Prime editing is a recent, CRISPR-derived genome editing technology capable of introducing precise nucleotide substitutions, insertions, and deletions. Here, we present prime editing approaches to correct L227R- and N1303K-CFTR, two mutations that cause cystic fibrosis and are not eligible for current market-approved modulator therapies. We show that, upon DNA correction of the CFTR gene, the complex glycosylation, localization, and, most importantly, function of the CFTR protein are restored in HEK293T and 16HBE cell lines. These findings were subsequently validated in patient-derived rectal organoids and human nasal epithelial cells. Through analysis of predicted and experimentally identified candidate off-target sites in primary stem cells, we confirm previous reports on the high prime editor (PE) specificity and its potential for a curative CF gene editing therapy. To facilitate future screening of genetic strategies in a translational CF model, a machine learning algorithm was developed for dynamic quantification of CFTR function in organoids (DETECTOR: \"detection of targeted editing of CFTR in organoids\").

Heterodyne detection based on interband cascade lasers (ICL) has been demonstrated in a wide range of different applications. However, it is still often limited to bulky tabletop systems using individual components such as dual laser setups, beam shaping elements, and discrete detectors. In this work, a versatile integrated ICL platform is investigated for tackling this issue. A RF-optimized, two-section ICL approach is employed, consisting of a short section typically used for efficient modulation of the cavity field and a long gain section. Such a laser is operated in reversed mode, with the entire Fabry-Pérot waveguide utilized as a semiconductor optical amplifier (SOA) and the electrically separated short section as detector. Furthermore, a racetrack cavity is introduced as on-chip single-mode reference generator. The field of the racetrack cavity is coupled into the SOA waveguide via an 800 nm gap. By external injection of a single mode ICL operating at the appropriate wavelength, a heterodyne beating between the on-chip reference and the injected signal can be observed on the integrated detector section of the SOA-detector.

Contamination of food and water with radioactive substances is a serious health problem. There are several methods to detect and measure radioactive materials, some of which have been developed in recent years. This paper aims to discuss the methods of detecting and measuring radioactive substances in food and water. The principles and the advantages and disadvantages of each method have been discussed. The results showed that some of these methods, such as spectrometry γ-ray high-purity germanium, portable radon gas surveyor SILENA, RAD7, and inductively coupled plasma mass spectrometry, have a higher sensitivity for detection and measurement. The spectrometry γ-ray high-purity germanium method has attracted more attention than other methods because it can measure a wide range of radionuclides with high resolution.

The X-ray Integral Field Unit (X-IFU) is one of the two focal plane detectors of Athena, a large-class high energy astrophysics space mission approved by ESA in the Cosmic Vision 2015-2025 Science Program. The X-IFU consists of a large array of transition edge sensor micro-calorimeters that operate at ~100 mK inside a sophisticated cryostat. To prevent molecular contamination and to minimize photon shot noise on the sensitive X-IFU cryogenic detector array, a set of thermal filters (THFs) operating at different temperatures are needed. Since contamination already occurs below 300 K, the outer and more exposed THF must be kept at a higher temperature. To meet the low energy effective area requirements, the THFs are to be made of a thin polyimide film (45 nm) coated in aluminum (30 nm) and supported by a metallic mesh. Due to the small thickness and the low thermal conductance of the material, the membranes are prone to developing a radial temperature gradient due to radiative coupling with the environment. Considering the fragility of the membrane and the high reflectivity in IR energy domain, temperature measurements are difficult. In this work, a parametric numerical study is performed to retrieve the radial temperature profile of the larger and outer THF of the Athena X-IFU using a Finite Element Model approach. The effects on the radial temperature profile of different design parameters and boundary conditions are considered: (i) the mesh design and material, (ii) the plating material, (iii) the addition of a thick Y-cross applied over the mesh, (iv) an active heating heat flux injected on the center and (v) a Joule heating of the mesh. The outcomes of this study have guided the choice of the baseline strategy for the heating of the Athena X-IFU THFs, fulfilling the stringent thermal specifications of the instrument.

OBJECTIVE: Single-isocenter multi-target intracranial stereotactic radiotherapy (SIMT) is an effective treatment for brain metastases with complex treatment plans and delivery optimization necessitating rigorous quality assurance. This work aims to assess five methods for quality assurance of SIMT treatment plans in terms of their suitability and sensitivity to delivery errors.
METHODS: Sun Nuclear ArcCHECK and SRS MapCHECK, GafChromic EBT Radiochromic Film, machine log files, and Varian Portal Dosimetry were all used to measure 15 variations of a single SIMT plan. Variations of the original plan were created with Python. They comprised various degrees of systematic MLC offsets per leaf up to 2 mm, random per-leaf variations with differing minimum and maximum magnitudes, simulated collimator, and dose miscalibrations (MU scaling). The erroneous plans were re-imported into Eclipse and plan-quality degradation was assessed by comparing each plan variation to the original clinical plan in terms of the percentage of clinical goals passing relative to the original plan. Each erroneous plan could be then ranked by the plan-quality degradation percentage following recalculation in the TPS so that the effects of each variation could be correlated with γ pass rates and detector suitability.
CONCLUSIONS: It was found that 2%/1 mm is a good starting point for the ArcCHECK, Portal Dosimetry, and the SRS MapCHECK methods, respectively, and provides clinically relevant error detection sensitivity. Looser dose criteria of 5%/1 mm or 5%/1.5 mm are suitable for film dosimetry and log-file-based methods. The statistical methods explored can be expanded to other areas of patient-specific QA and detector assessment.

