Full Stability Research Articles

Eigenvalue bounds and spectral stability of Lamé operators with complex potentials

This paper is devoted to providing quantitative bounds on the location of eigenvalues, both discrete and embedded , of non self-adjoint Lamé operators of elasticity − Δ ⁎ + V in terms of suitable norms of the potential V . In particular, this allows to get sufficient conditions on the size of the potential such that the point spectrum of the perturbed operator remains empty. In three dimensions we show full spectral stability under suitable form-subordinated perturbations: we prove that the spectrum is purely continuous and coincides with the non negative semi-axis as in the free case.

Relationship Between Inflation and Unemployment: Testing Philips Curve Hypotheses and Investigating the Causes of Inflation and Unemployment in Nigeria

The attainment of full employment and price stability are one of the most widely used measures of economic health. Inflation and unemployment are an integral part of an economy; however, there is a need to balance both such that neither inflation nor unemployment is too high. The persistent rise in inflation and unemployment rates has called for the need to investigate the relevance of Philip’s postulation of a trade-off between inflation and unemployment in Nigeria. In addition to the interdependency or independence of these variables, there is also a need to access factors that may contribute to the increasing inflation and unemployment rates in Nigeria. These will enable policymakers to formulate policies that affect inflation and unemployment and pay attention to other variables that may directly or indirectly affect inflation and unemployment. Therefore, the study aims to test the validity of Philip’s curve hypotheses and examine possible causes of inflation and unemployment in Nigeria. The study used secondary data sourced from the Central Bank of Nigeria and the World Bank. Vector Autoregressive and Error Correction methods were adopted for the analysis. The study revealed that there is no significant relationship between inflation and unemployment in Nigeria. Inefficiencies from the government’s side and insufficient domestic investment were observed to be the possible causes of unemployment, whereas; exchange rate depreciation and money supply are blamed for the rising price levels in Nigeria. The study concludes that the problems of inflation and unemployment arise from inefficiencies in both monetary and fiscal policies. Efficient use of fiscal and monetary policies was recommended to raise employment and output in all sectors to meet the steaming local demand and export. Also, the full implementation of economic diversification policies is recommended. Furthermore, the study recommends increasing government spending on social infrastructure and incentives to firms to promote investment in Nigeria. These will have an overall effect of increasing output, reducing unemployment and achieving non-inflationary growth in Nigeria.

Validation and clinical application of a method to quantify efavirenz in cervicovaginal secretions from flocked swabs using liquid chromatography tandem mass spectrometry

Background: A liquid chromatography tandem mass spectrometry method to quantify drugs in dried cervicovaginal secretions from flocked swabs was developed and validated using the antiretroviral efavirenz as an example. Methods: Cervicovaginal swabs (CVS) were prepared by submerging flocked swabs in efavirenz-spiked matrix. Time to full saturation, weight uniformity, recovery and room temperature stability were evaluated. Chromatographic separation was on a reverse-phase C18 column by gradient elution using 1mM ammonium acetate in water/acetonitrile at 400 µL/min. Detection and quantification were on a TSQ Quantum Access triple quadrupole mass spectrometer operated in negative ionisation mode. The method was used to quantify efavirenz in CVS samples from human immunodeficiency virus (HIV)-positive women in the VADICT study (NCT03284645). A total of 98 samples (35 paired intensive CVS and DBS samples, 14 paired sparse CVS and DBS samples) from 19 participants were available for this analysis. Results: Swabs were fully saturated within 15 seconds, absorbing 128 µL of matrix with coefficient of variation (%CV) below 1.3%. The method was linear with a weighting factor (1/X) in the range of 25-10000 ng/mL with inter- and intra-day precision (% CV) of 7.69-14.9%, and accuracy (% bias) of 99.1-105.3%. Mean recovery of efavirenz from CVS was 83.8% (%CV, 11.2) with no significant matrix effect. Efavirenz remained stable in swabs for at least 35 days after drying and storage at room temperature. Median (range) CVS efavirenz AUC0-24h was 16370 ng*h/mL (5803-22088), Cmax was 1618 ng/mL (610-2438) at a Tmax of 8.0 h (8.0-12), and Cmin was 399 ng/mL (110-981). Efavirenz CVS:plasma AUC0-24 ratio was 0.41 (0.20-0.59). Conclusions: Further application of this method will improve our understanding of the pharmacology of other therapeutics in the female genital tract, including in low- and middle-income countries.

