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Myelofibrosis (MF), a complex hematological malignancy, presents a diverse array of symptoms, including anemia, constitutional symptoms, bone marrow insufficiency, and splenomegaly. The latter, often necessitating blood transfusions, poses an essential obstacle to MF management. While conventional approaches predominantly involve the use of JAK inhibitors, the potential for exacerbating anemia introduces complexity to the treatment. Nonetheless, Momelotinib stands out as a promising pharmaceutical compound with the potential to revolutionize the field. Momelotinib is an ACVR1 antagonist and a dual inhibitor of the JAK1 and JAK2 enzymes. By targeting MF's hematological and fibrotic aspects, Momelotinib influences iron metabolism by regulating hepcidin. This results in reduced hepcidin expression and increased iron availability, ultimately leading to improved anemia and reduced dependency on blood transfusion. This study aims to provide a concise overview of the pathogenesis of MF and elucidate the mechanism of action of Momelotinib. Subsequently, our review offers a practical summary encompassing the effects of Momelotinib in monotherapy, combined comparative drug therapy, and its associated side effects. Additionally, we explore the application of Momelotinib in other cancer types and investigate predictors for treatment success. Furthermore, we examine the utilization of Momelotinib in patients with liver and kidney failure. Highlights: MF is a complex hematological malignancy that has the potential to transform into acute myeloid leukemia in 20 % of cases Anemia occurs in approximately one-third of MF patients Momelotinib is a novel ACVR1 antagonist and a dual inhibitor of the JAK1 and JAK2 enzymes just FDA approved on September 15 A comprehensive applied review of this novel agent is lacking [ABSTRACT FROM AUTHOR]

Origin recognition complex (ORC)-dependent loading of the replicative helicase MCM2-7 onto replication origins in G1-phase forms the basis of replication fork establishment in S-phase. However, how ORC and MCM2-7 facilitate genome-wide DNA licensing is not fully understood. Mapping the molecular footprints of budding yeast ORC and MCM2-7 genome-wide, we discovered that MCM2-7 loading is associated with ORC release from origins and redistribution to non-origin sites. Our bioinformatic analysis revealed that origins are compact units, where a single MCM2-7 double hexamer blocks repetitive loading through steric ORC binding site occlusion. Analyses of A-elements and an improved B2-element consensus motif uncovered that DNA shape, DNA flexibility, and the correct, face-to-face spacing of the two DNA elements are hallmarks of ORC-binding and efficient helicase loading sites. Thus, our work identified fundamental principles for MCM2-7 helicase loading that explain how origin licensing is realised across the genome. Correct loading of the MCM2-7 helicase is crucial for DNA replication and cell cycle progression. Here, the authors used high-resolution genomics to demonstrate how ORC is displaced from origins, which serves as a mechanism for distributive MCM loading onto DNA. [ABSTRACT FROM AUTHOR]

Economists have hypothesized that currency appreciation resulting from oil production in oil-rich countries can suppress the production of tradable goods, a phenomenon known as Dutch disease, often assessed using econometric models. This study leverages sanctions on Iranian oil exports, employing a quasi-experimental design with two distinct periods (1959–2020): one marked by sanctions (oil revenue recession) and the other by non-sanctions (oil revenue boom). The result shows a reversal of the Dutch disease effect during sanctions, leading to a real depreciation of the national currency and heightened production of tradable goods over non-tradable ones. The observed pattern of the real exchange rate aligns with Dutch disease dynamics, depreciating during sanctions and appreciating during non-sanction periods. Furthermore, the tradable sector exhibited increased share and real output growth compared to the non-tradable sector during the sanction period. [ABSTRACT FROM AUTHOR]

In this study, the efficacy of sublingual squalene in decreasing the mortality rate among patients with COVID-19 was investigated. Squalene was extracted from pumpkin seed oil with a novel method. Then, the microemulsion form of squalene was prepared for sublingual usage. In the clinical study, among 850 admitted patients, 602 eligible COVID-19 patients were divided in two groups of control (N = 301) and cases (N = 301) between Nov 2021 and Jan 2022. Groups were statistically the same in terms of age, sex, BMI, lymphocyte count on 1st admission day, hypertension, chronic kidney disease, chronic respiratory disease, immunosuppressive disease, and required standard treatments. The treatment group received five drops of sublingual squalene every 4 h for 5 days plus standard treatment, while the control group received only standard treatment. Patients were followed up for 30 days after discharge from the hospital. The sublingual form of squalene in the microemulsion form was associated with a significant decrease in the mortality rate (p < 0.001), in which 285 (94.7%) cases were alive after one month while 245 (81.4%) controls were alive after 1 month of discharge from the hospital. In addition, squalene appears to be effective in preventing re-hospitalization due to COVID-19 (p < 0.001), with 141 of controls (46.8%) versus 58 cases (19.3%). This study suggests sublingual squalene in the microemulsion as an effective drug for reducing mortality and re-hospitalization rates in COVID-19 patients. Trial Registration Number: IRCT20200927048848N3. [ABSTRACT FROM AUTHOR]

This study used a simple co-precipitation method to fabricate a novel polymer-based photocatalyst that displayed effective photocatalytic activity towards the degradation of methylene blue (MB) solution under visible light irradiation. Due to its excellent properties, intrinsic polarization, and asymmetric structure, polyphenylene sulfide (PPS) was utilized in the magnetic ternary PPS/PVA/Fe3O4 nanocomposite. The analytical techniques confirmed the desirable combination of the photo-initiated Fe3O4 nanoparticles as the strong oxidizers with the high adsorption capacity of PPS and the binding and conductive effects of polyvinyl alcohol (PVA). Binary nanocomposites of PPS/Fe3O4 and PVA/Fe3O4 were also prepared to compare their photocatalytic activities with that of the PPS/PVA/Fe3O4 sample. The optimum degradation occurred in PPS/PVA/Fe3O4, reaching 83% after 120 min. Its superior activity was attributed to the synergistic interactions, such as broader absorption of visible light, suppression of electron-hole pair recombination, and increment in the surface area of the mesoporous catalyst. Based on the effects of scavengers, it was concluded that hydroxyl radicals had a vital role in the photodegradation of methylene blue. Kinetically, the photocatalytic activity of PPS/PVA/Fe3O4 followed the pseudo-first-order kinetic model, which was about 3.9 and 3.1 times greater than those of PPS and PPS/Fe3O4, respectively. More specifically, the superparamagnetic behavior of PPS/PVA/Fe3O4 helped to be recovered with an external magnetic field and showed good reusability and stability after four successive runs. The current work suggests that PPS-based photocatalysts can provide promising opportunities for the photocatalytic degradation of organic pollutants and opens up a new perspective on water treatment. [ABSTRACT FROM AUTHOR]

This paper presents an analytical model to investigate the static behaviour of sandwich plates comprised of two isotropic face sheets and a honeycomb core. Through-thickness transverse shear stresses were considered using a unified displacement field with which various plate theories were implemented, i.e., exponential, third-order, hyperbolic, sinusoidal, fifth-order, Mindlin, and the classic plate theory. The equilibrium equations of a simply-supported sandwich panel were derived using the principle of virtual work and Navier solution was obtained under static transverse loading. After validating of the model, various mechanical and geometrical parameters were varied to characterise the behaviour of the structure under regular and auxetic response. It was found that the auxeticity of the core strongly affects the mechanical response, e.g., in controlling deflection, in-plane anisotropy, and Poisson's ratio. Cell wall angle was found to be most critical parameter that can be used to adjust anisotropy, out-of-plane shear modulus, transverse shear stress distribution, and deflection of the panel. Also the cell aspect ratio controls the sensitivity of the core response to other geometrical variations. In terms of the higher-order theories, the deflection-dependent parameter of the unified formulation seems to have more control of maximum deflection compared to independent rotations. Auxeticity of the core showed some benefits in controlling anisotropy, deflection and providing additional out-of-plane shear rigidity. Overall, since there is not one-to-one relationship between specific values of Poisson's ratio, anisotropy, and shear rigidity, careful design considerations must be invested to obtain a correct mechanical response. [ABSTRACT FROM AUTHOR]

