Vitamin D and calcium are required at the time of denosumab administration during osteoporosis treatment

To evaluate the differences in outcomes of treatment with denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients with primary osteoporosis. Patients were split into a denosumab monotherapy group （18 cases） or a denosumab plus vitamin D supplementation group （combination group; 23 cases）. We measured serum bone alkaline phosphatase （BAP）, tartrate-resistant acid phosphatase （TRACP）-5b and urinary N-terminal telopeptide of type-I collagen （NTX） at baseline, 1 week, as well as at I month and 2, 4, 8 and 12 months. We also measured bone mineral density （BMD） of L1-4 lumbar vertebrae （L）-BMD and bilateral hips （H）-BMD at baseline and at 4, 8 and 12 months. There was no significant difference in patient background. TRACP-5b and urinary NTX were significantly suppressed in both groups from I week to 12 months （except at 12 months for NTX）. In the combination group, TRACP-5b was significantly decreased compared with the denosumab monotherapy group at 2 and 4 months （P 〈 0.05）. BAP was significantly suppressed in both groups at 2-12 months. L-BMD significantly increased at 8 and 12 months （8.9%） in the combination group and at 4, 8 and 12 months （6.0%） in the denosumab monotherapy group, compared with those before treatment. H-BMD was significantly increased in the combination group （3.6%） compared with the denosumab group （1.2%） at 12 months （P 〈 0.05）. Compared with denosumab monotherapy, combination therapy of denosumab with vitamin D and calcium stopped the decrease in calcium caused by denosumab, inhibited bone metabolism to a greater extent, and increased BMD （especially at the hips）.

ToxR Is Required for Biofilm Formation and Motility of Vibrio Parahaemolyticus

Vibrio parahaemolyticus, the leading cause of seafood-borne gastroenteritis, has the ability to form biofilms on biotic and abiotic surfaces. Biofilm formation is a complicated process involving many specific structures and regulatory processes. The most significant of the structures and processes include polar and lateral flagella, mannose-sensitive hemagglutinin typeⅣpili, chitin-regulated pili,capsular polysaccharide (CPS), exopolysaccharide

Rho/Rock signal transduction pathway is required for MSC tenogenic differentiation

Mesenchymal stem cell （MSC）-based treatments have shown promise for improving tendon healing and repair. MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical stimuli, including into tenocytes. Cell elongation and cytoskeletal tension have been shown to be instrumental to the process of MSC differentiation. Previous studies have shown that inhibition of stress fiber formation leads MSCs to default toward an adipogenic lineage, which suggests that stress fibers are required for MSCs to sense the environmental factors that can induce differentiation into tenocytes. As the Rho/ROCK signal transduction pathway plays a critical role in both stress fiber formation and in cell sensation, we examined whether the activation of this pathway was required when inducing MSC tendon differentiation using rope-like silk scaffolds. To accomplish this, we employed a loss-of-function approach by knocking out ROCK, actin and myosin （two other components of the pathway） using the specific inhibitors Y-27632, Latrunculin A and blebbistatin, respectively. We demonstrated that independently disrupting the cytoskeleton and the Rho/ ROCK pathway abolished the expression of tendon differentiation markers and led to a loss of spindle morphology. Together, these studies suggest that the tension that is generated by MSC elongation is essential for MSC teno-differentiation and that the Rho/ROCK pathway is a critical mediator of tendon differentiation on rope-like silk scaffolds.

Effect of photovoltaic panel electric field on the wind speed required for dust removal from the panels

Methods to remove dust deposits by high-speed airflow have significant potential applications,with optimal design of flow velocity being the core technology.In this paper,we discuss the wind speed required for particle removal from photovoltaic(PV)panels by compressed air by analyzing the force exerted on the dust deposited on inclined photovoltaic panels,which also included different electrification mechanisms of dust while it is in contact with the PV panel.The results show that the effect of the particle charging mechanism in the electric field generated by the PV panel is greatly smaller than the effect of the Van der Waals force and gravity,but the effect of the particle charged by the contact electrification mechanism in the electrostatic field is very pronounced.The wind speed required for dust removal from the PV panel increases linearly with the PV panel electric field,so we suggest that the nighttime,when the PV electric field is relatively small,would be more appropriate time for dust removal.The above results are of great scientific importance for accurately grasping the dust distribution law and for achieving scientific removal of dust on PV panels.

