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Umbilical venous (UV) catheters (UVCs) are commonly used in severely ill neonates. Complications associated with UVC often result from an inappropriate UVC position. Calcification of the UV, a rare complication, was observed in an extremely low-birth-weight infant born at 23 weeks of gestation. After birth, the infant experienced respiratory and circulatory dysfunction, followed by disseminated intravascular coagulation (DIC). A UVC was inserted, and circulatory agonists and blood transfusions were administered, as well as a calcium gluconate infusion for hypocalcemia and hyperkalemia. Ten days after birth, calcification was detected in the UV, likely due to a tunica intima injury caused by UVC, a hypercoagulable state due to DIC, and a high-dose calcium gluconate infusion. Additionally, proximal port malpositioning of the double-lumen catheter might have contributed to calcification within the UV. To prevent such complications, real-time ultrasound confirmation with agitated saline contrast during UVC placement is recommended; in the absence of the facility or skills for ultrasonography, X-rays should be performed in the lateral and anteroposterior views. Furthermore, when using multi-lumen catheters, physicians should not only verify the tip position but also ensure proper placement of proximal ports and carefully select medications administered through the ports. [ABSTRACT FROM AUTHOR]

Developing experimental animal models that show clinical symptoms and methods for quantitative and objective evaluation are important for understanding food allergies. Therefore, this study aimed to develop an ovalbumin (OVA)-induced mouse model of food allergy and a useful method to evaluate the symptoms of food allergy. Mice were sensitized via intraperitoneal injection of OVA. Subsequently, local sensitization was performed once weekly by oral administration of OVA. Itching and nasal symptoms were observed after oral administration of the antigen. First, we examined the dose-dependency of the antigen. Symptoms were checked weekly. In order to confirm food allergy symptoms, the effect of histamine H 1 receptor antagonist was examined. Finally, we measured antigen-specific IgE antibody levels in the serum. Scratching behavior, sneezing and nasal rubbing were increased. Both itching and rhinitis symptoms increased steadily, after which, the number of symptoms remained almost constant. No difference was observed between the results of 3- and 5-week-old mice. Cetirizine inhibited these symptoms in a dose-dependent manner. In addition, antigen-specific IgE antibodies were produced in both 3- and 5-week-old mice. This method may be useful for evaluating the symptoms of skin and rhinitis that could not be assessed in the conventional food allergy model and could be induced with a low dose of antigen. In particular, the developed method, which measures the number of itching and nasal symptoms, may enable quantitative, objective, and noninvasive evaluation of food allergy severity. [ABSTRACT FROM AUTHOR]

Acoustic cavitation bubbles are considered to be generated due to heterogeneous nucleation because a smaller amount of energy is required in this case compared with homogeneous nucleation. A typical example of such nucleation sites is tiny cracks filled with gas, commonly termed as "gas pocket." Such microcracks can exist in abundance on the surface of reactor walls or sonotrodes used for the cavitation treatment. Eventually, the heterogeneously nucleated cavitation bubble is detached from the solid surface; however, the detachment mechanism has been unclear so far. Therefore, the present study numerically investigated the dynamic behavior of the cavitation bubble originated from the heterogeneous nucleation at wall cracks. During propagation of an ultrasound wave through a liquid, gas pockets in cracks oscillate sinusoidally when the sound pressure amplitude and crack radius are small. In this case, the bubble cannot detach from the surface. On the other hand, as the sound pressure amplitude, crack size, and/or contact angle become larger, the bubble begins to oscillate non-linearly that causes liquid jetting. The liquid jetting can cause the bubble detachment from the surface due to the interaction between the liquid jet and the bottom wall. Stronger liquid jetting makes many small detached bubbles. [ABSTRACT FROM AUTHOR]

Cases: We present 2 cases (19- and 40-year-old women) of lumbosacral spinal deformity with sacroiliac joint destruction. Reconstruction surgery using a fibular strut autograft was performed in both patients, and spinal reconstruction and fusion were successfully maintained without bone resorption for at least 7 years. Conclusion: This is the first report of reconstructive surgery using a fibular strut bone graft for lumbosacral deformity with destruction of the sacroiliac joint in patients with neurofibromatosis type 1 (NF-1). These findings suggest that reconstruction with a fibular strut autograft is useful for lumbosacral spinal deformity that includes destruction of the sacroiliac joints in NF-1. [ABSTRACT FROM AUTHOR]

• Mass transfer across a gas–liquid interface of acoustic cavitation is investigated. • Time-averaged Sherwood number is decreased with sound pressure amplitude. • Time-averaged Sherwood number can be negative value due to area and shell effect. • The instantaneous Sherwood number is varied in the range of O (101) ∼ O (102). In the present study, mass transfer across a gas–liquid interface of acoustic cavitation bubble is numerically investigated. The volume of fluid (VOF) method coupled with a continuous species transfer model is used to simulate the bubble dynamic behavior and mass transfer across the gas–liquid interface. Chemical species are transferred repeatedly between the liquid and gas phases in accordance with the bubble oscillation, and the chemical species are transferred into the bubble during an expansion phase, and to the outside of bubble during a compression phase. Time-averaged Sherwood number is decreased with an amplitude of sound pressure due to area effect and shell effect , and its value becomes negative at high pressure amplitude. Meanwhile, the instantaneous Sherwood number is largely varied in accordance with the bubble oscillation, and its magnitude becomes O (101) ∼ O (102). [ABSTRACT FROM AUTHOR]

The structure of written texts is analyzed by focusing on word sequences. As a method, word sequences in texts are transformed into rank sequences of the occurrence frequency of each word and return maps are drawn. The features of word sequences are extracted by comparing with the surrogate data, i.e., a sequence in which all the words are randomly rearranged. A total of 140 written texts consisting of ten languages are selected for analysis. To characterize the distribution in the return map quantitatively, two characteristic quantities are defined, the distance between the original distribution and surrogate distribution, and the correlation coefficient of the adjacent word ranks. The results show that there is a negative correlation in the rank of adjacent words in almost all languages, and features of return maps of the same language texts are similar. A clustering structure which implies the relation to language (sub)family is observed. A mathematical model is proposed for reproducing features of the return map for multiple languages. The numerical simulations achieve results similar to those of the real data quantitatively. [ABSTRACT FROM AUTHOR]

