Observation of Laser Power Amplification in a Self-Injecting Laser Wakefield Accelerator.

We report on the depletion and power amplification of the driving laser pulse in a strongly driven laser wakefield accelerator. Simultaneous measurement of the transmitted pulse energy and temporal shape indicate an increase in peak power from 187±11 TW to a maximum of 318±12 TW after 13 mm of propagation in a plasma density of 0.9×10^{18} cm^{-3}. The power amplification is correlated with the injection and acceleration of electrons in the nonlinear wakefield. This process is modeled by including a localized redshift and subsequent group delay dispersion at the laser pulse front.

TaylorActive--Examining the effectiveness of web-based personally-tailored videos to increase physical activity: a randomised controlled trial protocol.

BACKGROUND: Physical inactivity levels are unacceptably high and effective interventions that can increase physical activity in large populations at low cost are urgently needed. Web-based interventions that use computer-tailoring have shown to be effective, though people tend to 'skim' and 'scan' text on the Internet rather than thoroughly read it. The use of online videos is, however, popular and engaging. Therefore, the aim of this 3-group randomised controlled trial is to examine whether a web-based physical activity intervention that provides personally-tailored videos is more effective when compared with traditional personally-tailored text-based intervention and a control group. METHODS/DESIGN: In total 510 Australians will be recruited through social media advertisements, e-mail and third party databases. Participants will be randomised to one of three groups: text-tailored, video-tailored, or control. All groups will gain access to the same web-based platform and a library containing brief physical activity articles. The text-tailored group will additionally have access to 8 sessions of personalised physical activity advice that is instantaneously generated based on responses to brief online surveys. The theory-based advice will be provided over a period of 3 months and address constructs such as self-efficacy, motivation, goal setting, intentions, social support, attitudes, barriers, outcome expectancies, relapse prevention and feedback on performance. Text-tailored participants will also be able to complete 7 action plans to help them plan what, when, where, who with, and how they will become more active. Participants in the video-tailored group will gain access to the same intervention content as those in the text-tailored group, however all sessions will be provided as personalised videos rather than text on a webpage. The control group will only gain access to the library with generic physical activity articles. The primary outcome is objectively measured physical activity. Secondary outcomes include website engagement and retention, quality of life, depression, anxiety, stress, sitting time, sleep and psychosocial correlates of physical activity. Outcomes will be measured at baseline, 3, and 9 months. DISCUSSION: This study presents an ideal opportunity to study the effectiveness of an isolated feature within a web-based physical activity intervention and the knowledge generated from this study will help to increase intervention effectiveness. TRIAL REGISTRATION: Australian New-Zealand Clinical Trial Registry: ACTRN12615000057583 . Registered 22 January 2015. CQUniversity Ethics Project Number: H14/07-163.

Compact laser accelerators for X-ray phase-contrast imaging.

Advances in X-ray imaging techniques have been driven by advances in novel X-ray sources. The latest fourth-generation X-ray sources can boast large photon fluxes at unprecedented brightness. However, the large size of these facilities means that these sources are not available for everyday applications. With advances in laser plasma acceleration, electron beams can now be generated at energies comparable to those used in light sources, but in university-sized laboratories. By making use of the strong transverse focusing of plasma accelerators, bright sources of betatron radiation have been produced. Here, we demonstrate phase-contrast imaging of a biological sample for the first time by radiation generated by GeV electron beams produced by a laser accelerator. The work was performed using a greater than 300 TW laser, which allowed the energy of the synchrotron source to be extended to the 10-100 keV range.

A mobile phone enabled health promotion program for middle-aged males.

The prevalence of chronic diseases among middle aged males outweigh their female counterparts in developed countries. To prevent this, delivery of health promotion programs targeting lifestyle modifications of physical activity and nutrition in middle-aged males has been essential, but often difficult. ManUp health promotion program was a recent initiative that uses current advances in information and communication technology (ICT) to reach the middle-aged males. One of the key components of the ICT approach was the development of smartphone application to enable middle-aged men to uptake the program with their own mobile phone. The smart phone application was aimed at providing varied level of challenges towards physical activity and healthy eating behavior, with interactive and motivational feedback SMS messages. The ManUp program was recently implemented and trialed in a randomized control trial in Gladstone and Rockhampton, Queens. This paper describes the components of the smart phone application integrated within the ManUp health promotion program.

