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Structural variants (SVs) can be important drivers of human adaptation with strong effects, but previous studies have focused primarily on common variants with weak effects. Here, we used large-scale single-molecule long-read sequencing of 320 Tibetan and Han samples, to show that SVs are key drivers of selection under high-altitude adaptation. We expand the landscape of global SVs, apply robust models of selection and population differentiation combining SVs, SNPs and InDels, and use epigenomic analyses to predict driver enhancers, target genes, upstream regulators, and biological functions, which we validate using enhancer reporter and DNA pull-down assays. We reveal diverse Tibetan-specific SVs affecting the cis- and trans-regulatory circuitry of diverse biological functions, including hypoxia response, energy metabolism, lung function, etc. Our study greatly expands the global SV landscape, reveals the central role of gene-regulatory circuitry rewiring in human adaptation, and illustrates the diverse functional roles that SVs can play in human biology.

Antibody profile of pigs naturally infected with a virulent African swine fever virus (ASFV) strain under field conditions was studied. Twenty-three serum samples were collected from pigs surviving a natural ASFV infection: 17 samples from finishing pigs (∼7 months old) and 6 samples from sows (between 12 and 36 months old). Additionally, 24 serum samples were collected from ASFV-naïve pigs to serve as negative controls. All sera from ASFV-surviving pigs tested positive while all sera from control pigs tested negative by two different commercial ELISA kits. Antibody reactivity of each serum sample was simultaneously measured against six selected ASFV antigens including p12, p32, p54, pp62, C-type lectin and CD2v. All ASFV-surviving pigs had antibody against p32, p54 and pp62 while 91.3% surviving pigs had antibody against p12. Only small portions of ASFV-surviving pigs exhibited antibodies against C-type lectin (34.8%) and CD2v (26.1%). While antibodies against p12, p32, p54 and pp62 were similarly detected in both finishing pigs and sows, antibodies against C-type lectin and CD2v were mainly detected in sows but not in finishing pigs. These results suggest a differential humoral immune response to ASFV infection in sows and finishing pigs. Further studies are needed to better understand the nature of immune responses to ASFV infection in different pig populations.

In 2014, China introduced an ultra-low emissions (ULE) standards policy for renovating coal-fired power-generating units to limit SO2, NOX and PM emissions to 35, 50 and 10 mg m-3, respectively. The ULE standard policy had ambitious levels (surpassing those of all other countries) and implementation timeline. We estimate emission reductions associated with the ULE policy by constructing a nationwide, unit-level, hourly-frequency emissions dataset using data from a continuous emission monitoring systems network covering 96-98% of Chinese thermal power capacity during 2014-2017. We find that between 2014 and 2017 China’s annual power emissions of SO2, NOX and PM dropped by 65%, 60% and 72%, respectively. Our estimated emissions using actual monitoring data are 18-92% below other recent estimates. We detail the technologies used to meet the ULE standards and the determinants of compliance, underscoring the importance of ex-post evaluation and providing insights for other countries wishing to reduce their power emissions.

Single-cell isoform sequencing can reveal transcriptomic dynamics in individual cells invisible to bulk- and single-cell RNA analysis based on short-read sequencing. However, current long-read single-cell sequencing technologies have been limited by low throughput and high error rate. Here we introduce HIT-scISOseq for high-throughput single-cell isoform sequencing. This method was made possible by full-length cDNA capture using biotinylated PCR primers, and by our novel library preparation procedure that combines head-to-tail concatemeric full-length cDNAs into a long SMRTbell insert for high-accuracy PacBio sequencing. HIT-scISOseq yields > 10 million high-accuracy full-length isoforms in a single PacBio Sequel II 8M SMRT Cell, providing > 8 times more data output than the standard single-cell isoform PacBio sequencing protocol. We exemplified HIT-scISOseq by first studying transcriptome profiles of 4,000 normal and 8,000 injured corneal epitheliums from cynomolgus monkeys. We constructed dynamic transcriptome landscapes of known and rare cell types, revealed novel isoforms, and identified injury-related splicing and switching events that are previously not accessible with low throughput isoform sequencing. HIT-scISOseq represents a high-throughput, cost-effective, and technically simple method to accelerate the burgeoning field of long-read single-cell transcriptomics.

We present a numerical investigation of the breakup and freezing of a pendant hollow water drop beneath a cold curved surface. The drop contains a bubble surrounded by a shell of water that forms at an outer wetting angle of θo with the surface. The freezing begins on the cold curved surface and evolves in the direction of gravity. As it freezes, the water accumulates and forms a bulbous end at the bottom of the drop. Breakup can occur, inducing a daughter water drop. As a result, the freezing process of the remaining hollow drop attached to the surface takes less time, and the frozen drop shrinks. However, this breakup has no effect on the bubble. The various parameters under consideration include the Bond number Bo, the Stefan number St, the size of the bubble, and the angle θo. It is found that the breakup of the drop during freezing takes place for increasing Bo (from 0.1 to 3.0), increasing θo (from 60° to 120°), decreasing St (in the range of 0.01–0.64), or decreasing bubble size. On the other hand, the shape of the curved surface has little influence on the breakup of the drop. Phase diagrams of θo vs Bo and of St vs Bo are also presented to provide a more general picture of the breakup and freezing of the water drop.

