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Abstract Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. For the 2021–22 and 2022–23 influenza seasons, 26 forecasting teams provided national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one-to-four weeks ahead. Forecast skill is evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperform the baseline model across forecast weeks and locations in 2021–22 and 12 out of 18 models in 2022–23. Averaging across all forecast targets, the FluSight ensemble is the 2nd most accurate model measured by WIS in 2021–22 and the 5th most accurate in the 2022–23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degrade over longer forecast horizons. In this work we demonstrate that while the FluSight ensemble was a robust predictor, even ensembles face challenges during periods of rapid change.

During September 1, 2020–April 30, 2021, the California Department of Public Health, Richmond, California, USA, received 255 positive influenza molecular test results that matched with severe acute respiratory syndrome coronavirus 2 molecular test results; 58 (23%) persons were co-infected. Influenza activity was minimal in California, and co-infections were sporadic.

Abstract Dietary polyunsaturated fatty acids (PUFA) are increasingly recognized for their health benefits, whereas a high production of endogenous fatty acids – a process called de novo lipogenesis (DNL) - is closely linked to metabolic diseases. Determinants of PUFA incorporation into complex lipids are insufficiently understood and may influence the onset and progression of metabolic diseases. Here we show that fatty acid synthase (FASN), the key enzyme of DNL, critically determines the use of dietary PUFA in mice and humans. Moreover, the combination of FASN inhibition and PUFA-supplementation decreases liver triacylglycerols (TAG) in mice fed with high-fat diet. Mechanistically, FASN inhibition causes higher PUFA uptake via the lysophosphatidylcholine transporter MFSD2A, and a diacylglycerol O-acyltransferase 2 (DGAT2)-dependent incorporation of PUFA into TAG. Overall, the outcome of PUFA supplementation may depend on the degree of endogenous DNL and combining PUFA supplementation and FASN inhibition might be a promising approach to target metabolic disease.

BackgroundA conversational agent powered by artificial intelligence, commonly known as a chatbot, is one of the most recent innovations used to provide information and services during the COVID-19 pandemic. However, the multitude of conversational agents explicitly designed during the COVID-19 pandemic calls for characterization and analysis using rigorous technological frameworks and extensive systematic reviews. ObjectiveThis study aims to describe the general characteristics of COVID-19 chatbots and examine their system designs using a modified adapted design taxonomy framework. MethodsWe conducted a systematic review of the general characteristics and design taxonomy of COVID-19 chatbots, with 56 studies included in the final analysis. This review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to select papers published between March 2020 and April 2022 from various databases and search engines. ResultsResults showed that most studies on COVID-19 chatbot design and development worldwide are implemented in Asia and Europe. Most chatbots are also accessible on websites, internet messaging apps, and Android devices. The COVID-19 chatbots are further classified according to their temporal profiles, appearance, intelligence, interaction, and context for system design trends. From the temporal profile perspective, almost half of the COVID-19 chatbots interact with users for several weeks for >1 time and can remember information from previous user interactions. From the appearance perspective, most COVID-19 chatbots assume the expert role, are task oriented, and have no visual or avatar representation. From the intelligence perspective, almost half of the COVID-19 chatbots are artificially intelligent and can respond to textual inputs and a set of rules. In addition, more than half of these chatbots operate on a structured flow and do not portray any socioemotional behavior. Most chatbots can also process external data and broadcast resources. Regarding their interaction with users, most COVID-19 chatbots are adaptive, can communicate through text, can react to user input, are not gamified, and do not require additional human support. From the context perspective, all COVID-19 chatbots are goal oriented, although most fall under the health care application domain and are designed to provide information to the user. ConclusionsThe conceptualization, development, implementation, and use of COVID-19 chatbots emerged to mitigate the effects of a global pandemic in societies worldwide. This study summarized the current system design trends of COVID-19 chatbots based on 5 design perspectives, which may help developers conveniently choose a future-proof chatbot archetype that will meet the needs of the public in the face of growing demand for a better pandemic response.