Loss of a single Hic1 allele accelerates polyp formation in Apc(Δ716) mice.

Adenomatous polyposis coli (APC) gene mutations have been implicated in familial and sporadic gastrointestinal (GI) cancers. APC mutations are associated with autosomal dominant inheritance of disease in humans. Similarly, mice that contain a single mutant APC gene encoding a protein truncated at residue 716 (Apc(Δ716)) develop multiple polyps throughout the GI tract as early as 4 weeks after birth. Inactivation of another tumor suppressor gene, Hypermethylated in Cancer 1 (HIC1), often occurs in human colon cancers, among others, via CpG island hypermethylation. Homozygous deletion of Hic1 in mice results in major developmental defects and embryonic lethality. Hic1 heterozygotes have previously been shown to develop tumors of a variety of tissue types. We now report that loss of a single Hic1 allele can promote crypt hyperplasia and neoplasia of the GI tract, and Hic1(+/-), Apc(+/Δ716) double heterozygotes (DH) develop increased numbers of polyps throughout the GI tract at 60 days. Hic1 expression is absent in polyps from DH mice, with concomitant increased expression of two transcriptional repression targets of Hic1, Sirt1 and Sox9. Together, our data suggest that loss of a gene frequently silenced via epigenetic mechanisms, Hic1, can cooperate with loss of a gene mutated in GI cancer, Apc, to promote tumorigenesis in an in vivo model of multiple intestinal neoplasia.

Face emotion recognition is related to individual differences in psychosis-proneness.

BACKGROUND: Deficits in face emotion recognition (FER) in schizophrenia are well documented, and have been proposed as a potential intermediate phenotype for schizophrenia liability. However, research on the relationship between psychosis vulnerability and FER has mixed findings and methodological limitations. Moreover, no study has yet characterized the relationship between FER ability and level of psychosis-proneness. If FER ability varies continuously with psychosis-proneness, this suggests a relationship between FER and polygenic risk factors. METHOD: We tested two large internet samples to see whether psychometric psychosis-proneness, as measured by the Schizotypal Personality Questionnaire-Brief (SPQ-B), is related to differences in face emotion identification and discrimination or other face processing abilities. RESULTS: Experiment 1 (n=2332) showed that psychosis-proneness predicts face emotion identification ability but not face gender identification ability. Experiment 2 (n=1514) demonstrated that psychosis-proneness also predicts performance on face emotion but not face identity discrimination. The tasks in Experiment 2 used identical stimuli and task parameters, differing only in emotion/identity judgment. Notably, the relationships demonstrated in Experiments 1 and 2 persisted even when individuals with the highest psychosis-proneness levels (the putative high-risk group) were excluded from analysis. CONCLUSIONS: Our data suggest that FER ability is related to individual differences in psychosis-like characteristics in the normal population, and that these differences cannot be accounted for by differences in face processing and/or visual perception. Our results suggest that FER may provide a useful candidate intermediate phenotype.

Observation of a long-wavelength hosing modulation of a high-intensity laser pulse in underdense plasma.

We report the first experimental observation of a long-wavelength hosing modulation of a high-intensity laser pulse. Side-view images of the scattered optical radiation at the fundamental wavelength of the laser reveal a transverse oscillation of the laser pulse during its propagation through underdense plasma. The wavelength of the oscillation λ(hosing) depends on the background plasma density n(e) and scales as λ(hosing)∼n(e)(-3/2). Comparisons with an analytical model and two-dimensional particle-in-cell simulations reveal that this laser hosing can be induced by a spatiotemporal asymmetry of the intensity distribution in the laser focus which can be caused by a misalignment of the parabolic focusing mirror or of the diffraction gratings in the pulse compressor.

Electron bunch length measurements from laser-accelerated electrons using single-shot THz time-domain interferometry.

Laser-plasma wakefield-based electron accelerators are expected to deliver ultrashort electron bunches with unprecedented peak currents. However, their actual pulse duration has never been directly measured in a single-shot experiment. We present measurements of the ultrashort duration of such electron bunches by means of THz time-domain interferometry. With data obtained using a 0.5 J, 45 fs, 800 nm laser and a ZnTe-based electro-optical setup, we demonstrate the duration of laser-accelerated, quasimonoenergetic electron bunches [best fit of 32 fs (FWHM) with a 90% upper confidence level of 38 fs] to be shorter than the drive laser pulse, but similar to the plasma period.

