74 MHz nonthermal emission from molecular clouds: evidence for a cosmic ray dominated region at the galactic center.

We present 74 MHz radio continuum observations of the Galactic center region. These measurements show nonthermal radio emission arising from molecular clouds that is unaffected by free­free absorption along the line of sight. We focus on one cloud, G0.13-0.13, representative of the population of molecular clouds that are spatially correlated with steep spectrum (α(327MHz)(74MHz) = 1.3 ± 0.3) nonthermal emission from the Galactic center region. This cloud lies adjacent to the nonthermal radio filaments of the Arc near l 0.2° and is a strong source of 74 MHz continuum, SiO (2-1), and Fe I Kα 6.4 keV line emission. This three-way correlation provides the most compelling evidence yet that relativistic electrons, here traced by 74 MHz emission, are physically associated with the G0.13-0.13 molecular cloud and that low-energy cosmic ray electrons are responsible for the Fe I Kα line emission. The high cosmic ray ionization rate 10(­1)3 s(­1) H(­1) is responsible for heating the molecular gas to high temperatures and allows the disturbed gas to maintain a high-velocity dispersion. Large velocity gradient (LVG) modeling of multitransition SiO observations of this cloud implies H2 densities 10(4­5) cm(­3) and high temperatures. The lower limit to the temperature of G0.13-0.13 is 100 K, whereas the upper limit is as high as 1000 K. Lastly, we used a time-dependent chemical model in which cosmic rays drive the chemistry of the gas to investigate for molecular line diagnostics of cosmic ray heating. When the cloud reaches chemical equilibrium, the abundance ratios of HCN/HNC and N2H+/HCO+ are consistent with measured values. In addition, significant abundance of SiO is predicted in the cosmic ray dominated region of the Galactic center. We discuss different possibilities to account for the origin of widespread SiO emission detected from Galactic center molecular clouds.

Water on the sun: line assignments based on variational calculations.

The infrared spectrum of hot water observed in a sunspot has been assigned. The high temperature of the sunspot (3200 K) gave rise to a highly congested pure rotational spectrum in the 10-micrometer region that involved energy levels at least halfway to dissociation. Traditional spectroscopy, based on perturbation theory, is inadequate for this problem. Instead, accurate variational solutions of the vibration-rotation Schrödinger equation were used to make assignments, revealing unexpected features, including rotational difference bands and fewer degeneracies than anticipated. These results indicate that a shift away from perturbation theory to first principles calculations is necessary in order to assign spectra of hot polyatomic molecules such as water.

Astrochemical evolution along star formation: Overview of the IRAM Large Program ASAI.

Evidence is mounting that the small bodies of our Solar System, such as comets and asteroids, have at least partially inherited their chemical composition from the first phases of the Solar System formation. It then appears that the molecular complexity of these small bodies is most likely related to the earliest stages of star formation. It is therefore important to characterize and to understand how the chemical evolution changes with solar-type protostellar evolution. We present here the Large Program "Astrochemical Surveys At IRAM" (ASAI). Its goal is to carry out unbiased millimeter line surveys between 80 and 272 GHz of a sample of ten template sources, which fully cover the first stages of the formation process of solar-type stars, from prestellar cores to the late protostellar phase. In this article, we present an overview of the surveys and results obtained from the analysis of the 3 mm band observations. The number of detected main isotopic species barely varies with the evolutionary stage and is found to be very similar to that of massive star-forming regions. The molecular content in O- and C- bearing species allows us to define two chemical classes of envelopes, whose composition is dominated by either a) a rich content in O-rich complex organic molecules, associated with hot corino sources, or b) a rich content in hydrocarbons, typical of Warm Carbon Chain Chemistry sources. Overall, a high chemical richness is found to be present already in the initial phases of solar-type star formation.

Specific antibodies to diphtheria toxin and type 6A pneumococcal capsular polysaccharide induced by a model of semi-synthetic glycoconjugate antigen.

A molecular model of a carbohydrate-protein conjugate is described, involving the non-toxic mutant protein CRM197, serologically related to the diphtheria toxin, covalently bound to a characterized oligosaccharide derived from the molecular structure of type 6A pneumococcal capsular polysaccharide. Physicochemical and immunochemical characteristics of this oligosaccharide-protein conjugate were consistent with a molecule showing a molar carbohydrate/protein ratio of 8, an av. mol. wt of 75,000, and retention of complete immunochemical identity when tested towards the homologous antisera. The immunological characteristics obtained after immunization of 2 animal models showed a high immunogenicity of the glycoconjugate specifically directed towards diphtheria toxin and the type 6A pneumococcal capsular polysaccharide.

A molecular model of artificial glycoprotein with predetermined multiple immunodeterminants for gram-positive and gram-negative encapsulated bacteria.