Functional Expression and Characterization of the Highly Promiscuous Lanthipeptide Synthetase SyncM, Enabling the Production of Lanthipeptides with a Broad Range of Ring Topologies.

Lanthipeptides are ribosomally synthesized and post-translationally modified peptides characterized by the presence of lanthionine rings that provide stability and functionality. Genome mining techniques have shown their huge diversity and potential for the discovery of novel active molecules. However, in many cases, they are not easily produced under laboratory conditions. The heterologous expression of these molecules using well-characterized lanthipeptide biosynthetic enzymes is rising as an alternative system for the design and production of new lanthipeptides with biotechnological or clinical properties. Nevertheless, the substrate-enzyme specificity limits the complete modification of the desired peptides and hence, their full stability and/or biological activity. New low substrate-selective biosynthetic enzymes are therefore necessary for the heterologous production of new-to-nature peptides. Here, we have identified, cloned, and heterologously expressed in Lactococcus lactis the most promiscuous lanthipeptide synthetase described to date, i.e., SyncM from the marine cyanobacteria Synechococcus MITS9509. We have characterized the functionality of SyncM by the successful expression of 15 out of 18 different SyncA substrates, subsequently determining the dehydration and cyclization processes in six representatives of them. This characterization highlights the very relaxed substrate specificity of SyncM toward its precursors and the ability to catalyze the formation of exceptionally large rings in a variety of topologies. Our results suggest that SyncM could be an attractive enzyme to design and produce a wide variety of new-to-nature lanthipeptides with a broad range of ring topologies.

Capacitor-less Low-Dropout Regulator for Analog Sensing using 90nm Technology

The capacitor-less-output-low-dropout (CLO-LDO) regulator proposed in this study can manage a wide variety of load currents. To offer temperature independent controlled LDO output, the LDO's 0.844V reference voltage is obtained using BGR, the optimized design is presented that provide full range stability, fast transient response. These benefits allow the proposed LDO regulator to operate over a wide range of operating circumstances, with very high current efficiency 99.99% and low voltage drop 100mV, operating using very low quiescent current of 0.02µA, at the output of regulator. The proposed regulator design is constructed in 90nm CMOS technology, the structure of the regulator is implemented using a Two-stage operational amplifier to obtain large DC gain 50dB to improve supply noise rejection, and a feedback loop, and exhibits better performance in terms of large phase margin 64.516 degrees with no load and 70.63degree full load.

A Surrogate-Based Method for Compressible Boundary-Layer Transition Prediction

To improve robustness and efficiency of automatic transition prediction in aerodynamic design, a reduced model of linear stability analysis is usually adopted, such as -envelope or -database method. Nevertheless, building such a model is challenging when it comes to compressible flows, as the transition mechanism is more complex and multiple flow parameters should be taken into consideration. To address this problem, this paper proposes an efficient surrogate-based method for compressible boundary layers that uses pretrained surrogate models to substitute linear stability analysis, concerning stability analysis of both Tollmien–Schlichting and Mack modes, as well as transition prediction of flow over arbitrary-shaped airfoils. The proposed method is demonstrated by stability analysis of compressible flat-plate boundary layers at a wide range of Mach numbers of . It is also validated by transition prediction of flow over a low-speed natural-laminar-flow (NLF) airfoil NLF-0416 and a transonic NLF airfoil NPU-LSC-72613. Besides, a sample partitioning method is presented to accelerate surrogate-model training with large samples. Results show that the predicted growth rates of perturbations, factors, and corresponding transition locations by our method of using surrogate-based stability analysis agree well with those by a standard method of solving full linear stability equations.

