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Fractures can provide valuable information on the tectonic evolution of the Earth’s crust. Our field observation data, rock core data, and thin section observations reveal several horizontal fractures in the Cenozoic mudstone strata in the western Qaidam Basin, Qinghai Province, China. These horizontal fractures have rough surfaces and are filled by gypsum. The fractures are mainly curved; however, some straight fractures are also found. There are many intersections between adjacent curved fractures, which often adjoin to form “T” shape fractures. Fracture apertures are mainly between 1 mm and 1 cm, with a maximum of 3 cm. Both the size and density of fractures decrease as strata denudation thickness decreases and depth of burial increases. Horizontal fractures are only found in a core area of anticlines with severe strata denudation. Accordingly, these fractures are related to vertical extension due to residual stress in the process of rapid uplift and denudation. The horizontal fractures cut earlier vertical tectonic fractures, indicating their formation after tectonic extrusion. Electron spin resonance (ESR) dating of fracture-filling materials revealed that horizontal fractures appeared in two stages. The first stage was approximately 1.8 Ma ago, while the second stage was approximately 0.3 Ma ago. The size and density of the later-stage horizontal fractures are markedly greater than the earlier-stage fractures. Based on the driving stress when fractures are formed, which is obtained from fracture parameters, the denudation rate in the later stage was approximately 2∼3-fold greater than that in the earlier stage. According to the evidence, during the Quaternary, the western Qaidam Basin experienced pulsating tectonic extrusion, producing uplift and denudation and an increase in tectonic activity. Such findings suggest a gradual increase in episodic tectonic activity in the entire Tibetan Plateau region during the Quaternary.

Desire is an important philosophical topic that deeply impacts everyday life. Philosophical practice is an emerging trend that uses philosophical theories and methods as a guide to living a eudaimonic life. In this paper, we define desire philosophically and compare different theories of desire in specific Eastern and Western traditions. Based on the Lacanian conceptual–terminological triad of “Need-Demand-Desire”, the research of desire is further divided into three dimensions, namely, the subject of desire, the object of desire, and the desire itself. The concept of desire is then analyzed from this triad and these three dimensions through different philosophical theories. This paper selects Buddhism as the representative of Eastern tradition, and Stoicism as the representative of the West, paying special attention to Stoicism’s “spiritual exercises” following Pierre Hadot. By exploring and comparing the Buddhist paths to liberation from suffering (i.e., the Four Noble Truths and the Noble Eightfold Path) and the two theoretical pillars in Stoicism (i.e., the notions of “living according to nature” and “the dichotomy of control”), practical guidance is then provided for understanding and regulating desire in times of crisis. This understanding and regulation of desire constitutes a philosophical therapy for today’s troubles, particularly those caused by excessive or irrational desires.

The sudden outbreak of the COVID-19 pandemic has changed people’s long-standing group life, and “less gathering” has become a popular slogan during this period. People will probably feel lonely when they are physically, socially, or mentally distanced and isolated or excluded, and they usually perceive a deficiency in the quality or quantity of their social relationships. Although loneliness is easily conflated with solitude, loneliness as an emotion is generally regarded as negative while solitude can be positive. There are various causes and effects of loneliness during the COVID-19 pandemic, and loneliness has been found to have significant impacts on poorer physical and mental health. Religiosity and spirituality are specifically proven to have a great impact on handling loneliness during the COVID-19 pandemic. When regarding belongingness as the opposite of loneliness and social isolation, religious belonging means a feeling of being “at home” and “connected”. In this paper, from a comparative approach, we attempt to investigate how the three most prominent traditions in East Asia, i.e., Confucianism, Daoism, and Buddhism, can help manage the feeling of loneliness. Due to different understandings of loneliness, their coping strategies for loneliness also vary. Through a preliminary study of “benevolence and rites,” “wu-wei and freedom,” and “mindfulness and spiritual realization,” we can learn from the ancient wisdom about how to reduce loneliness and promote spiritual well-being during the COVID-19 pandemic.

Different DNA methylation patterns presented on different tissues or cell types are considered as one of the main reasons accounting for the tissue-specific gene expressions. In recent years, many methods have been proposed to identify differentially methylated regions (DMRs) based on the mixture of methylation signals from homologous chromosomes. To investigate the possible influence of homologous chromosomes on methylation analysis, this paper proposed a method (MHap) to construct methylation haplotypes for homologous chromosomes in CpG dense regions. Through comparing the methylation consistency between homologous chromosomes in different cell types, it can be found that majority of paired methylation haplotypes derived from homologous chromosomes are consistent, while a lower methylation consistency was observed in the breast cancer sample. It also can be observed that the hypomethylation consistency of differentiated cells is higher than that of the corresponding undifferentiated stem cells. Furthermore, based on the methylation haplotypes constructed on homologous chromosomes, a method (MHap_DMR) is developed to identify DMRs between differentiated cells and the corresponding undifferentiated stem cells, or between the breast cancer sample and the normal breast sample. Through comparing the methylation haplotype modes of DMRs in two cell types, the DNA methylation changing directions of homologous chromosomes in cell differentiation and cancerization can be revealed. The code is available at: https://github.com/xqpeng/MHap_DMR.

