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Diverse aerobic bacteria use atmospheric H2 as an energy source for growth and survival1. This globally significant process regulates the composition of the atmosphere, enhances soil biodiversity and drives primary production in extreme environments2,3. Atmospheric H2 oxidation is attributed to uncharacterized members of the [NiFe] hydrogenase superfamily4,5. However, it remains unresolved how these enzymes overcome the extraordinary catalytic challenge of oxidizing picomolar levels of H2 amid ambient levels of the catalytic poison O2 and how the derived electrons are transferred to the respiratory chain1. Here we determined the cryo-electron microscopy structure of the Mycobacterium smegmatis hydrogenase Huc and investigated its mechanism. Huc is a highly efficient oxygen-insensitive enzyme that couples oxidation of atmospheric H2 to the hydrogenation of the respiratory electron carrier menaquinone. Huc uses narrow hydrophobic gas channels to selectively bind atmospheric H2 at the expense of O2, and 3 [3Fe–4S] clusters modulate the properties of the enzyme so that atmospheric H2 oxidation is energetically feasible. The Huc catalytic subunits form an octameric 833 kDa complex around a membrane-associated stalk, which transports and reduces menaquinone 94 Å from the membrane. These findings provide a mechanistic basis for the biogeochemically and ecologically important process of atmospheric H2 oxidation, uncover a mode of energy coupling dependent on long-range quinone transport, and pave the way for the development of catalysts that oxidize H2 in ambient air.

Industry 4.0 (I4.0) is a relatively new and still emerging concept. Due to its novelty, companies find it extremely difficult to adopt I4.0 and reap the full benefit of the digital transformation of the fourth industrial revolution. Even though challenges to I4.0 adoption are well explored, the extant literature has hardly investigated the numerous human-based behavioural factors that are fundamental for I4.0 adoption. Human experience, engagement, and dedication to I4.0 adoption are crucial due to the complex nature of human behaviour and can significantly affect the success of I4.0 adoption. To address the gap, this paper aims to unveil the indispensable behavioural factors for I4.0 adoption and portray a hierarchical relationship among these factors. An extensive literature review is conducted to identify behaviour critical for I4.0 adoption to operationalise this research. Then, a decision support framework based on the Delphi technique and a revised rough DEMATEL method is used to map the relationships among the behavioural factors. The results reveal that the most critical behavioural factor to I4.0 adoption is “communication,” which is followed by “I4.0 training” and “resistance to I4.0 initiatives”. This study substantiates the research on I4.0 adoption and assists in I4.0 adoption. I4.0 adoption is also essential for a country’s competitiveness; therefore, the paper will support relevant policy formulation.

The electrochemical reduction of CO2 into useful fuels and chemical feedstocks offers great promise for conversion to a carbon-neutral economy. However, challenges in product selectivity continue to limit the practical application of electrocatalytic systems. In this Perspective, we outline the thermodynamic and kinetic factors for the design of improved catalysts for CO2 fixation and carbon–carbon bond formation, and draw parallels between synthetic systems and natural enzymes that perform analogous transformations. By identifying the primary features that underpin the highly efficient CO2 conversion reactions seen in nature, synthetic catalysts can be constructed to take advantage of similar chemical principles. Given the demonstrated prior success of bio-inspired molecular design, increased and dynamic interactions between the chemical, biological and materials science fields will advance catalyst development in a synergistic fashion. Electrochemical CO2 reduction is a complex process with many competing products, yet nature has evolved ways to overcome these issues. This Perspective makes connections between the motifs observed in nature and strategies that can be employed in synthetic systems for the advancement of selectivity in CO2 reduction.

Diffusion-weighted imaging (DWI) is a well-established MRI sequence for diagnosing early stroke and provides therapeutic implications. However, DWI yields pertinent information in various other brain pathologies and helps establish a specific diagnosis and management of other central nervous system disorders. Some of these conditions can present with acute changes in neurological status and mimic stroke. This review will focus briefly on diffusion imaging techniques, followed by a more comprehensive description of the utility of DWI in common neurological entities beyond stroke.