Stability study of metronidazole cream, extemporaneously made in pharmacy

Abstract Background Rosacea is a chronic recurrent disease, characterized by facial redness, dilated blood vessels, inflammatory rash elements on the face. The pharmacy produces 2% metronidazole cream extemporaneously for the treatment of the disease, as there is no such cream concentration on the market. The treatment of the disease is usually long, so the shelf life of the cream is very important for the patient, especially for those who do not have the opportunity to reach the manufacturing pharmacy. The aim of this investigation was to determine the stability and shelf life of metronidazole cream. Methods Long-term stability study of metronidazole cream was applied at 25 ± 2° C, 60 ± 5% relative humidity; accelerated stability test at 40 ± 2 °C, 75 ± 5% relative humidity. The influence of stress conditions were evaluated on the stability of metronidazole cream. It was determined metronidazole cream texture and microbiological examination was applied. Results It was found that color (white), odor (odorless), integrity (homogeneous), pH (6.8) did not change during storage of metronidazole (6 months). Mechanical properties of the metronidazole cream: firmness, shear, consistency and cohesion throughout the study remained stable. High performance liquid chromatography in the full stability study showed that metronidazole concentrations did not fluctuate within ± 5%. Stress factors such as acid media, alkaline media, hydrogen peroxide, daylight and heat did not affect the stability of the cream. A microbiological examination of the metronidazole cream suited European Pharmacopoeia requirements. Conclusions The extemporaneously made metronidazole cream were stable for 6 months.

Towards the Implementation of Monetary Management in Islamic Economic System Based on Recent Developments

Monetary management is an essential part of the objectives of Shari’ah under the umbrella of the preservation of wealth (Ma’al). Our primary sources: Qur’an and Sunn’ah, provide divine legislation on the prohibition of Riba to manage bases of monetary transaction. Further, the juristic tools facilitate scholars to propose solutions to meet the emerging issues on diversified aspects of society. Muslim scholars have always adapted and contributed to the Islamic finance system and regulation, theoretically and practically. In recent decades, Islamic banking and finance has seen strong momentum with double digit growth, fulfilling the monetary requirement of depositors on the liability side along with industry on the asset side. We seek to review the theoretical and empirical literature on Islamic monetary mangement. Monetary management in the Islamic economic context is still an area that needs more research. This paper examines how literature has been developed over time up until modern Islamic economic and banking practices. The findings suggest that Islamic monetary management has been gradually developed in recent years and such development is remarkable steps forward in pursuing Islamic monetary policy independently. In addition, Islamic monetary policy is proved to be relatively more effective compared to interest based conventional monetary policy. The implications of such findings have established new milestones for the central banks of all the countries, including the muslim majority countries for pursuing interest free Islamic monetary policy with full confidence. Furthermore, there are four major views on Islamic monetary policy and the central banks of the world should choose one of the best methods and views for the greater effectiveness of monetary policy because conventional monetary policy has been less effective in bringing full employment and price stability in recent years and financial crisis has crippled the interest based conventional economic systems quite badly.

Label-Free Electrochemical Test of Protease Interaction with a Peptide Substrate Modified Gold Electrode

Efficient deposition of biomolecules on the surface, maintaining their full activity and stability, is a most significant factor in biosensor construction. For this reason, more and more research is focused on the development of electrochemical biosensors that have the ability to electrically detect adsorbed molecules on electrode surface with high selectivity and sensitivity. The presented research aims to develop an efficient methodology that allows quantification of processes related to the evaluation of enzyme activity (proprotein convertase) using electrochemical methods. In this study we used impedance spectroscopy to investigate the immobilization of peptide substrate (Arg-Val-Arg-Arg) modified with 11-mercaptoundecanoic acid on the surface of gold electrode. Both the synthesis of the peptide substrate as well as the full electrochemical characteristics of the obtained electrode materials have been described. Experimental conditions, including concentration of peptide substrate immobilization, modification time, linker, and the presence of additional blocking groups have been optimized. The main advantages of the described method is that it makes it possible to observe the peptide substrate–enzyme interaction without the need to use fluorescent labels. This also allows observation of this interaction at a very low concentration. Both of these factors make this new technique competitive with the standard spectrofluorimetric method.