Object detection is considered as one of the most important applications of deep learning. However, the object detection techniques lose their effectiveness and reliability when they fall victim to adversarial attacks. This big flaw has made it challenging to fully adopt the object detection applications in important products and essential industries such as autonomous vehicles. While the field of adversarial robustness has witnessed a great deal of achievement in building sophisticated methods of attack and defense, the majority of the work has been focused on the task of image classification due to its simplicity in theory and practice. In this paper, we provide an up-to-date survey of recent advancements in the field of adversarial robustness for object detection. We review the prominent attack and defense mechanisms presented in the research community and provide discussions and insights on their strengths and weaknesses. In addition, we review the recent literature on adversarial robustness for applications related to autonomous vehicles, as a critical aspect of this high-impact emerging industry, in which the robustness of models is of vital importance. [ABSTRACT FROM AUTHOR]

Pharmaceutical wastewater treatment is an essential component of environmental protection and sustainable development. In this study, our aim was to investigate the morphology, characterization, and effectiveness of TiO2/graphene composite nanofiber photocatalysts in the treatment of pharmaceutical wastewater containing three different pharmaceutical groups, such as an antibiotic (rifampin), painkiller (phenazopyridine), and immunosuppressant (azathioprine). Various parameters such as pH, salt concentration, and initial pharmaceutical compound concentration were optimized to achieve maximum degradation kinetics and efficiency. The optimum conditions were determined to be 1.5% graphene content, 30 ppm initial concentration of pharmaceutical compound, pH=5, and a 0.5 g/L photocatalyst dose. The presence of salt slightly decreased the degradation kinetics, but it did not significantly affect the performance of the TiO2/graphene composite nanofibers photocatalyst. At optimum condition, TiO2/1.5% graphene composite nanofibers degraded 50% of phenazopyridine, 86.89% of rifampin, and completely azathioprine. Comparing with phenazopyridine, N heteroatom-rich molecule of azathioprine and hydroxyl-rich molecule of rifampin lead to being susceptible to photocatalytic degradation. The reuse of the photocatalyst in multiple cycles showed consistent performance, indicating its potential for practical and economic applications. [ABSTRACT FROM AUTHOR]

This paper compares the processing characteristics of advanced CMT (cold metal transfer) and conventional GMAW-S (gas metal arc welding with short-circuit metal transfer) processes for depositing Ni-WC MMC (nickel-based metal matrix composites reinforced with WC) overlays. In contrast to common expectations, advanced CMT technology with mechanically assisted droplet transfer could not demonstrate significant advantages over the GMAW-S process; on the contrary, CMT exhibits marginal disadvantages in terms of carbide transfer efficiency, volume fraction of retained WC, and deposition rate. Some carbides originally contained in the core of the feed wire are blown away and expelled out of the processing zone leading to physical losses of WC particles during the deposition processes, which is more significant for the CMT process owing to much higher waveform cycle frequency and cyclic feed wire retractions. CMT exhibits superior waveform stability, better control over penetration depth, marginally lower dilution level, and exceptional arc stability. The main parameters affecting carbide transfer efficiency and volume fraction of retained WC are wire feed speed and travel speed for both processes; increased wire feed speed and travel speed generally lead to decreased carbide transfer efficiency and reduced volume fraction of retained WC. Shielding gas may have different effects on the outcomes for the CMT and GMAW-S processes. CMT overlays show comparatively higher W and lower Fe concentration in the matrix, while GMAW-S overlays show a higher concentration of Fe in the matrix (due to elevated dilution level) with marginally higher matrix microhardness and more herringbone-like secondary carbide precipitates. [ABSTRACT FROM AUTHOR]

In this study, mechanical properties of lead core rubber bearing (LCRB) under variable pulse-like ground motions have been optimized to minimize the response quantities of interest at the level of the base isolation system, e.g., bearing acceleration and bearing displacement. Since the isolator period, effective damping ratio, superstructure mass, design displacement, and yielding displacement are major parameters that characterize the general behavior of the base isolation system, they have been selected as random variables. A single degree of seismically-isolated building as a shear beam-stick model has been implemented. Then, the dynamic response of the seismic isolation system is investigated considering the variability of mechanical properties of LCRB and superstructure mass over the base isolation system. In this investigation, the isolation device is developed using the Bouc–Wen model of hysteresis. To this end, Monte Carlo simulation has been conducted to provide comprehensive insight into the variability of seismic responses. Thus, 37,800 time-history analyzes have been performed and the effect of levels of uncertainty of the input parameters on the seismically isolated building's dynamic response is studied for 126 natural pulse-like ground motions whose pulse periods are between 0.6 and 13 s. Moreover, to find the best compound properties of LCRB parameters, the "desirability function optimization" method has been employed. Finally, the behavior of the LCRB has been optimized and increased its effectiveness to reduce the response criteria considering uncertainties in natural excitation parameters. [ABSTRACT FROM AUTHOR]

This study focused on the spatial effects of CO2 determinants, using data from 43 European countries between 1996 and 2018. Tests proved the existence of the spatial Durbin model. The findings indicate that the logarithm of GDP per capita, urbanization, and energy use have enhancing effects on CO2 emissions, but that these effects are meaningless for trade openness. Most of the coefficients provided insignificant results, while six financial development indicators were entered into the model in a straight line. The addition of the term "interaction between energy intensity and financial development" improved the effects of all of the components significantly. The phrase's negative and significant coefficient predicts increased energy intensity efficiency as a result of the development of multiple financial production components. The analysis of spatial effects reveals that control variables in adjacent countries have negligible effects on CO2 emissions. Overall, the findings show that CO2 emissions are falling as neighboring countries' productivity and financial development rise. The findings indicate that financial development in neighboring countries has comparable effects on CO2 emissions as domestic financial development. As a result of these findings, European countries have reached a point of financial integration. [ABSTRACT FROM AUTHOR]

When pursuing a controversial socio-scientific issue, readers are expected to construct balanced representations that include overlapping and opposing information. However, readers' mental representations are often biased towards their prior beliefs. Previous research on such text-belief consistency effects have been conducted mostly in monolingual contexts. The present study investigated whether document language, as a source characteristic, moderates text-belief consistency effects at the situation-model and text-base representation levels. Eighty-seven bilingual readers—selected from a larger initial sample—read two documents on the global spread of English. The documents were either presented in participants' first (Persian) and second (English) languages, or one was presented in Persian and the other one in English. A recognition task was used to assess situation-model strength and text-base strength. Overall, participants built stronger situation models for the belief-consistent information as opposed to belief-inconsistent information. However, document language moderated the text-belief consistency effect. When both texts were presented in English, the text-belief consistency effect was smaller than when both texts were presented in Persian. For the combination of English and Persian texts, the text-belief consistency effect was enlarged when the belief-consistent text was presented in English and the belief-inconsistent text in Persian but disappeared when the text-belief consistent text was presented in Persian and the belief-inconsistent text in English. These results suggest that document language can serve as a strong credibility cue that can eliminate belief effects, at least when the document language and the controversial issue are inherently related. [ABSTRACT FROM AUTHOR]