This review summarizes the presentations given at the 22nd International conference on Emerging Infectious Diseases in the Pacific Rim. The purpose of this annual meeting is to foster international collaborations and address important public health issues in the Asia-Pacific region. This meeting was held in Bangkok in February 2020 and focused on emerging virus infections. Unexpectedly, the SARS-CoV-2 pandemic was in the initial stages leading to a special session on COVID-19 in addition to talks on dengue, influenza, hepatitis, AIDS, Zika, chikungunya, rabies, cervical cancer and nasopharyngeal carcinoma. • Early recognition and response to SARS-CoV-2 entry into Thailand and Cambodia. • Pathogenesis of HIV, rabies, Lassa, chikungunya, coronavirus and paramyxovirus. • Improved diagnosis and treatment for norovirus, HBV and EBV infections. • Vaccine development for influenza, dengue, HIV, HCV and mosquito-borne pathogens. • Successful control of human papillomavirus infection through vaccination. [ABSTRACT FROM AUTHOR]

[Display omitted] • Largest reactor pressure vessel steel embrittlement database available includes test reactor and surveillance data. • Machine learning model for accurate prediction of embrittlement with low errors and large applicability domain. • Well-calibrated uncertainty estimates for informing uncertainty quantification on new predictions. • Use machine learning model to assess physical trends, construct embrittlement curves, and predict alloy life extension behavior. An essential aspect of extending safe operation of the world's active nuclear reactors is understanding and predicting the embrittlement that occurs in the steels that make up the Reactor pressure vessel (RPV). In this work we integrate state of the art machine learning methods using ensembles of neural networks with unprecedented data collection and integration to develop a new model for RPV steel embrittlement. The new model has multiple improvements over previous machine learning and hand-tuned efforts, including greater accuracy (e.g., at high-fluence relevant for extending the life of present reactors), wider domain of applicability (e.g., including a wide-range of compositions), uncertainty quantification, and online accessibility for easy use by the community. These improvements provide a model with significant new capabilities, including the ability to easily and accurately explore compositions, flux, and fluence effects on RPV steel embrittlement for the first time. Furthermore, our detailed comparisons show our approach improves on the leading American Society for Testing and Materials (ASTM) E900-15 standard model for RPV embrittlement on every metric we assessed, demonstrating the efficacy of machine learning approaches for this type of highly demanding materials property prediction. [ABSTRACT FROM AUTHOR]

Chain‐end‐functionalized poly(3‐hexylthiophene)s (P3HTs) with benzyl alcohol (─PhCH2OH), phenol (─PhOH), and benzoic acid (─PhCOOH) groups are directly synthesized based on the Negishi catalyst‐transfer polycondensation method utilizing the zincate complex of tBu4ZnLi2. In this system, neither protection nor deprotection steps are required, and also providing a living polymerization system to control the molecular weight while maintaining a low molar mass dispersity (ÐM) of the obtained P3HT derivatives. Indeed, the chain‐end‐functionalized P3HTs can be synthesized along with controlled number‐average molecular weights (Mn = 5100–20 000), low ÐM (1.06–1.14), and high chain‐end functionality (Fn = 46–86%). The Fn values for the alcohol and phenol groups are found to be high (86% for ─PhCH2OH and 71% for ─PhOH based on 1H NMR, respectively), as also confirmed by matrix‐assisted laser desorption/ionization time of flight mass spectroscopy. The easily synthesizable chain‐end‐functionalized P3HTs will be applicable for the facile synthesis of block and branched polymers containing P3HT as well as its related semiconducting polymer segments. [ABSTRACT FROM AUTHOR]

• Bubble fragmentation in a stirred vessel is categorized into three types: collision with a blade, boundary layer ahead of blade, and vortex-induced viscous shear stress. • Six-types fragmentation was observed according to the interaction between trailing vortices and bubble. • The bubble is fragmented by a single trailing vortex according to the two mechanisms: a trailing vortex cuts-off and a rotational flow of trailing vortex. • The bubble can be fragmented by several trailing vortices at the gap between them. We investigated the mechanism of single-bubble fragmentation during mechanical stirring under different trailing vortex conditions. Experiments and numerical simulations using the LES-VOF method were carried out under different bubble sizes and locations of bubble injection. We found that the following three phenomena can cause bubble fragmentation: collision with impeller blade; shear stress in the boundary layer ahead of the impeller blade; and interaction between trailing vortices and the bubble. In the last case, the mechanism of fragmentation can be categorized into six types, which are determined by the relationship between the bubble behavior and the trailing vortices. Thus, we clarified the relationship between trailing vortices and bubble fragmentation for the first time in a stirred vessel. [ABSTRACT FROM AUTHOR]

Highlights • Three types of transient free surface deformation are observed. • Local surface vortex is developed due to a low pressure-zone behind the impeller blade. • Entire rotation of free-surface elevation is generated due to the macro-instability. • Local free-surface elevation and deflection are generated due to trailing vortices. • The stirring method determines the contribution of each phenomena. Abstract The present study investigated the mechanism of surface vortex formation and free surface deformation in an unbaffled stirred vessel with on-axis and eccentric impellers having four paddle blades. To shed light on the mechanism of surface vortex formation and free surface deformation, we conducted experiments and numerical simulation in an unbaffled cylindrical stirred vessel. The surface vortex was found to be small in the eccentrically stirred vessel due to a vertical flow caused by the interaction between the discharged flow and sidewall. In the case of on-axis impeller, low-pressure zones at the rear faces of blades pulled the free surface, that causes the air entrainment. These phenomena could be seen in both the experimental observation and numerical simulation. The three types of transient free surface deformation were observed: local vortex formation due to the low-pressure zone mentioned above, entire rotation of free-surface elevation due to the macro-instabilities, and local elevation and deflection due to trailing vortices. [ABSTRACT FROM AUTHOR]

Several authors have reported the occurrence of extraforaminal L5 nerve root compression between lumbosacral transitional vertebrae (LSTV) and sacral ala, but reports on a lesion caused by an intervertebral osteophyte on the ventral and contralateral side of a unilateral abnormality by LSTV are hardly available. A 67-year-old woman presented with pain along the distribution of the L5 nerve root; straight leg raise test, femoral nerve stretch test, and Kemp test were positive on the left. Following plain radiographs, computerized tomography, magnetic resonance imaging, and selective nerve root block, an osteophyte bridging the L5 and S1 vertebral bodies in the ventral side was identified compressing the L5 nerve root. On account of resistance to conservative therapy and the delicate position of the lesion, surgical treatment was performed by an anterior decompression. Subsequently, the patient attained adequate relief from pain and could walk normally. We herein present a very rare case of extraforaminal L5 nerve root compression caused by an intervertebral osteophyte on the ventral and contralateral side of a unilateral abnormality by LSTV, which was managed by anterior decompression. [ABSTRACT FROM AUTHOR]

