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LASER APPARATUS AND EXTREME ULTRAVIOLET LIGHT GENERATING APPARATUS

A laser beam having desired properties is output at desired timings. A laser apparatus is a laser apparatus for use with an extreme ultraviolet light generating apparatus that generates extreme ultraviolet light at a repetition frequency which is set in advance, and may be equipped with: a semiconductor laser that outputs a laser beam when a trigger signal is input thereto; an optical switch that switches between a state in which the laser beam passes therethrough and a state in which the laser beam does not pass therethrough, provided along the optical path of the laser beam; and a control unit configured to output the trigger signal to the semiconductor laser at a frequency which is an integer multiple of the repetition frequency, and to control the optical switch such that the laser beam passes therethrough at the repetition frequency.




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DISINFECTION OF WATER MAINS USING ULTRAVIOLET LIGHT AND OXIDIZING AGENTS

Methods and systems are provided for disinfecting water mains using ultraviolet (UV) light and advanced oxidation processes. One or more UV light sources are provided and secured to a movable device that moves axially in a pipe. The frequency and intensity of the UV light is determined based on characteristics of the pipe, such as its material and size. The rate at which the movable device moves through the pipe is also determined so that the interior surface of the pipe is properly disinfected. The movable device is remotely caused to move through the pipe. An oxidant supply component having a dispensing portion dispenses an oxidizing agent into the pipe. A portion of the emitted UV light may convert the dispensed oxidizing agent into additional oxidizing agents that further disinfect the pipe.




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AAS launches Kicks & Snares + 50% OFF everything Ultra Analog VA-3

Applied Acoustics Systems has released its new sound pack Kicks & Snares, a collection of 100 drum sounds for the Ultra Analog VA-3 synthesizer and AAS Player plugin. You can never have too many kicks and snares! Resident sound designer Adam Pietruszko signs off on an expertly crafted and clever collection of punchy bass drum […]

The post AAS launches Kicks & Snares + 50% OFF everything Ultra Analog VA-3 appeared first on rekkerd.org.




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Trump raises question of ultraviolet light and COVID-19. We ask doctors, scientists.


President Donald Trump speculated about ultraviolet rays. But artificial UV techniques are ineffective and likely deadly for treating an infected person, scientists say — and some can be extremely dangerous used at home for disinfecting.




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Portable ultrasound device could see doctors throw away their stethoscopes, surgeon says

A small portable ultrasound machine connected to a mobile phone is set to make the stethoscope obsolete, according to a professor at the Royal Melbourne Hospital. It's faster, safer and more accurate.




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Ultra athletes like Kym Lynch push their body and mind for a challenge

Ultra athletes like Kym Lynch push their body and mind for a challenge





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New technique uses ultrasound to align living cells in 3D bioprinted tissues

One of the ways of making bioengineered tissues is to embed living cells within 3D printed structures. But one challenge has been organizing the cells in 3D bioprinted gels, so that the engineered tissue more closely mimics natural tissues.



  • 3D Printing Applications

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GE Research uses 3D printing to design Ultra Performance Heat Exchanger

GE Research is leading a $2.5 MM project through the Advanced Research Projects Agency’s (ARPA-E) High Intensity Thermal Exchange through Materials and Manufacturing Processes program (HITEMMP) to develop a high temperature, high pressure and super-compact heat exchanger enabled by additive manufacturing technology.



  • 3D Printing Applications

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Ultra endurance sports are gaining more popularity, but what drives competitors?

Running or riding hundreds of kilometres for fun, sport, and a physical and mental challenge.




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In re Ultra Petroleum Corp.

(United States Fifth Circuit) - Held that energy companies emerging from bankruptcy did not have to pay certain creditors a contractual make-whole amount, even though the companies were now solvent due to a rise in commodity prices. Vacated and remanded.




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In re Ultra Petroleum Corp.

(United States Fifth Circuit) - Held that energy companies emerging from bankruptcy did not have to pay certain creditors a contractual make-whole amount, even though the companies were now solvent due to a rise in commodity prices. Vacated and remanded.