Biomechanical study of brain injuries originated from mechanical damages to white matter tissue requires detailed information on mechanical characteristics of its main components, the axonal fibers and extracellular matrix, which is very limited due to practical difficulties of direct measurement. In this paper, a new theoretical framework was established based on microstructural modeling of brain white matter tissue as a soft composite for bidirectional hyperelastic characterization of its main components. First the tissue was modeled as an Ogden hyperelastic material, and its principal Cauchy stresses were formulated in the axonal and transverse directions under uniaxial and equibiaxial tension using the theory of homogenization. Upon fitting these formulae to the corresponding experimental test data, direction-dependent hyperelastic constants of the tissue were obtained. These directional properties then were used to estimate the strain energy stored in the homogenized model under each loading scenario. A new microstructural composite model of the tissue was also established using principles of composites micromechanics, in which the axonal fibers and surrounding matrix are modeled as different Ogden hyperelastic materials with unknown constants. Upon balancing the strain energies stored in the homogenized and composite models under different loading scenarios, fully coupled nonlinear equations as functions of unknown hyperelastic constants were derived, and their optimum solutions were found in a multi-parametric multi-objective optimization procedure using the response surface methodology. Finally, these solutions were implemented, in a bottom-up approach, into a micromechanical finite element model to reproduce the tissue responses under the same loadings and predict the tissue responses under unseen non-equibiaxial loadings. Results demonstrated a very good agreement between the model predictions and experimental results in both directions under different loadings. Moreover, the axonal fibers with hyperelastic characteristics stiffer than the extracellular matrix were shown to play the dominant role in directional reinforcement of the tissue. [ABSTRACT FROM AUTHOR]

Despite significant breakthroughs in diagnosis and treatment of colorectal cancer (CRC), the extent of morbidity and mortality secondary to CRC is still concerning. In this study, we evaluated the efficacy of our new tumor-selective nanoplatforms at induction of apoptosis and autophagy, which was tested using active 5-fluorouracil (5-Fu)-based targeting of tumor cells in a BALB/c murine model of CRC combined with magnetic thermal therapy. Nanoparticles were synthesized and characterized by zeta sizer, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The cytotoxicity and tissue uptake of 5-Fu-loaded folic acid (Fa)-modified magnetic nanoparticles (5-Fu/MNPs-Fa) was assessed using MTT, ICP-OES, and HPLC. The rate of apoptosis and autophagy, as two major indicators of antitumor activity, was measured based on protein expression of Bax, Bcl2, Caspase 3, mTOR, P-mTOR, Beclin-1, and LC3B in CT-26 murine CRC, along with tumor volume and survival time. The spherical 5-Fu/MNPs-Fa exhibited sustained thermal on/off switching drug release and higher therapeutic index compared to free 5-Fu. Our de novo synthetized magnetic nanoheaters successfully delivered the therapeutic agent to the tumor site, enhanced the conversion of radio frequency energy to heat in tumor cells, exhibited higher antitumor efficiency based on Bax/Bcl2 ratio and overexpression of Beclin-1 and LC3B, increased the survival time, and decreased the tumor volume (P < 0.05). Our findings indicated that magnetochemotherapy (MHC) was substantially more effective than hyperthermia and/or chemotherapy alone. From a translational standpoint, the 5-Fu/MNPs-Fa would be a promising candidate sustained drug targeting system that could improve cancer cell therapy via inducing apoptosis and autophagy. [ABSTRACT FROM AUTHOR]

The cost of software maintenance is heavily influenced by program understanding. When the source code is the only product accessible, maintainers spend a significant amount of effort trying to understand the structure and behavior of the software. Program module clustering is a useful reverse-engineering technique for obtaining the software structural model from source code. Finding the best clustering is regarded as an NP-hard optimization problem, and several meta-heuristic methods have been employed to solve it. The fundamental flaws of the prior approaches were their insufficient performance and effectiveness. The major goals of this research are to achieve improved software clustering quality and stability. A new method (Düzen) is proposed in this research for improving software module clustering. As a meta-heuristic memetic algorithm, this technique employs the shuffled frog-leaping algorithm. The Düzen results were investigated and compared to those produced using earlier approaches. In terms of obtaining the best clustering quality, the proposed method was shown to be better and more successful than the others; it also had higher data stability and data convergence to optimal replies in a fewer number of repetitions. Furthermore, it acquired a higher data mean and a faster clustering execution time. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) reactivation remains a common opportunistic infection with a prominent role in immune reconstitution in organ transplant recipients. CMVs as important drivers of natural killer (NK) cell differentiation has been indicated to prompt several phenotypic and functional alteration in these cells. We aimed to monitor the reconstitution of NK cells and change the signature of inflammatory proteins at the critical phase of CMV reactivation over six months after kidney transplantation. The present study indicated that CMV reactivation is associated with the development of IL-6, IL-10, and cytotoxic granules, including granzyme-B and granulysin, and the drop in the frequency of CD16 + NKG2A-CD57 + NK cell subset in kidney transplant recipients (KTRs) with reactivation versus non- reactivated ones. Our findings describe distinct immune signatures that emerged with CMV reactivation after kidney transplantation, which may be helpful in the timely management of CMV infection in KTRs. [ABSTRACT FROM AUTHOR]

Diabetic neuropathy (DN) is the most challenging microvascular complication of diabetes and there is no suitable treatment for it, so the development of new agents to relieve DN is urgently needed. Since oxidative stress and inflammation play an essential role in the development of DN, clearance of these factors are good strategies for the treatment of this disease. According to key role of cyclic adenosine monophosphate (cAMP) in the regulation of oxidative stress and inflammatory pathways, it seems that phosphodiesterase inhibitors (PDEIs) can be as novel drug targets for improving DN through enhancement of cAMP level. The aim of this study was to evaluate the effects of rolipram, a selective PDE4 inhibitor, and pentoxifylline, a general PDE inhibitor on experimental model of DN and also to determine the possible mechanisms involved in the effectiveness of these agents. We investigated the effects of rolipram (1 mg/kg) and pentoxifylline (100 mg/kg) and also combination of rolipram (0.5 mg/kg) and pentoxifylline (50 mg/kg), orally for five weeks in rats that became diabetic by STZ (55 mg/kg, i.p.). After treatments, motor function was evaluated by open-field test, then rats were anesthetized and dorsal root ganglion (DRG) neurons isolated. Next, oxidative stress biomarkers and inflammatory factors were assessed by biochemical and ELISA methods, and RT-PCR analysis in DRG neurons. Rolipram and/or pentoxifylline treatment significantly attenuated DN – induced motor function deficiency by modulating distance moved and velocity. Rolipram and/or pentoxifylline treatment dramatically increased the cAMP level, as well as suppressed DN – induced oxidative stress which was associated with decrease in LPO and ROS and increase in TAC, total thiol, CAT and SOD in DRG neurons. On the other hand, the level of inflammatory factors (TNF-α, NF-kB and COX2) significantly decreased following rolipram and/or pentoxifylline administration. The maximum effectiveness was with rolipram and/or pentoxifylline combination on mentioned factors. These findings provide novel experimental evidence for further clinical investigations on rolipram and pentoxifylline combination for the treatment of DN. [ABSTRACT FROM AUTHOR]

In the search for versatile and effective weld cladding processes to deposit ultra-wear-resistant Ni-WC MMC (Ni-based tungsten carbide metal matrix composite) overlays for mining applications, there is an increasing interest in exploring advanced low-heat-input cold metal transfer (CMT) method. Depositions of single weld bead tracks of Ni-WC MMCs on steel plates were performed by employing the CMT process; Taguchi's design of experiments was used to plan the experimental investigation. All weld tracks exhibit continuous and uniform bead profile and sound metallurgical bonding to the substrate. Retained WCs are present in the overlay tracks relatively uniformly. The formation of primary WC and secondary carbides is observed depending on the level of dilution. In contrast to standard gas metal arc welding processes, the volume fraction of retained WC, which is negatively correlated with dilution level, is not directly interrelated with heat input for the CMT process and can reach a high level together with improved weld bead appearance at high deposition rate. Deposition rate has a positive correlation with average instantaneous power, which is, in turn, positively correlated with wire feed speed. The addition of oxygen into shielding gas mixtures promotes carbide transfer from cored feed wire to the weld track and increases the volume fraction of retained WC. Analysis of signal-to-noise ratios shows that it is difficult to find a single set of optimized processing parameters, and trade-offs are needed in engineering practice. The present investigation demonstrates that the Taguchi method is a powerful tool in process improvement for weld cladding of Ni-WC MMC overlays. [ABSTRACT FROM AUTHOR]

