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We present a joint analysis of the galaxy S04590 at z = 8.496 based on NIRSpec, NIRCam, and NIRISS observations obtained as part of the Early Release Observations program of the James Webb Space Telescope (JWST) and the far-infrared [C ii] 158 mu m emission line detected by dedicated Atacama Large Millimeter/submillimeter Array (ALMA) observations. We determine the physical properties of S04590 from modeling of the spectral energy distribution (SED) and through the redshifted optical nebular emission lines detected with JWST/NIRSpec. The best-fit SED model reveals a low-mass (M-? = 10(7.2)-10(8) M-?) galaxy with a low oxygen abundance of derived from the strong nebular and auroral emission lines. Assuming that [C ii] effectively traces the interstellar medium, we estimate the total gas mass of the galaxy to be M-gas = (8.0 +/- 4.0) x 10(8) M-? based on the luminosity and spatial extent of [C ii]. This yields an exceptionally high gas fraction, f(gas) = M-gas/(M-gas + M-?) ? 90%, though one still consistent with the range expected for low metallicity. We further derive the metal mass of the galaxy based on the gas mass and gas-phase metallicity, which we find to be consistent with the expected metal production from Type II supernovae. Finally, we make the first constraints on the dust-to-gas (DTG) and dust-to-metal (DTM) ratios of galaxies in the epoch of reionization at z ? 6, showing overall low mass ratios of logDTG < -3.8 and logDTM < -0.5, though they are consistent with established scaling relations and in particular with those of the local metal-poor galaxy I Zwicky 18. Our analysis highlights the synergy between ALMA and JWST in characterizing the gas, metal, and stellar content of the first generation of galaxies., Carlsberg Foundation Reintegration Fellowship CF21-0103, VILLUM FONDEN through the Villum Experiment Programme, Carlsberg Foundation 17H06130, Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research (KAKENHI) NAS 5-03127, NAOJ ALMA Scientific Research, Association of Universities for Research in Astronomy, Inc., under NASA 2017-06B, Danmarks Grundforskningsfond CF20-0534 140

We present a set of multiwavelength mosaics and photometric catalogs in the Atacama Large Millimeter/ submillimeter Array (ALMA) lensing cluster survey fields. The catalogs were built by the reprocessing of archival data from the Complete Hubble Archive for Galaxy Evolution compilation, taken by the Hubble Space Telescope (HST) in the Reionization Lensing Cluster Survey, Cluster Lensing And Supernova survey with Hubble, and Hubble Frontier Fields. Additionally, we have reconstructed the Spitzer Infrared Array Camera 3.6 and 4.5 μm mosaics, by utilizing all the available archival IPAC Infrared Science Archive/Spitzer Heritage Archive exposures. To alleviate the effect of blending in such a crowded region, we have modeled the Spitzer photometry by convolving the HST detection image with the Spitzer point-spread function using the novel GOLFIR software. The final catalogs contain 218,000 sources, covering a combined area of 690 arcmin2, a factor of ∼2 improvement over the currently existing photometry. A large number of detected sources is a result of reprocessing of all available and sometimes deeper exposures, in conjunction with a combined optical–near-IR detection strategy. These data will serve as an important tool in aiding the search of the submillimeter galaxies in future ALMA surveys, as well as follow-ups of the HST dark and high-z sources with JWST. Coupled with the available HST photometry, the addition of the 3.6 and 4.5 μm bands will allow us to place a better constraint on the photometric redshifts and stellar masses of these objects, thus giving us an opportunity to identify high-redshift candidates for spectroscopic follow-ups and to answer the important questions regarding the Epoch of Reionization and formation of the first galaxies. The mosaics, photometric catalogs, and the best-fit physical properties are publicly available at https:// github.com/dawn-cph/alcs-clusters., Danmarks Grundforskningsfond 140, Villum Fonden 13160 37440, Carlsberg Foundation CF18-0388, European Commission 896225 European Research Council (ERC) European Commission 648179, Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research (KAKENHI) JP17H06130, NAOJ ALMA Scientific Research 2017-06B, NRAO Student Observing Support (SOS) SOSPA7-022, Beatriz Galindo senior fellowship BG20/00224, Ministry of Science and Innovation, Spain (MICINN) PID2020-114414GB-100 PID2020-113689GB-I00, Junta de Andalucia P20_00334 FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades -FQM-510-UGR20, RELICS Treasury Program GO 14096, National Aeronautics & Space Administration (NASA) NAS5-26555

