-di-fluorophenyl)-pyridinato-N,C 2′]picolinate (FIrpic) guest. In our bilayer system, the host–guest energy transfer process leads to a low optimal doping concentration of 2wt%, while the better charge balance is achieved by the better electron injection into the host layer from electron transport layer. Using these bilayer structures, we demonstrate a maximum current efficiency of 34cd/A in the device structure of ITO/TAPC: FIrpic (30nm, 2wt%)/3-(4-biphenyl-yl)-4-phenyl-5-(4-tert-butylphenyl)-1,2,4-triazole (50nm)/LiF/Al. [Copyright &y& Elsevier]

Standigm ASK™ revolutionizes healthcare by addressing the critical challenge of identifying pivotal target genes in disease mechanisms—a fundamental aspect of drug development success. Standigm ASK™ integrates a unique combination of a heterogeneous knowledge graph (KG) database and an attention-based neural network model, providing interpretable subgraph evidence. Empowering users through an interactive interface, Standigm ASK™ facilitates the exploration of predicted results. Applying Standigm ASK™ to idiopathic pulmonary fibrosis (IPF), a complex lung disease, we focused on genes (AMFR, MDFIC and NR5A2) identified through KG evidence. In vitro experiments demonstrated their relevance, as TGFβ treatment induced gene expression changes associated with epithelial–mesenchymal transition characteristics. Gene knockdown reversed these changes, identifying AMFR, MDFIC and NR5A2 as potential therapeutic targets for IPF. In summary, Standigm ASK™ emerges as an innovative KG and artificial intelligence platform driving insights in drug target discovery, exemplified by the identification and validation of therapeutic targets for IPF. [ABSTRACT FROM AUTHOR]

Finding relations between genes and diseases is essential in developing a clinical diagnosis, treatment, and drug design for diseases. One successful approach for mining the literature is the document-based relation extraction method. Despite recent advances in document-level extraction of entity-entity, there remains a difficulty in understanding the relations between distant words in a document. To overcome the above limitations, we propose an AI-based text-mining model that learns the document-level relations between genes and diseases using an attention mechanism. Furthermore, we show that including a direct edge (DE) and indirect edges between genetic targets and diseases when training improves the model's performance. Such relation edges can be visualized as graphs, enhancing the interpretability of the model. For the performance, we achieved an F1-score of 0.875, outperforming state-of-the-art document-level extraction models. In summary, the SCREENER identifies biological connections between target genes and diseases with superior performance by leveraging direct and indirect target-disease relations. Furthermore, we developed a web service platform named SCREENER (Streamlined CollaboRativE lEarning of NEr and Re), which extracts the gene-disease relations from the biomedical literature in real-time. We believe this interactive platform will be useful for users to uncover unknown gene-disease relations in the world of fast-paced literature publications, with sufficient interpretation supported by graph visualizations. The interactive website is available at: https://ican.standigm.com. [ABSTRACT FROM AUTHOR]