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The quantum phases of the electron paths driven by an ultrafast laser in high harmonic generation in an atomic gas depends linearly on the instantaneous cycle-averaged laser intensity. Using high laser intensities, a complete single ionisation of the atomic gas may occur before the laser pulse peak. Therefore, high harmonic generation could be localised only in a temporal window at the leading edge of laser pulse envelope. Varying the laser frequency chirp of an intense ultrafast laser pulse, the centre, and the width of the temporal window, that the high harmonic generation phenomenon occurs, could be controlled with high accuracy. This way, both the duration and the phase of the electron trajectories, that generate efficiently high harmonics, is fully controlled. A method of spectral control and selection of the high harmonic extreme ultraviolet light from distinct quantum paths is experimentally demonstrated. Furthermore, a phenomenological numerical model enlightens the physical processes that take place. This novel approach of the electron quantum path selection via laser chirp is a simple and versatile way of controlling the time-spectral characteristics of the coherent extreme ultraviolet light with applications in the fields of attosecond pulses and soft x-ray nano-imaging.

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Nanoacoustic strains are generated in Silicon by chirped femtosecond laser pulses using thin Titanium films as transducers. We investigate the effect that the generating laser pulse chirp has on the amplitude of the induced strains, manifested as Brillouin oscillations observed in degenerate femtosecond pump-probe transient reflectivity measurements. The strain amplitude is larger when negatively chirped pulses are used, which is attributed to the more efficient conversion of laser pulse light into acoustic strain in the Titanium transducer. Our present studies clearly show that the dependence of the Brillouin amplitude and the lattice strain is a non-monotonous function of the laser chirp parameter. An optimum negative laser pulse chirp is found for which the strain amplitude is maximized. A detailed thermomechanical model satisfactorily supports the experimental findings. In such a way, it is possible to suppress or enhance the induced nanoacoustic strain amplitude, thus all-optically controlling it by at least a factor of two.

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This study shows the rapid and differential production of the 40-43 kDa and the 70-90 kDa alpha1-acid glycoprotein (AGP) fucosylated glycoforms after treatment of the dorsal air pouch with bacterial lipopolysaccharide (LPS), HgCl(2) or Freund's complete adjuvant (FCA). The 40-43 kDa and the 70-90 kDa AGP production is peaked 1-3 h post-LPS treatment. We observed that the responses to LPS and FCA are similar in that both AGP isoforms are induced whereas they differ in that the FCA exhibits a 6 h lag period. The response to HgCl(2,) however, exhibits the specific biphasic induction only of the 40-43 kDa AGP. The serum 40-43 kDa AGP glycoform gradually increases in response to all of the above stimulants and peaks by 24 h post- treatment. The increase of the 70-90 kDa AGP levels in the air pouch occurs in association with the accumulation of polymorphonuclear (PMN) cells while dexamethasone (DEX) increases only the 40-43 kDa AGP production in the absence of PMN accumulation. Macrophage-monocyte lineage cells forming the air pouch lining tissue may potentially be the cells that secrete the 40-43 kDa AGP while polymorphonuclear cells that infiltrate the air pouch secrete the 70-90 kDa AGP. The 40-43 kDa and 70-90 kDa AGP production induced by LPS in the air pouch precedes that of interleukin-1 (IL-1) or interleukin-6 (IL-6) while the 40-43 kDa AGP glycoform potentially increases IL-6 production by air pouch PMN exudate cells. These significant differences suggest a local pro-inflammatory role of AGP. Honeybee venom suppressed arthritis development and exhibited differential local or systemic regulation of AGP in serum vs. air pouch exudate or synovial fluid. This study with the air pouch model of facsimile synovium tissue suggests that local alpha1-acid glycoprotein (AGP) production may contribute to pro-inflammatory and anti-inflammatory activities during the local acute phase response or during chronic inflammatory stress as in arthritis.

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PrP(C), the cellular isoform of prion protein, is widely expressed in most tissues. Despite its involvement in several bioprocesses it still has no apparent physiological role. During propagation of Transmissible Spongiform Encephalopathies, PrP(C) is converted to the pathological isoform, PrP(Sc), in a process believed to be mediated by unknown host factors. PrP(Sc) has altered biochemical properties and forms amyloid aggregates that display infectious characteristics. PrP(Sc) is also the major component in biochemically enriched infectious samples. Other molecules co-purify with it, but the protein content of these aggregates remains unknown. The goal of this project was to identify other host molecules with high affinity for PrP(Sc). Here, we present the identification of protein molecules that co-purify with PrP(Sc) isolated from naturally scrapie-infected ovine brain tissue. The infectious preparations were analyzed by two-dimensional gel electrophoresis and unknown proteins were identified by LC-MS/MS. These proteins may prove to be strategic targets for prevention and therapy of prion diseases.

