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Current influenza vaccines need to be updated annually due to mutations in the globular head of the viral surface protein, hemagglutinin (HA). To address this, vaccine candidates have been designed based on the relatively conserved HA stem domain and have shown protective efficacy in animal models. Oligomerization of the antigens either by fusion to oligomerization motifs or display on self-assembling nanoparticle scaffolds, can induce more potent immune responses compared to the corresponding monomeric antigen due to multivalent engagement of B-cells. Since nanoparticle display can increase manufacturing complexity, and often involves one or more mammalian cell expressed components, it is important to characterize and compare various display and oligomerization scaffolds. Using a structure guided approach, we successfully displayed multiple copies of a previously designed soluble, trimeric influenza stem domain immunogen, pH1HA10, on the ferritin like protein, MsDps2 (12 copies), Ferritin (24 copies) and Encapsulin (180 copies). All proteins were expressed in Escherichia coli. The nanoparticle fusion immunogens were found to be well folded and bound to the influenza stem directed broadly neutralizing antibodies with high affinity. An 8.5 Å Cryo-EM map of Msdps2-pH1HA10 confirmed the successful design of the nanoparticle fusion immunogen. Mice immunization studies with the soluble trimeric stem and nanoparticle fusion constructs revealed that all of them were immunogenic, and protected mice against homologous (A/Belgium/145-MA/2009) and heterologous (A/Puerto Rico/8/1934) challenge with 10MLD50 mouse adapted virus. Although nanoparticle display conferred a small but statistically significant improvement in protection relative to the soluble trimer in a homologous challenge, heterologous protection was similar in both nanoparticle-stem immunized and trimeric stem immunized groups. Such rapidly producible, bacterially expressed antigens and nanoparticle scaffolds are useful modalities to tackle future influenza pandemics.

In this manuscript, we report the application of graphene oxide (GO) in the preparation of cryo-electron microscopy (cryo-EM) and transmission electron microscopy (TEM) grids. We treated GO with water and organic solvents, such as, methanol, ethanol and isopropanol separately to isolate significantly large GO monolayer flake to fabricate the grids for cryo-EM and TEM study. We implemented a simplified approach to isolate flakes of GO monolayer for constructing the TEM grids, independent of expensive heavy equipment (Langmuir–Blodgett trough, glow-discharge system, carbon-evaporator or plasma-cleaner or peristaltic pumps). We employed confocal microscopy, SEM and TEM to characterize the flake size, stability and transparency of the GO monolayer and atomic force microscopy (AFM) to probe the depth of GO coated grids. Additionally, GO grids are visualized at cryogenic condition for suitability of GO monolayer for cryo-EM study. In addition, GO-Met-H2O grids reduce the effect of preferred orientation of biological macromolecules within the amorphous ice. The power-spectrum and contrast-transfer-function unequivocally suggest that GO-Met-H2O fabricated holey grids have excellent potential for application in high-resolution structural characterization of biomolecules. Furthermore, only 200 movies and ~8000 70S ribosome particles are selected on GO-coated grids for cryo-EM reconstruction to achieve high-resolution structure.

We present the time-dependent properties of a poorly known OH/IR star $-$ IRAS 18278+0931 (hereafter, IRAS 18+09) towards the Ophiuchus constellation. We have carried out long-term optical/near-infrared (NIR) photometric and spectroscopic observations to study the object. From optical $R$- and $I$-band light curves, the period of IRAS 18+09 is estimated to be 575 $\pm$ 30 days and the variability amplitudes range from $\Delta$R $\sim$ 4.0 mag to $\Delta$I $\sim$ 3.5 mag. From the standard Period-Luminosity (PL) relations, the distance ($D$) to the object, 4.0 $\pm$ 1.3 kpc, is estimated. Applying this distance in the radiative transfer model, the spectral energy distribution (SED) are constructed from multi-wavelength photometric and IRAS-LRS spectral data which provides the luminosity, optical depth, and gas mass-loss rate (MLR) of the object to be 9600 $\pm$ 500 $L_{\odot}$, 9.1 $\pm$ 0.6 at 0.55 $\mu$m and 1.0$\times$10$^{-6}$ M$_\odot$ yr$^{-1}$, respectively. The current mass of the object infers in the range 1.0 $-$ 1.5 $M_\odot$ assuming solar metallicity. Notably, the temporal variation of atomic and molecular features (e.g., TiO, Na I, Ca I, CO, H$_2$O) over the pulsation cycle of the OH/IR star illustrates the sensitivity of the spectral features to the dynamical atmosphere as observed in pulsating AGB stars., Comment: 14 pages, 7 figures, 5 tables. Accepted for publication in AJ

Prestellar cores are self-gravitating dense and cold structures within molecular clouds where future stars are born. They are expected, at the stage of transitioning to the protostellar phase, to harbor centrally concentrated dense (sub)structures that will seed the formation of a new star or the binary/multiple stellar systems. Characterizing this critical stage of evolution is key to our understanding of star formation. In this work, we report the detection of high-density (sub)structures on the thousand-astronomical-unit (au) scale in a sample of dense prestellar cores. Through our recent ALMA observations toward the Orion Planck Galactic Cold Clumps, we have found five extremely dense prestellar cores, which have centrally concentrated regions of ∼2000 au in size, and several 107 cm-3 in average density. Masses of these centrally dense regions are in the range of 0.30 to 6.89M⊙. For the first time, our higher resolution observations (0.8' ∼ 320 au) further reveal that one of the cores shows clear signatures of fragmentation; such individual substructures/fragments have sizes of 800-1700 au, masses of 0.08 to 0.84M⊙, densities of 2 - 8 × 107 cm-3, and separations of ∼1200 au. The substructures are massive enough (≳0.1M⊙) to form young stellar objects and are likely examples of the earliest stage of stellar embryos that can lead to widely (∼1200 au) separated multiple systems., L. acknowledges the support from the international partnership program of the Chinese Academy of Sciences through grant No.114231KYSB20200009, National Natural Science Foundation of China (NSFC) through grant NSFC No.12073061, and Shanghai Pujiang Program 20PJ1415500. N.H. acknowledges MoST 108-2112-M-001-017 and MoST 109-2112-M-001-023 grants. G.G. acknowledges support from ANID project AFB 170002. L.B. acknowledges support from ANID project AFB-170002. S.L.Q. is supported by the National Natural Science Foundation of China under grant No. U1631237. D.J. is supported by NRC Canada and by an NSERC Discovery Grant. V.M.P. acknowledges support by the Spanish MINECO under project AYA2017-88754-P, and financial support from the State Agency for Research of the Spanish Ministry of Science and Innovation through the “Unit of Excellence María de Maeztu 2020-2023” award to the Institute of Cosmos Sciences (CEX2019-000918-M). C.W.L. is supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2019R1A2C1010851). A.S. acknowledges financial support from the NSF through grant AST-1715876. The research was carried out in part at the Jet Propulsion Laboratory, which is operated for NASA by the California Institute of Technology. D. L. acknowledges support from NSFC No. 11911530226 and 11725313. K.T. was supported by JSPS KAKENHI grant No. 20H05645. J.H. thanks the NSFC grant No. 11873086 and Yunnan Province of China (No. 2017HC018).This work is sponsored (in part) by the Chinese Academy of Sciences (CAS), through a grant to the CAS South America Center for Astronomy (CASSACA) in Santiago, Chile.

