Broadband Microwave Spectrum And Structure Of Cyclopropyl Cyanosilane

The strucure of cyclopropane cyanosilane has been studied using chirped-pulse Fourier transform microwave (CP-FTMW) spectroscopy in the 6.5-18 GHz band. Two conformers of similar intensity were detected, one with a gauche orientation of the cyanosilane group with respect to the plane of the ring, and the other with a staggered conformation. The sensitivity of the CP-FTMW experiment was sufficient enough to assign spectra for all common singly-substituted heavy atom isotopologues ($^{13}$C, $^{29/30}$Si, $^{15}$N) for each conformer, resulting in a full heavy atom Kraitchman structure of the molecule in good agreement with the predicted structure. Additionally, the hyperfine effects have been analyzed for the $^{14}N$-containing parent species. Results will also be presented on the potential tunneling spectrum arising from the symmetric double well torsional potential of the gauche conformer. Some observed transitions, especially with frequencies near the upper end of the measured band, exhibit splittings that could potentially be associated with a tunneling splitting. However, the resolution is not sufficient to provide a complete quantitative analysis of this effect

Broadband Microwave Spectroscopy And Automated Analysis Of 12 Conformers Of 1-hexanal

The rotational spectrum of 1-hexanal is used as a test case for developing automated assignment algorithms in molecular rotational spectroscopy, for the purpose of lowering the barrier to new users of rotational spectroscopy. There are two ways that the automated fitting algorithm, implemented in the AUTOFIT program, is used: 1) Assignment of the rotational spectrum of a molecule expected to be in the sample mixture (in this case, a conformer of 1-hexanal), using quantum chemistry estimates of the spectroscopic parameters to efficiently guide the search for the experimental spectrum. 2) Once a new spectrum is assigned, the algorithm is used to automatically assign isotopologue spectra (sensitivity permitting) to provide verification of the molecular structure. Using a combination of quantum chemical calculations and automated spectral assignment, 12 conformations of 1-hexanal have been identified using chirped-pulse Fourier transform (CP-FTMW) spectroscopy in the 6.5-18, 18-26 and 26-40 GHz bands. Of these 12 conformers, the four lowest energy conformers were intense enough to resolve each of the six $^{13}$C isotopologues for each conformer, and sufficient intensity was achieved to assign the $^{18}$O isotopologues of the two lowest energy conformers. The full set of assignments were made using the AUTOFIT program, and a summary of results for all 38 observed species via automated assignment will be presented. Additionally, by using all 12 conformers of 1-hexanal as a benchmark set, a discussion of dispersion-corrected density functional theory for the purpose of automated broadband spectroscopic searches will be presented, with specific results regarding rotational constant prediction. Results will also be presented on the correlation between the predicted conformational energetics predicted by multiple levels of theory and the sensitivity limits of the 1-hexanal CP-FTMW spectrum

PROBING QUANTUM SOLVATION OF ASYMMETRIC ROTORS USING BROADBAND ROTATIONAL SPECTROSCOPY

Superfluid Helium-4 shows a variety of unique effects. For instance, the effective rotational constants for molecules embedded in $^{4}$He droplets are usually quite different than their gas-phase values. The observed molecular rotational constants shrink with increasing number of He atoms until the "turnaround point," where part of the $^{4}$He density rotationally decouples from a surrounding $^{4}$He superfluid shell, leading to anomalous rotational constants as the number of $^{4}$He atoms increases. Such behavior can appear well below the droplet limit; high-resolution studies of linear molecules embedded in small $^{4}$He clusters containing as few as 6 $^{4}$He atoms reveal superfluidic behavior.\footnote{[1] Tang, J.; Xu, Y.; McKellar, A. R. W.; Jäger, W. \textit{Science} \textbf{2002}, \textit{297}, 2030. [2] Dempster, S. P.; Sukhorukov, O.; Lei, Q. -Y.; Jäger, W., \textit{J. Chem. Phys.} \textbf{2012}, \textit{137}, 174303.} Although rovibrational spectra of asymmetric top molecules embedded in nanodroplets are routinely acquired using IR techniques, MW spectroscopy of small molecule-($^{4}$He)$_{n}$ clusters has been limited to linear molecules. In fact, only a small handful of theoretical studies of asymmetric tops embedded in superfluids are currently available.\footnote{[1] Zeng, T.; Li, H.; Roy, P. -N., \textit{J. Phys. Chem. Lett.} \textbf{2013}, \textit{4}, 18. [2] Zeng. T.; Roy, P. -N., \textit{Rep. Prog. Phys.} \textbf{2014}, \textit{77}, 046601.} The potential experimental complications are foreboding, and are exacerbated by limitations of the Balle-Flygare cavity experiments used in many of the early MW studies. Thankfully, chirped-pulse Fourier transform microwave (CP-FTMW) spectroscopy circumvents some of these limitations. Here, we show exciting new results on $^{4}$He clusters doped with pyridine and benzonitrile. These systems show intriguing and unexplained spectroscopic phenomena and dynamics. In the case of pyridine, we can identify spectroscopic transitions for clusters containing as many as 20 $^{4}$He atoms. We will also describe experimental techniques for sensitivity enhancement to detect such large molecule-doped helium clusters. These techniques, coupled with new efforts to characterize these systems theoretically, should extend generally to studies of more complicated chromophores