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FYI: Your browser can pick up ultrasonic signals you can't hear, and that sounds like a privacy nightmare to some

High-frequency audio could be used to stealthily track netizens

Technical folks looking to improve web privacy haven't been able to decide whether sound beyond the range of human hearing poses enough of a privacy risk to merit restriction.…




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Topo Designs Packable Ultralight Jacket




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#72: The Ultra Megazord Mailbag Edition




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2020 Ultraportable with 9 hours of life with great performance – Asus Zenbook




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Venus flytraps’ ultra-sensitive hairs help determine if an insect is worth trapping

Good news for bugs that weigh less than a sesame seed.




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Inside the ultra-competitive world of Kobe Bryant merchandise after his death

Hours after Kobe Bryant's death, speculators were registering domain names connected to the tragedy. Merchandise tied to the Lakers legend is in heavy demand.




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The ultra-rich are still buying $50-million homes (in case you were wondering)

Pandemic or not, the ultra-wealthy are still buying and selling prized properties across L.A. County




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How Rolls-Royce and Lamborghini are setting a new high bar for ultra-luxury SUVs

Fancy gas-powered 4x4s are bringing boutique brands more sales and new buyers




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Extreme ultraviolet imaging displays potential to enhance study of Alzheimer's disease

(University of Southampton) Scientists have published highly detailed images of lab-grown neurons using Extreme Ultraviolet radiation that could aid the analysis of neurodegenerative diseases.




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Ultraviolet light exposes contagion spread from improper PPE use

(Florida Atlantic University) Despite PPE use, reports show that many health care workers contracted COVID-19. A novel training technique reinforces the importance of using proper procedures to put on and take off PPE when caring for patients during the pandemic. Researchers vividly demonstrate how aerosol-generating procedures can lead to exposure of the contagion with improper PPE use. The most common error made by the health care workers was contaminating the face or forearms during PPE removal.




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Focused ultrasound opening brain to previously impossible treatments

(University of Virginia Health System) Focused ultrasound, the researchers hope, could revolutionize treatment for conditions from Alzheimer's to epilepsy to brain tumors -- and even help repair the devastating damage caused by stroke.




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PSMA PET/CT and standard plus PET/CT-Ultrasound fusion targeted prostate biopsy can diagnose clinically significant prostate cancer in men with previous negative biopsies

The purpose of this study was to investigate the feasibility and diagnostic efficacy of 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) combined with PET-ultrasound image-guided biopsy in the diagnosis of prostate cancer. Methods: A total of 31 patients with previously negative prostate biopsy, but persistent elevated serum prostate specific antigen (PSA), were imaged with a 68Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT ligand prior to undergoing repeat prostate biopsy. Based on the proposed PROMISE criteria, PSMA PET/CT results were interpreted as negative (miPSMA-ES 0-1) or positive (miPSMA-ES 2-3). All patients underwent standard template systematic biopsy with up to four additional PSMA PET-ultrasound fusion image-guided biopsy cores. The sensitivity, specificity, positive and negative predictive values, and accuracy of PSMA PET/CT were determined. In addition, the correlation between miPSMA-ES and detection rate of prostate cancer was also analyzed. Univariate logistic regression models were established using PSMA PET/CT semi-quantitative analysis parameters to predict the outcome of repeat prostate biopsy. Results: The median age of patients was 65 years (range 53-81), and the median PSA level was 18.0 ng/ml (range 5.48-49.77 ng/ml). Prostate cancer was detected in 15/31 patients (48.4%) and 12/31 patients (38.7%) had clinically significant disease. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 68Ga-PSMA PET/CT in the diagnosis of clinically significant prostate cancer were 100.0%, 68.4%, 66.7%, 100.0% and 80.6%, respectively. The detection rate of prostate cancer increased with the increase of miPSMA-ES score. The detection rate of clinically significant prostate cancer in miPSMA-ES 0-1, 2 and 3 groups were 0%, 54.5% and 85.7% respectively. Semi-quantitative analysis of 68Ga-PSMA PET/CT images showed that predictive models based on maximum standardized uptake value (SUVmax), tumor-to-background normal prostate SUV (SUVT/BGp) and tumor-to-background normal liver SUV (SUVratio) could effectively predict clinically significant prostate cancer; area under the curves were 0.930, 0.877, and 0.956, respectively. Conclusion: This study preliminarily confirmed that 68Ga-PSMA PET/CT imaging combined with PET-ultrasound fusion image-guided prostate biopsy can effectively detect clinically significant prostate cancer. Prebiopsy 68Ga-PSMA PET/CT has predictive value for clinically significant cancer in the studied patient population.




