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The understanding and quantification of ductility in crystalline metals, which has led to their widespread and effective usage as a structural material, is lacking in metallic glasses (MGs). Here, we introduce such a framework for ductility. This very practical framework is based on a MGs ability to support stable shear band growth, quantified in a stress gradient, gradSDB, which we measure and calculate for a range of MGs. Whether a MG behaves ductile or brittle in an application is determined by the comparison between gradsDB the applied stress field gradient, gradsapp. If gradsDB > gradsapp, the MG will behave brittle, if gradsDB < gradsapp, the MG will behave ductile, and gradsapp - gradsDB indicates how ductile. This framework can explain observed plastic properties of MGs and their apparent contradicting brittle and ductile characteristics. Looking forward, proposed framework provides the constitutive relation to quantitatively model their plastic behavior in any application, a requirement to use MGs as structural materials.

Nanofabrication techniques are limited by at least one of the required characteristics such as choice of material, control over geometry, fabrication requirements, yield, cost, and scalability. Our previously developed method of thermomechanical nanomolding fulfills these requirements, although it requires high processing temperatures. Here, we demonstrate low-temperature molding where we utilize the enhanced diffusivity on "eutectic interfaces". Gold nanorods are molded at room temperature using Au-Si alloy as feedstock. Instead of using alloy feedstock, these "eutectic interfaces" can also be established through a feedstock-mold combination. We demonstrate this by using pure Au as feedstock, which is molded into Si molds at room temperature, and also the reverse, Si feedstock is molded into Au molds forming high aspect ratio Au-Si core-shell nanorods. We discuss the mechanism of this low-temperature nanomolding in terms of lower homologous temperature at the eutectic interface. This technique, based on enhanced eutectic interface diffusion, provides a practical nanofabrication method that eliminates the previous high-temperature requirements, thereby expanding the range of the materials that can be practically nanofabricated.

Aiming at the shallow surface electromagnetic detection instrument system widely used in urban underground space exploration and underground target induction, a three-frequency resonance transmitting scheme is proposed to solve the problems of low efficiency in conventional single-frequency transmission method and high-voltage stress ( $d\text{v}/d\text{t}$ ) in multifrequency pseudorandom transmission method. According to the specific transmitting coil and the required transmitting frequency, a three-frequency resonant matching circuit is designed to transmit the current signal with three frequency components, the fundamental and two low-order harmonics. Compared with 2n sequence pseudorandom transmitting mode, the current of resonant method is continuous without step, which reduces the influence on the received signal. In this article, the principle of three-frequency resonance is analyzed. The simulation experiment and laboratory test are carried out to verify the feasibility of the proposed method.

© This open access article is distributed under Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND). How predictable are life trajectories? We investigated this question with a scientific mass collaboration using the common task method; 160 teams built predictive models for six life outcomes using data from the Fragile Families and Child Wellbeing Study, a high-quality birth cohort study. Despite using a rich dataset and applying machine-learning methods optimized for prediction, the best predictions were not very accurate and were only slightly better than those from a simple benchmark model. Within each outcome, prediction error was strongly associated with the family being predicted and weakly associated with the technique used to generate the prediction. Overall, these results suggest practical limits to the predictability of life outcomes in some settings and illustrate the value of mass collaborations in the social sciences.

For nanostructures in advanced electronic and plasmonic systems, a single-crystal structure with controlled orientation is essential. However, the fabrication of such devices has remained challenging, as current nanofabrication methods often suffer from either polycrystalline growth or the difficulty of integrating single crystals with substrates in desired orientations and locations to create functional devices. Here we report a thermomechanical method for the controlled growth of single-crystal nanowire arrays, which enables the simultaneous synthesis, alignment, and patterning of nanowires. Within such diffusion-based thermomechanical nanomolding (TMNM), the substrate material diffuses into nanosized cavities under an applied pressure gradient at a molding temperature of ∼0.4 times the material's melting temperature. Vertically grown face-centered cubic (fcc) nanowires with the [110] direction in an epitaxial relationship with the (110) substrate are demonstrated. The ability to control the crystal structure through the substrate takes TMNM a major step further, potentially allowing all fcc and body-centered cubic (bcc) materials to be integrated as single crystals into devices.