Near-GeV acceleration of electrons by a nonlinear plasma wave driven by a self-guided laser pulse.

The acceleration of electrons to approximately 0.8 GeV has been observed in a self-injecting laser wakefield accelerator driven at a plasma density of 5.5x10(18) cm(-3) by a 10 J, 55 fs, 800 nm laser pulse in the blowout regime. The laser pulse is found to be self-guided for 1 cm (>10zR), by measurement of a single filament containing >30% of the initial laser energy at this distance. Three-dimensional particle in cell simulations show that the intensity within the guided filament is amplified beyond its initial focused value to a normalized vector potential of a0>6, thus driving a highly nonlinear plasma wave.

Excited ions in intense femtosecond laser pulses: laser-induced recombination.

Electron-ion recombination in a laser-induced electron recollision is of fundamental importance as the underlying mechanism responsible for the generation of high-harmonic radiation and hence for the production of attosecond pulse trains in the extreme ultraviolet and soft x-ray spectral regions. By using an ion beam target, remotely prepared to be partially in long-lived excited states, the recombination process has for the first time been directly observed and studied.

Comparison of experimental and simulated Kalpha yield for 400 nm ultrashort pulse laser irradiation.

Ti Kalpha emission yields from foils irradiated with approximately 45 fs, p-polarized pulses of a frequency-doubled Ti:sapphire laser are presented. A simple model invoking vacuum heating to predict absorption and hot electron temperature was coupled with the cross section for K -shell ionization of Ti and the Bethe-Bloch stopping power equation for electrons. The peak predicted Kalpha emission was in generally good agreement with experiment. This contrasts strongly with previous work at the fundamental frequency. Similar predictions using particle-in-cell (PIC) code simulation to estimate the number and temperature of hot electrons also gave good agreement for yield.

Of Myc and Mnt.

Deregulation of Myc expression is a common feature in cancer and leads to tumor formation in experimental model systems. There are several potential barriers that Myc must overcome in order to promote tumorigenesis, including its propensity to sensitize many cell types to apoptotic cell death. Myc activities appear also to be constrained and fine-tuned by a set of proteins that include the Mxd (formerly named Mad) family and the related protein Mnt. Like Myc-family proteins, Mxd and Mnt proteins use Max as a cofactor for DNA binding. But Mnt-Max and Mxd-Max complexes are transcriptional repressors and can antagonize the transcriptional activation function of Myc-Max. Studies examining the relationship between Myc, Mxd and Mnt proteins suggest that whereas Mnt plays a general role as a Myc antagonist, Mxd proteins have more specialized roles as Myc antagonist that is probably related to their more restricted expression patterns. The interplay between these proteins is postulated to fine-tune Myc activity for cell-cycle entry and exit, proliferation rate and apoptosis.

Kalpha yields from Ti foils irradiated with ultrashort laser pulses.

We have studied the emission of Kalpha radiation from Ti foils irradiated with ultrashort (45 fs) laser pulses. We utilized the fundamental (800 nm) light from a Ti:sapphire laser on bare foils and foils coated with a thin layer of parylene E (CH). The focusing was varied widely to give a range of intensities from approximately 10(15) - 10(19) W cm(-2). Our results show a conversion efficiency of laser to Kalpha energy of approximately 10(-4) at tight focus for both types of targets. In addition, the coated targets exhibited strong secondary peaks of conversion at large defocus, which we believe are due to modification of the extent of preformed plasma due to the dielectric nature of the plastic layer. This in turn affects the level of resonance absorption. A simple model of Kalpha production predicts a much higher conversion than seen experimentally and possible reasons for this are discussed.

Monoenergetic beams of relativistic electrons from intense laser-plasma interactions.

