Uptake of methanol on mixed HNO3/H2O clusters: An absolute pickup cross section.

The uptake of atmospheric oxidized organics on acid clusters is relevant for atmospheric new particle formation. We investigate the pickup of methanol (CH3OH) on mixed nitric acid-water clusters (HNO3)M(H2O)N by a combination of mass spectrometry and cluster velocity measurements in a molecular beam. The mass spectra of the mixed clusters exhibit (HNO3)m(H2O)nH+ series with m = 0-3 and n = 0-12. In addition, CH3OH·(HNO3)m(H2O)nH+ series with very similar patterns appear in the spectra after the methanol pickup. The velocity measurements prove that the undoped (HNO3)m(H2O)nH+ mass peaks in the pickup spectra originate from the neutral (HNO3)M(H2O)N clusters which have not picked up any CH3OH molecule, i.e., methanol has not evaporated upon the ionization. Thus the fraction of the doped clusters can be determined and the mean pickup cross section can be estimated, yielding σs¯≈ 20 Å2. This is compared to the lower estimate of the mean geometrical cross section σg¯≈ 60 Å2 obtained from the theoretical cluster geometries. Thus the "size" of the cluster corresponding to the methanol pickup is at least 3-times smaller than its geometrical size. We have introduced a method which can yield the absolute pickup cross sections relevant to the generation and growth of atmospheric aerosols, as illustrated in the example of methanol and nitric acid clusters.

Irregular shapes of water clusters generated in supersonic expansions.

We report cross sections for pickup of guest molecules on neutral argon and water clusters with the mean sizes in the range from N = 50 to 600. The experiments are supported by molecular dynamics simulations and analytical models based on the interaction potentials. The cross sections for argon clusters are consistent with their assumed spherical shape and follow approximately the theoretically justified N(1/3) dependence. On the other hand, the cross sections of water clusters depart from this dependence and are considerably larger starting from N ≥ 300. We interpret this increase of cross section by the occurrence of highly irregular shapes of water clusters produced in the supersonic expansion of water vapor under the conditions of the large cluster generation.

Imaging of hydrogen halides photochemistry on argon and ice nanoparticles.

The photodissociation dynamics of HX (X = Cl, Br) molecules deposited on large ArN and (H2O)N, N̄ ≈ 10(2)-10(3), clusters is investigated at 193 nm using velocity map imaging of H and Cl photofragments. In addition, time-of-flight mass spectrometry after electron ionization complemented by pickup cross section measurements provide information about the composition and structure of the clusters. The hydrogen halides coagulate efficiently to generate smaller (HX)n clusters on ArN upon multiple pickup conditions. This implies a high mobility of HX molecules on argon. On the other hand, the molecules remain isolated on (H2O)N. The photodissociation on ArN leads to strong H-fragment caging manifested by the fragment intensity peaking sharply at zero kinetic energy. Some of the Cl-fragments from HCl photodissociation on ArN are also caged, while some of the fragments escape the cluster directly without losing their kinetic energy. The images of H-fragments from HX on (H2O)N also exhibit a strong central intensity, however, with a different kinetic energy distribution which originates from different processes: the HX acidic dissociation followed by H3O neutral hydronium radical formation after the UV excitation, and the slow H-fragments stem from subsequent decay of the H3O. The corresponding Cl-cofragment from the photoexcitation of the HCl·(H2O)N is trapped in the ice nanoparticle.

Ionization of large homogeneous and heterogeneous clusters generated in acetylene-Ar expansions: cluster ion polymerization.