Description, Thermomechanical nanomolding puts a wide range of materials combinations in reach for nanofabrication., Advancements in nanotechnology require the development of nanofabrication methods for a wide range of materials, length scales, and elemental distributions. Today’s nanofabrication methods are typically missing at least one demanded characteristic. Hence, a general method enabling versatile nanofabrication remains elusive. Here, we show that, when revealing and using the underlying mechanisms of thermomechanical nanomolding, a highly versatile nanofabrication toolbox is the result. Specifically, we reveal interface diffusion and dislocation slip as the controlling mechanisms and use their transition to control, combine, and predict the ability to fabricate general materials, material combinations, and length scales. Designing specific elemental distributions is based on the relative diffusivities, the transition temperature, and the distribution of the materials in the feedstock. The mechanistic origins of thermomechanical nanomolding and their homologous temperature-dependent transition suggest a versatile toolbox capable of combining many materials in nanostructures and potentially producing any material in moldable shapes on the nanoscale.

Chronic obstructive pulmonary disease (COPD) is a serious chronic respiratory disorder. One of the major risk factors for COPD progression is aging. Therefore, we investigated aging-related genes in COPD using bioinformatic analyses. Firstly, the Aging Atlas database containing 500 aging-related genes and the Gene Expression Omnibus database (GSE38974) were utilized to screen candidates. A total of 24 candidate genes were identified related to both COPD and aging. Using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we found that this list of 24 genes was enriched in genes associated with cytokine activity, cell apoptosis, NF-κB and IL-17 signaling. Four of these genes (

In this paper, we obtain the L p -boundedness of the Hilbert transform H γ for 1 p ∞ along a variable plane curve ( t , u ( x 1 , x 2 ) γ ( t ) ) , where u is a Lipschitz function with small Lipschitz norm, and γ is a general curve satisfying some suitable smoothness and curvature conditions.

Aims/Introduction Non‐alcoholic fatty liver disease and type 2 diabetes mellitus are closely related, and often occur simultaneously in patients. Type 2 diabetes increases the risk of diabetic peripheral neuropathy, resulting in intolerable pain and extremity amputation that reduces the quality of life. However, the role of non‐alcoholic fatty liver disease in the pathogenesis of diabetic peripheral neuropathy remains unclear. Thus, we evaluated the correlation of liver fibrosis and steatosis, which are representative histological morphologies of non‐alcoholic fatty liver disease, with diabetic peripheral neuropathy in type 2 diabetes patients. Materials and Methods Five hundred twenty individuals with type 2 diabetes were recruited. All the patients were detected nerve conduction study for diabetic peripheral neuropathy and fibro touch for liver steatosis and fibrosis. Correlation of DPN with liver steatosis and fibrosis were analysed with binary logistic analysis. Results Among the 520 patients, the prevalence of liver steatosis, fibrosis and diabetic peripheral neuropathy was 63.0% (n = 328), 18.1% (n = 94) and 52.1% (n = 271), respectively. The prevalence of diabetic peripheral neuropathy was significantly elevated in patients with liver steatosis (55.7 vs 44.9%, P = 0.03) and fibrosis (61.5 vs 50%, P = 0.04), and it increased as liver stiffness measurement increased. Additionally, both hepatic steatosis (odds ratio 1.48, 95% confidence interval 1.04–2.11, P = 0.03) and fibrosis (odds ratio 1.60, 95% confidence interval 1.02–2.51, P = 0.04) were correlated with diabetic peripheral neuropathy. After adjusting for age, sex, weight, height, body mass index, waist hip ratio, duration of type 2 diabetes, blood glucose, homeostatic model assessment of insulin resistance, blood pressure, serum lipid, liver enzyme, urea, uric acid, creatinine and inflammatory factors, liver fibrosis remained associated with diabetic peripheral neuropathy (odds ratio 2.24, 95% confidence interval 1.11–4.53, P = 0.02). Conclusions The prevalence of diabetic peripheral neuropathy was elevated in patients with liver steatosis and fibrosis. Liver fibrosis was also independently associated with an increased risk of diabetic peripheral neuropathy., Liver fibrosis was independently associated with DPN (OR = 2.24 (1.11–4.53), P = 0.02).

