Innovative ochre processing and tool use in China 40,000 years ago.

Homo sapiens was present in northern Asia by around 40,000 years ago, having replaced archaic populations across Eurasia after episodes of earlier population expansions and interbreeding1-4. Cultural adaptations of the last Neanderthals, the Denisovans and the incoming populations of H. sapiens into Asia remain unknown1,5-7. Here we describe Xiamabei, a well-preserved, approximately 40,000-year-old archaeological site in northern China, which includes the earliest known ochre-processing feature in east Asia, a distinctive miniaturized lithic assemblage with bladelet-like tools bearing traces of hafting, and a bone tool. The cultural assembly of traits at Xiamabei is unique for Eastern Asia and does not correspond with those found at other archaeological site assemblages inhabited by archaic populations or those generally associated with the expansion of H. sapiens, such as the Initial Upper Palaeolithic8-10. The record of northern Asia supports a process of technological innovations and cultural diversification emerging in a period of hominin hybridization and admixture2,3,6,11.

Earliest Prepared core technology in Eurasia from Nihewan (China): Implications for early human abilities and dispersals in East Asia.

Organized flaking techniques to obtain predetermined stone tools have been traced back to the early Acheulean (also known as mode 2) in Africa and are seen as indicative of the emergence of advanced technical abilities and in-depth planning skills among early humans. Here, we report one of the earliest known examples of prepared core technology in the archaeological record, at the Cenjiawan (CJW) site in the Nihewan basin of China, dated 1.1 Mya. The operational schemes reconstructed from the CJW refit sets, together with shaping patterns observed in the retouched tools, suggest that Nihewan basin toolmakers had the technical abilities of mode 2 hominins, and developed different survival strategies to adapt to local raw materials and environments. This finding predates the previously earliest known prepared core technology from Eurasia by 0.3 My, and the earliest known mode 2 sites in East Asia by a similar amount of time, thus suggesting that hominins with advanced technologies may have migrated into high latitude East Asia as early as 1.1 Mya.

Total Structure, Electronic Structure and Catalytic Hydrogenation Activity of Metal-Deficient Chiral Polyhydride Cu57 Nanoclusters.

Accurate identifying and in-depth understanding of the defect sites in a working nanomaterial could hinge on establishing specific defect-activity relationships. Yet, atomically precise coinage-metal nanoclusters (NCs) possessing surface vacancy defects are scarce primarily owing to challenges in the synthesis and isolation of such defective NCs. Herein we report a mixed-ligand strategy to synthesizing an intrinsically chiral and metal-deficient copper hydride-rich NC [Cu57 H20 (PET)36 (TPP)4 ]+ (Cu57 H20 ). Its total structure (including hydrides) and electronic structure are well established by combined experimental and computational results. Crystal structure reveals Cu57 H20 features a cube-like Cu8 kernel embedded in a corner-missing metal-ligand shell of Cu49 (PET)36 (TPP)4 . Single Cu vacancy defect site occurs at one corner of the shell, evocative of mono-lacunary polyoxometalates. Theoretical calculations demonstrate that the above-mentioned point vacancy causes one surface hydride exposed as an interfacial capping µ3 -H- , which is accessible in chemical reaction, as proved by deuterated experiment. Moreover, Cu57 H20 shows catalytic activity in the hydrogenation of nitroarene. The success of this work opens the way for the research on well-defined chiral metal-deficient Cu and other metal NCs, including exploring their application in asymmetrical catalysis.

The Paleolithic in the Nihewan Basin, China: Evolutionary history of an Early to Late Pleistocene record in Eastern Asia.

The Nihewan Basin of China preserves one of the most important successions of Paleolithic archeological sites in Eurasia. Stratified archeological sites and mammalian fossils, first reported in the 1920s, continue to be recovered in large-scale excavation projects. Here, we review key findings from archeological excavations in the Nihewan Basin ranging from ~1.66 Ma to 11.7 ka. We place particular emphasis on changes in stone tool technology over the long term. Though Pleistocene lithic industries from East Asia are often described as simple in character, re-evaluation of the stone tool evidence from the Nihewan Basin demonstrates significant, though periodic, innovations and variability in manufacturing techniques through time, indicating adaptive and technological flexibility on the part of hominins. Synthesis of paleoenvironmental and archeological data indicate changes in hominin occupation frequency in the Nihewan Basin, with chronological gaps suggesting that continuous presence in high, seasonal latitudes was not possible prior to the Late Pleistocene.

Beyond Fitts's Law: A Three-Phase Model Predicts Movement Time to Position an Object in an Immersive 3D Virtual Environment.