An artificial molecule was synthesized by covalently linking the oligosaccharide haptens derived frm Streptococcus pneumoniae type 6A and Neisseria meningitidis group C capsular polysaccharides to the non-toxic mutant protein CRM197, serologically related to diphtheria toxin. Immunochemical analysis using polyclonal and monoclonal antibodies showed in the glycoprotein the presence of specific immunodeterminants of the native polysaccharides and of the carrier protein. The immunological activity of this hybrid molecule tested in two animal models gave evidence for anamnestic induction of serum antibodies specifically directed to the three distinct native molecules. They neutralized the toxicity of diphtheria toxin, recognized the polysaccharide capsule of S. pneumoniae type 6A and 6B (group 6) strain and killed the N. meningitidis group C bacteria by complement-mediated bacterial lysis. These findings support the possibility of using in humans a multivalent antigen with immunogenic activity for several epidemiologically significant Gram-positive and Gram-negative encapsulated bacterial strains.

The formation of glycine and other complex organic molecules in exploding ice mantles.

Complex Organic Molecules (COMs), such as propylene (CH3CHCH2) and the isomers of C2H4O2 are detected in cold molecular clouds (such as TMC-1) with high fractional abundances (Marcelino et al., Astrophys. J., 2007, 665, L127). The formation mechanism for these species is the subject of intense speculation, as is the possibility of the formation of simple amino acids such as glycine (NH2CH2COOH). At typical dark cloud densities, normal interstellar gas-phase chemistries are inefficient, whilst surface chemistry is at best ill defined and does not easily reproduce the abundance ratios observed in the gas phase. Whatever mechanism(s) is/are operating, it/they must be both efficient at converting a significant fraction of the available carbon budget into COMs, and capable of efficiently returning the COMs to the gas phase. In our previous studies we proposed a complementary, alternative mechanism, in which medium- and large-sized molecules are formed by three-body gas kinetic reactions in the warm high density gas phase. This environment exists, for a very short period of time, after the total sublimation of grain ice mantles in transient co-desorption events. In order to drive the process, rapid and efficient mantle sublimation is required and we have proposed that ice mantle 'explosions' can be driven by the catastrophic recombination of trapped hydrogen atoms, and other radicals, in the ice. Repeated cycles of freeze-out and explosion can thus lead to a cumulative molecular enrichment of the interstellar medium. Using existing studies we based our chemical network on simple radical addition, subject to enthalpy and valency restrictions. In this work we have extended the chemistry to include the formation pathways of glycine and other large molecular species that are detected in molecular clouds. We find that the mechanism is capable of explaining the observed molecular abundances and complexity in these sources. We find that the proposed mechanism is easily capable of explaining the large abundances of all three isomers of C2H4O2 that are observationally inferred for star-forming regions. However, the model currently does not provide an obvious explanation for the predominance of methyl formate, suggesting that some refinement to our (very simplistic) chemistry is necessary. The model also predicts the production of glycine at a (lower) abundance level, that is consistent with its marginal detection in astrophysical sources.

Development and phase 1 clinical testing of a conjugate vaccine against meningococcus A and C.

A conjugate vaccine against meningococcus A and C was prepared using the non-toxic mutant of diphtheria toxin CRM 197 as a carrier protein. Capsular polysaccharides of Neisseria meningitidis group A and C were hydrolysed and the resulting oligosaccharides were then coupled to CRM 197 in order to obtain conjugates with a carbohydrate content of 25-30%. The final vaccine that contained 11 micrograms of each oligosaccharide and 88 micrograms of CRM 197 was used to immunize mice and rabbits. After the preclinical studies which showed that the vaccine was safe and immunogenic in animal models, a pilot phase 1 clinical trial, blind versus placebo, was performed on adult volunteers. The difference between the incidence of adverse reactions associated with vaccine and placebo administration was not statistically significant. All the volunteers who received the vaccine had a significant increase in antibodies to group A and C meningococcal capsular polysaccharides after the first dose.

Immunity to Haemophilus influenzae type b on sample population from central Italy.

A study on natural immunity to Haemophilus influenzae type b (Hib) was carried out in the province of Siena on 474 subjects ranging in age from 3 days to 70 years. The titration of antibody to capsular polysaccharide (PRP) was performed by the radioantigen-binding assay (RABA) method. A total of 66.67% of the population studied presented an antibody level considered to be protective (greater than or equal to 0.15 microgram ml-1). Seropositivity was 5.7% in the 5-7 month age group and 29.09% in the 8-17 month age group. This rose progressively in successive age groups reaching 79.54% between 4 and 6 years old and a value greater than 90% after 7 years old. From 3 to 17 months even the geometric mean of antibodies to PRP was below the protective limit. Our data indicate that, even in Italy, the majority of the infant population is not protected against H. influenzae, and therefore that vaccination should also be introduced in this country.