Background Pericoronary adipose tissue (PCAT) quantified from coronary computed tomography angiography (CCTA) is a new predictor of CT-derived high-risk plaque (HRP) and adverse cardiac events. There has been no report investigating the method to assess PCAT from non-contrast CT so far. In this present study, we developed a brand-new method to quantify the value of PCAT from electrocardiogram (ECG)-gated non-contrast CT (NC-PCAT). Purpose To develop a brand-new method to quantify NC-PCAT accurately, and evaluate its prognostic value. Methods We retrospectively studied two independent cohorts of patients undergoing CCTA and ECG-gated non-contrast CT for clinical indication of coronary artery disease (CAD). For former cohort of consecutive 300 patients, we validated the agreement between the NC-PCAT and PCAT, and evaluated the association between NC-PCAT and the prevalence of HRP. For latter cohort of consecutive 333 patients, we dichotomized them into two groups with median NC-PCAT, and assessed the prognostic value of NC-PCAT. To quantify NC-PCAT, we placed 15x15mm region of interest at epicardial fat tissue dorsally adjacent to right coronary ostium in axial slice of ECG-gated non-contrast CT, and defined NC-PCAT as the mean CT value of each 1x1mm pixel there. PCAT was quantified from CCTA using conventional method as described in former researches. Primary endpoint was defined as major adverse cardiac events (MACE), composite of all-cause death and non-fatal myocardial infarction. HRP was defined as coronary artery plaque which has two or more following features; positive remodeling, low attenuation, spotty calcification, and napkin-ring sign. Results NC-PCAT was well-correlated with PCAT (r=0.68, p Conclusions There was a positive correlation between NC-PCAT and PCAT. Higher NC-PCAT is significantly associated with not only the prevalence of HRP, but also worse clinical outcome. Funding Acknowledgement Type of funding sources: None.

We present the average [C ii] 158 μm emission line sizes of UV-bright star-forming galaxies at z ∼ 7. Our results are derived from a stacking analysis of [C ii] 158 μm emission lines and dust continua observed by the Atacama Large Millimeter/submillimeter Array (ALMA), taking advantage of the large program Reionization Era Bright Emission Line Survey. We find that the average [C ii] emission at z ∼ 7 has an effective radius r e of 2.2 ± 0.2 kpc. It is ≳2× larger than the dust continuum and the rest-frame UV emission, in agreement with recently reported measurements for z ≲ 6 galaxies. Additionally, we compared the average [C ii] size with 4 < z < 6 galaxies observed by the ALMA Large Program to INvestigate [C ii] at Early times (ALPINE). By analyzing [C ii] sizes of 4 < z < 6 galaxies in two redshift bins, we find an average [C ii] size of r e = 2.2 ± 0.2 kpc and r e = 2.5 ± 0.2 kpc for z ∼ 5.5 and z ∼ 4.5 galaxies, respectively. These measurements show that star-forming galaxies, on average, show no evolution in the size of the [C ii] 158 μm emitting regions at redshift between z ∼ 7 and z ∼ 4. This finding suggests that the star-forming galaxies could be morphologically dominated by gas over a wide redshift range.

Here, we describes a method for high-throughput counting and superresolution mapping of surface proteins on exosomes, using a combination of a single-molecule sensitive flow technique and an adaptive superresolution imaging method. Exosomes stained with membrane dye and dye-conjugated antibodies were analyzed using a microfluidic platform at a flow rate of 100 exosome/s to determine size and protein copy number. Superresolution mapping was performed with exosomes labeled with novel transistor-like, semiconducting polymer dots (Pdots), which exhibit spontaneous blinking with

Panitumumab, a therapeutic agent for unresectable advanced/recurrent colorectal cancer, is a human IgG2 monoclonal antibody that binds to and inhibits the activity of the epidermal growth factor receptor (EGFR). The onset of hypomagnesemia is a known side effect of anti-EGFR inhibitors, including panitumumab, and it is thought that inhibition of reabsorption of Mg in renal tubules is one of the causes. In addition, recent reports have shown that long-term administration of proton pump inhibitors (PPIs) reduces serum magnesium levels. Therefore, in this study, 102 patients who received oral PPIs treated with panitumumab were classified into a PPI combination group and a PPI non-combination group, and the effect of PPIs on the development of grade 2 or higher hypomagnesemia was investigated. The incidence of hypomagnesemia in the PPI combination group (46.9%, 15/32) was higher than that in the PPI non-combination group (25.7%, 18/70). A comparison of the backgrounds of the two groups of patients showed a significant difference in serum albumin levels. PPI administration was significantly associated with panitumumab-induced hypomagnesemia development when adjusted for known risk factors, serum albumin level, renal function, and oral magnesium oxide tablets in Cox proportional hazards regression analysis (hazard ratio 2.09; 95% confidence interval 1.03-4.22