Background The TM4 (UBAC2) protein, which contains 4 transmembrane domains and one ubiquitin binding domain, is mainly expressed in cell and nuclear membranes. The current research aimed to explore the role of TM4 in metabolic inflammation and to examine whether the ubiquitin–proteasome inhibitor PS-341 could regulate the function of TM4. Methods The metabolic phenotypes of TM4 knockout (KO) mice were studied. We next explored the association between the polymorphisms of TM4 and obesity in a Chinese Han population. TM4 expression in the visceral fat of obese patients who underwent laparoscopic cholecystectomy was also analysed. Finally, the effect of PS-341 on the degradation and function of the TM4 protein was investigated in vivo and in vitro. Results TM4 KO mice developed obesity, hepatosteatosis, hypertension, and glucose intolerance under a high-fat diet. TM4 counterregulated Nur77, IKKβ, and NF-kB both in vivo and in vitro. The TM4 SNP rs147851454 is significantly associated with obesity after adjusting for age and sex (OR 1.606, 95% CI 1.065–2.422 P = 0.023) in 3394 non-diabetic and 1862 type 2 diabetic adults of Han Chinese. TM4 was significantly downregulated in the visceral fat of obese patients. PS-341 induced TM4 expression through inhibition of TM4 degradation in vitro. In db/db mice, PS-341 administration led to downregulation of Nur77/IKKβ/NF-κB expression in visceral fat and liver, and alleviation of hyperglycaemia, hypertension, and glucose intolerance. The hyperinsulinaemic-euglycaemic clamp demonstrated that PS-341 improved the glucose infusion rate and alleviated insulin resistance in db/db mice. Conclusions PS-341 alleviates chronic low-grade inflammation and improves insulin sensitivity through inhibition of TM4 degradation.

Direct measurement of critical cooling rates has been challenging and only determined for a minute fraction of the reported metallic glass forming alloys. Here, we report a method that directly measures critical cooling rate of thin film metallic glass forming alloys in a combinatorial fashion. Based on a universal heating architecture using indirect laser heating and a microstructure analysis this method offers itself as a rapid screening technique to quantify glass forming ability. We use this method to identify glass forming alloys and study the composition effect on the critical cooling rate in the Al–Ni–Ge system where we identified Al51Ge35Ni14 as the best glass forming composition with a critical cooling rate of 104 K/s.

Background Ankylosing spondylitis (AS) is a common infammatory rheumatic disease that affects the axial skeleton. Traditional Chinese medicine (TCM) nonpharmacological interventions are gaining an increasing popularity for AS. Nevertheless, the evidence of efficacy and safety of random controlled trials (RCTs) remains controversial. This study aims to evaluate the efficacy and acceptability of different TCM nonpharmacological therapies by systematic review and network meta-analysis. Methods According to the strategy, the authors will retrieve a total of 7 electronic databases by December 2020, including PubMed, the Cochrane Library, EMbase, China National Knowledge Infrastructure, China Biological Medicine, Chongqing VIP, and Wan-fang databases After a series of screening, 2 researchers will use Aggregate Data Drug Information System and Stata software to analyze the data extracted from the randomized controlled trials of TCM nonpharmacological interventions for AS. The primary outcome will be the improvement of Pain intensity and functional status/disability and the secondary outcomes will include lobal improvement, health-related quality of life, satisfaction with treatment, and adverse events. Both classical meta-analysis and network meta-analysis will be implemented to investigate direct and indirect evidences on this topic. The quality of the evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation instrument. Results This study will provide a reliable evidence for the selection of TCM nonpharmacological therapies in the treatment of AS. Conclusion This study will generate evidence for different TCM nonpharmacological therapies for AS and provide a decision-making reference for clinical research. Ethics and dissemination This study does not require ethical approval. The results will be disseminated through a peer-reviewed publication. Osf registration number DOI 10.17605/OSF.IO/FHD2U.

