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In this study, we demonstrate inverted PTB7:PC71BM polymer solar cells featuring a solution-processed s-MoO3 hole transport layer that can, after thermal aging at 85 °C, retain their initial power conversion efficiency for at least 2200 h.

Studies on the neurobiological causes of anxiety disorders suggest that the GABA system in-creases synaptic concentration and enhances the affinity of GABAA (type A) receptors for ben-zo-diazepine ligands. Flumazenil antagonizes the benzodiazepine binding site of the GABA (γ-aminobutyric acid) type /benzodiazepine receptor (BZR) complex in the central nervous sys-tem (CNS). The integration of the metabolites of flumazenil by LC-tandem mass spectrometry will complete understanding of the in vivo metabolism of flumazenil and accelerate radio-pharmaceutical inspection and registration. The main goal of our study was to investigate using reversed-phase HPLC (PR-HPLC) coupled with electrospray ionization triple quadrupole tan-dem mass spectrometry (ESI-QqQ MS) for the identification of flumazenil and its metabolites in a hepatic matrix. And a carrier-free nucleophilic fluorination with automatic synthesizer for [18F]flumazenil which applied to in vivo nano-positron emission tomography (Nano-PET)/computed tomography (CT) imaging and ex vivo bio-distribution used to analyze in normal rats. The study showed that 50% of the flumazenil was bio-transformed at 60 min by the rat liver homogenate, while one metabolite (M1) was a methyl transesterification product of flumazenil. In a rat liver microsomes system, two metabolites were identified (M2 and M3) as its carboxylic acid and hydroxylated ethylester forms, respectively. [18F]flumazenil in vivo nanoPET/CT imag-ing and ex vivo bio-distribution assay also showed significant effects on GABAA receptor availa-bility in the amygdala, prefrontal cortex, cortex, and hippocampus in the rat brain, worriless about the formation of metabolites. We showed completion of the bio-transformed course of flumazenil by the hepatic system; and [18F]flumazenil can be a good ligand and serve as a PET agent for determination of GABAA/BZR complex for multiplex neurological syndromes in the clinical stage.

[99mTc]Tc TRODAT-1 is a widely used single photon emission tomography (SPECT) radiopharmaceutical in Asian practice for early detection of central dopaminergic disorders. However, its imaging quality remains sub-optimal. To overcome this problem, mannitol, an osmotic agent was used to observe its effect on improving striatal [99mTc]Tc TRODAT-1 uptake in rat brain by titrated human dosages to investigate a clinically feasible way to improve human imaging quality. [99mTc]Tc TRODAT-1 synthesis and quality control were performed as described. Sprague–Dawley rats were used for this study. The animal in vivo nanoSPECT/CT and ex vivo autoradiography were employed to observe and verify the striatal [99mTc]Tc TRODAT-1 uptake in rat brains using clinically equivalent doses (i.e., 0, 1 and 2 mL groups, each n = 5) of mannitol (20% w/v, equivalent to 200 mg/mL) by an intravenous administration. Specific binding ratios (SBRs) were calculated to express the central striatal uptake in different experimental groups. In the NanoSPECT/CT imaging, the highest SBRs of striatal [99mTc]Tc TRODAT-1 were reached at 75–90 min post-injection. The averaged striatal SBRs were 0.85 ± 0.13 (2 mL normal saline, the control group), 0.94 ± 0.26 (1 mL mannitol group) and 1.36 ± 0.12 (2 mL mannitol group, p < 0.01 which were significantly different than the control as well as 1 mL mannitol groups (p < 0.05). The SBRs from ex vivo autoradiography also showed a comparable trend of the striatal [99mTc]Tc TRODAT-1 uptake in the 2 mL, 1 mL mannitol and the control groups (1.76 ± 0.52, 0.91 ± 0.29, and 0.21 ± 0.03, respectively, p < 0.05). No remarkable changes of vital signs were found in the mannitol groups and the controls. Pre-treated mannitol revealed a significant increase of the central striatal [99mTc]Tc TRODAT-1 uptake in a rat model which not only enabled us to perform pre-clinical studies of dopaminergic related disorders but also provided a potential way to further optimize image quality in clinical practice.

We previously showed a hydroxamic acid‐based histone deacetylase inhibitor (HDACi), compound 13, provides neuroprotection against chronic cerebral hypoperfusion (CCH) both in vitro under oxygen‐glucose deprivation (OGD) conditions and in vivo under bilateral common carotid artery occlusion (BCCAO) conditions. Intriguingly, the protective effect of this HDACi is via H3K14 or H4K5 acetylation–mediated differential BDNF isoform activation. BDNF is involved in cell proliferation and differentiation in development, synaptic plasticity and in learning and memory related with receptors or synaptic proteins. B6 mice underwent BCCAO and were randomized into 4 groups; a sham without BCCAO (sham), BCCAO mice injected with DMSO (DMSO), mice injected with HDACi‐compound 13 (compound 13) and mice injected with suberoylanilide hydroxamic acid (SAHA). The cortex and hippocampus of mice were harvested at 3 months after BCCAO, and levels of BDNF, AMPA receptor and dopamine receptors (D1, D2 and D3) were studied using Western blotting analysis or immunohistochemistry. We found that the AMPA receptor plays a key role in the molecular mechanism of this process by modulating HDAC. This protective effect of HDACi may be through BDNF; therefore, activation of this downstream signalling molecule, for example by AMPA receptors, could be a therapeutic target or intervention applied under CCH conditions.