Cyclic Derivatives of the Chemerin C-Terminus as Metabolically Stable Agonists at the Chemokine-like Receptor 1 for Cancer Treatment.

Simple SummaryThe innate immune system is a key player in the fight against tumors and metastasis. Chemerin induces the migration of immune cells towards sites of inflammation and is crucial for recruiting natural killer cells towards cancerous tissue. Several cancer types are able to evade the immune system by downregulating levels of chemerin in their environment, which is often associated with decreased patient survival. Treatment with chemerin could counteract this strategy and thus be beneficial for cancer immunotherapy. Here, we report on the design of small synthetic peptides derived from chemerin that are biologically active and stable in blood plasma. They could be used to specifically deliver chemotherapeutics to tumors that express the chemokine-like receptor 1 (CMKLR1) or support the immune system in fighting cancer. Thus, they represent promising cancer therapeutics.Chemerin is a small chemotactic protein and a modulator of the innate immune system. Its activity is mainly mediated by the chemokine-like receptor 1 (CMKLR1), a receptor expressed by natural killer cells, dendritic cells, and macrophages. Downregulation of chemerin is part of the immune evasion strategy exploited by several cancer types, including melanoma, breast cancer, and hepatocellular carcinoma. Administration of chemerin can potentially counteract these effects, but synthetically accessible, metabolically stable analogs are required. Other tumors display overexpression of CMKLR1, offering a potential entry point for targeted delivery of chemotherapeutics. Here, we present cyclic derivatives of the chemerin C-terminus (chemerin-9), the minimal activation sequence of chemerin. Chemerin-9 derivatives that were cyclized through positions four and nine retained activity while displaying full stability in blood plasma for more than 24 h. Therefore, these peptides could be used as a drug shuttle system to target cancer cells as demonstrated here by methotrexate conjugates.

Experimental and Theoretical Studies of Sonically Prepared Cu–Y, Cu–USY and Cu–ZSM-5 Catalysts for SCR deNOx

The objective of our study was to prepare Y-, USY- and ZSM-5-based catalysts by hydrothermal synthesis, followed by copper active-phase deposition by either conventional ion-exchange or ultrasonic irradiation. The resulting materials were characterized by XRD, BET, SEM, TEM, Raman, UV-Vis, monitoring ammonia and nitrogen oxide sorption by FT-IR and Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS). XRD data confirmed the purity and structure of the Y/USY or ZSM-5 zeolites. The nitrogen and ammonia sorption results indicated that the materials were highly porous and acidic. The metallic active phase was found in the form of cations in ion-exchanged zeolites and in the form of nanoparticle metal oxides in sonochemically prepared catalysts. The latter showed full activity and high stability in the SCR deNOx reaction. The faujasite-based catalysts were fully active at 200–400 °C, whereas the ZSM-5-based catalysts reached 100% activity at 400–500 °C. Our in situ DRIFTS experiments revealed that Cu–O(NO) and Cu–NH3 were intermediates, also indicating the role of Brønsted sites in the formation of NH4NO3. Furthermore, the results from our experimental in situ spectroscopic studies were compared with DFT models. Overall, our findings suggest two possible mechanisms for the deNOx reaction, depending on the method of catalyst preparation (i.e., conventional ion-exchange vs. ultrasonic irradiation).

MMT’s policy prescriptions in Small and Open Economies: Addressing some Controversies

According to Modern Monetary Theory, a country that issues its own floating currency -and has no foreign exchange denominated debt- can simultaneously achieve both full employment and price stability through an Employer of Last Resort. The ELR is a policy option in which the government offers a job to anyone willing and able to work at the program's wage. Along with a zero interest rate policy, these prescriptions constitute MMT’s base case for analysis. Unfortunately, they are seldom considered as a whole by critics. Most criticisms of MMT emphasize the inflationary consequences of full employment policy. The author argues that, ultimately, it is the definition of full employment that seems to be the key when discussing the feasibility and desirability of an ELR program. Implementing an ELR program could result in an increase of the price level as measured by some index. Arguing that, as a consequence, full employment should not be pursued is tantamount to keep using unemployment to control the price level.

