Dissociative ionization and Coulomb explosion of CH4 in two-color asymmetric intense laser fields.

Directional fragment ejection from a tetrahedral molecule CH4 in linearly polarized two-color (ω and 2ω) asymmetric intense laser fields (50 fs, 1.4 × 1014 W cm-2, 800 nm and 400 nm) has been studied by three-dimensional ion coincidence momentum imaging. The H+ fragment produced from dissociative ionization, CH4 → H+ + CH3 + e-, is preferentially ejected on the larger amplitude side of the laser electric fields. Comparison with theoretical predictions by weak-field asymptotic theory shows that the observed asymmetry can be understood by the orientation selective tunneling ionization from the triply degenerated highest occupied molecular orbital (1t2) of CH4. A similar directional ejection of H+ was also observed for the low kinetic energy components of the two-body Coulomb explosion, CH4 → H+ + CH3+ + 2e-. On the other hand, the fragment ejection in the opposite direction were observed for the high energy component, as well as H2+ produced from the Coulomb explosion CH4 → H2+ + CH2+ + 2e-. Possible origins of the characteristic fragmentation are discussed.

Helicity-dependent dissociative tunneling ionization of CF4 in multicycle circularly polarized intense laser fields.

Dissociative tunneling ionization of tetrafluoromethane (CF4) in circularly polarized ultrashort intense laser fields (35 fs, 0.8 × 1014 W cm-2, 1035 nm), CF4 → CF4+ + e- → CF3+ + F + e-, has been studied by three-dimensional electron-ion coincidence momentum imaging. The photoelectron angular distribution in the recoil frame revealed that the dissociative tunneling ionization occurs efficiently when the laser electric field points from F to C. The obtained results are qualitatively consistent with the theoretical predictions by the weak-field asymptotic theory (WFAT) for tunneling ionization from the highest and next-highest occupied molecular orbitals, HOMO (1t1), and HOMO-1 (4t2), respectively. On the other hand, the angular distribution shows clear dependences on the polarization helicity, indicating that the breaking of the C-F bonds is sensitive to the helicity of the multicycle circularly polarized laser fields.

Protonation of aqueous alanine by photoionization of water.

Hydronium ions produced by photolysis of water are used to study the protonation dynamics of alanine zwitterions in water. The measurements are done by UV-VIS and UV-IR femtosecond transient absorption spectroscopy on alanine in H2O and D2O. It is estimated that the reaction rate constant for the deuteration of alanine zwitterions is 4 × 1010 M-1 s-1, while the reverse process has a rate constant of 2 × 108 s-1. In addition to hydronium ions the photolysis of water yields hydrogen atoms and hydrated electrons together with hydroxyl radicals and hydroxyl ions. However, no other products resulting from reactions between aqueous alanine and the photolysis products of water are positively identified during the first 530 ps after the photolysis. Potential secondary reactions that are not observed experimentally are discussed and an upper limit is set for their yield where possible.

Strain Elastography for Prediction of Malignancy in Soft Tissue Tumours--Preliminary Results.

PURPOSE: To evaluate the ability of strain elastography to predict malignancy in patients with soft tissue tumors, and to compare three evaluation methods of strain elastography: strain ratios, strain histograms and visual scoring. MATERIALS AND METHODS: 60 patients with 61 tumors were analyzed in the study. All patients were referred due to suspicion of malignant soft tissue tumors after diagnostic imaging (contrast-enhanced MRI, CT or PET-CT). Ultrasound-guided biopsy was preceded by the recording of strain elastography video clips, which were evaluated in consensus between three investigators. Strain ratio, strain histogram analysis and visual scoring using a five-point visual scale were compared with the final pathology from either biopsy or resection of the tumors. RESULTS: The difference between the mean strain ratio for malignant and benign tumors was significant (p = 0.043). The mean strain ratios for malignant and benign tumors were 1.94 (95% CI [0.37; 10.21]) and 1.35 (95% CI [0.32; 5.63]), respectively. There were no significant differences for strain histograms or visual scoring. Liposarcomas had lower mean strain ratio, strain histogram values, and visual scoring than other malignant tumors. When analyzing a subgroup of patients without fat-containing tumors (n = 46), based on appearance on MRI or CT, the difference between the mean strain ratios for malignant and benign tumors increased (p = 0.014). CONCLUSION: The mean strain ratios of malignant tumors were significantly higher than the mean strain ratios of benign tumors. There was no significant difference for strain histograms and visual scoring. Strain ratios may be used as an adjunct in soft tissue tumor diagnosis, possibly minimizing the number of biopsies.