Pure acetylene and mixed Ar-acetylene clusters are formed in supersonic expansions of acetylene/argon mixtures and analysed using reflectron time-of-flight mass spectrometer with variable electron energy ionization source. Acetylene clusters composed of more than a hundred acetylene molecules are generated at the acetylene concentration of ≈8%, while mixed species are produced at low concentrations (≈0.7%). The electron energy dependence of the mass spectra revealed the ionization process mechanisms in clusters. The ionization above the threshold for acetylene molecule of 11.5 eV results in the main ionic fragment progression (C2H2)n(+). At the electron energies ≥21.5 eV above the CH+CH(+) dissociative ionization limit of acetylene the fragment ions nominally labelled as (C2H2)nCH(+), n ≥ 2, are observed. For n ≤ 7 these fragments correspond to covalently bound ionic structures as suggested by the observed strong dehydrogenation [(C2H2)n - k × H](+) and [(C2H2)nCH - k × H](+). The dehydrogenation is significantly reduced in the mixed clusters where evaporation of Ar instead of hydrogen can stabilize the nascent molecular ion. The C3H3(+) ion was previously assigned to originate from the benzene molecular ion; however, the low appearance energy of ≈13.7 eV indicates that a less rigid covalently bound structure of C6H6(+) ion must also be formed upon the acetylene cluster electron ionization. The appearance energy of Arn(C2H2)(+) fragments above ≈15.1 eV indicates that the argon ionization is the first step in the fragment ion production, and the appearance energy of Arn≥2(C2H2)m≥2(+) at ≈13.7 eV is discussed in terms of an exciton transfer mechanism.

Energy and charge transfer in ionized argon coated water clusters.

We investigate the electron ionization of clusters generated in mixed Ar-water expansions. The electron energy dependent ion yields reveal the neutral cluster composition and structure: water clusters fully covered with the Ar solvation shell are formed under certain expansion conditions. The argon atoms shield the embedded (H2O)n clusters resulting in the ionization threshold above ≈15 eV for all fragments. The argon atoms also mediate more complex reactions in the clusters: e.g., the charge transfer between Ar(+) and water occurs above the threshold; at higher electron energies above ~28 eV, an excitonic transfer process between Ar(+)* and water opens leading to new products Ar(n)H(+) and (H2O)(n)H(+). On the other hand, the excitonic transfer from the neutral Ar* state at lower energies is not observed although this resonant process was demonstrated previously in a photoionization experiment. Doubly charged fragments (H2O)(n)H2(2+) and (H2O)(n)(2+) ions are observed and Intermolecular Coulomb decay (ICD) processes are invoked to explain their thresholds. The Coulomb explosion of the doubly charged cluster formed within the ICD process is prevented by the stabilization effect of the argon solvent.

Uptake of atmospheric molecules by ice nanoparticles: pickup cross sections.

Uptake of several atmospheric molecules on free ice nanoparticles was investigated. Typical examples were chosen: water, methane, NO(x) species (NO, NO(2)), hydrogen halides (HCl, HBr), and volatile organic compounds (CH(3)OH, CH(3)CH(2)OH). The cross sections for pickup of these molecules on ice nanoparticles (H(2)O)(N) with the mean size of N≈260 (diameter ~2.3 nm) were measured in a molecular beam experiment. These cross sections were determined from the cluster beam velocity decrease due to the momentum transfer during the pickup process. For water molecules molecular dynamics simulations were performed to learn the details of the pickup process. The experimental results for water are in good agreement with the simulations. The pickup cross sections of ice particles of several nanometers in diameter can be more than 3 times larger than the geometrical cross sections of these particles. This can have significant consequences in modelling of atmospheric ice nanoparticles, e.g., their growth.

Laparoscopic resection for recurrent Crohn's disease: safety, feasibility and short-term outcomes.

AIM: The safety, feasibility and short-term outcomes of laparoscopic resection were assessed in patients with recurrent ileocolic Crohn's disease. METHOD: A consecutive series of patients was identified from a prospectively collated database. Data included patient demographics, previous medical and surgical treatment, operative details and postoperative course. Data from the original index open operation were collected retrospectively by review of the case notes. RESULTS: Between 2005 and 2009, 27 patients [21 women, mean (range) age 31 years (16-51 years)] underwent laparoscopic resection for recurrent ileocolic Crohn's disease. All had histologically confirmed recurrent disease at the ileocolic anastomosis. Five (18.5%) patients required extended resection for Crohn's colitis, three (11.1%) had fistulating disease and one (3.4%) patient had a psoas abscess. The median (range) operative time was 110 min (70-170 min) with a conversion rate of two (7.4%) of 27 patients. The length of stay was 4 days (2-7 days) with time to return to work or full activity of 3.5 weeks (2-7 weeks). CONCLUSION: Laparoscopic resection of recurrent ileocolic Crohn's disease is safe, feasible and associated with short-term benefits.

Trends towards increased use of the laparoscopic approach in colorectal surgery.