Gas at high Galactic latitude is a relatively little-noticed component of the interstellar medium. In an effort to address this, forty-one Planck Galactic Cold Clumps at high Galactic latitude (HGal; $|b|>25^{\circ}$) were observed in $^{12}$CO, $^{13}$CO and C$^{18}$O J=1-0 lines, using the Purple Mountain Observatory 13.7-m telescope. $^{12}$CO (1-0) and $^{13}$CO (1-0) emission was detected in all clumps while C$^{18}$O (1-0) emission was only seen in sixteen clumps. The highest and average latitudes are $71.4^{\circ}$ and $37.8^{\circ}$, respectively. Fifty-one velocity components were obtained and then each was identified as a single clump. Thirty-three clumps were further mapped at 1$^\prime$ resolution and 54 dense cores were extracted. Among dense cores, the average excitation temperature $T_{\mathrm{ex}}$ of $^{12}$CO is 10.3 K. The average line widths of thermal and non-thermal velocity dispersions are $0.19$ km s$^{-1}$ and $0.46$ km s$^{-1}$ respectively, suggesting that these cores are dominated by turbulence. Distances of the HGal clumps given by Gaia dust reddening are about $120-360$ pc. The ratio of $X_{13}$/$X_{18}$ is significantly higher than that in the solar neighbourhood, implying that HGal gas has a different star formation history compared to the gas in the Galactic disk. HGal cores with sizes from $0.01-0.1$ pc show no notable Larson's relation and the turbulence remains supersonic down to a scale of slightly below $0.1$ pc. None of the HGal cores which bear masses from 0.01-1 $M_{\odot}$ are gravitationally bound and all appear to be confined by outer pressure., 35 pages, 13 figures

During the transition phase from a prestellar to a protostellar cloud core, one or several protostars can form within a single gas core. The detailed physical processes of this transition, however, remain unclear. We present 1.3 mm dust continuum and molecular line observations with the Atacama Large Millimeter/submillimeter Array toward 43 protostellar cores in the Orion molecular cloud complex (λ Orionis, Orion B, and Orion A) with an angular resolution of ∼0.″35 (∼140 au). In total, we detect 13 binary/multiple systems. We derive an overall multiplicity frequency (MF) of 28% ± 4% and a companion star fraction (CSF) of 51% ± 6%, over a separation range of 300-8900 au. The median separation of companions is about 2100 au. The occurrence of stellar multiplicity may depend on the physical characteristics of the dense cores. Notably, those containing binary/multiple systems tend to show a higher gas density and Mach number than cores forming single stars. The integral-shaped filament of the Orion A giant molecular cloud (GMC), which has the highest gas density and hosts high-mass star formation in its central region (the Orion Nebula cluster), shows the highest MF and CSF among the Orion GMCs. In contrast, the λ Orionis GMC has a lower MF and CSF than the Orion B and Orion A GMCs, indicating that feedback from H ii regions may suppress the formation of multiple systems. We also find that the protostars comprising a binary/multiple system are usually at different evolutionary stages., T.L. acknowledges support from the National Natural Science Foundation of China (NSFC) through grants No. 12073061 and No. 12122307, the International Partnership Program of the Chinese Academy of Sciences (CAS) through grant No. 114231KYSB20200009, the Shanghai Pujiang Program (20PJ1415500), and science research grants from the China Manned Space Project with no. CMS-CSST-2021-B06. K.T. was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI (grant No. 20H05645). D.J. and J.d.F. are supported by NRC Canada and by NSERC Discovery Grants. C.-F.L. acknowledge grants from the Ministry of Science and Technology of Taiwan (MoST 107-2119-M-001-040-MY3 and 110-2112-M-001-021-MY3) and Academia Sinica (Investigator Award AS-IA-108-M01). This research was carried out in part at the Jet Propulsion Laboratory, which is operated by the California Institute of Technology under a contract with the National Aeronautics and Space Administration (80NM0018D0004). J.-E.L. was supported by a National Research Foundation of Korea grant funded by the Korean government (MSIT) (grant No. 2021R1A2C1011718). J.H. acknowledges the support of NSFC projects 11873086 and U1631237. This work is sponsored (in part) by the CAS, through a grant to the CAS South America Center for Astronomy in Santiago, Chile. S.-L.Q. is supported by the NSFC with grant No. 12033005. S.Z. acknowledges the support of the China Postdoctoral Science Foundation through grant No. 2021M700248. L.B. gratefully acknowledges support by the ANID BASAL projects ACE210002 and FB210003. P.S. was supported by a Grant-in-Aid for Scientific Research (KAKENHI No. 18H01259) of JSPS. V.-M.P. acknowledges support by the grant PID2020-115892GB-I00 funded by MCIN/AEI/10.13039/501100011033.

We have selected six sources (G209.55–19.68S2, G205.46–14.56S1-A, G203.21–11.20W2, G191.90–11.21S, G205.46–14.56S3, and G206.93–16.61W2) from the Atacama Large Millimeter/submillimeter Array Survey of Orion Planck Galactic Cold Clumps (ALMASOP), in which these sources have been mapped in the CO (J = 2−1), SiO (J = 5−4), and C18O (J = 2−1) lines. These sources have high-velocity SiO jets surrounded by low-velocity CO outflows. The SiO jets consist of a chain of knots. These knots have been thought to be produced by semiperiodic variations in jet velocity. Therefore, we adopt a shock-forming model, which uses such variations to estimate the inclination angle and velocity of the jets. We also derive the inclination angle of the CO outflows using the wide-angle wind-driven shell model and find it to be broadly consistent with that of the associated SiO jets. In addition, we apply this shock-forming model to another three protostellar sources with SiO jets in the literature—HH 211, HH 212, and L1448C(N)—and find that their inclination angle and jet velocity are consistent with those previously estimated from proper-motion and radial-velocity studies.

Spike (S) glycoprotein of SARS-CoV2 exists chiefly in two conformations, open and closed. Most previous structural studies on S protein have been conducted at pH 8.0, but knowledge of the conformational propensities under both physiological and endosomal pH conditions is important to inform vaccine development. Our current study employed single-particle cryoelectron microscopy to visualize multiple states of open and closed conformations of S protein at physiological pH 7.4 and near-physiological pH 6.5 and pH 8.0. Propensities of open and closed conformations were found to differ with pH changes, whereby around 68% of S protein exists in open conformation at pH 7.4. Furthermore, we noticed a continuous movement in the N-terminal domain, receptor-binding domain (RBD), S2 domain, and stalk domain of S protein conformations at various pH values. Several key residues involving RBD-neutralizing epitopes are differentially exposed in each conformation. This study will assist in developing novel therapeutic measures against SARS-CoV2., Graphical abstract, In this study, Pramanick et al. demonstrate inherent structural flexibility of NTD, RBD, and stalk domain of SARS-CoV2 Spike glycoprotein. Eleven high-resolution cryo-EM structures obtained over a range of near-physiological pH values indicate a trend of increasing open conformational state of S protein at physiological pH 7.4.