Gait variability could associate with fall risk in older people. Rocker sole shoes are commonly prescribed to reduce plantar pressure and facilitate forward movement. Thus, it may affect gait stability. The purpose of this study was to investigate the effects of toe-only rocker shoes on gait variability in the elderly. Seventeen healthy elderly participants walked on a treadmill under six different conditions including barefoot (BF), normal shoe (NS), and four types of toe-only rocker sole shoes with various degrees of rocker angle (RS10, RS20, RS30, and RS40). Then the step length variability (SLV), the step time variability (STV), the step width variability (SWV), and the stance time variability were measured. Increasing rocker angle in toe-only rocker did not significantly affect gait variability more than the standard shoe. It seems that different rocker angles in toe-only rocker sole shoes do not pose a threat to gait variability compared to the standard shoes in healthy elderly. Findings of the study suggested that the toe-only rocker sole can be used to facilitate forward progression in the elderly. Further investigation is also required to examine the long-term effects of toe-only rocker sole shoes on gait variability in frail elderly. [ABSTRACT FROM AUTHOR]

Copy number variation (CNV) is one of the main sources of variation between different individuals that has recently attracted much researcher interest as a major source for heritable variation in complex traits. The aim of this study was to identify CNVs in Afghan indigenous sheep consisting of three Arab, Baluchi, and Gadik breeds using genomic arrays containing 53,862 single nucleotide polymorphism (SNP) markers. Data were analyzed using the Hidden Markov Model (HMM) of PennCNV software. In this study, out of 45 sheep studied, 97.8% (44 animals) have shown CNVs. In total, 411 CNVs were observed for autosomal chromosomes and the entire sequence length of around 144 Mb was identified across the genome. The average number of CNVs per each sheep was 9.13. The identified CNVs for Arab, Baluchi, and Gadik breeds were 306, 62, and 43, respectively. After merging overlapped regions, a total of 376 copy number variation regions (CNVR) were identified, which are 286, 50, and 40 for Arab, Baluchi, and Gadik breeds, respectively. Bioinformatics analysis was performed to identify the genes and QTLs reported in these regions and the biochemical pathways involved by these genes. The results showed that many of these CNVRs overlapped with the genes or QTLs that are associated with various pathways such as immune system development, growth, reproduction, and environmental adaptions. Furthermore, to determine a genome-wide pattern of selection signatures in Afghan sheep breeds, the unbiased estimates of FST was calculated and the results indicated that 37 of the 376 CNVRs (~ 10%) have been also under selection signature, most of those overlapped with the genes influencing production, reproduction and immune system. Finally, the statistical methods used in this study was applied in an external dataset including 96 individuals of the Iranian sheep breed. The results indicated that 20 of the 114 CNVRs (18%) identified in Iranian sheep breed were also identified in our study, most of those overlapped with the genes influencing production, reproduction and immune system. Overall, this is the first attempts to develop the genomic map of loss and gain variation in the genome of Afghan indigenous sheep breeds, and may be important to shed some light on the genomic regions associated with some economically important traits in these breeds. [ABSTRACT FROM AUTHOR]

Effect of tetrabromobisphenol A (TBBPA) as a flame retardant agent (FR) and recycled polyvinylchloride (r-PVC) as a self-extinguishing component on the thermal, mechanical, and flammability properties of recycled acrylonitrile–butadiene–styrene copolymer/polycarbonate (r-ABS/r-PC) blends has been investigated. r-PVC was used as a poorly recyclable polymer, and TBBPA consumption was reduced due to its toxic properties. The FR had a compatibility effect with the matrix. Simultaneous use of r-PVC and FR showed a synergistic effect so that at a lower percentage of FR, a high level of flame resistance and LOI value was achieved. The addition of FR and r-PVC individually and cumulatively reduced the decomposition temperature of the blend, although the residual percentage of these materials increased at 800 °C. The tensile and Izod strength of the blends increased and decreased with the addition of FR, respectively. However, the effect of r-PVC on the mechanical properties was the opposite of the TBBPA problem. [ABSTRACT FROM AUTHOR]

Despite their many advantages and positive features, the deep neural networks are extremely vulnerable against adversarial attacks. This drawback has substantially reduced the adversarial accuracy of the visual object detectors. To make these object detectors robust to adversarial attacks, a new Gabor filter-based method has been proposed in this paper. This method has then been applied on the YOLOv3 with different backbones, the SSD with different input sizes and on the FRCNN; and thus, six robust object detector models have been presented. In order to evaluate the efficacy of the models, they have been subjected to adversarial training via three types of targeted attacks (TOG-fabrication, TOG-vanishing, and TOG-mislabeling) and three types of untargeted random attacks (DAG, RAP, and UEA). The best average accuracy (49.6%) was achieved by the YOLOv3-d model, and for the PASCAL VOC dataset. This is far superior to the best performance and accuracy and obtained in previous works (25.4%). Empirical results show that, while the presented approach improves the adversarial accuracy of the object detector models, it does not affect the performance of these models on clean data. [ABSTRACT FROM AUTHOR]

Purpose: Although metformin is the first-line treatment of type 2 diabetes mellitus (T2DM), a few studies have evaluated the benefits of monotherapies (metformin) versus combination therapy (metformin and glibenclamide) for treatment of T2DM patients. The present study aimed to evaluate the effect of monotherapy with metformin compared to combination therapy with metformin and glibenclamide on the expression of RAGE, Nrf 2, and Sirt1genes. Methods: EightyT2DM patients and 40 healthy individuals participated in this case-control study. The patients in the treatment group were divided into two groups who received either metformin alone (n = 40) or metformin in combination with glibenclamide (n = 40). FBS, HbA1c, and fructosamine were measured. The expression of RAGE, Nrf 2, and Sirt 1 genes in PBMC of all subjects were assessed using real-time PCR. Results: RAGE gene expression in both treatment groups was significantly lower than the control (P < 0.05). RAGE gene expression was significantly reduced in the combination of metformin and glibenclamide treated group compared to metformin group (P < 0.05). Additionally, the expression of Sirt 1 and Nrf 2 genes in both treatment groups was higher than that of the control group (P < 0.05). The expression of Sirt 1 and Nrf 2 genes in metformin and glibenclamide treated group were higher than the metformin group (P < 0.05). Conclusion: Combination therapy (metformin and glibenclamide) showed stronger effect on repression of the RAGE gene and activation of Nrf 2 and Sirt 1 genes compared to monotherapy (metformin); therefore, it can be concluded that combination therapy may have more protective effects on the T2DM patients. No significant correlation was observed between HbA1c and RAGE, Sirt 1, and Nrf 2 genes expression. [ABSTRACT FROM AUTHOR]

Wound healing is a complex process and rapid healing necessitates a proper micro-environment. Therefore, design and fabrication of an efficacious wound dressing is an impressive innovation in the field of wound healing. The fabricated wound dressing in this scenario was designed using a combination of the appropriate coagulating and anti-bacterial materials like fibrinogen (as coagulating agent), nisin (as anti-bacterial agent), ethylenediaminetetraacetic acid (as anti-bacterial agent), and alginate (as wound healing agent). Biophysical characterization showed that the interaction of fibrinogen and alginate was associated with minor changes in the secondary structure of the protein. Conformational studies showed that the protein was structurally stable at 42 °C, is the maximum temperature of the infected wound. The properties of the hydrogel such as swelling, mechanical resistance, nisin release, antibacterial activity, cytotoxicity, gel porosity, and blood coagulation were assessed. The results showed a slow release for the nisin during 48 h. Antibacterial studies showed an inhibitory effect on the growth of Gram-negative and Gram-positive bacteria. The hydrogel was also capable to absorb a considerable amount of water and provide oxygenation as well as incorporation of the drug into its structure due to its sufficient porosity. Scanning electron microscopy showed pore sizes of about 14–198 µm in the hydrogel. Cell viability studies indicated high biocompatibility of the hydrogel. Blood coagulation test also confirmed the effectiveness of the synthesized hydrogel in accelerating the process of blood clot formation. In vivo studies showed higher rates of wound healing, re-epithelialization, and collagen deposition. According to the findings from in vitro as well as in vivo studies, the designed hydrogel can be considered as a novel attractive wound dressing after further prerequisite assessments. [ABSTRACT FROM AUTHOR]