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Thorough Performance Evaluation of 213 nm Ultraviolet Photodissociation for Top-down Proteomics [Technological Innovation and Resources]

Top-down proteomics studies intact proteoform mixtures and offers important advantages over more common bottom-up proteomics technologies, as it avoids the protein inference problem. However, achieving complete molecular characterization of investigated proteoforms using existing technologies remains a fundamental challenge for top-down proteomics. Here, we benchmark the performance of ultraviolet photodissociation (UVPD) using 213 nm photons generated by a solid-state laser applied to the study of intact proteoforms from three organisms. Notably, the described UVPD setup applies multiple laser pulses to induce ion dissociation, and this feature can be used to optimize the fragmentation outcome based on the molecular weight of the analyzed biomolecule. When applied to complex proteoform mixtures in high-throughput top-down proteomics, 213 nm UVPD demonstrated a high degree of complementarity with the most employed fragmentation method in proteomics studies, higher-energy collisional dissociation (HCD). UVPD at 213 nm offered higher average proteoform sequence coverage and degree of proteoform characterization (including localization of post-translational modifications) than HCD. However, previous studies have shown limitations in applying database search strategies developed for HCD fragmentation to UVPD spectra which contains up to nine fragment ion types. We therefore performed an analysis of the different UVPD product ion type frequencies. From these data, we developed an ad hoc fragment matching strategy and determined the influence of each possible ion type on search outcomes. By paring down the number of ion types considered in high-throughput UVPD searches from all types down to the four most abundant, we were ultimately able to achieve deeper proteome characterization with UVPD. Lastly, our detailed product ion analysis also revealed UVPD cleavage propensities and determined the presence of a product ion produced specifically by 213 nm photons. All together, these observations could be used to better elucidate UVPD dissociation mechanisms and improve the utility of the technique for proteomic applications.




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Episode 22 - The Internet of Ultra Balls (IoUB) Pokemon Go, Playstation VR and iOS 10

In Matt Egan's absence first time host Henry Burrell heroically steps in to chat about Pokemon Go with producer Chris. Then fellow staff writer Chris Minasians discusses iOS 10 beta and all of the rumoured features for the latest Apple operating system, including dark mode (10:30). Finally, Lewis Painter, staff writer at PC Advisor, talks about Playstation VR being released for the PS4, pricing and games (23:30).  


See acast.com/privacy for privacy and opt-out information.




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"We don't really know the impact of these products on our health": Ultraprocessed food & cancer risk

A study published by The BMJ today reports a possible association between intake of highly processed (“ultra-processed”) food in the diet and cancer. Ultra-processed foods include packaged baked goods and snacks, fizzy drinks, sugary cereals, ready meals and reconstituted meat products - often containing high levels of sugar, fat, and salt, but...




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Preoperative Localization of Adenomas in Primary Hyperparathyroidism: The Value of 11C-Choline PET/CT in Patients with Negative or Discordant Findings on Ultrasonography and 99mTc-Sestamibi SPECT/CT

We aimed to assess the value of 11C-choline PET in patients with primary hyperparathyroidism and negative or discordant results on 99mTc-sestamibi imaging and neck ultrasound. Methods: Eighty-seven such patients were assessed and subsequently underwent parathyroidectomy. PET/CT image data were analyzed semiquantitatively using SUVmax and SUV ratios (target to contralateral thyroid gland and carotid artery). A positive PET/CT result was defined as focal uptake significantly higher than regular thyroid tissue. Ectopic foci were also considered positive. Inconclusive PET/CT cases were defined as a lesion with uptake equal to normal thyroid tissue. If no prominent or ectopic uptake was detectable, the PET/CT result was considered negative. Results: When dichotomizing the 11C-choline PET/CT imaging results by defining lesions with both positive and inconclusive uptake as positive, we found 84 of 92 lesions (91.3%) to have true-positive uptake whereas 8 lesions (8.7%) had false-positive uptake. One lesion showed false-negative uptake; the sensitivity was 98.8%. The corresponding positive predictive value for lesions was 91.3%. The mean SUVmax was 6.15 ± 4.92 in 72 lesions with positive uptake (70 patients) and 2.96 ± 2.32 in 20 lesions with inconclusive uptake (18 patients). Conclusion: These results in a large group of patients indicate that 11C-choline PET/CT is a promising tool for parathyroid adenoma localization when ultrasound and 99mTc-sestamibi imaging yield negative or discordant results.




