Selective cross-metathesis of cellobiose derivatives with amido-functionalized olefinic structures: A model study for synthesis of cellulosic diblock copolymers.

This work describes a model study for synthesis of cellulose-based block copolymers, investigating selective coupling of peracetyl ß-d-cellobiose and perethyl ß-d-cellobiose at their reducing-ends by olefin cross-metathesis (CM). Herein we explore suitable pairs of ω-alkenamides that permit selective, quantitative coupling by CM. Condensation reactions of hepta-O-acetyl-ß-d-cellobiosylamine or hepta-O-ethyl-ß-d-cellobiosylamine with acyl chlorides afforded the corresponding N-(ß-d-cellobiosyl)-ω-alkenamide derivatives with an aromatic olefin or linear olefinic structures. Among the introduced olefinic structures, CM of the undec-10-enamide (Type I olefin) and the acrylamide (Type II olefin) gave the hetero-block tetramers, N-(hepta-O-ethyl-ß-d-cellobiosyl)-N'-(hepta-O-acetyl-ß-d-cellobiosyl)-alkene-α,ω-diamides, with >98 % selectivity. Moreover, selectivity was not influenced by the cellobiose substituents when a Type I olefin with a long alkyl tether was used. Although the amide carbonyl group could chelate the ruthenium atom and reduce CM selectivity, the results indicated that such chelation is suppressed by sterically hindered pyranose rings or the long alkyl chain between the amido group and the double bond. Based on this model study, selective end-to-end coupling of tri-O-ethyl cellulose and acetylated cellobiose was accomplished, proving the concept that this model study with cellobiose derivatives is a useful signpost for selective synthesis of polysaccharide-based block copolymers.

Identification of novel lactic acid bacteria with enhanced protective effects against influenza virus.

Lactic acid bacteria (LAB) exert health-beneficial effects by regulating innate immunity in the intestinal tract. Due to growing health awareness, the demand for LAB and studies have focused on identifying beneficial LAB strains is increasing, especially those that stimulate innate immunity. In this study, the LAB strain D279 (NITE_BP-03645, Latilactobacillus sakei) was isolated from among 741 LAB strains that were analyzed for their ability to induce interleukin 12 (IL-12) production and was subsequently characterized. D279 induced the highest expression of IL-12 among the screened LABs. Furthermore, D279 significantly activated antiviral genes and preferentially induced interferon (IFN)λ expression in vitro, which plays a critical role in the epithelial tissue, thereby conferring strong anti-influenza potency without inflammation. However, it decreased the IFNα levels. The administration of pasteurized D279 to mice resulted in strong anti-influenza potency, with higher natural killer (NK) cell activity and a lower viral load in the lung than in the control. Importantly, none of the D279-administered mice were sacrificed during the viral infection tests. These results suggest that D279 administration confers beneficial effects by regulating innate immunity and that it may be relevant for commercial use in the future.

[Effects of Phantom Factor on Shape Differences in Tomotherapy Water-equivalent Phantoms].

PURPOSE: The purpose of this study was to evaluate the effects of phantom factor on the verification of measured doses using cheese phantoms in tomotherapy. METHODS: Two plans for dose verification (plan classes and plan class phantom sets with a virtual organ at the risk set) were evaluated. The calculated and measured doses were compared with and without the phantom factor using cheese phantoms. Additionally, the phantom factor was evaluated for two conditions (TomoHelical/TomoDirect) in clinical cases (breast and prostate). RESULTS: When applying a phantom factor of 1.007, the deviation between the calculated and measured doses increased in Plan-Class and TomoDirect, decreased in TomoHelical, and increased in both clinical cases. CONCLUSION: When conducting dose verification, the effects of one phantom factor on measurement conditions may differ depending on when phantom factors were obtained (irradiation technique and irradiation field). It is therefore necessary to consider changes in measured doses due to changes in phantom scattering.

DEVELOPMENT OF ABSOLUTE MEASUREMENT SYSTEM FOR 𝑾AIR IN 60CO GAMMA RAYS.