Nitric oxide improves the hemodynamic performance of the hypoxic goldfish (Carassius auratus) heart.

Goldfish tolerate prolonged and severe hypoxia, thus representing a well-suited model to study the maintenance of cardiac function when O(2) availability represents a limiting factor. Using a working heart preparation, we explored the role of the intracardiac nitric oxide synthase (NOS)-derived nitric oxide (NO) under normoxic and hypoxic conditions. Cardiac performance was examined both under basal (constant preload and afterload) and loading conditions, i.e. preload-induced increases in stroke volume (SV) and hence cardiac output at constant afterload (the Frank-Starling response). Hypoxic hearts showed an increased basal mechanical performance compared to the normoxic counterpart. Under basal conditions, in both normoxic and hypoxic hearts, NOS and soluble guanylyl cyclase (sGC) inhibition increased SV, while exogenous NO supply decreased it. The normoxic heart was very sensitive to filling pressure increases; the maximum SV = 1.08 ± 0.09 mL/kg body mass was obtained at 0.4 kPa. Acute hypoxia increased this sensitivity, SV reaching the maximum value (1.45 ± 0.12 mL/kg body mass) at 0.25 kPa. NOS inhibition by L-NMMA reduced the Frank-Starling response under normoxia, but was ineffective under acute hypoxia, where NO may come from nitrite reduction. In both conditions, sGC inhibition induced a reduction of the cardiac response to preload. Moreover, under acute hypoxia, NO scavenging significantly reduced the Frank-Starling response. The hypoxia-induced hemodynamic patterns were complemented by Western blotting analysis which revealed increased expressions of NOS and hypoxia inducible factor α(HIF-1α). In conclusion, we demonstrated that intracardiac NO/NOS enhances goldfish heart performance, remarkably expanding its hypoxic tolerance.

Decay rate measurement of the first vibrationally excited state of MgH+ in a cryogenic Paul trap.

We present a method to measure the decay rate of the first excited vibrational state of polar molecular ions that are part of a Coulomb crystal in a cryogenic linear Paul trap. Specifically, we have monitored the decay of the |ν = 1, J = 1)(X) towards the |ν = 0, J = 0)(X) level in MgH+ by saturated laser excitation of the |ν = 0, J = 2)(X)-|ν = 1, J = 1)(X) transition followed by state selective resonance enhanced two-photon dissociation out of the |ν = 0, J=2)(X) level. The experimentally observed rate of 6.32(0.69) s(-1) is in excellent agreement with the theory value of 6.13(0.03) s(-1) (this Letter). The technique enables the determination of decay rates, and thus absorption strengths, with an accuracy at the few percent level.

Dolphin whistles: a functional misnomer revealed by heliox breathing.

Delphinids produce tonal whistles shaped by vocal learning for acoustic communication. Unlike terrestrial mammals, delphinid sound production is driven by pressurized air within a complex nasal system. It is unclear how fundamental whistle contours can be maintained across a large range of hydrostatic pressures and air sac volumes. Two opposing hypotheses propose that tonal sounds arise either from tissue vibrations or through actual whistle production from vortices stabilized by resonating nasal air volumes. Here, we use a trained bottlenose dolphin whistling in air and in heliox to test these hypotheses. The fundamental frequency contours of stereotyped whistles were unaffected by the higher sound speed in heliox. Therefore, the term whistle is a functional misnomer as dolphins actually do not whistle, but form the fundamental frequency contour of their tonal calls by pneumatically induced tissue vibrations analogous to the operation of vocal folds in terrestrial mammals and the syrinx in birds. This form of tonal sound production by nasal tissue vibrations has probably evolved in delphinids to enable impedance matching to the water, and to maintain tonal signature contours across changes in hydrostatic pressures, air density and relative nasal air volumes during dives.