Tipping over avoidance is critical for the success of mobile manipulation, especially in the cases that the onboard manipulators or the mobile vehicles move rapidly. Due to strong dynamics coupling between the onboard manipulator and mobile vehicle, online evaluation of dynamic stability of mobile manipulators and generation of strategies for tip-over avoidance still remain challenging. This paper presents an improvement tip-over moment stability criterion dealing with wheel-terrain and vehicle-manipulator interaction and proposes a real-time tip-over avoidance algorithm to minimize the tip-over moment transfer through either adjusting the posture of the onboard manipulators or changing the running velocity of the vehicle. The simulations and experiments on a four-wheeled mobile manipulator validate the correctness and feasibility of the proposed method.

The concept of spirituality has a long philosophical history. Based on detailed studies of a history of spiritual exercises from Socrates, the Stoics, Epicureanism, to early Christianity, the former catholic priest Pierre Hadot conceives philosophical practice as spiritual exercises in learning how to live a philosophical life. Following this idea, a number of philosophers such as Gerd B. Achenbach started the contemporary movement of philosophical practice in the 1980s, which aimed to apply philosophical theories and methods to discussions about issues people constantly encounter in life, mainly in the forms of philosophical counseling and philosophical therapy. In this paper, after showing that philosophical practice has already become a new frontier in philosophical research, we further argue that philosophical practice as spiritual exercises is an exercise of reason and logos, while certain kinds of religious exercises such as Zen arts can also constitute an important part of philosophical practice. We conclude that in light of the distinct plurality of the methods and modes of philosophical practice and the spiritual exercises involved, philosophical practice can be considered a meaningful and applicable approach to pursuing truth, wisdom, and virtue, which is of great didactic and ethical significance in the post-COVID-19 era.

Every person differs from every other person regarding their physical appearance, susceptibility to disease, response to medications, and so on. However, 99.9 percent of human DNA is the same. As such, differences in human genomes are very worthy of study. Single-Nucleotide Polymorphisms (SNPs) are the simplest form and most common source of genetic polymorphism. SNPs have been used to successfully identify defective genes that cause Mendelian diseases. However, most common human diseases are complex and are caused by multiple SNPs. Each SNP explains only a small fraction of genetic causes. Experiments on individual SNPs may reveal their non-detectable effects on complex diseases. Pathogenesis is a complicated topic, and it is difficult to correctly predict multiple SNPs. As such, the analysis of SNP data is a critical task in the study of genetic diseases. In this paper, we divide the methods for genome-wide SNP data analysis into two categories: single-trait Genome-Wide Association Studies (GWAS) in which pathology is mined from data of a single phenotype, and multiple-trait GWAS which identifies cross-phenotype associations. For single-trait GWAS, we review methods ranging from the simple to the complex, including TEAM, BOOST, AntEpiSeeker, SNPRuler, EDCF, HiSeeker, ORF, MLR-tagging, MSCD, and MIC. For multiple-trait GWAS, we describe methods in terms of their employed regression models, dimension-reduction methods, and meta-analysis methods. We also list the advantages and disadvantages of these methods. Finally, we discuss the future directions of SNP data analysis for genome-wide association.

Accumulation of α-synuclein (α-syn) into Lewy bodies (LBs) and mitochondrial abnormalities are the two cardinal pathobiological features of Parkinson’s disease (PD), which are associated with the loss of dopaminergic neurons. Although α-syn accumulates in many different cellular and mouse models, these models generally lack LB features. Here, we generated midbrain dopaminergic (mDA) neuronal cultures from induced pluripotent stem cells (iPSCs) derived from familial PD (fPD) patients and healthy controls. We show that mDA neuronal cultures from fPD patients with A53T mutation and α-syn gene (SNCA) triplication display pathological α-syn deposits, which spatially and morphologically resemble LBs. Importantly, we did not find any apparent accumulation of pathological α-syn in mDA neuronal culture derived from a healthy donor. Furthermore, we show that there are morphological abnormalities in the mitochondrial network in mDA neuronal cultures from fPD patients. Consequently, these cells were more susceptible to mitochondrial damage compared with healthy donor-derived mDA neuronal cultures. Our results indicate that the iPSC-derived mDA neuronal culture platform can be used to investigate the spatiotemporal appearance of LBs, as well as their composition, architecture, and relationship with mitochondrial abnormalities.