PURPOSE The dicentric chromosome assay (DCA), the gold standard for radiation biodosimetry, evaluates an individual absorbed radiation dose by the analysis of DNA damage in human lymphocytes. The conventional (C-DCA) and QuickScan (QS-DCA) scoring methods are sensitive for estimating radiation dose. The Biodosimetry Laboratory at Institute of Nuclear Energy Research (INER), Taiwan, participated in intercomparison exercises conducted by Health Canada (HC) in 2014, 2015 and 2018 to validate the laboratory's accuracy and performance. MATERIAL AND METHODS Blood samples for the conventional dose response curve for Taiwan were irradiated with 0, 0.25, 0.5, 1, 2, 3, 4 and 5 Gy. Ten blind blood samples were provided by HC. Either or both of two methods of conventional (C) or QuickScan (QS) scoring could be chosen for the HC's intercomparison. For C-DCA triage scoring, only cells with 46 centromeres were counted and each scorer recorded the number of dicentrics in the first 50 metaphases or stopped scoring when 30 dicentrics were reached. Scorers also recorded how much time it took to analyze 10, 20, and 50 cells. Subsequently, the data were entered into the Dose Estimate software (DoseEstimate_v5.1) and dose estimates were calculated. With QS-DCA scoring, a minimum of 50 metaphase cells (or 30 dicentrics) were scored in apparently complete metaphases without verification of exactly 46 centromeres. RESULTS For the blinded blood samples irradiated at HC and shipped to INER, the mean absolute deviation (MAD) derived after scoring 50 cells for C-DCA and QS-DCA was

Protobothrops mucrosquamatus is one of the common venomous snakes in Southeast Asia. This retrospective cohort study conducted in six medical institutions in Taiwan aimed to obtain information on the optimal management strategies for P. mucrosquamatus snakebite envenomation. Data were extracted from the Chang Gung Research Database from January 2006 to December 2016. The association between early antivenom administration and patient demographics, pain requiring treatment with analgesic injections, and hospital length of stay was analyzed. A total of 195 patients were enrolled; 130 were administered antivenom within 1 hour after emergency department arrival (early group), whereas 65 were treated later than 1 hour after arrival (late group). No in-hospital mortality was identified. The difference in surgical intervention rates between the early and late groups was statistically insignificant (P = 0.417). Compared with the early group, the late group showed a higher rate of antivenom skin test performance (46.9% versus 63.1%, respectively, P = 0.033), longer hospital stay (42 ± 62 hours versus 99 ± 70 hours, respectively, P = 0.016), and higher rate of incidences of pain requiring treatment with analgesic injections (29.2% versus 46.2%, respectively, P = 0.019). After adjusting for confounding factors, early antivenom administration was associated with decreased pain requiring treatment with analgesic injections (adjusted odds ratio: 0.51, 95% CI: 0.260–0.985). Antivenom administration within 1 hour of arrival was associated with a decreased likelihood of experiencing pain and hospital length of stay in patients with P. mucrosquamatus snakebites. Antivenom skin testing was associated with delays in antivenom administration.

Graphical abstract, Highlights • Genes from stools have molecular significance with CRC tumorgenesis. • SCFAs, the metabolites of microbiota, can suppress CRC tumorigenesis. • Relationship between colonic genes, gut microbiota, or their metabolites is significant. • Changes of PLAC8 and butyrate-producing organisms were found in stools of CRC patients. • Butyrate can reduce the CRC formation through regulating PLAC8 expression., Tumor metastasis or recurrence often occurs in patients with curative resection of colorectal cancer (CRC). Placental-specific 8 (PLAC8), which has increased expression in stool, may be associated with CRC recurrence. Insights into the role of PLAC8 in CRC recurrence and its clinical significance may support to develop strategies for preventing CRC recurrence and deterioration. Clinical tissues, cell and animal models were used to clarify the roles of PLAC8 in CRC tumorigenesis, invasion, and migration. Next-generation sequencing of 16S ribosomal DNA has been used to assess the gut microbiota in stool of CRC patients. We found that PLAC8 was upregulated in tissues from patients with late-stage CRC. In our in vitro studies, PLAC8 was dynamically regulated in mitotic cells. Overexpressed PLAC8 was nucleated at the centrosome during mitosis, and therefore, PLAC8 overexpression might increase cell growth and migration (all p

In bladder cancer, urothelial carcinoma is the most common histologic subtype, accounting for more than 90% of cases. Pathogenic effects due to the dysbiosis of gut microbiota are localized not only in the colon, but also in regulating bladder cancer distally. Butyrate, a short-chain fatty acid produced by gut microbial metabolism, is mainly studied in colon diseases. Therefore, the resolution of the anti-cancer effects of butyrate-producing microbes on bladder urothelial cells and knowledge of the butyrate-responsive molecules must have clinical significance. Here, we demonstrate a correlation between urothelial cancer of the bladder and Butyricicoccus pullicaecorum. This butyrate-producing microbe or their metabolite, butyrate, mediated anti-cancer effects on bladder urothelial cells by regulating cell cycle, cell growth, apoptosis, and gene expression. For example, a tumor suppressor against urothelial cancer of the bladder, bladder cancer-associated protein, was induced in butyrate-treated HT1376 cells, a human urinary bladder cancer cell line. In conclusion, urothelial cancer of the bladder is a significant health problem. To improve the health of bladder urothelial cells, supplementation of B. pullicaecorum may be necessary and can further regulate butyrate-responsive molecular signatures.