Planck Galactic Cold Clumps (PGCCs) are contemplated to be the ideal targets to probe the early phases of star formation. We have conducted a survey of 72 young dense cores inside PGCCs in the Orion complex with the Atacama Large Millimeter/submillimeter Array (ALMA) at 1.3\,mm (band 6) using three different configurations (resolutions $\sim$ 0$\farcs$35, 1$\farcs$0, and 7$\farcs$0) to statistically investigate their evolutionary stages and sub-structures. We have obtained images of the 1.3\,mm continuum and molecular line emission ($^{12}$CO, and SiO) at an angular resolution of $\sim$ 0$\farcs$35 ($\sim$ 140\,au) with the combined arrays. We find 70 substructures within 48 detected dense cores with median dust-mass $\sim$ 0.093\,M$_{\sun}$ and deconvolved size $\sim$ 0$\farcs$27. Dense substructures are clearly detected within the central 1000\,au of four candidate prestellar cores. The sizes and masses of the substructures in continuum emission are found to be significantly reduced with protostellar evolution from Class\,0 to Class\,I. We also study the evolutionary change in the outflow characteristics through the course of protostellar mass accretion. A total of 37 sources exhibit CO outflows, and 20 ($>$50\%) show high-velocity jets in SiO. The CO velocity-extents ($\Delta$Vs) span from 4 to 110 km/s with outflow cavity opening angle width at 400\,au ranging from $[\Theta_{obs}]_{400}$ $\sim$ 0$\farcs$6 to 3$\farcs$9, which corresponds to 33$\fdg$4$-$125$\fdg$7. For the majority of the outflow sources, the $\Delta$Vs show a positive correlation with $[\Theta_{obs}]_{400}$, suggesting that as protostars undergo gravitational collapse, the cavity opening of a protostellar outflow widens and the protostars possibly generate more energetic outflows., Comment: 43 pages, 25 figures (14 in the main text, 9 in the appendix), accepted for publication in the Astrophysical Journal Supplement Series (ApJS)

We present here optical I-band photometric variability study down to $\simeq$ 19 mag of a young ($\sim$2-3 Myr) star-forming region IC 348 in the Perseus molecular cloud. We aim to explore the fast rotation (in the time-scales of hours) in Very Low Mass stars (VLMs) including Brown Dwarfs (BDs). From a sample of 177 light-curves using our new I-band observations, we detect new photometric variability in 22 young M-dwarfs including 6 BDs, which are bonafide members in IC 348 and well-characterized in the spectral type of M-dwarfs. Out of 22 variables, 11 M dwarfs including one BD show hour-scale periodic variability in the period range 3.5 - 11 hours and rest are aperiodic in nature. Interestingly, an optical flare is detected in a young M2.75 dwarf in one night data on 20 December 2016. From the flare light curve, we estimate the emitted flared energy of 1.48 $\times$ 10$^{35}$ ergs. The observed flared energy with an uncertainty of tens of per cent is close to the super-flare range ($\sim$ 10$^{34}$ ergs), which is rarely observed in active M dwarfs., 12 pages, 5 figures

We present here identification and characterization of the young stellar population associated with an active star-forming site Sh2-242. We used our own new optical imaging and spectroscopic observational data, as well as several archival catalogs, e.g., Pan-STARRS 1, $Gaia$ DR2, IPHAS, WIRCam, 2MASS, and $Spitzer$. Slit spectroscopic results confirm the classification of the main ionizing source BD+26 980 as an early-type star of spectral type B0.5 V. The spectrophotometric distance of the star is estimated as 2.08 $\pm$ 0.24 kpc, which confirms the source as a member of the cluster. An extinction map covering a large area (diameter $\sim$ 50') is generated with $H$ and $K$ photometry toward the region. From the map, three distinct locations of peak extinction complexes ($A_{V}$ $\simeq$ 7$-$17 mag) are identified for the very first time. Using the infrared color excess, a total of 33 Class I and 137 Class II young objects are classified within the region. The IPHAS photometry reveals classification of 36 H$\alpha$ emitting sources, which might be class II objects. Among 36 H$\alpha$ emitting sources, 5 are already identified using infrared excess emission. In total, 201 young objects are classified toward S242 from this study. The membership status of the young sources is further windowed with the inclusion of parallax from the $Gaia$ DR2 catalog. Using the optical and infrared color-magnitude diagrams, the young stellar objects are characterized with an average age of $\sim$ 1 Myr and the masses in the range 0.1$-$3.0 $M_\odot$. The census of the stellar content within the region is discussed using combined photometric and spectroscopic data., Comment: 17 pages, 12 figures, Published in the Astronomical Journal

The presence of complex organic molecules (COMs) in the interstellar medium (ISM) is of great interest since it may link to the origin and prevalence of life in the universe. Aiming to investigate the occurrence of COMs and their possible origins, we conducted a chemical census toward a sample of protostellar cores as part of the ALMA Survey of Orion Planck Galactic Cold Clumps (ALMASOP) project. We report the detection of 11 hot corino sources, which exhibit compact emissions from warm and abundant COMs, among 56 Class 0/I protostellar cores. All the hot corino sources discovered are likely Class 0 and their sizes of the warm region ($>$ 100 K) are comparable to 100 au. The luminosity of the hot corino sources exhibits positive correlations with the total number of methanol and the extent of its emissions. Such correlations are consistent with the thermal desorption picture for the presence of hot corino and suggest that the lower luminosity (Class 0) sources likely have a smaller region with COMs emissions. With the same sample selection method and detection criteria being applied, the detection rates of the warm methanol in the Orion cloud (15/37) and the Perseus cloud (28/50) are statistically similar when the cloud distances and the limited sample size are considered. Observing the same set of COM transitions will bring a more informative comparison between the cloud properties., 34 pages. 14 figures. 1 figure set. 1 machine-readable table. Accepted for publication in ApJ

Jets and outflows trace the accretion history of protostars. High-velocity molecular jets have been observed from several protostars in the early Class 0 phase of star formation, detected with the high-density tracer SiO. Until now, no clear jet has been detected with SiO emission from isolated evolved Class I protostellar systems. We report a prominent dense SiO jet from a Class I source G205S3 (HOPS-315: T bol ∼ 180 K, spectral index ∼0.417), with a moderately high mass-loss rate (∼0.59 × 10−6 M ⊙ yr−1) estimated from CO emission. Together, these features suggest that G205S3 is still in a high-accretion phase, similar to that expected of Class 0 objects. We compare G205S3 to a representative Class 0 system G206W2 (HOPS-399) and literature Class 0/I sources to explore the possible explanations behind the SiO emission seen at the later phase. We estimate a high inclination angle (∼40°) for G205S3 from CO emission, which may expose the infrared emission from the central core and mislead the spectral classification. However, the compact 1.3 mm continuum, C18O emission, location in the bolometric luminosity to submillimeter fluxes diagram, outflow force (∼3.26 × 10−5 M ⊙ km s−1 yr−1) are also analogous to that of Class I systems. We thus consider G205S3 to be at the very early phase of Class I, and in the late phase of high accretion. The episodic ejection could be due to the presence of an unknown binary, a planetary companion, or dense clumps, where the required mass for such high accretion could be supplied by a massive circumbinary disk.