In the ICRU Report 90, the uncertainty of the recommendation for ${{W}}_{{air}}$ was changed from 0.15 to 0.35%. The purpose of this study is to develop an absolute measurement system for ${{W}}_{{air}}$ in electrons with lower uncertainty using 60Co gamma rays. ${{W}}_{{air}}$ was determined by the ratio of the energy deposition to the number of ion pairs created in a given volume of air using a graphite calorimeter and a graphite-wall ionisation chamber. The obtained value for ${{W}}_{{air}}$ was 33.91 eV with a relative standard uncertainty of 0.08 eV (k = 1), and was in good agreement with the recommended value of the ICRU Report 90 (33.97 eV). Additionally, the uncertainty for ${{W}}_{{air}}$ obtained in this investigation is 0.23% and is comparable with that reported by Burns et al., which is the lowest uncertainty in recent studies determining ${{W}}_{{air}}$ In the future, the proposed system can be used to measure ${{W}}_{{air}}$ in high-energy electron beams.

[A Survey of Dosimetry in the Magnetic Field of MR-Linacs].

In recent years, MR-Linac, a radiotherapy linear accelerator (linac) equipped with magnetic resonance (MR) imaging, has been deployed in clinical facilities across Japan. Because of the magnetic field of MR-Linac, which can affect the dose distributions and dose response of ionization chambers, conventional reference dosimetry for absorbed dose to water using an ionization chamber becomes impractical. Consequently, the magnetic field effect should be considered in the reference dosimetry for MR-Linac. Although numerous studies have delved into this matter and several magnetic field correction methods have been proposed to extend the conventional formalism, a practical protocol for reference dosimetry for MR-Linac remains elusive.The purpose of this review are as follows: (i) to summarize and evaluate literature and existing datasets as well as identify any gaps that highlight areas for the future research on this topic; (ii) to elucidate dosimetric challenges associated with ionization chamber dosimetry in magnetic fields; and (iii) to propose a formalism for reference dosimetry for MR-Linac based on available literature and datasets. This review focuses on studies based on commercially available MR-Linacs and datasets, specifically tailored for reference-class cylindrical ion chambers.

Relationship Between Anterior Knee Laxity and General Joint Laxity During the Menstrual Cycle.

BACKGROUND: Anterior cruciate ligament (ACL) injury has been reported to have a higher incidence in women than in men. PURPOSE/HYPOTHESIS: The purpose was to examine the relationship of anterior knee laxity (AKL), stiffness, and generalized joint laxity (GJL) with respect to the menstrual cycle. It was hypothesized that AKL and GJL would increase during the ovulation phase, when estrogen levels are high. STUDY DESIGN: Descriptive laboratory study. METHODS: A total of 15 female university students aged >20 years and with normal menstrual cycles were evaluated. AKL was measured as anterior tibial displacement of the femur after application of 44-, 89-, and 133-N loads to the tibia. Stiffness was calculated as Δ force/Δ displacement at loads between 44 and 89 N and between 89 and 133 N. The University of Tokyo joint laxity test was used for evaluation of GJL. The participants' menstrual cycle was divided into the early follicular, late follicular, ovulation, and luteal phases using the basal body temperature method and an ovulation kit; AKL and GJL were measured once during each phase. Participants were also stratified according to the presence or absence of genu recurvatum (GR). RESULTS: There was no significant difference in AKL, stiffness, or GJL among the menstrual phases. In the GR group, AKL values at 89 N and 133 N were significantly higher in the ovulation phase than in the early follicular phase (P = .025 and P =.018, respectively); there were no significant differences in AKL among the phases in the non-GR group. In addition, the GR group in the ovulation phase had significantly higher AKL values at 44 N, 89 N, and 133 N compared with the non-GR group (P = .013, P = .005, and P = .010, respectively). There were no significant differences in GJL among the phases in the GR or non-GR groups. CONCLUSION: Women with GR may have increased AKL in the ovulation phase when compared with the early follicular phase, which may be a risk factor for ACL injury. CLINICAL RELEVANCE: The results of this study suggest that the ovulation phase may be related to the greater incidence of ACL injuries in women.

Experimental study of humidity effect on charge measurement of reference ionization chambers in clinical high-energy photon beams.