Carbohydrates (polysaccharides) such as chitosan, alginate, carrageenan or salep are suitable candidates to make hydrogels for drug delivery applications. Generally, salep is obtained from tubers of Orchis. It is a rich source of glucomannan carbohydrate. In this regard, magnetic multi-walled carbon nanotubes (MMWCNT) hydrogel nanocomposite based on poly(acrylic acid) grafted onto salep carbohydrate can act as a potential carrier for novel drug delivery systems. The MMWCNT / hydrogel nanocomposite was prepared via conventional radical polymerization using salep as a natural carbohydrate. Following characterization of salep hydrogel nanocomposite, diffusion coefficients and the mechanism of release of Tetracycline hydrochloride (TCH) from the carbohydrate hydrogel was investigated. According to our findings, diffusion exponent ‘n’ has 0.46 and 0.26 values for TCH release from hydrogel without MMWCNTs and with MMWCNTs, indicating non-Fickian transport and Fickian transport, respectively. Moreover, the effect of pH on the tetracycline release has been studied by changing the pH medium. Additionally, experiments were conducted to evaluate TCH release at different pressures and temperatures. These parameters confirmed the efficiency of this salep carbohydrate based hydrogel nanocomposite for tetracycline hydrochloride release. [ABSTRACT FROM AUTHOR]

In this paper, the effect of bonding time on the microstructural and mechanical properties of a dissimilar joint between Inconel 625 and AISI 316L was investigated using a Cu interlayer. For this purpose, the bonding was performed at the bonding temperature of 1100 °C for 15, 30 and 60 minutes. Field emission scanning electron microscope equipped with energy-dispersive x-ray spectroscopy was used for microstructural analysis. X-ray diffraction was used to identify the formed phases in the different zones of joint bonding. Shear strength and hardness tests were performed to evaluate the mechanical properties of the joints. Microstructural observations showed that the interface of Inconel 625 with the Cu interlayer contained Mo- and Nb-rich MC type carbide. Also, microstructural investigations showed that the bonding zone contains (Ni, Cr, Fe)-rich nanosized deposits in the Cu matrix. The specimen bonded at 1100 °C for 30 minutes demonstrated the maximum shear strength of 470 MPa, and its fractography dominantly showed a ductile dimple fracture. The isothermal solidification of Cu showed that the TLP bonding is controlled by both the diffusion kinetics and diffusion thermodynamics in the solidification of Cu. The asymmetric diffusion of Cu into the base metals caused the bonding interface shifts to 316L side. [ABSTRACT FROM AUTHOR]

In this project, the fibers were applied to increase the tensile strength of the concrete and produce fiber reinforced concrete (FRC). Polypropylene (PP) is employed as a fiber due to its economic benefit and richness. Based on the hydrophobic nature and lack of functional groups in polypropylene fibers, they could not bond efficiently with the concrete. Therefore, the hydrophilicity of the fibers was increased by the plasma oxidation technique for enhancing the tensile strength of the concrete. The effect of plasma oxidation time was explored on the pullout force, tensile strength, Young's modulus, and the characteristics of six analyzed samples. The oxidation process was approved by XPS analysis, FTIR spectroscopy, and SEM techniques. Afterward, the strength of bonded fibers to concrete was measured at different degrees of oxidation by adding fibers to the concrete and pulling them out and it was confirmed by SEM images. Finally, the optimum plasma oxidation times for maximum adhesion of fibers to concrete were achieved at 3 min. The fibers which were oxidized at 3 min showed a 14.3% upgrade in stress compared to raw ones. Also, 3 min oxidized fibers embedded in concrete showed 47.8 and 97.16% improvement in tensile strength compared to raw fibers and 5 min oxidized fibers embedded in concrete, respectively. The XPS spectrum revealed 57.49% carbon and 32.47% oxygen, indicating the oxidation process on the fiber. The PP fibers have improved the transmission and control of microcracks at the microscopic level. [ABSTRACT FROM AUTHOR]

The asymmetric diffusion of Cu during the TLP bonding of Inconel 625 to 316L stainless steel with Cu interlayer was investigated. For this purpose, the bonding was performed at 1100°C for the 15, 30 and 60 min. Field Emission Scanning Electron Microscope equipped with Energy Dispersive x-ray spectroscopy and Transmission Electron Microscope were used for microstructural analysis. Also, Cu diffusion in the base metals was simulated with finite element method. The results of microstructural analysis showed that the diffusion of Cu towards Inconel 625 is 28 times more than that of the 316L stainless steel. In addition, with the diffusion of Cu towards the Inconel 625, the interface of the joint moves to the 316L stainless steel side. The simulation results showed that the diffusion of Cu on the 316L stainless steel side is less than the diffusion of Cu obtained from the experimental results. While the diffusion of Cu on the Inconel 625 side is more than the diffusion of Cu obtained from the experimental results. [ABSTRACT FROM AUTHOR]

Among them, sinapic acid, caffeic acid, thymol, coumarin, eugenol, carvacrol, myricetin, and naringenin were not detected in I C. aurantifolia i pomace extracts. I trans i -Ferulic acid was a major polyphenol compound in all studied extracts and was varied from 2.30 (60°C water extract) to 2.86 mg/g (water extract) in I C. aurantifolia i . [Extracted from the article]

In this paper, the concept of the functional mechanism of copolymer membrane formation is explained and analyzed from the theoretical and experimental points of view. To understand the phase inversion process and control the final membrane morphology, styrene-acrylonitrile copolymer (SAN) membrane morphology through the self-assembly phenomena is investigated. Since the analysis of the membrane morphology requires the study of both thermodynamic and kinetic parameters, the effect of different membrane formation conditions is investigated experimentally; In order to perceive the formation mechanism of the extraordinary structure membrane, a thermodynamic hypothesis is also developed based on the hydrophilic coil migration to the membrane surface. This hypothesis is analyzed according to Hansen Solubility Parameters and proved using EDX, SAXS, and contact angle analysis of SAN25. Moreover, the SAN30 membrane is fabricated under different operating conditions to evaluate the possibility of morphological prediction based on the developed hypothesis. [ABSTRACT FROM AUTHOR]

Environmental challenges are as vast as the universe, allowing for numerous studies on their various dimensions. Using 17 data sets from Asia-Pacific countries between 2000 and 2017, this study attempted to investigate the economic factors influencing the ecological footprint of the fishing sector. The primary contribution of this study is to examine the effects of nine economic freedom indicators, as well as other control variables, on the status of fishery resources due to environmental pressure. The findings confirm the environmental Kuznets curve (EKC) hypothesis in the fishing grounds footprint, indicating that GDP per capita growth has a positive and significant effect, even though its squared form coefficient is negative. Other control variables, including natural resource rents, urbanization, and energy intensity, do not significantly affect the fishing footprint. The different components of economic freedom show different effects, while their cumulative effects in the form of the total economic freedom index positively affect the footprint of fishing and lead to increased extraction from fishing resources. The results show that the government integrity, tax burden, business freedom, and monetary freedom indices increase the fishing footprint. In contrast, indices of trade freedom and investment freedom, by highlighting the adverse effects of fishing on the environment, help countries reduce pressure on their aquatic resources. The findings of this study highlight the importance of examining how various dimensions of economic freedom affect the ability to manage fishery resources effectively. [ABSTRACT FROM AUTHOR]