High-power lasers that fit into a university-scale laboratory can now reach focused intensities of more than 10(19) W cm(-2) at high repetition rates. Such lasers are capable of producing beams of energetic electrons, protons and gamma-rays. Relativistic electrons are generated through the breaking of large-amplitude relativistic plasma waves created in the wake of the laser pulse as it propagates through a plasma, or through a direct interaction between the laser field and the electrons in the plasma. However, the electron beams produced from previous laser-plasma experiments have a large energy spread, limiting their use for potential applications. Here we report high-resolution energy measurements of the electron beams produced from intense laser-plasma interactions, showing that--under particular plasma conditions--it is possible to generate beams of relativistic electrons with low divergence and a small energy spread (less than three per cent). The monoenergetic features were observed in the electron energy spectrum for plasma densities just above a threshold required for breaking of the plasma wave. These features were observed consistently in the electron spectrum, although the energy of the beam was observed to vary from shot to shot. If the issue of energy reproducibility can be addressed, it should be possible to generate ultrashort monoenergetic electron bunches of tunable energy, holding great promise for the future development of 'table-top' particle accelerators.

Human immunodeficiency virus type 1 protease regulation of tat activity is essential for efficient reverse transcription and replication.

The human immunodeficiency virus type 1 (HIV-1) Tat protein enhances reverse transcription, but it is not known whether Tat acts directly on the reverse transcription complex or through indirect mechanisms. Since processing of Tat by HIV protease (PR) might mask its presence and, at least in part, explain this lack of data, we asked whether Tat can be cleaved by PR. We used a rabbit reticulocyte lysate (RRL) system to make Tat and PR. HIV-1 PR is expressed as a Gag-Pol fusion protein, and a PR-inactivated Gag-Pol is also expressed as a control. We showed that Tat is specifically cleaved in the presence of PR, producing a protein of approximately 5 kDa. This result suggested that the cleavage site was located in or near the Tat basic domain (amino acids 49 to 57), which we have previously shown to be important in reverse transcription. We created a panel of alanine-scanning mutations from amino acids 45 to 54 in Tat and evaluated functional parameters, including transactivation, reverse transcription, and cleavage by HIV-1 PR. We showed that amino acids 49 to 52 (RKKR) are absolutely required for Tat function in reverse transcription, that mutation of this domain blocks cleavage by HIV-1 PR, and that other pairwise mutations in this region modulate reverse transcription and proteolysis in strikingly similar degrees. Mutation of Tat Y47G48 to AA also down-regulated Tat-stimulated reverse transcription but had little effect on transactivation or proteolysis by HIV PR, suggesting that Y47 is critical for reverse transcription. We altered the tat gene of the laboratory strain NL4-3 to Y47D and Y47N so that overlapping reading frames were not affected and showed that Y47D greatly diminished virus replication and conveyed a reverse transcription defect. We hypothesize that a novel, cleaved form of Tat is present in the virion and that it requires Y47 for its role in support of efficient reverse transcription.

Experimental study of proton emission from 60-fs, 200-mJ high-repetition-rate tabletop-laser pulses interacting with solid targets.

Measurements of proton emission have been made from a variety of solid targets irradiated by a 60-fs, 200-mJ, 7 x 10(18)-W cm(-2) laser system operating at 2 Hz. Optimum target conditions were found in terms of target material and thickness. For Mylar targets of thickness 20-40 microm, a maximum proton energy of 1.5 MeV was measured. For aluminum targets, a maximum energy of 950 keV was measured for 12 microm, and for copper, 850 keV for 12.5 microm.

The first strand transfer reaction of HIV-1 reverse transcription is more efficient in infected cells than in cell-free natural endogenous reverse transcription reactions.

BACKGROUND: In the presence of dNTPs, intact HIV-1 virions are capable of reverse transcribing at least part of their genome, a process known as natural endogenous reverse transcription (NERT). PCR analysis of virion DNA produced by NERT revealed that the first strand transfer reaction (1stST) was inefficient in intact virions, with minus strand (-) strong stop DNA (ssDNA) copy numbers up to 200 times higher than post-1stST products measured using primers in U3 and U5. This was in marked contrast to the efficiency of 1stST observed in single-round cell infection assays, in which (-) ssDNA and U3-U5 copy numbers were indistinguishable. OBJECTIVES: To investigate the reasons for the discrepancy in first strand transfer efficiency between intact cell-free virus and the infection process. STUDY DESIGN: Alterations of both NERT reactions and the conditions of cell infection were used to test whether uncoating and/or entry play a role in the discrepancy in first strand transfer efficiency. RESULTS AND CONCLUSIONS: The difference in 1stST efficiency could not be attributed simply to viral uncoating, since addition of very low concentrations of detergent to NERT reactions removed the viral envelope without disrupting the reverse transcription complex, and these conditions resulted in no improvement in 1stST efficiency. Virus pseudotyped with surface glycoproteins from either vesicular stomatitis virus or amphotrophic murine leukaemia virus also showed low levels of 1stST in low detergent NERT assays and equivalent levels of (-) ssDNA and 1stST in single-round infections of cells, demonstrating that the gp120-mediated infection process did not select for virions capable of carrying out 1stST. These data indicate that a post-entry event or factor may be involved in efficient HIV-1 reverse transcription in vivo.