Nrf2 is required for normal postnatal bone acquisition in mice

A large body of literature suggests that bone metabolism is susceptible to the ill effects of reactive species that accumulate in the body and cause cellular dysfunction. One of the body＇s front lines in defense against such damage is the transcription factor, Nrf2. This transcription factor regulates a plethora of antioxidant and cellular defense pathways to protect cells from such damage. Despite the breadth of knowledge of both the function of Nrf2 and the effects of reactive species in bone metabolism, the direct role of Nrf2 in skeletal biology has yet to be thoroughly examined. Thus, in the current study, we have examined the role of Nrf2 in postnatal bone metabolism in mice. Mice lacking Nrf2 （Nrf2-/-） exhibited a marked deficit in postnatal bone acquisition, which was most severe at 3 weeks of age when osteoblast numbers were 12-fold less than observed in control animals. While primary osteoblasts from Nrf2-/- mice functioned normally in vitro, the colony forming capacity of bone marrow stromal cells （BMSCs） from these mice was significantly reduced compared to controls. This defect could be rescued through treatment with the radical scavenger N-acetyl cysteine （NAC）, suggesting that increased reactive species stress might impair early osteoblastogenesis in BMSCs and lead to the failure of bone acquisition observed in Nrf2-/- animals. Taken together, these studies suggest Nrf2 represents a key pathway in regulating bone metabolism, which may provide future therapeutic targets to treat osteoporosis.

An improved method to assess the required strength of cemented backfill in underground stopes with an open face

Backfill is increasingly used in underground mines to reduce the surface impact from the wastes produced by the mining operations. But the main objectives of backfilling are to improve ground stability and reduce ore dilution. To this end, the backfill in a stope must possess a minimum strength to remain self-standing during mining of an adjacent stope. This required strength is often estimated using a solution proposed by Mitchell and co-workers, which was based on a limit equilibrium analysis of a wedge exposed by the open face. In this paper, three dimensional numerical simulations have been performed to assess the behavior of the wedge model. A new limit equilibrium solution is proposed, based on the backfill displacements obtained from the simulations. Comparisons are made between the proposed solution and experimental and numerical modeling results. Compared with the previous solution, a better agreement is obtained between the new solution and experimental results for the required cohesion and factor of safety. For large scale(field) conditions, the results also show that the required strength obtained from the proposed solution corresponds quite well to the simulated backfill response.

LRP6 in mesenchymal stem cells is required for bone formation during bone growth and bone remodeling

Lipoprotein receptor-related protein 6 （LRP6） plays a critical role in skeletal development and homeostasis in adults. However, the role of LRP6 in mesenchymal stem cells （MSCs）, skeletal stem cells that give rise to osteoblastic lineage, is unknown. In this study, we generated mice lacking LRP6 expression specifically in nestin＋ MSCs by crossing nestin-Cre mice with LRP6 flox mice and investigated the functional changes of bone marrow MSCs and skeletal alterations. Mice with LRP6 deletion in nestin＋ cells demonstrated reductions in body weight and body length at I and 3 months of age. Bone architecture measured by microCT （uCT） showed a significant reduction in bone mass in both trabecular and cortical bone of homozygous and heterozygous LRP6 mutant mice. A dramatic reduction in the numbers of osteoblasts but much less significant reduction in the numbers of osteoclasts was observed in the mutant mice. Osterix＋ osteoprogenitors and osteocalcin＋ osteoblasts significantly reduced at the secondary spongiosa area, but only moderately decreased at the primary spongiosa area in mutant mice. Bone marrow MSCs from the mutant mice showed decreased colony forming, cell viability and cell proliferation. Thus, LRP6 in bone marrow MSCs is essential for their survival and proliferation, and therefore, is a key positive regulator for bone formation during skeletal growth and remodeling.

