Survey, Excavation, and Geophysics at Songjiaheba—A Small Bronze Age Site in the Chengdu Plain

Archaeological survey in the Chengdu Plain of Sichuan Province has revealed settlement patterns surrounding Late Neolithic walled sites, including large numbers of small settlements from the Neolithic, Bronze Age, and Han Dynasty eras. Here geophysical survey and excavation at one of these small-scale sites dating to the Middle Bronze Age are reported, showing for the first time the value of high-resolution geophysics for evaluating site size and integrity in the Chengdu region

Investigating ancient landscapes and settlement patterns in the Chengdu Plain, Sichuan, China

Introduction This paper introduces an integrated survey methodology that is being employed by the Chengdu Plain Archaeological Survey (CPAS) to examine settlement patterns in the context of natural and social landscapes in Sichuan Province, China. The discoveries of the Bronze Age sites of Sangxingdui and Jinsha in the Chengdu Plain have raised questions about the emergence of a complex society in this region, especially as it compares with other societies in the Yellow River valley in Northe..

Survey, Excavation, and Geophysics at Songjiaheba—A Small Bronze Age Site in the Chengdu Plain

The Chengdu 成都 Plain, in the northwest corner of the Sichuan 四川Basin (Figure 1), was the setting for the emergence of a complex civilization in the second millennium BC. This civilization is most notably associated with the site of Sanxingdui 三星堆, in Guanghan 廣漢, where two sacrificial pits discovered in 1986 revealed a rich and unexpected collection of jade objects, ceramics, elephant tusks, and elaborate bronze and gold objects (Bagley 2001; Flad 2012; Sichuan 1999). The discovery of the Sanxingdui pits was followed by research at other sites in the Chengdu Plain, including several loci in the city of Chengdu that post-date Sanxingdui, such as an elite residential location called Shi’erqiao 十二橋 (Sichuan et al. 1987; Jiang 1998), a zone of ritual deposits, cemeteries, and settlement areas named Jinsha 金沙 (Chengdu Institute 2006; Chengdu & Beijing 2002; Zhu et al. 2003), and Shangyejie 商業街, a Late Bronze Age elite burial site with large log coffins filled with lacquers and other elite objects (Chengdu 2002). Based on the excavations of these sites, we now know that bronze-producing communities that commanded multi-community networks of resource acquisition existed in the 2 Chengdu Plain starting at least as early as the middle of the second millennium BC (Flad and Chen 2013).Anthropolog

The genetic determinants of recurrent somatic mutations in 43,693 blood genomes

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences

Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes

Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation

Validation of Human Telomere Length Multi-Ancestry Meta-Analysis Association Signals Identifies POP5 and KBTBD6 as Human Telomere Length Regulation Genes

Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes

Efficient free-space optical switching harnessing quasi-guided modes in a corrugated lithium niobate grating

We report and demonstrate an efficient free-space optical switching scheme by harnessing the high-Q resonances of quasi-guided modes (QGMs) supported by a corrugated Lithium Niobate grating on a slab waveguide. The well-confined guided modes in the slab are inaccessible by free-space radiations, so the incident light has a transmittance close to unity. However, when the refractive index of every second ridge is changed by Pockels effect at the presence of an applied voltage, the grating period increases by a factor of 2, leading to the transition from the guided modes into QGMs. The QGMs possess ultra-high Q factors allowing their efficient excitation through incident radiations, and then a near-zero transmittance at the wavelength of the QGM resonance is observed. The large contrast in the optical transmittance between the cases w/ and w/o the applied voltage shows that an efficient optical switch is achieved. Although the ultra-high Q factors of the QGMs make it challenging to match the working wavelength to the resonance, we further depict that this problem can be addressed by exploiting the large spatial dispersion of the QGMs, which enables an easy tuning of the resonance to a certain wavelength by changing the incident angle

Transition Metal Catalyst Free Cross-Coupling Reaction of Tertiary Propargylic Alcohols with Hetero-Areneboronic Acids

We report a perfluorophenylboronic acid catalyzed cross coupling reaction of tertiary propargylic alcohols and hetero-areneboronic acids for valuable benzo[b]thiophene and cyclopenta[a]indene derivates. This coupling reaction proceeds efficiently with a wide array of substrates scope in up to 89% yield and excellent regioselectivity. A significant advantage of our protocol is the transition metal catalyst free and mild conditions needed. This strategy provides direct and facile access to medicinally important benzo[b]thiophene and cyclopenta[a]indene scaffold containing a quaternary carbon center

Ligand Accelerated Hydrogen Isotope Exchange: Switching C-H Activation from Functionalization Towards C-D Bond Formation

Hydrogen isotope exchange (HIE) has emerged as a unique strategy for labelling, affording plenty of deuterated chemicals with varieties in patterns. Although the HIE based on electrophilic C-H activation could utilize the economic heavy water as deuterium source, the poor kinetic feature, as well as the side reactions still hampered its further application. In this work, an acceleration strategy for HIE development had been proposed based on ligand-modified C-H activation intermediate. According to the strategy, high efficiency HIE condition could be stemmed from the moderate-potency conditions in the corresponding functionalizations, which may fail in balancing the C-H activation and the subsequent coupling. Thus, as a proof of concept, experimental evidence was provided by different ligand preferences of HIE and functionalizations based on a non-directed Pd-catalyzed dual-ligand system. The competing experiment suggested the functionalization could be partially suppressed by using steric MPAA ligands, which facilitated the progression of C-D bond formation