With its ease of implementation, low cost, high throughput, and excellent feature replication accuracy, nanoimprinting is used to fabricate structures for electrical, optical, and biological applications or to modify surface properties. If ultraprecise and/or subnanometer-sized patterns are desired, nanoimprinting has shown only limited success with polymers, silica glasses, or crystalline materials. In contrast, the absence of an intrinsic length scale that would interfere with imprinting resolution enables bulk metallic glasses (BMGs) to replicate structures down to the atomic scale through thermoplastic forming (TPF). However, only a small number of BMG-forming alloys can be used for TPF-based atomic-scale imprinting. Here, we demonstrate an alternative sputter deposition-based approach for the replication of atomic-scale features that is suited for a very broad range of amorphous alloys, thereby dramatically extending the available chemistries. Additional advantages are the method's scalability, its ability to replicate a wide range of molds, its low material consumption, and the fact that the films can readily be applied onto almost any workpiece, which together open up new avenues to atomically defined surface structuring and functionalization. Our method constitutes the advancement from proof of concept to a practical and highly versatile toolbox of atomic-scale imprinting to be explored for the science and technology of atomic-scale imprinting.

Endothelial injury plays a critical role in the pathogenesis of cardiovascular disorders and metabolic-associated vascular complications which are the leading cause of death worldwide. However, the mechanism underlying endothelial dysfunction is not completely understood. The study is aimed at investigating the role of tubulin polymerization-promoting protein family member 3 (TPPP3) in palmitic acid- (PA-) induced endothelial injury. The effect of TPPP3 on human umbilical vein endothelial cells (HUVECs) was determined by evaluating apoptosis, tube formation, and reactive oxygen species (ROS) production. TPPP3 silencing inhibited PA overload-induced apoptosis and production of ROS, along with the alteration of apoptosis-related key proteins such as BCL-2 and Bax. Mechanically, voltage-dependent anion channel 1 (VDAC1) was identified as a novel functional binding partner of TPPP3, and TPPP3 promoted VDAC1 protein stability and its activity. Further studies indicated that TPPP3 could promote apoptosis, ROS production, tube formation, and proapoptotic protein expression and reduce antiapoptotic protein expression through increasing VDAC1 expression under mildly elevated levels of PA. Collectively, these results demonstrated that TPPP3 could promote PA-induced oxidative damage in HUVECs via a VDAC1-dependent pathway, suggesting that TPPP3 might be considered as a potential therapeutic target in vascular disease.

In electromagnetic sounding, the detection areas of time-domain and frequency-domain electromagnetic detection methods cannot be effectively connected, and the detection processes for these two methods must be implemented separately. To combine time-domain and frequency-domain electromagnetic detection methods and simplify the detection process, a time-frequency fusion transmission method is proposed to simultaneously excite the earth to produce transient and steady-state responses. By analyzing the characteristics of the time-domain and frequency-domain excitation current waveforms, a pseudorandom transmission waveform with dead time is designed, and a transmission system for a time-frequency fusion electromagnetic detection method is developed. In this detection mode, the pseudorandom transmission waveform contains several frequencies, and the transient induction field can be received during the dead time. The time-domain and frequency-domain responses can be obtained by the same procedure. At the same time, a self-adaptive pseudoload device is designed and matched with the corresponding control sequence to reduce the influence of dead-time. The experimental results show that the self-adaptive pseudoload transmitter can effectively reduce the current fluctuation, and the time-frequency electromagnetic transmission system can effectively excite the earth to produce transient and steady-state responses. The time-frequency fusion electromagnetic transmission method proposed in this paper can be used in electromagnetic detection instruments to improve the efficiency of electromagnetic sounding.

Nanomolding usually refers to a top-down fabrication method by which a formable or moldable material is shaped using a mold of nanoscale dimensions. Nanomolding is the underlying mechanism for a wide range of nanofabrication methods including template-based deposition, extrusion, nanoembossing, soft lithography, nanoimprint lithography, thermomechanical nanomolding, and nanoimprinting. Its suitability for nanofabrication in a wide range of materials and states of matter makes it one of the most versatile nanofabrication methods. It offers solutions for improving lithography techniques and the fabrication of a wide range of nanomaterials for applications including catalysts, energy, devices, and a wide range of surface functionalization. This review discusses the various physical mechanisms underlying the nanomolding process, and how they relate to the specifics of the states of matter and the material classes. Nanofabrication methods will then be categorized based on their underlying mechanism, materials that they can fabricate, and technological characteristics such as scalability, costs, precision, and versatility. This will help the reader navigate the numerous, often very specific, methods of this advanced field, and identify the most appropriate process and state of matter for a specific application. A general discussion on nanomolding follows, from accomplishments to date and the challenges that lie ahead in realizing the many potential nanodevices and structures that researchers have envisioned. Particularly the recent advances of nanomolding have resulted in a paradigm shift of nanofabrication in which the design of nanodevices is no longer limited by material and nanostructured geometries but can be selected from a very wide palette of materials.