(Cu0.5-xKxTl0.5)Ba2Ca2Cu3-y-z ZnyCdzO10-δ (x = 0, 0.25; y = z = 0, 0.25, 0.5, 0.75, 1) samples are synthesized for the investigation of role of an-harmonic oscillations in the mechanism of high Tc superconductivity. In the conducting planes, the carrier density is enhanced by K doping at the charge reservoir layer (Cu0.5Tl0.5)Ba2O4-δ by synthesizing (Cu0.25K0.25Tl0.5)Ba2Ca2Cu3-y-zZnyCdzO10-δ (y = z = 0, 0.25, 0.5, 0.75, 1) samples. The (Cu0.5-xKxTl0.5)Ba2Ca2Cu3-y-z ZnyCdzO10-δ (x = 0, 0.25; y = z = 0, 0.25, 0.5, 0.75, 1) samples were prepared by employing two-step solid-state reaction method accomplished at 860 °C and understand their superconducting properties by resistivity measurements, X-ray diffraction analysis, and FTIR absorption measurements. The orthorhombic unit cell of our samples was confirmed via XRD analysis. The analysis also reflected the increase in c-axis length and the volume of the unit cell with the enhanced dopants (Cd and Zn) concentration. The suppression of Tc(onset) and Tc(R = 0) was found with the increasing concentration of Zn and Cd. An improvement in the Tc(onset) observed in samples doped by K that arises due to increase in the density of free carriers supplied by alkali atoms. With the increasing content of Cd and Zn, the unit cell exhibits the softening of Cu(1)-OA-Cu(2) and Tl-OA-Cu(2) apical oxygen mode and hardening of planar oxygen mode. From FIC analysis, the Tcmf and T* and various cross over temperature were shifted towards lower temperature with the enhanced Zn and Cd dopant concentration. The value of α determining the defect density also increases with the increasing dopant (Zn and Cd) concentration. The numerical values of different parameter like Bc0(T), Bc1(T), Jc(0), and Ebreak showing increasing trend but the phase relaxation time of the carriers τφ points out decreasing trend with the enhanced doping of Cd and Zn. Moreover, these parameters reflected inferior values in K-doped samples relative to K-undoped samples. The value of other parameter like coherence length ξc(0) along c-axis, interlayer coupling J, magnetic field penetration depth λp.d, the Ginzburg Landau (GL) parameter κ, and the Fermi velocity VF of the carriers decreases as doping of Zn and Cd enhanced. These parameters show superior values in K-doped samples relative to K-undoped samples due to increase in the density of free carriers supplied by K atoms. The negative values of real part of dielectric constant suppress in both K undoped and K doped samples with increasing concentration of Cd and Zn. The imaginary part of dielectric constant and ac conductivity showing suppression in their negative values in K undoped samples while showing increase in absolute values in K doped samples with increasing concentration of Cd and Zn.

The RAPID© software is the most commonly used computed tomography perfusion (CTP) software in stroke centers. It is estimated that about 1300 hospitals in the world are using this software for decision-making in ischemic stroke. The software provides the estimated volume of infarction and ischemic penumbra, so it is the backbone of treatment planning in these patients. In this manuscript, we present two cases of subacute infarction with misleading CTP using RAPID© software. We believe that given the popularity of this software and increasing application of CTP in subacute infarction, this pitfall is likely underdiagnosed in many patients. In a subacute phase of infarction, we recommend diffusion-weighted imaging magnetic resonance imaging (DWI-MRI) for estimation of infarction to avoid this pitfall and possible mismanagement.

The Mucopolysaccharidoses (MPS) are group of inherited metabolic diseases caused by the deficiency of enzymes required to degrade glycosaminoglycans (GAGs) in the lysosomes. GAGs are sulfated polysaccharides involving repeating disaccharides, uronic acid and hexosamines including chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS) and keratan sulfate (KS). Hyaluronan is excluded in terms of being non-sulfated in the GAG family. Different types of mutations have been identified as the causative agent in all types of MPS. Herein, we planned to investigate the pathogenic mutations in different types of MPS including type I (IDUA gene), IIIA (SGSH) and IIIB (NAGLU) in the eight Iranian patients. Autozygosity mapping was performed to identify the potential pathogenic variants in these 8 patients indirectly with the clinical diagnosis of MPSs. so three panels of STR (Short Tandem Repeat) markres flanking IDUA, SGSH and NAGLU genes were selected for multiplex PCR amplification. Then in each family candidate gene was sequenced to identify the pathogenic mutation. Our study showed two novel mutations c.469 T > C and c.903C > G in the IDUA gene, four recurrent mutations: c.1A > C in IDUA, c.220C > T, c.1298G > A in SGSH gene and c.457G > A in the NAGLU gene. The c.1A > C in IDUA was the most common mutation in our study. In silico analysis were performed as well to predict the pathogenicity of the novel variants.