The developing ovary of the South American plains vizcacha, Lagostomus maximus (Mammalia, Rodentia): massive proliferation with no sign of apoptosis-mediated germ cell attrition.

Apoptosis-dependent massive germ cell death is considered a constitutive trait of the developing mammalian ovary that eliminates 65-85% of the germinal tissue depending on the species. After birth and during adult lifetime, apoptotic activity moves from the germ cell proper to the somatic compartment, decimating germ cells through follicular atresia until the oocyte reserve is exhausted. In contrast, the South American rodent Lagostomus maximus shows suppressed apoptosis-dependent follicular atresia in the adult ovary, with continuous folliculogenesis and massive polyovulation, which finally exhausts the oocyte pool. The absence of follicular atresia in adult L. maximus might arise from a failure to move apoptosis from the germinal stratum to the somatic compartment after birth or being a constitutive trait of the ovarian tissue with no massive germ cell degeneration in the developing ovary. We tested these possibilities by analysing oogenesis, expression of germ cell-specific VASA protein, apoptotic proteins BCL2 and BAX, and DNA fragmentation by TUNEL assay in the developing ovary of L. maximus. Immunolabelling for VASA revealed a massive and widespread colonisation of the ovary and proliferation of germ cells organised in nests that disappeared at late development when folliculogenesis began. No sign of germ cell attrition was found at any time point. BCL2 remained positive throughout oogenesis, whereas BAX was slightly detected in early development. TUNEL assay was conspicuously negative throughout the development. These results advocate for an unrestricted proliferation of germ cells, without apoptosis-driven elimination, as a constitutive trait of L. maximus ovary as opposed to what is normally found in the developing mammalian ovary.

Search for production of invisible final states in single-photon decays of Υ(1S).

We search for single-photon decays of the Υ(1S) resonance, Υ â†’ γ + invisible, where the invisible state is either a particle of definite mass, such as a light Higgs boson A°, or a pair of dark matter particles, χχ. Both A° and χ are assumed to have zero spin. We tag Υ(1S) decays with a dipion transition Υ(2S) → π⁺π⁻Υ(1S) and look for events with a single energetic photon and significant missing energy. We find no evidence for such processes in the mass range m(A°) ≤ 9.2 GeV and m(χ) ≤ 4.5 GeV in the sample of 98 × 106 Υ(2S) decays collected with the BABAR detector and set stringent limits on new physics models that contain light dark matter states.

Interaction of Amyloid-ß-(1-42) Peptide and Its Aggregates with Lipid/Water Interfaces Probed by Vibrational Sum-Frequency Generation Spectroscopy.

In this study, we use surface-sensitive vibrational sum-frequency generation (VSFG) spectroscopy to investigate the interaction between model lipid monolayers and Aß(1-42) in its monomeric and aggregated states. Combining VSFG with atomic force microscopy (AFM) and thioflavin T (ThT) fluorescence measurements, we found that only small aggregates with probably a ß-hairpin-like structure adsorbed to the zwitterionic lipid monolayer (DOPC). In contrast, larger aggregates with an extended ß-sheet structure adsorbed to a negatively charged lipid monolayer (DOPG). The adsorption of small, initially formed aggregates strongly destabilized both monolayers, but only the DOPC monolayer was completely disrupted. We showed that the intensity of the amide-II' band in achiral (SSP) and chiral (SPP) polarization combinations increased in time when Aß(1-42) aggregates accumulated at the DOPG monolayer. Nevertheless, almost no adsorption of preformed mature fibrils to DOPG monolayers was detected. By performing spectral VSFG calculations, we revealed a clear correlation between the amide-II' signal and the degree of amyloid aggregates (e.g., oligomers or (proto)fibrils) of various Aß(1-42) structures. The calculations showed that only structures with a significant amyloid ß-sheet content have a strong amide-II' intensity, in line with previous Raman studies. The combination of the presented results substantiates the amide-II(') band as a legitimate amyloid marker.