Shiou-Shiow Farn,1,2 Kang-Wei Chang,3 Wan-Chi Lin,1 Hung-Man Yu,1 Kun-Liang Lin,1 Yu-Chin Tseng,1 Yu Chang,1 Chung-Shan Yu,2,4 Wuu-Jyh Lin1 1Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, 32546, Taiwan; 2Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu, 300, Taiwan; 3Laboratory Animal Center, Office of Research and Development, Taipei Medical University, Taipei, 11031, Taiwan; 4Institute of Nuclear Engineering and Science, College of Nuclear Science, National Tsing-Hua University, Hsinchu, 300, TaiwanCorrespondence: Wuu-Jyh Lin; Chung-Shan Yu Email WJLin@seecurellc.com; csyu@mx.nthu.edu.twIntroduction: Novel radiotracer development for imaging dopamine transporters is a subject of interest because although [99mTc]TRODAT-1, [123I]β-CIT, and [123I]FP-CIT are commercially available; 99Mo/99mTc generator is in short supply and 123I production is highly dependent on compact cyclotron. Therefore, we designed a novel positron emission tomography (PET) tracer based on a tropane derivative through C-2 modification to conjugate NOTA for chelating 68Ga, a radioisotope derived from a 68Ge/68Ga generator.Methods: IPCAT-NOTA 22 was synthesized and labeled with [68Ga]GaCl4− at room temperature. Biological studies on serum stability, LogP, and in vitro autoradiography (binding assay and competitive assay) were performed. Furthermore, ex vivo autoradiography, biodistribution, and dynamic PET imaging studies were performed in Sprague Dawley rats.Results: [68Ga]IPCAT-NOTA 24 obtained had a radiochemical yield of ≥ 90% and a specific activity of 4.25 MBq/nmol. [68Ga]IPCAT-NOTA 24 of 85% radiochemical purity (RCP%) was stable at 37°C for up to 60 minutes in serum with a lipophilicity of 0.88. The specific binding ratio (SBR%) reached 15.8 ± 6.7 at 60 minutes, and the 85% specific uptake could be blocked through co-injection at 100- and 1000-fold of the cold precursor in in vitro binding studies. Tissue regional distribution studies in rats with [68Ga]IPCAT-NOTA 24 showed striatal uptake (0.02% at 5 minutes and 0.007% at 60 minutes) with SBR% of 6%, 25%, and 62% at 5– 15, 30– 40, and 60– 70 minutes, respectively, in NanoPET studies. The RCP% of [68Ga]IPCAT-NOTA 24 at 30 minutes in vivo remained 67.65%.Conclusion: Data described here provide new information on the design of PET probe of conjugate/pendent approach for DAT imaging. Another chelator or another direct method of intracranial injection must be used to prove the relation between [68Ga]IPCAT-NOTA 24 uptake and transporter localization.Keywords: Parkinson disease, dopamine transporter, Ga-68

Protobothrops mucrosquamatus is one of the common venomous snakes in Southeast Asia. This retrospective cohort study conducted in six medical institutions in Taiwan aimed to obtain information on the optimal management strategies for P. mucrosquamatus snakebite envenomation. Data were extracted from the Chang Gung Research Database from January 2006 to December 2016. The association between early antivenom administration and patient demographics, pain requiring treatment with analgesic injections, and hospital length of stay was analyzed. A total of 195 patients were enrolled; 130 were administered antivenom within 1 hour after emergency department arrival (early group), whereas 65 were treated later than 1 hour after arrival (late group). No in-hospital mortality was identified. The difference in surgical intervention rates between the early and late groups was statistically insignificant (P = 0.417). Compared with the early group, the late group showed a higher rate of antivenom skin test performance (46.9% versus 63.1%, respectively, P = 0.033), longer hospital stay (42 ± 62 hours versus 99 ± 70 hours, respectively, P = 0.016), and higher rate of incidences of pain requiring treatment with analgesic injections (29.2% versus 46.2%, respectively, P = 0.019). After adjusting for confounding factors, early antivenom administration was associated with decreased pain requiring treatment with analgesic injections (adjusted odds ratio: 0.51, 95% CI: 0.260–0.985). Antivenom administration within 1 hour of arrival was associated with a decreased likelihood of experiencing pain and hospital length of stay in patients with P. mucrosquamatus snakebites. Antivenom skin testing was associated with delays in antivenom administration.

