The archaeal ATPase PINA interacts with the helicase Hjm via its carboxyl terminal KH domain remodeling and processing replication fork and Holliday junction.

PINA is a novel ATPase and DNA helicase highly conserved in Archaea, the third domain of life. The PINA from Sulfolobus islandicus (SisPINA) forms a hexameric ring in crystal and solution. The protein is able to promote Holliday junction (HJ) migration and physically and functionally interacts with Hjc, the HJ specific endonuclease. Here, we show that SisPINA has direct physical interaction with Hjm (Hel308a), a helicase presumably targeting replication forks. In vitro biochemical analysis revealed that Hjm, Hjc, and SisPINA are able to coordinate HJ migration and cleavage in a concerted way. Deletion of the carboxyl 13 amino acid residues impaired the interaction between SisPINA and Hjm. Crystal structure analysis showed that the carboxyl 70 amino acid residues fold into a type II KH domain which, in other proteins, functions in binding RNA or ssDNA. The KH domain not only mediates the interactions of PINA with Hjm and Hjc but also regulates the hexameric assembly of PINA. Our results collectively suggest that SisPINA, Hjm and Hjc work together to function in replication fork regression, HJ formation and HJ cleavage

Transcranial photoacoustic computed tomography based on a layered back-projection method

A major challenge of transcranial human brain photoacoustic computed tomography (PACT) is correcting for the acoustic aberration induced by the skull. Here, we present a modified universal back-projection (UBP) method, termed layered UBP (L-UBP), that can de-aberrate the transcranial PA signals by accommodating the skull heterogeneity into conventional UBP. In L-UBP, the acoustic medium is divided into multiple layers: the acoustic coupling fluid layer between the skull and detectors, the skull layer, and the brain tissue layer, which are assigned different acoustic properties. The transmission coefficients and wave conversion are considered at the fluid–skull and skull–tissue interfaces. Simulations of transcranial PACT using L-UBP were conducted to validate the method. Ex vivo experiments with a newly developed three-dimensional PACT system with 1-MHz center frequency demonstrated that L-UBP can substantially improve the image quality compared to conventional UBP

Evaluating Potential Risks of Food Allergy and Toxicity of Soy Leghemoglobin Expressed in \u3ci\u3ePichia pastoris\u3c/i\u3e

Scope: The Soybean (Glycine max) leghemoglobin c2 (LegHb) gene was introduced into Pichia pastoris yeast for sustainable production of a heme-carrying protein, for organoleptic use in plant-based meat. The potential allergenicity and toxicity of LegHb and 17 Pichia host-proteins each representing ≥ 1% of total protein in production batches are evaluated by literature review, bioinformatics sequence comparisons to known allergens or toxins, and in vitro pepsin digestion. Methods and results: Literature searches found no evidence of allergenicity or toxicity for these proteins. There are no significant sequence matches of LegHb to known allergens or toxins. Eleven Pichia proteins have modest identity matches to minor environmental allergens and 13 Pichia proteins have significant matches to proteins from toxic sources. Yet the matched allergens and toxins have similar matches to proteins from the commonly consumed yeast Saccharomyces cerevisiae, without evidence of food allergy or toxicity. The demonstrated history of safe use indicates additional tests for allergenicity and toxicity are not needed. The LegHb and Pichia sp. proteins were rapidly digested by pepsin at pH 2. Conclusion: These results demonstrate that foods containing recombinant soy LegHb produced in Pichia sp. are unlikely to present an unacceptable risk of allergenicity or toxicity to consumers

Distinguishing Attack and Second-Preimage Attack on the CBC-like MACs

In this paper, we first present a new distinguisher on the CBC-MAC based on a block cipher in Cipher Block Chaining (CBC) mode. It can also be used to distinguish other CBC-like MACs from random functions. The main results of this paper are on the second-preimage attack on CBC-MAC and CBC-like MACs include TMAC, OMAC, CMAC, PC-MAC and MACs based on three-key encipher CBC mode. Instead of exhaustive search, this attack can be performed with the birthday attack complexity

Distinguishing and Forgery Attacks on Alred and Its AES-based Instance Alpha-MAC

In this paper, we present new distinguishers of the MAC construction \textsc{Alred} and its specific instance \textsc{Alpha}-MAC based on AES, which is proposed by Daemen and Rijmen in 2005. For the \textsc{Alred} construction, we describe a general distinguishing attack which leads to a forgery attack directly. The complexity is $2^{64.5}$ chosen messages and $2^{64.5}$ queries with success probability 0.63. We also use a two-round collision differential path for \textsc{Alpha}-MAC, to construct a new distinguisher with about $2^{65.5}$ queries. The most important is that the new distinguisher can be used to recover the internal state, which is an equivalent secret subkey, and leads to a second preimage attack. Moreover, the distinguisher on \textsc{Alred} construction is also applicable to the MACs based on CBC and CFB encryption mode