OBJECTIVE: The study examines the factors determining the movement time (MT) of positioning an object in an immersive 3D virtual environment. BACKGROUND: Positioning an object into a prescribed area is a fundamental operation in a 3D space. Although Fitts's law models the pointing task very well, it does not apply to a positioning task in an immersive 3D virtual environment since it does not consider the effect of object size in the positioning task. METHOD: Participants were asked to position a ball-shaped object into a spherical area in a virtual space using a handheld or head-tracking controller in the ray-casting technique. We varied object size (OS), movement amplitude (A), and target tolerance (TT). MT was recorded and analyzed in three phases: acceleration, deceleration, and correction. RESULTS: In the acceleration phase, MT was inversely related to object size and positively proportional to movement amplitude. In the deceleration phase, MT was primarily determined by movement amplitude. In the correction phase, MT was affected by all three factors. We observed similar results whether participants used a handheld controller or head-tracking controller. We thus propose a three-phase model with different formulae at each phase. This model fit participants' performance very well. CONCLUSION: A three-phase model can successfully predict MT in the positioning task in an immersive 3D virtual environment in the acceleration, deceleration, and correction phases, separately. APPLICATION: Our model provides a quantitative framework for researchers and designers to design and evaluate 3D interfaces for the positioning task in a virtual space.

Design, synthesis and biological evaluation of novel series of 2H-benzo[b][1,4]oxazin-3(4H)-one and 2H-benzo[b][1,4]oxazine scaffold derivatives as PI3Kα inhibitors.

The abnormal activation of PI3K signaling pathway leads to the occurrence of various cancers. The PI3Kα is frequently mutated and overexpressed in many human cancers. Therefore, the PI3Kα was considered as a promising target in therapeutic treatment of cancer. In this study, two series of compounds containing 2H-benzo[b][1,4]oxazin-3(4H)-one and 2H-benzo[b][1,4]oxazine scaffold were synthesized and evaluated antiproliferative activities against three cancer cell lines, including HCT-116, MDA-MB-231 and SNU638. Compound 7f with the most potent antiproliferative activity was selected for further evaluation on normal cells and PI3K kinase. Studies indicated that compound 7f could decrease the phospho-Akt (T308) in a dose-dependent manner. Four key hydrogen bonding interactions were found in the docking of 7f with PI3K enzyme. All the results suggested that 7f was a potent PI3Kα inhibitor.

ESR dating of the Majuangou and Banshan Paleolithic sites in the Nihewan Basin, North China.

The fluvio-lacustrine sequences in the Nihewan Basin, northern China provide an important source of Paleolithic settlements and therefore early human occupation in the eastern Old World. Here we present electron spin resonance (ESR) chronology for the Majuangou (MJG-III, MJG-II and MJG-I) and Banshan (BS) Paleolithic sites in this basin by the quartz Ti-Li center ESR dating. Results show that the ages of MJG-III and MJG-II could be estimated to be ∼1.70 Ma (millions of years ago); of MJG-I, ∼1.40 Ma; and BS, ∼1.35 Ma. This ESR chronology is consistent with the previous magnetochronology, thus providing strong support for the earliest human presence at the high northern latitudes of Northeast Asia.

Initial Upper Palaeolithic material culture by 45,000 years ago at Shiyu in northern China.

The geographic expansion of Homo sapiens populations into southeastern Europe occurred by ∼47,000 years ago (∼47 ka), marked by Initial Upper Palaeolithic (IUP) technology. H. sapiens was present in western Siberia by ∼45 ka, and IUP industries indicate early entries by ∼50 ka in the Russian Altai and 46-45 ka in northern Mongolia. H. sapiens was in northeastern Asia by ∼40 ka, with a single IUP site in China dating to 43-41 ka. Here we describe an IUP assemblage from Shiyu in northern China, dating to ∼45 ka. Shiyu contains a stone tool assemblage produced by Levallois and Volumetric Blade Reduction methods, the long-distance transfer of obsidian from sources in China and the Russian Far East (800-1,000 km away), increased hunting skills denoted by the selective culling of adult equids and the recovery of tanged and hafted projectile points with evidence of impact fractures, and the presence of a worked bone tool and a shaped graphite disc. Shiyu exhibits a set of advanced cultural behaviours, and together with the recovery of a now-lost human cranial bone, the record supports an expansion of H. sapiens into eastern Asia by about 45 ka.

A combination of eye-gaze and head-gaze interactions improves efficiency and user experience in an object positioning task in virtual environments.