Does the EVA valuation model explain the market value of equity better under changing required return than constant required return?

Through the Economic-Value-Added(EVA)valuation model,the expected market value of equity can be determined by adding the book value of equity with the present value of expected EVAs under the assumption of constant required return and constant return on equity.The equation of EVA valuation model has taken its shape under the assumption of constant required return and constant return on equity.However,a large body of empirical evidence indicates that required rate of return never remain constant.The EVA-valuation model formulated under constant required return cannot be implemented under the scenario of changing required return.In this study,we explored whether the EVA valuation model could be implemented under changing required return by making any changes in the model and found that it could be implemented under the scenario of changing required return by replacing the book value of the equity of the existing model with the present value of required earnings or normal market earnings.We further examined whether the explanatory ability of the EVA valuation model under the assumption of changing required return is better than that of the valuation model under the assumption of constant required return.Relative information content analyses were conducted by considering sample of the intrinsic value of equities determined by valuation models and the market value of equities of 69 large-cap,88 mid-cap,and 79 small-cap companies.The results showed that the EVA-based valuation model with changing normal market return outperformed the EVA-based valuation model with constant required return.

Gas6-Tyro3 signaling is required for Schwann cell myelination and possible remyelination

Myelin plays important roles in vertebrates,ensuring the rapid propagation of action potentials and the long-term integrity of axons,but the molecular mechanisms of myelin formation remain poorly understood.Recent studies have demonstrated that myelination is regulated by the TYRO3,AXL（also known as UFO）and MERTK.

Inositol-requiring enzyme 1α is required for gut development in Xenopus lavies embryos

AIM:To investigate the role of inositol-requiring enzyme 1α(IRE1α) in gut development of Xenopus lavies embryos.METHODS:Xenopus embryos were obtained with in vitro fertilization and cultured in 0.1 × MBSH.One and half nanogram of IRE1α,1 ng of IRE1α-GR mRNA,1 ng of IRE1αΔC-GR mRNA,and 50 ng of IRE1α morpholino oligonucleotide(MO) or XBP1(C)MO were injected into four blastomeres at 4-cell stage for scoring the phenotype and marker gene analysis.To rescue the effect of IRE1α MO,1 ng of IRE1α-GR mRNA was coinjected with 50 ng of MO.For the activation of the GR-fusion proteins,dexamethasone was prepared as 5 mmol/L stock solutions in 100% ethanol and applied to the mRNA injected embryos at desired stages in a concentration of 10 μmol/L in 0.1 × MBSH.Embryos were kept in dexamethasone up to stage 41.Whole-mount in situ hybridization was used to determine specific gene expression,such as IRE1α,IRE1β,Xbra and Xsox17α.IRE1α protein expression during Xenopus embryogenesis was detected by Western blotting.RESULTS:In the whole-mount in situ hybridization analysis,xenopus IRE1α and IRE1β showed quite different expression pattern during tadpole stage.The relatively higher expression of IRE1α was observed in the pancreas,and significant transcription of IRE1β was found in the liver.IRE1α protein could be detected at all developmental stages analyzed,from stage 1 to stage 42.Gain-of-function assay showed that IRE1α mRNA injected embryos at tailbud stage were nearly normal and the expression of the pan-mesodermal marker gene Xbra and the endodermal gene Xsox17α at stage 10.5 was not significantly changed in embryos injected with IRE1α mRNA as compared to uninjected control embryos.And at tadpole stage,the embryos injected with IRE1α-GR mRNA did not display overt phenotype,such as gut-coiling defect.Loss-of-function assay demonstrated that the IRE1α MO injected embryos were morphologically normal before the tailbud stages.We did not observe a significant change of mesodermal and endodermal marker gene expression,while after stage 40,about 80% of the MO injected embryos exhibited dramatic gut defects in which the guts did not coil,but other structures outside the gastrointestinal tract were relatively normal.To test if the phenotypes were specifically caused by the knockdown of IRE1α,a rescue experiment was performed by co-injection of IRE1α-GR mRMA with IRE1α MO.The data obtained demonstrated that the gut coiling defect was rescued.The deletion mutant of IRE1α was constructed,consisting of the N-terminal part without the C-terminal kinase and RNase domains named IRE1αΔC,to investigate the functional domain of IRE1α.Injection of IRE1αΔCGR mRNA caused similar morphological alterations with gut malformation by interfering with the function of endogenous xIRE1α.In order to investigate if IRE1α/XBP1 pathway was involved in gut development,50 ng of XBP1 MO was injected and the results showed that knockdown of XBP1 resulted in similar morphological alterations with gut-coiling defect at tadpole stage.CONCLUSION:IRE1α is not required for germ layer formation but for gut development in Xenopus lavies and it may function via XBP1-dependent pathway.

