In the Korean construction industry, legal and institutional safety management improvements are continually being pursued. However, there was a 4.5% increase in the number of workers’ deaths at construction sites in 2017 compared to the previous year. Failure to wear safety helmets seems to be one of the major causes of the increase in accidents, and so it is necessary to develop technology to monitor whether or not safety helmets are being used. However, the approaches employed in existing technical studies on this issue have mainly involved the use of chinstrap sensors and have been limited to the problem of whether or not safety helmets are being worn. Meanwhile, improper wearing, such as when the chinstrap and harness fixing of the safety helmet are not properly tightened, has not been monitored. To remedy this shortcoming, a sensing safety helmet with a three-axis accelerometer sensor attached was developed in this study. Experiments were performed in which the sensing data were classified whether the safety helmet was being worn properly, not worn, or worn improperly during construction workers’ activities. The results verified that it is possible to differentiate among wearing status of the proposed safety helmet with a high accuracy of 97.0%

Cold gas-dynamic spray (cold spray) is an evolving coating deposition and restoration technology in which particles are deposited above the sonic speed. This paper presents the non-destructive three-dimensional characterization of cold sprayed stainless steel coating. The visualization of coating morphology and volumetric porosity, and the analyses of porosity size and spatial distributions confirmed that dense stainless steel coating with non-connected, micron-sized gradient porosity is successfully produced by cold spray. The suitability of X-ray tomography for characterizing cold sprayed coatings is assessed.

Object. Utilization of pedicle screws (PS) for spine stabilization is common in spinal surgery. With reliance on visual inspection of anatomical landmarks prior to screw placement, the free-hand technique requires a high level of surgeon skill and precision. Three-dimensional (3D) computer-assisted virtual neuronavigation improves the precision of PS placement and minimize steps. Methods. Twenty-three patients with degenerative, traumatic, or neoplastic pathologies received treatment via a novel three-step PS technique that utilizes a navigated power driver in combination with virtual screw technology. 1) Following visualization of neuroanatomy using intraoperative CT, a navigated 3-mm match stick drill bit was inserted at anatomical entry point with screen projection showing virtual screw. 2) Navigated Stryker Cordless Driver with appropriate tap was used to access vertebral body through pedicle with screen projection again showing virtual screw. 3) Navigated Stryker Cordless Driver with actual screw was used with screen projection showing the same virtual screw. One hundred and forty-four consecutive screws were inserted using this three-step, navigated driver, virtual screw technique. Results. Only 1 screw needed intraoperative revision after insertion using the three-step, navigated driver, virtual PS technique. This amounts to a 0.69% revision rate. One hundred percent of patients had intraoperative CT reconstructed images to confirm hardware placement. Conclusions. Pedicle screw placement utilizing the Stryker-Ziehm neuronavigation virtual screw technology with a three step, navigated power drill technique is safe and effective.

With large-scale distributed generators (DGs) in an active distribution network (ADN), conventional load flow convergence failure is incurred by heavy power transmission. The Holomorphic Embedding Load Flow Method (HELM) has proven to be more robust than the Newton–Raphson method under heavy power transmission. At present, HELM is mainly designed for balanced transmission networks. In this study, we developed a three-phase HELM model to accommodate DGs, delta connection loads, and ZIP loads for ADN. The effectiveness and better performance of the proposed method under heavy load situations were validated using modified unbalanced IEEE 13, 34, 37, and 123 test feeders.

Effect of abrasive shape on the three-body abrasion behaviors of monocrystalline silicon was investigated by Molecular dynamics modelling. The axial ratio of abrasive particle was varied from 1.00, i.e., a complete sphere, to 0.40 to mimic abrasive shape. The particle’s movement turns toward sliding from rolling when the axial ratio becomes less than a critical value 0.46. In the abrasion process, the friction force and normal force showed an approximately sinusoid-like fluctuation for the rolling ellipsoidal particles, while the front cutting of particle caused that friction force increased and became larger than normal force for sliding particles. The phase transformation process was tracked under different particle’ movement patterns. The Si-II and Bct5 phase producing in loading process can partially transform to Si-III/Si-XII phase and backtrack to original crystal silicon under pressure release, which also occurred in the abrasion process. The secondary phase transformation showed difference for particles’ rolling and sliding movements after three-body abrasion. The rolling of particle induced the periodical and inhomogeneous deformation of substrates, while the sliding benefited producing high-quality surface in CMP process. This study aiming to construct more precise model to understand the wear mechanism benefits evaluating the MEMS wear and CMP process of crystal materials.

Synaptic transmission is essential for nervous system function and the loss of synapses is a known major contributor to dementia. Alzheimer’s disease dementia (ADD) is characterized by synaptic loss in the mesial temporal lobe and cerebral neocortex, brain areas associated with memory and cognition. The association of synaptic loss and ADD was established in the late 1980s and it has been estimated that 30-50% of neocortical synaptic protein is lost in ADD, but there has not yet been a quantitative profiling of different synaptic proteins in different brain regions in ADD from the same individuals. Very recently, PET imaging of synapses is being developed, accelerating the focus on the role of synaptic loss in ADD and other conditions. In this study, we quantified densities of two synaptic proteins, the presynaptic protein SNAP25 and the postsynaptic protein PSD95 in human brain using enzyme-linked immunosorbent assays (ELISA). Protein was extracted from the cingulate, hippocampus, frontal, visual, and entorhinal cortex from cognitively unimpaired controls, subjects with mild cognitive impairment (MCI) and demented subjects with different levels of Alzheimer’s pathology. SNAP25 is significantly reduced in ADD when compared to controls in frontal cortex, visual cortex and cingulate; while hippocampus showed a smaller, non-significant reduction and entorhinal cortex concentrations were not different. In contrast, all brain areas showed lower PSD95 concentrations in ADD when compared to non-demented controls, although in hippocampus this failed to reach significance. Interestingly, cognitively unimpaired cases with high levels of AD pathology had higher levels of both synaptic proteins in all brain regions. SNAP25 and PSD95 concentrations significantly correlated with densities of neurofibrillary tangles, amyloid plaques and Mini Mental State Examination scores. Our results suggest that synaptic transmission is affected by ADD in multiple brain regions. Differences were less marked in entorhinal cortex and hippocampus, most likely due to a ceiling effect imposed by the very early development of neurofibrillary tangles in older people in these brain regions.

Aedes aegypti is the main vector of various arboviruses including dengue, yellow fever, Zika and chikungunya virus. This mosquito species originated in Africa but has a wide range of distribution, colonising various ecological zones. The transmission dynamics of arboviruses depends on environmental factors, but also on mosquito life history traits including development time, fecundity, and longevity. The objective of the current study was to assess the Aedes aegypti immature development time, adult longevity, fecundity and body variation from different sampling localities. Aedes aegypti mosquitoes were collected as eggs from different geographical zones and cohorts of mosquitoes were reared in standardized laboratory conditions to assess the life history traits parameters. Emerged adults were discriminated into morphotypes according to the density of white scales on the first abdominal tergite. The means of fecundity, longevity, development time and body size were assessed, and linear models were fitted to the traits parameters to assess the effects of other covariables. Average Aedes aegypti development time was estimated to 7.35 days; 7.40 days; 6.98 days and 7.40 days respectively for Dori, 1200 logements, Bobo-Dioulasso and Toudweogo. The fecundity did not vary across study sites and was not associated with the body size. The longevity varied according to the study sites with the mosquitoes from Bobo-Dioulasso having the longest longevity while the shortest longevity was found at Dori. Fed mosquitoes had longer longevity compared to unfed ones. Morphological identification showed that Aedes aegypti aegypti-like mosquitoes were more predominant than Aedes aegypti formosus-like mosquitoes in all the study sites, suggesting the predominance of Aedes aegypti in the urban environment. Our data suggest that the geographical origin of Aedes aegypti mosquitoes in Burkina Faso has a little effect on its life history traits.

This study aimed to overcome the difficulty of conducting the horizontal-well cavity leaching test in the field and to investigate the long-term stability of the horizontal-well salt-cavity natural gas storage. The simulation test design is combined with the similarity theory to study the cavity expansion characteristics and the influence law of cavity leaching parameters. Through the design of a rubber hose connection, an integrated closed test system for multi-stage horizontal-well cavity leaching and brine drainage was built. The test system also realises the repeatable backward movement of the injection well during the test. A similarity simulation of the test design was carried out, and the test platform was constructed to carry out multi-stage horizontal-well leaching tests with a nitrogen cushion. In the horizontal-well leaching tests with a nitrogen cushion, the influence laws of the well spacing, flow rate and liquid level position on cavity expansion were investigated. Based on the morphological characteristics of the horizontal-well cavity, a numerical model of the horizontal-well salt cavity was developed, which reflects the real cavity morphology leached in the test. The long-term stability of the horizontal-well salt-cavity natural gas storage under different internal pressures was investigated through numerical simulation.

Background: This study aimed to investigate the molecular profiles of stage III CRC patients from the international IDEA study. It also sought to correlate these profiles with Toll-like and vitamin D receptor polymorphisms, clinicopathological and epidemiological characteristics, and patient outcomes. Methods: Whole Exome Sequencing and PCR-RFLP on surgical specimens and blood samples, respectively, were performed to identify molecular profiling and the presence of Toll-like and vitamin D polymorphisms. Bioinformatic analysis revealed mutational status. Results: Among the enrolled patients, 63.7% were male, 66.7% had left-sided tumors, and 55.7% received CAPOX as adjuvant chemotherapy. Whole exome sequencing identified 59 mutated genes in 11 different signaling pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) CRC panel. On average, patients had 8 mutated genes (range, 2-21 genes). Mutations in ARAF and MAPK10 emerged as independent prognostic factors for reduced DFS (p=0.027 and p<0.001, respectively), while RAC3 and RHOA genes emerged as independent prognostic factors for reduced OS (p=0.029 and p=0.006, respectively). Right-sided tumors were also identified as independent prognostic factors for reduced DFS (p=0.019) and OS (p=0.043). Additionally, patients with tumors in the transverse colon had mutations in genes related to apoptosis, PIK3-Akt, Wnt, and MAPK signaling pathways. Conclusions: Molecular characterization of tumor cells can enhance our understanding of the disease course. Mutations may serve as promising prognostic biomarkers, offering improved treatment options. Confirming these findings with require larger patient cohorts and international collaborations to establish correlations between molecular profiling, clinicopathological and epidemiological characteristics and clinical outcomes.

ccurate recording of growth indicators for aquaculture species at different stages is essential for evaluating aquaculture production effectiveness and the rationality of feed formulations. Due to their convenience and non-invasiveness, weight, length, and condition factor are commonly used to assess the growth of aquaculture species . However, fish growth indicators, can vary significantly with age structure and feed components(nutrition), and relying on a single indicator may lead to misjudgments . In this study we investigated the growth indicators of gibel carp (Carassius auratus gibelio var. CAS V) at different growth stages (juvenile and adult) and different feed formulations. Meanwhile, fish weight-length relationship () was used to assess the growth indicators. The results showed that the weight-length relationship of gibel carp varied significantly with age and feed formulations. Additionally, the condition factor calculated depended on the weight-length relationship was more consistent with weight/length changes than measured. Weight analysis indicated that both weight, length, height, back thickness, and carcass ration had higher weights in analyzing fish growth. Therefore, during aquaculture production, fish growth evaluating requires considering diverse indicators such as weight, length,body height, back thickness, carcass ration,as well as condition factor to avoid misjudging the actual growth situation. Meanwhile, the use of the condition factor should consider the sufficient amount of data and whether the assumptions (such as being in a isometric growth period) are met.

This paper proposes a single-stage asymmetrical half-bridge fly-back (AHBF) converter with resonant mode using dual-mode control. The presented converter has an integrated boost converter and asymmetrical half-bridge fly-back converter and operates in resonant mode. The boost-cell always operates in discontinuous conduction mode (DCM) to achieve high power factor. The presented converter operates simultaneously using a variable-frequency-controller (VFC) and pulse-width-modulation (PWM) controller. Unlike the conventional single-stage design, the intermediate bus voltage of this controller can be regulated depending on the main power switch duty ratio. The asymmetrical half-bridge fly-back converter utilizes a variable switching frequency controller to achieve the output voltage regulation. The asymmetrical half-bridge fly-back converter can achieve zero-voltage-switching (ZVS) operation and significantly reduce the switching losses. Detailed analysis and design of this single-stage asymmetrical half-bridge fly-back converter with resonant mode is described. A wide AC input voltage ranging from 90 to 264 Vrms and output 19 V/ 120 W prototype converter was built to verify the theoretical analysis and performance of the presented converter.