Abstract A series of Fe-3 to 18 at.% Cr binary ferritic alloys were neutron irradiated side by side, in the Advanced Test Reactor (ATR) at a temperature of ∼320 °C to a dose of ∼1.8 dpa. Three types of features that form under irradiation are relevant: (i) solute clusters; (ii) α′ precipitates; and, (iii) dislocation loops. The size and number density of the precipitates and loops were measured by transmission electron microscopy (TEM) and compared to previous atom probe tomography (APT) observations. The loop density systematically decreases with increasing Cr, while the number of α′ precipitates increase at 9Cr and above. A major objective of this work is to estimate the dispersed barrier obstacle strength factors (α j) for loops, clusters and α′ precipitates, based on the combined microstructural observations and corresponding irradiation hardening measurements. Standard dispersed barrier-hardening models and computationally derived superposition rules were least square fit to determine the α j. The optimized hardening predictions are in very good agreement with experiment if mixed linear sum and root square sum superposition rules are used. Five increments of 168 h isochronal anneals of the 6Cr alloy between 300 and 400 °C coarsened the loops, while 300 h anneals of the 18Cr at 500 and 600 °C coarsened and dissolved the α′ precipitates, respectively, consistent with the Fe-Cr phase diagram. [ABSTRACT FROM AUTHOR]

Highlights • Bubbles move behind the impeller blade due to pressure distribution. • Most bubbles in an unbaffled stirred vessel are fragmented in the trailing vortices. • The fragmented bubbles are transported by the trailing vortices, the core of which traps the bubble. • Smaller and more complicated bubbles are generated with increasing the impeller rotation rate. • More bubbles are agglomerated near the shaft with increasing the impeller rotation rate due to pressure distribution. Abstract The present study investigated the mechanism of small bubble breakup in an unbaffled vessel stirred by a 4-blade paddle impeller. Bubbles were injected underneath the rotating blades. Numerical simulation and experimental observations were performed to investigate the related phenomena. The Volume of Fluid (VOF) method was utilized to simulate a gas-liquid multiphase flow. The injected bubbles were broken behind the impeller blade, where they were transported due to a decreasing pressure gradient caused by the impeller rotation. At the behind of the blade, bubbles were elongated and fragmented due to the trailing vortices developing from the rear surface of blade. The fragmented bubbles were entrapped at the cores of trailing vortices, and then floated up in the space where the trailing vortices became weak. The size of the broken bubbles was dependent on the impeller rotation rate. [ABSTRACT FROM AUTHOR]

The development of a universal influenza vaccine that can provide a robust and long-lasting protection against a broader range of influenza virus strains is a global public health priority. One approach to improve vaccine efficacy is to use an adjuvant to boost immune responses to the target antigens; nevertheless, the role of adjuvants in the context of influenza vaccines is not fully understood. We have previously developed the K3-schizophyllan (SPG) adjuvant, which is composed of nanoparticulated oligodeoxynucleotides K3, a TLR9 agonist, with SPG, a non-agonistic β-glucan ligand of Dectin-1. In this study, K3-SPG given with conventional influenza hemagglutinin (HA) split vaccine (K3-SPG HA) conferred protection against antigenically mismatched heterologous virus challenge. While K3-SPG HA elicited robust cross-reactive HA-specific IgG2c and CD8 T-cell responses, CD8 T-cell depletion had no impact on this cross-protection. In contrast, K3-SPG HA was not able to confer protection against heterologous virus challenge in FcRγ-deficient mice. Our results indicated that FcγR-mediated antibody responses induced by the HA antigen and K3-SPG adjuvant were important for potent protection against antigenically mismatched influenza virus infection. Thus, we demonstrated that the K3-SPG-adjuvanted vaccine strategy broadens protective immunity against influenza and provides a basis for the development of next-generation influenza vaccines. [ABSTRACT FROM AUTHOR]

This study investigated the flow characteristics of aluminum melt agitated by differently shaped impellers. A typical impeller used in the aluminum industry has twisted blades. The present study examined the effect of twisting angle on the flow pattern through PIV experiments and numerical simulation using water model. The results revealed that the twisting angle affects the strength and direction of discharge flow. The strength of discharge flow became weaker with increasing the twisting angle while the flow direction was influenced by both the front blade surface of impeller and space interval between the adjacent blades. The structure of trailing vortices was found to be also varied depending on the impeller twisting angle. [ABSTRACT FROM AUTHOR]

Aiming at improving the efficiency of cavitation treatment, this work investigates characteristics of acoustic streaming and cavitation generated in water by dumbbell-shaped sonotrodes with plane, truncated and conical tips. The main emphasis was placed on elucidating the effects of tip shape and vibration amplitude ranged from 40 to 60  μ m . The PIV technique and Weissler reaction were used to measure flow pattern and velocity of acoustic streaming, and cavitation efficiency, respectively. To provide a theoretical explanation to the experimental results, a self-developed mathematical model was used to simulate the acoustic streaming and predict the size of cavitation zone numerically. Both the experimental and numerical results revealed that the sonotrode tip shape affects the acoustic streaming significantly, altering the flow magnitude and direction from fast and downward under the plane and truncated tips to relatively slow and upward near the conical tip. Besides, the conical tip provides a more efficient cavitation treatment in comparison with the plane and truncated tips. The simulation results showed that widening of cavitation zone and altering of acoustic streaming velocity and direction near the sonotrode tip are responsible for the enhancement of cavitation treatment efficiency. [ABSTRACT FROM AUTHOR]

Abstract Since polymers of cyclic topology have no main chain terminus, and the conformation is limited, they show physical and chemical properties different from those of linear polymers even the composition and molecular weight are the same. In order to pursue functions based on the topology of polymers, we have developed synthetic methods for cyclic polymers and constructed nanostructures by self-assembly. As a result, it was found that micelles and vesicles formed by cyclic polymers exhibit characteristics, which were greatly changed as compared with those of linear polymers. Based on cyclic-to-linear transformation, a gelling agent was developed, and furthermore, the reversible and repeatable topological conversion was achieved. Moreover, monolayer assemblies such as self-assembled monolayers on a gold surface and Langmuir–Blodgett films were constructed from cyclic macromolecules. [ABSTRACT FROM AUTHOR]

In the present study, an optimized low-cost numerical model has been developed to simulate melt stirring and mass transfer in aluminum melting furnace. To validate the numerical model, scaled-down water model experiments were also conducted. The present numerical results revealed good agreement with the experimental observations. Faster speeds of impeller rotation could improve the stirring efficiency; however, a strong surface vortex was formed at the free surface under these conditions. The perfect mixing time was the longest at middle immersion depth of impeller and the strong surface vortex was generated at the largest immersion depth. The mechanism of surface vortex generation was explained in terms of pressure distribution around the blades, which is created by the impeller rotation. [ABSTRACT FROM AUTHOR]