The common pheasant (Phasianus colchicus) in the order Galliformes and the family Phasianidae, has 30 subspecies distributed across its native range in the Palearctic realm and has been introduced to Europe, North America, and Australia. It is an important game bird often subjected to wildlife management as well as a model species to study speciation, biogeography and local adaptation. However, the genomic resources for the common pheasant are generally lacking. We sequenced a male individual of the subspecies torquatus of the common pheasant with the Illumina Hiseq platform. We obtained 94.88 Gb of usable sequences by filtering out low-quality reads of the raw data generated. This resulted in a 1.02 Gb final assembly, which equals the estimated genome size. BUSCO analysis using chicken as a model showed that 93.3% of genes were complete. The contig N50 and scaffold N50 sizes were 178 kb and 10.2 Mb, respectively. All these indicate that we obtained a high-quality genome assembly. We annotated 16,485 protein-coding genes and 123.3 Mb (12.05 % of the genome) of repetitive sequences by ab initio and homology-based prediction. Furthermore, we applied a RAD-sequencing approach for another 45 individuals of seven representative subspecies in China and identified 4,376,351 novel single nucleotide polymorphism (SNPs) markers. Using this unprecedented dataset, we uncover the geographic population structure and genetic introgression among common pheasants in China. Our results provide the first high-quality reference genome for the common pheasant and a valuable genome-wide SNP database for studying population genomics and demographic history.

Background Chronic obstructive pulmonary disease (COPD) is recognized as a chronic lung disease with incomplete reversible airflow limitation, but its pathophysiology was still not clear. This study aimed at investigating regulatory roles of special miRNA–mRNA axis in COPD development. Methods Differentially expressed miRNAs and downstream mRNAs were screened from the Gene Expression Omnibus (GEO) dataset by using the LIMMA package in R software. Weighted Gene Co-expression Network Analysis (WGCNA) was used to construct a co-expression network for COPD. The correlation of dysregulated miRNA(s) and COPD was analyzed, and miRNAs with significant differences were validated in peripheral blood mononuclear cells (PBMCs) from COPD patients by real-time PCR. Regulatory roles of candidate miRNAs and targeted mRNAs were investigated in vitro study. Results Thirteen modules of co-expressed miRNAs and mRNAs were constructed from a selected cohort with WGCNA. Turquoise module with 12 differentially expressed miRNAs and 120 mRNAs was significantly correlated with COPD. The expression of hsa-miR-664a-3p, an upregulated miRNA in the module, was increased both in lung tissue and PBMCs from COPD patients, whereas that targeted four and a half LIM domains 1 (FHL1) gene was decreased and positively correlated with forced expiratory volume in 1 sec (FEV1)/forced vital capacity (FVC%) (r = 0.59, p < 0.01). In vitro, luciferase activity assay revealed FHL1 as a target of hsa-miR-664a-3p and it could be directly downregulated by overexpression of hsa-miR-664a-3p. Furthermore, cigarette smoke extract could increase hsa-miR-664a-3p level and decrease FHL1 level in Beas-2B cells. Conclusion The present study validated significant upregulation of hsa-miR-664a-3p in COPD patients, and its target gene FHL1 was downregulated and positively correlated with FEV1/FVC%; both hsa-miR-664a-3p and FHL1 could be regulated by cigarette smoke extract. Results of bioinformatic analyses and expanded validation suggest that the axis from hsa-miR-664a-3p to FHL1 might play a key role in cigarette smoke-induced COPD, and the exact mechanism should be confirmed in further studies.