Pathogenesis of of cytomegalovirus infection. I. Activation of virus from bone marrow-derived lymphocytes by in vitro allogenic reaction.

After infection in utero or at birth with a cell culture adapted strain of mouse cytomegalovirus (MCMV), several mouse strains developed a latent virus infection in the presence of specific antiviral antibodies. Up to 5 mo after infection, MCMV could be activated and recovered from spleen lymphocytes of the infected animals that were co-cultivated with histoincompatible (H-2 foreign) mouse embryo cells from uninfected animals. In contrast, co-cultivation of lymphoid cells from infected mice with mouse embryo cells from syngeneic, histocompatible (H-2 similar) donors did not activate MCMV. Similarly, MCMV was not recovered from sonicated lymphoid cells. Virus was activated by treating viable lymphoid cells with lipopolysaccharide, a B-cell mitogen, but was not activated by a variety of other mitogens such as phytohemagglutinin, concanavalin A, or pokeweed mitogen. Subsequent purification of lymphoid cells from the infected mice by a variety of techniques indicated that MCMV was harbored in the B-lymphocyte population.

Lymphocytes transformed by Epstein-Barr virus. Induction of nuclear antigen reactive with antibody in rheumatoid arthritis.

Sera from approximately two-thirds of patients with rheumatoid arthritis contain an antibody which is reactive with a nuclear antigen present in human B-lymphocyte tissue culture cells. The immunological reaction can be demonstrated by precipitation and immunofluorescence. Evidence is present that the reactive nuclear antigen is associated with Epstein-Barr (EB) virus-transformed lymphocytes. Normal human peripheral blood lymphocytes did not contain the nuclear antigen reactive with rheumatoid arthritis sera, but after infection with EB virus, they showed increasing amounts of reactive nuclear antigen as the cells were transformed into continuous lines. Several established human and simian lymphocyte cell lines known to carry EB viral genomes were shown to contain rheumatoid arthritis-associated nuclear antigen. Evidence is presented which suggests that the rheumatoid arthritis-associated nuclear antigen is different from the previously described EB nuclear antigen.

In vitro effects of Epstein-Barr virus on peripheral blood mononuclear cells from patients with rheumatoid arthritis and normal subjects.

Peripheral blood mononuclear cells from 10 patients with rheumatoid arthritis and 9 control subjects were cultured in vitro for 30 days with and without infection by Epstein-Barr virus. All cultures showed polyclonal stimulation of B cells as indicated by rising levels of IgM in the culture supernates, reaching maximal at 18-24 days, and with no quantitative or kinetic difference between the RA and control cells. IgM anti-IgG was also produced in both groups and maximally at 18-24 days, but in greater quantity by the RA lymphocytes. The anti-IgG made by the RA lymphocytes was more easily absorbed by solid phase IgG than was the anti-IgG made by the normal lymphocytes and thus was judged to be of higher affinity. RA lymphocytes uninfected with EBV had higher transformation scores than did the normal controls and developed spontaneously into permanent cell lines in six instances.

Lysis of RNA tumor viruses by human serum: direct antibody-independent triggering of the classical complement pathway.

In earlier studies we found that human serum, but not serum from multiple other species, inactivated and lysed oncornaviruses from a number of diverse sources in the apparent absence of antibody. A detailed analysis of the role of the human complement (C) system in mediating this lytic process indicates that human C1q interacts directly, in the absence of immunoglobulin, with oncornaviruses. Binding of C1 via C1q in this manner leads to activation of C1r, C1s, and thus of the classical C pathway. Integrity of the classical pathway is an absolute requirement for lysis although activation of the alternative pathway considerably amplifies the amount of lysis obtained, possibly through involvement of the C3b-dependent feedback mechanism. Activation of C is accompanied by deposition of C components on the viral surface and lysis on completion of the C reaction sequence. Thus in this system, the C1q subunit of C1 subserves a specific recognition function normally associated with antibody. This ability of human serum to inactivate oncornaviruses may represent a natural defense mechanism operative in vivo which deters expression of intact oncornaviruses in human malignancies.

Immunopathogenicity and oncogenicity of murine leukemia viruses. I. Induction of immunologic disease and lymphoma in (BALB-c times NZB)F1 mice by Scripps leukemia virus.