The [CII] 158$~\mu$m emission line represents so far one of the most profitable tools for the investigation of the high-redshift galaxies in the early Universe. Being one of the brightest cooling lines in the rest-frame far-infrared regime of star-forming galaxies, it has been successfully exploited as a tracer of star-formation rate (SFR) in local sources. The picture is more complex at higher redshifts, where its usability in this context is still under investigation. Recent results from the ALMA Large Program to INvestigate [CII] at Early times (ALPINE) survey suggest that there is no (or weak) evolution of the L$\mathrm{_{[CII]}}$-SFR relation up to $z\sim6$ but their reliability is hampered by the presence of a large population of [CII] non-detected galaxies. In this work, we characterize the population of [CII] non-detections in ALPINE. By stacking their ALMA spectra, we obtain a signal detected at $\sim5.1\sigma$, resulting in a [CII] luminosity of $\mathrm{log(L_\mathrm{[CII]}}/\mathrm{L_{\odot}})$ $\sim7.8$. When combining this value with those from the [CII] detections, we find a $\mathrm{L_{[CII]}}$-SFR relation with a slope $b=1.14\pm0.11$, in agreement within the uncertainties both with the linear relation found in the local Universe, and with the previous findings from ALPINE at $z\sim5$. This suggests that the [CII] line can be considered a good tracer of star formation up to the distant Universe. Finally, we show that the galaxies of our sample that most deviate from the observed L$_\mathrm{[CII]}$-SFR relation could suffer from a less precise redshift estimation, perhaps artificially reducing their [CII] luminosity. In this respect, we claim that there is no evidence in favour of a deficit of [CII] content in high-z galaxies, in contrast with earlier studies., Comment: Accepted for publication in A&A. 10 pages, 5 figures

Getters are among the key functional components in the tritium-producing burnable absorber rods (TPBARs) of light water reactors (LWRs) and are used to capture the released tritium gas. They are nickel-plated zircaloy-4 tubes that, upon exposure to irradiation or tritium in the light water reactors, undergo alteration in structure, chemical composition, and chemistry. Understanding the radial tritium distribution is key to gaining insight into the evolution of new chemistry upon irradiation to predict getter performance. The holy grail is to develop a method akin to selectively peeling off the layers of an onion in an effort to get a radial map of elements and particularly tritium across the getter. Toward this goal, the overall aim of this work is to establish a correlative technique that can be used to determine radial tritium distribution across getters. To this end, this work specifically focuses on the validation of a correlative method for controlled radial dissolution of nickel-plated getters. Here, pristine getters as well as getters loaded with different mass ratios of hydrogen and deuterium are used as the nonradioactive surrogates of tritium, the idea being that the methodology can be readily extended to tritiated getter components. Here, the surface nickel layers as well as the bulk zirconium layers are sequentially dissolved in a controlled, uniform way using voltage-assisted electrochemical dissolution techniques. The dissolution is complemented by periodic elemental analysis of the electrolyte solution during and post dissolution. This is complemented by microscopic analyses on the exposed surfaces to provide a correlative technique for a complete picture of the radial distribution of various elements across the getter.

Rapid, selective, and in situ detection of pertechnetate (TcO4–) in multicomponent matrices consisting of interfering anions such as the ubiquitous NO3– and Cl– or the isostructural CrO42– is chall...

Kidney international 102(1), 160-172 (2022). doi:10.1016/j.kint.2022.02.042, Published by Elsevier, New York, NY