Background Transcription factor 7-like 2 (TCF7L2), which previously known as TCF-4, is a major form of transcription factor involved in the downstream WNT signaling and exhibits the strongest association to diabetes susceptibility. Although we still do not know mechanistically how TCF7L2 exerts its physiological functions on pancreatic endocrine cells, it had been suggested that TCF7L2 may directly affect β-cell function by regulating the activation of PI3K/AKT signaling pathway. Methods MIN6 cells were transfected with TCF7L2 knockdown virus or lenti-TCF7L2 virus for 48 h to evaluate the contribution of TCF7L2 to the PI3K/AKT signaling pathway and pancreatic β-cell function. This was confirmed by measuring the expression of PI3K p85 and p-Akt by western blotting and insulin secretion by enzyme-linked immunosorbent assay (ELISA), respectively. Chromatin immunoprecipitation (ChIP) and polymerase chain reaction (PCR) experiments were performed to explore the genomic distribution of TCF7L2-binding sites in the promoter of PIK3R1, the affinity between which was analyzed by the luciferase reporter assay. Results In the present study, we strikingly identified that TCF7L2 could profoundly inhibit the expression of PIK3R1 gene and its encoding protein PI3K p85, which then could lead to the activation of PI3K/AKT signaling and stimulate insulin secretion in pancreatic β-cells. However, the integrity and stability of evolutionarily conserved TCF7L2-binding motif plays a very crucial role in the binding events between transcription factor TCF7L2 and its candidate target genes. We also found that the affinity of TCF7L2 to the promoter region of PIK3R1 alters upon the specific binding sites, which further provides statistical validation to the necessity of TCF7L2-binding motif. Conclusions This study demonstrated that TCF7L2 is closely bound to the specific binding regions of PIK3R1 promoter and prominently controls the transcription of its encoding protein p85, which further affects the activation of PI3K/AKT signaling pathway and insulin secretion.

In the process of cold creep forming, the temperature control has problems such as low accuracy and slow response speed. Moreover, the conventional PID temperature controller has poor anti-interference ability and low control accuracy.This paper designs a PID control strategy based on improved ant colony algorithm which is applied to the temperature control of cold creep forming. With the help of Matlab simulation software, a temperature controller simulation model is established, and certain improvements are made to the model on the basis of the traditional ant colony algorithm, applying to search for the optimal parameter combination in PID control. The simulation results show that the designed control strategy can find a better parameter combination than the PID control of the ant colony algorithm. Therefore, the application of this control method to the cold creep forming temperature control system can effectively improve the product quality and production efficiency of the cold creep forming process.

We consider a broad range of 13 BMGs from different alloy systems to represent the material class of bulk metallic glasses (BMGs) and characterize their fracture toughness. To determine the effect of composition on the fracture toughness within one alloy system, we consider alloys in Zr-Al-Ni-Cu and Pd-Ni-Cu-P BMG forming alloy systems, specifically Zrx(Al0.25Ni0.25Cu0.5)100-x (at.%) and Pdx(NiCu2)(80-x)/3P20. Sample preparation follows a thermoplastic forming based method ensuring constant fictive temperature, which allows us to eliminate extrinsic effects and detangle the effect of fictive temperature and alloy chemistry on the fracture toughness. We found that fracture toughness varies significantly with composition, even in a non-monotonic way. Within one alloy system, fracture toughness correlates closely with the ratio of shear modulus over bulk modulus. Such correlation however is not present when comparing BMGs across alloy systems. Observed behavior suggests that shear modulus and bulk modulus serves as an incomplete proxy describing the BMGs ability to resist shear and cavitation. Further, our results reveal a general inverse correlation between fracture toughness and glass forming ability suggesting a trade-off of both desired properties. Such trade-off is not necassary present in metal-metalloid containing BMGs, where our results reveal a possibility to optimize alloys for both GFA and fracture toughness simultaneously.

Bulk metallic glasses (BMGs) exhibit remarkable mechanical properties, such as high strength and elasticity, which is often paired with fracture toughness. Their supercooled liquid region gives rise to plastic-like processing and suggests parts and shapes that can otherwise not be obtained for crystalline metals. However, current processing techniques only allow for limited options in terms of geometry, thicknesses uniformity, and shape complexity. Here we introduce a new processing technique, “stretch blow molding,” to expand the range of possible parts and increase the available geometries that can be fabricated with BMGs. Additionally, a model is derived that allows for the quantification and prediction of stretch blow molding and provides insight into its potential use and limitations. We demonstrate that with stretch blow molding overall strains exceeding 2000% are achievable, compared to the previously reported ∼150% of blow molding. With the ability to stretch blow mold shapes that were previously unachievable with any other metal fabrication technique in a fast and economical manner, and the superb properties of BMGs, we look forward to a broad commercial adaptation of this technique.