Microelectromechanical System (MEMS) based complaint displacement amplification mechanism capable of producing different displacement amplification factors in three different configurations is designed and experimented. Microprobe system having an acupuncture needle and high-resolution camera has been used to measure displacements, forces and stiffness of the designed mechanism. Configuration 1 gives amplification factor 7.6 with natural frequency of 222.13 kHz. Configuration 2 amplifies displacement 16 times with natural frequency of 258.62 kHz. Amplification factor of 16.14 and natural frequency of 215.51 kHz is achieved with 3rd configuration. Modal analyses of all the three configurations of the mechanism match well with the experimental values. The mechanism is analytically modeled and simulated using Finite Element Method techniques and fabricated using commercially available fabrication process PolyMUMPs. Kinematic sensitivity and performance analysis of the proposed mechanism is carried out to predict the behavior of mechanism with respect to different geometric parameters. The results show that with increasing angle of flexure, amplification factor decreases, and it becomes constant at angles higher than 6° with increasing input displacement. It further shows a significant change in amplification factor with increasing length but after 600 μm the change in amplification factor becomes insignificant. Analyses results demonstrate the viability of mechanism as a displacement amplification mechanism. A good agreement is found between numerical and experimental results. This amplification mechanism can be used independently or integrated with any conventional actuation as well as sensing mechanism in a microsystem where amplified displacement is desired for improved sensitivity and performance.

Urokinase plasminogen activator receptor (uPAR) is implicated in tumor growth and metastasis due to its ability to activate latent growth factors, proteases, and different oncogenic signaling pathways upon binding to different ligands. Elevated uPAR expression is correlated with the increased aggressiveness of cancer cells, which led to its credentialing as an attractive diagnostic and therapeutic target in advanced solid cancer. Here, we examine the antitumor effects of a humanized anti-uPAR antibody (huATN-658) alone and in combination with the approved bisphosphonate Zometa (Zoledronic acid) on skeletal lesion through a series of studies in vitro and in vivo. Treatment with huATN-658 or Zometa alone significantly decreased human MDA-MB-231 cell proliferation and invasion in vitro, effects which were more pronounced when huATN-658 was combined with Zometa. In vivo studies demonstrated that huATN-658 treatment significantly reduced MDA-MB-231 primary tumor growth compared with controls. In a model of breast tumor-induced bone disease, huATN-658 and Zometa were equally effective in reducing skeletal lesions. The skeletal lesions were significantly reduced in animals receiving the combination of huATN-658 + Zometa compared with monotherapy treatment. These effects were due to a significant decrease in osteoclastic activity and tumor cell proliferation in the combination treatment group. Transcriptome analysis revealed that combination treatment significantly changes the expression of genes from signaling pathways implicated in tumor progression and bone remodeling. Results from these studies provide a rationale for the continued development of huATN-658 as a monotherapy and in combination with currently approved agents such as Zometa in patients with metastatic breast cancer.

Transportation sector with the consumption of 25% of energy play a major role in Iranian economy. This sector produces 27% of total undesirable greenhouse gases in Iran which has directly harmful effects on the environment. Hence, performance assessment of energy efficiency of transportation sector is one of the most important issues for policy makers. In this paper, energy efficiency of transportation sector of 20 provinces in Iran is evaluated based on data envelopment analysis (DEA)—cooperative game approach. First, selected inputs and outputs are categorized into energy and non-energy inputs and desirable and undesirable outputs. Then, classical DEA model is applied to evaluate and rank the provinces. Since, the classical DEA model can’t distinguish between efficient provinces, so, this paper ranks the provinces based on combination of cross-efficiency DEA and cooperative game approaches. In the cooperative game theory, each province is considered as a player and the suitable characteristic function is defined for players. Finally, by calculating the Shapley value for each player, the final ranks of transportation sectors in provinces are concluded. The results indicate that some smaller provinces have better energy efficiency in transportation sector in comparison with big provinces.

Massive integration of biosensors into design of Internet-of-Things (IoT) is vital for progress of healthcare. However, the integration of biosensors is challenging due to limited availability of battery-less biosensor designs. In this work, a combination of nanomaterials for wireless sensing of biological redox reactions is described. The design exploits silver nanoparticles (AgNPs) as part of the RFID tag antenna. We demonstrate that a redox enzyme, particularly, horseradish peroxidase (HRP), can convert AgNPs into AgCl in the presence of its substrate, hydrogen peroxide. This strongly changes the impedance of the tag. The presented example exploits gold nanoparticle (AuNP)-assisted electron transfer (ET) between AgNPs and HRP. We show that AuNP is a vital intermediate for establishing rapid ET between the enzyme and AgNPs. As an example, battery-less biosensor-RFID tag designs for H2O2 and glucose are demonstrated. Similar battery-less sensors can be constructed to sense redox reactions catalysed by other oxidoreductase enzymes, their combinations, bacteria or other biological and even non-biological catalysts. In this work, a fast and general route for converting a high number of redox reaction based sensors into battery-less sensor-RFID tags is described.