A numerical simulation study was carried out to examine the transport phenomena occurring during the Top-Seeded Solution Growth (TSSG) process of SiC. The simulation model includes the contributions of radiative and conductive heat transfer in the furnace, mass transfer and fluid flow in the melt, and the induced electric and magnetic fields. Results show that the induced Lorentz force is dominant in the melt compared with that of buoyancy. At the relatively low coil frequencies, the effect of the Lorentz force on the melt flow is significant, and the corresponding flow patterns loose their axisymmetry and become almost fully disturbed. However, at the relatively higher frequency values, the flow is steady and the flow patterns remain axisymmetric. [ABSTRACT FROM AUTHOR]

Microstructural evolutions in two variants of the F82H 8 wt%Cr tempered martensitic steel under dual (He+ plus Fe3+) ion irradiations at 500 °C have been characterized by transmission electron microscopy. Emphasis is on understanding the combined effects of displacements per atom (dpa) and the helium/dpa ratio (He/dpa) on cavity evolution and void swelling (f v). The dual ion database includes 231 alloy-dpa-He/dpa conditions for irradiations up to ∼ 82 dpa and 3700 appm helium. We hypothesize that the large "scatter" observed in the f v data is primarily due to local microstructural variations, especially those that shield regions at shallower depths from the effects of injected interstitial atoms, which would otherwise reduce f v. More generally, our hypothesis is that the highest f v data, at a specified dpa and He/dpa, provides the most appropriate estimate of swelling for fusion neutron irradiation conditions. The dose dependence of f v can be described by an incubation dpa i , marking the onset of significant void growth, and a post-incubation swelling rate, f v ' = Δf v /Δdpa. Both dpa i and f v ' decrease with increasing He/dpa. The f v ' data are quantitatively consistent with a simple model for defect partitioning between evolving bubble, void, and dislocation sinks strengths and biases. Most notably, the model correctly predicts both the incubation dpa i , and the subsequent f v ', in spite of the fact that they reflect somewhat different physics. Our analysis also suggests that defect recombination is modest at 500 °C. Along with other considerations, this supports the hypothesis that, even at high dpa rates, dual ion irradiations can be used to reasonably emulate void nucleation and growth for a range of fusion-relevant neutron irradiation service conditions. A companion paper incorporates the results of this study in a reduced-order, data-driven void swelling model. [ABSTRACT FROM AUTHOR]

The UCSB database on cavity evolution in 9-12Cr tempered martensitic steels (TMS), includes the results for both dual heavy and helium ion (DII), and High Flux Isotope Reactor (HFIR) in situ helium injection (ISHI) neutron irradiations at 500°C. These results were combined with literature single ion and fission neutron irradiation data to derive a model for the void volume fraction, f v , as a function of displacements per atom (dpa) and transmutant helium concentrations in atomic parts per million (appm). The scientific foundation for the paper is described in a companion paper entitled "Cavity Evolution and Void Swelling in Dual Ion Irradiated Tempered Martensitic Steels ". Here, we show that f v (dpa, He/dpa) is described by the incubation dose, dpa i , for the onset of void growth, and the post-incubation growth rate, f v '(%/dpa). Both dpa i and f v ' decrease with increasing He/dpa at > ∼ 5. The dpa i is also lower for the ISHI neutron irradiations at the same He/dpa. Single heavy ion and fission reactor neutron irradiations, with low He/dpa ratios, have a much larger dpa i. Based on a combined analysis of DII, single ion, ISHI and fission neutron data, we further show that the post-incubation f v data analyzed here have a common empirical curve shape, with f v ' reaching up to ∼ 0.2%/dpa at very high dpa. We also show that f v ' can be predicted based on a physical model of defect partitioning between evolving sinks. At 500°C and fusion relevant He/dpa ≈ 10, the best-fit model predicts nominal swelling, S = f v /(1-f v), of ∼ 1.1, 4.9 and 16% at 50, 100 and 200 dpa, respectively. The physically motivated, data-driven model includes estimated uncertainties for both dpa i and f v '. [ABSTRACT FROM AUTHOR]

A global numerical simulation was performed for the induction heating Top-Seeded Solution Growth (TSSG) process of SiC. Analysis included the furnace and growth melt. The effects of interfacial force due to free surface tension gradient, the RF coil-induced electromagnetic body force, buoyancy , melt free surface deformation , and seed rotation were examined. The simulation results showed that the contributions of free surface tension gradient and the electromagnetic body force to the melt flow are significant. Marangoni convection affects the growth process adversely by making the melt flow downward in the region under the seed crystal. This downward flow reduces carbon flux into the seed and consequently lowers growth rate. The effects of free surface deformation and seed rotation, although positive, are not so significant compared with those of free surface tension gradient and the electromagnetic body force. Due to the small size of the melt the contribution of buoyancy is also small. [ABSTRACT FROM AUTHOR]

Aims/Introduction We devised a new system called 'Educational Guidance' (E-Guide) for nutritional education based on self-efficacy. The present study aimed to examine the effects of E-Guide use on glycemic control among patients with type 2 diabetes. Materials and Methods We carried out an interventional and observational study that included 74 patients with type 2 diabetes. The extent of glycemic control in the 39 patients who received guidance through the E-Guide (E-Guide group) was compared with that of 35 patients who received conventional nutritional guidance (control group). We carried out a 1-year follow-up survey (subanalysis) based on the electronic health records of 18 patients from the E-guide group and 19 patients from the control group. These patients continued treatment at Hikone Municipal Hospital, Hikone, Shiga, Japan. Changes in glycated hemoglobin levels, body mass index and medication dose were examined from time of enrollment to the end of the 1-year intervention, and during the 1-year follow-up. Results Decreases in glycated hemoglobin levels were more pronounced in the E-Guide group than in the control group during the intervention period ( P < 0.05). The levels further decreased during the follow-up period ( P < 0.01). In the E-Guide group, body mass index decreased significantly throughout the follow-up period ( P < 0.001). Additionally, increased medication doses were significantly less common in the E-Guide group than in the control group ( P < 0.01). Conclusions Intervention based on our 'E-Guide' is more useful and powerful than the conventional methods for glycemic control and self-care behavior among patients with type 2 diabetes in Japan. [ABSTRACT FROM AUTHOR]

The volume-averaging continuum technique has been utilized to obtain numerical predictions for the transport phenomena occurring during the dissolution process of GaSb into InSb melt in a sandwich system. Dissolution and subsequent growth in this system are achieved by the application of a temperature gradient. The developed model was first verified for two test cases [(i) fluid/solid conjugate heat transfer and (ii) the solidification process of the binary system]. The code was then utilized to simulate the dissolution process of GaSb into InSb in the GaSb/InSb/GaSb sandwich system. The present results show that the developed volume-averaging model provides accurate predictions. [ABSTRACT FROM PUBLISHER]