We report on a thermomechanical nanomolding method for crystalline metals. Quantified by the aspect ratio, this process becomes easier with decreasing mold diameter. As the responsible underlying diffusion mechanism is present in all metals and alloys, the discovered nanomolding process provides a toolbox to shape essentially any metal and alloy into a nanofeature. Technologically, this highly versatile and practical thermomechanical nanomolding technique offers a method to fabricate high-surface-area metallic nanostructures which are impactful in diverse fields of applications including catalysts, sensors, photovoltaics, microelectronics, and plasmonics.

The Hardy spaces for Fourier integral operators $\mathcal{H}_{FIO}^{p}(\mathbb{R}^{n})$, for $1\leq p\leq \infty$, were introduced by Smith in [Smith,1998] and Hassell et al. in [Hassell-Portal-Rozendaal,2020]. In this article, we give several equivalent characterizations of $\mathcal{H}_{FIO}^{1}(\mathbb{R}^{n})$, for example in terms of Littlewood--Paley $g$ functions and maximal functions. This answers a question from [Rozendaal,2021]. We also give several applications of the characterizations., Comment: 24 pages. Minor changes to the previous version. To appear in Studia Mathematica

Our previous studies demonstrated that depletion of tubulin polymerization promoting protein family member 3 (TPPP3) inhibits proliferation and induces apoptosis of HeLa cells. However, the expression and roles of TPPP3 in cancers remain largely unknown. In this study, we investigated the expression of TPPP3 in clinicopathological correlations in non-small-cell lung cancer (NSCLC) samples by immunohistochemistry. TPPP3 expression was significantly upregulated in NSCLC tissues, and high TPPP3 expression was positively associated with tumor size, lymph node metastasis, clinical stage, and poor survival. Furthermore, knockdown of TPPP3 by shRNA significantly inhibited cell proliferation and induced cell apoptosis and cell cycle arrest in vitro. In addition, depletion of TPPP3 inhibited lung cancer growth in vivo in the xenografts of H1299 cells; this effect was accompanied by the suppression of Ki67 expression. Our data suggested that TPPP3 might act as an oncogene in NSCLC. TPPP3 warrants consideration as a therapeutic candidate with anti-tumor potential.

The pineal hormone melatonin influences the secretion of insulin by pancreatic islets via the G‑protein‑coupled melatonin receptors 1 and 2 that are expressed in pancreatic β‑cells. Genome‑wide association studies indicate that melatonin receptor 1B (MTNR1B) single nucleotide polymorphisms are tightly associated with type 2 diabetes mellitus (T2DM). However, the underlying mechanism is unclear. Raf‑1 serves a critical role in the mitogen‑activated protein kinase (MAPK) pathways in β‑cell survival and proliferation and, therefore, may be involved in the mechanism by which melatonin impacts on T2DM through MTNR1B. In the present study, the mRNA expression of the two mouse insulin genes Ins1 and Ins2 was investigated in MIN6 cells treated with different concentrations of melatonin, and insulin secretion was detected under the same conditions. Following the overexpression or silencing of MTNR1B, the activities of components of the MAPK signaling pathway, including Raf‑1 and ERK, were evaluated. The impact of MTNR1B knockdown on the melatonin‑regulated insulin gene expression and insulin secretion were also investigated. The results demonstrated that exogenous melatonin inhibited the expression of insulin mRNA in the MIN6 cells. Insulin secretion by the MIN6 cells, however, was not affected by melatonin. The MAPK signaling pathway was inhibited in MIN6 cells by treatment with melatonin or the overexpression of MTNR1B. The knockdown of MTNR1B totally attenuated the regulating effect of melatonin on insulin gene expression. Additionally, the inductive effect of melatonin on the expression of insulin mRNA was attenuated when the activities of Raf‑1 or ERK were blocked using the chemical inhibitors GW5074 and U0126, respectively. It may be concluded that melatonin exerts an inhibitory effect on insulin transcription via MTNR1B and the downstream MAPK signaling pathway.