As a new plant slope protection technology, living stumps can effectively improve slope stability. The current study attemptes to investigate the mechanical characteristics of the root system of living stumps and their reinforcement mechanism on slopes by carrying out a three-dimensional living stump slope modeling test. Using ABS materials, a 3D model of a living elm stump was created by 3D printing and a slope model test was carried out. The reinforcement mechanism of the living stump was studied through a combination of model testing and numerical simulation. The results indicate that, due to the presence of living stumps in the lower and middle parts of the slope, the maximum shear stress area of the soil moved to a deeper direction. The stress state of the soil around the living stump was effectively improved due to the existence of the lateral root system.Living stumps in the lower part of the slope cross the potential sliding surface and transferred the soil shear stress gradually to the root system through root-soil interaction. Moreover, the tap roots and lateral roots of living stumps form a robust spatial structure that bears the shear stress of soil together, thus increasing the stability of the slope.

To solve the problem of a uneven load for a dual-input counter-rotating transmission system, this research is based on Small Displacement Torsor Jacobian-Torsor theory.Considering the influence of the local parallel chain of a gearbox on the calculation accuracy of the backlash,the processing method of a meshing tooth pair parallel chain is proposed. The probability distribution of the tolerance band of gearbox manufacturing and assembly errors is modeled, the three-dimensional tolerance analysis model of a dual-input counter-rotating gearbox is established, and the Monte Carlo method is used to solve the backlash of the output end. The output backlash is solved with the Monte Carlo method, and the theoretical design backlash is combined with the output backlash to derive the gearbox side clearance range. The gearbox shaft system is analyzed statically, the range of the equal load coefficient is calculated, and the equal load performance optimization method based on the matching relationship between the gear backlash and the elastic shaft torsional stiffness is proposed. The correctness of the three-dimensional tolerance analysis combined with the elastic deflection angle used to optimize the equal load performance of the dual-input counter-rotating transmission system is verified by comparison with the relevant test data.

In this paper we study a special kind of finite mixture model. The sample drawn from the model consisits of three parts. The first two parts are drawn from specified distributions f1 and f2, while the third one is drawn from the mixture. A problem of interest is whether the two distributions f1 and f2 are the same. To test this hypothesis, we first define the regular location and scale family of distributions and assume that f1 and f2 are regular denisty functions. Then the hypothesis transforms to the equalities of the location and scale parameters, respectively. To utilize the information in the sample, we use Bayes’ theorem to obtain the posterior distribution and give the sampling method. Then we propose the posterior p-value to test the hypothesis. The simulation studies show that our posterior p-value largely improves the power in both normal and logistic cases while nicely controls the Type-I error. A real halibut dataset is used to illustrate the validity of our method.

The main goal of this work is to develop a novel boundary element method (BEM) model for analyzing ultrasonic wave propaga-tion in three-temperature anisotropic viscoelastic porous media. Because of strong nonlinearity of ultrasonic wave propagation in three-temperature porous media problems, the analytical or numerical solutions to the problems under consideration are always challenging, necessitating the development of new computational techniques. As a result, we use a new BEM model to solve such problems. A time stepping procedure based on the linear multistep method is obtained after solving the discretized boundary in-tegral equation with the quadrature rule. The calculation of a double integral is required to obtain fundamental solutions, but this increases the total BEM computation time. Our proposed BEM technique is used to solve the current problem and improve the formulation efficiency. The numerical results are graphed to demonstrate the effects of viscosity and anisotropy on the nonlinear ultrasonic stress waves in three-temperature porous media. The validity, accuracy, and efficiency in the proposed methodology were demonstrated by comparing obtained results to the corresponding solution obtained from finite difference method (FDM).

Groundwater plays a crucial role in triggering and reactivating deep-seated landslides. However, classical hydrogeological investigations have limitations in their applicability to deep-seated landslides due to anisotropic and heterogeneous media[16]. The Huangtupo landslide in the Three Gorges reservoir area has garnered significant attention in China due to its large volume, complex geological structure, and high hazard potential. Recent monitoring data has shown notable deformation in the NO.1 Riverside Sliding Mass (HTP-1), one of the four parts of the Huangtupo landslide, making it the primary focus of landslide research. This study aimed to investigate the water sources in the HTP-1 landslide using environmental stable isotopes as tracers. The isotopic analysis results indicated that the groundwater in the landslide area (LGW) is a mixture of remote karst groundwater (KGW) from the adjacent up-slope and local precipitation (LP). The karst groundwater is a major contributor to the recharge of the landslide groundwater system, causing a high slope groundwater level that can easily exceed the critical level during heavy rainfall events. Furthermore, based on the differential distribution of the LP fraction of LGW at different locations, the groundwater in the landslide can be classified into three groups. Groundwater at the sliding rupture surface has the highest fractions of local precipitation, followed by the groundwater at the rear of the landslide. Combined with the monitoring data of groundwater level in boreholes during the rainy season, this indicates that fissures and fractures in the sliding rupture zone and at the back of the landslide are well connected, which could be a critical factor in the mass movement of the creeping slope.

A method of direction-of-arrival (DoA) estimation for FMCW radars is presented. In addition to MUSIC and ESPRIT, which are well-known high-resolution DoA estimation algorithms, deep learning has recently emerged as a very promising alternative. It is proposed in this paper to use a 3D convolutional neural network (CNN) for DoA estimation. The 3D-CNN extracts from the radar data cube spectrum features of the region of interest (RoI) centered on the potential positions of the targets, thereby capturing the spectrum phase shift information, which corresponds to DoA, along the antenna axis. Finally, the results of simulations and field experiments are provided to demonstrate the superior performance, as well as the limitations, of the proposed 3D-CNN.

Manual measurement of rock discontinuities is time-consuming and subjective according to the experience of the surveyor. This work proposes a three-dimensional laser scanning-based method for the semi-automatic identification of rock discontinuities. Multisite cloud scanning is performed with real-time kinematic (RTK)-assisted orientation to estimate the rock fracturing degree; then, discontinuity orientations are extracted with the man–machine interactive method or automatic method. The proposed method was applied to actual examples to illustrate its accuracy at identifying rock discontinuities. The sensitivity of the identification accuracy to different parameters was investigated.

The Equator Principle is the goal of promoting the harmonious development of my country's economy and society. It promotes the green transformation and upgrading of the industrial structure by strictly controlling the flow of commercial bank funds, so as to achieve the goal of environmental protection and the coordinated development of the national economy. This paper uses factor analysis to reduce the dimensions of 10 financial indicators and non-financial indicators that measure the operating performance and development potential of joint-stock commercial banks, and then compares the comprehensive operating performance, liquidity, and safety of Industrial Bank and comparable banks. And the level of profitability, analyze the difference in comprehensive operating performance of joint-stock commercial banks joining the Equator Principles compared with commercial banks that have not joined the Equator Principles. The results of the study found that joining the Equator Principles of joint-stock commercial banks can improve comprehensive operating performance in the short term. In the long run, the development trend of Industrial Bank will be similar to that of comparable banks in the same category. Joining the Equator Principles of Industrial Bank can improve its liquidity and profitability, but it will not in the long run. Conducive to the improvement of the asset quality of joint-stock commercial banks. In this regard, the government, enterprises and financial institutions should work together to help commercial banks achieve an effective balance between operating performance and social responsibility, so as to achieve the goals of "carbon peak" and "carbon neutral".

Even though materialistic atoms are having independent existence in this current accelerating universe, they are not allowing scientists and engineers to explore the secrets of gravity at atomic scale. This may be due to incomplete unification paradigm, inadequacy of known physics and technological difficulties etc. In this challenging scenario, one fundamental question to be answered is: Is Newtonian gravitational constant having a physical existence? We would like to suggest that, it’s a man created empirical constant and is having no physical existence. Clearly speaking, it’s not real but virtual. For understanding the secrets of large scale gravitational effects, scientists consider it as a physical constant. In the same way, each atomic interaction can be allowed to have its own gravitational constant. With further study, their magnitudes can be refined for a better understanding of the nature. Thinking in this way, we tried to fit the Newtonian gravitational constant. It’s estimated value seems to be 6.679855x10^(-11) m3/kg/sec2. Proceeding further, the famous radiation constants can be shown to be complex or secondary physical constants. By considering proton neutron stability, nuclear binding energy, nuclear charge radii, neutron life time, Fermi’s weak coupling constant and strong coupling constant, we are trying to understand the validity of the proposed three atomic gravitational constants. It needs further study.

A single qubit may be represented on the Bloch sphere or similarly on the 3-sphere S3. Our goal is to dress this correspondence by converting the language of universal quantum computing (UQC) to that of 3-manifolds. A magic state and the Pauli group acting on it define a model of UQC as a positive operator-valued measure (POVM) that one recognizes to be a 3-manifold M3. More precisely, the d-dimensional POVMs defined from subgroups of finite index of the modular group PSL(2, Z) correspond to d-fold M3- coverings over the trefoil knot. In this paper, one also investigates quantum information on a few ‘universal’ knots and links such as the figure-of-eight knot, the Whitehead link and Borromean rings, making use of the catalog of platonic manifolds available on the software SnapPy. Further connections between POVMs based UQC and M3’s obtained from Dehn fillings are explored.

A single qubit may be represented on the Bloch sphere or similarly on the $3$-sphere $S^3$. Our goal is to dress this correspondence by converting the language of universal quantum computing (uqc) to that of $3$-manifolds. A magic state and the Pauli group acting on it define a model of uqc as a POVM that one recognizes to be a $3$-manifold $M^3$. E. g., the $d$-dimensional POVMs defined from subgroups of finite index of the modular group $PSL(2,\mathbb{Z})$ correspond to $d$-fold $M^3$- coverings over the trefoil knot. In this paper, one also investigates quantum information on a few \lq universal' knots and links such as the figure-of-eight knot, the Whitehead link and Borromean rings, making use of the catalog of platonic manifolds available on SnapPy. Further connections between POVMs based uqc and $M^3$'s obtained from Dehn fillings are explored.

This paper addresses the problem of assessing and optimizing acoustic positioning system for underwater target localization with range measurements only. We present a new three-dimensional assessment model to assess the optimal geometric beacon formation whether meet user needs. For the sake of mathematical tractability, it is assumed that the measurements of the range between the target and beacons are corrupted with white Gaussian noise with variance is distance-dependent. Then by adopting dilution of precision (DOP) parameters in the assessment model, the relationship between DOP parameters and positioning accuracy is derived. In addition, the optimal geometric beacon formation that will yield the best performance is achieved by minimizing the values of geometric dilution of precision (GDOP) on condition that the position of target is known and fixed. Next, in order to make sure whether the estimate positioning accuracy over interesting region satisfy the precision needed by the users, geometric positioning accuracy (GPA), horizonal positioning accuracy (HPA) and vertical positioning accuracy (VPA) are utilized to assess the optimal geometric beacon formation. Simulation examples are designed to illustrate the exactness of the conclusion. Unlike other work which only use GDOP to optimize the formation and cannot assess the performance of the specified dimensions, this new three-dimensional assessment model can assess the optimal geometric beacon formation in each dimension for any point in three-dimensional space, which can provide users with guidance advices to optimize performance of every specified dimension.

Resistive patch array incorporating with metallic backplane provided an effective way to the achievement of broadband metamaterial absorbers(MAs). When loading metallic metamaterial to resistive MA, the outstanding construction helps realize more flexible and diversified forms of broadband absorption. In this paper, we attempted to load metallic resonators(MRs) to resistive MA in the three-dimensional construction, which benefits further enhancement of lower-frequency absorption. Simulation showed that the partial absorption band was separated to lower frequency, while the rest of broadband absorption was unaffected. Meanwhile, after combining multi-unit of the proposed MAs, the stair-stepping broadband absorption was also achieved. At last, three samples were fabricated. The agreements between simulations and experimental results demonstrated that resistive MA loaded with MRs provided an effective way for further enhancement of lower-frequency absorption with almost no change of the absorbing structure and areal density. Thus, it is worthy to expect a wide range of applications to emerge inspired from the proposed attempt.

Non-Small Cell Lung Cancer (NSCLC) is the most common pulmonary malignancy, most frequently diagnosed at an advanced stage (III/IV). Patients in the Locally-Advanced Stage Subgroup (IIIA) are relatively few, yet compose of heterogenic phenotypes posing a diagnostic and treating challenge, leading to lack of clinical guidelines regarding the optimal standard of care. Several approaches exist, with a general agreement that a combined oncological and surgical modality approach is required. In this current retrospective descriptive study, operable Stage IIIA NSCLC patients who underwent surgery between 2013-2020 were evaluated on several aspects, including initial diagnosis, neoadjuvant regimens, outcomes of surgical intervention, overall survival at 2-years and 5-years following treatment. A total of 35 patients had neoadjuvant oncological treatment (mostly chemoradiation therapy) prior to surgery, out of which 28 patients were diagnosed with Stage IIIA NSCLC. In post-operative assessment of pathological staging, downstaging was reported in 20 patients, of which 7 (25%) cases were defined as complete pathological response. The 2-years overall survival rate was 65% and the 5-years overall survival rate was 60%. The main pattern of disease recurrence was distant metastasis.

