Soybean (Glycine max) is a major protein crop, because soybean protein has an amino acid score comparable to that of beef and egg white. However, many allergens have been identified among soybean ...proteins. A decrease in allergenic protein levels would be useful for expanding the market for soybean proteins and processed foods. Recently, the CRISPR/Cas9 system has been adopted as a powerful tool for the site-directed mutagenesis in higher plants. This system is expected to generate hypoallergenic soybean varieties.
We used two guide RNAs (gRNAs) and Agrobacterium-mediated transformation for simultaneous site-directed mutagenesis of two genes encoding the major allergens Gly m Bd 28 K and Gly m Bd 30 K in two Japanese soybean varieties, Enrei and Kariyutaka. We obtained two independent T
Enrei plants and nine T
Kariyutaka plants. Cleaved amplified polymorphic sequence (CAPS) analysis revealed that mutations were induced in both targeted loci of both soybean varieties. Sequencing analysis showed that deletions were the predominant mutation type in the targeted loci. The Cas9-free plants carrying the mutant alleles of the targeted loci with the transgenes excluded by genetic segregation were obtained in the T
and T
generations. Variable mutational spectra were observed in the targeted loci even in T
and T
progenies of the same T
plant. Induction of multiple mutant alleles resulted in six haplotypes in the Cas9-free mutants derived from one T
plant. Immunoblot analysis revealed that no Gly m Bd 28 K or Gly m Bd 30 K protein accumulated in the seeds of the Cas9-free plants. Whole-genome sequencing confirmed that a Cas9-free mutant had also no the other foreign DNA from the binary vector. Our results demonstrate the applicability of the CRISPR/Cas9 system for the production of hypoallergenic soybean plants.
Simultaneous site-directed mutagenesis by the CRISPR/Cas9 system removed two major allergenic proteins from mature soybean seeds. This system enables rapid and efficient modification of seed components in soybean varieties.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Clinical development of bromodomain and extra‐terminal (BET) protein inhibitors differs from the traditional course of drug development. These drugs are simultaneously being evaluated for treating a ...wide spectrum of human diseases due to their novel mechanism of action. BET proteins are epigenetic “readers,” which play a primary role in transcription. Here, we briefly describe the BET family of proteins, of which BRD4 has been studied most extensively. We discuss BRD4 activity at latent enhancers as an example of BET protein function. We examine BRD4 redistribution and enhancer reprogramming in embryonic development, cancer, cardiovascular, autoimmune, and metabolic diseases, presenting hallmark studies that highlight BET proteins as attractive targets for therapeutic intervention. We review the currently available approaches to targeting BET proteins, methods of selectively targeting individual bromodomains, and review studies that compare the effects of selective BET inhibition to those of pan‐BET inhibition. Lastly, we examine the current clinical landscape of BET inhibitor development.
Background: Here we compare the performance of the high-throughput BD COR System (COR) to the Viper LT System (Viper) using the BD Onclarity HPV assay.
Research Design and Methods: Remnant clinical ...specimens, contrived specimens in SurePath (BD) and PreservCyt (Hologic) media, and prospective clinical specimens in BD Cervical Brush Diluent (CBD) were tested. Outcomes included intra-laboratory agreement of Onclarity results on COR and inter-system agreement between COR and Viper.
Results: Onclarity reproducibility on COR resulted in standard deviation and correlation of variation of Ct values ranging from 0.14 to 1.98 and 0.49% to 2.15%, respectively, for contrived specimens, and 0.9-3.08 and 2.89-9.21%, respectively, for clinical specimens. In the COR and Viper clinical agreement study, OPA for Onclarity ranged from 97.1%-98.9%, depending on the collection media type. PPA values for pooled, HPV(+) specimens at low positive (C
95
), and moderate positive (3XC
95
) target concentrations were ≥95.0% and 100%, respectively; PPA values associated with HPV 16, 18, 31, 45, 33/58, 52, 35/39/68, 51, and 56/59/66, individually, ranged from 93.8%-100%.
Conclusions: Onclarity performance on COR is equivalent to Viper, and is accurate and reproducible for detection of all high-risk HPV genotypes, with a throughput of 330 results from a single 8-hour shift.
ABSTRACT
Transiting Exoplanet Survey Satellite photometry of the extremely helium-rich hot subdwarfs BD+37°442 and BD+37°1977 demonstrates multiperiodic low-amplitude variability with principal ...periods of 0.56 and 1.14 d, respectively, and with both first and second harmonics present. The light curves are not perfectly regular, implying additional periodic and/or non-periodic content. Possible causes are examined, including the binary hypothesis originally introduced to explain X-ray observations, differentially rotating surface inhomogeneities, and pulsations. If the principal photometric periods correspond to the rotation periods, the stars are rotating at approximately 0.7 and 0.3 × break-up, respectively. Surface Rossby waves (r modes) therefore provide the most likely solution.