Navigated Transsacral Screw Fixation for the Treatment of Bilateral Sacral Insufficiency Fractures.

Nondisplaced and minimally displaced sacral insufficiency fractures are increasingly being recognized as a cause of immobilizing low back pain in the elderly. These insufficiency fractures are most accurately diagnosed by visualizing sacral bone marrow edema on magnetic resonance imaging, which is the radiologic imaging modality with the highest sensitivity for identifying these fractures. Successful treatment options range from nonsurgical (eg, bed rest, pain medication, mobilization, antiosteoporotic medication, low-intensity-pulsed ultrasound, etc.) to surgical management (ie, sacroplasty and/or osteosynthesis with iliosacral screws or lumbosacral hinge fixation with or without application of reinforcing bone cement). The appropriate surgical treatment for frail subjects requires a less-invasive technique that establishes full weight-bearing stability for successful early remobilization of affected elderly and multimorbid individuals. Iliosacral screw osteosynthesis with a single C-arm is a common surgical technique for stabilizing the posterior pelvic ring after traumatic instabilities or fractures of the sacrum. Bilateral injuries are generally addressed from both sides of the pelvis. This article describes the surgical technique of 3D image-guided transsacral screw fixation for unilateral and bilateral nondisplaced sacral insufficiency fractures in the elderly using a single-sided approach, and specifies the associated preoperative and postoperative management. The procedure is illustrated in an instructional video that demonstrates step-by-step, how the navigated surgical procedure is performed.

Abraham Accords: Palestine issue should be addressed for a peaceful Middle East

Decades of tensions in the Middle East have left many regional countries in tatters. The Abraham Accords – a joint declaration of the United States, Israel, and the United Arab Emirates, was signed alongside a peace agreement, although there has never been a state of war or conflict between Israel and the UAE. To achieve full peace and stability in the region, the resolution of the Palestine-Israeli conflict is vital. The United States and Israel have a long history of cooperation in the maintenance of the security of Israel that ensures the protection of US interests to the detriment of other regional powers that may have the potential to become influential in the region, and that ignore Western interests. Geopolitical changes in the Middle East over the last decade have altered the threat perspective of the Arab monarchies. Support for the creation of an independent Palestine has diminished as the issue has started to be seen as a distraction from the real and immediate threats from emerging regional powers. Although the Gulf nations may wish to present themselves as the Arab protector of Palestine, they clarify that “every tub must stand on its own bottom.” The US support of a peaceful environment was a result of the Chinese presence in the region, which the former perceived as a threat to its hegemony. However, long-term peace cannot be achieved without taking into account the Palestinian issue, as the primary conflict. In the same vein, countries such as Iran and Turkey did not welcome the normalization situation between Israel and the Arab states due to the ignorance of the Palestinians’ interests. There are weaknesses of the Accords perhaps due to its impatient timing, and its contradiction with the international community, such as the UN, and its disregard of the two-state solution.

Multifunctional silica-coated mixed polymeric micelles for integrin-targeted therapy of pediatric patient-derived glioblastoma