Introduction Novel radiotracer development for imaging dopamine transporters is a subject of interest because although [99mTc]TRODAT-1, [123I]β-CIT, and [123I]FP-CIT are commercially available; 99Mo/99mTc generator is in short supply and 123I production is highly dependent on compact cyclotron. Therefore, we designed a novel positron emission tomography (PET) tracer based on a tropane derivative through C-2 modification to conjugate NOTA for chelating 68Ga, a radioisotope derived from a 68Ge/68Ga generator. Methods IPCAT-NOTA 22 was synthesized and labeled with [68Ga]GaCl4− at room temperature. Biological studies on serum stability, LogP, and in vitro autoradiography (binding assay and competitive assay) were performed. Furthermore, ex vivo autoradiography, biodistribution, and dynamic PET imaging studies were performed in Sprague Dawley rats. Results [68Ga]IPCAT-NOTA 24 obtained had a radiochemical yield of ≥90% and a specific activity of 4.25 MBq/nmol. [68Ga]IPCAT-NOTA 24 of 85% radiochemical purity (RCP%) was stable at 37°C for up to 60 minutes in serum with a lipophilicity of 0.88. The specific binding ratio (SBR%) reached 15.8 ± 6.7 at 60 minutes, and the 85% specific uptake could be blocked through co-injection at 100- and 1000-fold of the cold precursor in in vitro binding studies. Tissue regional distribution studies in rats with [68Ga]IPCAT-NOTA 24 showed striatal uptake (0.02% at 5 minutes and 0.007% at 60 minutes) with SBR% of 6%, 25%, and 62% at 5–15, 30–40, and 60–70 minutes, respectively, in NanoPET studies. The RCP% of [68Ga]IPCAT-NOTA 24 at 30 minutes in vivo remained 67.65%. Conclusion Data described here provide new information on the design of PET probe of conjugate/pendent approach for DAT imaging. Another chelator or another direct method of intracranial injection must be used to prove the relation between [68Ga]IPCAT-NOTA 24 uptake and transporter localization.

Background Epidermal growth factor receptor (EGFR) overexpressed in colorectal cancer (CRC) is a tumor target for developing the anti-tumor theranostic agents. Cetuximab, an anti-EGFR monoclonal antibody against EGFR-positive tumors, inhibits cell proliferation and growth was labeled with radioactive 111indium (111In) in this study for diagnosing EGFR-positive CRC. The aim of this study was to evaluate the efficacy of noninvasive nuclear imaging agent 111In-cetuximab and investigate the biological distribution of 111In-cetuximab in the HCT-15-induced EGFR-positive CRC tumor xenografts. Methods We conjugated cetuximab with an isotope chelator, diethylene triamine penta acetic acid (DTPA), and consequently labeled cetuximab-DTPA with 111In and measured the labeling efficacy by an instant thin layer chromatography (iTLC). Furthermore, the 111In-cetuximab was investigated and compared for imaging small (50 mm3) and large (250 mm3) tumor of CRC xenografts, respectively. Results The conjugated ratio between cetuximab and DTPA was 1:6 measured by MALDI-TOF-MS. The better labeling concentration of cetuximab with 10 mCi of 111In was calculated and experimented as 48 μg, resulting in labeling efficacy >80% detected by iTLC. The results revealed that the 111In-cetuximab accumulated in the both sizes of tumors as a reliable noninvasive diagnostic agent, whereas the ratio of tumor to muscle in the large tumor was 7.5-fold. The biodistribution data indicated that the 111In-cetuximab bound to tumor specifically that was higher than that in other organs. Conclusion We suggested that the 111In-cetuximab was potential for early diagnosis and prognostic monitor of EGFR-positive CRC in further clinical practice.

Cut foliage of Monstera deliciosa is widely used in flower arrangement due to its long vase life and striking foliage pattern. Variegated Monstera of commercial importance is scarce. Therefore, we examined the potential of mutagenesis in obtaining variegated mutants by gamma ray irradiating the seeds. The germination rate was reduced by increasing the irradiation dosage. The LD50 dosage was between 10 to 25 Gy. We further compared the survival rate of seeds from different source at 0, 7.5, 10, and 12.5 Gy. Dosage higher than 12.5 Gy was required to achieve LD50 germination rate. Next, seeds pre-soaked for 5 days were compared to dry seeds for their sensitivity to gamma irradiation at various dosages (10, 12.5, 15, 17.5, 20, and 22.5 Gy). The highest germination rate was obtained by 10 Gy of dry seeds and 12.5 Gy of soaked seeds. The lowest germination rate was observed by 22.5 Gy for both dry and soaked seeds. The soaked seeds apparently were more tolerant to the damage caused by higher dosage of irradiation. Different pattern of leaf variegation was obtained after gamma ray irradiation, including light green to yellow green sectors.

A new naphthol derivative, [F-18]FEONM, has been designed to be a new Tau protein PET imaging molecule for detecting Tau tangle status of Alzheimer's disease in a transgenic mouse model. In order to synthesize this molecule, 2-acetyl-6-methoxynaphthalene was the starting compound and needed five steps preparation to bonding functional and leaving group for preparing the precursor. Radiofluorination on the precursor was carried out by a modified [F-18]FDG autosynthesizer. After half an hour processing, it yielded more than 99% chemical and radiochemical purity product at up to 60% yield. Radiofluorination kinetic study showing 80% [F-18]FEONM would be produced within the first 5 min. The radiofluorination gap function factor is 0.122 for 150 min reaction. Recovery yield of crude [F-18]FEONM could be up to 60% by semi-preparative HILIC HPLC column purification with 95% ethanol elution. Brain glioma tumor mice PET imaging were performed after tail vein injecting [F-18]FEONM. Binding in mice brain tumor reached steady state after 30 min injection and shows 30–70% higher uptake compared to normal mouse. The static brain tumor uptake showed the summation accumulation binding rate was 60% faster than normal mouse. In vitro postmortem AD patient brain slice binding showed 70% higher uptake than normal brain. The uptake of spherical stem cells also showed higher association with neuronal differentiation and PET imaging of Tau and ABeta transgenic mice also showed visualized difference. The specific binding ratio of hippocampus to cerebellum of control mouse is 46.56%, cortex to cerebellum is 11.08% in a 12-month-old P301S Tau transgenic mouse; hippocampus to cerebellum is 106.66%, cortex to cerebellum is 82.48%. Relative ratio of hippocampus to cerebellum of a P301S mouse to control mouse is 2.29, cortex to cerebellum is 7.44.

