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PDF file, 6050K, SrtA ligation reactions displayed on full length SDS-PAGE gels stained by coomassie blue.

Cicatricial pemphigoid (CP) with tracheal involvement is a rare and potentially deadly condition. Here, we report the first case in which Nd:YAG laser (1064nm) laser ablation bronchoscopy was used to treat CP with tracheal involvement. Our patient is a 71-year-old male with a history of CP refractory to medical therapy affecting his trachea who presented to the emergency department with dyspnea. He ultimately underwent bronchoscopy with Nd: YAG laser (1064nm) laser ablation, which resulted in a temporary alleviation of his respiratory symptoms. A repeat laser ablation was planned in hopes of prolonging the patient’s remission, but due to interval changes in the patient’s airway anatomy, it was deemed unsafe. While our patient’s uniquely advanced disease was not amenable to further laser-mediated intervention, it is possible that patients with less advanced disease may experience better outcomes with similar therapy. This case shows the promise laser ablation could hold for patients with tracheal cicatricial pemphigoid.

The need for solutions to combat new and existing infections has never been so topical. The current SARS-CoV-2 pandemic and the rise in antimicrobial resistance in previously treatable microbial diseases are two examples requiring antimicrobial solutions for systemic or topical treatment or as preventative measures, including empowering improved infection control measures. At the same time, the sustainability of ingredients, formulation excipients and the drive to use more natural ingredients in products have led to increased research outputs on natural products or novel compounds, and to a reflection on formulations and how these can improve the efficacy of antimicrobials.

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.

Bacterial products can act on neurons to alter signaling and function. Here, we find that dorsal root ganglia (DRG) sensory neurons are enriched for ANTXR2, the high-affinity receptor for anthrax toxins. Anthrax toxins are composed of protective antigen (PA), which binds to ANTXR2, and the protein cargoes Edema Factor (EF) and Lethal Factor (LF). Intrathecal administration of Edema Toxin (ET; PA+EF) targeted DRG neurons and induced analgesia in mice. ET inhibited mechanical and thermal sensation, and pain caused by formalin, carrageenan, and nerve injury. Analgesia depended on ANTXR2 expressed by Na(v)1.8(+) or Advillin(+) neurons. ET modulated PKA signaling in mouse sensory and human iPS-derived sensory neurons and attenuated spinal cord neurotransmission. We further engineered anthrax toxins to introduce exogenous protein cargoes, including botulinum toxin, into DRG neurons to silence pain. Our study highlights interactions between a bacterial toxin and nociceptors which may lead to the development of novel pain therapeutics.

Background Proactively monitoring infliximab levels is an emerging area of interest in pediatric Crohn’s disease. There are only limited data on therapeutic drug monitoring for children with Crohn’s disease. The goal of our study was to determine the utility of therapeutic drug monitoring in achieving clinical remission in a cohort of pediatric Crohn’s disease patients receiving infliximab. Methods This prospective single-center study enrolled 37 patients with Crohn’s disease at the start of infliximab infusions and monitored trough levels at 6-month intervals for 18 months. Each participant was matched to a historic control for the modified pediatric Crohn’s disease activity index (mPCDAI) at baseline, age and sex. The primary outcome was an mPCDAI score of ≤7.5 at 6, 12 and 18 months. A multivariate logistic regression analysis was performed. Results Data were available for all 37 cases at 6 and 12 months and for 34 cases at 18 months. Demographics and disease characteristics were similar between groups. All 34 cases demonstrated clinical remission at 18 months (100% vs. 88%, P=0.114). Univariate and multivariate analyses did not show statistical significance. Dose intensification was seen more often in the cases at 18 months. Conclusion All of our moderate-to-severe pediatric Crohn’s disease patients who received prospective therapeutic drug monitoring of infliximab were in clinical remission at follow up, but this was not statistically significantly different from the 88% clinical remission rate of the control group.

Over the past years, the frequency and scope of disasters affecting the United States have significantly increased. Government agencies have made efforts in improving the nation’s disaster response framework to minimize fatalities and economic loss due to disasters. Disaster response has evolved with the emergency management agencies incorporating systematic changes in their organization and emergency response functions to accommodate lessons learned from past disaster events. Technological advancements in disaster response have also improved the agencies’ ability to prepare for and respond to natural hazards. The transportation and logistics sector has a primary role in emergency response during and after disasters. In this light, this paper seeks to identify how effective policy changes and new technology have aided the transportation and logistics sector in emergency response and identify gaps in current practices for further improvement. Specifically, this study compares and contrasts the transportation and logistical support to emergency relief efforts during and after two major Hurricane events in the U.S., namely Hurricane Katrina (which affected New Orleans in 2005) and Hurricane Harvey (which affected Houston in 2017). This comparison intends to outline the major steps taken by the government and the private entities in the transportation and logistics sector to facilitate emergency response and the issues faced during the process. Finally, the paper summarizes the lessons learned from both the Hurricane events and provides recommendations for further improvements in transportation and logistical support to disaster response.