We report here CCD $I$-band time-series photometry of a young (2$-$5 Myr) cluster NGC 2282 to identify and understand the variability of pre-main-sequence (PMS) stars. The $I$-band photometry, down to $\sim$ 20.5 mag, enables us to probe the variability towards the lower mass end ($\sim$ 0.1 M$_\odot$) of the PMS stars. From the light curves of 1627 stars, we identified 62 new photometric variable candidates. Their association with the region was established from H$\alpha$ emission and infrared (IR) excess. Among 62 variables, 30 young variables exhibit H$\alpha$ emission, near-IR (NIR)/mid-IR (MIR) excess or both, and they are candidate members of the cluster. Out of 62 variables, 41 are periodic variables with the rotation rate ranging from 0.2 to 7 days. The period distribution exhibits a median period at $\sim$ 1-day as in many young clusters (e.g., NGC~2264, ONC, etc.), but it follows a uni-modal distribution unlike others having bimodality with the slow rotators peaking at $\sim$ 6$-$8 days. To investigate the rotation-disk and variability-disk connection, we derived NIR excess from $\Delta$(I$-$K) and MIR excess from $Spitzer$ [3.6]$-$[4.5] $\mu$m data. No conclusive evidence of slow rotation with the presence of disks around stars and fast rotation for diskless stars is obtained from our periodic variables. A clear increasing trend of the variability amplitude with the IR excess is found for all variables.

The ESCRT pathway functions at different subcellular membranes to induce their negative curvature, and it has been largely characterized in model eukaryotes belonging to Opisthokonta. But searches of the genomes of many nonopisthokonts belonging to various supergroups indicate that some of them may harbour fewer ESCRT components. Of the genomes explored thus far, one of the most minimal set of ESCRT components was identified in the human pathogen Giardia lamblia, which belongs to Excavata. Here we report that an ESCRT-mediated pathway most likely operates at the peripheral vesicles, which are located at the cell periphery and the bare zone of this protist. Functional comparison of all the identified putative giardial ESCRT components, with the corresponding well-characterized orthologues from Saccharomyces cerevisiae, indicated that only some of the ESCRT components could functionally substitute for the corresponding yeast proteins. While GlVps25, GlVps2, and all three paralogues of GlVps4, tested positive in functional complementation assays, GlVps22, GlVps20, and GlVps24 did not. Binary interactions of either GlVps22 or GlVps25, with other ESCRT-II components from Giardia or yeast indicate that the giardial Vps36 orthologue is either completely missing or highly diverged. Interactions within the giardial ESCRT-III components also differ from those in yeast; while GlVps46a interacts preferentially with Vps24 compared to Vps2, GlVps46b, like the yeast orthologue, interacts with both.

Thermostable direct hemolysin (TDH) of

We present optical $I$-band light curves of the stars towards a star-forming region Cygnus OB7 from 17 nights photometric observations. The light curves are generated from a total of 381 image frames with very good photometric precision. From the light curves of 1900 stars and their periodogram analyses, we detect 31 candidate variables including five previously identified. 14 out of 31 objects are periodic and exhibit the rotation rates in the range of 0.15 to 11.60 days. We characterize those candidate variables using optical/infrared colour-colour and colour-magnitude diagrams. From spectral indices of the candidate variables, it turns out that four are probably Classical T-Tauri stars (CTTSs), rest remain unclassified from present data, they are possibly field stars or diskless pre-main sequence stars towards the region. Based on their location on the various colour-magnitude diagrams, the ages of two T Tauri Stars were estimated to be $\sim$ 5 Myr. The light curves indicate at least five of the periodic variables are eclipsing systems. The spatial distribution of young variable candidates on Planck 857 GHz (350 $\mu$m) and 2MASS $K_s$ images suggest that at least two of the CTTSs are part of the active star-forming cloud Lynds 1003., Comment: 14 pages, 12 figures

Virtually all SARS-CoV-2 vaccines currently in clinical testing are stored in a refrigerated or frozen state prior to use. This is a major impediment to deployment in resource-poor settings. Furthermore, several of them use viral vectors or mRNA. In contrast to protein subunit vaccines, there is limited manufacturing expertise for these nucleic-acid-based modalities, especially in the developing world. Neutralizing antibodies, the clearest known correlate of protection against SARS-CoV-2, are primarily directed against the receptor-binding domain (RBD) of the viral spike protein, suggesting that a suitable RBD construct might serve as a more accessible vaccine ingredient. We describe a monomeric, glycan-engineered RBD protein fragment that is expressed at a purified yield of 214 mg/l in unoptimized, mammalian cell culture and, in contrast to a stabilized spike ectodomain, is tolerant of exposure to temperatures as high as 100 °C when lyophilized, up to 70 °C in solution and stable for over 4 weeks at 37 °C. In prime:boost guinea pig immunizations, when formulated with the MF59-like adjuvant AddaVax, the RBD derivative elicited neutralizing antibodies with an endpoint geometric mean titer of ∼415 against replicative virus, comparing favorably with several vaccine formulations currently in the clinic. These features of high yield, extreme thermotolerance, and satisfactory immunogenicity suggest that such RBD subunit vaccine formulations hold great promise to combat COVID-19.

We report the detection of four new hot corino sources, G211.47-19.27S, G208.68-19.20N1, G210.49-19.79W and G192.12-11.10 from a survey study of Planck Galactic Cold Clumps in the Orion Molecular Cloud Complex with the Atacama Compact Array (ACA). Three sources had been identified as low mass Class 0 protostars in the Herschel Orion Protostar Survey (HOPS). One source in the lambda Orionis region is firstly reported as a protostellar core. We have observed abundant complex organic molecules (COMs), primarily methanol but also other oxygen-bearing COMs (in G211.47-19.27S and G208.68-19.20N1) and the molecule of prebiotic interest NH2CHO (in G211.47-19.27S), signifying the presence of hot corinos. While our spatial resolution is not sufficient for resolving most of the molecular emission structure, the large linewidth and high rotational temperature of COMs suggest that they likely reside in the hotter and innermost region immediately surrounding the protostar. In G211.47-19.27S, the D/H ratio of methanol ([CH2DOH]/[CH3OH]) and the 12C/13C ratio of methanol ([CH3OH]/[13CH3OH]) are comparable to those of other hot corinos. Hydrocarbons and long carbon-chain molecules such as c-C3H2 and HCCCN are also detected in the four sources, likely tracing the outer and cooler molecular envelopes., 37 pages, 51 figures, to be published in ApJ

Metabotropic glutamate receptors are family C G-protein-coupled receptors. They form obligate dimers and possess extracellular ligand-binding Venus flytrap domains, which are linked by cysteine-rich domains to their 7-transmembrane domains. Spectroscopic studies show that signalling is a dynamic process, in which large-scale conformational changes underlie the transmission of signals from the extracellular Venus flytraps to the G protein-coupling domains-the 7-transmembrane domains-in the membrane. Here, using a combination of X-ray crystallography, cryo-electron microscopy and signalling studies, we present a structural framework for the activation mechanism of metabotropic glutamate receptor subtype 5. Our results show that agonist binding at the Venus flytraps leads to a compaction of the intersubunit dimer interface, thereby bringing the cysteine-rich domains into close proximity. Interactions between the cysteine-rich domains and the second extracellular loops of the receptor enable the rigid-body repositioning of the 7-transmembrane domains, which come into contact with each other to initiate signalling.