Incorporating radioactive Tc-99 into glass during vitrification of low-activity waste (LAW) at the U.S. Department of Energy's Hanford Site is a scientific challenge. Previous studies have suggested that the presence of sulfate salts in the melt hinder the incorporation of Re, a non-radioactive surrogate for Tc-99, into nuclear waste glass. In this study, we assessed the capability of a Ba Sn composite material to sequester sulfate during vitrification of AN-102 LAW feed and the resulting effects on Re retention in the glass. We also investigated a feed in which the initial soluble sulfate source in the simulated LAW (Na2SO4) was replaced with insoluble BaSO4. The Ba Sn composite-treated feed and BaSO4-substitute feed were compared to a control, AN-102 baseline. The feeds were prepared and then heated to temperatures ranging from 400 to 1000 °C at a 5 °C/min rate and then air-quenched to room temperature. The heated samples and dried feeds were leached in deionized water. The solutions from the leach test were analyzed by inductively coupled plasma optical emission spectroscopy to determine the amount of soluble sulfate as a function of temperature, and the resulting solids were analyzed for Re retention. Although the Ba Sn composite material successfully sequestered sulfate in the as-prepared LAW feed, heating to 400 °C resulted in most of the sulfate partitioning to a soluble salt phase. By 700 °C, sulfate partitioning in the composite-treated feed was identical to that of the baseline feed. Throughout the entire temperature range, the BaSO4-substitute feed behaved similarly to the composite-treated feed. The results of the study show that sequestering sulfate in a BaSO4 phase is not effective for Re retention as the sulfate salt behavior was nearly identical in the three feeds at ≥700 °C. The fraction of Re retained in the glass at 1000 °C varied from 39.4 to 46.6% for the three feeds, which is shown to be a statistically insignificant difference.

Rapid and sensitive detection and quantification of trace and ultra-trace analytes is critical to environmental remediation, analytical chemistry and defense from chemical and biological contaminants. Though affinity based electrochemical sensors have gained immense popularity, they frequently do not meet the requirements of desired sensitivity and detection limits. Here, we demonstrate a complementary luminescence mode that can significantly enhance sensitivity of impedance or voltammetric electrochemical sensors. Our methodology involves using a redox probe, whose luminescence properties change upon changing the oxidation state. By tailoring the system such that these luminescence changes can be correlated with the capture of target analytes, we are able to significantly lower the detection limit and improve the efficiency of detection compared to the electrochemical modes alone. Our proof-of-concept demonstration, using a model system designed for Ca2+ capture, illustrated that the luminescent mode allowed us to lower the limits of detection by three-orders of magnitude compared to the impedance or voltammetric modes alone without requiring any modification of electrode design or cell configuration. Further, the linear ranges of detection are 10−8 to 10−3 M in the voltammetry mode, 10−8 to 10−5 M in the impedance mode and 2.5 × 10−11 to 10−7 M in the luminescent mode, providing a large range of operational flexibility.

Extracellular vesicles (EVs) are membranous particles released by most cells in our body, and which are involved in many cell-to-cell signaling processes. Given the nanometer sizes and heterogeneity of EVs, highly sensitive methods with single-molecule resolution are fundamental to investigating their biophysical properties. Here, we demonstrate the sizing of extracellular vesicles (EVs) using a fluorescence-based flow analyzer with single-molecule sensitivity. Using a dye that selectively partitions into the vesicle’s membrane, we show that the fluorescence intensity of a vesicle is proportional to its diameter. We discuss constraints in sample preparation which are inherent to sizing nanoscale vesicles with a fluorescent membrane dye, and propose several guidelines to improve data consistency. After optimizing staining conditions, we were able to measure the size of vesicles in the range ~35–300 nm, covering the spectrum of EV sizes. Lastly, we developed a method to correct the signal intensity from each vesicle based on its travelling speed inside the microfluidic channel, by operating at a high sampling rate (10 kHz) and measuring the time required for the particle to cross the laser beam. Using this correction, we obtained a 3-fold greater accuracy in EV sizing, with a precision of ±15–25%.

Cervical cancer is the fourth-leading cause of cancer deaths among women worldwide and most cases occur in developing countries. Detection of high-risk (HR) HPV, the etiologic agent of cervical cancer, is a primary screening method for cervical cancer. However, the current gold standard for HPV detection, real-time PCR, is expensive, time-consuming, and instrumentation-intensive. A rapid, low-cost HPV detection method is needed for cervical cancer screening in low-resource settings. We previously developed a digital loop-mediated isothermal amplification (dLAMP) assay for rapid, quantitative detection of nucleic acids without the need for thermocycling. This assay employs a microfluidic self-digitization chip to automatically digitize a sample into an array of nanoliter wells in a simple assay format. Here we evaluate the dLAMP assay and self-digitization chip for detection of the commonly tested 14 high-risk HPVs in clinical samples. The dLAMP platform provided reliable genotyping and quantitative detection of the 14 high-risk HPVs with high sensitivity, demonstrating its potential for simple, rapid, and low-cost diagnosis of HPV infection.

