Demonstration of stable, long-term operation of a nanosecond pulsed DPSSL at 10 J, 100 Hz.

We report on stable, long-term operation of a diode-pumped solid-state laser (DPSSL) amplifying 15 ns pulses at 1029.5 nm wavelength to 10 J energy at 100 Hz pulse rate, corresponding to 1 kW average power, with 25.4% optical-to-optical efficiency. The laser was operated at this level for over 45 minutes (∼3 · 105 shots) in two separate runs with a rms energy stability of 1%. The laser was also operated at 7 J, 100 Hz for 4 hours (1.44 · 106 shots) with a rms long-term energy stability of 1% and no need for user intervention. To the best of our knowledge, this is the first time that long-term reliable amplification of a kW-class high energy nanosecond pulsed DPSSL at 100 Hz has been demonstrated.

Generation of Joule-level green bursts of nanosecond pulses from a DPSSL amplifier.

A new approach to generation of a burst of high-energy green pulses by placing a high-energy multi-slab Yb:YAG DPSSL amplifier and SHG crystal inside a regenerative cavity is presented. In a proof-of-concept test, stable generation of a burst of six green (515 nm) pulses, each 10 ns in duration and separated by 29.4 ns (34 MHz), with 2.0 J total energy has been demonstrated at 1 Hz from a non-optimized ring cavity design. A maximum individual green pulse energy of 580 mJ was produced from a 1.78 J circulating infrared (1030 nm) pulse (average fluence 0.9 J/cm2), corresponding to a SHG conversion efficiency of 32%. Experimental results have been compared with predicted performance from a simple model. Efficient generation of a burst of high energy green pulses offers an attractive pump source for Ti:Sa amplifiers, providing the potential to reduce the impact of amplified stimulated emission by reducing instantaneous transverse gain.

Improved stability second harmonic conversion of a diode-pumped Yb:YAG laser at the 0.5 kW level.

We report on efficient and stable, type-I phase-matched second harmonic conversion of a nanosecond high-energy, diode-pumped, Yb:YAG laser. With a frequency-doubling crystal in an enclosed, temperature controller with optical windows, 0.5% energy stability was achieved for approximately half an hour. This resulted in 48.9 J pulses at 10 Hz (489 W) and a conversion efficiency of 73.8%. These results are particularly important for stable and reliable operation of high-energy, frequency-doubled lasers.

Modelling and measurement of thermal stress-induced depolarisation in high energy, high repetition rate diode-pumped Yb:YAG lasers.

In this paper, we present a model to predict thermal stress-induced birefringence in high energy, high repetition rate diode-pumped Yb:YAG lasers. The model calculates thermal depolarisation as a function of gain medium geometry, pump power, cooling parameters, and input polarisation state. We show that model predictions are in good agreement with experimental observations carried out on a DiPOLE 100 J, 10 Hz laser amplifier. We show that single-pass depolarisation strongly depends on input polarisation state and pumping parameters. In the absence of any depolarisation compensation scheme, depolarisation varies over a range between 5% and 40%. The strong dependence of thermal stress-induced depolarisation on input polarisation indicates that, in the case of multipass amplifiers, the use of waveplates after every pass can reduce depolarisation losses significantly. We expect that this study will assist in the design and optimisation of Yb:YAG lasers.

150 J DPSSL operating at 1.5 kW level.

We report on obtaining output energy of 146 J in 10 ns long pulses at 10 Hz repetition rate from Bivoj, a multi-Joule multi-slab cryogenic gas-cooled diode pumped solid state laser, by overcoming its damage threshold bottleneck. This is a 40% energy and power increase of the laser system in comparison to our previous publication and to the most powerful multi-Joule high power laser system.

Second and third harmonic conversion of a kilowatt average power, 100-J-level diode pumped Yb:YAG laser in large aperture LBO.

We report on the successful demonstration of second and third harmonic conversion of a high pulse energy, high average power 1030 nm diode pumped Yb-doped yttrium aluminum garnet (Yb:YAG) nanosecond pulsed laser in a large aperture lithium triborate (LBO) crystal. We demonstrated generation of 59.7 J at 10 Hz (597 W) at 515 nm (second harmonic) and of 65.0 J at 1 Hz (65 W) at 343 nm (third harmonic), with efficiencies of 66% and 68%, respectively. These results, to the best of our knowledge, represent the highest energy and power reported for frequency conversion to green and UV-A wavelengths.

A novel, safe, fast and efficient treatment for Her2-positive and negative bladder cancer utilizing an EGF-anthrax toxin chimera.