Solution Structure of SECIS, the mRNA Element Required for Eukaryotic Selenocysteine Insertion──Interaction Studies Withthe SECIS-Binding Protein SBP

Selenocysteine, a selenium-containing analog of cysteine, is found in the prokaryotic and eukaryotic kingdoms in active sites of enzymes involved in oxidation-reduction reactions. This aminoacid is cotranslationally incorporated at UGA codons which usually act as translation stop codons. In eukaryotes, decoding of selenocysteine necessitates the participation of the selenocysteine insertion sequence (SECIS), an element lying in the 3' -untranslated region of selenoprotein mRNAs. A detailed experimental study of the secondary structures of the SECIS elements of rat and human type 1 iodothyronine deiodinases and rat glutathione peroxidase was performed. Enzymatic and chemical structure probing led us to propose a secondary structure model, supported by sequence comparison of 23 SECIS mRNAs. The secondary structure model revealed the existence of a novel type of RNA motif composed of four consecutive non-Watson-Crick base-pairs. Using gel shift experiments, we identified in several mammalian cell type extracts the protein SBP,for SECIS-binding protein, that specifically recognizes the iodothyronine deiodinases and glutathione peroxidase SECIS elements. The structural model that we derived for the SECIS RNAs discloses RNA features possibly implicated in the binding of SBP and/or SECIS function

Classification and Comprehension of Software Requirements Using Ensemble Learning

The software development process mostly depends on accurately identifying both essential and optional features.Initially,user needs are typically expressed in free-form language,requiring significant time and human resources to translate these into clear functional and non-functional requirements.To address this challenge,various machine learning(ML)methods have been explored to automate the understanding of these requirements,aiming to reduce time and human effort.However,existing techniques often struggle with complex instructions and large-scale projects.In our study,we introduce an innovative approach known as the Functional and Non-functional Requirements Classifier(FNRC).By combining the traditional random forest algorithm with the Accuracy Sliding Window(ASW)technique,we develop optimal sub-ensembles that surpass the initial classifier’s accuracy while using fewer trees.Experimental results demonstrate that our FNRC methodology performs robustly across different datasets,achieving a balanced Precision of 75%on the PROMISE dataset and an impressive Recall of 85%on the CCHIT dataset.Both datasets consistently maintain an F-measure around 64%,highlighting FNRC’s ability to effectively balance precision and recall in diverse scenarios.These findings contribute to more accurate and efficient software development processes,increasing the probability of achieving successful project outcomes.

An Investigation on Open-RAN Specifications:Use Cases,Security Threats,Requirements,Discussions

The emergence of various technologies such as terahertz communications,Reconfigurable Intelligent Surfaces(RIS),and AI-powered communication services will burden network operators with rising infrastructure costs.Recently,the Open Radio Access Network(O-RAN)has been introduced as a solution for growing financial and operational burdens in Beyond 5G(B5G)and 6G networks.O-RAN promotes openness and intelligence to overcome the limitations of traditional RANs.By disaggregating conventional Base Band Units(BBUs)into O-RAN Distributed Units(O-DU)and O-RAN Centralized Units(O-CU),O-RAN offers greater flexibility for upgrades and network automation.However,this openness introduces new security challenges compared to traditional RANs.Many existing studies overlook these security requirements of the O-RAN networks.To gain deeper insights into the O-RAN system and security,this paper first provides an overview of the general O-RAN architecture and its diverse use cases relevant to B5G and 6G applications.We then delve into specifications of O-RAN security threats and requirements,aiming to mitigate security vulnerabilities effectively.By providing a comprehensive understanding of O-RAN architecture,use cases,and security considerations,thisworkserves as a valuable resource for future research in O-RAN and its security.