PURPOSE: In the practice code of dosimetry, humidity effect is assumed to be constant as far as the measurements are performed in the relative humidity (RH) range of (20-80)%; thus, the humidity effect can be ignored with a dose uncertainty of 0.15%. This assumption is based on the previous experimental results by Niatel and Guiho. Rogers and Ross calculated the stopping power ratio of humid air and dry air for high-energy electron beams by using a Monte Carlo code. They demonstrate that the W value, the mean energy required to create an ion pair in air, is independent of the beam quality when the air is dry, and that the traditional humidity correction can be used also for high-energy photon and electron beams; however, this was only a computational study. In the present study, we measured the humidity correction of Farmer-type ionization chambers in high-energy photon beams and determined the W values of humid air using the calculated energy deposition of humid air with a Monte Carlo code. Furthermore, we proposed an analytical expression to determine a practical humidity correction for an ionization chamber as a function of absolute humidity. METHOD: Experiments were carried out using a clinical linear accelerator (linac, Elekta Precise) at the National Metrology Institute of Japan (NMIJ). A shield box was constructed downstream of the linac and connected to an air processor, which maintained the temperature around 22°C and controlled the humidity in the range of (10-70)% inside the box. We prepared two Farmer-type ionization chambers: PTW 30013 and Exradin A19. Each ionization chamber was placed inside the box and irradiated with 6-, 10-, and 15-MV high-energy photon beams from the clinical linac. The energy deposition to the humid air inside the ionization chamber was calculated using the Electron Gamma Shower Version 5 (EGS5) code system. RESULTS: Stabilization for the humidity of the ionization chamber was completed within 3 h. The polarity and ion recombination corrections did not show any change in the humidity range studied. The measured humidity correction and the evaluated W values of humid air in high-energy photon beams were in good agreement with those by Rogers in TG-21 and by Niatel in the range of RH (10-70)%. CONCLUSION: Humidity correction of ionization chambers in high-energy photon beams from the clinical linac was determined experimentally. Using the analytical expression for the energy depositions by EGS5, the analytical expression for the W values was also derived.

Role of activating transcription factor-4 in 24-hour rhythm of serotonin transporter expression in the mouse midbrain.

Serotonin (5-HT) transporter (5-HTT) plays a key role in the control of 5-HT neuronal activity by reuptaking extracellular 5-HT from the synapse cleft. We have previously demonstrated that 5-HTT mRNA expression levels and its uptake activity in the mouse midbrain are significantly higher in the dark phase than those in the light phase. However, the molecular mechanisms of time-dependent expression of 5-HTT have not been clarified. In this study, expression of 5-HTT mRNA in the mouse midbrain showed a significant 24-h rhythm and was higher in the dark phase. Although such an oscillation was eliminated by a Clock gene mutation, CLOCK and BMAL1 did not activate 5-HTT transcription in the luciferase reporter assay. Activating transcription factor-4 (ATF4), a member of the ATF/cAMP response element (CRE)-binding protein family, is a component responsible for sustaining circadian oscillations of CRE-mediated gene expression. ATF4 significantly activated 5-HTT transcription in vitro and time dependently bound to the CRE site in the 5-HTT promoter in the mouse midbrain. In addition, mutation of the Clock gene disrupted temporal binding of ATF4 to the CRE site in the 5-HTT promoter. These results indicated that the circuit of circadian-basis molecular regulation between the clockwork system and mouse 5-HTT gene was connected by the ATF4 signaling pathway.

Initial experience with computed tomographic colonography applied for noncolorectal cancerous conditions.