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The little book of lost words : collywobbles, ultracrepidarian and other surprisingly useful terms worth resurrecting / Joe Gillard.

English language -- Glossaries, vocabularies, etc.




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Physics-informed neural network for ultrasound nondestructive quantification of surface breaking cracks. (arXiv:2005.03596v1 [cs.LG])

We introduce an optimized physics-informed neural network (PINN) trained to solve the problem of identifying and characterizing a surface breaking crack in a metal plate. PINNs are neural networks that can combine data and physics in the learning process by adding the residuals of a system of Partial Differential Equations to the loss function. Our PINN is supervised with realistic ultrasonic surface acoustic wave data acquired at a frequency of 5 MHz. The ultrasonic surface wave data is represented as a surface deformation on the top surface of a metal plate, measured by using the method of laser vibrometry. The PINN is physically informed by the acoustic wave equation and its convergence is sped up using adaptive activation functions. The adaptive activation function uses a scalable hyperparameter in the activation function, which is optimized to achieve best performance of the network as it changes dynamically the topology of the loss function involved in the optimization process. The usage of adaptive activation function significantly improves the convergence, notably observed in the current study. We use PINNs to estimate the speed of sound of the metal plate, which we do with an error of 1\%, and then, by allowing the speed of sound to be space dependent, we identify and characterize the crack as the positions where the speed of sound has decreased. Our study also shows the effect of sub-sampling of the data on the sensitivity of sound speed estimates. More broadly, the resulting model shows a promising deep neural network model for ill-posed inverse problems.




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Neonatal lung ultrasonography

9789402415490 (electronic bk.)




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Quantitative Ultrastructural Analysis of Hippocampal Excitatory Synapses

Thomas Schikorski
Aug 1, 1997; 17:5858-5867
Articles




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Ultra-high-resolution fMRI of Human Ventral Temporal Cortex Reveals Differential Representation of Categories and Domains

Human ventral temporal cortex (VTC) is critical for visual recognition. It is thought that this ability is supported by large-scale patterns of activity across VTC that contain information about visual categories. However, it is unknown how category representations in VTC are organized at the submillimeter scale and across cortical depths. To fill this gap in knowledge, we measured BOLD responses in medial and lateral VTC to images spanning 10 categories from five domains (written characters, bodies, faces, places, and objects) at an ultra-high spatial resolution of 0.8 mm using 7 Tesla fMRI in both male and female participants. Representations in lateral VTC were organized most strongly at the general level of domains (e.g., places), whereas medial VTC was also organized at the level of specific categories (e.g., corridors and houses within the domain of places). In both lateral and medial VTC, domain-level and category-level structure decreased with cortical depth, and downsampling our data to standard resolution (2.4 mm) did not reverse differences in representations between lateral and medial VTC. The functional diversity of representations across VTC partitions may allow downstream regions to read out information in a flexible manner according to task demands. These results bridge an important gap between electrophysiological recordings in single neurons at the micron scale in nonhuman primates and standard-resolution fMRI in humans by elucidating distributed responses at the submillimeter scale with ultra-high-resolution fMRI in humans.

SIGNIFICANCE STATEMENT Visual recognition is a fundamental ability supported by human ventral temporal cortex (VTC). However, the nature of fine-scale, submillimeter distributed representations in VTC is unknown. Using ultra-high-resolution fMRI of human VTC, we found differential distributed visual representations across lateral and medial VTC. Domain representations (e.g., faces, bodies, places, characters) were most salient in lateral VTC, whereas category representations (e.g., corridors/houses within the domain of places) were equally salient in medial VTC. These results bridge an important gap between electrophysiological recordings in single neurons at a micron scale and fMRI measurements at a millimeter scale.




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Apple's iPhone 11 captures 68% of India's 'ultra-premium' smartphone market



While Apple has yet to make substantial inroads into India's mainstream smartphone market, the tech giant's latest flagship iPhones continue to dominate top-tier category sales.




