Comparing large covariance matrices has important applications in modern genomics, where scientists are often interested in understanding whether relationships (e.g., dependencies or co-regulations) among a large number of genes vary between different biological states. We propose a computationally fast procedure for testing the equality of two large covariance matrices when the dimensions of the covariance matrices are much larger than the sample sizes. A distinguishing feature of the new procedure is that it imposes no structural assumptions on the unknown covariance matrices. Hence, the test is robust with respect to various complex dependence structures that frequently arise in genomics. We prove that the proposed procedure is asymptotically valid under weak moment conditions. As an interesting application, we derive a new gene clustering algorithm which shares the same nice property of avoiding restrictive structural assumptions for high-dimensional genomics data. Using an asthma gene expression dataset, we illustrate how the new test helps compare the covariance matrices of the genes across different gene sets/pathways between the disease group and the control group, and how the gene clustering algorithm provides new insights on the way gene clustering patterns differ between the two groups. The proposed methods have been implemented in an R-package HDtest and are available on CRAN.

Evaluation of actual zero energy buildings (ZEBs) performance and identification of its regional characteristics are of great significance for similar future projects. Based on more than 400 cases in cold regions, this study compared the post-evaluation and drivers of ZEBs from China, the US and the European Union (EU). Results found that ZEB definition, energy drivers, standard, regional policies, technology adoption and their adoption ratio determine the energy performance of cases. Not all EU and China cases reach the net-zero energy target; however, most ZEBs in the US do. ZEBs in cold regions adopted multiple technologies to achieve high energy-efficiency. The adoption ratio of passive technologies is higher than that of active technologies, especially in China. The active technologies in cold regions are mainly seen in the application of advanced HVAC systems. Such application of renewable technologies exhibits strong regional characteristics; for example, the EU's carbon emission reduction policies promoted the use of biomass-based technologies. The analysis also found that energy policies greatly enhance the development of ZEBs. Overall, achieving zero energy is a process, not an endpoint and many projects need further refinement after occupancy.

The AAA protein Msp1 extracts mislocalized tail-anchored membrane proteins and targets them for degradation, thus maintaining proper cell organization. How Msp1 selects its substrates and firmly engages them during the energetically unfavorable extraction process remains a mystery. To address this question, we solved cryo-EM structures of Msp1-substrate complexes at near-atomic resolution. Akin to other AAA proteins, Msp1 forms hexameric spirals that translocate substrates through a central pore. A singular hydrophobic substrate recruitment site is exposed at the spiral's seam, which we propose positions the substrate for entry into the pore. There, a tight web of aromatic amino acids grips the substrate in a sequence-promiscuous, hydrophobic milieu. Elements at the intersubunit interfaces coordinate ATP hydrolysis with the subunits' positions in the spiral. We present a comprehensive model of Msp1's mechanism, which follows general architectural principles established for other AAA proteins yet specializes Msp1 for its unique role in membrane protein extraction.

When renewing building facades in most Chinese cities, covers are often designed and installed to conceal the outdoor units of residential split air conditioners for congruousness of building facades. However, how those covers impact airflow and energy efficiency should be thoroughly examined. This study investigates two popular designs of cover (louver and circular-hole) and selects Nanjing, renowned for its hot summers, as the case city. This study employs Computational Fluid Dynamics models to simulate airflow obstruction caused by the covers surrounding the outdoor units. Grey Model, trained from the CFD results, quantifies interactions between design of cover and inlet air temperature. Additionally, a thermodynamic model assesses the covers' impact on the coefficient of performance of air conditioners. The findings reveal that the primary cause of outdoor unit overheating is warm air backflow from the outlet to the inlet. A mere 1 °C increase in inlet air temperature can reduce COP by 4.1%–8.7%. The maximum temperature differences caused by different designs of cover are 4.5 °C for the louver type and 4.4 °C for the circular-hole type. To mitigate these negative impacts, optimal design recommendations are provided: a minimum distance between the cover and outdoor unit of 0.29 m for louver type and 0.1 m for circular-hole type, both feasible in most installations. These findings can help designers, manufacturers, installers and policymakers, to facilitate the design and installation of optimal covers for outdoor air-conditioning units, thus minimizing energy efficiency losses.

In eukaryotic cells, stressors reprogram the cellular proteome by activating the integrated stress response (ISR). In its canonical form, stress-sensing kinases phosphorylate the eukaryotic translation initiation factor eIF2 (eIF2-P), which ultimately leads to reduced levels of ternary complex required for initiation of mRNA translation. Previously we showed that translational control is primarily exerted through a conformational switch in eIF2's nucleotide exchange factor, eIF2B, which shifts from its active A-State conformation to its inhibited I-State conformation upon eIF2-P binding, resulting in reduced nucleotide exchange on eIF2 (Schoof et al. 2021). Here, we show functionally and structurally how a single histidine to aspartate point mutation in eIF2B's β subunit (H160D) mimics the effects of eIF2-P binding by promoting an I-State like conformation, resulting in eIF2-P independent activation of the ISR. These findings corroborate our previously proposed A/I-State model of allosteric ISR regulation.