Genetic studies aimed at understanding the molecular basis of complex human phenotypes require the genotyping of many thousands of single-nucleotide polymorphisms (SNPs) across large numbers of individuals. Public efforts have so far identified over two million common human SNPs; however, the scoring of these SNPs is labor-intensive and requires a substantial amount of automation. Here we describe a simple but effective approach, termed whole-genome sampling analysis (WGSA), for genotyping thousands of SNPs simultaneously in a complex DNA sample without locus-specific primers or automation. Our method amplifies highly reproducible fractions of the genome across multiple DNA samples and calls genotypes at >99% accuracy. We rapidly genotyped 14,548 SNPs in three different human populations and identified a subset of them with significant allele frequency differences between groups. We also determined the ancestral allele for 8,386 SNPs by genotyping chimpanzee and gorilla DNA. WGSA is highly scaleable and enables the creation of ultrahigh density SNP maps for use in genetic studies. [ABSTRACT FROM AUTHOR]

In this paper, a multi-module electrodynamic exciter based on moving-magnet disk voice coil motor is presented to meet the demands of high torque and high bandwidth in a dynamic torsional stiffness test. A variable pole-arc ratio disk Halbach array (VPAR-DHA) is proposed, so that both high torque density and low rotor inertia can be obtained through enhancing the magnetic field in the working range. The analytical quasi-3-D model of VPAR-DHA was set up by using the harmonic function method, with the consideration of end-effects by a correction function. Electromagnetic structure optimization was carried out with the analytical model, and verified by 3-D finite-element (FEM) results. The proposed design was experimentally tested and verified with a prototype that achieved a peak dynamic torque output of 40 Nm at a frequency of 120 Hz, and a stroke of ±1°. The proposed method can also be easily extended to satisfy various demands of dynamic torsional stiffness test.

We present a genotyping method for simultaneously scoring 116,204 SNPs using oligonucleotide arrays. At call rates >99%, reproducibility is >99.97% and accuracy, as measured by inheritance in trios and concordance with the HapMap Project, is >99.7%. Average intermarker distance is 23.6 kb, and 92% of the genome is within 100 kb of a SNP marker. Average heterozygosity is 0.30, with 105,511 SNPs having minor allele frequencies >5%. [ABSTRACT FROM AUTHOR]

In this study, a novel method based on μ analysis is presented to search for the upper/lower bounds of uncertainty parameters in microgrids (MGs). It is well known that uncertainty parameters have important effects in a MG, and they may cause instability. Previous studies have mainly focused on identifying the stability of a MG with its uncertainty parameters, but they did not address the problem of the upper/lower bounds of uncertainty parameters, i.e., how far the uncertainty parameters can be extended while the system remains stable in the small-signal sense. Thus, we developed an approach for identifying the bounds of uncertainty in MGs. In the current paper, first, a method is proposed for linear fractional transformation (LFT) configuration to express the uncertainty parameters, which makes the stability of the nominal MG system independent of any extension of the bounds. An algorithm based on this configuration is then designed to find the upper/lower bounds for both single parameter and multiple uncertainty parameters in a MG. Finally, the two cases are discussed, and the accuracy of the proposed method is confirmed using the conventional eigenvalue method.

Enteropathogenic E. coli (EPEC) and related enterobacteria rely on a type III secretion system (T3SS) effector NleE to block host NF-κB signaling. NleE is a first in class, novel S-adenosyl-L-methionine (SAM)-dependent methyltransferase that methylates a zinc-coordinating cysteine in the Npl4-like Zinc Finger (NZF) domains in TAB2/3 adaptors in the NF-κB pathway, but its mechanism of action and other human substrates are unknown. Here we solve crystal structure of NleE-SAM complex, which reveals a methyltransferase fold different from those of known ones. The SAM, cradled snugly at the bottom of a deep and narrow cavity, adopts a unique conformation ready for nucleophilic attack by the methyl acceptor. The substrate NZF domain can be well docked into the cavity, and molecular dynamic simulation indicates that Cys673 in TAB2-NZF is spatially and energetically favorable for attacking the SAM. We further identify a new NleE substrate, ZRANB3, that functions in PCNA binding and remodeling of stalled replication forks at the DNA damage sites. Specific inactivation of the NZF domain in ZRANB3 by NleE offers a unique opportunity to suggest that ZRANB3-NZF domain functions in DNA repair processes other than ZRANB3 recruitment to DNA damage sites. Our analyses suggest a novel and unexpected link between EPEC infection, virulence proteins and genome integrity.

Colloids near the glass concentration are often taken as models for molecular glasses. Yet, an important aspect of the dynamics of molecular glasses, structural recovery, has not been elucidated in colloids. We take advantage of a thermosensitive colloidal suspension to study the structural recovery after concentration jumps by using diffusing wave spectroscopy. The three classical aging signatures observed in molecular glasses are studied and the results are compared with those typical of molecular glasses. For the intrinsic isotherms, unlike molecular glasses, the colloid shows huge changes in relaxation time at equilibrium while the times required to reach the equilibrium state are nearly constant. For asymmetry of approach, we find a similar nonlinearity to that observed in the molecular glasses. For the memory experiment, while a memory effect is seen, the response is qualitatively different from that in molecular glasses. [ABSTRACT FROM AUTHOR]

Reports on the utilization of the analysis of single nucleotide polymorphisms in investigating the genetic cause of complex human disease in the U.S. Risk factor for developing chronic mucocutaneous candidiasis and thyroid disease; Feasibility of locus-specific amplification in terms of oligonucleotide synthesis; Complexity of the one-primer amplification assay; Accuracy of the genotype-calling algorithm.