PURPOSE: The aim of this study was to asses retrospectively the performance of computed tomography colonography (CTC) for noncolorectal cancerous conditions. MATERIAL AND METHODS: A total of 44 patients with non-colorectal cancerous conditions underwent CTC. We researched the indications for CTC or present illness and evaluated the CTC imaging findings. We assessed whether diagnosis by CTC reduced conventional colonoscopic examinations. RESULTS: A total of 47 examinations were performed in 44 patients. The indications for CTC or a present illness were as follows: 15 patients with impossible or incomplete colonoscopy, 7 with diverticular disease, 6 with malignancy (noncolorectal cancer), 6 with Crohn's disease, 4 suspected to have a submucosal tumor on colonoscopy, 2 with ischemic colitis, and 4 with various other diseases. Colonic findings were diagnosed on CTC in 36 examinations, and extracolonic findings were identified in 35 of 44 patients. In all, 17 patients had undergone colonoscopy previously, 9 (52.9%) of whom did not require further colonoscopy by CTC. Five patients underwent colonoscopy after CTC. CONCLUSION: The indications for CTC were varied for patients with noncolorectal cancerous conditions. CTC examinations could be performed safely. Unlike colonoscopy or CT without preparation, CTC revealed colonic and extracolonic findings and may reduce the indication of colonoscopy in patients with noncolorectal cancerous conditions.

Isolation and identification of dieldrin-degrading Pseudonocardia sp. strain KSF27 using a soil-charcoal perfusion method with aldrin trans-diol as a structural analog of dieldrin.

We isolated a novel aerobic dieldrin-degrading bacterium from an enrichment culture in a soil-charcoal perfusion system. Enrichment culture using a soil-charcoal perfusion system was an effective way to obtain microorganisms that degrade recalcitrant compounds. The soil-charcoal perfusion was performed using aldrin trans-diol, which was a metabolite of dieldrin. Aldrin trans-diol had higher bioavailability (2.5 mg/l) than dieldrin (0.1-0.25 mg/l), therefore it is possible for microorganisms to utilize it as a substrate in soil. After 100 days of circulation and three exchanges of the medium, the enriched charcoal was harvested and a bacterium isolated. The isolate was designated as strain KSF27 and was found to be closely related to Pseudonocardia spp. as determined by 16S rRNA sequencing analysis. Strain KSF27 degraded aldrin trans-diol by 0.05 µmol/l from an initial concentration of 25.5 µmol/l. The metabolite of aldrin trans-diol was detected by HPLC/MS and determined to be aldrindicarboxylic acid based on retention time and the MS fragment. Moreover, strain KSF27 degraded dieldrin from 14.06 µmol/l to 2.01 µmol/l over a 10-day incubation at 30°C. This strain degraded dieldrin and other persistent organochlorine pesticides, such as α-endosulfan, ß-endosulfan, endosulfan sulfate, heptachlor, heptachlor epoxide and chlordecone.

Biodegradation of dieldrin by a soil fungus isolated from a soil with annual endosulfan applications.

An aerobic dieldrin-degrading fungus, Mucor racemosus strain DDF, was isolated from a soil to which endosulfan had been annually applied for more than 10 years until 2008. Strain DDF degraded dieldrin to 1.01 microM from 14.3 microM during a 10-day incubation at 25 degrees C. Approximately 0.15 microM (9%) of aldrin trans-diol was generated from the dieldrin degradation after a 1-day incubation. The degradation of dieldrin by strain DDF was detected over a broad range of pH and concentrations of glucose and nitrogen sources. Extracellular fluid without mycelia also degraded dieldrin. Strain DDF degraded not only dieldrin but also heptachlor, heptachlor epoxide, endosulfan, endosulfan sulfate, DDT, and DDE. Endosulfan sulfate and heptachlor were degraded by 0.64 microM (95%) and 0.75 microM (94%), respectively, whereas endosulfan and DDE were degraded by 2.42 microM (80%) and 3.29 microM (79%), respectively, and DDT and heptachlor epoxide were degraded by 6.95 microM (49.3%) and 5.36 microM (67.5%), respectively, compared with the control, which had a concentration of approximately 14 microM. These results suggest that strain DDF could be a candidate for the bioremediation of sites contaminated with various persistent organochlorine pesticides including POPs.

Synthesis and anti-angiogenic activity of cortistatin analogs.

Analogs of cortistatins, a series of anti-angiogenic compounds isolated from the Indonesian marine sponge Cortisium simplex, were synthesized from estrone by using the Suzuki-Miyaura coupling reaction as the key step. The estrone-isoquinoline hybridized compound showed selective inhibitory activity against the proliferation and VEGF-induced migration of HUVEC.