The curious case of (caffeine).(benzoic acid): how heteronuclear seeding allowed the formation of an elusive cocrystal

Cocrystals are modular multicomponent solids with exceptional utility in synthetic chemistry and materials science. A variety of methods exist for the preparation of cocrystals yet, some promising cocrystal phases have proven to be intractable synthetic targets. We describe a strategy for the synthesis of the pharmaceutically relevant (caffeine).(benzoic acid) cocrystal (1), which persistently failed to form using a broad range of established techniques. State-of-the-art crystal structure prediction methods were employed to assess the possible existence of a thermodynamically stable form of 1, and to identify appropriate heteronuclear seeds for corystallization. Once introduced, the designed heteronuclear seeds facilitated the formation of 1 and, significantly, continued to act as long-lasting laboratory .contaminants., which encouraged cocrystal formation even when present at such low levels as to evade detection. The seeding technique described thus enables the synthesis of cocrystals regarded as unobtainable under desired conditions, and potentially signifies a new direction in the field of materials research

Low-energy p-d Scattering: High Precision Data, Comparisons with Theory, and Phase-Shift Analyses

Angular distributions of sigma(theta), A_y, iT_11, T_20, T_21, and T_22 have been measured for d-p scattering at E_c.m.=667 keV. This set of high-precision data is compared to variational calculations with the nucleon-nucleon potential alone and also to calculations including a three-nucleon (3N) potential. Agreement with cross-section and tensor analyzing power data is excellent when a 3N potential is used. However, a comparison between the vector analyzing powers reveals differences of approximately 40% in the maxima of the angular distributions which is larger than reported at higher energies for both p-d and n-d scattering. Single-energy phase-shift analyses were performed on this data set and a similar data set at E_c.m.=431.3 keV. The role of the different phase-shift parameters in fitting these data is discussed.Comment: 18 pages, 6 figure

Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose

Objective: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. Methods: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). Results: At D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- positivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and prednisone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05‒0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05‒0.88, p = 0.034). After six months (D69‒D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduction occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. Conclusion: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698)

Field Measurements of Terrestrial and Martian Dust Devils

Surface-based measurements of terrestrial and martian dust devils/convective vortices provided from mobile and stationary platforms are discussed. Imaging of terrestrial dust devils has quantified their rotational and vertical wind speeds, translation speeds, dimensions, dust load, and frequency of occurrence. Imaging of martian dust devils has provided translation speeds and constraints on dimensions, but only limited constraints on vertical motion within a vortex. The longer mission durations on Mars afforded by long operating robotic landers and rovers have provided statistical quantification of vortex occurrence (time-of-sol, and recently seasonal) that has until recently not been a primary outcome of more temporally limited terrestrial dust devil measurement campaigns. Terrestrial measurement campaigns have included a more extensive range of measured vortex parameters (pressure, wind, morphology, etc.) than have martian opportunities, with electric field and direct measure of dust abundance not yet obtained on Mars. No martian robotic mission has yet provided contemporaneous high frequency wind and pressure measurements. Comparison of measured terrestrial and martian dust devil characteristics suggests that martian dust devils are larger and possess faster maximum rotational wind speeds, that the absolute magnitude of the pressure deficit within a terrestrial dust devil is an order of magnitude greater than a martian dust devil, and that the time-of-day variation in vortex frequency is similar. Recent terrestrial investigations have demonstrated the presence of diagnostic dust devil signals within seismic and infrasound measurements; an upcoming Mars robotic mission will obtain similar measurement types

Highly unsaturated fatty acid synthesis in marine fish: Cloning, functional characterization, and nutritional regulation of fatty acyl delta6 desaturase of Atlantic cod (Gadus morhua L.)

Fish contain high levels of the n-3 highly unsaturated fatty acids (HUFA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids that are crucial to the health of higher vertebrates. Biosynthesis of HUFA requires enzyme-mediated desaturation of fatty acids. Here we report cloning and functional characterisation of a ∆6 fatty acyl desaturase of Atlantic cod (Gadus morhua), and describe its tissue expression and nutritional regulation. PCR primers were designed based on the sequences of conserved motifs in available fish desaturases and used to isolate a cDNA fragment from liver of cod. The full-length cDNA was obtained by Rapid Amplification of cDNA Ends (RACE). The cDNA for the putative fatty acyl desaturase was shown to comprise 1980bp which included a 5’-UTR of 261bp and a 3’-UTR of 375bp. Sequencing revealed that the cDNA included an ORF of 1344 bp that specified a protein of 447 amino acids. The protein sequence included three histidine boxes, two transmembrane regions, and an N-terminal cytochrome b5 domain containing the haem-binding motif HPGG, all of which are characteristic of microsomal fatty acid desaturases. The cDNA displayed Δ6 desaturase activity in a heterologous yeast expression system. Quantitative real time PCR assay of gene expression in cod showed that the ∆6 desaturase gene, was highly expressed in brain, relatively highly expressed in liver, kidney, intestine, red muscle and gill, and expressed at much lower levels in white muscle, spleen and heart. In contrast, the abundance of a cod fatty acyl elongase transcript was high in brain and gill, with intermediate levels in kidney, spleen, intestine and heart, and relatively low expression in liver. The expression of the Δ6 desaturase gene and the PUFA elongase gene may be under a degree of nutritional regulation, with levels being marginally increased in livers and intestine of fish fed a vegetable oil blend by comparison with levels in fish fed fish oil. However, this was not reflected in increased Δ6 desaturase activity in hepatocytes or enterocytes, which showed very little highly unsaturated fatty acid biosynthesis activity irrespective of diet. The study described has demonstrated that Atlantic cod express a fatty acid desaturase gene with functional Δ6 activity in a yeast expression system. This is consistent with an established hypothesis that the poor ability of marine fish to synthesise HUFA is not due to lack of a Δ6 desaturase, but rather to deficiencies in other parts of the biosynthetic pathway. However, further studies are required to determine why the Δ6 desaturase appears to be barely functional in cod under the conditions tested

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV

The Lambda(b) differential production cross section and the cross section ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7 TeV using data collected by the CMS experiment at the LHC. The measurements are based on Lambda(b) decays reconstructed in the exclusive final state J/Psi Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and Lambda to proton pion, using a data sample corresponding to an integrated luminosity of 1.9 inverse femtobarns. The product of the cross section times the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls faster than that of b mesons. The measured value of the cross section times the branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06 +/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are statistical and systematic, respectively.Comment: Submitted to Physics Letters

Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at sqrt(s) = 7 TeV

A search is presented for physics beyond the standard model (BSM) in final states with a pair of opposite-sign isolated leptons accompanied by jets and missing transverse energy. The search uses LHC data recorded at a center-of-mass energy sqrt(s) = 7 TeV with the CMS detector, corresponding to an integrated luminosity of approximately 5 inverse femtobarns. Two complementary search strategies are employed. The first probes models with a specific dilepton production mechanism that leads to a characteristic kinematic edge in the dilepton mass distribution. The second strategy probes models of dilepton production with heavy, colored objects that decay to final states including invisible particles, leading to very large hadronic activity and missing transverse energy. No evidence for an event yield in excess of the standard model expectations is found. Upper limits on the BSM contributions to the signal regions are deduced from the results, which are used to exclude a region of the parameter space of the constrained minimal supersymmetric extension of the standard model. Additional information related to detector efficiencies and response is provided to allow testing specific models of BSM physics not considered in this paper.Comment: Replaced with published version. Added journal reference and DO