Human immunodeficiency virus type 1 reverse transcription is stimulated by tat from other lentiviruses.

The tat gene is required by HIV-1 for efficient reverse transcription and this function of Tat can be distinguished from its role in transcription by RNA polymerase II using tat point mutations that abrogate each function independently. The mechanism of Tat's role in reverse transcription, however, is not known, nor is it known whether this role is conserved among trans-activating factors in other retroviruses. Here we examine the abilities of heterologous viral trans-activating proteins from jembrana disease virus (jTat), HIV-2 (Tat2), and equine infectious anemia virus (eTat) to substitute for HIV-1 Tat (Tat1) and restore reverse transcription in HIV-1 carrying an inactivated tat gene. Natural endogenous reverse transcription assays showed that trans-activators from some retroviruses (Tat2 and jTat, but not eTat) could substitute for Tat1 in complementation of HIV-1 reverse transcription. Finally, we show that Y47 is critical for Tat1 to function in reverse transcription, but not HIV-1 gene expression. We mutated the homologous position in jTat to H62Y and found it did not improve its ability to stimulate reverse transcription, but an H62A mutation did inhibit jTat complementation. These data highlight the finding that the role of Tat in reverse transcription is not related to trans-activation and demonstrate that other tat genes conserve this function.

Gag-Pol supplied in trans is efficiently packaged and supports viral function in human immunodeficiency virus type 1.

The intracellular trafficking and subsequent incorporation of Gag-Pol into human immunodeficiency virus type 1 (HIV-1) remains poorly defined. Gag-Pol is encoded by the same mRNA as Gag and is generated by ribosomal frameshifting. The multimerization of Gag and Gag-Pol is an essential step in the formation of infectious viral particles. In this study, we examined whether the interaction between Gag and Gag-Pol is initiated during protein translation in order to facilitate the trafficking and subsequent packaging of Gag-Pol into the virion. A conditional cotransfection system was developed in which virion formation required the coexpression of two HIV-1-based plasmids, one that produces both Gag and Gag-Pol and one that only produces Gag-Pol. The Gag-Pol proteins were either immunotagged with a His epitope or functionally tagged with a mutation (K65R) in reverse transcriptase that is associated with drug resistance. Gag-Pol packaging was assessed to determine whether the Gag-Pol incorporated into the virion was preferentially packaged from the plasmid that expressed both Gag and Gag-Pol or whether it could be packaged from either plasmid. Our data show that translation of Gag and Gag-Pol from the same mRNA is not critical for virion packaging of the Gag-Pol polyprotein or for viral function.

A new psychosocial screening instrument for use with cancer patients.

The authors performed a principal components factor analysis on the 18-item Brief Symptom Inventory (BSI-18), a new brief screening inventory. The factor analysis, in which four factors were specified, is consistent with findings in a previous community sample. The study sample consisted of 1,543 cancer patients who completed the full BSI as part of their entry into care at a regional cancer center. The reliability of the BSI-18 was determined based on the calculation of the internal consistency, mean item scores, and correlations with the total score of the BSI. In addition, sensitivity and specificity was calculated to determine the ability of the BSI-18 to discriminate positive and negative cases. The BSI-18 is a shortened version of the BSI that can serve as a brief psychological screening instrument. The BSI-18 can be incorporated into outpatient clinics to prospectively and rapidly identify cancer patients with elevated levels of distress who are in need of clinical interventions. Early identification of distress with appropriate interventions can reduce distress, enhance quality of life, and decrease health care costs.