AIM: To identify the contribution of CDKAL1 to the development of diabetic retinopathy (DR) in Chinese population. METHODS: A case-control study was performed to investigate the genetic association between DR and polymorphic variants of CDKAL1 in Chinese Han population with type 2 diabetes mellitus (T2DM). A well-defined population with T2DM, consisting of 475 controls and 105 DR patients, was recruited. All subjects were genotyped for the genetic variant (rs10946398) of CDKAL1. Genotyping was performed by iPLEX technology. The association between rs10946398 and T2DM was assessed by univariate and multivariate logistic regression (MLR) analysis. RESULTS: There were significant differences in C allele frequencies of rs10946398 (CDKAL1) between control and DR groups (45.06% versus 55.00%, P

Personal calendar applications develop rapidly in recent years, while the enterprise calendar is lagging behind. This paper describes the protocol stack and content of standard calendar service, and then analyzes the similarities and differences between standard calendar and enterprise calendar from several perspectives such as the enterprise calendar scenarios, authorization structure and producing / consuming patterns of information. Considering the enterprise calendar features, we discuss the architectures of enterprise calendar from multiple angles - data architecture, authentication and authorization, daily management etc. Finally, we discuss several urgent tasks in the future.

Background Peroxisome proliferator-activated receptor gamma coactivator-1α (PPARGC1A/ PGC-1α) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. The activity of PGC-1α or genetic variations in the gene encoding the enzyme may contribute to individual variations in mitochondrial function and insulin resistance or diabetes. The objective of this study was to assess the extent to which PPARGC1A (rs8192678) and serum uric acid (UA) and its interaction impact on T2DM susceptibility in Chinese Han population. Method We conducted a study in a cohort that included 1166 T2DM patients and 1135 controls, and was genotyped for the presence of the PPARGC1A rs8192678 polymorphisms. Genotyping was performed by iPLEX technology. The association between rs8192678 or UA and T2DM was assessed by univariate and multivariate logistic regression (MLR) analysis controlling for confounders. The interaction between rs8192678 and UA for T2DM susceptibility was also assessed by MLR analysis. Results The generalized linear regression analysis failed to show an association between the PPARGC1A rs8192678 polymorphisms and T2DM. Interestingly, the present study provided data suggesting that the minor A-allele of PPARGC1A (rs8192678) had a protective effect against T2DM in subjects with higher level of UA (ORint =1.50 95% CI: 1.06-2.12 for allele and P = 0.02, ORint =1.63 95% CI: 1.17-2.26 for genotype and P = 0.004). Conclusion The combination of higher level of UA and PPARGC1A (rs8192678) was an independent predictor for T2DM.

For the universities' business system, to realize secure storage of historical data and long-term retention, saving high-end storage, online database backup pressure relief. A record-level data archiving method was proposed based on oracle dual database structure. This method included three aspects: related works, related technologies and strategy on data archive. For universities' business system, analysis of some problems need to concern and solution when the data archive, included four aspects: business analysis, storage analysis, data analysis and technical analysis. Finally, effectiveness of this method was validated by an application example in Tsinghua University. Index Terms—information flow, data management, data archiving, hierarchical storage management

Background The objective of this study was to systematically evaluate the contribution of the insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) to type 2 diabetes mellitus (T2DM) and its interaction with obesity to T2DM susceptibility. Methods To clarify whether IGF2BP2 is an independent risk factor for T2DM in Chinese population, we conducted a study with a total of 2,301 Chinese Han subjects, including 1,166 T2DM patients and 1,135 controls, for the genotype of a most common and widely studied polymorphism—rs4402960 of IGF2BP2. Genotyping was performed by iPLEX technology. Gene and environment interaction analysis was performed by using multiple logistic regression models. Results The repeatedly confirmed association between IGF2BP2 (rs4402960) and T2DM had not been replicated in this cohort (P = 0.182). Interestingly, we found that obese subjects (body mass index (BMI) ≥ 28.0 kg/m2) bearing the minor A allele had an increased risk to develop T2DM (P = 0.008 for allele analysis and P