A small waterplane area twin hull (SWATH) has excellent seakeeping performance and low wave-making resistance, and it has been applied to small working craft, pleasure boats, and unmanned surface vehicles. However, with the increase in speed, the hydrodynamic resistance of SWATH will increase exponentially because of its large wet surface, followed by the uncomfortable situation of the hull underwater part relative to the water level and in terms of high trim by stern and high sinkage. A way to improve this situation is to reduce the depth of the draft at high speeds to ensure that all or a part of the volume of the submerged bodies is above the water level. Based on this idea, a new type of semi-SWATH hull form was analyzed in this paper. The two submerged bodies of the SWATH have a catamaran boat shape. This paper employed Siemens PLM Star-CCM+ to study the hydrodynamic performance of an advanced semi-SWATH model. Bare-hull resistance was estimated for both SWATH and CAT (CATAMARAN) modes in calm water. Moreover, the effect of fixed stabilizing fins with different angles on the vertical motions of the vessel in regular head waves was investigated with an overset mesh approach. The vertical motion responses were estimated at different wave encounter frequencies, and the present numerical method results have been verified by already published experimental data. [ABSTRACT FROM AUTHOR]

In this study, several titanium-based electrodes (e.g., Ti, Ti/SnO2–Sb–Ni, Ti/SnO2–Sb–Ni-MWCNTs, Ti/TiHx/SnO2–Sb–Ni and Ti/TiHx/SnO2–Sb–Ni-MWCNTs) were fabricated by spin-coating and pyrolysis methods for electrochemical ozone generation. The modified electrodes were characterized by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) techniques. These electrodes are used as an anode for electrochemical ozone generation. The ozone generation at the surface of the electrodes was investigated. The optimum molar ratio of metal salts and multi-walled carbon nanotubes (MWCNTs) (Sn/ Sb/ Ni/ MWCNTs) was obtained 500:8:1:15. The repetition coating time, electrolysis time, electrolysis current density and kind of electrolytes (H3PO4, HClO4 and H2SO4) at different concentrations (0.1, 0.05, 0.1, 0.2, 0.5 and 1 M) were investigated and, respectively, were determined (i.e., 22 times, 120 s, 20 mA cm−2, HClO4 and 0.1 M). As the results showed, in 4 mL HClO4 (0.1 M) after 25 min electrolysis under a constant current of 12.8 mA, at the surface of the Ti/TiHx/SnO2–Sb–Ni-MWCNTs electrode (A = 0.64 cm2) could produce 19.9 mg L−1 of ozone, which is triple the amount produced by the electrodes not modified with MWCNTs. Also, the best-modified electrode (Ti/TiHx/SnO2–Sb–Ni-MWCNTs) was used for electrooxidation of three types of disperse dyes. The results showed that Ti/TiHx/SnO2–Sb–Ni-MWCNTs electrode can remove the dye (100 mg L−1) molecules up to 97%, 90% and 86% for C.I. Disperse yellow 54 (DY 54), C.I. Disperse blue 198 (DB 198) and C.I. Disperse red 167 (DR 167), respectively. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Rolipram and pentoxifylline combination ameliorates experimental diabetic neuropathy through inhibition of oxidative stress and inflammatory pathways in the dorsal root ganglion neurons" published in the journal Metabolic Brain Disease. The correction addresses an error in Figure 8 of the original article, where the image of HE-stained DRG neurons was mistakenly placed. The corrected Figure 8 has been provided, and the authors state that this error does not affect the results and conclusion of the paper. The correction notice also includes the names of the authors involved in the study. [Extracted from the article]

Purpose: Coenzyme Q10 (CoQ10), having potent antioxidant and anti-inflammatory pharmacological properties, has recently been shown to be a safe and promising agent in maintaining remission of ulcerative colitis (UC). This trial was, therefore, designed to determine CoQ10 efficacy on inflammation and antioxidant status, antimicrobial peptides, and microRNA-146a expression in UC patients. Methods: In this randomized double-blind controlled trial, 88 mild-to-moderate UC patients were randomly allocated to receive CoQ10 (200 mg/day) or placebo (rice flour) for 2 months. At the baseline and at an 8-week follow-up, serum levels of Nrf2, cathelicidin LL-37, β-defensin 2, IL-10, IL-17, NF-κB p65 activity in peripheral blood mononuclear cells (PBMCs), simple clinical colitis activity index questionnaire (SCCAIQ), and quality of life (IBDQ-32 score), as well as an expression rate of microRNA-146a were measured. Results: A significant reduction was detected in the serum IL-17 level, activity of NF-κB p65 in PBMCs, and also SCCAI score in the CoQ10 group compared to the placebo group, whereas IL-10 serum concentrations and IBDQ-32 score of the CoQ10 group considerably increased versus the control group; the changes of these variables were also significantly different within and between groups at the end of the study. Furthermore, CoQ10 remarkably increased serum levels of cathelicidin LL-37. A significant change in serum cathelicidin LL-37 levels was also observed between the two groups. No statistical difference, however, was seen between the two groups in terms of the serum levels of Nrf2 and β-defensin 2 and the relative expression of microRNA-146a. Conclusions: Our results indicate that CoQ10 supplementation, along with drug therapy, appears to be an efficient reducer of inflammation in patients with mild-to-moderate UC at a remission phase. Trial Registration: The research has also been registered at the Iranian Registry of Clinical Trials (IRCT): IRCT20090822002365N17. [ABSTRACT FROM AUTHOR]

In this research, the Cu phytoremediation capacity of common mullein (Verbascum thapsus L.) was evaluated concerning plant growth, antioxidant enzymes, and photosynthetic activities. Plants were subjected to five Cu concentrations (0, 125, 250, 375, and 500 mg/L) under the hydroponic conditions for 2 weeks. The results showed that at 125 mg/L, root and shoot biomass and chlorophylls remained the same as that of the control and then declined with increasing concentrations of Cu, when compared with control. The carotenoid contents remained unchanged up to 250 mg/L compared with control and then dropped with raising Cu dose. The raising of antioxidant enzymes activity reflected the occurrence of stress due to Cu exposure as manifested by increased MDA and ion leakage level. However, increased antioxidant enzymes may be associated with the tolerance capacity of V. thapsus to protect the plant from oxidative damage. Except for the highest concentration (500 mg/L), Cu accumulation in the roots and shoots all increased significantly with increasing Cu concentration, and the Cu accumulation in shoots was greater than roots. The Cu accumulation reached its maximum level at 375 mg/L Cu concentration, with 492.8 and 447.3 mg/kg DW in shoots and roots, respectively, which is highly greater than the threshold value for a Cu (hyper)accumulator plant. The extraction coefficient (EC) close to 1, and translocation factor (TF) > 1 from 125 to 375 mg/L Cu, suggested that V. thapsus could be used as a viable plant species for Cu phytoextraction. [ABSTRACT FROM AUTHOR]