Requirements ranking based on crowd-sourcing high-end product USs

Based on the characteristics of high-end products,crowd-sourcing user stories can be seen as an effective means of gathering requirements,involving a large user base and generating a substantial amount of unstructured feedback.The key challenge lies in transforming abstract user needs into specific ones,requiring integration and analysis.Therefore,we propose a topic mining-based approach to categorize,summarize,and rank product requirements from user stories.Specifically,after determining the number of story categories based on py LDAvis,we initially classify“I want to”phrases within user stories.Subsequently,classic topic models are applied to each category to generate their names,defining each post-classification user story category as a requirement.Furthermore,a weighted ranking function is devised to calculate the importance of each requirement.Finally,we validate the effectiveness and feasibility of the proposed method using 2966 crowd-sourced user stories related to smart home systems.

Strategic Vision Required

Chinese enterprises in Africa need to understand local conditions to succed LIKe all local officials in Africa, Veueza Kasiringua from Namibia hopes she can provide momentum for local economic development and the improvement of people＇s livelihood during her tenure. ＂China has more than 30 years＇ experience in this regard that could be shared with Africa,＂ Veueza Kasiringua, Chairperson of the Management Committee of Tsumeb Municipality in Namib-

Estimating minimum ecological water required of the western route first stage project of China＇s south-to-north water transfer scheme for water exporting rivers

It is well known that there is abundant water resources in basin of the Yangtze River, the first largest river in China, which is mainly located in Southern China. However, water resources is very scarce in the basin of the Yellow River, which is mainly located in Northern China. So the western route project of south-north water transfer scheme （WRP-SNWTS） aims to transfer water from the Yangtze River to the Yellow River. The area of WRP-SNWT, located in the upper reaches of the Yangtze River and the main areas of Sichuan and the marginal areas of the Qinghai-Tibet Plateau, has sufficient water resources but fragile ecology and environment. Therefore, it is necessary for WRP-SNWT to analyze the ecology water required. Based on the planning principles of from low elevation to high elevation, from small to large, from short to long and from easy to difficulty, the WRP-SNWT will be constructed through three stage projects. The western route first stage project of the south-north water transfer scheme （WRFST-SNWTS） is planned to transfer 4×10^9m^3/a from six tributaries of the Yalong river and from Dadu river to Jiaqu of Yellow River.. Daqu river and Niqu river are the branches of Xianshui river. Sequ river, Duke river, Make river and Ake river are the branches of Dadu river, which account for 65-70% of the total river run-off. It need more research and the rest run-off can satisfy channel ecology water required. According to analysis ecological water required which mainly satisfy for aquicolous biology in water-exporting region, such as low air temperature. Fish and aquicolous biology main living from May to August, and rivers are iced up from December to March of next year, ecology water required mainly for fish and aquicolous biology. The flow criterion of Tennant method is modified. The ecology water required of WRFSP-SNWTS is estimated by the flow data of Zhuwo gauging station, Zhuba gauging station, Chuosijia gauging station and Zumuzu gauging station. The result show that the ecology water required calculated by modified Tennant less 1 l percent than that of Tennant. This estimating result can supply more water resources for transferring to Yellow River. Meanwhile, this can supply gist for research transferring water of WRFSP-SNWTS.

Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes

BACKGROUND Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus(T2DM),that is,patients who have insulin resistance,obesity,and other cardiovascular risk factors,suggesting that the presence of glutamic acid decarboxylase(anti-GAD65),islet antigen 2(anti-IA2),and zinc transporter 8(anti-Zn8T)antibodies could have deleterious effects on beta cell function,causing failure and earlier requirement for insulin treatment.AIM To evaluate anti-GAD65,anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of T2DM.METHODS This was a case–control study in patients with clinically diagnosed with T2DM(68 cases and 64 controls with and without early insulin dependence respectively),male and female,aged 12–18 years.Somatometry,blood pressure,glucose,insulin,C-peptide,glycated hemoglobin A1c,and lipid profiles were assessed.ELISA was used to measure anti-GAD65,anti-IA2,and anti-Zn8T antibodies.Descriptive statistics,Pearson'sχ2 test,Student's t test,and logistic regression was performed.P<0.05 was considered statistically significant.RESULTS There were 132 patients(53.8%female),with a mean age was 15.9±1.3 years,and there was a disease evolution time of 4.49±0.88 years.The presence of anti-GAD65,anti-IA2,and anti-Zn8T positivity was found in 29.5%,18.2%,and 15.9%,respectively.Dividing the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity:anti-GAD65 odds ratio(OR):2.42(1.112–5.303,P=0.026);anti-IA2:OR:1.55(0.859–2.818,P=0.105);and anti-Zn8T:OR:7.32(2.039–26.279,P=0.002).CONCLUSION Anti-GAD65 positivity was high in our study.Anti-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype,leading to an increased risk of early insulin dependence.

Towards Improving the Quality of Requirement and Testing Process in Agile Software Development:An Empirical Study

Software testing is a critical phase due to misconceptions about ambiguities in the requirements during specification,which affect the testing process.Therefore,it is difficult to identify all faults in software.As requirement changes continuously,it increases the irrelevancy and redundancy during testing.Due to these challenges;fault detection capability decreases and there arises a need to improve the testing process,which is based on changes in requirements specification.In this research,we have developed a model to resolve testing challenges through requirement prioritization and prediction in an agile-based environment.The research objective is to identify the most relevant and meaningful requirements through semantic analysis for correct change analysis.Then compute the similarity of requirements through case-based reasoning,which predicted the requirements for reuse and restricted to error-based requirements.Afterward,the apriori algorithm mapped out requirement frequency to select relevant test cases based on frequently reused or not reused test cases to increase the fault detection rate.Furthermore,the proposed model was evaluated by conducting experiments.The results showed that requirement redundancy and irrelevancy improved due to semantic analysis,which correctly predicted the requirements,increasing the fault detection rate and resulting in high user satisfaction.The predicted requirements are mapped into test cases,increasing the fault detection rate after changes to achieve higher user satisfaction.Therefore,the model improves the redundancy and irrelevancy of requirements by more than 90%compared to other clustering methods and the analytical hierarchical process,achieving an 80%fault detection rate at an earlier stage.Hence,it provides guidelines for practitioners and researchers in the modern era.In the future,we will provide the working prototype of this model for proof of concept.

How to implement a knowledge graph completeness assessment with the guidance of user requirements

In the context of big data, many large-scale knowledge graphs have emerged to effectively organize the explosive growth of web data on the Internet. To select suitable knowledge graphs for use from many knowledge graphs, quality assessment is particularly important. As an important thing of quality assessment, completeness assessment generally refers to the ratio of the current data volume to the total data volume.When evaluating the completeness of a knowledge graph, it is often necessary to refine the completeness dimension by setting different completeness metrics to produce more complete and understandable evaluation results for the knowledge graph.However, lack of awareness of requirements is the most problematic quality issue. In the actual evaluation process, the existing completeness metrics need to consider the actual application. Therefore, to accurately recommend suitable knowledge graphs to many users, it is particularly important to develop relevant measurement metrics and formulate measurement schemes for completeness. In this paper, we will first clarify the concept of completeness, establish each metric of completeness, and finally design a measurement proposal for the completeness of knowledge graphs.

Research Progress on Nutritional Requirements of Carp

Carp is a temperate freshwater fish native to Asia,distributed in all regions of the world except Australia and South America.With the improvement of comprehensive and healthy breeding technology of carp,the unit yield has been greatly increased mainly due to the exten-sive use of compound feed.In this study,the nutritional requirements of carp were summarized from the aspects of protein,amino acids,fat,carbohydrate,calcium and phosphorus,vitamins and taurine.This study provides a certain theoretical reference for scientific formula of carp feed.