Contains fulltext : 225968.pdf (Publisher’s version ) (Closed access) Immunosuppression in IgA nephropathy (IgAN) should be reserved for patients at high-risk of disease progression, which KDIGO guidelines determine based solely on proteinuria 1g or more/day. To investigate if treatment decisions can be more accurately accomplished using individualized risk from the International IgAN Prediction Tool, we simulated allocation of a hypothetical immunosuppression therapy in an international cohort of adults with IgAN. Two decision rules for treatment were applied based on proteinuria of 1g or more/day or predicted risk from the Prediction Tool above a threshold probability. An appropriate decision was defined as immunosuppression allocated to patients experiencing the primary outcome (50% decline in eGFR or ESKD) and withheld otherwise. The net benefit and net reduction in treatment are the proportion of patients appropriately allocated to receive or withhold immunosuppression, adjusted for the harm from inappropriate decisions, calculated for all threshold probabilities from 0-100%. Of 3299 patients followed for 5.1 years, 522 (15.8%) experienced the primary outcome. Treatment allocation based solely on proteinuria of 1g or more/day had a negative net benefit (was harmful) because immunosuppression was increasingly allocated to patients without progressive disease. Compared to using proteinuria, treatment allocation using the Prediction Tool had a larger net benefit up to 23.4% (95% confidence interval 21.5-25.2%) and a larger net reduction in treatment up to 35.1% (32.3-37.8%). Thus, allocation of immunosuppression to high-risk patients with IgAN can be substantially improved using the Prediction Tool compared to using proteinuria.

The exactly-solvable Kitaev model of two-dimensional honeycomb magnet leads to a quantum spin liquid (QSL) characterized by Majorana fermions, relevant for fault-tolerant topological quantum computations. In the high-field paramagnetic state of $\alpha$-RuCl3, half-integer quantization of thermal Hall conductivity has been reported as a signature of edge current, but the bulk nature of this state remains elusive. Here, from high-resolution heat capacity measurements under in-plane field rotation, we find strongly angle-dependent low-energy excitations in bulk $\alpha$-RuCl3. The excitation gap has a sextuple node structure, and the gap amplitude increases with field, exactly as expected for itinerant Majorana fermions in the Kitaev model. Our thermodynamic results are fully linked with the transport quantization properties, providing the first demonstration of the bulk-edge correspondence in a Kitaev QSL. Moreover, at higher fields where the quantum thermal Hall effect vanishes, we find the possible emergence of a novel nematic QSL state with two-fold rotational symmetry., Comment: This is the submitted version. Revisions have been made and a revised version with extended Supplementary Information will be published in Nature Physics

Isolation and analysis of circulating tumor cells (CTCs) from the blood of patients at risk of metastatic cancers is a promising approach to improving cancer treatment. However, CTC isolation is difficult due to low CTC abundance and heterogeneity. Previously, we reported an ensemble-decision aliquot ranking (eDAR) platform for the rare cell and CTC isolation with high throughput, greater than 90% recovery, and high sensitivity, allowing detection of low surface antigen-expressing cells linked to metastasis. Here we demonstrate a sequential eDAR platform capable of isolating rare cells from whole blood with high purity. This improvement in purity is achieved by using a sequential sorting and flow stretching design in which whole blood is sorted and fluid elements are stretched using herringbone features and the parabolic flow profile being sorted a second time. This platform can be used to collect single CTCs in a multiwell plate for downstream analysis.

Selective sequestration of sulfate (SO42−) in the form of barite (BaSO4) from alkaline solutions of high ionic strength containing carbonate is problematic due to the preferential formation of BaCO3. Incorporation of sulfate into the insoluble and thermally stable BaSO4 phase can potentially benefit radioactive waste processing by reducing operational challenges and suppressing volatilization of other waste components such as technetium-99. To enhance selectivity of SO42− sequestration, a series of Ba–Sn nanocomposite materials was prepared using simple hydrothermal synthesis from different Sn(II) and Sn(IV) precursors. Structural characterization indicated that all obtained products predominantly contained BaSn(OH)6 and Ba2SnO2(OH)4·10H2O nanocrystalline phases which were disrupted upon exposure to SO42− due to formation of BaSO4. Performance of the Ba–Sn materials was tested using complex alkaline solutions simulating radioactive waste containing 0.094 M SO42− and 0.5 M CO32− among other constituents. About 54–66% of SO42− was converted to BaSO4 when a quantity of Ba–Sn material containing approximately a stoichiometric amount of Ba2+ relative to SO42− was used. In comparison, previous studies indicate negligible BaSO4 formation under similar conditions when a simple Ba2+ salt is used. This improvement is attributed to the selective replacement of the stannate by SO42−. Thermal stability of the sulfate-loaded product material up to 1100 °C was demonstrated. The obtained materials promise a convenient and economical option for the selective sequestration or removal of SO42− from complex carbonate containing solutions.