The methanol extract of the bark of Entada rheedii has been fractionated to afford petroleum ether, dichloromethane, ethyl acetate and aqueous soluble fraction through modified Kupchan partitioning protocol and those fractions has been subjected to repeated-chromatographic separation by Sephadex size exclusion chromatography and purification processes to isolate the secondary metabolites. A total of seven compounds have been isolated from the bark of E. rheedii, which were identified as epicatechin (1), liquiritigenin (2), glabridin (3), 4′-O-methylglabridin (4), isoliquiritigenin (5), hispaglabridin A (6) and shinflavanone (7). This is the first report of isolation of these compounds from E. rheedii.

Introduction Deregulation of the cell cycle machinery is often found in human cancers. Modulations in the cell cycle regulator function and expression result not only in proliferative advantages, but also lead to tumor progression and invasiveness of the cancer. In particular, cyclin D1 and p21 are often over-expressed in human cancers, correlating with high tumor grade, poor prognosis and increased metastasis. This prompted us to investigate the role of the cyclin D1/p21 signaling axis downstream of transforming growth factor beta (TGFβ) in breast cancer progression. Methods Cyclins mRNA and protein expressions were assessed by quantitative real-time PCR and Western blot in triple negative breast cancer cell lines. Co-localization and interaction between cyclin D1 and p21 were performed by immunocytochemistry and co-immunoprecipitation, respectively. Cell migration was assessed by wound healing and quantitative time-lapse imaging assays. In addition, the effects of cyclin D1 on cellular structure and actin organization were examined by staining with F-actin marker phalloidin and mesenchymal intermediate filament vimentin. Finally, a mammary fat pad xenograft mouse model was used to assess mammary tumor growth and local invasion. Results We found TGFβ to specifically up-regulate the expression of cyclin D1 in triple negative breast cancer cells. Induction of cyclin D1 is also required for TGFβ-mediated cell migration. Suppression of cyclin D1 expression not only resulted in a rounded and epithelial-like phenotype, but also prevented TGFβ-induced vimentin and F-actin co-localization at the cell edge as well as invadopodia formation. Furthermore, TGFβ promoted the nuclear co-localization and physical interaction between cyclin D1 and p21. The co-expression of cyclin D1 and p21 proteins are required for the initial steps of tumor development, as double knockdown of these two molecules prevented primary tumor formation in a Xenograft mouse model. Moreover, the in vivo studies indicated that locally advanced features of the invasive tumors, including skeletal muscle, mammary fat pad and lymphovascular invasion, as well as ulcerated skin, were attenuated in the absence of cyclin D1 and p21. Conclusions Thus, our findings highlight the cyclin D1/p21 signaling axis as a critical regulator of TGFβ-mediated tumor growth initiation and local tumor cell invasion, both in vitro and in vivo.

Cellular senescence is characterized by a permanent cell-cycle arrest and a pro-inflammatory secretory phenotype, and can be induced by a variety of stimuli, including ionizing radiation, oxidative stress, and inflammation. In endothelial cells, this phenomenon might contribute to vascular disease. Plasma levels of the inflammatory cytokine tumor necrosis factor alpha (TNFα) are increased in age-related and chronic conditions such as atherosclerosis, rheumatoid arthritis, psoriasis, and Crohn’s disease. Although TNFα is a known activator of the central inflammatory mediator NF-κB, and can induce the intracellular generation of reactive oxygen species (ROS), the question whether TNFα can induce senescence has not been answered conclusively. Here, we investigated the effect of prolonged TNFα exposure on the fate of endothelial cells and found that such treatment induced premature senescence. Induction of endothelial senescence was prevented by the anti-oxidant N-acetyl cysteine, as well as by plumericin and PHA-408, inhibitors of the NF-κB pathway. Our results indicated that prolonged TNFα exposure could have detrimental consequences to endothelial cells by causing senescence and, therefore, chronically increased TNFα levels might possibly contribute to the pathology of chronic inflammatory diseases by driving premature endothelial senescence.