Broadly neutralizing antibodies (bNAbs) have demonstrated protective effects against HIV-1 in primate studies and recent human clinical trials. Elite neutralizers are potential candidates for isolation of HIV-1 bNAbs. The coexistence of bNAbs such as BG18 with neutralization-susceptible autologous viruses in an HIV-1-infected adult elite controller has been suggested to control viremia. Disease progression is faster in HIV-1-infected children than in adults. Plasma bNAbs with multiple epitope specificities are developed in HIV-1 chronically infected children with more potency and breadth than in adults. Therefore, we evaluated the specificity of plasma neutralizing antibodies of an antiretroviral-naive HIV-1 clade C chronically infected pediatric elite neutralizer, AIIMS_330. The plasma antibodies showed broad and potent HIV-1 neutralizing activity with >87% (29/33) breadth, a median inhibitory dilution (ID(50)) value of 1,246, and presence of N160 and N332 supersite-dependent HIV-1 bNAbs. The sorting of BG505.SOSIP.664.C2 T332N gp140 HIV-1 antigen-specific single B cells of AIIMS_330 resulted in the isolation of an HIV-1 N332 supersite-dependent bNAb, AIIMS-P01. The AIIMS-P01 neutralized 67% of HIV-1 cross-clade viruses, exhibited substantial indels despite limited somatic hypermutations, interacted with native-like HIV-1 trimer as observed in negative stain electron microscopy, and demonstrated high binding affinity. In addition, AIIMS-P01 neutralized the coexisting and evolving autologous viruses, suggesting the coexistence of vulnerable autologous viruses and HIV-1 bNAbs in the AIIMS_330 pediatric elite neutralizer. Such pediatric elite neutralizers can serve as potential candidates for isolation of novel HIV-1 pediatric bNAbs and for understanding the coevolution of virus and host immune response. IMPORTANCE More than 50% of the HIV-1 infections globally are caused by clade C viruses. To date, there is no effective vaccine to prevent HIV-1 infection. Based on the structural information of the currently available HIV-1 bNAbs, attempts are under way to design immunogens that can elicit correlates of protection upon vaccination. Here, we report the isolation and characterization of an HIV-1 N332 supersite-dependent bNAb, AIIMS-P01, from a clade C chronically infected pediatric elite neutralizer. The N332 supersite is an important epitope and is one of the current HIV-1 vaccine targets. AIIMS-P01 potently neutralized the contemporaneous and autologous evolving viruses and exhibited substantial indels despite low somatic hypermutations. Taken together with the information on infant bNAbs, further isolation and characterization of bNAbs contributing to the plasma breadth in HIV-1 chronically infected children may help provide a better understanding of their role in controlling HIV-1 infection.

The {\it Planck} Galactic Cold Clumps (PGCCs) are the possible representations of the initial conditions and the very early stages of star formation. With an objective to understand better the star and star cluster formation, we probe the molecular cloud associated with PGCC G108.37-01.06 (hereafter, PG108.3), which can be traced in a velocity range $-$57 to $-$51 km s$^{-1}$. The IPHAS images reveal H$\alpha$ emission at various locations around PG108.3, and optical spectroscopy of the bright sources in those zones of H$\alpha$ emission disclose two massive ionizing sources with spectral type O8-O9V and B1V. Using the radio continuum, we estimate ionizing gas parameters and find the dynamical ages of \hii regions associated with the massive stars in the range 0.5$-$0.75 Myr. Based on the stellar surface density map constructed from the deep near-infrared CHFT observations, we find two prominent star clusters in PG108.3; of which, the cluster associated with \hii region S148 is moderately massive ($\sim$ 240 M$\sun$). A careful inspection of JCMT $^{13}$CO(3$-$2) molecular data exhibits that the massive cluster is associated with a number of filamentary structures. Several embedded young stellar objects (YSOs) are also identified in the PG108.3 along the length and junction of filaments. We find the evidence of velocity gradient along the length of the filaments. Along with kinematics of the filaments and the distribution of ionized, molecular gas and YSOs, we suggest that the cluster formation is most likely due to the longitudinal collapse of the most massive filament in PG108.3., Comment: 22 pages, 17 figures, Accepted for publication in Astrophysical Journal

Small heat shock proteins (sHSPs) are ATP-independent molecular chaperones present ubiquitously in all kingdoms of life. Their low molecular weight subunits associate to form higher order structures. Under conditions of stress, sHSPs prevent aggregation of substrate proteins by undergoing rapid changes in their conformation or stoichiometry. Polydispersity and dynamic nature of these proteins have made structural investigations through crystallography a daunting task. In pathogens like Mycobacteria, sHSPs are immuno-dominant antigens, enabling survival of the pathogen within the host and contributing to disease persistence. We characterized sHSPs from Mycobacterium marinum M and determined the crystal structure of one of these. The protein crystallized in three different conditions as dodecamers, with dimers arranged in a tetrahedral fashion to form a closed cage-like architecture. Interestingly, we found a pentapeptide bound to the dodecamers revealing one of the modes of sHSP-substrate interaction. Further, we have observed that ATP inhibits the chaperoning activity of the protein.

The wave of resolution revolution in cryo-EM has touched, and made a significant impact on, the structural biology of GPCRs. High-resolution structures of several GPCR-G-protein complexes are now determined by cryo-EM and they illuminate fine structural details of this central macromolecular complex involved in cellular signaling.

We describe the time-dependent properties of a new spectroscopically confirmed Mira variable, which was discovered in 2013 as MASTER-Net Optical Transient (OT) J212444.87+321738.3 towards the Cygnus constellation. We have performed long-term optical/near-infrared (NIR) photometric and spectroscopic observations to characterize the object. From the optical/NIR light curves, we estimate a variability period of 465 $\pm$ 30 days. The wavelength-dependent amplitudes of the observed light-curves range from $\Delta$I$\sim$4 mag to $\Delta$K$\sim$1.5 mag. The (J-K) color-index varies from 1.78 to 2.62 mag over phases. Interestingly, a phase lag of $\sim$60 days between optical and NIR light curves is also seen, as in other Miras. Our optical/NIR spectra show molecular features of TiO, VO, CO, and strong water bands which are a typical signature of oxygen-rich Mira. We rule out S- or C-type as ZrO bands at 1.03 and 1.06 $\mu$m and $C_2$ band at 1.77 $\mu$m are absent. We estimate the effective temperature of the object from the SED, and distance and luminosity from standard Period-Luminosity relations. The optical/NIR spectra display time-dependent atomic and molecular features (e.g. TiO, NaI, CaI, H$_2$O,CO), as commonly observed in Miras. Such spectroscopic observations are useful for studying pulsation variability in Miras., Comment: 17 pages, 6 figures, accepted for publication in The Astronomical Journal

Binding to the von Willebrand factor (VWF) D′D3 domains protects factor VIII (FVIII) from rapid clearance. We performed single-particle electron microscopy (EM) analysis of negatively stained specimens to examine the architecture of D′D3 alone and in complex with FVIII. The D′D3 dimer ([D′D3]2) comprises 2 antiparallel D3 monomers with flexibly attached protrusions of D′. FVIII-VWF association is primarily established between the FVIII C1 domain and the VWF D′ domain, whereas weaker interactions appear to be mediated between both FVIII C domains and the VWF D3 core. Modeling the FVIII structure into the three-dimensional EM reconstructions of [D′D3]2-FVIII ternary and quaternary complexes indicates conformational rearrangements of the FVIII C domains compared with their disposition in the unbound state. These results illustrate the cooperative plasticity between VWF and FVIII that coordinate their high-affinity interaction.