Eye-gaze and head-gaze are two hands-free interaction modes in virtual reality, each of which has demonstrated different strengths. Selecting suitable interaction modes in different scenarios is important to achieve efficient interaction in virtual scenes. This study compared the movement time in an object positioning task by examining eye-gaze interaction and head-gaze interaction in various conditions. In turn, it identified the superior zones for each mode, respectively. Based on this information, we designed a combination mode - utilizing eye-gaze interaction at the acceleration phase and deceleration phase and head-gaze interaction at the correction phase - to achieve the optimal interaction mode, which has allowed us to obtain higher efficiency and subjective satisfaction. This study provides a comprehensive analysis of the characteristics of the eye-gaze and head-gaze interaction modes and provides valuable insights into selecting the appropriate interaction modes for virtual reality applications.

Controllable spontaneous resolution in ultrasmall Cu-Ag bimetallic cluster ion pairs from achiral components.

Bimetallic cluster ion pairs containing a quaternary phosphonium and an ultrasmall Cu2Ag3 anionic cluster protected by thiolates: (PPh3R'')[Cu2Ag3(SR')6] (R'SH = cyclohexylthiol (CySH), R'' = Ph, 1; Me, 2; Et, 3; Pr, 4; R'SH = tert-butylthiol (tBuSH) and R'' = Ph, 5) were reported. Without any chiral source, 1 crystallizes as conglomerate crystals with homochiral packings and spontaneous resolution occurs, while four other clusters 2-5 crystallize as racemic crystals with heterochiral packings. These results indicate that racemic and homochiral crystallization in the cluster system could be controlled through fine-tuning internal achiral structural components.

Technological innovations at the onset of the Mid-Pleistocene Climate Transition in high-latitude East Asia.

The interplay between Pleistocene climatic variability and hominin adaptations to diverse terrestrial ecosystems is a key topic in human evolutionary studies. Early and Middle Pleistocene environmental change and its relation to hominin behavioural responses has been a subject of great interest in Africa and Europe, though little information is available for other key regions of the Old World, particularly from Eastern Asia. Here we examine key Early Pleistocene sites of the Nihewan Basin, in high-latitude northern China, dating between ∼1.4 and 1.0 million years ago (Ma). We compare stone-tool assemblages from three Early Pleistocene sites in the Nihewan Basin, including detailed assessment of stone-tool refitting sequences at the ∼1.1-Ma-old site of Cenjiawan. Increased toolmaking skills and technological innovations are evident in the Nihewan Basin at the onset of the Mid-Pleistocene Climate Transition (MPT). Examination of the lithic technology of the Nihewan sites, together with an assessment of other key Palaeolithic sites of China, indicates that toolkits show increasing diversity at the outset of the MPT and in its aftermath. The overall evidence indicates the adaptive flexibility of early hominins to ecosystem changes since the MPT, though regional abandonments are also apparent in high latitudes, likely owing to cold and oscillating environmental conditions. The view presented here sharply contrasts with traditional arguments that stone-tool technologies of China are homogeneous and continuous over the course of the Early Pleistocene.

Drug-related Virtual Reality Cue Reactivity is Associated with Gamma Activity in Reward and Executive Control Circuit in Methamphetamine Use Disorders.

BACKGROUND: Accumulated studies in substance use disorders indicated that the mesocorticolimbic reward circuit and executive control circuit played interactive roles in the cue-reactivity and gamma oscillatory in the cortex, as well as autonomic nervous activity was associated with it. AIM OF THE STUDY: This study aimed to explore the mechanism of processing drug-related cues. METHODS: Sixty methamphetamine users were recruited and exposed to the drug-related virtual reality (VR) environments. Self-reported craving was assessed and skin conductance level (SCL) and heart rate variability were used to measure the autonomic nervous reactivity. With source estimation, gamma current density was used to measure the activity of medial prefrontal cortex/orbitofrontal cortex (MPFC/OFC) and dorsolateral prefrontal cortex (DLPFC) which are responsible for the mesocorticolimbic reward circuit and the executive control circuit. RESULTS: The VR drug-related cue induced an increased craving and SCL compared with the neutral condition. Gamma activity in MPFC/OFC and right DLPFC were decreased after cue exposure and predicted the SCL changes. However, no association was found between self-reported craving and electrophysiological response. CONCLUSIONS: Cue-reactivity in cortex and ANS, as well as their association, were observed in this study. Cue-induced electrophysiological responses were related to gamma activity in the mesocorticolimbic reward circuit and the executive control circuit.

Uplift, climate and biotic changes at the Eocene-Oligocene transition in south-eastern Tibet.

