Static graph approximations of dynamic contact networks for epidemic forecasting.

Epidemic modeling is essential in understanding the spread of infectious diseases like COVID-19 and devising effective intervention strategies to control them. Recently, network-based disease models have integrated traditional compartment-based modeling with real-world contact graphs and shown promising results. However, in an ongoing epidemic, future contact network patterns are not observed yet. To address this, we use aggregated static networks to approximate future contacts for disease modeling. The standard method in the literature concatenates all edges from a dynamic graph into one collapsed graph, called the full static graph. However, the full static graph often leads to severe overestimation of key epidemic characteristics. Therefore, we propose two novel static network approximation methods, DegMST and EdgeMST, designed to preserve the sparsity of real world contact network while remaining connected. DegMST and EdgeMST use the frequency of temporal edges and the node degrees respectively to preserve sparsity. Our analysis show that our models more closely resemble the network characteristics of the dynamic graph compared to the full static ones. Moreover, our analysis on seven real-world contact networks suggests EdgeMST yield more accurate estimations of disease dynamics for epidemic forecasting when compared to the standard full static method.

Incorporating dynamic flight network in SEIR to model mobility between populations.

Current efforts of modelling COVID-19 are often based on the standard compartmental models such as SEIR and their variations. As pre-symptomatic and asymptomatic cases can spread the disease between populations through travel, it is important to incorporate mobility between populations into the epidemiological modelling. In this work, we propose to modify the commonly-used SEIR model to account for the dynamic flight network, by estimating the imported cases based on the air traffic volume and the test positive rate. We conduct a case study based on data found in Canada to demonstrate how this modification, called Flight-SEIR, can potentially enable (1) early detection of outbreaks due to imported pre-symptomatic and asymptomatic cases, (2) more accurate estimation of the reproduction number and (3) evaluation of the impact of travel restrictions and the implications of lifting these measures. The proposed Flight-SEIR is essential in navigating through this pandemic and the next ones, given how interconnected our world has become.

Iridium-catalyzed asymmetric hydrogenation yielding chiral diarylmethines with weakly coordinating or noncoordinating substituents.

Diarylmethine-containing stereocenters are present in pharmaceuticals and natural products, making the synthetic methods that form these chiral centers are important in industry. We have applied iridium complexes with novel N,P-chelating ligands to the asymmetric hydrogenation of trisubstituted olefins, forming diarylmethine chiral centers in high conversions and excellent enantioselectivities (up to 99% ee) for a broad range of substrates. Our results support the hypothesis that steric hindrance in one specific area of the catalyst is playing a key role in stereoselection, as the hydrogenation of substrates differing little at the prochiral carbon occurred with high enantioselectivity. As a result, excellent stereodiscrimination was obtained even when the prochiral carbon bore, for example, phenyl and p-tolyl groups.

Nuclear factor-Y and Epstein Barr virus in nasopharyngeal cancer.

PURPOSE: The Epstein Barr virus (EBV) is intimately associated with nasopharyngeal cancer (NPC) in a latent state expressing a limited number of genes. The process of switching from latency to replication is not well understood, particularly in response to DNA stress; hence, the focus of this study is on an EBV-positive NPC model. EXPERIMENTAL DESIGN: C666-1 cells were exposed to radiation (2-15 Gy) or cisplatin (0.1-50 microg/mL) assayed subsequently for relative EBV copy number (BamHI) and lytic gene expression (BRLF1 and BZLF1) using quantitative real-time PCR. Chromatin immunoprecipitation was conducted to assess the interaction of the transcription factor nuclear factor-Y (NF-Y) with promoter sequences. RESULTS: Radiation-induced and cisplatin-induced BamHI expression, along with increased levels of BRLF1 and BZLF1 in a dose-dependent and time-dependent manner, associated with the immediate nuclear transactivation of the transcription factor NF-Y and its own increased transcription of NF-Y subunits 8 h posttreatment. In silico analysis revealed three putative NF-Y consensus-binding sequences in the promoter region of BRLF1, which all interacted with NF-Y in response to radiation and cisplatin, confirmed using chromatin immunoprecipitation. Introduction of dominant-negative NF-YA reduced BRLF1 expression after radiation and cisplatin by 2.8-fold; in turn, overexpression of NF-YA resulted in a 2-fold increase in both BRLF1 and BZLF1 expression. CONCLUSIONS: These results show that NF-Y is an important mediator of EBV stress response in switching from a latent to lytic state. This novel insight could provide a potential therapeutic strategy to enhance NPC response to radiation and cisplatin.