AIM: The aim of the study was to identify the trend towards laparoscopic resection in the practice of one surgeon and to determine whether the default approach to all colorectal procedures could be by means of minimally invasive techniques with an associated low rate of conversion. METHOD: A prospective database of primary colorectal resections under the care of one colorectal surgeon collected between July 2003 and December 2008 was analysed to determine the trend in the use of the laparoscopic approach and the rate of conversion of an intention-to-treat policy for laparoscopic procedures. Patients with recurrent rectal or colonic malignancy were excluded from the study. RESULTS: A total of 598 patients underwent elective colorectal resection of which 371 (62%) were carried out laparoscopically with a rate of conversion of 3.2%. The proportion of all colorectal resections that were undertaken laparoscopically in the first 1 year was 26% (22/85) (no conversions). This proportion rose to 100% (127/127) in the fifth year of the study of which 4.0% were converted. The introduction of more complex procedures did not have an adverse effect on the trend towards more laparoscopic resections The commencement of a laparoscopic colorectal fellowship in 2006 was associated with a marked increase in the number of laparoscopic cases. CONCLUSION: A conscious decision to make the laparoscopic approach the default for all colorectal resections can be achieved safely with a low conversion rate. This can be achieved within the context of training a 'novice' laparoscopic colorectal surgeon.

Dual role of the Drosophila pattern gene tailless in embryonic termini.

One of the first zygotically active genes required for formation of the terminal domains of the Drosophila embryo is tailless (tll). Expression of the tll gene is activated ectopically in gain-of-function mutants of the maternal terminal gene torso (tor); this suggests that tor normally activates the tll gene in the termini. Ectopic expression of tll under the control of an inducible promoter results in differentiation of ectopic terminal-specific structures, the Filzkörper, and leads to the activation of at least one gene, hunchback, that is required to form these structures. Ectopic expression of the tll gene also represses segmentation by repressing the gap genes Krüppel and knirps and probably also pair rule genes.

Multimedia article. Laparoscopic abdominosacral composite resection.

Primary rectal cancer with direct invasion into the sacrum requires en bloc resection that encompasses both the rectum and the sacrum. Application of laparoscopic techniques to the abdominal component should potentially provide the patient with the short-term benefits of a minimally invasive approach and permit adequate mobilization to permit completion of the procedure via the transsacral route. The aim of this video was to describe the operative details of such a technique.

Pharmacokinetic studies of (-)-deprenyl and some of its metabolites in mouse.

(-)-Deprenyl is a selective irreversible inhibitor of MAO-B. The parent compound is responsible for the enzyme inhibitory effect, but its metabolites are also playing a role in the complex pharmacological activity of the substance. In the present studies male NMRI mice were treated orally, subcutaneously, intraperitoneally and intravenously with 5 mg/kg of (-)-deprenyl. The time related changes of the plasma concentrations of the parent compound and its main metabolites (methamphetamine, desmethyl-deprenyl and amphetamine) were determined by GC/ MSD technique. The main pharmacokinetic parameters (C(max), t(max), t1/2beta, AUC(0-6), AUC(0-infinity)) have been calculated. (-)-Deprenyl is well absorbed after oral and parental treatment. The peak concentrations (C(max)) were reached at 15 min after treatment and the absorption was followed by a fast elimination (t1/2beta < or = 2h). (-)-Deprenyl has an intensive "first pass" metabolism after oral treatment; only 25% of the parent compound reaches the systemic circulation. Increased bioavailability was detected after subcutaneous (87.1%) and intraperitoneal (78.7%) administration. The main metabolic pathway of (-)-deprenyl is the N-depropargylation, leading to the formation of methamphetamine. N-demethylation of (-)-deprenyl leads to formation of desmethyl-deprenyl. Amphetamine is produced from both former metabolites. After oral treatment the plasma concentrations of methamphetamine are higher during the first 6 h than that of (-)-deprenyl, while the opposite was found after parental treatment. The results indicate, that (-)-deprenyl, a potent MAO-B inhibitor, might induce a different spectrum of activity (e.g. antidepressant), when it is administered parenterally (transdermally). The new spectrum can be due to the special pharmacokinetic behaviour of the inhibitor.

Embryonic head involution and rotation of male terminalia require the Drosophila locus head involution defective.