Recent trends in the aluminum industry toward increasing the recycling rate of aluminum alloys have led to difficulties in controlling the formation of intermetallic compounds (IMCs). The up-to-date investigations have revealed that ultrasonic irradiation is a promising tool to refine and modify the intermetallic compounds formed in the melt before or during casting, and the reported mechanisms include ultrasound-assisted nucleation and fragmentation of compounds. This work presents results concerning the modification effect of ultrasound on model Al 3 Zr compounds with emphasis on the effect of vibration amplitudes. The results reveal that needle-like Al 3 Zr compounds can be significantly modified to thicker shape when amplitude increases from 38 µm to 48 µm, and then change to more rounded shape with the further increase of amplitude. Theoretical consideration and numerical simulation show that in addition to the above-mentioned mechanisms, cavitation-induced heat generation and mircrojet-driven mass transfer are also of prime importance in controlling the morphology and growth of IMCs. • A wide range of ultrasound vibration amplitude is examined. • Needle-like Al 3 Zr compounds can be significantly modified to more rounded shape when amplitude increases. • Behavior of cavitation bubble near compound particle is simulated numerically. • Cavitation-induced heat generation and microjet-driven mass transfer play a prominent role in controlling the morphology and growth of primary Al 3 Zr compounds. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus type 1 (HIV-1) reporter cell lines are critical tools for drug development. However, one disadvantage of HIV-1 reporter cell lines is that reductions in reporter gene activity need to be normalized to cytotoxicity, i.e., live cell numbers. Here, we developed a dual luciferase assay based on a R. reniformis luciferase (hRLuc)-expressing R5-type HIV-1 (NLAD8-hRLuc) and a CEM cell line expressing CCR5 and firefly luciferase (R5CEM-FiLuc). The NLAD8-hRLuc reporter virus was replication competent in peripheral blood mononuclear cells. The level of hRLuc was correlated with p24 antigen levels ( p < 0.001, R = 0.862). The target cell line, R5CEM-FiLuc, stably expressed the firefly luciferase (FiLuc) reporter gene and allowed the simultaneous monitoring of compound cytotoxicity. The dual reporter assay combining a NLAD8-hRLuc virus with R5CEM-FiLuc cells permitted the accurate determination of drug susceptibility for entry, reverse transcriptase, integrase, and protease inhibitors at different multiplicities of infection. This dual reporter assay provides a rapid and direct method for the simultaneous monitoring of HIV infection and cell viability. [ABSTRACT FROM AUTHOR]

This study demonstrates the comprehensive investigation on the reversible linear-cyclic topological conversion of hydrophilic and hydrophobic polymers with various molecular weights. The reactions were triggered by light or heat, which reversibly dimerize and cleave the anthryl or coumarinyl end groups of the telechelics. Poly(ethylene oxide) telechelics with anthryl end groups attached through electron-donating (Ant-O-PEO and Ant-CH2-PEO) and electron-withdrawing (Ant-CO2-PEO) linking groups were synthesized. While Ant-O-PEO and Ant-CH2-PEO decomposed upon photoirradiation at 365 nm, Ant-CO2-PEO efficiently cyclized through the photodimerization of the anthryl end groups both in water and in organic solvents shown by NMR, SEC, and MALDI-TOF MS. The lower the molecular weight, the faster the cyclization proceeded. When cyclized Ant-CO2-PEO was heated at 150 °C in bulk, the polymers quantitatively converted back into the original linear topology. Furthermore, repeatable linear-cyclic topological conversion was confirmed. The reversible topological conversion of hydrophobic poly(tetrahydrofuran) telechelics with anthryl end groups (Ant-PTHF) was also successful. In addition, poly(ethylene oxide) telechelics with coumarinyl end groups (Cou-PEO) were also cyclized by irradiation at 365 nm in water. However, the cyclization hardly occurred when performed in methanol likely due to the lack of sufficient hydrophobic interaction of the coumarinyl end groups. Cyclized Cou-PEO was irradiated at 254 nm to test for linearization, finding the linear product and cyclic precursor were likely photoequilibrated. [ABSTRACT FROM AUTHOR]

A pentacyclic quadruply fused polymer topology has been constructed for the first time through alkyne-azide addition (click) and olefin metathesis (clip) reactions in conjunction with an electrostatic self-assembly and covalent fixation (ESA-CF) process. Thus, a spiro-type, tandem tetracyclic poly(tetrahydrofuran), poly(THF), precursor having two allyloxy groups at the opposite positions of the four ring units was prepared by the click-linking of one unit of an eight-shaped precursor having alkyne groups at the opposite positions with two units of a single-cyclic counterpart having an azide and an alkene group at the opposite positions. Both are obtainable through ESA-CF. The subsequent metathesis clip-folding of the tetracyclic precursor could afford a pentacyclic quadruply fused polymer product, of 'shippo' form, in 19 % yield. [ABSTRACT FROM AUTHOR]

A pentacyclic quadruply fused polymer topology has been constructed for the first time through alkyne-azide addition (click) and olefin metathesis (clip) reactions in conjunction with an electrostatic self-assembly and covalent fixation (ESA-CF) process. Thus, a spiro-type, tandem tetracyclic poly(tetrahydrofuran), poly(THF), precursor having two allyloxy groups at the opposite positions of the four ring units was prepared by the click-linking of one unit of an eight-shaped precursor having alkyne groups at the opposite positions with two units of a single-cyclic counterpart having an azide and an alkene group at the opposite positions. Both are obtainable through ESA-CF. The subsequent metathesis clip-folding of the tetracyclic precursor could afford a pentacyclic quadruply fused polymer product, of 'shippo' form, in 19 % yield. [ABSTRACT FROM AUTHOR]

Formation of a high density of Mn–Ni–Si nanoscale precipitates in irradiated Cu-free and Cu-bearing reactor pressure vessel steels could lead to severe unexpected embrittlement. Models long ago predicted that these precipitates, which are not treated in current embrittlement prediction models, would emerge only at high fluence. However, the mechanisms and variables that control Mn–Ni–Si precipitate formation, and their detailed characteristics, have not been well understood. High flux irradiations of six steels with systematic variations in Cu and Ni contents were carried out at ∼295 °C to high and very high neutron fluences of ∼1.3 × 10 20 and ∼1.1 × 10 21 n cm −2 . Atom probe tomography shows that significant mole fractions of Mn–Ni–Si-dominated precipitates form in the Cu-bearing steels at ∼1.3 × 10 20 n cm −2 , while they are only beginning to develop in Cu-free steels. However, large mole fractions of these precipitates, far in excess of those found in previous studies, are observed at 1.1 × 10 21 n cm −2 at all Cu contents. At the highest fluence, the precipitate mole fractions primarily depend on the alloy Ni, rather than Cu, content. The Mn–Ni–Si precipitates lead to very large increases in measured hardness, corresponding to yield strength elevations of up to almost 700 MPa. [ABSTRACT FROM AUTHOR]