The performance of micro-machined sensors is primarily determined via the sensitivity of sensing electrode to displacement. This paper presents the design, modelling, optimization and fabrication of an active gap reduction mechanism used on a conventional comb drive to enhance the capacitance in a three axes capacitive micro accelerometer. The design parameters of the active gap reduced comb drive (AGRCD) are optimized for best performance. The finite element analysis of the AGRCD is performed for design verification. The modeling and simulation results demonstrated a 534 % increase in sensitivity of the three axes capacitive micro accelerometer. The three axes capacitive micro accelerometer with AGRCD is fabricated using a commercially available standard metal-multi user MEMS processes.

Tailor-welded blanks (TWBs) consisted of metal sheets with different characteristics welded into a single flat blank prior to pressing in order to achieve the optimal material arrangement and weight reduction for cars, and to increase machine flexibility and process efficiency. The movement of weld line in TWBs is always a challenging issue during manufacturing process. In this research, a new analytical method for prediction of weld line movement in TWBs is developed. A comparison between the analytical results with those obtained from finite element simulation as well as the experimental data indicates good compatibility between the predictions of the developed method in the case of both weld line movement and dome height of TWBs. Furthermore, the developed analytical method can appropriately consider the effect of thickness ratio on both weld line movement and dome height. It was observed that weld line movement increases as thickness ratio enhances.

The complete mathematical modeling and design verification of a novel monolithically integrated tri-axes MEMS capacitive accelerometer is presented in this paper. The designed accelerometer is a single structure having three individual single axis accelerometers, integrated on a single substrate uniformly centered on single axis with chip size of 3.2 mm × 3.5 mm. We have used standard commercially available surface micromachining technology MetalMUMPs available from MEMSCAP Inc. The designed accelerometer is optimized by analytical technique using Matlab. The physical level simulation is done in the Analyzer module of CoventorWare to verify the structural model of designed accelerometer. It is concluded that the results obtained from the physical level simulation are in good agreement with the analytically calculated results. The design has been successfully verified using the Finite Element Analysis.

Lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) are one of the most common urologic disorders in men. Accurate history-taking and focused physical examination allows us to diagnose the majority of cases. A better understanding of risk factors helps us tailor our treatment and predict outcomes more accurately. Population studies are crucial in our understanding of LUTS/BPH natural history. Temporary prostatic urethral stents that are used for the management of urinary retention may also be used for evaluation of patients with detrusor hypo-contractility. The use of ultrasound to measure intravesical prostatic protrusion (IPP) and the Doppler study for prostate capsular artery resistive index are promising. Near-infrared spectroscopy (NIRS) examines the tissue oxygenation that may be affected by bladder outlet obstruction. The mathematical algorithm needs some fine-tuning, and its reproducibility is debatable. Serum and urinary biomarkers may help us to diagnose the disorder, and more effectively monitor patients' response to therapy. Among all, IPP is clinically more applicable at this time.

Forming limit diagrams (FLDs) are extensively used in industries, particularly the auto industry. The establishment of these diagrams using a predictive approach can lead to reduction in both cost and time. In the present work, Gurson-Tvergaard-Needleman (GTN), a porosity-based model, was used to predict the FLD of an interstitial-free steel via finite element simulation. Optimum values of the GTN model were obtained by applying a response surface methodology (RSM) based on central composite design. Results show that RSM is a good method for an appropriate determination of the GTN model parameters, such as initial void volume fraction, effective void volume fraction, critical void volume fraction, and final void volume fraction. Furthermore, the experimental FLD of the specimen steel was considerably predicted using the obtained GTN model parameters.

This paper presents design of a structurally decoupled 3-DoF non-resonant MEMS gyroscope with increased robustness and gain. The proposed design utilizes dynamic amplification in 2-DoF drive mode oscillator to achieve large gain. The device performance is verified through behavioral model simulations considering the fabrication limitations of standard electroplated nickel micromachining process, MetalMUMPs, of 20 μm structural layer thickness. A wide operational bandwidth of 1.74 kHz with dynamically amplified again of 0.2 μm is achieved at low actuation voltages. A design sensitivity and Monte Carlo analysis is carried out to show the robustness of the design, without any feedback control, within the fabrication process tolerances. Moreover to verify the device performance under the application of angular velocity, a rate table characterization is carried out which resulted in sense mass displacement of 30 nm corresponding to the rotation induced Coriolis force at actuation voltage of 20 $$V_{ac}$$ and 30 $$V_{dc}$$ with angular rotation of 50 rad/s. Behavioral model simulations proved to be an cost-effective and time-saving alternative to the traditional iterative fabrications and physical level simulations.