Background: Circulating rare cells participate in breast cancer evolution as systemic components of the disease and thus, are a source of theranostic information. Exploration of cancer-associated rare cells is in its infancy. We determined the validity of a rare-cell detection platform and demonstrated the usefulness of a certain rare cell subset as a novel approach to characterize the breast cancer system. Methods: Linearity of the Rarmax® platform was established using a spike-in approach. The platform includes red blood cell lysis, leukocyte depletion and high-resolution fluorescence image recording. Rare cell analysis was conducted on 28 samples (before and after surgery) from 14 patients with breast cancer, 20 healthy volunteers and 9 non-cancer control volunteers. In-depth identification of rare cells, including circulating tumor cells, endothelial-like cells, erythroblasts and inflammation-associated cells, was performed using a phenotype and morphology-based classification system. Results: The platform performed linearly over a range of 5-950 spiked cells, with an average recovery of 84.6%. Circulating epithelial and endothelial-like cell subsets have been demonstrated to be associated with or independent of cancer with tumor presence. Furthermore, certain cell patterns may be associated with treatment-related adverse effects. The sensitivity in detecting tumor-presence and cancer-associated abnormality before surgery was 50% and 85.7%, respectively and the specificity was 100% and 96.6%, respectively. Conclusion: The present study supports the idea of a cancer-associated rare cell abnormality to represent tumor entities as well as systemic cancer. The latter is independent of the apparent clinical cancer.

Existing research concerning the effects of the sitting birth position during the second stage of labour on maternal and neonatal outcomes remains controversial, and there is a lack of studies to explore its effect on the childbirth experience. The objective of this study is to explore whether the sitting birth position would influence maternal and neonatal outcomes, as well as the childbirth experience reported by Chinese women using the Childbirth Experience Questionnaire (CEQ). A total of 296 women (including primiparous women and multiparous women) were enrolled in our study, and they were divided into the sitting position cohort (n=106) or the lithotomy position cohort(n=116). The study found that primiparous women in the sitting position cohort had a shorter duration of the second stage of labour, higher spontaneous vaginal birth rates, lower episiotomy rates and better childbirth experience (p<0.01). There was no significant difference for perineal lacerations, 2h-postpartum haemorrhage (P>0.05) between the two cohorts of primiparous women. After adjusting for confounding factors through multiple linear and logistic regression analyses, the results remained consistent with those reported above. No neonate in each cohort had Apgar scores at 1min and 5 min postpartum less than 7 or the Cord artery pH less than 7.00, regardless of parity. In addition, among multiparous women, there was no significant difference in any maternal and neonatal outcomes and women’s CEQ scores (p>0.05) between two cohorts. Based on the findings, we recommend that women could take the sitting birth position into account when giving birth for a positive childbirth experience, especially for primiparous women. The study could also serve as a reference for healthcare providers in the management of childbirth positions and the development of high-quality maternal care.

(1) Background: This article reviews the available scientific literature on drug-related problems and negative outcomes associated with medications identified by medication review with follow-up for end-stage renal disease and discussed with the physicians; (2) Methods: A systematic review was conducted of the scientific literature retrieved from the following databases: MEDLINE (via PubMed), Web of Science, SCOPUS, Cochrane Library: The Cochrane Central Register and Control Trials (CENTRAL) and Literatura Latinoamericana y del Caribe (LILACS), Medicina en Español (MEDES), and the SciELO bibliographic database (collection of scientific journals). The following terms were used as descriptors and searched in free text: "end-stage renal disease", "medication review", and "drug-related problems” and “negative outcomes associated with medication". The following limits were applied: "humans" and "adults (more than 18 years)”; (3) Results: A total of 59 references were recovered and after applying inclusion/exclusion criteria, 16 articles were selected. Of these selected articles, 15 provided information on drug-related problems and only 1 on negative outcomes associated with medications; (4) Conclusions: It can be concluded that drug-related problems and negative outcomes associated with medication affect patients with end-stage renal disease, mainly those receiving renal replacement therapy. More evidence is needed, especially on negative outcomes associated with medication.

18F-fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET-CT) is increasingly used in the diagnosis, prognosis, staging, and treatment monitoring of many tumor types. However, only a small number of studies have reported the use of 18F-FDG PET-CT in intrahepatic cholangiocarcinoma (ICC). This study aimed to examine the accuracy of tumor staging in ICC by using 18F-FDG PET-CT. Between January 2009 and December 2020, patients with suspected ICC were retrospectively enrolled in the study and underwent imaging. The sensitivity and specificity of 18F-FDG PET-CT, CT, and magnetic resonance imaging (MRI) in detecting tumors, satellite focus, vascular invasion, and lymph node metastases were analyzed. The efficacy of 18F-FDG PET-CT for tumor staging was evaluated. Of the 110 patients who were enrolled in the study, 52 underwent surgical treatment and 45 were histologically diagnosed with ICC. When compared with CT or MRI, 18F-FDG PET-CT had similar sensitivity and specificity values for diagnosing satellite focus and vascular and bile duct invasion; however, PET-CT showed higher accuracy in diagnosing regional lymph node metastases. The accuracy of tumor staging by 18F-FDG PET-CT was higher than that by CT/MRI. Thus, 18FDG PET-CT may support tumor staging in ICC.

This study attempted to explain the definition, objectives, and key stages in mud crab nursery activities. The nursery stages of Scylla spp was started from megalopa stage to several crablet instar stages or started from earlier crablet stage to several crablet stages. Direct stocking of megalopa into ponds is not recommended due to their sensitivity. Instead, nursery rearing is needed to produce mud crab of larger size before stocking. Individual nursery rearing results in higher survival rate (up to 100%), but with reduced growth rate, and a more complicated maintenance process compared with communal rearing. Nursery of mud crab can be done indoors, or outdoors, with adequate shelter and feed required to obtain good survival and growth performance. Artemia nauplii are the main, established nursery feed, particularly at megalopa stage, while survival rate may be improved if combined with artificial feed, such as micro bound diet formulations. Water quality parameters, identical to those proposed in tiger shrimp culture, can followed. Crablets may be transported to the pond location with, or without water. The provision of monosex seeds from mud crab hatcheries is expected to become more common, increasing seed price, and thus improving income of farmers. Numerous aspects of mud crab nursery, including nutrition, feeding strategies, understanding of their behaviour, i.e., cannibalism, control of environmental factors, and practical rearing techniques, still need further improvement.

Background. Pregnancy rates in women on dialysis have increased in the last decades, thus making it a topic of growing interest. The rarity of this event is predominantly due to fertility problems and to the high rates of pregnancy failure including stillbirth, fetal and neonatal deaths [1]. Methods. We conducted a narrative review of existent literature in order to analyse the major issues about pregnancy on dialysis to give the reader a full updated prospective about this topic which, even if not common, is becoming more and more frequent. Results. Even if recently acquired knowledge has improved diagnosis and treatment of dialysis pregnancies focusing on several aspects, pregnancy on dialysis remains a great challenge for obstetricians and should be managed by a multidisciplinary expertise team. Conclusion. Dialysis in pregnancy may be necessary for women previously affected by end stage renal disease (ESRD) becoming pregnant, or in case of acute renal injury presenting for the first time during gestation or, again in case of existent renal pathology worsening during pregnancy and requiring dialysis. Although some evidence suggests that more intensive dialysis regimens are correlated with better obstetric outcomes, the optimal therapeutic protocol still remains to be established.

Organisms in the wild have cryptic life stages that are sensitive to changing environmental conditions and can be difficult to survey. In this study, I used mark-recapture methods to repeatedly survey Anaea aidea (Nymphalidae) caterpillars in nature, then modeled caterpillar demography as a hidden Markov process to assess if temporal variability in temperature and density influence the survival and growth of A. aidea over time. Individual encounter histories result from the joint likelihood of being alive and observed in a particular stage, and I included hidden states by separating demography and observations into parallel and independent processes. I constructed a demographic matrix containing the probabilities of all possible fates for each stage, including hidden states, e.g., eggs and pupae. I observed both dead and live caterpillars with high probability. Peak caterpillar abundance attracted multiple predators, and survival of fifth instars declined as per capita predation rate increased through spring. A time lag between predator and prey abundance was likely the cause of improved fifth instar survival estimated at high density. Growth rates showed an increase with temperature, but the most likely model did not include temperature. This work illustrates how state-space models can include unobservable stages and hidden state processes to evaluate how environmental factors influence vital rates of cryptic life stages in the wild.

The coseismic surface three-dimensional deformation fields were significant for quantified the geometric and kinematic characteristics of earthquake rupture faults. Traditional geodetic techniques were constrained by their intrinsic limitations, such as InSAR, which could only extract far-field deformation fields due to its incoherence, and GNSS, which could only acquire deformations at discrete points. The recently developing optical pixel correlation technique based on high resolution remote sensing images could acquire the near-field coseismic horizontal deformation. In this study, the vertical displacement field of the 2022 Mw 6.6 Menyuan earthquake was obtained by differencing the pre- and post-earthquake DEMs from GaoFen-7 stereo satellite images. Further, the line-of-sight (LOS) and azimuthal (AZI) directions far-field deformations by InSAR, the horizontal near-field deformation by optical pixel correlation based on pre- and post-earthquake GF-2/7 images, and the vertical deformation by differencing the pre- and post-earthquake DEMs, were incorporated to comprehensively solve the complete three-dimensional deformation fields of the 2022 Mw 6.6 Menyuan earthquake. Firstly, the vertical displacement field by differencing DEMs indicated there were significant vertical displacements about 1 m at the bend region, which was induced by the local compressive stress. In addition, at the epicenter on the middle segment of ruptured Lenglongling fault (LLLF), the maximum lifting occurred on the southern sides of the main and secondary faults exceeded 2 m. Secondly, the three-dimensional deformation fields solved by multiple deformation data demonstrated that the near-field deformation field calculated by optical pixel correlation method could quantify the displacements distributed over the rupture fault zone, which were not available on the InSAR deformation maps. Finally, the surface 2D strain derived from the displacement maps calculated by optical pixel correlation revealed high strain concentration on the rupture fault zone. Our study focused on the complete surface three-dimensional deformation estimation from multiple far- and near-field deformation data, and provided a new perspective for a deeper understanding of the characteristics of coseismic surface deformation and the rupture pattern of the fault.

The three-pronged sliding universal coupling is a new kind of three-pronged coupling. To study its kinematic and dynamic characteristics, directional cosine matrices are utilized as tools to analyze the coordinate systems by establishing simplified geometric models and corresponding motions. Through the analysis of the motions of the input and output shafts and employing the method of single-force element, a set of equilibrium equations for the forces acting on the output shaft and the input shaft are formulated for solution analysis. The research indicates that during the rotation process, there exists a small angular difference between the input shaft and the intermediate shaft, demonstrating the quasi-constant angular velocity characteristics of the new tripod sliding universal coupling. The curves of the forces and torques acting on each component of the coupling approximate sinusoidal curves. The optimal operating angle range for the new tripod universal coupling is at angle , during which the system exhibits good transmission and mechanical performance.

Adjustable frequency converters are widely used in modern automated asynchronous drives due to their high efficiency and high responsiveness control strategies. Control algorithms for frequency converters are divided into two main groups: constant frequency commutation and random frequency commutation. Research results on various commutation frequencies, conducted using Matlab/Simulink software, show that the use of random frequency commutation provides better efficiency by significantly reducing the amplitude of harmonic oscillations at different frequencies, with a reduction in switching losses in transistors. Currently, a converter with random frequency commutation is being researched and applied in the direct torque control system. The traditional direct control system, based on a two-level inverter, is widely used due to its simplicity and ease of implementation. However, this method results in the output current of the two-level converter, supplied to the motor stator, having many harmonic distortions, leading to strong torque fluctuations regardless of the rotation speed and ultimately causing additional losses in the stator windings and reducing the motor's lifespan. To enhance the efficiency of automated asynchronous drives, this article presents an algorithm for a direct control system based on a three-level NPC inverter using a PI speed regulator. The proposed algorithm's research is validated in the Matlab/Simulink environment. The research results show that in the absence of harmonic filtering, the stator current harmonic distortion coefficient is approximately 11%, and torque fluctuations are less than 5% of the resistive torque. The fluctuations between the two capacitors remain almost unchanged throughout the entire process.