CubeSats have emerged as cost-effective platforms for biological research in low Earth orbit (LEO). However, they have traditionally been limited to optical absorbance sensors for studying microbial growth. This work has made improvements to the sensing capabilities of these small satellites by incorporating electrochemical ion-selective pH and pNa sensors with optical absorbance sensors to enrich biological experimentation and greatly expand the capabilities of these payloads. We have designed, built, and tested a multi-modal multi-array electrochemical-optical sensor module and its ancillary systems, including a fluidic card and an on-board payload computer with custom firmware. Laboratory tests showed that the module could endure high flow rates (1 mL/min) without leakage, and the 27-well, 81-electrode sensor card accurately detected pH (71.0 mV/pH), sodium ion concentration (75.2 mV/pNa), and absorbance (0.067 AU), with the sensors demonstrating precise linear responses (R2 ≈ 0.99) in various test solutions. The successful development and integration of this technology conclude that CubeSat bio-payloads are now poised for more complex and detailed investigations of biological phenomena in space, marking a significant enhancement of small-satellite research capabilities.

The main object of this research was to develop a security system to evaluate the intrusion into an object through a glass pane. More specifically, this study deals with sensing and evaluating signals from a contact glass-break detector, which is part of an intruder alarm system. Each alarm detector in an alarm system must accomplish certain security level requirements that strictly describe the requirements for the area of use and the detector\'s reliability. To date, no contact glass-break detector has been developed and fully tested to meet the stringent requirements of the highest security level. A contact glass-break detector was developed whose main part is an accelerometer that transmits signals from the glass pane. These signals were evaluated according to the developed methodology. It was verified that the proposed system can distinguish at the highest security level between false alarms and situations where the building has been intruded.

Terrorist organizations have compelled security authorities of every nation to make an increasingly significant commitment toward mitigating the risk of mass casualties and severe financial and property damages. As a result, various security measures have been implemented, including the use of advanced equipment and an uptick in intelligence activities. One of the most effective tools that has yielded outstanding results is the use of explosive detection dogs (EDDs). The nature of EDDs demands a high level of sensitivity given the inherent danger and severity of real threat situations that may involve the risk of explosion. Moreover, the operating procedures for EDDs are unique and distinguishable from other forms of detection. We conducted a review to ensure a comprehensive understanding of the subject, highlighting the EDDs\' personality profile, selection, training methods, performance, and employment, incorporating insights from diverse fields, conducting an analysis, and presenting a perspective on using EDDs to prevent explosion threats.

UNASSIGNED: In this study an evaluation of the imaging performance of an electronic portal imaging device (EPID) is presented. The evaluation performed employing the QC-3V image quality phantom.
UNASSIGNED: An EPID system of a 6 MV LINAC, was used to obtain images of a QC-3V EPID phantom. The X-ray source to phantom distance was 100 cm and the field size was 15x15 cm2. The irradiation conditions comprised Dose Rates (DR) of 200, 400 and 600 for a 2 MU-100 MU range. The Contrast Transfer Function (CTF), the Noise Power Spectrum (NPS), the Normalized Noise Power Spectrum (NNPS) and the Contrast-to-Noise Ratio (CNR) were studied. In addition, an alternative factor showing a frequency related output signal-to-noise ratio (SNR), the Signal-to-Noise-Frequency Response (SNFR), has been introduced. SNFR is a comprehensive quality index, easily determined in clinical environment.
UNASSIGNED: The CTF curves were found comparable to each other. The lowest values were measured at 2 MU and 200 MU/min. Concerning the NPS and NNPS graphs it was found that the values decrease up to approximately 0.3 lp/mm and demonstrate a white noise shape afterwards. SNFR values were found reducing with spatial frequency. Highest CNR were found between the region 7 and 11 of the phantom.
UNASSIGNED: The influence of MU and DR on EPID performance were investigated. Image quality was assessed using the QC-3V phantom. The presented results can lead to image quality amelioration and act supportively to current image quality control routine protocols.

The unique diffraction geometry of ESRF beamline ID06-LVP offers continuous static 2D or azimuthally resolving data collections over all accessible solid angles available to the tooling geometry. The system is built around a rotating custom-built Pilatus3 CdTe 900k-W detector from Dectris, in a configuration equivalent to three butted 300k devices. As a non-standard geometry, here the method of alignment, correction and subsequent integration for any data collected over all solid angles accessible, or over any azimuthal range contained therein, are provided and illustrated by parameterizing and extending existing pyFAI routines. At 1° integrated intervals, and typical distances (2.0 m), the system covers an area of near 2.5 m2 (100 Mpx square equivalent), to 0.65 Å resolution, at 53 keV from a total dataset of some 312 Mpx. Standard FWHMs of SRM660a LaB6 vary from 0.005° to 0.01°, depending on beam size, energy and sample dimensions, and are sampled at an elevated rate. The azimuthal range per static frame ranges from <20° to ∼1° over the full range of the detector surface. A full 2θ-intensity data collection at static azimuth takes 1-3 s typically, and can be reduced to ms-1 rates for measurements requiring time-rate determination. A full solid-angle collection can be completed in a minute. Sample detector distances are accessible from 1.6 m to 4.0 m.