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PrP(C), the cellular isoform of prion protein, is widely expressed in most tissues, including brain, muscle and gastrointestinal tract. Despite its involvement in several bioprocesses, PrP has still no apparent physiological role. During propagation of transmissible spongiform encephalopathies (TSE), prion protein is converted to the pathological isoform, PrP(Sc), in a process believed to be mediated by unknown host factors. The identification of proteins associated with PrP may provide information about both the biology of prions and the pathogenesis of TSE. Thus far, PrP(C) has been shown to interact with synaptic proteins, components of the cytoskeleton and intracellular proteins involved in signalling pathways. Here, we describe the association of PrP with the beta4 subunit of nicotinic acetylcholine receptor (nAChR), as indicated by co-immunoprecipitation assays and double-label immunofluorescence. The interaction between prion protein and native beta4 subunit was further studied by affinity chromatography, using immobilized and refolded recombinant PrP as a bait and brain homogenates from normal individuals. Additionally, the participation of beta4 subunit in the pathogenesis of TSE was studied by in vivo assays. beta4(-/-) and wild-type mice were challenged with the RML (Rocky Mountain Laboratories) infectious agent. Transgenic animals displayed altered incubation times but the deletion of beta4 subunit did not result in a significant change of the incubation period of the disease. Our results suggest that PrP(C) is a member of a multiprotein membrane complex participating in the formation and function of alpha3beta4 nAChR.

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Prion propagation involves conversion of host PrP(C) to a disease-related isoform, PrP(Sc), which accumulates during disease and is the principal component of the transmissible agent. Proteolysis seems to play an important role in PrP metabolism. Plasminogen, a serine protease precursor, has been shown to interact with PrP(Sc). Plasminogen can be proteolytically activated by tissue plasminogen activator (tPA). Recent reports imply a crosstalk between tPA-mediated plasmin activation and PrP. In our study, both tPA activity and tPA gene expression were found elevated in TSE-infected brains as compared to their normal counterparts. Furthermore, it was proved that PrP(Sc), in contrast to PrP(C), could not be degraded by plasmin. In addition, it was observed that TSE symptoms and subsequent death of plasminogen-deficient and tPA-deficient scrapie challenged mice preceded that of wild-type controls. Our data imply that enhanced tPA activity observed in prion infected brains may reflect a neuro-protective response.

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We describe the quality of a rabbit polyclonal antiserum (Sal1) that was raised against mature human recombinant prion protein (rhuPrP). Epitope mapping demonstrated that the Sal1 antiserum recognized six to eight linear antigenic sites, depending on the animal species. The versatility of the antiserum was evident from the range of animal species and immunochemical techniques where it could be applied successfully. Antigen absorption studies revealed differences in the location and number of epitopes remaining after incubation with soluble or aggregated antigen.Our knowledge concerning immunoprophylaxis against prion diseases and the important role played by conformational changes of PrP is increasing rapidly. The findings reported here should add to this body of knowledge.

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OBJECTIVE: To examine the utility of using PRIME-MD (Primary Care Evaluation of Mental Disorders) for diagnosing mental disorders in American Indians. METHOD: One hundred randomly selected, adult, American-Indian patients who receive health care services at an urban Indian Health Service primary care clinic were evaluated for mental disorder by three primary care physicians using the PRIME-MD diagnostic assessment procedure. The main outcome measures were PRIME-MD diagnoses, diagnoses by an independent mental health professional, and treatment/referral decisions. RESULTS: Eighteen percent of the patients had a threshold (met full DSM-IV criteria ) PRIME-MD diagnosis, and an additional 17 percent had a subthreshold PRIME-MD diagnosis. The most frequently occurring PRIME-MD diagnoses were: probable alcohol abuse/dependence, major depressive disorder, and generalized anxiety disorder. Over 60 percent of the patients with a PRIME-MD diagnosis who were known "somewhat" or "fairly well" to their physician had not been recognized as having that psychiatric disorder prior to the PRIME-MD assessment. Therapy and/or referral was initiated for nineteen of the twenty-seven patients with a PRIME-MD diagnosis who were not previously receiving treatment. The primary care physicians were able to complete the PRIME-MD evaluations within an average of 7.8 minutes. There was a fair agreement between the PRIME-MD diagnoses and the diagnoses of the mental health professional (kappa = 0.56; overall accuracy rate = 79%). CONCLUSIONS: The present study represents the first formal examination of the use of PRIME-MD with American Indians. The results are encouraging. Further studies using PRIME-MD with other urban groups and reservation populations are recommended.

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