Since the beginning of the mass immunization with COVID-19 vaccines of patients with multiple sclerosis, many data on the efficacy and safety of these vaccines have been produced. Considering that MS is an autoimmune disease whose pathology can be explained by an altered immune system and that some DMTs seem to be able to decrease the antibody response against COVID-19 vaccines, we carried out this retrospective study with the aim to evaluate the safety in terms of AEFIs occurrence and the antibody response after the third dose of COVID-19 vaccines in people with MS. Third doses were administered from October 2021 to January 2022. Two hundred and ten patients (64.8% female; mean age: 46 years) received the third dose of the mRNA-based COVID-19 vaccine and were included in the study. The majority of patients (n=193) were diagnosed with RRMS and EDSS values were ≤3.0 in 72.4% of them. DMTs most commonly used by included patients were interferon Beta 1-a, dimethyl fumarate, natalizumab and fingolimod. Overall, 160 patients (68.8% female) experienced 294 AEFIs, of which about 90% were classified as short-term, while 9.2% were classified as long-term. The most commonly reported following the booster dose were pain at the injection site, flu-like symptoms, headache, fever and fatigue. Regarding the immune response, consistently with literature data, we found that patients receiving ocrelizumab and fingolimod had lower IgG titer than patients receiving other DMTs.

Abstract: Self-regulated Learning has become one of educational psychology's most critical research areas. Contemporary research indicates that student creativity is crucial to the success of arts education. However, there is limited research on creativity in arts education in Self-regulated Learning. Therefore, this study aims to define the creativity characteristics that determine the quality of students’ work. This study implemented a creative competition in painting and composition for first-year undergraduates. It evaluated the characteristics of creativity during the three main phases of the task: planning, execution, and completion. We discovered through semi-open questionnaires (n=178)，and using the content analysis method. According to the competition results, the students with the highest scores in Flow, Inspiration, and Idea Generation in the Performance phase had the best quality work. In the Forethought phase, Analogical Thinking and Idea Generation worked best for most students, while in the Performance phase, Flow Sense, Idea Generation, and Idea Manipulation worked best.Data on creativity characteristics at different work phases and final quality might adequately guide and organize educational procedures. These findings can serve as a theoretical foundation for quantifying the creativity phase in Self-regulated Learning and offer arts educators a reference for creativity instruction.

Voltage Source Inverters (VSI) are the integral part of Electrical Vehicles (EV) to enhance the reliability of supply power to critical loads in vehicle to load (V2L) applications. Inherent properties of sliding mode control (SMC) makes it one of the best vailable options to achieve desired voltage quality under variable load conditions. Intrinsic characteristic of robustness associated with SMC is achieved generally at the cost of unwanted chattering along the sliding surface. To manage this compromise better, optimal selection of sliding surface coefficient is applied with proposed composite exponential reaching law (C-ERL). The novelty of proposed C-ERL is associated with the intelligent mix of exponential, power and difference functions blended with rotating sliding surface selection (RSS) technique for three phase two level VSI. Moreover, proposed reaching law along with power rate exponential reaching law(PRERL), enhanced exponential reaching law(EERL) and repeatitive reaching law(RRL) are implemented on two level three phase VSI under variable load condtions. Comparative analysis of which strongly advocates the authenticity and effectiveness of proposed reaching law in achieving well regulated output voltage, with high level of robustness, reduced chattering and low %THD.

The three-dimensional structure of Gulf of Mexico’s warm-core rings, detaching from the Loop Current, is investigated using satellite altimetry and a large set of ARGO float profiles. Reconstruction of the Loop Current rings (LCRs) vertical structure from sea surface height observations is made possible by the use of the gravest empirical modes method (GEM). The GEMs are transfer functions that associate a value of temperature and salinity for each variable pair {dynamic height;pressure}, and are computed by estimating an empirical relationship between dynamic height and the vertical thermohaline structure of the ocean. Between 1993 and 2021, 40 LCRs were detected in the altimetry and their three-dimensional thermohaline structure was reconstructed, as well as a number of dynamically relevant variables (geostrophic and cyclogeostrophic velocity, relative vorticity, potential vorticity, available potential energy and kinetic energy density etc.). The structure of a typical LCR was computed by fitting an analytical stream function to the LCRs dynamic height signature and reconstructing its vertical structure with the GEM. The total heat and salt contents and energy of each LCR were computed and their cumulative effect on the Gulf of Mexico’s heat, salt and energy balance is discussed. We show that LCRs have a dramatic impact on these balances and estimate that residual surface heat fluxes of -13 Wm−2 are necessary to compensate their heat input, while the fresh water outflow of the Mississippi river approximately compensates for their salt excess input. An average energy dissipation of O[10−10−10−9] Wkg−1 would be necessary to balance their energy input.

This study aims to evaluate the land surface temperature (LST) and the thermal characteristics of the Urban Canopy Layer (UCL) of the urban canyon in Avenida Rio Branco in the Central Business District (CBD) of Rio de Janeiro during summer. In order to conduct this evaluation, two methods were employed: 1) TIRS Landsat-8 sensor for data selection and processing (latest generation, 2011-2020); ; 2) field survey using nine sampling points — seven along two mobile transects, one fixed point, and one vertical measurement point, which required the use of a RPA (Remotely Piloted Aircraft). Three categories of analysis were established for the field survey based on the prevailing synoptic situations: stability, instability, and post-instability. The CBD is characterized by extensive areas with surface heat islands, in which temperatures were higher than 38.9°C; the areas with milder LSTs were Campo do Santana, Avenida Rio Branco, and one of the Mixed-Use Zones (Praça Mauá). With respect to Rio Branco Avenue, the LST niches of lowest elevation were derived through building shadowing; however, the orbital data diverged from the observation data of the ten field-study days. In situ data revealed that the characteristics urban morphology of Avenida Rio Branco is susceptible to the formation of heat islands, presenting heat islands of very strong magnitude (over 6.1°C) in atmospheric stability, strong magnitude (4.1-6.0°C) in atmospheric instability, and moderate magnitude (2.1°C-4.0°C) in post-atmospheric instability. Despite the synoptic situation, thermal cores were concentrated at 1 pm. The intersection between Avenida Rio Branco, Rua do Ouvidor, and Praça Mauá stored most of the solar energy received during the day due to the greater sky obstruction caused by the verticalization. Finally, vertical analysis demonstrated the formation of a thermal inversion on the night of the highest mean air temperature (29.5°C), probably, due to the roughness and number of buildings in the urban canyon.

Salmon farming has been blamed for the collapse of the sea trout (Salmo trutta) fishery in Loch Maree on Scotland’s west coast despite the absence of any direct evidence. Stocks of west coast demersal marine fish, especially around the Clyde Estuary have also declined over a similar time span. The decline of these marine fish stocks can be attributed to the removal of the “three-mile fishing limit” in 1984 by UK Government legislation. Sea trout inhabit the same inshore waters as targeted demersal fish and can be caught as by-catch. Comparisons of the decline of demersal species and the sea trout from Loch Maree and the west coast show a high degree of correlation. Stocks of whiting (Merlangius merlangus) from inshore waters have found to consist of small fish which mirrors the stock makeup of the Loch Maree sea trout stock.

Background. The molecular mechanisms underlying de novo metastasis of luminal breast cancer (dnMBC) remain largely unknown. Materials & Methods. Newly diagnosed dnMBC patients (grade 2/3, ER+, PR+/-, HER2-), with available core needle biopsy (CNB), collected from the primary tumor, were selected from our clinical-pathological database. Tumors from dnMBC patients were 1:1 pairwise matched (n=32) to tumors from newly diagnosed patients who had no distant metastases at baseline (eBC group). RNA was extracted from 5 x 10µm sections of FFPE CNBs. RNA sequencing was performed using the Illumina platform. Differentially expressed genes (DEG)s were assessed using EdgeR, deconvolution was performed using CIBERSORTx to assess immune cell fractions. Paired Wilcoxon test was used to compare dnMBC and eBC groups, and corrected for false discovery rate (FDR). Results. Many regulatory DEGs were significantly downregulated in dnMBC compared to eBC. Also, immune-related and hypoxia-related signatures were significantly upregulated. Paired Wilcoxon analysis showed that CCL17 and neutrophils fraction were significantly upregulated, whereas the memory B-cell fraction was significantly downregulated in the dnMBC group. Conclusion. Primary luminal tumors of dnMBC patients display significant transcriptomic and immunological differences compared to comparable tumors from eBC patients.

With the spread of compulsory education emerged school management problems continued, and the quality of school management in compulsory education has attracted a great deal of attention in China. However, the application of information technology in the field is not yet detailed and wide, resulting in problems of heavy workload and high difficulty in the whole evaluation process. Accordingly, we use big data technologies such as Apache Spark, Apache Hive, and SPSS to carry out data cleaning, correlation analysis, dynamic factor analysis, principal component analysis, and visual display on 1760 sample data from 40 primary and secondary schools in Q Province in China, and constructs a model school management of quality evaluation in the compulsory education stage, which reduces the 22 management tasks required for previous evaluation to 5, greatly reducing the workload and difficulty of evaluation. It has improved the efficiency and accuracy of evaluation, and further promoted the simultaneous development of education of five domains and education equity in the compulsory education stage.

We report the first case of Daratumumab interference of allogeneic crossmatch tests repeatedly causing aberrant false-positive results, which inadvertently delayed transplant for a waitlisted renal patient with multiple myeloma. Daratumumab is an IgG1κ human monoclonal antibody commonly used to treat multiple myeloma, characterized by cancerous plasma cells and often leads to renal failure requiring kidney transplant, by depleting CD38-expressing plasma cells. In this case study, the patient had end-stage renal disease secondary to multiple myeloma and was continuously receiving Daratumumab infusions. The patient did not have any detectable antibodies to human leukocyte antigens but repeatedly had unexpected positive crossmatch by the flow cytometry-based method with 26 of the 27 potential deceased organ donors, implying donor-recipient immunological incompatibility. However, further review and analysis suggested that the positive crossmatches were likely false-positive as a result of interference from Daratumumab binding to donor cell surface CD38 as opposed to the presence of donor-specific antibodies. The observed intensity of the false-positive crossmatches was also highly variable, potentially due to donor- and/or cell-dependent expression of CD38. The variability of CD38 expression was, therefore, for the first time, characterized on the T and B cells isolated from various tissues and peripheral blood of 78 individuals. Overall, T cells were found to have a lower CD38 expression profile than the B cells, and no significant difference was observed between deceased and living individuals. Finally, we show that a simple cell treatment by dithiothreitol can effectively mitigate Daratumumab interference thus preserving the utility of pre-transplant crossmatch in multiple myeloma patients awaiting kidney transplant.

Image segmentation is a new challenge prob- lem in medical application. The use of medical imaging has become an integral part of research, as it allows us to see inside the human body without surgical intervention. Many researcher have studied brain segmentation. One stage method is used to segment the brain tissues. In this paper, we proposed the multi-stage generative ad- versarial network to solve the problem of information loss in the one-stage. We utilize the coarse-to-fine to improve brain segmentation using multi-stage generative adversar- ial networks (GAN). In the first stage, our model generated a coarse outline for (i) background and (ii) brain tissues. Then, in the second stage, the model generated outline for (i) white matter (WM), (ii) gray matter (GM) and (iii) cerebrospinal fluid (CSF). A good result can be achieved by fusing the coarse outline and refine outline. We conclude that our model is more efficient and accu- rate in practice for both infant and adult brain segmenta- tion. Moreover, we observe that multi-stage model is faster than prior models. To be more specific, the main goal of multi-stage model is to see the performance of the model in a few shot learning case where a few labeled data are available. For medical image, this proposed model can work in a wide range of image segmentation where the convolution neural networks and one-stage methods have failed.

Various products of the Integrated Multisatellite Retrievals for GPM (IMERG) and passive mi-crowave (PMW) sensors are assessed with respect to near-surface wet-bulb temperature (Tw), precipitation intensity, and surface type (i.e., with and without snow and ice on the surface) over the CONUS and using Stage-IV product as reference precipitation. IMERG products include precipitation estimates from infrared (IR), combined PMW, and their combination. PMW products generally have higher skills than IR over snow- and ice-free surfaces. Over snow- and ice-covered surfaces (1) PMW products (except AMSR-2) show a higher correlation coefficient than IR, (2) IR and PMW precipitation products tend to overestimate precipitation, but at colder temperatures (e.g., Tw<-10oC) PMW products tend to underestimate and IR product continues to show large overestimations, and (3) PMW sensors show higher overall skill in detecting precipitation oc-currence, but not necessarily at very cold Tw. The results suggest that the current approach of IMERG (i.e., replacing PMW with IR precipitation estimates over snow- and ice-surfaces) may need to be revised.