Considerations for Master Protocols Using External Controls

There has been an increasing use of master protocols in oncology clinical trials because of its efficiency and flexibility to accelerate cancer drug development. Depending on the study objective and design, a master protocol trial can be a basket trial, an umbrella trial, a platform trial, or any other form of trials in which multiple drugs and/or multiple subpopulations are studied in parallel under a single protocol. External data and evidence (EDE) can be used in the design and analysis of master protocols such as external controls for treatment effect estimation, which can further improve efficiency of the master protocol trial. This paper provides an overview of different types of external controls and their unique features when used in master protocols. Some key considerations in master protocols with external controls are discussed including construction of estimands and assessment of fit-for-use real-world data. A targeted learning-based causal roadmap is presented which constitutes three key steps: (1) define a target statistical estimand that aligns with the causal estimand for the study objective, (2) use an efficient estimator to estimate the target statistical estimand and its uncertainty, and (3) evaluate the impact of causal assumptions on the study conclusion by performing a sensitivity analysis. Two illustrative examples are provided for master protocols using external controls

Usability Test of Personality Type within a Roommate Matching Website: A Case Study

We designed and built a roommate matching website, exclusively for students, which allow students to have a central point in which they can meet credible roommate candidates, search for verified housing, and easily reach out to these individuals to further their relationship, and eventually share living space. Our website aims to allow a user to search for compatible roommates not just by living habits, but by tying in the personality of candidates in reference to their own personality type. This type of personality matching in conjunction with a standard behavioral survey is the basis of the algorithm used for roommate matching. In addition to designing and building this website, we also conducted a research around two questions. First, does the idea of personality type in conjunction with living habits have the capacity to form a stronger foundation on which roommates can be selected? Second, is there a means in which we can collect this information from a user and apply it, while avoiding the typical result of survey fatigue that is inherent in existing personality quizzes? We found that majority of our respondents felt that knowing the personality compatibility would influence their decision of sharing a living space with someone. Our respondents also preferred a more visual and interactive quiz to determine personality type in comparison to questionnaires

Engineering Properties of Sweet Potato Starch for Industrial Applications by Biotechnological Techniques Including Genome Editing

Sweet potato (Ipomoea batatas) is one of the largest food crops in the world. Due to its abundance of starch, sweet potato is a valuable ingredient in food derivatives, dietary supplements, and industrial raw materials. In addition, due to its ability to adapt to a wide range of harsh climate and soil conditions, sweet potato is a crop that copes well with the environmental stresses caused by climate change. However, due to the complexity of the sweet potato genome and the long breeding cycle, our ability to modify sweet potato starch is limited. In this review, we cover the recent development in sweet potato breeding, understanding of starch properties, and the progress in sweet potato genomics. We describe the applicational values of sweet potato starch in food, industrial products, and biofuel, in addition to the effects of starch properties in different industrial applications. We also explore the possibility of manipulating starch properties through biotechnological means, such as the CRISPR/Cas-based genome editing. The ability to target the genome with precision provides new opportunities for reducing breeding time, increasing yield, and optimizing the starch properties of sweet potatoes

Untargeted LC–MS/MS-Based Metabolomic Profiling for the Edible and Medicinal Plant Salvia miltiorrhiza Under Different Levels of Cadmium Stress

Salvia miltiorrhiza, a medicinal and edible plant, has been extensively applied to treat cardiovascular diseases and chronic hepatitis. Cadmium (Cd) affects the quality of S. miltiorrhiza, posing serious threats to human health. To reveal the metabolic mechanisms of S. miltiorrhiza's resistance to Cd stress, metabolite changes in S. miltiorrhiza roots treated with 0 (CK), 25 (T1), 50 (T2) and 100 (T3) mg kg−1 Cd by liquid chromatography coupled to mass spectrometry (LC–MS/MS) were investigated. A total of 305 metabolites were identified, and most of them were amino acids, organic acids and fatty acids, which contributed to the discrimination of CK from the Cd-treated groups. Among them, S. miltiorrhiza mainly upregulated o-tyrosine, chorismate and eudesmic acid in resistance to 25 mg kg−1 Cd; DL-tryptophan, L-aspartic acid, L-proline and chorismite in resistance to 50 mg kg−1 Cd; and L-proline, L-serine, L-histidine, eudesmic acid, and rosmarinic acid in resistance to 100 mg kg−1 Cd. It mainly downregulated unsaturated fatty acids (e.g., oleic acid, linoleic acid) in resistance to 25, 50, and 100 mg kg−1 Cd and upregulated saturated fatty acids (especially stearic acid) in resistance to 100 mg kg−1 Cd. Biosynthesis of unsaturated fatty acids, isoquinoline alkaloid, betalain, aminoacyl-tRNA, and tyrosine metabolism were the significantly enriched metabolic pathways and the most important pathways involved in the Cd resistance of S. miltiorrhiza. These data elucidated the crucial metabolic mechanisms involved in S. miltiorrhiza Cd resistance and the crucial metabolites that could be used to improve resistance to Cd stress in medicinal plant breeding