Bladder cancer is the sixth most common cancer in the United States, and it exhibits an alarming 70% recurrence rate. Thus, the development of more efficient antibladder cancer approaches is a high priority. Accordingly, this work provides the basis for a transformative anticancer strategy that takes advantage of the unique characteristics of the bladder. Unlike mucin-shielded normal bladder cells, cancer cells are exposed to the bladder lumen and overexpress EGFR. Therefore, we used an EGF-conjugated anthrax toxin that after targeting EGFR was internalized and triggered apoptosis in exposed bladder cancer cells. This unique agent presented advantages over other EGF-based technologies and other toxin-derivatives. In contrast to known agents, this EGF-toxin conjugate promoted its own uptake via receptor microclustering even in the presence of Her2 and induced cell death with a LC50 < 1 nM. Furthermore, our data showed that exposures as short as ≈3 min were enough to commit human (T24), mouse (MB49) and canine (primary) bladder cancer cells to apoptosis. Exposure of tumor-free mice and dogs with the agent resulted in no toxicity. In addition, the EGF-toxin was able to eliminate cells from human patient tumor samples. Importantly, the administration of EGF-toxin to dogs with spontaneous bladder cancer, who had failed or were not eligible for other therapies, resulted in ~30% average tumor reduction after one treatment cycle. Because of its in vitro and in vivo high efficiency, fast action (reducing treatment time from hours to minutes) and safety, we propose that this EGF-anthrax toxin conjugate provides the basis for new, transformative approaches against bladder cancer.

Stable high-energy, high-repetition-rate, frequency doubling in a large aperture temperature-controlled LBO at 515 nm.

We report on frequency doubling of high-energy, high-repetition-rate ns pulses from a cryogenically gas cooled, multi-slab Yb:YAG laser system, using a type-I phase-matched lithium triborate (LBO) crystal. Pulse energy of 4.3 J was extracted at 515 nm for a fundamental input of 5.4 J at 10 Hz (54 W), corresponding to a conversion efficiency of 77%. However, during long-term operation, a significant reduction of efficiency (more than 25%) was observed owing to the phase mismatch arising due to the temperature-dependent refractive index change in the crystal. This forced frequent angle tuning of the crystal to recover the second-harmonic generation (SHG) energy. More than a five-fold improvement in energy stability of SHG was observed when the LBO crystal was mounted in an oven, and its temperature was controlled at 27°C. Stable frequency doubling with 0.8% rms energy variation was achieved at a higher input power of 74 W when the LBO temperature was controlled at 50°C.

High energy, high repetition rate, second harmonic generation in large aperture DKDP, YCOB, and LBO crystals.

We report on type-I phase-matched second harmonic generation (SHG) in three nonlinear crystals: DKDP (98% deuteration), YCOB (XZ plane), and LBO (XY plane), of 8 J, 10 Hz cryogenic gas cooled Yb:YAG laser operating at 1029.5 nm. DKDP exhibited an efficiency of 45% at a peak fundamental intensity of 0.24 GW/cm2 for 10 Hz operation at 10 ns. At the same intensity and repetition rate, YCOB and LBO showed 50% and 65% conversion efficiencies, respectively. Significant improvement in conversion efficiency, to a maximum of 82%, was demonstrated in LBO at 0.7 GW/cm2 and 10 Hz, generating output energy of 5.6 J at 514.75 nm, without damage or degradation. However, no improvement in conversion efficiency was recorded for YCOB at this increased intensity. Additionally, we present theoretically calculated temperature maps for both 10 J and 100 J operation at 10 Hz, and discuss the suitability of these three crystals for frequency conversion of a 100 J, 10 Hz diode pumped solid state laser (DPSSL).

100 J-level nanosecond pulsed diode pumped solid state laser.

We report on the successful demonstration of a 100 J-level, diode pumped solid state laser based on cryogenic gas cooled, multi-slab ceramic Yb:YAG amplifier technology. When operated at 175 K, the system delivered a pulse energy of 107 J at a 1 Hz repetition rate and 10 ns pulse duration, pumped by 506 J of diode energy at 940 nm, corresponding to an optical-to-optical efficiency of 21%. To the best of our knowledge, this represents the highest energy obtained from a nanosecond pulsed diode pumped solid state laser. This demonstration confirms the energy scalability of the diode pumped optical laser for experiments laser architecture.

DiPOLE: a 10 J, 10 Hz cryogenic gas cooled multi-slab nanosecond Yb:YAG laser.