Polyketide natural products constitute a broad class of compounds with diverse structural features and biological activities. Their biosynthetic machinery, represented by type I polyketide synthases (PKSs), has an architecture in which successive modules catalyse two-carbon linear extensions and keto-group processing reactions on intermediates covalently tethered to carrier domains. Here we used electron cryo-microscopy to determine sub-nanometre-resolution three-dimensional reconstructions of a full-length PKS module from the bacterium Streptomyces venezuelae that revealed an unexpectedly different architecture compared to the homologous dimeric mammalian fatty acid synthase. A single reaction chamber provides access to all catalytic sites for the intramodule carrier domain. In contrast, the carrier from the preceding module uses a separate entrance outside the reaction chamber to deliver the upstream polyketide intermediate for subsequent extension and modification. This study reveals for the first time, to our knowledge, the structural basis for both intramodule and intermodule substrate transfer in polyketide synthases, and establishes a new model for molecular dissection of these multifunctional enzyme systems. Polyketide synthases are multidomain enzymes that produce polyketides, which form the basis of many therapeutic agents; here, electron cryo-microscopy is used to establish the structure of a bacterial full-length module, and to elucidate the structural basis of both intramodule and intermodule substrate transfer. Polyketide synthases (PKSs) are multi-domain enzyme complexes producing polyketides, a large class of secondary metabolites — in other words, natural products. Two papers from Georgios Skiniotis and colleagues use cryo-electron microscopy to probe the structure of an intact module of a full-length multienzyme PKS module involved in pikromycin biosynthesis in the bacterium Streptomyces venezuelae in different functional states. The structures reveal how the ketosynthase, acyltransferase, ketoreductase and acyl carrier protein (ACP) domains interact during the catalytic cycle. In each state the ACP is differentially positioned to facilitate intermediate transfer for the next catalytic step and for transfer to the next module.

Polyketide synthases (PKSs) are multidomain enzymes that produce polyketides, which form the basis of many therapeutic agents; here, electron cryo-microscopy is used to probe the structure of an intact module of a multi-enzyme PKS in different functional states. Polyketide synthases (PKSs) are multi-domain enzyme complexes producing polyketides, a large class of secondary metabolites — in other words, natural products. Two papers from Georgios Skiniotis and colleagues use cryo-electron microscopy to probe the structure of an intact module of a full-length multienzyme PKS module involved in pikromycin biosynthesis in the bacterium Streptomyces venezuelae in different functional states. The structures reveal how the ketosynthase, acyltransferase, ketoreductase and acyl carrier protein (ACP) domains interact during the catalytic cycle. In each state the ACP is differentially positioned to facilitate intermediate transfer for the next catalytic step and for transfer to the next module. The polyketide synthase (PKS) mega-enzyme assembly line uses a modular architecture to synthesize diverse and bioactive natural products that often constitute the core structures or complete chemical entities for many clinically approved therapeutic agents1. The architecture of a full-length PKS module from the pikromycin pathway of Streptomyces venezuelae creates a reaction chamber for the intramodule acyl carrier protein (ACP) domain that carries building blocks and intermediates between acyltransferase, ketosynthase and ketoreductase active sites (see accompanying paper2). Here we determine electron cryo-microscopy structures of a full-length pikromycin PKS module in three key biochemical states of its catalytic cycle. Each biochemical state was confirmed by bottom-up liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometry. The ACP domain is differentially and precisely positioned after polyketide chain substrate loading on the active site of the ketosynthase, after extension to the β-keto intermediate, and after β-hydroxy product generation. The structures reveal the ACP dynamics for sequential interactions with catalytic domains within the reaction chamber, and for transferring the elongated and processed polyketide substrate to the next module in the PKS pathway. During the enzymatic cycle the ketoreductase domain undergoes dramatic conformational rearrangements that enable optimal positioning for reductive processing of the ACP-bound polyketide chain elongation intermediate. These findings have crucial implications for the design of functional PKS modules, and for the engineering of pathways to generate pharmacologically relevant molecules.

The surname of author Toon Laeremans was misspelled ‘Laermans’. This error has been corrected online.

Phospholipase C-β (PLCβ) is directly activated by Gαq, but the molecular basis for how its distal C-terminal domain (CTD) contributes to maximal activity is poorly understood. Herein we present both the crystal structure and cryo-EM three-dimensional reconstructions of human full-length PLCβ3 in complex with mouse Gαq. The distal CTD forms an extended monomeric helical bundle consisting of three antiparallel segments with structural similarity to membrane-binding bin-amphiphysin-Rvs (BAR) domains. Sequence conservation of the distal CTD suggests putative membrane and protein interaction sites, the latter of which bind the N-terminal helix of Gαq in both the crystal structure and cryo-EM reconstructions. Functional analysis suggests that the distal CTD has roles in membrane targeting and in optimizing the orientation of the catalytic core at the membrane for maximal rates of lipid hydrolysis.

A major goal for HIV-1 vaccine development is an ability to elicit strong and durable broadly neutralizing antibody (bNAb) responses. The trimeric envelope glycoprotein (Env) spikes on HIV-1 are known to contain multiple epitopes that are susceptible to bNAbs isolated from infected individuals. Nonetheless, all trimeric and monomeric Env immunogens designed to date have failed to elicit such antibodies. We report the structure-guided design of HIV-1 cyclically permuted gp120 that forms homogeneous, stable trimers, and displays enhanced binding to multiple bNAbs, including VRC01, VRC03, VRC-PG04, PGT128, and the quaternary epitope-specific bNAbs PGT145 and PGDM1400. Constructs that were cyclically permuted in the V1 loop region and contained an N-terminal trimerization domain to stabilize V1V2-mediated quaternary interactions, showed the highest homogeneity and the best antigenic characteristics. In guinea pigs, a DNA prime-protein boost regimen with these new gp120 trimer immunogens elicited potent neutralizing antibody responses against highly sensitive Tier 1A isolates and weaker neutralizing antibody responses with an average titer of about 115 against a panel of heterologous Tier 2 isolates. A modest fraction of the Tier 2 virus neutralizing activity appeared to target the CD4 binding site on gp120. These results suggest that cyclically permuted HIV-1 gp120 trimers represent a viable platform in which further modifications may be made to eventually achieve protective bNAb responses.

Myers and Payne discuss work by De et al. describing the unique structure of Vps13 and its role in trafficking, Yeast Vps13 is a member of a conserved protein family that includes human homologues associated with neurodegenerative and developmental disorders. In this issue, De et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201606078) establish direct roles for Vps13 and its surprising binding partner, the calcium-binding centrin Cdc31, in trans-Golgi network (TGN) to endosome traffic and TGN homotypic fusion.