Calcitonin may relieve pain by modulating central serotonin activity. Calcitonin partly reversed the hypersensitivity to pain induced by ovariectomy. This suggests that the anti-nociceptive effects of calcitonin in the treatment of osteoporosis may be mediated by alterations in neural serotonin transporter (SERT) activity. This study used a rat model of osteoporosis to evaluate the role of the cerebral serotonin system in the anti-nociceptive effect of calcitonin, a drug used to treat post-menopausal osteoporosis. Osteoporosis was induced in rats by ovariectomy (OVX). Rats were then randomized to the following four groups: sham operation, OVX, OVX plus calcitonin, or OVX plus alendronate. OVX led to alterations in bone micro-architecture; alendronate strongly reversed this effect, and calcitonin moderately reversed this effect. OVX increased hyperalgesia (determined as the time for hind paw withdrawal from a heat source); calcitonin reduced this effect, but alendronate had no effect. OVX increased the expression of c-Fos (a neuronal marker of pain) in the thalamus; calcitonin strongly reversed this effect, and alendronate moderately reversed this effect. OVX also reduced SERT but increased 5-HT1A receptor expression and activity; calcitonin aggravated this effect, but alendronate had no effect on recovery of SERT/5-HT1A activity and expression. Our study of a rat model of osteoporosis suggests that OVX-induced enhancement of the serotonergic system may protect against hyperalgesia. However, the anti-nociceptive effects of calcitonin in osteoporosis may be mediated by decreased neural SERT activity and increased activation of 5-HT1 receptors in the thalamus.

Antivenom reactions are a common complication of snake antivenom. This study aimed to identify predicators of antivenom reaction and the involvement of antivenom skin test in antivenom reaction development. This retrospective cohort study was conducted in six medical institutions in Taiwan. Data were extracted from the Chang Gung Research Database (CGRD) from January 2006 to December 2016. The association between antivenom reaction and patient demographics, type and dose of antivenom, and skin test results was analyzed. The study enrolled 799 patients, including 219 who developed antivenom reactions. Compared to patients receiving both freeze-dried hemorrhagic (FH) and freeze-dried neurotoxic (FN) antivenom, those administered a single type had a lower antivenom reaction risk (adjusted odds ratios [aORs]: 0.5 and 0.4, 95% confidence interval [CI]: 0.35-0.74 and 0.24-0.69, FH and FN respectively). Patients administered a higher antivenom dose (≥ 5 vials) had higher antivenom reaction risk (aOR: 1.8, 95% CI: 1.23-2.76). A positive skin test result was also associated with antivenom reaction (aOR: 16.7, 95% CI: 5.42-51.22). The skin test showed high specificity (98.5%, 95% CI: 97.49%-99.83%) but low sensitivity (17.5%, 95% CI: 10.74%-24.18%). The antivenom skin test should be abolished because of the extremely low sensitivity and possible misinterpretation of results because of the limitation of this examination.

[18F]-FDDNP was synthesized and characterized as a positron-emitting probe to identify Alzheimer’s disease (AD) in transgenic mouse models (Tg2576 and dE9) expressing the AD pathology. We observed in in vitro, in vivo, and ex vivo studies that [18F]-FDDNP accumulated specifically in the Ab-overexpressing brain regions and that this accumulation was significantly reduced by co-incubation with non-radioactive FDDNP. In ex vivo and in vivo studies of brain sections, the retention of radioactivity was more specific in Tg2576 mice than in dE9 mice. Using in vitro, ex vivo, in vivo, and ELISA analyses, we characterized the utility of [18F]-FDDNP in mapping b-amyloid in the Tg2576 mouse brain, to assess its potential application in imaging strategies.

This paper presents a Dynamic RB (Resource Blocks) Allocation (DRBA) in LTE (LongTerm Evolution) networks by utilizing Automatic Repeated Request (ARQ). From the ARQ status report, an Evolved-Node Base Station (eNodeB) computes the successfully received packets per unit time for each User Equipment (UE). Thus, an eNB can adequately allocate Resource Blocks (RB) for a UE. In DRBA, we consider three different traffic types (audio, video, and data) with the priority from the highest to the lowest. To prevent the starvation of data traffic, we set an upper bound of RBs for audio and video traffic. To demonstrate the superiority of DRBA, we perform NS-3 simulation. Simulation results show that DRBA can perform much better than the traditional Automatic Modulation and Coding (AMC) scheme. In particular, when a UE is in high interference/noise environment, DRBA can achieve higher utilization, lower blocking rate, and admit more successfully connected UE.