Background: The phase III KEYNOTE-604 study confirmed the benefit of pembrolizumab combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer(ES-SCLC). Intergrated the clinical benefits of pembrolizumab and its high cost into account, this study aim to assess the cost-effectiveness of adding pembrolizumab to standard first-line etoposide-platinum (EP) for patients with ES-SCLC from the the US payer perspective. Methods: A Markov model was developed to compared the costs and quality-adjusted life-years (QALYs) of pembrolizumab plus EP and placebo plus EP over a 10-year time horizon. Clinical efficacy, treatment utilization and safety data were pooled from the KEYNOTE-604 trial. Utilities were obtained from published resources. Costs were mainly collected from Medicare in 2020. Sensitivity analyses were performed to examined the robustness of our model. Results: Adding pembrolizumab to standard first-line EP, resulted in better effectiveness than the use of EP alone for ES-SCLC by 0.22 QALYs. Pembrolizumab plus EP was dominated economically by placebo plus EP, leading to an incremental cost-effectiveness ratio(ICER) of $334,373/ QALY. Deterministic sensitivity analyses indicated that the uncertainty in model parameters exerts no substantial effect on our results. Probability sensitivity analysis indicated that probabilities for pembrolizumab plus EP being cost-effective within a wide rang of willingness to pay were modest. Conclusion: From the US payer perspective, the first-line treatment for ES-SCLC with pembrolizumab plus EP was not cost-effective compare with placebo plus EP. Although pembrolizumab combination chemotherapy was beneficial to the survival of ES-SCLC, price reduction may be the necessary measure to improve its cost-effectiveness.

Background: This retrospective study evaluates the survival effects of metronomic maintenance therapy with fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. Methods: We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen adjuvant chemotherapy. The clinicopathological features and effects of metronomic maintenance therapy on survival according to treatment group and EGFR expression were analyzed. By conducting an in vitro cell line study and in vivo study through knockdout of EGFR gene, we analyzed the capacities of cell proliferation and migration. Results: Postoperative relapse and mortality were significantly more common in the FOLFOX group. Metronomic maintenance therapy was a significantly independent predictive factor of postoperative relapse and mortality, as well as a prognostic factor of disease-free survival and overall survival. The significant differences of survival between the two groups were only observed in patients with positive EGFR expression. Conclusions: The present study suggested EGFR expression as the prognostic factor in patients with stage III CRC receiving metronomic maintenance therapy. By analyzing EGFR expression, we can identify the potential candidates with optimal survival benefit from metronomic maintenance therapy in patients with stage III CRC.

Background: This retrospective study evaluate the survival effects of metronomic maintenance therapy with fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. Methods: We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen adjuvant chemotherapy. The clinicopathological features and effects of metronomic maintenance therapy on survival according to treatment group and EGFR expression were analyzed. By conducting an in vitro cell line study and in vivo study through knockdout of EGFR gene, we analyzed the capacities of cell proliferation and migration. Results: Postoperative relapse and mortality were significantly more common in the FOLFOX group. Metronomic maintenance therapy was a significantly independent predictive factor of postoperative relapse and mortality, as well as a prognostic factor of disease-free survival and overall survival. We also demonstrated that EGFR-knockout Caco2 cells are more sensitive to the inhibition effect of fluoropyrimidine than the control those. Conclusions: The present study suggested EGFR expression as the prognostic factor in patients with stage III CRC receiving metronomic maintenance therapy. By analyzing EGFR expression and treatment strategies, we can identify the potential candidates with optimal survival benefit from metronomic maintenance therapy in patients with stage III CRC.

This study aims to examine the non-volatile Particle Number (PN) emissions of a retrofitted Heavy-Duty Spark-Ignition (HD-SI) engine powered by liquefied petroleum gas (LPG) under both steady-state and transient conditions. The engine was tested under seven steady-state operating points to investigate the PN behavior and Particle Size Distribution (PSD) upstream and down-stream of the Three-Way Catalyst (TWC). This analysis intends to assess the impact of including particles with diameters ranging from 10 nm to 23 nm in the total particle count, a consideration for future regulations. The study employed the World Harmonized Transient Cycle (WHTC) for transient conditions to encompass the same engine working region used in the steady-state analysis. A Dekati FPS-4000 diluted the exhaust sample to measure the PSD and PN for particle diameters between 5.6 nm and 560 nm using the TSI-Engine Exhaust Particle Sizer (EEPS) 3090. Findings indicate that PN levels tend to increase downstream of the TWC under steady-state conditions in operating points with low exhaust gas temperatures and flows (equal to or less than 500 °C and 120 kg/h). Furthermore, the inclusion of particles with diameters between 10 nm and 23 nm leads to an increase in PN emissions by 17.70% to 40.84% under steady conditions and by an average of 40.06% under transient conditions, compared to measurements that only consider particles larger than 23 nm. Notably, in transient conditions, most PN emissions occur during the final 600 seconds of the cycle, linked to the most intense phase of the WHTC.

Fractional flow reserve (FFR) is well recognized as a gold standard measure for the estimation of functional coronary stenosis. Technological progressions in image processing have empowered the reconstruction of three-dimensional models of the coronary arteries via both non-invasive imaging modalities, such as Coronary Computed Tomography Angiography (CCTA), and invasive coronary angiography or intravascular imaging. The application of computational fluid dynamics (CFD) techniques to coronary 3D anatomical models allows the virtual evaluation of the hemodynamic significance of a coronary lesion with high diagnostic accuracy in comparison to the invasive FFR using pressure wires. These opportunities providing hemodynamic information based on anatomy have given rise to a new era of functional angiography and coronary imaging. However, further validations are needed to overcome several scientific and computational challenges before these methods are applied in everyday clinical practice. This review aims to present all the data on the studies and methodologies that have been presented for the virtual estimation of FFR, and the diagnostic execution of the virtual tools for the hemodynamic assessment of coronary lesions compared to the invasive FFR.

The time evolution of the continuous measure symmetry for the system built of the three bodies interacting via the potential U(r)~1/r is reported. Gravitational and electrostatic interactions between the point bodies were addressed. In the case of the pure gravitational interaction the three-body-system deviated from its initial symmetrical location, described by the Lagrange equilateral triangle, comes to collapse, accompanied by the growth of the continuous measure of symmetry. When three point bodies interact via the Coulomb repulsive interaction, the time evolution of CMS is quite different. CMS calculated for all of studied initial configurations of the point charges and all of their charge-to-mass ratios always comes to its asymptotic value with time, evidencing the stabilization of the shape of the triangle, constituted by the interacting bodies.

The application of warm-mixing technology brings considerable economical and environment benefits by decreasing the mixing temperature during warm asphalt mixture(WMA) production. However, the possible water residue also generates concerns in moisture susceptibility. For deep investigation on the influencing factors and mechanism of the moisture susceptibility of WMA, surface free energy(SFE) test and laboratory tests are applied in this research. A novel indicator based on SFE namely effective adhesion work is proposed to assess the asphalt-aggregate adhesion with different moisture contents. Then, given the mixing procedure of dry mixing method, an advanced three-phase model as form of asphalt-aggregate-warm mixing additive is introduced improving from the conventional two-phase asphalt-aggregate model for better reflecting the separate addition of warm mixing additive during mixing. Afterwards, the influence of aggregate types, asphalt type, aggregate moisture contents, warm-mixing agent types and warm-mixing process on the moisture susceptibility of WMA is analyzed utilizing the models and indicators proposed. Finally, the validity of the SFE indicator is verified by comparing the calculation of effective adhesion work with freeze-thaw splitting test result. The results show that all of the above factors impact the moisture susceptibility of WMA by influencing the interfacial adhesion, with the effect of moisture content being the most significant. Meanwhile, effective adhesion work and the three-phase model brought out in this research are proven to be feasible to characterize the adhesion properties of WMA, offering theoretical support to the research on warm mixing technology.

The current neural networks for tomato leaf disease recognition have problems such as large model parameters, long training time, and low model accuracy. To solve these problems, a lightweight convolutional neural network LBFNet is proposed in this paper.First, a lightweight convolutional neural network LBFNet is established as the base model. Secondly, a three-channel attention mechanism module is introduced to learn the disease features in tomato leaf disease images and reduce the interference of redundant features. Finally, a cascade module is introduced to increase the depth of the model, solve the gradient descent problem, and reduce the loss caused by increasing the depth of the model. The quantized pruning technique is also used to further compress the model parameters and optimize the model performance. The results show that the LBFNet model achieves 99.06% accuracy on the LBFtomato dataset, with a training time of 996s and a single classification accuracy of over 94%. Further training using the saved weight file after quantized pruning makes the model accuracy reach 97.66%. Compared with the base model, the model accuracy was improved by 28%, and the model parameters were reduced by 96.7% compared with the traditional Resnet50. It was found that LBFNet can quickly and accurately identify tomato leaf diseases in complex environments, providing effective assistance to agricultural producers.

The purpose of this study was to clarify the attachment types of the tibialis anterior tendon (TAT) in Japanese fixed cadavers and to determine the attachment site area in three dimensions. We examined 100 feet from 50 Japanese cadavers. The TAT was classified according to differences in the number of fiber bundles as: Type I, with one fiber bundle; Type II, with two fiber bundles; and Type III, with three fiber bundles. The attachment site area of the TAT was measured using a three-dimensional scanner. Cases were Type II in 95% and Type III in 5%, with no cases of Type I identified. In Type II, mean attachment site areas were 85.2 ± 18.2 mm2 for the medial cuneiform bone (MCB) and 72.4 ± 19.0 mm2 for the first metatarsal bone (1MB), showing a significantly larger area for MCB than for 1MB. These findings suggest the possibility of ethnic differences in TAT attachment types and suggest that TAT attachments in Japanese individuals are highly likely to be Type II, with rare cases of Type III. Accurate measurement of attachment site areas is possible with appropriate three-dimensional measurements.

Three finger toxins (3FTX) are a group of peptides that affect multiple receptor types. One group of proteins affected by 3FTX are nicotinic acetylcholine receptors (nAChR). Structural information on how neurotoxins interact with nAChR is limited and are confined to a small group of neurotoxins. Therefore, in silico methods are valuable in understanding the interactions between 3FTX and different nAChR subtypes, but there are no established protocols to model 3FTX – nAChR interactions. We developed a homology modeling and protein docking protocol to address this issue and tested its success on three different systems. First, neurotoxin peptides co-crystallized with acetylcholine binding protein (AChBP) were re-docked to assess whether Rosetta protein – protein docking can reproduce the native poses. Second, experimental data on peptide binding to AChBP was used to test whether the docking protocol can qualitatively distinguish AChBP-binders from non-binders. Finally, we docked eight peptides with known α7 and muscle-type nAChR binding properties to test whether the protocol can explain the differential activities of the peptides at the two receptor subtypes. Overall, our docking protocol succeeded in predicting both qualitative and specific aspects of 3FTX binding to nAChR and shed light on some unknown aspects of 3FTX binding to different receptor subtypes.

Protein is the proteios building block of life. Evolutionarily, its sequence is not as conserved as its structure, making it more reasonable for protein structure, instead of protein sequence, to be the descriptor of protein function. Yet, in the National Center for Biotechnology Information (NCBI) database, the number of experimentally identified protein sequences is in great excess of that of experimentally determined protein structures inside the almost-half-a-century old Protein Data Bank (PDB). For instance, GPR151 is an proton-sensing G-protein coupled receptor (GPCR) originally identified as homologous to galanin receptors. As of March 19, 2020, GPR151’s structure has not been experimentally determined and deposited in PDB yet. Thus, an ab initio modelling approach was employed here to build a three-dimensional structure of GPR151. Overall, the ab initio GPR151 model presented herein constitutes the first structural hypothesis of GPR151 to be experimentally tested in future with previously published, currently ongoing and future GPR151 studies.

We replace the current industry-standard empirical forecasts of oil production from hydrofractured horizontal wells in shales with a statistically and physically robust, accurate and precise approach, using the Bakken shale as an illustration. The proposed oil production forecasting method extends our previous work on predicting fieldwide gas production in the Barnett shale and merges it with our new scaling of oil production in shales. We first divide the existing 14,678 horizontal oil wells in the Bakken into 12 static samples in which depositional settings and completion technologies are similar. For each sample, we construct a purely data-driven P50 well prototype by merging the GEV distribution fits of oil production from appropriate well cohorts. We fit the parameters of our physics-based scaling curve to the statistical well prototypes, and obtain their smooth extrapolations to 30 years on production. By calculating the number of potential wells of each Bakken region, and scheduling future drilling programs, we stack up the extended well prototypes to achieve the most plausible forecast. We predict that Bakken will ultimately produce 5 billion barrels of oil from the existing wells, with the possible increments of 2 and 6 billion barrels from core and noncore areas.

This paper proposes a novel three-phase voltage source inverter dead-time compensation strategy for accurate compensation in wide current regions of the inverter. In particular, an analysis of the output voltage distortion of the inverter, which appears as parasitic components of the switches, has been conducted for proper voltage compensation in the low current region, and an on-line compensation voltage controller has been proposed. Also, a new trapezoidal compensation voltage implementation method using the current phase is proposed to simplify realizing the trapezoidal shape of the three-phase compensation voltages. Finally, when the proposed dead-time compensation strategy is applied, the maximum phase voltage magnitude in the linear modulation voltage regions is defined to achieve smooth operation even at high modulation index. Simulations and experiments were conducted to verify the performance of the proposed dead-time compensation scheme.