This report clearly demonstrates that a systemic lupus erythematosus (SLE)-like syndrome and lymphoma can be induced in immunologically normal (BALB/c x NZB)F(1) mice by infection of neonates with a murine leukemia virus (MuLV) (Scripps leukemia virus [SLV] 60A) isolated from NZB lymphoblasts. SLV 60A was titered in vitro (XC test) and administered to newborn and adult (BALB/c x NZB)F(1) mice over six log(10) dilutions. Propagation of MuLV in the newborn recipients was indicated by greatly elevated serum Mu gs-1 levels which were proportional to the dose of virus given. The SLE-like syndrome was characterized by antinuclear antibodies (ANA) and immune complex-type glomerulonephritis. ANA production was related to the dose of virus and reached the highest levels at 8-16 wk. The incidence of glomerulonephritis was also correlated with the dose of virus and reached nearly 50% in the animals given the highest virus dose. Both titers of ANA and incidence of glomerulonephritis were greater in females than in males, although the amounts of Mu gs-1 in sera of both sexes were equal. The incidence of direct Coombs' positivity was not significantly affected by inoculation of this virus. The incidence and time of onset of thymocytic lymphoma were linearly related to the amount of virus inoculated. High serum Mu gs-1 levels predicted lymphoma development and reflected increases in the amount of infectious virus in the spleen. No induction of tumors, autoimmunity, or high serum Mu gs-1 levels followed administration of SLV 60A to 6-wk old (BALB/c x NZB)F(1) mice or inactivated 60A or active AKR virus to newborns.

Low-calorie diet selectively reduces expression of retroviral envelope glycoprotein gp70 in sera of NZB x NZW F1 hybrid mice.

The effect of dietary restriction on the expression of retroviral envelope glycoprotein, gp70, and the formation of gp70-anti gp70 immune complexes was investigated in lupus-prone NZB x NZW F1 hybrid mice. Restricting total calorie intake from the usual 20 to only 10 calories per day after weaning markedly reduced serum levels of both free and antibody-complexed gp70, prevented renal disease, and increased the life spans of these mice. The reduction in serum gp70 was evident after only 2 wk of feeding these animals the low-calorie diet, and the concentration remained virtually unchanged throughout the course of 10 mon experimentation. However, serum concentrations of the major structural protein, p30, of endogenous retroviruses were not altered by restricting calories. Amounts of the serum glycoprotein, haptoglobin, decreased parallel to those of gp70 but amounts of albumin did not. These results suggest that the expression of gp70 in serum is controlled independently of the production of complete viral particles, and regulated by a mechanism similar to that for other serum glycoproteins, such as haptoglobin.

Long-term high-physiological-dose growth hormone reduces intra-abdominal fat in HIV-infected patients with a neutral effect on glucose metabolism.

OBJECTIVES: The aim of the study was to investigate the effect of long-term high-physiological-dose recombinant human growth hormone (rhGH) therapy on fat distribution and glucose metabolism in HIV-infected patients. METHODS: Forty-six HIV-infected Caucasian men on highly active antiretroviral therapy (HAART), with an age range of 21-60 years and no significant comorbidity, were included in this randomized, placebo-controlled, double-blind, single-centre trial. Twenty-eight subjects were randomized to 0.7 mg/day rhGH, and 18 subjects to placebo, administered as daily subcutaneous injections between 1 and 3 pm for 40 weeks. Endpoints included changes in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), limb fat mass, percentage of limb fat, plasma lipids, insulin resistance and glucose tolerance. RESULTS: VAT and trunk fat mass decreased significantly in the GH group compared with the placebo group [-19 cm(2) (-11%) vs. 12 cm(2) (6%), P=0.03, and -548 g (-9%) vs. 353 g (6%), P<0.01, respectively]. The beneficial fat redistribution in the GH group occurred without concomitant changes in subcutaneous fat at the abdomen or extremities. rhGH therapy was well tolerated. Insulin resistance, glucose tolerance, and total plasma cholesterol and triglycerides did not significantly change during intervention. CONCLUSIONS: Daily 0.7 mg rhGH treatment for 40 weeks reduced abdominal visceral fat and trunk fat mass in HIV-infected patients. This treatment appeared to be safe with respect to glucose tolerance and insulin sensitivity.