This article presents a multipolar neural stimulation and mixed-signal neural data acquisition (DAQ) chipset for fully implantable bi-directional brain-computer interfaces (BD-BCIs). The stimulation ...system employs four 40 V compliant current-stimulators, each capable of sourcing/sinking a maximum 12.75 mA stimulation current, connected to 16 output channels through a high-voltage (HV) switch fabric. A novel time-based charge balancing (TBCB) technique is introduced to reduce the residual voltage on the electrode-electrolyte interface during the inter-pulse time interval, achieving 2 mV charge balancing precision. Additionally, an analytical study of the charge balancing accuracy for the proposed technique is provided. The recording system incorporates a dual-mode DAQ architecture that consists of a 32-element front-end array and a mixed-signal back-end including analog-to-digital converters (ADCs) for both training (i.e., full-band) and decoding (i.e., baseband) operations. Leveraging the flexibility of the multipolar operation, stimulation-side contour shaping (SSCS) artifact cancellation is adopted to significantly suppress stimulation artifacts by up to 45 dB. SSCS method prevents the recording front-ends from saturation and greatly relaxes the dynamic range requirement of the recording system, enabling a truly bi-directional operation. The prototype chipset is fabricated in an HV 180-nm CMOS process and demonstrates a significant performance improvement compared to the prior art.
Big Data in Capturing Business Value Olszak, Celina M.; Zurada, Jozef
Information systems management,
07/2020, Letnik:
37, Številka:
3
Journal Article
Recenzirano
The study investigates an issue of Big Data (BD) and elements shaping BD-based business value creation. The outcome of this research is to build and verify a framework to provide value based on BD. ...The framework contains three components: dynamic capabilities of organizations, integrated process of BD resource exploration and exploitation, and identification and measurement of business value creation. The framework has been subjected to initial verification by conducting the survey among 25 organizations.
Escherichia coli contains two cytochrome bd oxidases, bd-I and bd-II. The structure of both enzymes is highly similar, but they exhibit subtle differences such as the accessibility of the active site ...through a putative proton channel. Here, we demonstrate that the duroquinol:dioxygen oxidoreductase activity of bd-I increased with alkaline pH, whereas bd-II showed a broad activity maximum around pH 7. Likewise, the pH dependence of NO release from the reduced active site, an essential property of bd oxidases, differed between the two oxidases as detected by UV/vis spectroscopy. Both findings may be attributed to differences in the proton channel leading to the active site heme d. The channel comprises a titratable residue (Asp58B in bd-I and Glu58B in bd-II). Conservative mutations at this position drastically altered NO release demonstrating its contribution to the process.
Display omitted
•E. coli expresses two bd type oxidases.•Activity and NO binding of both oxidases show different pH profiles.•Reduced Cyt bd-II shows no NO release at a pH above 8.•D58B (bd-I) and E58B (bd-I) are critical for NO release.
Symbiotic radio (SR) is a promising technology to alleviate the tremendous spectrum demand from massive Internet of Things (IoT) devices. We notice that the throughput of SR systems with multiple ...passive IoT devices highly relies on how these devices are scheduled, i.e., which backscatter device (BD) transmits passively when there is an active ambient terminal. Due to the dynamics of wireless channels and the random access of terminals in ambient networks, the scheduling of BDs needs to be adjusted adaptively while ensuring fairness among them. In this work, we design a transmission protocol for an SR network where an ambient system adopts a contention-based channel access protocol, and formulate a multi-BD scheduling problem considering fairness among BDs. To solve this problem, we propose a soft actor-critic-based learning algorithm. Simulation results have illustrated the effectiveness of the proposed algorithm. They have also demonstrated a throughput-fairness tradeoff, and the impact caused by the timeliness of channel state information.
Introduction:
Endoscopic ultrasound-guided biliary drainage (EUS-BD) is the procedure of choice for patients who cannot undergo endoscopic retrograde cholangiopancreatography (ERCP). The outcomes of ...patients undergoing surgery after EUS-BD for malignancy are unknown.
Methods:
We conducted an international, multicenter retrospective comparative study of patients who underwent hepatobiliary surgery after having undergone EUS-BD or ERCP from 6 tertiary care centers. Patient demographics, procedural data, and follow-up care were collected in a registry.
Results:
One hundred forty-five patients were included: EUS-BD n=58 (mean age 66, 45% male), ERCP n=87 (mean age 68, 53% male). The majority of patients had pancreatic cancer, cholangiocarcinoma, or gallbladder malignancy. In the EUS-BD group, 29 patients had hepaticogastrostomy, 24 had choledochoduodenostomy, and 5 had rendezvous technique done. The most common surgery was Whipple in both groups (n=41 EUS-BD, n=56 ERCP) followed by partial hepatectomy (n=7 EUS-BD, n=14 ERCP) and cholecystectomy (n=2 EUS-BD, n=2 ERCP). Endoscopy clinical success was comparable in both groups (98% EUS-BD, 94% ERCP). Adverse event rates were similar in both groups: EUS-BD (n=10, 17%) and ERCP (n=23, 26%). Surgery technical success and clinical success were significantly higher in the EUS-BD group compared with the ERCP group (97% vs. 83%, 97% vs. 75%). Total Hospital stay from surgery to discharge was significantly higher in the ERCP group (19 d vs. 10 d,
P
=0.0082).
Discussion:
Undergoing EUS-BD versus ERCP before hepatobiliary surgery is associated with fewer repeat endoscopic interventions, shorter duration between endoscopy and surgical intervention, higher rates of surgical clinical success, and shorter length of hospital stay after surgery.