The Diode Pumped Optical Laser for Experiments (DiPOLE) project at the Central Laser Facility aims to develop a scalable, efficient high pulse energy diode pumped laser amplifier system based on cryogenic gas cooled, multi-slab ceramic Yb:YAG technology. We present recent results obtained from a scaled down prototype laser system designed for operation at 10 Hz pulse repetition rate. At 140 K, the system generated 10.8 J of energy in a 10 ns pulse at 1029.5 nm when pumped by 48 J of diode energy at 940 nm, corresponding to an optical to optical conversion efficiency of 22.5%. To our knowledge, this represents the highest pulse energy obtained from a cryo cooled Yb laser to date and the highest efficiency achieved by a multi-Joule diode pumped solid state laser system. Additionally, we demonstrated shot-to-shot energy stability of 0.85% rms for the system operated at 7 J, 10 Hz during several runs lasting up to 6 hours, with more than 50 hours in total. We also demonstrated pulse shaping capability and report on beam, wavefront and focal spot quality.

Transmission grating stretcher for contrast enhancement of high power lasers.

We propose, for the first time, a transmission grating stretcher for high power lasers and demonstrate its superiority over conventional, reflective gold grating stretchers in terms of pulse temporal quality. We show that, compared to a conventional stretcher with the same stretching factor, the transmission-grating based stretcher yields more than an order of magnitude improvement in the contrast pedestal. We have also quantitatively characterized the roughness of the grating surfaces and estimated its impact on the contrast pedestal.

Energy coupling in short pulse laser solid interactions and its impact for space debris removal.

Significant advances have been made over the last decade to improve the performance, efficiency, and contrast of high peak and average power laser systems, driven by their use in a wide variety of fields, from the industrial to the scientific. As the contrast of the lasers has improved, interactions with contrasts of 1012 are now routinely undertaken. At such high contrasts, there is negligible preplasma formation and the ionized surface layer created by subpicosecond-duration pulses typically forms a highly reflective "plasma mirror" capable of reflecting between 70% and 90% of the incident energy. Although such interactions are of significant interest for applications such as harmonic source production and to enable the underlying physics to be studied, their low absorption can limit their usefulness for applications such as space debris removal.

Microbiology of explanted suture segments from infected and noninfected surgical patients.

Sutures under selective host/environmental factors can potentiate postoperative surgical site infection (SSI). The present investigation characterized microbial recovery and biofilm formation from explanted absorbable (AB) and nonabsorbable (NAB) sutures from infected and noninfected sites. AB and NAB sutures were harvested from noninfected (70.9%) and infected (29.1%) sites in 158 patients. At explantation, devices were sonicated and processed for qualitative/quantitative bacteriology; selective sutures were processed for scanning electron microscopy (SEM). Bacteria were recovered from 85 (53.8%) explanted sites; 39 sites were noninfected, and 46 were infected. Suture recovery ranged from 11.1 to 574.6 days postinsertion. A significant difference in mean microbial recovery between noninfected (1.2 isolates) and infected (2.7 isolates) devices (P < 0.05) was noted. Staphylococcus epidermidis, Staphylococcus aureus, coagulase-negative staphylococci (CNS), Peptostreptococcus spp., Bacteroides fragilis, Escherichia coli, Enterococcus spp., Pseudomonas aeruginosa, and Serratia spp. were recovered from infected devices, while commensal skin flora was recovered from noninfected devices. No significant difference in quantitative microbial recovery between infected monofilament and multifilament sutures was noted. Biofilm was present in 100% and 66.6% of infected and noninfected devices, respectively (P < 0.042). We conclude that both monofilament and braided sutures provide a hospitable surface for microbial adherence: (i) a significant difference in microbial recovery from infected and noninfected sutures was noted, (ii) infected sutures harbored a mixed flora, including multidrug-resistant health care-associated pathogens, and (iii) a significant difference in the presence or absence of a biofilm in infected versus noninfected explanted devices was noted. Further studies to document the benefit of focused risk reduction strategies to minimize suture contamination and biofilm formation postimplantation are warranted.

Temperature dependent emission and absorption cross section of Yb3+ doped yttrium lanthanum oxide (YLO) ceramic and its application in diode pumped amplifier.

Temperature dependent absorption and emission cross-sections of 5 at% Yb(3+) doped yttrium lanthanum oxide (Yb:YLO) ceramic between 80K and 300 K are presented. In addition, we report on the first demonstration of ns pulse amplification in Yb:YLO ceramic. A pulse energy of 102 mJ was extracted from a multi-pass amplifier setup. The amplification bandwidth at room temperature confirms the potential of Yb:YLO ceramic for broad bandwidth amplification at cryogenic temperatures.

Flexible Sigmoidoscopy Utility in the Diagnosis of Pediatric Gastrointestinal Disorders.