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Accuracy of Point-of-Care Ultrasound for Diagnosis of Skull Fractures in Children

Head injuries and concern for skull fracture are common in pediatrics. Point-of-care ultrasound is an imaging tool that can be used to diagnose fractures. However, there are scant data regarding the accuracy of point-of-care ultrasound in skull fracture diagnosis.

Clinicians with focused point-of-care ultrasound training are able to diagnose skull fractures in children with high specificity. Ultrasound may be valuable to diagnose skull fractures in children at the point of care. (Read the full article)




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Usefulness of Routine Head Ultrasound Scans Before Surgery for Congenital Heart Disease

Routine head ultrasound scans (HUSs) are frequently performed in the preoperative evaluation of the infants with congenital heart disease, and brain MRI is being increasingly used in the research setting. The utility of HUSs in this population has not yet been established.

This is the first study to prospectively evaluate the utility of routine HUSs compared with MRIs in asymptomatic newborns and young infants undergoing cardiac surgery. Our findings suggest that routine HUS is not indicated in asymptomatic term or near-term neonates undergoing surgery for CHD. (Read the full article)




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Ultrasound as a Screening Test for Genitourinary Anomalies in Children With UTI

Current guidelines recommend renal ultrasound as a screening test after febrile urinary tract infection, with voiding cystourethrogram (VCUG) only if the ultrasound is abnormal. Few studies have evaluated the accuracy of ultrasound as a screening test for VCUG-identified abnormalities.

This study shows that ultrasound is a poor screening test for genitourinary abnormalities identified on VCUG, such as vesicoureteral reflux. Neither positive nor negative ultrasounds reliably identify or rule out such abnormalities. Ultrasound and VCUG provide different, but complementary, information. (Read the full article)




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Ultrasonography/MRI Versus CT for Diagnosing Appendicitis

Previous studies have confirmed feasibility of MRI for diagnosis of appendicitis in adults and children. No study has assessed clinical end points when using ultrasound and MRI compared with computed tomography for diagnosis of appendicitis in children.

Radiation-free imaging with ultrasound selectively followed by MRI does not change clinical endpoints compared with CT for diagnosing appendicitis in children, with no difference in time to antibiotic administration, time to appendectomy, negative appendectomy rate, perforation rate, or length of stay. (Read the full article)




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Use of Neonatal Chest Ultrasound to Predict Noninvasive Ventilation Failure

Lung ultrasound outperforms conventional radiology in the emergency diagnosis of pneumothorax and pleural effusions. In the pediatric age, lung ultrasound has been also successfully applied to the fluid-to-air transition after birth and to rapid pneumonia diagnosis.

Nasal ventilation has dramatically decreased the need for invasive mechanical respiratory support. This study demonstrates that, after a short trial on nasal continuous positive airway pressure, lung ultrasonography reliably predicts the failure of noninvasive ventilation unlike the conventional chest radiogram. (Read the full article)




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Late Diagnosis of Coarctation Despite Prenatal Ultrasound and Postnatal Pulse Oximetry

Neonatal coarctation of the aorta (CoA) is a life-threatening cardiac defect, but because symptoms may be lacking initially, newborns with this defect are frequently discharged from the hospital undiagnosed. Delayed diagnosis of CoA is associated with increased morbidity and mortality.

This population-based study analyzes the contribution of prenatal ultrasound and postnatal pulse oximetry screening to the timely diagnosis of neonatal CoA. Both screening methods had low sensitivity for CoA. Nearly half of all newborns with isolated CoA were discharged undiagnosed. (Read the full article)




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Inappropriate Use of Ultrasound in Management of Pediatric Cryptorchidism

The value of ultrasound imaging for the diagnosis, prognosis, and surgical planning of cryptorchidism is limited at best.