[Display omitted] • Design strategy of phase change material properties are developed for low-energy memory application. • Low operation energy condition is explored automatically through Bayesian optimization. • Operation energy is lowered by decreasing thermal conductivity, ratio of volume resistance to contact resistance and phase change temperature. • According to the developed design strategy, operation energy of typical Ge-Sb-Te can be decreased to less than 1/100 in phase change memory application. Aiming at reducing energy consumptions in data writing, the development of new memory materials is highly required. To develop new phase change materials (PCMs) with extremely low operation energy used in non-volatile memory, such as storage-class memory, we performed Bayesian optimization for the physical properties of PCMs through numerical simulations. In this numerical simulation, the electrical potential and temperature distribution were solved simultaneously. It was found that a PCM with low thermal conductivity, low melting temperature, and low ratio of contact resistance to volumetric resistance results in a low operation energy of a PCM-based memory application. Finally, we developed a design strategy for PCMs. New PCMs should be developed by lowering the operation energy E , described as E = κ (1 + C)Δ T /Δ z , where κ is the thermal conductivity of the PCM, Δ T is the melting temperature, C is the ratio of contact resistance to the volumetric resistance, and Δ z is the thickness of the PCM. The present results clarify the relationship between thermal and electrical properties for lowering operation energy ever hidden in previous studies. According to the design strategy, an operation energy in phase change memory application can be decreased to less than 1/100 compared with conventional Ge-Sb-Te compounds. [ABSTRACT FROM AUTHOR]

The proliferation and differentiation of skeletal muscle cells are usually controlled by serum components. Myogenic differentiation is induced by a reduction of serum components in vitro. It has been recently reported that serum contains not only various growth factors with specific actions on the proliferation and differentiation of myogenic cells, but also exogenous exosomes, the function of which is poorly understood in myogenesis. We have found that exosomes in fetal bovine serum are capable of exerting an inhibitive effect on the differentiation of C2C12 myogenic cells in vitro. In this process of inhibition, the downregulation of Tceal5 and Tceal7 genes was observed. Expression of these genes is specifically increased in direct proportion to myogenic differentiation. Loss- or gain- of function studies with Tceal5 and Tceal7 indicated that they have the potential to regulate myogenic differentiation via exosomes in fetal bovine serum. [ABSTRACT FROM AUTHOR]

• Investigation on gas injection during ACAP process is conducted. • Argon provides a better efficiency of Rhodamine B degradation compared to air. • Hydrogen and oxygen-containing radicals are generated in larger amount during argon injection. • Argon dissolves in water that lowers breakdown voltage and improves cavitation treatment. Underwater plasma has been long recognized as a "green" alternative to conventional chemicals in the wastewater treatment processes. However, practical application of underwater plasma is still challenging due to insufficient treatment performance. Recently, we proposed a novel process named ACAP utilizing acoustic cavitation in order to stabilize the plasma generation and to enlarge the plasma processing region. This work continues our investigation regarding the ACAP treatment process focusing on effects of gas injection. Experiments were performed using an ultrasonic installation equipped with a specially designed sonotrode (Diam. 48 mm) operated at a frequency of 20 kHz and acoustic power of 120 W. The results revealed that the degradation efficiency of Rhodamine B, which was used as a model wastewater pollutant, remains almost unchangeable in the case of air injection, but it is doubled when argon is injected into the ACAP reactor. It was found that the argon injection enhances the degradation efficiency significantly even without ultrasound irradiation. Results of additional measurements suggest that the effect of argon is attributed to its ability to yield high temperature during cavitation, comparatively good solubility in water and a better ability to reduce the breakdown voltage in water compared to the air case. [ABSTRACT FROM AUTHOR]

Abstract: A pair of four-armed star and dicyclic 8-shaped poly(tetrahydrofuran)s, poly(THF)s, possessing a perylene diimide group at the core position (Ia and Ib, respectively) were synthesized by means of an electrostatic self-assembly and covalent fixation (ESA–CF) protocol. Mono- and bifunctional poly(THF)s having N-phenylpiperidinium salt end groups accompanying a perylene diimide tetracarboxylate as a counteranion were prepared by the ion-exchange reaction, and the subsequent covalent conversion by reflux in toluene afforded the corresponding core-fluorescent four-armed star and dicyclic 8-shaped poly(THF)s, (Ia and Ib, respectively) for the use of single-molecule fluorescence microscopy measurements. [Copyright &y& Elsevier]

Cavity evolutions in a normalized and tempered martensitic steel (TMS) and two nanostructured ferritic alloys (NFA) under Fe3+ and He+ dual ion beam irradiations (DII) at 500°C and 650°C were characterized. The irradiation conditions encompass a wide range of displacement per atom damage (dpa), He and He/dpa. The 500°C DII produced damage and He levels of ≈10–47dpa and ≈400–2000appm, respectively. Transmission electron microscopy (TEM) showed that DII of a 8Cr TMS, at 500°C to up to 60dpa and 2100appm He, produced a moderate density of non-uniformly distributed cavities with bimodal sizes ranging from ≈1nm He bubbles to ≈20nm faceted voids, and swelling ≈0.44%. In contrast, the same irradiation conditions produced only small ≈1.3nm diameter bubbles and swelling of ≈0.05% in the NFA MA957. Similar bubble distributions were observed in MA957 and a developmental NFA DII at 650°C up to ≈80dpa and ≈3900appm He. These results demonstrate the outstanding He management capability of the oxide nano-features in the NFA. The various data trends are shown as a function of dpa, He, He/dpa and He*dpa. [ABSTRACT FROM AUTHOR]

Unprecedented tetracyclic polymer topologies with spiro- and a bridged-type quatrefoil forms are effectively constructed through an alkyne-azide, click-linking reaction by employing a kyklo-telechelic poly(tetrahydrofuran), poly(THF), precursor having an azide group, obtained through an electrostatic self-assembly and covalent fixation (ESA-CF) process, and complementary tetrafunctional alkyne reagents of either a pentaerythritol derivative or a four-armed star telechelic polymer precursor. [ABSTRACT FROM AUTHOR]