Quantitative microscopy is needed to understand reactions or phenomena carried out by biological molecules such as enzymes, receptors, and membrane-localized proteins. Counting the biomolecules of interest in single organelles or cellular compartments is critical in these approaches. In this brief perspective, we focus on the development of quantitative fluorescence microscopies that measure the precise copy numbers of proteins in cellular organelles or purified samples. We introduce recent improvements in quantitative microscopies to overcome undercounting or overcounting errors in certain conditions. We conclude by discussing biological applications.

A Neutron/Gamma-ray combined inspection system for hidden special nuclear materials (SNMs) in cargo containers has been developed under a program of Japan Science and Technology Agency in Japan. This inspection system consists of an active neutron-detection system for fast screening and a laser Compton backscattering gamma-ray source in coupling with nuclear resonance fluorescence (NRF) method for precise inspection. The inertial electrostatic confinement fusion device has been adopted as a neutron source and two neutron-detection methods, delayed neutron noise analysis method and high-energy neutron-detection method, have been developed to realize the fast screening system. The prototype system has been constructed and tested in the Reactor Research Institute, Kyoto University. For the generation of the laser Compton backscattering gamma-ray beam, a race track microtron accelerator has been used to reduce the size of the system. For the NRF measurement, an array of LaBr3(Ce) scintillation detectors has been adopted to realize a low-cost detection system. The prototype of the gamma-ray system has been demonstrated in the Kansai Photon Science Institute, National Institutes for Quantum and Radiological Science and Technology. By using numerical simulations based on the data taken from these prototype systems and the inspection-flow, the system designed by this program can detect 1 kg of highly enriched 235U (HEU) hidden in an empty 20-ft container within several minutes.

We present a method to determine the concentration of nucleic acids in a sample by partitioning it into droplets with a nonuniform volume distribution. This digital PCR method requires no special equipment for partitioning, unlike other methods that require nearly identical volumes. Droplets are generated by vortexing a sample in an immiscible oil to create an emulsion. PCR is performed, and droplets in the emulsion are imaged. Droplets with one or more copies of a nucleic acid are identified, and the nucleic acid concentration of the sample is determined. Numerical simulations of droplet distributions were used to estimate measurement error and dynamic range and to examine the effects of the total volume of droplets imaged and the shape of the droplet size distribution on measurement accuracy. The ability of the method to resolve 1.5- and 3-fold differences in concentration was assessed by using simulations of statistical power. The method was validated experimentally; droplet shrinkage and fusion during amplification were also assessed experimentally and showed negligible effects on measured concentration.

The purpose of this study is to extend the three-dimensional (3-D) passive dynamic biped walker to a 3-D dynamic biped walker, i.e., a walker that can walk on a horizontal surface based on a passive dynamic walking. A new prototype of 3-D biped walker called RW04, which has telescopic knee joints, was developed and its ability for walking was validated through some experiments. A sinusoidal oscillation, which is regarded as a central pattern generator with no sensory feedback, was provided to the knee joints to achieve the biped walking. The results showed that the biped gait of RW04 was possible only via a sinusoidal oscillation of the knee joint. Moreover, the 3-D dynamic walking gait via frequency response and zero moment point (ZMP) trajectory was also analyzed. The biped locomotion had a resonance, i.e., the frequency matched the natural frequency of the locomotion in the gain property. An “8” shaped ZMP trajectory was observed, which was found to be similar to that of the human gait. However, the simple sinusoidal oscillation had limitations such as stride reduction or discontinuation by phase difference. Therefore, in future work, more adaptable control strategy such as a sensory feedback using ZMP should be provided.