A reversed-phase high-performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was applied to study the forced degradation behavior and stability of epidepride. 123 I radioisotope-labeled epidepride, [(-)- N -{[(2 S )-1-ethylpyrrolidin-2-yl]methyl}-5-iodo-2,3- dimethoxybenzamide] is a radiotracer with a high affinity for dopamine D 2 receptors in the brain and has been used as an imaging agent for single-photon emission computed tomography. HPLC studies were performed using 127 I-epidepride (the nonradioactive compound), instead of 123 I-epidepride, with an RP-18 column using a mobile phase consisting of methanol, acetonitrile, and ammonium acetate (pH 7.0, 10 mM). The eluent flow rate and the wavelength for HPLC detection were 0.5 mL/min and 210 nm, respectively. The ligand was exposed to acid (1 N HCl) and alkaline (1 N NaOH) media and was subjected to oxidative decomposition at room temperature using 3% H 2 O 2 and to thermal decomposition at 50°C. After various reaction times (30 minutes, 1 hour, 2 hours, 8 hours, and 24 hours), the substances were investigated by HPLC and LC-MS/MS. Although no decomposition products were observed after the acidic, alkaline, and thermal treatments, >80% of the initial amount of 127 I-epidepride was oxidized within 24 hours in the presence of H 2 O 2 . Only one major oxidation product with an m/z value of 435 was observed, in addition to the 127 I-epidepride species (m/z 419). The product was characterized by LC-MS/MS fragmentation, and the deteriorated type and fragmentation pathways were proposed for epidepride.

With increasing demand on higher performance for high-speed blade servers, the signal integrity aware (SI-aware) layouts and equalization have been attributed as the critical techniques to improve the electrical performance. This paper describes the SI-aware layouts of patterned ground and capsule-shaped antipad to enhance the connector performance. Besides, a new differential equalizer by taking advantage of differential via-stubs is proposed to restore the deteriorated eye diagram. Their application of a 117.5-cm SATA-II links demonstrates significant improvement in eye height and timing jitter. Furthermore, a viable approach is suggested to successfully reopen the eyes when the data rate increases from the current 3 to 12 Gb/s. The measurement results are also provided to validate the proposed design concepts.

3,4-Methylenedioxymethamphetamine (MDMA), a common recreational drug, is known to cause serotonergic neurotoxicity in the brain. Dextromethorphan (DM) is a widely used antitussive reported to exert anti-inflammatory effect in vivo. In this study, we examined the long-term effect of MDMA on the primate serotonergic system and the protective property of DM against MDMA-induced serotonergic abnormality using single photon emission computed tomography (SPECT). Nine monkeys (Macaca cyclopis) were divided into three groups, namely control, MDMA and co-treatment (MDMA/DM). [123I]-ADAM was used as the radioligand for serotonin transporters (SERT) in SPECT scans. SERT levels of the brain were evaluated and presented as the uptake ratios (URs) of [123I]-ADAM in several regions of interest of the brain including midbrain, thalamus and striatum. We found that the URs of [123I]-ADAM were significantly lower in the brains of MDMA than control group, indicating lower brain SERT levels in the MDMA-treated monkeys. This MDMA-induced decrease in brain SERT levels could persist for over four years. However, the loss of brain SERT levels was not observed in co-treatment group. These results suggest that DM may exert a protective effect against MDMA-induced serotonergic toxicity in the brains of the non-human primate.

Epidermal growth factor receptor (EGFR) overexpressed in colorectal cancer (CRC) is a tumor target for developing the anti-tumor theranostic agents. Cetuximab, an anti-EGFR monoclonal antibody against EGFR-positive tumors, inhibits cell proliferation and growth was labeled with radioactiveWe conjugated cetuximab with an isotope chelator, diethylene triamine penta acetic acid (DTPA), and consequently labeled cetuximab-DTPA withThe conjugated ratio between cetuximab and DTPA was 1:6 measured by MALDI-TOF-MS. The better labeling concentration of cetuximab with 10 mCi ofWe suggested that the

[(123)I]Epidepride is a radio-tracer with very high affinity for dopamine D(2)/D(3) receptors in brain. The importance of alteration in dopamine D(2)/D(3) receptor binding condition has been wildly verified in schizophrenia. In the present study we set up a rat schizophrenia model by chronic injection of a non-competitive NMDA receptor antagonist, MK-801, to examine if [(123)I]epidepride could be used to evaluate the alterations of dopamine D(2)/D(3) receptor binding condition in specific brain regions.Rats were given repeated injection of MK-801 (dissolved in saline, 0.3mg/kg) or saline for 1month. Afterwards, total distance traveled (cm) and social interaction changes were recorded. Radiochemical purity of [(123)I]epidepride was analyzed by Radio-Thin-Layer Chromatography (chloroform: methanol, 9:1, v/v) and [(123)I]epidepride neuroimages were obtained by ex vivo autoradiography and small animal SPECT/CT. Data obtained were then analyzed to determine the changes of specific binding ratio.Chronic MK-801 treatment for a month caused significantly increased local motor activity and induced an inhibition of social interaction. As shown in [(123)I]epidepride ex vivo autoradiographs, MK-801 induced a decrease of specific binding ratio in the striatum (24.01%), hypothalamus (35.43%), midbrain (41.73%) and substantia nigra (37.93%). In addition, [(123)I]epidepride small animal SPECT/CT neuroimaging was performed in the striatum and midbrain. There were statistically significant decreases in specific binding ratio in both the striatum (P.01) and midbrain (P.05) between the saline and MK-801 group.These results suggest that [(123)I]epidepride is a useful radio-tracer to reveal the alterations of dopamine D(2)/D(3) receptor binding in a rat schizophrenia model and is also helpful to evaluate therapeutic effects of schizophrenia in the future.