Ultrasound remains grossly overused by referring physicians throughout Ontario, Canada, which resulted in a 3-month delay to definitive surgery and unnecessary expenditures. (Read the full article)




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Biochemical Characterization of QPX7728, a New Ultra-Broad-Spectrum Beta-lactamase Inhibitor of Serine and Metallo-Beta-Lactamases [Mechanisms of Resistance]

QPX7728 is a new ultra-broad-spectrum inhibitor of serine and metallo beta-lactamases from a class of cyclic boronates that gave rise to vaborbactam. The spectrum and mechanism of beta-lactamase inhibition by QPX7728 were assessed using purified enzymes from all molecular classes. QPX7728 inhibits class A ESBLs (IC50 range 1-3 nM) and carbapenemases such as KPC (IC50 2.9±0.4 nM) as well as class C P99 (IC50 of 22±8 nM) with a potency that is comparable or higher than recently FDA approved BLIs avibactam, relebactam and vaborbactam. Unlike those other BLIs, QPX7728 is also a potent inhibitor of class D carbapenemases such as OXA-48 from Enterobacteriaceae and OXA enzymes from A. baumannii (OXA-23/24/58, IC50 range 1-2 nM) as well as MBLs such as NDM-1 (IC50 55±25 nM), VIM-1 (IC50 14±4 nM) and IMP-1 (IC50 610±70 nM). Inhibition of serine enzymes by QPX7728 is associated with progressive inactivation with a high efficiency k2/K ranging from of 6.3 x 104 (for P99) to 9.9 x 105 M-1 s-1 (for OXA-23). This inhibition is reversible with variable stability of the QPX7728-beta-lactamase complexes with target residence time ranging from minutes to several hours: 5-20 minutes for OXA carbapenemases from A. baumanii, ~50 minutes for OXA-48 and 2-3 hours for KPC and CTX-M-15. QPX7728 inhibited all tested serine enzymes at 1:1 molar ratio. Metallo-beta-lactamases NDM, VIM, and IMP were inhibited by a competitive mechanism with fast-on-fast-off kinetics, with Kis of 7.5±2.1 nM, 32±14 nM and 240±30 nM for VIM-1, NDM-1 and IMP-1, respectively. QPX7728 ultra-broad-spectrum of BLI inhibition combined with its high potency enables combinations with multiple different beta-lactam antibiotics.




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Telacebec for ultra-short treatment of Buruli ulcer in a mouse model [Clinical Therapeutics]

Telacebec (Q203) is a new anti-tubercular drug with extremely potent activity against Mycobacterium ulcerans. Here, we explored the treatment-shortening potential of Q203 alone or in combination with rifampin (RIF) in a mouse footpad infection model. The first study compared Q203 at 5 and 10 mg/kg doses alone and with rifampin. Q203 alone rendered most mouse footpads culture-negative in 2 weeks. Combining Q203 with rifampin resulted in relapse-free cure 24 weeks after completing 2 weeks of treatment, compared to a 25% relapse rate in mice receiving RIF+clarithromycin, the current standard of care, for 4 weeks.

The second study explored the dose-ranging activity of Q203 alone and with RIF, including the extended activity of Q203 after treatment discontinuation. The bactericidal activity of Q203 persisted for ≥ 4 weeks beyond the last dose. All mice receiving just 1 week of Q203 at 2-10 mg/kg were culture-negative 4 weeks after stopping treatment. Mice receiving 2 weeks of Q203 at 0.5, 2 and 10 mg/kg were culture-negative 4 weeks after treatment. RIF did not increase the efficacy of Q203. A pharmacokinetics sub-study revealed that Q203 doses of 2-10 mg/kg in mice produce plasma concentrations similar to those produced by 100-300 mg doses in humans, with no adverse effect of RIF on Q203 concentrations.

These results indicate the extraordinary potential of Q203 to reduce the duration of treatment necessary for cure to ≤ 1 week (or 5 doses of 2-10 mg/kg) in our mouse footpad infection model and warrant further evaluation of Q203 in clinical trials.