Zircaloy-4 (Zr-4) based liners and getters are the principle functional components of Tritium-Producing Burnable Absorber Rods (TPBARs) in light water nuclear reactors where they reduce tritiated water into tritium gas. Upon tritium exposure, zirconium tritide is formed, which changes the chemical composition, structure and morphology of these materials. Their thermodynamic properties are affected by (i) the hydride phase identity, (ii) radial and spatial tritide/hydride (T/H) distribution, and (iii) the changes in structure and morphology of the material upon T/H-migration, and their comprehensive knowledge is needed to predict performance of these materials. This work demonstrates that controlled potential electrochemistry techniques to be highly efficient for controlled oxidative radial dissolution of Zr-4 based liners (both unloaded and loaded with hydride/deuteride as chemical surrogates for tritium). The electrodissolution is further combined with microscopic techniques to accurately determine the distribution of hydride phases. This work demonstrates a reliable technique for radially etching the liners after irradiation to provide insight into the radial and spatial distribution of tritium within the TPBAR, improving the fundamental understanding of tritium transport and providing a basis for validating predictive models.

We describe here a flow platform for quantifying the number of biomolecules on individual fluorescent nanoparticles. The platform combines line-confocal fluorescence detection with near nanoscale channels (1–2 µm in width and height) to achieve high single-molecule detection sensitivity and throughput. The number of biomolecules present on each nanoparticle was determined by deconvolving the fluorescence intensity distribution of single-nanoparticle-biomolecule complexes with the intensity distribution of single biomolecules. We demonstrate this approach by quantifying the number of streptavidins on individual semiconducting polymer dots (Pdots); streptavidin was rendered fluorescent using biotin-Alexa647. This flow platform has high throughput (hundreds to thousands of nanoparticles detected per second) and requires minute amounts of sample (~ 5 µL at a dilute concentration of 10 pM). This measurement method is an additional tool for characterizing synthetic or biological nanoparticles.

Dust-enshrouded, starbursting, submillimeter galaxies (SMGs) at $z \geq 3$ have been proposed as progenitors of $z \geq 2$ compact quiescent galaxies (cQGs). To test this connection, we present a detailed spatially resolved study of the stars, dust and stellar mass in a sample of six submillimeter-bright starburst galaxies at $z \sim 4.5$. The stellar UV emission probed by HST is extended, irregular and shows evidence of multiple components. Informed by HST, we deblend Spitzer/IRAC data at rest-frame optical finding that the systems are undergoing minor mergers, with a typical stellar mass ratio of 1:6.5. The FIR dust continuum emission traced by ALMA locates the bulk of star formation in extremely compact regions (median $r_{\rm{e}} = 0.70 \pm 0.29$ kpc) and it is in all cases associated with the most massive component of the mergers (median $\log (M_{*}/M_{\odot}) = 10.49 \pm 0.32$). We compare spatially resolved UV slope ($\beta$) maps with the FIR dust continuum to study the infrared excess ($\rm{IRX} = L_{\rm{IR}}/L_{\rm{UV}}$)-$\beta$ relation. The SMGs display systematically higher $\rm{IRX}$ values than expected from the nominal trend, demonstrating that the FIR and UV emissions are spatially disconnected. Finally, we show that the SMGs fall on the mass-size plane at smaller stellar masses and sizes than cQGs at $z = 2$. Taking into account the expected evolution in stellar mass and size between $z = 4.5$ and $z = 2$ due to the ongoing starburst and mergers with minor companions, this is in agreement with a direct evolutionary connection between the two populations., Comment: Accepted by ApJ. 25 pages, 6 figures

This paper focuses on the multi-scale wake structures of a new asymmetric side mirror of a race car, which can generate the aerodynamic downforce. The turbulent wake generated by symmetric bluff bodies of triangle and semi-cylinder and an asymmetric bluff body (called CT-cylinder) were experimentally investigated and were compared. Firstly, the instantaneous velocity and vorticity were quantitatively measured by high-speed PIV at a Reynolds number of 14,440 in the circulating water channel. Then a one- and two-dimensional wavelet multi-resolution techniques were used to analyze the instantaneous velocity and vorticity in order to decompose turbulent structures into a number of subsets based on their central frequencies. It is found that the CT-cylinder wake generates the asymmetric flow structures and separation region that is smaller than that of the triangle wake. The contribution to vorticity concentration comes from the large-scale structure of CT-cylinder wake in the (x, y)-plane, and the intermediate-scale structure of the CT-cylinder wake dominates the flow structure in the (x, z)-plane. There is no evident difference among the three wakes in the relatively small-scale structures. The large-scale structures of three wakes exhibit the main contributions to the Reynolds shear stress, accounting for almost 82–92%. However, the small-scale structures make less contribution to Reynolds shear stresses. The phase-averaging and spectral analyses indicate that the CT-cylinder wake generates the relatively smaller vortices and smaller separation region and the CT-cylinder wake exhibits lower fluctuation in the shear layer.