The integrated stress response (ISR) is activated by phosphorylation of the translation initiation factor eIF2 in response to various stress conditions. Phosphorylated eIF2 (eIF2-P) inhibits eIF2's nucleotide exchange factor eIF2B, a twofold symmetric heterodecamer assembled from subcomplexes. Here, we monitor and manipulate eIF2B assembly in vitro and in vivo. In the absence of eIF2B's α-subunit, the ISR is induced because unassembled eIF2B tetramer subcomplexes accumulate in cells. Upon addition of the small-molecule ISR inhibitor ISRIB, eIF2B tetramers assemble into active octamers. Surprisingly, ISRIB inhibits the ISR even in the context of fully assembled eIF2B decamers, revealing allosteric communication between the physically distant eIF2, eIF2-P, and ISRIB binding sites. Cryo-electron microscopy structures suggest a rocking motion in eIF2B that couples these binding sites. eIF2-P binding converts eIF2B decamers into 'conjoined tetramers' with diminished substrate binding and enzymatic activity. Canonical eIF2-P-driven ISR activation thus arises due to this change in eIF2B's conformational state.

The Named-data Link State Routing protocol (NLSR) is a protocol for intra-domain routing in Named Data Networking (NDN). It is an application level protocol similar to many IP routing protocols, but NLSR uses NDN's interest/data packets to disseminate routing updates, directly benefiting from NDN's built-in data authenticity. The NLSR design, which was first developed in 2013 and deployed on the NDN test bed in August 2014, has undergone significant changes. Following an application-driven design approach, NLSR's development helped drive the development of the trust/security functionality of NDN libraries as well as a number of features in NDN's forwarding daemon and ChronoSync. In this paper, we describe the current design and implementation of NLSR, with emphasis on those features that differentiate it from an IP-based link state routing protocol: 1) naming: a hierarchical naming scheme for routers, keys, and routing updates; 2) security: a hierarchical trust model for routing within a single administrative domain; 3) routing information dissemination: using ChronoSync to disseminate routing updates; and 4) multipath routing: a simple way to calculate and rank multiple forwarding options. Although NLSR is designed in the context of a single domain, its design patterns may offer a useful reference for future development of inter-domain routing protocols.

Extensive electric power is required to maintain indoor thermal comfort using heating, ventilation and air conditioning (HVAC) systems, of which, water-cooled chiller plants consume more than 50% of the total electric power. To improve energy efficiency, supervisory optimisation control can be adopted. The controlled variables are usually optimised according to instant building cooling load and ambient wet bulb air temperature at regular time intervals. In this way, the energy efficiency of chiller plants has been improved. However, with an inherent assumption that the instant building cooling load and ambient wet bulb temperature remain constant in the coming time interval, the energy efficiency potential has not been fully realised, especially when cooling loads vary suddenly and extremely. To solve this problem, a cooling load forecasting-based predictive optimisation method is proposed. Instead of minimising the instant system power according to the instant building cooling load and ambient wet bulb temperature, the controlled variables are derived to minimise the sum of the instant system power and one-time-step-ahead future system power according to both instant and forecasted future building cooling loads. With this method, the energy efficiency potential of a chiller plant can be further improved without shortening the operation time interval. 80% redundant energy consumption has been reduced for the sample chiller plant; energy can be saved for chiller plants that work for years. The evaluation on the effect of cooling load forecasting accuracy turns out that the more accurate the forecasts are, the more redundant energy consumption can be reduced.

This research focuses on durable, high-performance materials and interfaces for advanced water splitting, enabling a clear pathway for achieving <$2/KgH2 (on scale) via anion exchange membrane (AEM)-based electrolysis. We aim to advance this goal via an improved fundamental understanding of both hydrogen and oxygen evolution reactions (HER/OER) leading to platinum group metal (PGM)-free catalyst materials. Here, we use NiFeCo and NiMo as OER and HER catalysts, respectively, in a full alkaline electrolysis cell. A thermally stable, multi-cation AEM is used to operate the cell at elevated temperatures thereby lowering the operating potential by increasing the kinetics of the respective catalytic reactions. The transition metal catalysts, paired with this novel AEM, have been used to achieve an operating potential of 1.79 V at 1 A/cm2. This potential is 300 mV lower than similar electrolysis cells equipped with PGM-based catalysts. We have also demonstrated the efficacy of the less caustic potassium carbonate solution as a replacement for potassium hydroxide as an electrolyte. By using a carbonate-based electrolyte, the hydroxide ion required for the anodic reaction is continuously replenished by re-establishing an equilibrium with water. This consideration, coupled with the reduced alkalinity of the carbonate solution, yields an electrolysis cell capable of sustained operation with minimal increase in operating potential.