This paper describes the early-stage prototyping process developed to probe into the socio-cultural dimensions of the Co-Drive project, which is a new service concept for traveling and socializing by car between a real driver on a semi-automated car and a remote passenger connected via virtual reality from home. By focusing on the intertwining journeys of the two actors of the experience, the driver and the remote passenger, three key interactions have been isolated and addressed as separate prototyping interventions in the wild. Such a seamful prototyping strategy enabled the users to experiment the whole service although the technology was not yet completely developed, and more specifically it allowed them to accommodate and appropriate each part of the experience into their everyday activities, revealing initial evidences of the potential social impact drawn by a future deployment of the service.

Transport electrification is essential for reducing CO2 emissions, and technologies such as hybrid and range-extended electric vehicles will play a crucial transitional role. Such vehicles employ an internal combustion engine for on-board chemical energy conversion. The Wankel rotary engine should be an excellent candidate for this purpose, offering high power-to-weight ratio, simplicity, compactness, perfect balance, and low cost. Until recently, however, it has not been in production in the automotive market, due, in part, to relatively low combustion efficiency and high fuel consumption and unburnt hydrocarbon emissions, which can be traced to constraints on flame speed, an elongated combustion chamber, and relatively low compression ratios. This work uses large-eddy simulation to study the in-chamber flow in a peripherally ported 225cc Wankel rotary engine, providing insight into these limitations. Flow structures created during the intake phase play a key role in turbulence production but presence of the pinch point inherent to Wankel engine combustion chambers inhibits flame propagation. Two efficiency-enhancement technologies are introduced as disruptive solutions: (i) pre-chamber jet ignition and (ii) the two-stage rotary engine. These concepts overcome the traditional efficiency limitations and show that Wankel rotary engine design can be further enhanced for its role as a range extender in electrified vehicles.

Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) is the virus that caused COVID-19 around the world. The disease starts off as a flu-like symptom and then eventually spreads in the human body.Infections are easily transmitted from human to human which makes it more severe among individuals. SARS-CoV-2 virus is in the same family of viruses SARS and MERS.As of today, there is no approved vaccine that can cure COVID-19. However, potential treatments showing promising improvement results among affected COVID-19 patients. In this review, the effectiveness of the current treatments for COVID-19 has been explored.

Motor functions are deteriorated by aging. Some conditions may magnify this deterioration. To examine whether hemodialysis (HD) process would negatively impact gait and balance beyond diabetes condition among mid-age adults (48-64 years) and older adults (65+ years). One hundred and ninety-six subjects (age=66.2±9.1 years, body-mass-index=30.1±6.4 kg/m², female=56%) in 5 groups were recruited: mid-age adults with diabetes undergoing HD (Mid-age HD+, n=38) and without HD (Mid-age HD-, n=40); older adults with diabetes undergoing HD (Older HD+, n=36) and without HD (Older HD-, n=37); and non-diabetic older adults (Older DM-, n=45). Gait parameters (stride velocity, stride length, gait cycle time, and double support) and balance parameters (ankle, hip, and center of mass sways) were quantified using validated wearable platforms. Groups with diabetes had overall poorer gait and balance compared to the non-diabetic group (p<0.050). Among people with diabetes, the HD+ had significantly worsened gait and balance when comparing to the HD- (Cohen’s effect size d=0.63-2.32, p<0.050). Between-group difference was more pronounced among older adults with the largest effect size observed for stride length (d=2.32, p<0.001). Results suggested that deterioration in gait speed among the HD+ was correlated with age (r=-0.440, p<0.001), while this correlation was diminished among the HD-. Interestingly, results also suggested that poor gait in the Older HD- related to poor balance, while no correlation was observed between poor balance and poor gait among the Older HD+. Using objective assessments, results confirmed that the presence of diabetes can deteriorate gait and balance, and this deterioration can be magnified by HD process. Among non-HD people with diabetes, poor static balance described poor gait. However, among people with diabetes undergoing HD, age was a dominate factor describing poor gait irrespective of static balance. Results also suggested feasibility of using wearable platforms to quantify motor performance during routine dialysis clinic visits. These objective assessments may assist in identifying early deterioration in motor function, which in turn may promote timely intervention.

The growing attention for plug-in electric vehicles, and the associated high-performance demands, have initiated a development trend towards highly efficient and compact on-board battery chargers. These isolated ac-dc converters are most commonly realized using two conversion stages, combining a non-isolated power factor correction (PFC) rectifier with an isolated dc-dc converter. This, however, involves two loss stages and a relatively high component count, limiting the achievable efficiency and power density and resulting in high costs. In this paper a single-stage converter approach is analyzed to realize a single-phase ac-dc converter, combining all functionalities into one conversion stage and thus enabling a cost-effective efficiency and power density increase. The converter topology consists of a quasi-lossless synchronous rectifier followed by an isolated dual active bridge (DAB) dc-dc converter, putting a small filter capacitor in between. To show the performance potential of this bidirectional, isolated ac-dc converter, a comprehensive design procedure and multi-objective optimization with respect to efficiency and power density is presented, using detailed loss and volume models. The models and procedures are verified by a 3.7 kW hardware demonstrator, interfacing a 400 V dc-bus with the single-phase 230 V, 50 Hz utility grid. Measurement results indicate a state-of-the-art efficiency of 96.1% and power density of 2.2 kW/dm³, confirming the competitiveness of the investigated single-stage DAB ac-dc converter.

First, a recently developed eigenfunction expansion technique, based in part on separation of the thickness-variable and partly utilizing a modified Frobenius type series expansion technique in conjunction with the Eshelby-Stroh formalism, is employed to derive three-dimensional singular stress fields in the vicinity of the front of an interfacial crack weakening an infinite bicrystalline superlattice plate, made of orthorhombic (cubic, hexagonal and tetragonal serving as special cases) phases, of finite thickness and subjected to the far-field extension/bending, in-plane shear/twisting and anti-plane shear loadings, distributed through the thickness. Crack-face boundary and interface contact conditions as well as those that are prescribed on the top and bottom surfaces of the bicrystalline superlattice plate are exactly satisfied. It also extends a recently developed concept of lattice crack deflection (LCD) barrier to a superlattice, christened superlattice crack deflection (SCD) energy barrier for studying interfacial crack path instability, which can explain crack deflection from a difficult interface to an easier neighboring cleavage system. Additionally, the relationships of the nature (easy/easy, easy/difficult or difficult/difficult) interfacial cleavage systems based on the present solutions with the structural chemistry aspects of the component phases (such as orthorhombic, tetragonal, hexagonal as well as FCC (face centered cubic) transition metals and perovskites) of the superlattice are also investigated. Finally, results pertaining to the through-thickness variations of mode I/II/III stress intensity factors and energy release rates for symmetric hyperbolic sine distributed load and their skew-symmetric counterparts that also satisfy the boundary conditions on the top and bottom surfaces of the bicrystalline superlattice plate under investigation, also form an important part of the present investigation.

The analysis of water inflow is a key issue in the construction of subsea tunnels. However, present research on the water inflow of subsea tunnels is predominantly focused on single-bore tunnels. Given the current practices in engineering, it is common to see a parallel configuration of three bores. In such cases, the proximity of tunnels to one another might result in alterations to the water inflow due to the interplay of seepage fields. This paper begins by conducting a numerical simulation to assess the water inflow characteristics of a three-bore parallel subsea tunnel. The study then investigates the impact of many factors, including the permeability coefficient of the surrounding rock, the depth of the seawater, the depth of the tunnel, the spacing between tunnels, and the relative size of the tunnels, on the water inflow phenomenon. Furthermore, based on the principles of the analytic hierarchy process and fuzzy mathematics, a comprehensive assessment framework is developed to evaluate the water inflow of three-bore parallel subsea tunnels. Ultimately, this grade of water inflow is used in practical engineering. The results show that there is mutual influence between the three parallel tunnels, and the predicted water inflow will be too large if the single tunnel model is adopted. The interaction between tunnels should be considered in the water inflow grade evaluation system of the three-hole parallel submarine tunnel. Engineering cases show that using a single-hole tunnel model without considering the interaction between tunnels will lead to higher water inflow grades. The research results of this paper can provide guidance for the waterproofing and drainage design of three parallel subsea tunnels and the stability analysis of surrounding rocks.

In this paper, we succeed to discover the new exact wave solutions to the truncated M-fractional complex three coupled Maccari’s system by utilizing the Sardar sub-equation scheme. The obtained solutions are in the form of trigonometric and hyperbolic forms. These solutions have many applications in nonlinear optics, fiber optics, deep water-waves, plasma physics, mathematical physics, fluid mechanics, hydrodynamics and engineering where the propagation of nonlinear waves is important. Achieved solutions are verified with the use of Mathematica software. Some of the achieved solutions are also described graphically by 2-dimensional, 3-dimensional and contour plots with the help of Maple software. The gained solutions are helpful for the further development of concerned model. Finally, this technique is simple, fruitful and reliable to handle the nonlinear FPDEs.

Deformation monitoring is beneficial to ensure the service safety of long tunnel. An three-direction (vertical, transverse and axial) deformation estimation method using long-gauge fiber Bragg grating (FBG) sensing technology is proposed and applied to a long tunnel by integrating mechanical analysis and field monitoring during the service state. The key issues of the proposed method for identifying the three-direction deformation are discussed, such as establishing the separation model of coupling strain on cross section, deriving the theory of deformation identification in three directions, and determining the sensor layout of the long tunnel. A major advantage of the proposed method is that the three-direction deformation of the tunnel can be monitored in real time using distributed long-gauge strain sensors. The numerical analysis and field test results verify the feasibility of the proposed method.

The increasing popularity of unconventional wells has sparked a heightened interest in evaluating and predicting their production performance. With the use of extended reach well structures, these wells are able to generate and access larger reservoir volumes. Hence, it is crucial to understand how the well's lateral trajectory affects its transient production performance. The assessment of lateral trajectory undulating amplitude effect on the flow behavior is performed in the current study based on the experimental results obtained at the University of North Dakota, Undulated Two-Phase (UTP) Flow Loop, injecting air and water mixture through a variable undulating amplitude section followed by a vertical section. The experiments showed that the undulating amplitude increase induced lower translational velocity, frequency, and length, with a consistent slug acceleration through the system profile from the inlet to the vertical section and a decreasing frequency when the slugs travel through the vertical section. Measured data shows that an increase of the horizontal pressure losses and variability is expected with a higher undulation amplitude, translating the fact that larger instabilities are observed for higher amplitudes. The numerical simulation predicted lower translational velocity and frequency, higher slug’s lengths, and similar vertical pressure losses when compared to the experimental results.

The use of spirocycles in drug discovery and medicinal chemistry has been booming in the last two decades. This has clearly translated in the landscape of approved drugs. Among two dozen clinically used medicines containing a spirocycle, 50% have been approved in the 21st century. The present review focuses on the notable synthetic routes to such drugs invented in industry and academia and is intended to serve as a useful reference source of synthetic as well as general drug information for researchers engaging in the design of new spirocyclic scaffolds for medicinal use or embarking upon analog syntheses inspired by the existing approved drugs.

We reveal the significance of plasmonic nanoparticle’s (NP) shape and its surface morphology en route to an efficient self-assembled plasmonic nanoparticle cluster. A simplified model is simulated in the form of free-space dimer and trimer nanostructures (NPs in shape of sphere, cube, and disk). A ~ 200 % to ~ 125% raise in near field strength (gap mode enhancement) is observed for spherical NPs in comparison with cubical NPs (from 2 nm to 8 nm gap sizes). Full-width three-quarter maximum reveals better broad-spectral optical performance in a range of ~ 100 nm (dimer) and ~ 170 nm (trimer) from spherical NPs as compared to a cube (~ 60 nm for dimer and trimer). These excellent properties for sphere-based nanostructures are merited from its dipole mode characteristics.

We present a new analytical method to find the asymptotic stable equilibria states based on the Markov chain technique. We reveal this method on the SIR-type epidemiological model that we developed for viral diseases with long-term immunity memory pandemic. This is a large-scale model containing 15 nonlinear ODE equations, and classical methods have failed to analytically obtain its equilibria. The proposed method is used to conduct a comprehensive analysis by a stochastic representation of the dynamics of the model, followed by finding all asymptotic stable equilibrium states of the model for any values of parameters and initial conditions.