Objective\ud \ud EpiNet was established to encourage epilepsy research. EpiNet is used for multicenter cohort studies and investigator‐led trials. Physicians must be accredited to recruit patients into trials. Here, we describe the accreditation process for the EpiNet‐First trials.\ud Methods\ud \ud Physicians with an interest in epilepsy were invited to assess 30 case scenarios to determine the following: whether patients have epilepsy; the nature of the seizures (generalized, focal); and the etiology. Information was presented in two steps for 23 cases. The EpiNet steering committee determined that 21 cases had epilepsy. The steering committee determined by consensus which responses were acceptable for each case. We chose a subset of 18 cases to accredit investigators for the EpiNet‐First trials. We initially focused on 12 cases; to be accredited, investigators could not diagnose epilepsy in any case that the steering committee determined did not have epilepsy. If investigators were not accredited after assessing 12 cases, 6 further cases were considered. When assessing the 18 cases, investigators could be accredited if they diagnosed one of six nonepilepsy patients as having possible epilepsy but could make no other false‐positive errors and could make only one error regarding seizure classification.\ud Results\ud \ud Between December 2013 and December 2014, 189 physicians assessed the 30 cases. Agreement with the steering committee regarding the diagnosis at step 1 ranged from 47% to 100%, and improved when information regarding tests was provided at step 2. One hundred five of the 189 physicians (55%) were accredited for the EpiNet‐First trials. The kappa value for diagnosis of epilepsy across all 30 cases for accredited physicians was 0.70.\ud Significance\ud \ud We have established criteria for accrediting physicians using EpiNet. New investigators can be accredited by assessing 18 case scenarios. We encourage physicians with an interest in epilepsy to become EpiNet‐accredited and to participate in these investigator‐led clinical trials.

In 2003 in China, Peng et al. invented the recombinant adenovirus expressing p53 (Gendicine) for clinical tumor virotherapy. This was the first clinically approved gene therapy and tumor virotherapy drug in the world. An oncolytic herpes simplex virus expressing granulocyte-macrophage colony-stimulating factor (Talimogene laherparepvec) was approved for melanoma treatment in the United States in 2015. Since then, oncolytic viruses have been attracting more and more attention in the field of oncology, and may become novel significant modalities of tumor precision imaging and radiotherapy after further improvement. Oncolytic viruses carrying reporter genes can replicate and express genes of interest selectively in tumor cells, thus improving in vivo noninvasive precision molecular imaging and radiotherapy. Here, the latest developments and molecular mechanisms of tumor imaging and radiotherapy using oncolytic viruses are reviewed, and perspectives are given for further research. Various types of tumors are discussed, and special attention is paid to gastrointestinal tumors.

The expression of mRNAs for three P2X receptor subtypes (PX21, P2X2, P2X4) in the rat vascular system was studied by in situ hybridization and RT-PCR. In heart sections mRNAs transcripts for all three receptors were colocalized in smooth muscle cells of coronary vessels, while no specific positivity was apparent in myocardium. Coexpression of P2X receptor mRNA transcripts were also observed in other peripheral vessels, including aorta, pulmonary artery, internal and external iliac arteries, renal artery and femoral artery. By contrast, no mRNA transcripts of the above receptors were found in the superior mesenteric artery. RT-PCR performed on microdissected tissues (coronary arteries, aorta and myocardium from various heart areas) confirmed the presence of P2X1, P2X2 and P2X4 receptor mRNAs. Furthermore, in the same tissues two splice variants of the P2X2 receptor were identified. These results reveal an important molecular heterogeneity of P2X receptors, thus substantiating the possibility of a heteropolymeric assembly of ATP-gated ion channels in the cardiovascular system.

A bench-scale test program has been performed to evaluate the concept of placing a porous cylindrical surface (such as a metal screen) at the core of a container and spinning the surface with an external motor for fine particulate/gas separation. The rotating surface enhances the centrifugal effects in the annular region and provides a smooth transition between the flow in the annular and core regions and acts like an enhanced cyclone. It is therefore called a rotary cyclone.'' The porous surface is self-cleaning and offers good steady-state pressure drop characteristics. Objectives of this project are: (1) to carry out theoretical and experimental investigations using the rotary cyclone concept to capture particulates in the 0.5 to 10 micron size range; and (2) to evaluate its economic feasibility based on an engineering scale-up and comparison with conventional fabric filter and electrostatic precipitator systems. It was demonstrated that the efficiency in separating fine particulates is governed by two major characteristics, i.e., the magnitude of the centrifugal force and the approach velocity or the gas-to-surface area ratio. Results from the bench-scale tests have shown a collection efficiency of well over 99% for a typical fly ash. A preliminary conceptual design for a 40 MWmore » installation was developed based on the experimental work. 4 refs., 4 figs., 8 tabs.« less