Immunoelectrophoretic characterization of the molecular weight polydispersion of polysaccharides in multivalent bacterial capsular polysaccharide vaccines.

The molecular weight polydispersion of single antigens present in multivalent bacterial capsular polysaccharide vaccines has been characterized by an immunoelectrophoretic method. Chromatographic effluents from Sepharose gel of bacterial capsular polysaccharide vaccines were tested by fused-rocket immunoelectrophoresis and the distribution coefficient (Kd) of each polysaccharide present in the mixture was calculated. The method appeared to be efficient and reproducible. However, different Kd values were obtained by immunoelectrophoretic and chemical or physical analysis of the chromatographic effluents of each single polysaccharide component. The use of this immunoelectrophoretic procedure was extended to the potency control of multivalent meningococcal and pneumococcal polysaccharide vaccines in order to detect changes in the molecular weight polydispersion of each antigen with time.

A semi-synthetic glycoconjugate antigen prepared by chemical glycosilation of pertussis toxin by a meningococcal group C oligosaccharide hapten.

The preparation of a hybrid molecule obtained by chemical glycosilation of pertussis toxin (PT) is reported, with the purpose of obtaining a semi-synthetic glycoprotein antigen with bivalent antigenicity. The chemical glycosilation was performed using an oligosaccharide hapten derived from the purified capsular polysaccharide of Neisseria meningitidis group C. The semi-synthetic molecule was investigated by chemico-physical and immunochemical analysis. The oligosaccharide haptens appeared exposed on the surface of the carrier protein PT, since the glycoprotein inhibited the immunoprecipitate between a specific polyclonal antiserum and the native bacterial capsular polysaccharide. By contrast, the main antigenic regions recognized in the native protein PT by specific polyclonal antibodies appeared lost after the coupling procedure involving PT as the carrier protein.

Water Vapor Line Assignments in the Near Infrared.

The high-resolution spectrum of water vapor between 13 200 and 16 500 cm-1 recorded by J.-Y. Mandin, J-P. Chevillard, C. Camy-Peyret, J.-M. Flaud, and J. W. Brault (1986. J. Molec. Spectrosc., 116, 167) is analyzed using high-accuracy linelists obtained using ab initio calculations and spectroscopically determined potential. Assignments to H216O transitions are presented for 663 of the 795 unassigned lines presented in the original paper. In addition, 38 lines are reassigned. The majority of these assignments and reassignments are confirmed by combination differences. These assignments significantly extend the measured data for the 4nu and 4nu + delta polyads and provide the first information on the (240), (033), (160), (170), and (071) bands. It is likely that a significant fraction of the remaining unassigned lines belong to H218O. Copyright 1998 Academic Press.

Intestinal histological and ultrastructural inflammatory changes in spondyloarthropathy and rheumatoid arthritis.

To determine the prevalence of morphologic bowel lesions in patients with inflammatory rheumatic diseases and to better define the interactions between intestinal and articular pathology, 177 patients [39 with reactive arthritis (ReA), 40 with psoriatic arthritis (PsA), 23 with ankylosing spondylitis (AS), 21 with undifferentiated spondyloarthropathy (USpA) and 54 with rheumatoid arthritis (RA)] underwent ileocolonoscopy followed by multiple biopsies of the large bowel and the ileum and ileocecal valve. Biopsies were then examined with light and electron microscopy. During the endoscopic examination various degrees of gut inflammation were observed in 13% of ReA, 5% of PsA, 26% of AS, 14% of USpA and 11% of RA patients. At the histological examination those percentages were respectively 51%, 45%, 48%, 38%, and 15%, and at the electron microscopic examination 76%, 53%, 90%, 60%, and 50%. Our results show that an involvement of the gut is a factor in a large percentage of patients with spondyloarthropathy and, to a lesser extent, with RA. The involvement of the intestine in RA manifests itself mainly in ultrastructural lesions, thus this involvement is not so obvious as in the spondyloarthropathies; however, it could nonetheless play an important role in the etiopathogenesis of this disease.

High-Temperature Rotational Transitions of Water in Sunspot and Laboratory Spectra

Assignments are presented for spectra of hot water obtained in absorption in sunspots (T approximately 3000°C and 750

Size fractionation of bacterial capsular polysaccharides for their use in conjugate vaccines.

We have developed a chromatographic method suitable for the fractionation of polysaccharides having a negatively charged group. The method permits the removal of all those polysaccharide fragments having a short sequence and which are likely unsuitable for conjugate vaccine construction. The selected polysaccharide fragments can be used to produce glycoconjugate vaccines containing a restricted saccharide polydispersion. We have applied this chromatographic method to three different antigens, Haemophilus influenzae type b and Neisseria meningitidis group A and group C polysaccharides. The method is easily adapted for manufacturing purposes.