CHARACTERIZATION OF INTERMOLECULAR INTERACTIONS AT PLAY IN THE 2,2,2-TRIFLUOROETHANOL TRIMERS USING CAVITY AND CHIRPED-PULSE MICROWAVE SPECTROSCOPY

2,2,2-trifluoroethanol (TFE) is a common aqueous co-solvent in biological chemistry which may induce or destabilize secondary structures of proteins and polypeptides, thanks to its diverse intermolecular linkages originating from the hydrogen bonding potential of both the hydroxyl and perfluoro groups.footnote{M. Buck, Q. Rev. Biophys. 1998, 31, 297-335.} Theoretically, the TFE monomer is predicted to have two stable textit{gauche} (textit{gauche}$^{+}$/textit{gauche}$^{-}$) conformations whereas the textit{trans} form is unstable or is supported only by a very shallow potential. Only the gauche conformers have been identified in the gas phase, whereas liquid phase studies suggest a textit{trans}:textit{gauche} ratio of 2:3.footnote{I. Bakó, T. Radnai, M. Claire, B. Funel, J. Chem. Phys. 2004, 121, 12472-12480. } The question at which sample (cluster) size the textit{trans} form of TFE would appear was one major motivation for our study.\_x000d_ _x000d_ Here, we report the detection of three trimers of TFE using Balle-Flygare cavity and chirped-pulse Fourier transform microwave spectroscopy (CP-FTMW) techniques. The most stable observed trimer features one textit{trans}- and two textit{gauche}-TFE subunits. The other two trimers, observed using a newly constructed 2-6 GHz CP-FTMW spectrometer, consist of only the two textit{gauche} conformers of TFE. Quantum Theory of Atoms in Molecules (QTAIM)footnote{R. F. W. Bader, Chem. Rev. 1991, 91, 893-928.} and non-covalent interactions (NCI)footnote{E. R. Johnson, S. Keinan, P. Mori-Sánchez, J. Contreras-Garcia, A. J. Cohen, W. Yang, J. Am. Chem. Soc., 2010, 132, 6498-6506.} analyses give detailed insights into which intermolecular interactions are at play to stabilize the textit{trans} form of TFE in the most stable trimer

Broadband Fourier transform rotational spectroscopy for structure determination: The water heptamer

Over the recent years chirped-pulse, Fourier-transform microwave (CP-FTMW) spectrometers have chan- ged the scope of rotational spectroscopy. The broad frequency and large dynamic range make possible structural determinations in molecular systems of increasingly larger size from measurements of heavy atom (13C, 15N, 18O) isotopes recorded in natural abundance in the same spectrum as that of the parent isotopic species. The design of a broadband spectrometer operating in the 2–8 GHz frequency range with further improvements in sensitivity is presented. The current CP-FTMW spectrometer performance is benchmarked in the analyses of the rotational spectrum of the water heptamer, (H2O)7, in both 2– 8 GHz and 6–18 GHz frequency ranges. Two isomers of the water heptamer have been observed in a pulsed supersonic molecular expansion. High level ab initio structural searches were performed to pro- vide plausible low-energy candidates which were directly compared with accurate structures provided from broadband rotational spectra. The full substitution structure of the most stable species has been obtained through the analysis of all possible singly-substituted isotopologues (H218O and HDO), and a least-squares rm(1) geometry of the oxygen framework determined from 16 different isotopic species compares with the calculated O–O equilibrium distances at the 0.01 Å level