With the diversified development of media forms, livestreaming e-commerce has become a new sales model. Unlike the traditional sales model, this paper constructs a three-party game model composed of manufacturers, social media influencers and consumers based on the livestreaming model. It explores the equilibrium strategy selections of each participant in the supply chain system. In analyzing the evolutionary game stability of each participant, this paper obtains the equilibrium strategy and stability factors by analysis of the income and expenditure matrix. It uses the simulation model to analyze reasons for strategy selections of different game participants in the livestreaming e-commerce model. The results show that the strategies of manufacturers, social media influencers and consumers' selections have different impacts on their decision-making mechanism, and man-ufacturers are more sensitive to consumers' active participation in livestreaming e-commerce.

Studying the two famous old problems that why the moon can move around the Sun and why the orbit of the Moon around the Earth cannot be broken off by the Sun under the condition that calculating with F=GMm/R^2, the attractive force of the Sun on the Moon is almost 2.2 times that of the Earth. We found that the planet and moon are unified as one single gravitational unit which results in that the Sun cannot have the force of F=GMm/R^2 on the moon. The moon is moved by the gravitational unit orbiting around the Sun. It could indicate that the gravitational field of the moon is limited inside the unit and the gravitational fields of both the planet and moon is unified as one single field interacting with the Sun. The findings are further clarified by reestablishing Newton’s repulsive gravity.

Magnetometric Resistivity(MMR) Method, which can use the power supply method of the traditional apparent resistivity method to measure the magnetic field. At present, the application research abroad is relatively extensive, but the domestic(China) research on the application of the MMR method is very few, and it is not even well-known. This paper is based on the MMR theoretical method under the point source DC condition, combined with the abnormal potential method and the modified Biot-Savart law, and using the three-dimensional numerical calculation method of the finite difference method to calculate the abnormal potential field, electric field, and magnetic field on the matlab2018a platform. Calculate, realize the multi-physics simulation in the electromagnetic field through Matlab platform programming, and verify the correctness of the algorithm by the spherical anomaly model with an analytical solution. Through the visual simulation of the three-dimensional data volume of the multi-physics field in the electromagnetic field, we can better understand the response mechanism of the electromagnetic field under DC conditions and grasp their three-dimensional spatial distribution rules. It is hoped that the research in this article can help the research of MMR Personnel better use this method for exploration.

Multispectral remote sensing data may contain component images which are heavily corrupted by noise and pre-filtering (denoising) procedure is often applied to enhance these component images. To do this, one can use reference images – component images having relatively high quality and which are similar to the image subject to pre-filtering. Here we study the following problems: how to select component images that can be used as references (e.g., for the Sentinel multispectral remote sensing data) and how to perform the actual denoising. We demonstrate that component images of the same resolution as well as component images of a better resolution can be used as references. Examples of denoising of real-life images demonstrate high efficiency of the proposed approach.

The integration of renewable energy and hybrid energy storage system (HESS) into electrified railways to build electric railway smart microgrid system (ERSMS) is beneficial for reducing fossil fuel consumption and minimizing energy waste. However, the fluctuations of renewable energy generation and traction load challenge the energy management effectiveness for such a complex system. In this work, an energy management strategy is proposed which firstly decomposes the renewable energy into low-frequency and high-frequency components by an integrated empirical mode decomposition (IEMD). Then, a two-stage energy distribution approach is utilized to appropriately distribute the energy flow among the ERSMS. Finally, the feasibility and effectiveness of the proposed solution are validated through case study.

The circuitry of the summarized "floating" differential stages (FDS) based on complementary field-effect transistors with a control p-n junction (CJFET), intended for use in low-noise analog microcircuits, for example, operational amplifiers. The results of modeling the flow characteristics of one of the CJFET FDSs in the LTSpice XVII environment at low temperatures (down to -197 ⁰С) and exposure to a neutron flux in the range of 1e13 ÷ 1e15 n / cm² are presented.

This paper presents the experimental implementations of the mathematical models and algorithms developed in Part I. Two experiments are carried out. The first experiment aims at the determinations of the correction coefficients of the mathematical model. The dot grid target is measured and the measurement data are processed by our developed and validated algorithms introduced in Part I. The values of the coefficients are indicated and analysed. Uncertainties are evaluated with implementation of the Monte Carlo method. The second experiment measures a different area of the dot grid target. The measurement results are corrected according to the coefficients determined in the first experiment. The mean residual between the measured points and their corresponding certified values reduced 29.6% after the correction. The sum of squared errors reduced 47.7%. The methods and the algorithms for raw data processing, such as data partition, fittings of dots’ centres, K-means clustering, etc., are the same for both two experiments. The experimental results demonstrate that our method for the correction of the errors produced by the movement of lateral stage of confocal microscope is meaningful and practicable.

Healthy life style is associated with decreased risk of chronic kidney disease (CKD) and mortality in the general population. However, there is no definitive evidence on the benefits of physical activity and other health-related behaviors in the early-stage CKD. This study aimed to explore the association between health-related behaviors and end-stage renal disease (ESRD) and mortality in the early stages of CKD. The National Health Insurance Service (NHIS) database from January 1st, 2009 to December 31st, 2016 was used to screen 83,470 subjects with early stage CKD. Cox proportional hazard regression analysis was used to evaluate the association between health-related behaviors and ESRD and death. Kaplan-Meier curves for mortality and ESRD were plotted according to the physical activity, smoking status and alcohol consumption pattern. Risk of death decreased significantly in subjects who engaged in sufficient physical activity (adjusted Hazard Ratio (HR) 0.73; 95% CI: 0.64-0.83; p < 0.001). Risk of ESRD and death increased significantly in the current smoker with adjusted HR of 1.44 (95% CI: 1.06-1.95; p < 0.02) and 1.61 (95% CI: 1.44-1.80; p < 0.001) respectively. Therefore, systematic interventions to encourage physical activity and smoking cessation need to be actively considered in the early stages of CKD.

In recent, Chae found that, at weak gravitational acceleration g_N≲10⁻⁹ms⁻², the observed orbit of the wide binary stars is not accordant with current theory of binary star. Here, we present, this finding should be an observational evidence for that Newtonian theory of orbit perturbation is still valid in galactic scale.

Right-sided ligamentum teres (RSLT) is a rare anatomic variant in which the fetal umbilical vein connects to the right portal vein. Patients with RSLT frequently have hepatic vasculature and bile duct anomalies, which increase the risk of complications with hepatectomy. Most patients with RSLT undergo open hepatectomy. We describe a patient with RSLT and hepatocellular carcinoma who underwent laparoscopic hepatectomy. The patient was a 69-year-old man with hepatocellular carcinoma located in the left liver based on computed tomography (CT) and magnetic resonance imaging. Imaging also demonstrated RSLT. Three-dimensional CT analysis revealed independent right lateral type anomalies of the portal vein and bile duct. Laparoscopic extended left lateral sectionectomy was performed after careful surgical planning. Ultrasonography was used frequently during surgery to avoid damaging the right hepatic vasculature. The left lateral and partial left median sections were removed as planned. The patient’s postoperative recovery was uneventful. Avoiding injury to the right hepatic vasculature is essential when performing left lobectomy, including left lateral sectionectomy, in patients with RSLT. Laparoscopic hepatectomy can be performed safely in patients with RSLT, provided that careful surgical planning is conducted using preoperative three-dimensional CT analysis and intraoperative ultrasonography is used.

The shape of the knee is a chain-like structure of an ellipsoid. This suggests that, in the latest study, in addition to rolling, there is slippage in the motion of the knee. This paper selects a mechanical braking model for cattle based on two mechanical structures in different directions at the joints. The experimental results show that the modified dynamical system has strong chaotic properties. This can be one of the basis for judging various health states.

The 32CA reactions of a series of pairs of bent three-atom-components (B-TACs) and linear TACs (L-TACs) towards electrophilic dicyanoethylene (DCE) have been studied within the Molecular Electron Density Theory in order to understand their different reactivity. ELF analysis indicates that while pseudodiradical B-TACs change their electronic structure to pseudoradical or carbenoid L-TACs upon dehydrogenation, zwitterionic B-TACs experience no remarkable change. Analysis of the CDFT indices indicates that five of the nine studied TACs have a strong nucleophilic character, thus participating in polar reactions towards electrophilic ethylenes. The activation energies of the 32CA reactions of the nine TACs towards electrophilic DCE range from 0.6 to 22.0 kcal·mol-1, which are by between 2.0 and 10.1 kcal·mol-1 lower than those involved in the non-polar 32CA reactions with ethylene. In general, B-TACs are more reactive than their L-TAC counterparts. A change of the regioselectivity is found in these polar 32CA reactions; in general, while B-TACs are meta regioselective, L-TACs are ortho regioselective. Analysis of the geometrical parameters indicates that at all TSs, the formation of the single bond involving the most electrophilic C4 carbon of DCE is more advanced than that involving the C5 one. A change of the asynchronicity in the reactions involving B-TACs and L-TACs is also found.

This research is aimed at determining the characteristics of the current level of entrepreneurial potential of the Three Seas Initiative (3SI) countries, the ability to overcome the consequences of extraordinary events, such as COVID-19 and prospects for the return to an accelerated development once the destabiliser of the economic system, the coronavirus pandemic, has ceased. Eurostat, World Bank and the World Economic Forum data for 2015-2019 were used for the purpose of the research. The research was divided into three stages, i.e. assessment of economic development on the basis of a synthetic ratio of economic anchor development, for which a relative benchmark method based on spatial median (so-called L1 median or Weber point) was used, identification of conditions for the development of entrepreneurial capacity and statistical analysis showing the correlation between economic anchor measures and selected factors of the 3SI countries economic development. Our study found that the entrepreneurial capacity of the 3SI countries in 2015-2019 was determined by nine characteristics, belonging to six areas, i.e. local economy, demographic situation, social situation, trade exchange, innovation and tourism economy. The entrepreneurial potential of the 3SI countries was spatially diversified, and its development was determined, among others, by the entrepreneurial activity of residents (entrepreneurship index) and the conditions for running a business.

The tumor organoid (tumoroid) model in three-dimensional (3D) culture systems has been developed to reflect more closely the in vivo tumors than 2D-cultured tumor cells. Notably, extracellular vesicles (EVs) are efficiently collectible from the culture supernatant of gel-free tumoroids. Matrix metalloproteinase (MMP) 3 is a multi-functional factor playing crucial roles in tumor progression. However, roles of MMP3 within tumor growth and EVs have not unveiled. Here, we investigated the protumorigenic roles of MMP3 on integrities of tumoroids and EVs. We generated MMP3-knockout (KO) cells using the CRISPR/Cas9 system from rapidly metastatic LuM1 tumor cells. Moreover, we established fluorescent cell lines with palmitoylation signal-fused fluorescent proteins (tdTomato and enhanced GFP). Then we confirmed the exchange of EVs between cellular populations and tumoroids. LuM1-tumoroids released large EVs (300-1000 nm) and small EVs (50-200 nm) while the knockout of MMP3 resulted in the additional release of broken EVs from tumoroids. The loss of MMP3 leads to a significant reduction in tumoroid size and to the development of the necrotic area within tumoroids. MMP3 and CD9 (a category-1 EV marker tetraspanin protein) were significantly down-regulated in MMP3-KO cells and their EV fraction. These weakened phenotypes by MMP3 KO were markedly rescued by the addition of MMP3-rich EVs or conditioned medium (CM) collected from LuM1-tumoroids, which caused a dramatic rise in the expression of MMP3, CD9, and Ki-67 (a marker of proliferating cells) in the MMP3-null/CD9-low tumoroids. Notably, MMP3 enriched in tumoroids-derived EVs and CM deeply penetrated into recipient MMP3-KO tumoroids, resulting in a remarkable enlargement of solid tumoroids, while MMP3-null EVs did not. These data demonstrate that EVs can mediate molecular transfer of MMP3 resulting in increasing the proliferation and CD9+ tumorigenesis, indicating crucial roles of MMP3 in tumor progression.

One challenging problem is the representation of three-dimensional datasets that vary with time. These datasets can be though as a cloud of points that gradually deforms. But point-wise variations lack of information about the overall deformation pattern, and more importantly, about the extreme deformation locations inside the cloud. The present article applies a technique in computational mechanics to derive the strain-rate state of a time-dependent and three-dimensional data distribution, by which one can characterize its main trends of shift. Indeed, the tensorial analysis methodology is able to determine the global deformation rates in the entire dataset. With the use of this technique, one can characterize the significant fluctuations in a reduced multivariate description of an urban system and identify the possible causes of those changes: calculating the strain-rate state of a PCA-based multivariate description of an urban system, we are able to describe the clustering and divergence patterns between the districts of the city and to characterize the temporal rate in which those variations happen.