We have characterized the head involution defective (hid) locus which is located within the chromosomal region 75B8-C1,2. During the morphogenetic reorganization of the embryonic head region, hid+ function is necessary for the movement of the dorsal fold across the procephalon and clypeolabrum, a process that forms the frontal sac. The absence of the frontal sac in the hid mutant embryos affects the formation of the dorsal bridge and disrupts the development of the larval cephalopharyngeal skeleton. In addition to its embryonic role, this same hid function is also required during pupal development for the 360 degrees rotation of the male terminalia about the anterior-posterior body axis, and for a late step of wing blade morphogenesis. Although the abnormal wing phenotype caused by the Wrinkled (W) mutation is quite different from the one resulting from the loss-of-function hid mutations, the characterization of EMS-induced W revertants reveals that W is actually an antimorphic allele of hid.

The thick veins gene of Drosophila is required for dorsoventral polarity of the embryo.

We have discovered a new member of the class of genes controlling embryonic dorsoventral patterning. Mutants of the thick veins (tkv) gene have been described previously (as slater alleles) as embryonic lethal, lacking dorsal epidermis, but not as showing a recognizable dorsoventral phenotype. We show here that maternal alteration of function coupled with zygotic reduction of function of tkv is strongly ventralizing. In addition, in double heterozygous combinations in the mother, tkv mutations increase the ventralizing effect of dominant, weakly ventralizing alleles of the maternal effect, dorsoventral genes easter and cactus. An interaction is also seen with zygotic dorsoventral genes: tkv interacts maternally and zygotically in double heterozygotes with decapentaplegic and zygotically with screw in double homozygotes. We conclude that both maternally and zygotically supplied wild-type tkv product can play a role in dorsoventral patterning of the early embryo. On the basis of the phenotype of trans-heterozygous adult escapers, we propose that tkv might act by potentiating the activity of the zygotically acting decapentaplegic gene.

Identification of genes controlling malpighian tubule and other epithelial morphogenesis in Drosophila melanogaster.

The Drosophila Malpighian tubule is a model system for studying genetic mechanisms that control epithelial morphogenesis. From a screen of 1800 second chromosome lethal lines, by observing uric acid deposits in unfixed inviable embryos, we identified five previously described genes (barr, fas, flb, raw, and thr) and one novel gene, walrus (wal), that affect Malpighian tubule morphogenesis. Phenotypic analysis of these mutant embryos allows us to place these genes, along with other previously described genes, into a genetic pathway that controls Malpighian tubule development. Specifically, wal affects evagination of the Malpighian tubule buds, fas and thr affect bud extension, and barr, flb, raw, and thr affect tubule elongation. In addition, these genes were found to have different effects on development of other epithelial structures, such as foregut and hindgut morphogenesis. Finally, from the same screen, we identified a second novel gene, drumstick, that affects only foregut and hindgut morphogenesis.

Single amino acid exchanges in separate domains of the Drosophila serendipity delta zinc finger protein cause embryonic and sex biased lethality.

The Drosophila serendipity (sry) delta (delta) zinc finger protein is a sequence-specific DNA binding protein, maternally inherited by the embryo and present in nuclei of transcriptionally active cells throughout fly development. We report here the isolation and characterization of four ethyl methanesulfate-induced zygotic lethal mutations of different strengths in the sry delta gene. For the stronger allele, all of the lethality occurs during late embryogenesis or the first larval instar. In the cases of the three weaker alleles, most of the lethality occurs during pupation; moreover, those adult escapers that emerge are sterile males lacking partially or completely in spermatozoa bundles. Genetic analysis of sry delta thus indicates that it is an essential gene, whose continued expression throughout the life cycle, notably during embryogenesis and pupal stage, is required for viability. Phenotypic analysis of sry delta hemizygote escaper males further suggests that sry delta may be involved in regulation of two different sets of genes: genes required for viability and genes involved in gonadal development. All four sry delta alleles are fully rescued by a wild-type copy of sry delta, but not by an additional copy of the sry beta gene, reinforcing the view that, although structurally related, these two genes exert distinct functions. Molecular characterization of the four sry delta mutations revealed that these mutations correspond to single amino acid replacements in the sry delta protein. Three of these replacements map to the same (third out of seven) zinc finger in the carboxy-terminal DNA binding domain; interestingly, none affects the zinc finger consensus residues. The fourth mutation is located in the NH2-proximal part of the protein, in a domain proposed to be involved in specific protein-protein interactions.