Echolocation in sympatric Peale's dolphins (Lagenorhynchus australis) and Commerson's dolphins (Cephalorhynchus commersonii) producing narrow-band high-frequency clicks.

An increasing number of smaller odontocetes have recently been shown to produce stereotyped narrow-band high-frequency (NBHF) echolocation clicks. Click source parameters of NBHF clicks are very similar, and it is unclear whether the sonars of individual NBHF species are adapted to specific habitats or the presence of other NBHF species. Here, we test whether sympatric NBHF species sharing the same habitat show similar adaptations in their echolocation clicks and whether their clicks display signs of character displacement. Wide-band sound recordings were obtained with a six-element hydrophone array from wild Peale's (Lagenorhynchus australis) and Commerson's (Cephalorhynchus commersonii) dolphins off the Falkland Islands. The centroid frequency was different between Commerson's (133+/-2 kHz) and Peale's (129+/-3 kHz) dolphins. The r.m.s. bandwidth was 12+/-3 kHz for both species. The source level was higher for Peale's dolphin (185+/-6 dB re 1 muPa p.-p.) than for Commerson's (177+/-5 dB re 1 muPa p.-p.). The mean directivity indexes were 25 dB for both species. The relatively low source levels in combination with the high directivity index may be an adaptation to reduce clutter when foraging in a coastal environment. We conclude that the small species-specific shifts in distribution of centroid frequencies around 130 kHz may reflect character displacement in otherwise-stereotyped NBHF clicks.

Skin signs in Ehlers-Danlos syndrome: clinical tests and para-clinical methods.

OBJECTIVE: The criteria for Ehlers-Danlos syndrome (EDS) and the hypermobility syndrome (HMS) should be reliable. Examination for general joint hypermobility has high reliability but there is only sparse information on the reliability of skin tests, and no information on the level of normal skin extensibility. The present study aimed to assess skin signs by means of clinical and para-clinical methods. METHODS: A total of 31 EDS patients and 28 healthy controls were examined blinded and in random order. Inter-examiner analysis of clinical tests for skin extensibility, consistency, scarring, and bruising was performed, followed by analyses of extensibility with the suction cup (SC), consistency with a soft tissue stiffness meter (STSM), and thickness with ultrasonography (US). Semi-quantitative assessment of skin extensibility in healthy controls was incorporated in the tests. RESULTS: The clinical analyses demonstrated kappa values of: 0.72 for extensibility, 0.23 for consistency, 0.53 for scarring, and 0.63 for bruising. Skin extensibility measurements in healthy controls (n = 28) were 2.79 and 2.93 cm (mean + 2 SD), respectively, by the two examiners. There were significant differences between patients with classical-type EDS and controls with respect to skin extensibility by SC (4.91 vs. 12.52 kPa/mm) and skin consistency by STSM (0.59 vs. 0.76 N). We found no difference in skin thickness. CONCLUSION: The reproducibility of the clinical skin tests was substantial to good, apart from the consistency measurements. We suggest that skin consistency is withdrawn as a diagnostic criterion. The upper level for normal skin extensibility should be 3 cm. SC and STSM are promising para-clinical methods, but their diagnostic sensitivity and specificity need to be determined.

Oncogenicity by DNA tumor viruses: enhancement after ultraviolet and cobalt-60 radiations.

Simian virus-40, polyoma, and LLE46 virus preparations were treated with ultraviolet or gamma radiations (cobalt-60) in a frozen state. Infectivity and induction of complement-fixing antigen and DNA synthesis declined as a logarithmic function of dose, the latter two properties being more resistant than infectivity to radiation by a factor of 2 to 5. Oncogenicity of all three viruses did not decrease with progressive amounts of both types of irradiation, but actually increased in absolute and relative terms (per infectious unit), even at the maximum dose of irradiation used (24,000 ergs per square millimeter per minute and 2.7 x 10(6) rads).