AIM:  Although flexible sigmoidoscopy (FS) is utilized in children for the diagnosis of pediatric gastrointestinal conditions, such as inflammatory bowel disease and juvenile polyp disorders, the diagnostic yield of FS in pediatric patients is unknown. MATERIALS AND METHODS:  We retrospectively reviewed FS cases in children under 18 years of age over a five-year period at our institution. Indications for the procedure, endoscopic visual findings, histologic findings, final diagnosis, and any management changes based on FS findings were included. RESULTS:  A total of 354 cases were included in the analysis for which 40 cases (11.3%) had abnormal visual findings, 48 cases (13.6%) had abnormal histologic findings, and 13 cases (3.7%) had both abnormal endoscopic visual and histologic findings. Of the 88 cases with abnormal visual and/or histologic abnormalities, only the results of 34 of these FS cases led to a change in management based on endoscopic findings (9.6%). Most patients with a non-diagnostic FS had a final diagnosis of functional abdominal pain; most patients with a diagnostic FS had a final diagnosis of colitis, not otherwise specified. CONCLUSION:  Our findings suggest that FS is not a helpful diagnostic endoscopic intervention in pediatric patients, especially in children with reassuring history and physical exam findings.

The essential genome of a bacterium.

Caulobacter crescentus is a model organism for the integrated circuitry that runs a bacterial cell cycle. Full discovery of its essential genome, including non-coding, regulatory and coding elements, is a prerequisite for understanding the complete regulatory network of a bacterial cell. Using hyper-saturated transposon mutagenesis coupled with high-throughput sequencing, we determined the essential Caulobacter genome at 8 bp resolution, including 1012 essential genome features: 480 ORFs, 402 regulatory sequences and 130 non-coding elements, including 90 intergenic segments of unknown function. The essential transcriptional circuitry for growth on rich media includes 10 transcription factors, 2 RNA polymerase sigma factors and 1 anti-sigma factor. We identified all essential promoter elements for the cell cycle-regulated genes. The essential elements are preferentially positioned near the origin and terminus of the chromosome. The high-resolution strategy used here is applicable to high-throughput, full genome essentiality studies and large-scale genetic perturbation experiments in a broad class of bacterial species.

High-efficiency 10 J diode pumped cryogenic gas cooled Yb:YAG multislab amplifier.

We report on the first demonstration of a diode-pumped, gas cooled, cryogenic multislab Yb:YAG amplifier. The performance was characterized over a temperature range from 88 to 175 K. A maximum small-signal single-pass longitudinal gain of 11.0 was measured at 88 K. When amplifying nanosecond pulses, recorded output energies were 10.1 J at 1 Hz in a four-pass extraction geometry and 6.4 J at 10 Hz in a three-pass setup, corresponding to optical to optical conversion efficiencies of 21% and 16%, respectively. To our knowledge, this represents the highest pulse energy so far obtained from a cryo-cooled Yb-laser and the highest efficiency from a multijoule diode pumped solid-state laser system.

Gamma-irradiation sterilization in an inert environment: a partial solution.

BACKGROUND: In the mid to late 1990 s, to sterilize UHMWPE bearings, manufacturers changed from gamma-irradiation-in-air (gamma-air) sterilization, which initiated oxidation leading to bearing fatigue, to gamma-irradiation sterilization in an inert environment (gamma-inert). The change to gamma-inert sterilization reportedly prevented shelf oxidation before implantation but not in vivo oxidation. QUESTIONS/PURPOSES: We asked: (1) Has the change to gamma-inert sterilization prevented shelf oxidation that led to early in vivo fatigue damage in gamma-air-sterilized tibial inserts? And (2) has the change to gamma-inert sterilization prevented the occurrence of fatigue secondary to in vivo oxidation? METHODS: We rated 183 retrieved gamma-air- and 175 retrieved gamma-inert-sterilized tibial inserts for clinical fatigue damage and analyzed 132 gamma-air- and 174 gamma-inert-sterilized tibial inserts for oxidation by Fourier transform infrared spectroscopy. RESULTS: Oxidation led to decreased mechanical properties in shelf-aged gamma-air-sterilized tibial inserts. Barrier packaging prevented shelf oxidation in gamma-inert-sterilized tibial inserts. Gamma-air- and gamma-inert-sterilized inserts oxidized in vivo. Fatigue damage (delamination) occurred more frequently in inserts retrieved after longer time in vivo. Longer in vivo time correlated with higher oxidation and more accumulated cycles of use. CONCLUSIONS: Published oxidation projections suggest gamma-inert-sterilized tibial inserts would reach the critical oxidation for the onset of fatigue after 11 to 14 years in vivo. These retrievals appear to follow the projected oxidation trends. Frequency of fatigue damage increased with increasing oxidation. CLINICAL RELEVANCE: Fatigue of tibial inserts becomes more likely, especially in active patients, after more than a decade of good clinical performance.