Serotonin is one of the key neuromodulators involved in fundamental cerebral functions and behaviors. Previous study has demonstrated that somatization symptoms are probably associated with central serotonergic circuits, which are implicated in anxiety and nociception regulation. This study aims to examine the correlation between somatization subscale score and serotonin transporter (SERT) availability in healthy volunteers. Sixty-four healthy participants, 26 males and 38 females, were enrolled from the community and were administered the single somatization subscale of the Chinese symptom checklist 90 revised (SCL90-R). Single photon emission computed tomography with [123I] 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine was also performed to examine SERT availability. The somatization scores were negatively correlated with SERT availability (Spearman’s ρ = −0.35, p = 0.005), particularly in males (Spearman’s ρ = −0.54, p = 0.004). This result reconfirmed the correlation between central serotonergic activity and the intensity of somatization symptoms, even in healthy participants. However, a gender difference exists in this correlation.

Alzheimer's disease (AD) is a neurodegenerative disorder that results in memory deficits. The effect of AD is the leading cause of dementia in the United States and constitutes a burgeoning public health problem. AD is characterized by the presence of two aberrant structures, senile plaques, and neurofibrillary tangles, present in the brain of the patients. [(18)F]FDDNP and [(123)I]IMPY were developed for the early diagnosis of AD by Dr. J. Barrios and Dr. H. Kung, respectively. These two radiotracers could bind with the amyloid location site in the AD patient brain. The aim of this study was to analyze the acute single toxic effects dose of two nonradiochemical labeled compounds in rats. Animals were injected from the tail vein with nonlabeled-FDDNP (0- 5 mg/kg) and nonlabeled-IMPY (0-300 microg/kg), respectively, and observed for 2 weeks. These doses provide safety margins of 35,000- to 140-fold and 1,000- to 100-fold over the maximal recommend human dose (0.1 mg/70 kg) and (20 microg/60 kg) (by FDDNP and IMPY), respectively. With IMPY, there were no changes in mortality, clinical situation, and gross necropsy. With FDDNP, the high dose (5 mg/kg) produced mortality in 2 of 5 and 1 of 5 in male and female rats, respectively. The high dose of FDDNP showed liver damage in dying animals. No other adverse toxic effects at dose levels up to 1.0 mg/kg of FDDNP were noted. FDDNP exerted no adverse toxic effects in rats given doses up to 1 mg/kg and IMPY at the dose levels up to 300 microg/kg.

Changes in regional metabolic activities induced by middle cerebral artery occlusion (MCAO) can influence patient outcome. Our aim was to demonstrate in a rat model that 18F-FDG with positron emission tomography (PET) imaging is a quantitative, reproducible approach for identifying acute and sub-acute metabolic variations in infarct regions. We found that imaging with 18F-FDG/PET enabled detection and quantification of ischemia-induced metabolic deficits and provided a sensitive and reliable means of assessing cerebral ischemic lesions compared with conventional neurological scoring systems in rodents.

Purpose: The radioprotective effects of Antrodia cinnamomea (AC) were investigated for understanding the potential usefulness of AC as an adjunct treatment for reducing radiation side-effects.In this study, we determined the ability of AC extracts (AC539) to reduce radiation side-effects by analyzing cellular viability in normal mouse spleen immune cells and human cancer cells with different radiosensitivity. We further detected the effect of AC on radiation-induced changes in cytokine- and inflammatory-related gene expressions. Furthermore, apoptosis assay was performed to determine whether AC could inhibit radiation-induced cytotoxicity.We found that an AC dose of 100-150 μg/ml in a time-dependent manner was the most effective in blocking radiation-induced cytotoxicity, in vitro. Radiation-induced cytotoxicity was inhibited in spleen immune cells by 37-56%; however, pretreatment of human colorectal cancer cell line HT-29 with AC did not have any effect on radiation-induced cytotoxicity, while pretreatment of radiosensitive human breast cancer cell lines BT-474 with AC caused a moderate enhancement of radiation-induced damage. Furthermore, AC pretreatment differentially regulated the mRNA expression of several important immunomodulatory genes in response to irradiation in normal and cancer cells.Our data indicate that AC may inhibit important immunoregulatory signaling which could be vital in the avoidance of an over-activated cytotoxic and inflammatory response of the immune system caused by radiation-induced tissue damage. Additionally, AC does not provide a radioprotective effect to tumor cells but instead enhances radiation-induced inflammation and cytotoxicity in cancer.

[(18)F]Flurobutyl ethacrynic amide ([(18)F]FBuEA) was prepared from the precursor tosylate N-Boc-N-[4-(toluenesulfonyloxy)butyl]ethacrynic amide with a radiochemical yield of 3%, a specific activity of 48 GBq/μmol and radiochemical purity of 98%. Chemical conjugation of [(18)F]FBuEA with glutathione (GSH) via a self-coupling reaction and enzymatic conjugation under catalysis of glutathiontransferase alpha (GST-α) and π provided about 41% yields of radiochemical conjugated product [(18)F]FBuEA-GSH, 85% and 5-16%, respectively. The catalytic selectivity of this tracer toward GST-alpha was addressed. Positron emission tomography (PET) imaging of [(18)F]FBuEA in normal rats showed that a homogeneous pattern of radioactivity was distributed in the liver, suggesting a catalytic role of GST. By contrast, PET images of [(18)F]FBuEA in rats with thioacetamide-induced cholangiocarcinoma displayed a heterogeneous pattern of radioactive accumulation with cold spots in tumor lesions. PET imaging with [(18)F]FBuEA could be used for early diagnosis of hepatic tumor with a low GST activity as well as liver function.