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Spectrum of Beta-Lactamase Inhibition by the Cyclic Boronate QPX7728, an Ultra-Broad-Spectrum Beta-lactamase Inhibitor of Serine and Metallo Beta-Lactamases: Enhancement of Activity of Multiple Antibiotics Against Isogenic Strains Expressing Single {beta}

QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor with potent inhibition of key serine and metallo beta-lactamases observed in biochemical assays. Microbiological studies using characterized strains were used to provide a comprehensive characterization of the spectrum of beta-lactamase inhibition by QPX7728. The MIC of multiple IV only (ceftazidime, piperacillin, cefepime, ceftolozane and meropenem) and orally bioavailable (ceftibuten, cefpodoxime, tebipenem) antibiotics alone and in combination with QPX7728 (4 μg/ml), as well as comparator agents, were determined against the panels of laboratory strains of P. aeruginosa and K. pneumoniae expressing over 55 diverse serine and metallo beta-lactamases. QPX7728 significantly enhanced the potency of antibiotics against the strains expressing Class A extended spectrum beta-lactamases (CTX-M, SHV, TEM, VEB, PER) and carbapenemases (KPC, SME, NMC-A, BKC-1), consistent with beta-lactamase inhibition demonstrated in biochemical assays. It also inhibits both plasmidic (CMY, FOX, MIR, DHA) and chromosomally encoded (P99, PDC, ADC) Class C beta-lactamases and Class D enzymes including carbapenemases such as OXA-48 from Enterobacteriaceae and OXA enzymes from Acinetobacter baumannii (OXA-23/24/72/58). QPX7728 is also a potent inhibitor of many class B metallo beta-lactamases (NDM, VIM, CcrA1, IMP, GIM but not SPM or L1). Addition of QPX7728 (4 μg/ml) reduced the MICs in a majority of strains to the level observed for the vector alone control, indicative of complete beta-lactamase inhibition. The ultra-broad-spectrum beta-lactamase inhibition profile makes QPX7728 a viable candidate for further development.




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The Impact of Intrinsic Resistance Mechanisms on Potency of QPX7728, a New Ultra-Broad-Spectrum Beta-lactamase Inhibitor of Serine and Metallo Beta-Lactamases in Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii. [Mechanisms of Resis

QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor that demonstrates inhibition of key serine and metallo beta-lactamases at a nano molar range in biochemical assays with purified enzymes. The broad-spectrum inhibitory activity of QPX7728 observed in biochemical experiments translates into enhancement of the potency of many beta-lactams against strains of target pathogens producing beta-lactamases. The impact of bacterial efflux and permeability on inhibitory potency were determined using isogenic panels of KPC-3 producing isogenic strains of K. pneumoniae and P. aeruginosa and OXA-23-producing strains of A. baumannii with various combinations of efflux and porin mutations. QPX7728 was minimally affected by multi-drug resistance efflux pumps in either Enterobacteriaceae, or in non-fermenters such as P. aeruginosa or A. baumannii. In P. aeruginosa, the potency of QPX7728 was further enhanced when the outer membrane is permeabilized. The potency of QPX7728 in P. aeruginosa is not affected by inactivation of the carbapenem porin OprD. While changes in OmpK36 (but not OmpK35) reduced the potency of QPX7728 (8-16-fold), QPX7728 (4 μg/ml) nevertheless completely reversed KPC-mediated meropenem resistance in strains with porin mutations, consistent with a lesser effect of these mutations on the potency of QPX7728 compared to other agents. The ultra-broad-spectrum beta-lactamase inhibition profile combined with enhancement of the activity of multiple beta-lactam antibiotics with varying sensitivity to the intrinsic resistance mechanisms of efflux and permeability indicate QPX7728 is a useful inhibitor for use with multiple beta-lactam antibiotics.




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Lung Ultrasound in Children With COVID-19

Marco Denina
Apr 21, 2020; 0:peds.2020-1157v1-e20201157
Research Brief




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Deals: SanDisk Ultra MicroSDXC, Seagate Backup Plus Hub

Today you can save up to 30 percent on select laptops, networking devices, and storage drives at Amazon. Also, the highly anticipated game Cyberpunk 2077 is $10 off when you pre-order it.




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Snag a 50-Inch Sceptre 4K Ultra HD TV for Just $200

Normally $399.99, the Sceptre U515CV-U is available at Walmart right now for just $199.99. Don't miss this chance to snag it for half off.




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Samsung Galaxy S20 Ultra

The Galaxy S20 Ultra has the potential to become the best phone you can buy, but it's not worth $1,400 until Samsung fixes some bugs.




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Verizon 5G Ultra Wideband Enters AT&T's Home Turf

With its latest expansion into parts of Dallas and Omaha, Verizon's 5G network sits in 15 cities nationwide.