Programmed Death 1 (PD-1) expression by human/simian immunodeficiency virus (HIV/SIV)-specific CD8 T cells has been associated with defective cytokine production and reduced in vitro proliferation capacity. However, the cellular mechanisms that sustain PD-1high virus-specific CD8 T cell responses during chronic infection are unknown. Here, we show that the PD-1high phenotype is associated with accelerated in vivo CD8 T cell turnover in SIV-infected rhesus macaques, especially within the SIVspecific CD8 T cell pool. Mathematical modeling of 5-bromo-2= deoxyuridine (BrdU) labeling dynamics demonstrated a significantly increased generation rate of PD-1high compared to PD-1low CD8 T cells in all memory compartments. Simultaneous analysis of Ki67 and BrdU kinetics revealed a complex in vivo turnover profile whereby only a small fraction of PD-1high cells, but virtually all PD-1low cells, returned to rest after activation. Similar kinetics operated in both chronic and acute SIV infection. Our data suggest that the persistence of PD-1high SIV-specific CD8 T cells in chronic infection is maintained in vivo by a mechanism involving high production coupled with a high disappearance rate. [ABSTRACT FROM AUTHOR]

Abstract: The rotational spectrum of AgSH was observed in a dc discharge absorption cell in the range of 192–312GHz. The AgSH molecule was generated in a reaction of H2S with Ag sputtered from silver sheets lining a stainless-steel cathode. The spectra of 107AgSH, 109AgSH, 107AgSD, and 109AgSD correspond to that of a near-prolate asymmetric top. Molecular constants were determined by least-squares method. A harmonic force field analysis for AgSH combined with its copper analog, CuSH, enabled the determination of the structure of both molecules. AgSH and CuSH molecules possess highly bent structures indicating considerable covalent character. [Copyright &y& Elsevier]

CD4 T follicular helper (TFH) cells interact with and stimulate the generation of antigen-specific B cells. TFH cell interaction with B cells correlates with production of SIV-specific immunoglobulins. However, the fate of TFH cells and their participation in SIV-induced antibody production is not well understood. We investigated the phenotype, function, location, and molecular signature of TFH cells in rhesus macaques. Similar to their human counterparts, TFH cells in rhesus macaques represented a heterogeneous population with respect to cytokine function. In a highly differentiated subpopulation of TFH cells, characterized by CD150lo expression, production of Th1 cytokines was compromised while IL-4 production was augmented, and cells exhibited decreased survival, cycling, and trafficking capacity. TFH cells exhibited a distinct gene profile that was markedly altered by SIV infection. TFH cells were infected by SIV; yet, in some animals, these cells actually accumulated during chronic SIV infection. Generalized immune activation and increased IL-6 production helped drive TFH differentiation during SIV infection. Accumulation of TFH cells was associated with increased frequency of activated germinal center B cells and SIV-specific antibodies. Therefore, chronic SIV does not disturb the ability of TFH cells to help B cell maturation and production of SIV-specific immunoglobulins. [ABSTRACT FROM AUTHOR]

Abstract: The millimeter- and submillimeter-wave spectra of PtS in the state were observed by employing a source-modulated microwave spectrometer. The PtS radical was generated in a free space cell by using a dc glow plasma of H2S and Ar. Platinum atoms were supplied from a small piece of platinum sheet lining the inner surface of a stainless steel cathode by the sputtering reaction. Rotational transitions were recorded for four dominant isotopomers, 194PtS, 195PtS, 196PtS, and 198PtS in the ground state, and the spectroscopic constants for each isotopomer were determined using a Hund’s case (c) Hamiltonian. The lower limit of the energy separation is estimated from a Hund’s case (a) analysis. [Copyright &y& Elsevier]

In our previous study, a novel method combining underwater high-voltage plasma discharge with acoustic cavitation (ACAP) was developed and implemented using rhodamine B (RhB) as a model organic pollutant. Results revealed that injecting argon gas into the ACAP reactor positively influences RhB decomposition efficiency, but there is still further potential for improvement. The aim of this study was therefore to further improve the efficiency of the ACAP process through Fenton reactions. Two options for ferrous ion supply were considered: the addition of FeCl2 or the dissolution of iron from ACAP reactor steel parts into the RhB-containing solution. The results revealed that the degradation efficiency is increased by 20% due to the Fenton reactions when the concentration of ferrous ions reaches an optimal value. Lower pH was found to be desirable for the effect of Fenton reactions. Based on measurements using high performance liquid chromatography, a plausible mechanism of RhB degradation by the ACAP process assisted by Fenton reactions is additionally proposed and discussed. [ABSTRACT FROM AUTHOR]

Abstract: Ongoing challenges in topological polymer chemistry are reviewed. In particular, we focus on recent developments in an “electrostatic self-assembly and covalent fixation (ESA–CF)” process in conjunction with effective linking/cleaving chemistry including a metathesis process and an alkyne–azide click reaction. A variety of novel cyclic polymers having specific functional groups and unprecedented multicyclic macromolecular topologies have been realized by combining intriguing synthetic protocols. [Copyright &y& Elsevier]

Summary: In skeletal muscle differentiation, muscle-specific genes are regulated by two groups of transcription factors, the MyoD and MEF2 families, which work together to drive the differentiation process. Here, we show that ERK5 regulates muscle cell fusion through Klf transcription factors. The inhibition of ERK5 activity suppresses muscle cell fusion with minimal effects on the expression of MyoD, MEF2, and their target genes. Promoter analysis coupled to microarray assay reveals that Klf-binding motifs are highly enriched in the promoter regions of ERK5-dependent upregulated genes. Remarkably, Klf2 and Klf4 expression are also upregulated during differentiation in an ERK5-dependent manner, and knockdown of Klf2 or Klf4 specifically suppresses muscle cell fusion. Moreover, we show that Sp1 transcription factor links ERK5 to Klf2/4, and that nephronectin, a Klf transcriptional target, is involved in muscle cell fusion. Therefore, an ERK5/Sp1/Klf module plays a key role in the fusion process during skeletal muscle differentiation. [Copyright &y& Elsevier]

Background: The differentiation of CD8+T lymphocytes following priming of naïve cells is central in the establishment of the adaptive immune response. Yet, the molecular events underlying this process are not fully understood. MicroRNAs have been recently shown to play a key role in the regulation of haematopoiesis in mouse, but their implication in peripheral lymphocyte differentiation in humans remains largely unknown. Methods: In order to explore the potential implication of microRNAs in CD8+T cell differentiation in humans, microRNA expression profiles were analysed using microarrays and quantitative PCR in several human CD8+T cell subsets defining the major steps of the T cell differentiation pathway. Results: We found expression of a limited set of microRNAs, including the miR-17∼92 cluster. Moreover, we reveal the existence of differentiation-associated regulation of specific microRNAs. When compared to naive cells, miR-21 and miR-155 were indeed found upregulated upon differentiation to effector cells, while expression of the miR- 17∼92 cluster tended to concomitantly decrease. Conclusions: This study establishes for the first time in a large panel of individuals the existence of differentiation associated regulation of microRNA expression in human CD8+T lymphocytes in vivo, which is likely to impact on specific cellular functions. [ABSTRACT FROM AUTHOR]