Control of tailless expression by bicoid, dorsal and synergistically interacting terminal system regulatory elements.

Three different maternal morphogen gradients regulate expression of the gap gene tailless (tll), which is required to establish the acron and telson of the Drosophila embryo. To identify elements in the tll promoter that respond to these different maternal systems, we have generated promoter-lacZ fusions and transformed them into the germline. Expression of these constructs in both wild type and mutant embryos revealed the presence of at least two separate but synergistically interacting regions that mediate tll expression by the terminal system. This functional synergism between regulatory elements may play a role in the translation of the torso (tor) morphogen gradient into the sharp boundary of tll gene activity. In addition to regions mediating activation by the terminal system, regions mediating both activation and repression by bicoid (bcd), and repression by dorsal (dl) were identified. Binding sites of bcd protein in a 0.5 kb region, revealed by DNaseI footprinting, could be crucial for the bcd-dependent activation of tll expression in the anterior stripe.

Graded effect of tailless on posterior gut development: molecular basis of an allelic series of a nuclear receptor gene.

By marking cells of early gastrula stage embryos, we showed that in embryos mutant for a strong tll allele the fate map is shifted posteriorly and the hindgut anlage is deleted. We therefore used aspects of hindgut development to characterize the phenotype of new and previously described tll alleles. In embryos mutant for the various alleles, relative levels of blastoderm expression of Trg (T-related gene, required to establish the hindgut) and of mature hindgut size were determined; the results of these assays correlated with each other. Of the alleles that map to the sequence encoding the Tailless nuclear receptor protein, all (four) affect the zinc fingers of the DNA binding domain; surprisingly, substitutions of highly conserved residues allow a range of activities as detected by our bioassays.

Detection of Nepsilon-monomethyllysine using high-performance liquid chromatography and high-performance liquid chromatography-mass spectrometry.

Nepsilon-Monomethyllysine was identified in the serum, urine, brain, and liver samples of rats treated per os with L-deprenyl. The identification procedure included reaction with Fmoc chloride, clean-up, and analysis using HPLC-UV-MS. Oral administration of (-)-N-14C-methyl-N-propynyl(2-phenyl-1-methyl)ethylammonium hydrochloride L-deprenyl) to rats resulted in transfer of the radiolabelled methyl group to the Nepsilon-amino group of the endogenous lysine. The radiolabelled Nepsilon-monomethyllysine was urinary eliminated together with the other radiolabelled deprenyl metabolites, such as deprenyl-N-oxide and methamphetamine. The presence of Nepsilon-monomethyllysine has also been traced, and its concentrations were compared in the serum, liver and brain of rats subjected to L-deprenyl treatment. Methyl group transfer from the L-deprenyl to endogenous compounds; and the urinary elimination of their products may offer a vital way to eliminate or to decrease the degree of drug transmethylation to the lysine constituents of blood vessels' proteins.

HPLC and HPLC-MS analysis of urinary N(epsilon)-monomethyl-lysine.

Administration of (14)C-labelled L-deprenyl to rats results in the urinary elimination of a 14C-labelled compound. The 9-fluorenylmethoxycarbonyl chloride-reacted urine sample is fractionated by high-performance liquid chromatography (HPLC) on an octadecyl silica stationary phase. N(epsilon)-Monomethyl-lysine is identified in the fraction containing the majority of the radioactivity. Structural elucidation is carried out using HPLC-mass spectrometry in atmospheric pressure chemical ionization mode. Identification of the 14C-labelled fragment in Ne-monomethyl-lysine is an experimental proof that an N-methylated amino acid is generated by transmethylation from a well-known drug. This type of transmethylation may have basic importance in the positive side effects of certain drugs.

Expression and sequence analysis of the Drosophila blastoderm-specific gene bsg25A.

By differential screening of a genomic library, we have cloned a gene expressed specifically during the blastoderm stage of Drosophila embryogenesis. Northern blot analysis and in situ hybridization to embryos reveal that the transcript is maximally expressed during the late syncytial blastoderm stage, disappears rapidly during the cellular blastoderm stage and is not detected at any other point in the Drosophila life cycle. On the basis of its temporally restricted expression and its polytene chromosomal map position at 25A1,2, we have designated this gene blastoderm-specific gene 25A (bsg25A). bsg25A encodes a novel protein of 23 kDa.