Targeting of antigens to erythrocytes can be used to selectively mitigate their immunogenicity, but the methods to equip a variety of cargoes with erythrocyte-targeting properties are limited. Here we identified a D-peptide that targets murine erythrocytes and decreases anti-drug antibody responses when conjugated to the protective antigen from Bacillus anthracis, a protein of therapeutic interest. The D-peptide likewise decreases inflammatory anti-ovalbumin (OVA) CD8+ T cell responses when attached to a peptide antigen derived from OVA. To discover this targeting ligand, we leveraged mass spectrometry to decode a randomized D-peptide library selected in mice, extending the application of synthetic libraries to in vivo affinity selections.

Bacterial products can act on neurons to alter signaling and function. In the present study, we found that dorsal root ganglion (DRG) sensory neurons are enriched for ANTXR2, the high-affinity receptor for anthrax toxins. Anthrax toxins are composed of protective antigen (PA), which binds to ANTXR2, and the protein cargoes edema factor (EF) and lethal factor (LF). Intrathecal administration of edema toxin (ET (PA + EF)) targeted DRG neurons and induced analgesia in mice. ET inhibited mechanical and thermal sensation, and pain caused by formalin, carrageenan or nerve injury. Analgesia depended on ANTXR2 expressed by Na

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.

Bacterial toxins are able to act on neurons to modulate signaling and function. Here, we find that nociceptive sensory neurons that mediate pain are enriched in the receptor for anthrax toxins, ANTXR2. Anthrax Edema Toxin (ET) induced cAMP and PKA signaling in Nav1.8+nociceptive neurons and modulated painin vivo. Peripherally administered ET mediated mechanical allodynia in naïve mice and duringB. anthracisinfection. Intrathecally administered ET produced analgesic effects, potently blocking pain-like behaviors in multiple mouse models of inflammatory and chronic neuropathic pain. Nociceptor-specific ablation of ANTXR2 attenuated ET-induced signaling and analgesia. Modified anthrax toxin successfully delivered exogenous protein cargo into nociceptive neurons, illustrating utility of the anthrax toxin system as a molecular platform to target pain. ET further induced signaling in human iPSC-derived sensory neurons. Our findings highlight novel interactions between a bacterial toxin and nociceptors that may be utilized for developing new pain therapeutics.SUMMARYANTXR2 expression on nociceptive neurons allows selective targeting and modulation of pain by native and engineered anthrax toxins.

We compare for the first time the influence of different Yb:YAG gain media on the performance of a large-area, high average–power laser system with an output energy of up to 6 J. Monocrystalline slabs grown by a new technique without central growth defect are compared with ceramics. Small signal gain, maximum output energy and thermal lensing are compared for ceramic slabs with co-sintered amplified spontaneous emission (ASE) absorber cladding, monocrystalline slab with and without optically bonded ASE absorber cladding, and surface structured monocrystalline slabs. We show that these large monocrystals with optically bonded absorber cladding have similar performance to cladded ceramics, so far the only material for high-energy Yb:YAG lasers.

We report on the successful demonstration of a 150 J nanosecond pulsed cryogenic gas cooled, diode-pumped multi-slab Yb:YAG laser operating at 1 Hz. To the best of our knowledge, this is the highest energy ever recorded for a diode-pumped laser system.

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.

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 LC(50) < 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.

In this letter, we investigate the effect of orbital angular momentum (OAM) on elastic photon-photon scattering in vacuum for the first time. We define exact solutions to the vacuum electro-magnetic wave equation which carry OAM. Using those, the expected coupling between three initialwaves is derived in the framework of an effective field theory based on the Euler-Heisenberg La-grangian and shows that OAM adds a signature to the generated photons thereby greatly improvingthe signal-to-noise ratio. This forms the basis for a proposed high-power laser experiment utilizingquantum optics techniques to filter the generated photons based on their OAM state, Comment: 7 Pages, 3 Figures (color), added supplemental materials to elaborate on some arguments and added some relevant references

Acoustic signals recorded from laser shock peening (LSP) of aluminium, titanium and stainless steel alloys were analysed for different laser pulse widths, energy and confinement conditions. In this paper, we report that different materials and conditions registered unique acoustic signatures. Further, the acoustic signatures in the time domain were transformed to the frequency domain and were fitted to a lognormal distribution, yielding a unique set of parameters for each material and set of conditions. These parameters were benchmarked using the measurements of residual stress by the incremental centre hole-drilling (ICHD) method. Detailed analysis of the acoustic signal reveals that this method once calibrated with few ICHD data, can identify successful peening of materials.

The Petawatt beamline at the Vulcan laser facility is capable of delivering pulses with 500J of energy in

We present a comparative thermo-optical study of various gain media geometries to minimize depolarization losses and wavefront distortions for a concept of 10 J/ 100 Hz cryo HEC-DPSSL based on 10 J/10 Hz Bivoj/DiPOLE system.

We present a new PW beamline for Vulcan facility with the focus on the ps Front End. This fully OPCPA system is designed to deliver 30 J, 30 fs pulses with a 5 min repetition rate.

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.