The uplift history of south-eastern Tibet is crucial to understanding processes driving the tectonic evolution of the Tibetan Plateau and surrounding areas. Underpinning existing palaeoaltimetric studies has been regional mapping based in large part on biostratigraphy that assumes a Neogene modernization of the highly diverse, but threatened, Asian biota. Here, with new radiometric dating and newly collected plant-fossil archives, we quantify the surface height of part of the south-eastern margin of Tibet in the latest Eocene (∼34 Ma) to be ∼3 km and rising, possibly attaining its present elevation (3.9 km) in the early Oligocene. We also find that the Eocene-Oligocene transition in south-eastern Tibet witnessed leaf-size diminution and a floral composition change from sub-tropical/warm temperate to cool temperate, likely reflective of both uplift and secular climate change, and that, by the latest Eocene, floral modernization on Tibet had already taken place, implying modernization was deeply rooted in the Palaeogene.

Design, synthesis and biological evaluation of novel 4-aminoquinazolines as dual target inhibitors of EGFR-PI3Kα.

The overexpression of EGFR correlates with rapidly progressive disease, resistance to chemotherapy and poor prognosis. In certain human cancers, PI3K works synergistically with EGFR to promote proliferation, survival, invasion and metastasis. Development of dual-target drugs against EGFR and PI3K has therapeutic advantage and was an attractive approach against tumors. In this work, based on the molecular docking and previous studies, a series of 4-aminoquinazolines derivatives containing 6-sulfonamide substituted pyridyl group were rationally designed and identified as potent EGFR and PI3K dual inhibitors. The cytotoxicity experiment results showed that this series of compounds could effectively inhibit cell growth. The kinase assay demonstrated that 6c and 6i had high inhibition for EGFR and selectivity for PI3Kα distinguished from other isoforms. Further experiments showed that 6c could induce cell cycle arrest in G1 phase and apoptosis in BT549 cells. The western blot assay indicated that 6c inhibited the proliferation of BT549 cell through EGFR and PI3Kα/Akt signaling pathway. Our study suggested that compound 6c was a potential dual inhibitors of EGFR and PI3Kα.

The lithic assemblages of Donggutuo, Nihewan basin: Knapping skills of early pleistocene hominins in North China.

Donggutuo (DGT) is one of the richest archaeological localities in the Nihewan Basin of North China, thereby providing key information about the technological behaviours of early hominins in eastern Asia. Although DGT has been subject of multiple excavations and technological studies over the past several decades, few detailed studies on the lithic assemblages have been published. Here we summarize and describe the DGT lithic assemblages, examining stone tool reduction methods and technological skills. DGT dates to ca. 1.1 Ma, close to the onset of the mid-Pleistocene climate transition (MPT), indicating that occupations at DGT coincided with increased environmental instability. During this time interval, the DGT knappers began to apply innovative flaking methods, using free hand hard hammer percussion (FHHP) to manufacture pre-determined core shapes, small flakes and finely retouched tools, while occasionally using the bipolar technique, in contrast to the earlier and nearby Nihewan site of Xiaochangliang (XCL). Evidence for some degree of planning and predetermination in lithic reduction at DGT parallels technological developments in African Oldowan sites, suggesting that innovations in early industries may be situational, sometimes corresponding with adaptations to changes in environments and local conditions.

Correction: The lithic assemblages of Donggutuo, Nihewan basin: Knapping skills of Early Pleistocene hominins in North China.

[This corrects the article DOI: 10.1371/journal.pone.0185101.].

The Lithic Assemblages of Xiaochangliang, Nihewan Basin: Implications for Early Pleistocene Hominin Behaviour in North China.

Xiaochangliang (XCL), located in the Nihewan Basin of North China, is a key archaeological locality for understanding the behavioural evolution of early humans. XCL dates to ca. 1.36 Ma, making it one of the earliest sites in Northeast Asia. Although XCL represents the first excavation of an Early Pleistocene site in the Nihewan Basin, identified and excavated in the 1970's, the lithic assemblages have never been published in full detail. Here we describe the lithic assemblages from XCL, providing information on stone tool reduction techniques and the influence of raw materials on artefact manufacture. The XCL hominins used both bipolar and freehand reduction techniques to manufacture small flakes, some of which show retouch. Bipolar reduction methods at XCL were used more frequently than previously recognized. Comparison of XCL with other Early Pleistocene sites in the Nihewan Basin indicates the variable use of bipolar and freehand reduction methods, thereby indicating a flexible approach in the utilization of raw materials. The stone tools from XCL and the Nihewan sites are classifiable as Mode I lithic assemblages, readily distinguished from bifacial industries manufactured by hominins in Eastern Asia by ca. 800 ka.