Phoenix dactylifera L. (Arecaceae) spathe has antioxidant and anti-inflammatory effects. Effects of hydro-alcoholic extract of Phoenix dactylifera spathe were examined in streptozotocin (STZ)-induced diabetic rats. Forty-nine male Wistar rats were randomly divided into seven groups; group 1 received normal saline solution daily, group 2 received STZ (50 mg/kg) on the first day, group 3 received STZ (50 mg/kg, ip) at the beginning of the study and metformin (150 mg/kg), daily for 30 days, groups 4–6 received STZ (50 mg/kg, ip) at the beginning of the study and were treated with Phoenix dactylifera spathe extract (PDSE; 50, 100, and 200 mg/kg, respectively) for 30 days, and group 7 received PDSE (200 mg/kg) for 30 days. Fasting blood sugar (FBS), insulin, weight change, adipokine leptin, tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hsCRP), lipid profile, and oxidative stress biomarkers were assessed. Qualitative analyses of extracts revealed the presence of flavonoids, phenols, and alkaloids but the absence of steroids and saponins. PDSE significantly reduced serum level of FBS, triglyceride, low lipoprotein density, cholesterol, adipokine leptin, TNF-α, hsCRP, and malondialdehyde. PDSE significantly increased the serum levels of high lipoprotein density, insulin, total antioxidant capacity, reduced glutathione, as well as the body weight of diabetic rats. Our results showed that PDSE improves glycemic and lipidemic profile in STZ-induced diabetic rats. This suggests that PDSE may be a promising agent to mitigate diabetic symptoms in diabetic patients. [ABSTRACT FROM AUTHOR]

The present study was an attempt to test a hypothesized educational psychology model investigating the relationship among perceived teacher affective support, intrinsic motivation, shame emotion and academic burnout among Iranian EFL (English as a foreign language) learners. To this end, 306 EFL learners were conveniently sampled, and were asked to complete relevant questionnaires. SPSS was used for tabulating the data and running descriptive statistics, and Confirmatory Factor Analysis was conducted to assure the construct validity of the questionnaires used. A Structural Equation Model (SEM) was hypothesized and tested through AMOS program with maximum likelihood estimation. The SEM analysis indicated that the final model had acceptable fit to the data set. The significant standard coefficients of the drawn paths showed that teacher affective support, intrinsic motivation and shame directly predicted academic burnout. In addition, teacher affective support exerted indirect effect on academic burnout through the mediation of intrinsic motivation and shame. Implications are discussed and suggestions are provided for future research. [ABSTRACT FROM AUTHOR]

Magnetic activated carbon/cobalt nanocomposite (MAC/Co) has been produced in the form of a new environment-friendly adsorbent for the first time. Energy dispersive X-ray, Fourier transform infrared spectroscopy (FTIR), surface area, scanning electron microscopy (SEM) and X-ray diffraction methods have been applied to describe its chemical composition, functional groups, surface and morphological features. Cr(VI) ions from wastewater samples have been removed by using the MAC/Co. Adsorption efficiency has been estimated to be 95.3% within 15 min at pH 5 at room temperature. Freundlich, Langmuir, and Temkin isotherm models have been used for evaluating equilibrium in order to examine the procedure appropriateness. Kinetics studies indicated that Elovich model is a well fitness model for explaining adsorption mechanisms. Thermodynamic findings indicated endothermic and spontaneous nature of adsorption procedure. Separation of the MAC/Co from water samples can be readily performed by an exterior magnet. By using 0.1 mol/L NaOH solution, desorbing adsorbed Cr(VI) ions have been done with great efficiency. It is possible to reuse the MAC/Co nanocomposite to more than 5 cycles. Thus, the developed nanocomposite will be efficient and a hopeful adsorbent to cleaning treatment of Cr(VI) ions from wastewater via a large scale designed adsorption structure. [ABSTRACT FROM AUTHOR]

Measurement of muscle forces related to aging can help to better identify the gait impairment mechanisms in the elderly. To this end, musculoskeletal modeling has been developed to estimate muscle forces. This study aimed to check the validity of OpenSim modeling (i.e., computed muscle control) approach in elderly subjects. Kinematic and kinetic data and Electromyography (EMG) signals for four different muscles were collected in nine healthy elderly males during walking. Dynamic simulation was done within OpenSim. Correlation analysis was performed to quantitatively compare the maximum estimated muscle forces with maximum measured muscle activities during the first double limb support, single limb support, and the second double limb support phases. The area-time plots of OpenSim and EMG data during gait cycle were obtained for qualitative assessment. In quantitative assessment, a low to moderate correlation was observed for the peak of muscle force and muscle activation of four muscles during sub phases of gait. The muscle forces pattern from OpenSim was found to be relatively similar to the muscle activity pattern from EMG especially for Gastrocnemius Medialis. A low to moderate consistency between OpenSim and EMG in the elderly can be explained by using a single mathematical estimation approach. [ABSTRACT FROM AUTHOR]

The performance and productivity of livestock have consistently improved by natural and artificial selection over the centuries. Both these selections are expected to leave patterns on the genome and lead to changes in allele frequencies, but natural selection has played the major role among indigenous populations. Detecting selective sweeps in livestock may assist in understanding the processes involved in domestication, genome evolution and discovery of genomic regions associated with economically important traits. We investigated population genetic diversity and selection signals in this study using SNP genotype data of 14 indigenous sheep breeds from Middle East and South Asia, including six breeds from Iran, namely Iranian Balochi, Afshari, Moghani, Qezel, Zel, and Lori-Bakhtiari, three breeds from Afghanistan, namely Afghan Balochi, Arabi, and Gadik, three breeds from India, namely Indian Garole, Changthangi, and Deccani, and two breeds from Bangladesh, namely Bangladeshi Garole and Bangladesh East. The SNP genotype data were generated by the Illumina OvineSNP50 Genotyping BeadChip array. To detect genetic diversity and population structure, we used principal component analysis (PCA), admixture, phylogenetic analyses, and Runs of homozygosity. We applied four complementary statistical tests, FST (fixation index), xp-EHH (cross-population extended haplotype homozygosity), Rsb (extended haplotype homozygosity between-populations), and FLK (the extension of the Lewontin and Krakauer) to detect selective sweeps. Our results not only confirm the previous studies but also provide a suite of novel candidate genes involved in different traits in sheep. On average, FST, xp-EHH, Rsb, and FLK detected 128, 207, 222, and 252 genomic regions as candidates for selective sweeps, respectively. Furthermore, nine overlapping candidate genes were detected by these four tests, especially TNIK, DOCK1, USH2A, and TYW1B which associate with resistance to diseases and climate adaptation. Knowledge of candidate genomic regions in sheep populations may facilitate the identification and potential exploitation of the underlying genes in sheep breeding. [ABSTRACT FROM AUTHOR]

CD4 and CD8 mark helper and cytotoxic T cell lineages, respectively, and serve as coreceptors for MHC-restricted TCR recognition. How coreceptor expression is matched with TCR specificity is central to understanding CD4/CD8 lineage choice, but visualising coreceptor gene activity in individual selection intermediates has been technically challenging. It therefore remains unclear whether the sequence of coreceptor gene expression in selection intermediates follows a stereotypic pattern, or is responsive to signaling. Here we use single cell RNA sequencing (scRNA-seq) to classify mouse thymocyte selection intermediates by coreceptor gene expression. In the unperturbed thymus, Cd4+Cd8a- selection intermediates appear before Cd4-Cd8a+ selection intermediates, but the timing of these subsets is flexible according to the strength of TCR signals. Our data show that selection intermediates discriminate MHC class prior to the loss of coreceptor expression and suggest a model where signal strength informs the timing of coreceptor gene activity and ultimately CD4/CD8 lineage choice. Developing T cells commit to either CD4/helper or CD8/cytotoxic lineage in the thymus, but how CD4 and CD8 coreceptors and TCR signaling dictate this selection process is still unclear. Here the authors use single cell RNA sequencing of mouse thymocytes to show that, in selection intermediates, TCR signaling strength informs coreceptor expression timing. [ABSTRACT FROM AUTHOR]