The Role of Non-Covalent Interactions on Cluster Formation: Pentamer, Hexamers and Heptamer of Difluoromethane

The role of non-covalent interactions (NCIs) has broadened with the inclusion of new types of interactions and a plethora of weak donor/acceptor partners. This work illustrates the potential of chirped-pulse Fourier transform microwave technique, which has revolutionized the field of rotational spectroscopy. In particular, it has been exploited to reveal the role of NCIs' in the molecular self-aggregation of difluoromethane where a pentamer, two hexamers and a heptamer were detected. The development of a new automated assignment program and a sophisticated computational screening protocol was essential for identifying the homoclusters in conditions of spectral congestion. The major role of dispersion forces leads to less directional interactions and more distorted structures than those found in polar clusters, although a detailed analysis demonstrates that the dominant interaction energy is the pairwise interaction. The tetramer cluster is identified as a structural unit in larger clusters, representing the maximum expression of bond between dimers.We thank MINECO (CTQ2017-89150-R), Basque Government (IT1162-19 and PIBA2018-11), the UPV/EHU (PPG17/10, GIU18/207), CSIC (2018FR0036, LINKA20249), University of Bologna (RFO), Fondazione CARISBO (2018/0353) and NSF (CHE-1903871 and CHE-2018427) for the financial support. C.C thanks MINECO for a Juan de la Cierva contract. L.E. was supported by Marie Curie fellowship PIOF-GA-2012-32840

The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells

Pentraxin 3 (PTX3) is a fluid-phase pattern recognition receptor of the humoral innate immune system with ancestral antibody-like properties but unknown antibody-inducing function. In this study, we found binding of PTX3 to splenic marginal zone (MZ) B cells, an innate-like subset of antibody-producing lymphocytes strategically positioned at the interface between the circulation and the adaptive immune system. PTX3 was released by a subset of neutrophils that surrounded the splenic MZ and expressed an immune activation–related gene signature distinct from that of circulating neutrophils. Binding of PTX3 promoted homeostatic production of IgM and class-switched IgG antibodies to microbial capsular polysaccharides, which decreased in PTX3-deficient mice and humans. In addition, PTX3 increased IgM and IgG production after infection with blood-borne encapsulated bacteria or immunization with bacterial carbohydrates. This immunogenic effect stemmed from the activation of MZ B cells through a neutrophil-regulated pathway that elicited class switching and plasmablast expansion via a combination of T cell–independent and T cell–dependent signals. Thus, PTX3 may bridge the humoral arms of the innate and adaptive immune systems by serving as an endogenous adjuvant for MZ B cells. This property could be harnessed to develop more effective vaccines against encapsulated pathogens.European Advanced grant ERC-2011-ADG-20110310, Ministerio de Ciencia e Innovación grant SAF2011-25241, and Marie Curie reintegra -tion grant PIRG-08-GA-2010-276928 to A. Cerutti; Sara Borrell post-doctoral fellow -ships to A. Chorny; and US National Institutes of Health grants R01 AI57653, U01 AI95613, P01 AI61093, and U19 096187 to A. Cerutti. C. Cunha and A. Carvalho were funded by grants from Fundação para a Ciência e Tecnologia, co-funded by Programa Operacional Regional do Norte (ON.2—O Novo Norte)., and from the Quadro de Referência Estratégico Nacional (SFRH/BPD/96176/2013 to C. Cunha and grant IF/00735/2014 to A. Carvalho) through the Fundo Europeu de Desenvolvimento Regional and Projeto Estratégico (LA 26 – 2013–2014; PEst-C/SAU/LA0026/2013

Genome Sequencing Reveals Widespread Virulence Gene Exchange among Human Neisseria Species

Commensal bacteria comprise a large part of the microbial world, playing important roles in human development, health and disease. However, little is known about the genomic content of commensals or how related they are to their pathogenic counterparts. The genus Neisseria, containing both commensal and pathogenic species, provides an excellent opportunity to study these issues. We undertook a comprehensive sequencing and analysis of human commensal and pathogenic Neisseria genomes. Commensals have an extensive repertoire of virulence alleles, a large fraction of which has been exchanged among Neisseria species. Commensals also have the genetic capacity to donate DNA to, and take up DNA from, other Neisseria. Our findings strongly suggest that commensal Neisseria serve as reservoirs of virulence alleles, and that they engage extensively in genetic exchange

Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network

Objectives In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.Conclusions Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required