Purpose: The purpose of this planning study was to evaluate the dosimetric effect of dose escalation for intracranial stereotactic radiotherapy by volumetric modulated arc therapy (RapidArc) with simultaneous integrated boost (SIB‐VMAT). Methods: Dynamic conformal arc therapy (DCA), VMAT, and SIB‐VMAT plans using Novalis Tx (Varian/BrainLAB) were performed for twenty target volumes in patients with intracranial metastases with median PTV of 16.0 cm3 (range 2.4–35.2 cm3). PTV was created with 2 mm expansion from GTV. All plans were generated with a prescribed dose of 35 Gy in 5 fractions to the PTV (D95 = 95%), and dose escalation up to 40 Gy (SIB‐VMAT40) and 45 Gy (SIB‐VMAT45) was performed only to the PTV‐boost (PTV shrunk by 5 mm) for SIB‐VMAT. Each plan was compared using conformity parameters. Results: The average Paddick conformity index (CI) was 0.78, 0.90, 0.91, and 0.89 for DCA, VMAT, SIB‐VMAT40, and SIB‐VMAT45, respectively. The average healthy tissue overdosage factor (HTOF), suggested by SALT was 0.118, 0.006, 0.007, and 0.011 for DCA, VMAT, SIB‐VMAT40, and SIB‐VMAT45, respectively. The average V30, V20, and V10 of normal brain for VMAT and SIB‐VMAT decreased by 3.0 cm3 (range 0.1–8.2 cm3), 3.0 cm3 (range 0.1–8.7 cm

Multiplexed optical encoding is emerging as a powerful technique for high-throughput cellular analysis and molecular assays. Most of the developed optical barcodes, however, either suffer from large particle size or are incompatible with most commercial optical instruments. Here, a new type of nanoscale fluorescent barcode (Pdot barcodes) was prepared from semiconducting polymers. The Pdot barcodes possess the merits of small size (~20 nm in diameter), narrow emission bands (full-width-at-half-maximum (fwhm) of 30–40 nm), three-color emissions (blue, green, and red) under single-wavelength excitation, a high brightness, good pH and thermal stability, and efficient cellular uptake. The Pdot barcodes were prepared using a three-color and six-intensity encoding strategy; for ratiometric readout of the barcodes, one of the colors might be used as an internal reference. We used the Pdot barcodes to label 20 sets of cancer cells and then distinguished and identified each set based on the Pdot barcodes using flow cytometry. We also monitored and tracked single cells labeled with different Pdot barcodes, even through rounds of cell division. These results suggest Pdot barcodes are strong candidates for discriminating different labeled cell and for long-term cell tracking.

Background and aims The toll-like receptors (TLRs) are critical participants in vertebrate innate immune recognition of pathogen-associated molecular patterns (PAMPs). Diverse ligands act as “danger signals” detected by this component of the innate immune system. TLR7 and 8 are located in the endosomes of specific immune subpopulations, and are activated by single-stranded RNA from viruses or by autologous RNA fragments bound to immune complexes, inducing the generation of cytokines such as interferons (specifically IFN-alpha) and IL-6. Strong genetic evidence supports variants in TLR7 as contributors to development of systemic lupus erythematosus (SLE). Methods In vitro and in vivo assays were used to guide development of potent and specific small molecule inhibitors. Results We describe novel and selective small molecule non-oligonucleotide TLR7/8 antagonists for the treatment of SLE. They exhibit potent activity in vitro in TLR-specific reporter systems (IC50 of ˜100 nM) and in primary human blood cells (IC50 of 50–500 nM across various ligands and cytokine readouts), suppressing TLR7 and TLR8 but with no activity against TLR9 or other TLRs tested. Exploration of mechanism of action shows direct interaction of the lead compound with the external domain of TLR8. The compounds are orally available and active in a mouse model of R848 challenge. When tested in long-term dosing in pristane-induced or spontaneous NZB/W disease the compounds slow the advance of autoantibody titers and efficiently suppress development of nephritis and associated proteinuria. Conclusions We have identified novel small molecule antagonists of human TLR7 and TLR8 with beneficial activity in mouse models of systemic lupus.