Despite the crucial impact of leptin signaling on metabolism and body weight, little is known about the structure of the liganded leptin receptor (LEP-R) complex. Here, we applied single-particle electron microscopy (EM) to characterize the architecture of the extracellular region of LEP-R alone and in complex with leptin. We show that unliganded LEP-R displays significant flexibility in a hinge region within the cytokine homology region 2 (CHR2) that is connected to rigid membrane-proximal FnIII domains. Leptin binds to CHR2 in order to restrict the flexible hinge and the disposition of the FnIII "legs." Through a separate interaction, leptin engages the Ig-like domain of a second liganded LEP-R, resulting in the formation of a quaternary signaling complex. We propose that the membrane proximal domain rigidification in the context of a liganded cytokine receptor dimer is a key mechanism for the transactivation of Janus kinases (Jaks) bound at the intracellular receptor region.

The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are paramyxoviruses discovered in the mid- to late 1990s that possess a broad host tropism and are known to cause severe and often fatal disease in both humans and animals. HeV and NiV infect cells by a pH-independent membrane fusion mechanism facilitated by their attachment (G) and fusion (F) glycoproteins. Here, several soluble forms of henipavirus F (sF) were engineered and characterized. Recombinant sF was produced by deleting the transmembrane (TM) and cytoplasmic tail (CT) domains and appending a glycosylphosphatidylinositol (GPI) anchor signal sequence followed by GPI-phospholipase D digestion, appending a trimeric coiled-coil (GCNt) domain (sF GCNt ), or deleting the TM, CT, and fusion peptide domain. These sF glycoproteins were produced as F 0 precursors, and all were apparent stable trimers recognized by NiV-specific antisera. Surprisingly, however, only the GCNt-appended constructs (sF GCNt ) could elicit cross-reactive henipavirus-neutralizing antibody in mice. In addition, sF GCNt constructs could be triggered in vitro by protease cleavage and heat to transition from an apparent prefusion to postfusion conformation, transitioning through an intermediate that could be captured by a peptide corresponding to the C-terminal heptad repeat domain of F. The pre- and postfusion structures of sF GCNt and non-GCNt-appended sF could be revealed by electron microscopy and were distinguishable by F-specific monoclonal antibodies. These data suggest that only certain sF constructs could serve as potential subunit vaccine immunogens against henipaviruses and also establish important tools for further structural, functional, and diagnostic studies on these important emerging viruses.

A critical review of past earthquakes reveals damage/failure of important lifeline facilities like elevated water tanks in recurrence, leading to serious hazards even after the event. In the context of such hazards indicating deficiencies in the existing seismic design strategy of such structures, dynamic characteristics of elevated tanks supported by cylindrical shaft (shaft staging) are comprehensively studied in the first part of present investigation. The same is made through analytical formulations developed and validated by rigorous finite element analysis and small-scale experimentation. Subsequent examination on seismic response of representative tanks indicates that the columns of the frame-supported tanks (tanks with frame staging) and the wall of the shaft-staging of such reinforced concrete ( R / C ) tanks are susceptible to tension, particularly at tank empty condition. Such possibility seems to be further aggravated if the effect of soil–structure interaction (SSI) is ignored in design. Identifying the deficiencies in current design, simple design procedure of such elevated tanks utilizing the formulations developed is proposed. Torsional vulnerability of shaft-supported elevated water tanks is also identified to be marginal as opposed to the same for frame supported ones.

Nipah virus (NiV) is a paramyxovirus that infects host cells through the coordinated efforts of two envelope glycoproteins. The G glycoprotein attaches to cell receptors, triggering the fusion (F) glycoprotein to execute membrane fusion. Here we report the first crystal structure of the pre-fusion form of the NiV-F glycoprotein ectodomain. Interestingly this structure also revealed a hexamer-of-trimers encircling a central axis. Electron tomography of Nipah virus-like particles supported the hexameric pre-fusion model, and biochemical analyses supported the hexamer-of-trimers F assembly in solution. Importantly, structure-assisted site-directed mutagenesis of the interfaces between F trimers highlighted the functional relevance of the hexameric assembly. Shown here, in both cell-cell fusion and virus-cell fusion systems, our results suggested that this hexamer-of-trimers assembly was important during fusion pore formation. We propose that this assembly would stabilize the pre-fusion F conformation prior to cell attachment and facilitate the coordinated transition to a post-fusion conformation of all six F trimers upon triggering of a single trimer. Together, our data reveal a novel and functional pre-fusion architecture of a paramyxoviral fusion glycoprotein., Author Summary Paramyxoviruses infect host cells through the coordinated functions of two envelope glycoproteins. The G glycoprotein attaches to cell receptors triggering the fusion (F) glycoprotein to execute membrane fusion. The crystal structure of the NiV-F protein has not been reported. Additionally, many molecular details of the virus-cell fusion process remain elusive, including how the higher-energy pre-fusion conformation state of the F glycoprotein is stabilized, or how many copies of the F glycoprotein are required for fusion. This manuscript reports the pre-fusion crystal structure of NiV-F glycoprotein, and a functional hexamer-of-trimers assembly, with six F trimers encircling a central axis. Multidisciplinary data suggested that this assembly plays a role in the stability of the pre-fusion F conformation prior to cell attachment and F-triggering to a post-fusion conformation. Thus this assembly may coordinate this transition in all six F trimers upon triggering of a single trimer during membrane fusion pore formation.

3D mesh data acquisition is often afflicted by undesirable measurement noise. Such noise has an aversive impact to further processing and also to human perception, and hence plays a pivotal role in mesh processing. We present here a fast saliency-based algorithm that can reduce the noise while preserving the finer details of the original object. In order to capture the object features at multiple scales, our mesh denoising algorithm estimates the mesh saliency from Gaussian weighted curvatures for vertices at fine and coarse scales. The proposed algorithm finds wide application in digitization of archaeological artifacts, such as statues and sculptures, where it is of paramount importance to capture the 3D surface with all its details as accurately as possible. We have tested the algorithm on several datasets, and the results exhibit its speed and efficiency.

We present the analysis of the stellar content of NGC~2282, a young cluster in the Monoceros constellation, using deep optical $BVI$ and IPHAS photometry along with infrared (IR) data from UKIDSS and $Spitzer$-IRAC. Based on the stellar surface density analysis using nearest neighborhood method, the radius of the cluster is estimated as $\sim$ 3.15$\arcmin$. From optical spectroscopic analysis of 8 bright sources, we have classified three early B-type members in the cluster, which includes, HD 289120, a previously known B2V type star, a Herbig Ae/Be star (B0.5 Ve) and a B5 V star. From spectrophotometric analyses, the distance to the cluster has been estimated as $\sim$ 1.65 kpc. The $K$-band extinction map is estimated using nearest neighborhood technique, and the mean extinction within the cluster area is found to be A$_V$ $\sim$ 3.9 mag. Using IR colour-colour criteria and H$_\alpha$-emission properties, we have identified a total of 152 candidate young stellar objects (YSOs) in the region, of which, 75 are classified as Class II, 9 are Class I YSOs. Our YSO catalog also includes 50 H$_\alpha$-emission line sources, identified using slitless spectroscopy and IPHAS photometry data. Based on the optical and near-IR colour-magnitude diagram analyses, the cluster age has been estimated to be in the range of 2 $-$ 5 Myr, which is in agreement with the estimated age from disc fraction ($\sim$ 58\%). Masses of these YSOs are found to be $\sim$ 0.1$-$2.0 M$_\odot$. Spatial distribution of the candidate YSOs shows spherical morphology, more or less similar to the surface density map., Comment: 16 pages, 19 Figures

In addition to the zirconation of benzylic hydrocarbons, Ar−CH3, by di-n-butylzirconium diethoxide and the ensuing C−C bond formation from (Ar−CH2)2Zr(OEt)2 to yield Ar−CH2−CH(ZrH(OEt)2)−Ar, it has now been found that Bu2Zr(OEt)2 in ethers can also cleave the C−C bond in bibenzylic hydrocarbons, Ar−CH2−CH2−Ar‘, into benzylic zirconium fragments, (Ar−CH2)(Ar‘−CH2)Zr(OEt)2, as fostered by LiOEt and donor solvents. The role of SET processes in such C−C bond cleavages and the potential relevance to practical alkane metathesis are considered.