Osteoid osteoma of the spine is a relatively rare bone-forming tumor. Pain that is worse at night and relieved by aspirin and muscle contracture are the most characteristic symptoms of spinal osteoid osteoma. Although radicular pain occasionally occurs in spinal osteoid osteoma, spinal cord and nerve root compression is absent in most cases. Although radicular pain appears to be associated with tumorous inflammation, there have been no presentations of histological findings of inflammation around the nerve root. We present here two rare cases of spinal osteoid osteoma causing radiculopathy and the first histological evidence of tumorous inflammation as a cause of radiculopathy in osteoid osteoma near the intervertebral foramen. [ABSTRACT FROM AUTHOR]

Background: In response to viral infection, the innate immune system recognizes viral nucleic acids and then induces production of proinflammatory cytokines and type I interferons (IFNs). Toll-like receptor 7 (TLR7) and TLR9 detect viral RNA and DNA, respectively, in endosomal compartments, leading to the activation of nuclear factor kB (NF-κB) and IFN regulatory factors (IRFs) in plasmacytoid dendritic cells. During such TLR signaling, TNF receptor-associated factor 6 (TRAF6) is essential for the activation of NF-κB and the production of type I IFN. In contrast, RIG-like helicases (RLHs), cytosolic RNA sensors, are indispensable for antiviral responses in conventional dendritic cells, macrophages, and fibroblasts. However, the contribution of TRAF6 to the detection of cytosolic viral nucleic acids has been controversial, and the involvement of TRAF6 in IRF activation has not been adequately addressed. Principal Findings: Here we first show that TRAF6 plays a critical role in RLH signaling. The absence of TRAF6 resulted in enhanced viral replication and a significant reduction in the production of IL-6 and type I IFNs after infection with RNA virus. Activation of NF-κB and IRF7, but not that of IRF3, was significantly impaired during RLH signaling in the absence of TRAF6. TGFb-activated kinase 1 (TAK1) and MEKK3, whose activation by TRAF6 during TLR signaling is involved in NF-κB activation, were not essential for RLH-mediated NF-κB activation. We also demonstrate that TRAF6-deficiency impaired cytosolic DNAinduced antiviral responses, and this impairment was due to defective activation of NF-κB and IRF7. Conclusions/Significance: Thus, TRAF6 mediates antiviral responses triggered by cytosolic viral DNA and RNA in a way that differs from that associated with TLR signaling. Given its essential role in signaling by various receptors involved in the acquired immune system, TRAF6 represents a key molecule in innate and antigen-specific immune responses against viral infection. [ABSTRACT FROM AUTHOR]

Dietary restriction is the most effective and reproducible intervention to extend lifespan in divergent species. In mammals, two regimens of dietary restriction, intermittent fasting (IF) and chronic caloric restriction, have proven to extend lifespan and reduce the incidence of age-related disorders. An important characteristic of IF is that it can increase lifespan even when there is little or no overall decrease in calorie intake. The molecular mechanisms underlying IF-induced longevity, however, remain largely unknown. Here we establish an IF regimen that effectively extends the lifespan of Caenorhabditis elegans, and show that the low molecular weight GTPase RHEB-1 has a dual role in lifespan regulation; RHEB-1 is required for the IF-induced longevity, whereas inhibition of RHEB-1 mimics the caloric-restriction effects. RHEB-1 exerts its effects in part by the insulin/insulin growth factor (IGF)-like signalling effector DAF-16 in IF. Our analyses demonstrate that most fasting-induced upregulated genes require RHEB-1 function for their induction, and that RHEB-1 and TOR signalling are required for the fasting-induced downregulation of an insulin-like peptide, INS-7. These findings identify the essential role of signalling by RHEB-1 in IF-induced longevity and gene expression changes, and suggest a molecular link between the IF-induced longevity and the insulin/IGF-like signalling pathway. [ABSTRACT FROM AUTHOR]

Abstract: Dendritic cells (DCs) are professional antigen-presenting cells that possess a unique capacity to cross-present exogenous antigens efficiently to CD8+ T cells. We previously demonstrated that monocyte-derived DCs (MDDCs) pulsed with yeast-derived HIV-1 Gag virus-like particles (VLPs) were able to activate Gag-specific CD8+ T cells from HIV-1-infected individuals. Yeast VLPs are abundantly mannosylated (high-mannose type: HmVLPs) and are highly immunogenic. Because lectin receptors are shown to negatively regulate Th1 responses, we investigated the relationship between VLP mannosylation level and MDDC cross-presentation activity. Poorly mannosylated VLPs (low-mannose type: LmVLPs) were prepared using a yeast mnn9 mutant strain that lacks a core mannosylation enzyme. We found that MDDCs pulsed with LmVLPs activated Gag-specific T cells more strongly than those pulsed with HmVLPs. However, MDDCs showed similar antigen uptake and intracellular transport of both types of VLPs. Interestingly, LmVLPs induced IL-12 production slightly more than HmVLPs (yet statistically significant). Furthermore, the level of LPS-induced IL-10 production was enhanced by pulsing with HmVLPs, but not with LmVLPs. These results indicate that lectin receptors recognizing mannose may influence the Th1/Th2 balance of the immune response, resulting in reduced efficiency of CD8+ T cell activation by a heavily mannosylated antigen presented by DCs. [Copyright &y& Elsevier]

Dendritic cells (DCs) are essential antigen-presenting cells for the induction of T cell immunity against HIV. On the other hand, due to the susceptibility of DCs to HIV infection, virus replication is strongly enhanced in DC-T cell interaction via an immunological synapse formed during the antigen presentation process. When HIV-1 is isolated from individuals newly infected with the mixture of R5 and X4 variants, R5 is predominant, irrespective of the route of infection. Because the early massive HIV-1 replication occurs in activated T cells and such T-cell activation is induced by antigen presentation, we postulated that the selective expansion of R5 may largely occur at the level of DC-T cell interaction. Thus, the immunological synapse serves as an infectious synapse through which the virus can be disseminated in vivo. We used fluorescent recombinant X4 and R5 HIV-1 consisting of a common HIV-1 genome structure with distinct envelopes, which allowed us to discriminate the HIV-1 transmitted from DCs infected with the two virus mixtures to antigen-specific CD4+ T cells by flow cytometry. We clearly show that the selective expansion of R5 over X4 HIV-1 did occur, which was determined at an early entry step by the activation status of the CD4+ T cells receiving virus from DCs, but not by virus entry efficiency or productivity in DCs. Our results imply a promising strategy for the efficient control of HIV infection. [ABSTRACT FROM AUTHOR]