The Colebrook equation ζ is implicitly given in respect to the unknown flow friction factor λ ; λ=ζ(Re,ε*,λ) which cannot be expressed explicitly in exact way without simplifications and use of approximate calculus. Common approach to solve it is through the Newton-Raphson iterative procedure or through the fixed-point iterative procedure. Both requires in some case even eight iterations. On the other hand numerous more powerful iterative methods such as three-or two-point methods, etc. are available. The purpose is to choose optimal iterative method in order to solve the implicit Colebrook equation for flow friction accurately using the least possible number of iterations. The methods are thoroughly tested and those which require the least possible number of iterations to reach the accurate solution are identified. The most powerful three-point methods require in worst case only two iterations to reach final solution. The recommended representatives are Sharma-Guha-Gupta, Sharma-Sharma, Sharma-Arora, Džunić-Petković-Petković; Bi-Ren-Wu, Chun-Neta based on Kung-Traub, Neta, and Jain method based on Steffensen scheme. The recommended iterative methods can reach the final accurate solution with the least possible number of iterations. The approach is hybrid between iterative procedure and one-step explicit approximations and can be used in engineering design for initial rough, but also for final fine calculations.

Developing particles of different geometric anisotropic shapes are the hot topic since decades as they guarantee some special features of properties not possible through other means. Again, controlling atoms to develop certain size and shape particle is a quite challenging job. In this study, gold particles of different shapes are developed via pulse-based electronphoton-solution interface process. Here, it is discussed that gold atoms under certain transition state amalgamated at solution surface to develop monolayer assembly around the light glow of electrons and photons, which is known in plasma, generating through flowing argon gas copper capillary, which is known in cathode. The rate of uplifting gold atoms to solution surface is controlled under the fixed optimized entrance of forced energy electron streams and photons of high forcing energy. Uplifting gold atoms dissociated on dissociation of precursor under the dissipating heat energy resulted by propagating photonic current through graphite rod immersed in the solution, which is known in anode. On the other hand, packets of nano shape energy resulted by the controlled tuned pulse protocol developing tiny particles of own shape by binding transition state atoms of compact monolayer assembly. At solution surface, adjusting atoms of monolayer tiny particle into one-dimensional arrays under the disconcerted lateral forces following by their elongation under uniformly exerted opposite poles forces. This results into convert them in a structure of smooth elements where adjacently placed electrons and those in the outer rings of elongated atoms inter-connecting side-to-side by introducing orientational-based stretching of clamped energy knots. Tiny sized particles developed their atoms of one-dimensional arrays in structure of smooth elements exert an immersing force at favorable side tips and where many such tiny particles around the light glow work as one unit for each case resulting into pack by inter-connecting at inside their common point to nucleate the shape of certain particle. Depending on the development zone of such tiny sized particles and their amount of simultaneous packing under naturally maintained orientations develop their different geometric anisotropic shaped particles. At fixed precursor concentration, increasing the process time results into develop particles of low aspect ratio. Under tuned parameters, developing mechanisms of particles of high aspect ratio exhibiting unprecedented features are discussed.

Carotid atherosclerotic lesions are a major cause of cerebrovascular disease (CVD). Identification and quantification of carotid plaques are important for categorizing the vulnerability of plaques for rupture and assessing the impact of treatments. The irregularity of plaque surface is associated with previous plaque rupture and plays an important role in the risk of stroke. Thus, the aim of this study is to develop and validate novel vulnerability biomarkers from three-dimensional ultrasound (3DUS) images by analyzing the surface morphological characterization of carotid plaque using fractal geometry features. 3D box-counting and 3D blanket are the two types of 3D fractal dimension that were employed to describe the smoothness of plaques. This fractal dimension analysis tool was used to evaluate the effect of atorvastatin using 3DUS carotid images, which were acquired from 6 patients treated with atorvastatin with 80 mg daily and 5 patients with placebo. The Student's T Test results showed that those two fractal features were effective for detecting the statin-related changes in carotid atherosclerosis with p<0.0068 and p<0.015 respectively, suggesting that 3D fractal dimension measurements can be used effectively to analyze the surface characteristics of carotid plaques, especially for evaluating the impact of the treatment.

In the evolving landscape of vibration analysis, the integration of machine learning technologies for semi-automated analytical processes presents challenges in establishing clear cause-and-effect relationships in decision-making formulas. This research addresses this gap by exploring analytical diagnosis through residual signals, enabling the identification of anomalies and underperformance in machinery. Vibration signature analysis, focusing on distinctive vibration patterns, proves instrumental in detecting bearing defects and optimizing maintenance for enhanced operational efficiency and safety. Mathematical modeling, particularly worst-case analysis, provides a structured framework for decision-making under uncertainty. The research employs descriptive methods to analyze bearing wear data, transforming it into quantitative data for multiple regression equations. The derived equations reveal the dominance of harmonics in determining bearing wear stages, with PeakVue and overall vibration further indicating damage progression. The findings emphasize the significance of harmonic detection and high-frequency vibration analysis in predicting bearing health, offering a comprehensive approach to enhance machinery reliability. The study concludes with practical recommendations for bearing damage diagnosis based on the developed mathematical models, providing valuable insights for predictive maintenance strategies.

We analyzed mineralogical characteristics, and major as well as rare earth element concentrations from a cryptotephra layer in sediments of the infilled maar of Auel (Eifel, Germany). The results of detailed geochemical analyses of clinopyroxenes and their glassy rim of the specific layer are most similar to those from the Campanian Ignimbrite (CI) Tephra occurrence in a loess section at Urluia (Romania). Both records show idiomorphic green clinopyroxenes and formation of twisted minerals up to millimeter scale. The cryptotephra in the Auel core has an age of around 39,940 yr b2k in the ELSA-20 chronology, almost identical to the latest Ar/Ar dates for the Campanian Ignimbrite/Y5 eruption. These observations suggest that parts of the CI ash cloud were transported also northwestward into Central Europe, whereas the main branch of the CI ash plume was transported from southern Italy towards the NE, E and SE.

This paper aims to present a smart high speed battery charger, powered by a photovoltaic module array, for a LiFePO4 battery as a solar energy storage device. With a battery charging strategy, the presented battery charger involves a Buck converter as the core equipped with a simple maximum power point (MPP) tracker. Considering complexity reduction and easy hardware implementation, a constant voltage MPP tracking approach is adopted such that the maximum amount of output power can be delivered to the load in response to an arbitrary change in the solar radiation. A smart two-stage charging strategy, with a constant current mode followed by a constant voltage mode, is employed in such a way that the battery charge process can be accelerated largely, while the damage caused by overcharging can be prevented. In the end, the performance of this proposal is validated experimentally.

In India, where the transport sector contributes significantly to CO2 emissions, there has been a growing shift towards electric vehicles (EVs), particularly in the three-wheeler segment. Traditional auto-rickshaws, a staple in urban transportation, are often powered by internal combustion engines, leading to pollution and high fuel consumption. Electric three-wheelers, or e-rickshaws, have emerged as a cleaner, more efficient alternative, with zero tailpipe emissions. However, the successful adoption of electric three-wheelers depends on understanding the preferences and challenges faced by auto-rickshaw drivers, who are key to the Intermediate Public Transport (IPT) system. Based on this motivation, the study contributed to the literature by analyzing stated preference survey data from 2,403 respondents who purchased electric tricycles in 2023. We provide insights into the relationship between consumer demographics (such as age, income, gender, education), Vehicle operations, Vehicle financing and Electrification perspective and their preferences for specific electric and fuel tricycle segments. Finally, we estimate consumers' preference for electric tricycles and fuel tricycles. To do this, we use a discrete choice model and estimate the impact factor of Indian consumers in purchasing electric tricycles to obtain market penetration strategies for future electric tricycles.

Global warming is increasing the frequency and intensity of compound drought-heat events (CDHEs), potentially leading to larger and more extreme fire seasons in mesic forests. Wildfire activity in subtropical China, under the influence of monsoonal rainfall, was historically limited to dry winters and rare in rainy summers. Here we seek to test that this area is on the brink of a major change in its fire regime characterized by larger fire seasons, extending into the summer, leading to increases in burned area. We analyze fire activity in Chongqing Municipality (46,890 km2), an important area in subtropical China hosting the Three Gorges Reservoir Area. We observed significant increases in summer forest fires under anomalous dry-hot summer conditions, where total burned area was 3-6 higher than the historical annual mean (largely confined to the winter season). Vapor pressure deficit, an indicator of hot and dry conditions, was a strong predictor of fire activity, with major wildfires occurring on days where VPD was higher than 3.5kPa. Results indicate that major wildfire activity may occur in the area as a result of climate change, unless strong fire prevention policies are implemented.

A unified critical state model has been developed for both clean sand and silty sand using the modified Cam-clay model (MCC). The main feature of the proposed model is a new critical state line equation in the e-ln(p) plane that is capable of handling both straight and curved test results. With this feature, the error in calculating plastic volumetric strain is eliminated in theory. Another crucial feature of the model is the transformed stress tensor based on the SMP (spatially mobilized plane) criterion, which takes into account the proper shear yield and failure of soil under three-dimensional stresses. Additionally, the proposed model applies the intergranular void ratio with the fines influence factor for silty sand. Only eight soil parameters are required for clean sand, and a total number of twelve soil parameters are needed for silty sand.

In order to enhance the gain of antenna suitable for the airplane mounted platform, a conformal tightly coupled antenna array is investigated in this paper. Especially, three-dimensional (3-D) inkjet printing technique is used to implement the conformal property. The printing of antenna substrate and radiation layer is implemented by combining the fused deposition modelling and microdroplet injection molding technologies based on the existing 3-D printer. Here, through a unique combination of 3-D and 2-D inkjet printing of dielectric material and metallic ink, respectively, we demonstrate a monolithically integrated to a nonplanar antenna for the first time. Antenna measurements show that the complete characterization of this new process in terms of minimum feature sizes and achievable conductivities. This antenna configuration offers a high-gain performance with low-cost and rapid fabrication technique by using 3-D printing. The voltage standing wave ratio and radiation patterns are tested after adding the newly designed feed structure. Results shown the design process much efficient. Both antenna element and the array with good properties, which are in very good agreement with the specially mounted platform.

Single-layer core corrugated sandwich panels generally consist of a corrugated core and two layers of panels, while multi-layer core corrugated sandwich panels are formed by stacking multiple layers of panels with multiple layers of core layers. In this study, integrated multilayer core corrugated sandwich panels with different shapes of corrugated cores (triangular, trapezoidal, and rectangular) and the different number of core layers were fabricated using 3D printing technology, and the mechanical behavior of such multilayer core corrugated sandwich panels under quasi-static three-point bending was investigated using experiments and numerical simulations. The effects of core shape and number of core layers on the bending deformation process, damage mode, load carrying capacity, and bending energy dissipation capacity of multilayer core sandwich panels are discussed. Parametric design of multilayer triangular core corrugated sandwich panels was also carried out by finite element software ABAQUS. It was found that a new multilayer corrugated sandwich panel with a multi-layer core is better than the single core shape multilayer corrugated sandwich panel in terms of bending load capacity, energy dissipation capacity and deformation capacity can be obtained through the combination design of different core shapes.

Immunotherapy has gained great momentum with chimeric antigen receptor T cell (CAR-T) therapy, in which patient’s T lymphocytes are genetically manipulated to recognize tumor-specific antigens increasing tumor elimination efficiency. In the last years, CAR-T cell immunotherapy for hematological malignancies achieved a great response rate on patients and is a very promising therapy for several other malignancies. Each new CAR design requires a preclinical proof-of-concept experiment using immunodeficient mouse models. The absence of a functional immune system in these mice makes them simple and suitable to be mathematically modeled. In this work, we developed a three population mathematical model to describe tumor response to CAR-T cell immunotherapy in immunodeficient mouse models, encompassing interactions between a non-solid tumor and CAR-T cells (effector and long-term memory). We account for several phenomena, such as tumor-induced immunosuppression, memory pool formation, and conversion of memory into effector CAR-T cells in the presence of new tumor cells. Individual donor and tumor specificities were considered as uncertainties in the model parameters. Our model is able to reproduce several CAR-T cell immunotherapy scenarios, with different CAR receptors and tumor targets reported in the literature. We found that therapy effectiveness mostly depends on some specific parameters such as the differentiation of effector to memory CAR-T cells, CAR-T cytotoxic capacity, tumor growth rate, and tumor-induced immunosuppression. In summary, our model can contribute to reduce and optimize the number of in vivo experiments with in silico tests to select specific scenarios that could be tested in experimental research. Such in silico laboratory was made available in a Shiny R-based platform called CARTmath. It is an open-source, easy to run simulator, available at github.com/tmglncc/CARTmath or directly on the webpage cartmath.lncc.br, containing this manuscript results as examples and documentation. The developed model, together with the CARTmath platform, provides potential use for assessing different CAR-T cell immunotherapy protocols and associated efficacy, becoming an accessory towards in silico trials.

Within the scope of observed materialistic physical systems, without addressing the roots of H-Bar and big G, it is impossible to construct a workable model of final unification. With reference to our earlier proposed three large atomic gravitational constants, it is possible to reform and compactify the 10 dimensional String theory to 3+1 dimensions