A broad survey of both the simple and double decomposition modes of transition metal alkyls has been undertaken. From the two main processes of C–M bond rupture, homolysis, and β-metal hydride elimination, the following modes of decomposition and types of useful reagents generated can be distinguished: 1) reductive decomposition of RnMEm–n to yield subvalent, carbene- or free-radical-like MEm–n, which can cleave π- or σ-bonds by direct epimetallation; 2) β-metal hydride elimination to produce hydrometallating agents; 3) combined reductive and β-metal hydride eliminations to produce anionic, and hence more nucleophilic, epimetallating agents; 4) α-metal hydride elimination thought to be involved in the transition state leading to C–C bond coupling from (RR'HC)2ME2 derivatives; 5) α,μ-elimination from lithiated RHC(Li)–MEn–1, which produces alkylidenes, RHC=MEn–2, capable of ROMP catalysis; 6) metal–hydrogen metathesis, whereby sufficiently acidic C–H bonds become C–M bonds; 7) metal–metal metathesis, whereby RR'ME2 undergoes an equilibrating redistribution reaction to form R2ME2 and R'2ME2; 8) transfer epimetallation, in which epimetallation (point 1) is achieved with R2ME2 in one step by transfer of ME2 to the substrate with the concomitant loss of R groups; and 9) transfer epimetallation of olefins by R2TiE2 in hydrocarbons to produce titana(IV)cyclopropanes, which serve as active sites in Ziegler–Natta polymerization. In each situation, the reaction-mechanistic features are analyzed in terms of existing experimental data and evidence. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

The mechanism of the rearrangement of diorganylzirconium dialkoxides, such as R1(R2CH2)Zr(OEt)2, into organylzirconium hydride alkoxides of the type R1R2CHZr(OEt)2H, has been investigated as a function of the R1 and R2 substituents and been found to involve optimally an intramolecular migration of R1 to an sp3-hybridized C−H center. A remarkably rapid transfer hydrozirconation between Bun2Zr(OEt)2 and the olefin RCHCH2 now permits the synthesis of (RCH2CH2)2Zr(OEt)2, whose rearrangement offers a route to the linear olefin dimer R(CH2)4R.

The frame stagings with a single row of columns placed along the periphery of a circle, are generally adopted for elevated water tanks to support the tank container. Apart from this usual staging configuration, some alternate configurations are also used in practice. These alternate configurations are made by adding few structural members to the usual configuration. These staging configurations are advantageous for adoption from a few different viewpoints. The present paper aims to observe the effect of soil–structure interaction on two dynamic characteristics namely, the impulsive lateral period which regulates lateral seismic behaviour and the impulsive torsional-to-lateral period ratio which regulates torsional vulnerability of the structure. The analytical expressions for these two dynamic characteristics have been derived considering the effect of soil-flexibility for elevated water tanks with these alternate configurations. These formulations have been validated against the results of finite element analysis for a few example tanks. A parametric study with limited example tanks based on these formulations shows that the frame staging with all kinds of alternate configurations having less panel heights, more number of columns, larger column diameter and stiffer circumferential beams compared to columns encounters the strongest influence of soil–structure interaction effect. The study on the example tanks with different alternate configurations shows that the design of elevated tanks based on a fixed base assumption may lead to wrong assessment of seismic base shear. The underestimation of base shear may lead to unsafe design whereas overestimation may cause uneconomic design. Neglecting soil-flexibility may also cause overlooking the possibility of occurring axial tension in columns and wrong assessment of torsional vulnerability of the staging structures.

Two-Faced Viral Protein Flaviviruses cause human diseases such as West Nile fever and dengue fever. The flavivirus nonstructural protein 1 (NS1) has multiple functions in flavivirus biology and is a target for vaccine development. Dimeric NS1 is essential for replication of the viral genome inside host cells, while hexameric NS1 is secreted and plays a role in evasion of the immune system. Akey et al. (p. 881 , published online 6 February; see the Perspective by Shi ) report crystal structures for full-length glycosylated NS1 from West Nile and dengue viruses. The structures show a hexamer comprised of three dimers. The structural analysis together with liposome and mutational studies identify a membrane interacting surface on one face of the dimer and an immune evasion surface on the other.

We present an improved mesh denoising method based on 3D geometric bilateral filtering. Its novelty is that it can preserve the details of the object as well as reduce the noise in an effective manner. The previous approach of geometric bilateral filtering for 3D-scan points has a limitation that it reduces the point density, thereby losing the details present in the object. The approach proposed by us, on the contrary, works on the surface mesh obtained after triangulating the 3D-scan points without any data downsampling. Each vertex of the mesh is repositioned appropriately based on the estimated centroid of the vertices in its local neighborhood and a Gaussian weight function. Experimental results demonstrate its strength, efficiency, and robustness.

Vibrio cholerae hemolysin (HlyA) is a 65 kDa pore-forming toxin which causes lysis of target eukaryotic cells by forming heptameric channels in the plasma membrane. Deletion of the 15 kDa C-terminus β-prism carbohydrate-binding domain generates a 50 kDa truncated variant (HlyA50) with 1000-fold-reduced pore-forming activity. Previously, we showed by cryo-electron microscopy that the two toxin oligomers have central channels, but the 65 kDa toxin oligomer is a seven-fold symmetric structure with bowl-, ring-, and arm-like domains, whereas the 50 kDa oligomer is an asymmetric jar-like heptamer. In the present study, we determined three-dimensional(3D) structures of HlyA and HlyA50 in presence of erythrocyte stroma and observed that interaction of the 65 kDa toxin with the stroma induced a significant decrease in the height of the β-barrel oligomer with a change in conformation of the ring- and arm-like domains of HlyA. These features were absent in interaction of HlyA50 with stroma. We propose that this conformational transition is critical for membrane-insertion of the toxin.

This paper presents the design perspectives of a low-cost portable 3D laser scanning mechanism. The hardware is simple in design, easy to fabricate, and costs much less compared to the cheapest ones available in the market. Moreover, it is noninvasive and able to generate high-quality data sets. We present the complete design pipeline and discuss how to implement and put together the most recent algorithms. We propose this design for its wide applications to virtual reality simulation, 3D modeling, digitization of archaeological artifacts, automated defect inspection, object recognition etc.