Serotonin is one of the key neuromodulators involved in fundamental cerebral functions and behaviors. Previous study has demonstrated that somatization symptoms are probably associated with central serotonergic circuits, which are implicated in anxiety and nociception regulation. This study aims to examine the correlation between somatization subscale score and serotonin transporter (SERT) availability in healthy volunteers.Sixty-four healthy participants, 26 males and 38 females, were enrolled from the community and were administered the single somatization subscale of the Chinese symptom checklist 90 revised (SCL90-R). Single photon emission computed tomography with [(123)I] 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine was also performed to examine SERT availability.The somatization scores were negatively correlated with SERT availability (Spearman's ρ = -0.35, p = 0.005), particularly in males (Spearman's ρ = -0.54, p = 0.004).This result reconfirmed the correlation between central serotonergic activity and the intensity of somatization symptoms, even in healthy participants. However, a gender difference exists in this correlation.

It is predicted that depression will become the most common neurological disease in the new millennium. Its incidence is currently about 3% of diseases worldwide. Serotonin is an essential neurotransmitter for the central and peripheral nervous systems and plays a crucial role in neuropsychiatric disorders. (123)I-labeled ADAM was developed to facilitate an early diagnosis of serotonin transporter (SERT) abnormalities in the brain. Many studies have confirmed that the binding of this radiotracer to SERTs is associated with depression. The aim of this study was to evaluate the acute and subacute toxicity of ADAM and to determine its no observed adverse effect level (NOAEL) by administering it via intravenous injection to Sprague-Dawley rats for 14 consecutive days. None of the animals died, and no treatment-related clinical signs were observed. Urinalysis, hematology, and clinical chemistry analysis revealed that daily administration of ADAM (2-2-dimethylaminomethylphenylthio-5-iodophenylamine) for 2 weeks had no toxicological effects. It is concluded that ADAM exerts no adverse toxic effects on this animal model. The NOAEL was 155 microg/kg/day.

6-[ 124 I]iodo-2-(4′-N,N-dimethylamino)-phenylimidazo[1,2-a]pyridine ([ 124 I]IMPY) was synthesized and characterized as a positron-emitting probe to identify Alzheimer's disease in transgenic mouse models. A significant reduction in radioactivity retention in the hippocampus and frontal cortex by co-incubation with nonradioactive IMPY was observed. Highly specific retention of radioactivity in beta-amyloid-rich regions of brain sections was also noted. This study demonstrated that [ 124 I]IMPY was a promising probe for the mouse model and may be useful for positron emission tomography to image beta-amyloid plaques in the human brain.

Benzo[a]pyrene (B[a]P) has been shown to produce DNA adducts and to initiate pulmonary carcinogenesis in animals. We observed differential susceptibility to B[a]P in two human lung adenocarcinoma cell lines, A427 and CL3. DNA adducts were induced by B[a]P treatment in CL3 cells, however, A427 cells were much less responsive to B[a]P treatment. Cytochrome P450 1A1 (CYP1A1) is involved in bioactivation of B[a]P in nonhepatic tissues. Cotreatment with α-naphthoflavone, a CYP1A1 inhibitor, abolished DNA adduct formation by B[a]P in CL3 cells. Nevertheless, CYP1A1 inducer β-naphthoflavone, enhanced DNA adduct formation by B[a]P in both A427 and CL3 cells. Both enzyme activity and mRNA levels of CYP1A1 were highly induced by 1 or 10 μM B[a]P treatment for 24 hr in CL3 cells but not in A427 cells. Protein levels of AhR and aryl hydrocarbon receptor nuclear translocator (Arnt) were similar in A427 and CL3 cells before B[a]P treatment. However, B[a]P induced a retarded band with the [32P]-dioxin responsive element in CL3 cells, but not in A427 cells. This study demonstrated that variation in AhR-mediated CYP1A1 induction contributes to differential susceptibility to B[a]P-DNA adduct formation in human lung cells. Since AhR and/or Arnt function is impaired in A427 cells, this cell line offers a model for investigating the repression mechanisms of CYP1A1 induction by B[a]P in lung cells.

This study is concerned with the development of an agent for single photon emission computer tomography (SPECT) for imaging inflammation and tumor progression. [ 123 I]Iodooctyl fenbufen amide ([ 123 I]IOFA) was prepared from the precursor N-octyl-4-oxo-4-(4 0 -(trimethylstannyl)biphenyl-4-yl) butanamide with a radiochemical yield of 15%, specific activity of 37 GBq/mmol, and radiochemical purity of 95%. Analysis of the binding of [ 123 I]IOFA to COX-1 and COX-2 enzymes by using HPLC and a gel filtration column showed a selectivity ratio of 1:1.3. An assay for the competitive inhibition of substrate transfer showed that IOFA exhibited a comparable IC50 value compared to fenbufen. In the normal rat liver, a lower level and homogeneous pattern of [ 123 I]IOFA radioactivity was observed by SPECT. In contrast, in the rat liver with thioacetamide-induced cholangiocarcinoma, a higher uptake and heterogeneous pattern of [ 123 I]IOFA radioactivity was seen as hot spots in tumor lesions by SPECT imaging. Importantly, elevated COX-1 and COX-2 expressions from immunostaining were found in the bile ducts of tumor rats but not of normal rats. Therefore, [ 123 I]IOFA was found to exhibit the potential for imaging tumors that over-express COX.