Background: Trastuzumab, a humanized monoclonal antibody targeting Human Epidermal growth factor Receptor 2 (HER2), is a therapeutic option used for the treatment of patients with HER2-overexpressing breast cancers. The primary purpose of the present study was to establish a trastuzumab-based antibody drug conjugate (ADC) to enhance the biopharmaceutical profile of trastuzumab. Methods: In this study, trastuzumab was linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE) through a peptide linker. Following conjugation, MMAE-trastuzumab ADCs were characterized using SDS-PAGE, UV/VIS, and cell-based ELISA. The inhibitory effects of the ADCs were measured on MDA-MB-453 (HER2-positive cells) and HEK-293 (HER2-negative cells) using in vitro cell cytotoxicity and colony formation assays. Results: Our findings showed that approximately 3.4 MMAE payloads were conjugated to trastuzumab. MMAE-trastuzumab ADCs produced six bands, including H2L2, H2L, HL, H2, H, and L in non-reducing SDS-PAGE. The conjugates exhibited the same binding ability to MDA-MB-453 as unconjugated trastuzumab. The MTT assay showed a significant improvement in the trastuzumab activity following MMAE conjugation, representing a higher antitumor activity as compared with unconjugated trastuzumab. Furthermore, ADCs were capable of potentially inhibiting colony formation in HER2-positive cells, as compared with trastuzumab. Conclusion: MMAE-trastuzumab ADCs represent a promising therapeutic strategy to treat HER2-positive breast cancer. [ABSTRACT FROM AUTHOR]

Siloxane/graphene oxide (GO) nanocomposites were synthesized by hydrolysis and condensation of tetraethyl orthosilicate in the presence of GO nanosheets through a sol-gel process. The influence of synthesis parameters on the properties of the siloxane/GO samples was studied and their structural, morphological and physicochemical characteristics were compared using various techniques. Polyether sulfone-supported GO and siloxane/GO thin film membranes were prepared using a pressure-assisted self-assembly method using a dead-end cell, and their separation performance and antifouling ability were evaluated. Siloxane/GOs appeared to have higher interlayer spacing, higher zeta potential and thus higher dispersion stability in aqueous media compared to GO. This gave rise to slower and more uniform sedimentation of the siloxane/GOs during the filtration process and formation of thin film membranes possessing denser and smoother morphology. The porosity, mean pore radius, water contact angle and pure water flux of the prepared membranes were compared. The separation performance of the prepared membranes to remove methylene blue (MB) and penicillin G-procaine (PG-P) from water was evaluated as a function of used GO solution concentration. The antifouling ability of membranes was studied by determining reversible fouling (Rr), irreversible fouling (Rir) resistances and flux recovery ratio (FRR). The siloxane/GO thin film membranes containing larger siloxane network exhibited the highest rejection percentage for MB (∼99%) and PG-P (∼88%), which were about 40% and 90% higher than that achieved for GO thin film membranes, while the water flux remained as high as 78.1 l·m−2h−1. Furthermore, these membranes exhibited the highest chlorine resistance, stability under ultrasonication, FRR (89%) and Rr (57%) values, implying higher chemical and mechanical stability, flux recovery capacity and antifouling ability. [ABSTRACT FROM AUTHOR]

Gentamicin (GEN) is an antibiotic to treat severe gram-negative infections. Nephrotoxicity is the major adverse effect limiting clinical use of GEN. Zingerone (ZIN), an important component of ginger root, has several pharmacological effects including antioxidant, anti-inflammatory, and free radical scavenging activity. The present study investigated the effects of ZIN against GEN-induced nephrotoxicity. Twenty-eight rats were randomly divided into four groups: group I received normal saline, group II was treated with GEN (100 mg/kg/day, i.p.), group III was treated with ZIN (10 mg/kg/day, orally) and GEN (100 mg/kg/day, i.p.), and group IV was treated only with ZIN (10 mg/kg/day, orally). The level of creatinine (Cr), blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) was assessed in the serum of animals. The content of protein carbonylation (PC), malondialdehyde (MDA), nitric oxide (NO•), and glutathione (GSH) and the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT), as well as histopathological parameters were evaluated in the kidney tissues. Treatment with ZIN (10 mg/kg/day) remarkably improved GEN-induced alteration in histopathological parameters; these protective effects were associated with the reduction in GEN-induced elevation in the serum level of Cr, BUN, NGAL, and KIM-1. Zingerone also reduced MDA, PC, and NO• levels as well as increased GSH content and SOD and CAT activity in the kidney tissues. Our results suggest that ZIN may inhibit GEN-induced nephrotoxicity through scavenging reactive free radicals and increasing intracellular antioxidant capacity. [ABSTRACT FROM AUTHOR]

Space-time duality in paraxial optical wave propagation implies the existence of intriguing effects when light interacts with a material exhibiting two refractive indexes separated by a boundary in time. The direct consequence of such time-refraction effect is a change in the frequency of light while leaving the wavevector unchanged. Here, we experimentally show that the effect of time refraction is significantly enhanced in an epsilon-near-zero (ENZ) medium as a consequence of the optically induced unity-order refractive index change in a sub-picosecond time scale. Specifically, we demonstrate broadband and controllable shift (up to 14.9 THz) in the frequency of a light beam using a time-varying subwavelength-thick indium tin oxide (ITO) film in its ENZ spectral range. Our findings hint at the possibility of designing (3 + 1)D metamaterials by incorporating time-varying bulk ENZ materials, and they present a unique playground to investigate various novel effects in the time domain. Here, the authors present an experimental demonstration of adiabatic frequency conversion using the concept of time boundary by exploiting the properties of an ITO film operating near its epsilon-near-zero frequency. They demonstrate a large and controllable shift up to 14.9 THz. [ABSTRACT FROM AUTHOR]

A glassy carbon electrode has been modified by electrochemical polymerization of dianix yellow along with multi-walled carbon nanotubes (MWCNTs) and utilized for the selective determination of dopamine (DA), ascorbic acid (AA) and uric acid (UA). Atomic force microscopy and scanning electron microscopy images were obtained to compare the surface morphology and topography of the bare and modified electrodes. Also, the electrochemical activities of DA, AA, and UA on the bare and modified electrodes were evaluated with the use of cyclic, linear sweep and differential pulse voltammetry (DPV). Large peak separation, good sensitivity, and stability allow to apply the poly-dianix yellow/MWCNTs modified electrode for the determination of DA individually and in the presence of AA and UA. The DPV data showed the linearity of DA, AA, and UA peak currents in the concentrations ranges of 7–2500 nM, 5–110 µM, and 0.100–7.500 µM with the detection limits of 6.1, 99 and 8.9 nM, respectively. The proposed electrode was applied for the quantification of dopamine in human blood serum samples. [ABSTRACT FROM AUTHOR]

Owing to the rise in population, lifestyle changes, high traffic rates in urban areas and environmental pollution, respiratory diseases have become much more prevalent on both regional and urban scales. Respiratory diseases affect over 300 million people worldwide and are thus among the major threats to humans' general well-being. The identification of underlying factors and the specification of accompanying risk areas for the temporal exacerbation of respiratory diseases are effective steps in managing the damage caused by such disorders. Here, we demonstrate a strategy for modelling the risk zone of respiratory diseases temporally, using a location-based social network (LBSN) and an artificial neural network (ANN). The main contribution of this paper is to consider the environmental and infrastructural factors and identify their relationships with the geographical locations of respiratory attacks. The study also utilizes Telegram, which is the most popular and conventional social media platform, in order to observe temporal changes in the location of respiratory attacks in Iran, in the form of a developed Telegram bot known as @respiratoryassociation. The relations between the factors behind and the location of respiratory attacks are determined using a multilayer perceptron (MLP) ANN. All the required data have been collected on a daily basis over a 5-year period from December 2013 to December 2018 in Tehran, Iran. The results indicated air pollution, especially pollution from carbon monoxide (CO) and suspended particulate matter (PM) as the most decisive factors. Following air pollution, the amount of exposure to the polluted area was determined as the second most decisive factor, which in turn increased as a result of escalations in traffic jams. Land use was determined as the third most decisive factor. Furthermore, the results revealed that the ANN performed satisfactorily, implying that the model can be used to examine the spatio-temporal behaviour of the time series of respiratory diseases with respect to environmental and infrastructural factors. [ABSTRACT FROM AUTHOR]