Abstract Cytochrome c (cyt c) is widely used as a model protein to study (i) folding and stability aspects of the protein folding problem and (ii) structure–function relationship from the evolutionary point of view. Databases of cyts c now contain 285 cyt c sequences from different organisms. A sequence alignment of all these proteins with respect to horse cyt c led to several important conclusions. One of them is that Leu94 is always conserved in all 30 mammalian cyts c. It is known that mutation L94G of the wild type (WT) horse cyt c is destabilizing and mutant exists as molten globule under the native condition (buffer pH 6 and 25 °C). We have expressed and purified uniformly labeled (13C and 15N) and unlabeled WT horse cyt c and its L94G mutant. We report that labeling does not affect the thermodynamic stability of proteins. To support this conclusion, the secondary and tertiary structure of each protein in labeled and unlabeled forms was determined by conventional techniques (UV–Vis absorption and circular dichroism spectroscopy).

Abstract Src homology domain containing leukocyte protein of 65 kDa (SLP65), the growth factor receptor binding protein 2 (Grb2), and the guanine nucleotide exchange factor for the Rho family GTPases (Vav), self associate in unstimulated B cells as components of the preformed B cell receptor transducer module, in an SH3-dependent manner. The complex enables the B cell to promptly respond to BCR aggregation, resulting in signal amplification. It also facilitates Vav translocation to the membrane rafts, for activation. Here we uncover the molecular mechanism by which the complex may be formed in the B cell. The C-terminal SH3 domain (SH3C) of Grb2 bivalently interacts with the atypical non-PxxP proline rich region of SLP65, and the N-terminal SH3 domain (SH3N) of Vav, both the interactions crucial for the proper functioning of the B cell. Most surprisingly, the two ligands bind the same ligand binding site on the surface of Grb2 SH3C. Addition of SLP65 peptide to the Grb2-Vav complex abrogates the interaction completely, displacing Vav. However, the addition of Vav SH3N to the SLP65-Grb2 binary complex, results in a trimeric complex. Extrapolating these results to the in vivo conditions, Grb2 should bind the SLP65 transducer module first, and then Vav should associate.

Use of digital images is expanding as a tool for glacier monitoring, and small-format time-lapse cameras are increasingly being used for glacier monitoring of fast-flowing glaciers. Stereoscopic imagery is preferable since it yields direct displacement results but stereo photogrammetry has more requirements regarding geometry in set-up and control points, as well as the additional cost of another complete camera system. We investigate a combination of methods to achieve satisfactory control of accuracy with resulting significant day-to-day velocity variations ranging from 1.5–4 m day−1 made at a distance of 2 km. Validation of results was made by comparing different methods, partly using the same image material, but also in combination with aerial and satellite images. Monoscopic results can also be used to gain continuity in a stereo data set when geometry or visibility is poor. We also explore the use of ordinary photographs taken from airliners for compilation of orthoimages as a potential low cost method for detection of sudden changes. The method, showing some tens of metres accuracy, was verified for monitoring velocities and front positions during a glacier surge and was also used to validate monoscopic time-lapse images.

Pyrococcus furiosus rubredoxin (PfRd), a small, monomeric, 53 residues-long, iron-containing, electron-transfer protein of known structure is sometimes referred to as being the most structurally-stable protein known to man. Here, using a combination of mutational and spectroscopic (CD, fluorescence, and NMR) studies of differently made holo- and apo-forms of PfRd, we demonstrate that it is not the presence of iron, or even the folding of the PfRd chain into a compact well-folded structure that causes holo-PfRd to display its extraordinary thermal stability, but rather the correct iron binding-guided packing of certain residues (specifically, Trp3, Phe29, Trp36, and also Tyr10) within a tight aromatic cluster of six residues in PfRd's hydrophobic core. Binding of the iron atom appears to play a remarkable role in determining subtle details of residue packing, forcing the chain to form a hyper-thermally stable native structure which is kinetically stable enough to survive (subsequent) removal of iron. On the other hand, failure to bind iron causes the same chain to adopt an equally well-folded native-like structure which, however, has a differently-packed aromatic cluster in its core, causing it to be only as stable as any other ordinary mesophile-derived rubredoxin. Our studies demonstrate, perhaps for the very first time ever that hyperthermal stability in proteins can owe to subtle differences in residue packing vis a vis mesostable proteins, without there being any underlying differences in either amino acid sequence, or bound ligand status.