Glioblastoma multiforme (GBM) remains a major cause of mortality because treatments are precluded by to the limited transport and penetration of chemotherapeutics across the blood–brain barrier. Pitavastatin (PTV) is a hydrophobic Food and Drug Administration (FDA)-approved anticholesterolemic agent with reported anti-GBM activity. In the present study, we encapsulate PTV in silica-coated polymeric micelles (SiO2 PMs) surface-modified with the cyclic peptide Arg-Gly-Asp-Phe-Val (cRGDfV) that actively targets the αvβ3 integrin overexpressed in the BBB endothelium and GBM. A central composite design is utilized to optimize the preparation process and improve the drug encapsulation ratio from 131 to 780 μg/mL. The silica shell provides full colloidal stability upon extreme dilution and enables a better control of the release kinetics in vitro with 28% of the cargo released after 12 h. Furthermore, SiO2 PMs show excellent compatibility and are internalized by human BBB endothelial cells, astrocytes and pericytes, as shown by confocal laser scanning fluorescence microscopy and flow cytometry. Finally, the anticancer efficacy is assessed in a pediatric patient-derived glioma cell line expressing high levels of the integrin subunits αv, β3 and β5. This PTV-loaded nanocarrier triggers apoptosis by reducing the mRNA level of anti-apoptotic genes NF-kβ, IL-6, BIRC1 and BIRC5 by 89%, 33%, 81% and 63%, respectively, and the cell viability by >60%. Overall, our results suggest the potential of these hybrid nanocarriers for the targeted therapy of GBM and other tumors overexpressing integrin receptors.

New Simple Breakage Index for Crushable Granular Soils

Abstract Degradation of geomaterials, that is, particle breakage, can be harmful to the full life-cycle stability of practical engineering; for example, rockfill dam, energy-pile foundation, railwa...

Chaos in a melting pot

Abstract

Analisa Perencanaan Regional - Tangerang Selatan

This study intends to analyze sectoral economic development in South Tangerang City, as a study of Regional Economics. Talking about Regional Economics is certainly not talking about an individual activity, but analyzing areas that have diverse potential and how to make policies to accelerate economic growth in all regions evenly. the main objectives of the economy are: full employment economic growth and price stability. There are several things that can be better regulated in the regions, and are additional main objectives, namely: environmental sustainability, equitable regional development, determination of leading sectors in the region, creating better linkages between sectors in the region, so that it becomes more synergistic and sustainability and Fulfillment of regional needs. The purpose of this research is to be able to use it as a regional economic development and a stimulus for a wider and systematic movement of economic activity, in planning the potential of sectors: slow growing nationally, uncompetitive sectors and backward sectors, in order to grow and developing, to be implemented in South Tangerang, as a buffer zone for the economy of the capital city of Jakarta.

Characterization of Recombinant Adeno-Associated Viruses (rAAVs) for Gene Therapy Using Orthogonal Techniques.

Viruses are increasingly used as vectors for delivery of genetic material for gene therapy and vaccine applications. Recombinant adeno-associated viruses (rAAVs) are a class of viral vector that is being investigated intensively in the development of gene therapies. To develop efficient rAAV therapies produced through controlled and economical manufacturing processes, multiple challenges need to be addressed starting from viral capsid design through identification of optimal process and formulation conditions to comprehensive quality control. Addressing these challenges requires fit-for-purpose analytics for extensive characterization of rAAV samples including measurements of capsid or particle titer, percentage of full rAAV particles, particle size, aggregate formation, thermal stability, genome release, and capsid charge, all of which may impact critical quality attributes of the final product. Importantly, there is a need for rapid analytical solutions not relying on the use of dedicated reagents and costly reference standards. In this study, we evaluate the capabilities of dynamic light scattering, multiangle dynamic light scattering, and SEC–MALS for analyses of rAAV5 samples in a broad range of viral concentrations (titers) at different levels of genome loading, sample heterogeneity, and sample conditions. The study shows that DLS and MADLS® can be used to determine the size of full and empty rAAV5 (27 ± 0.3 and 33 ± 0.4 nm, respectively). A linear range for rAAV5 size and titer determination with MADLS was established to be 4.4 × 1011–8.7 × 1013 cp/mL for the nominally full rAAV5 samples and 3.4 × 1011–7 × 1013 cp/mL for the nominally empty rAAV5 samples with 3–8% and 10–37% CV for the full and empty rAAV5 samples, respectively. The structural stability and viral load release were also inferred from a combination of DLS, SEC–MALS, and DSC. The structural characteristics of the rAAV5 start to change from 40 °C onward, with increasing aggregation observed. With this study, we explored and demonstrated the applicability and value of orthogonal and complementary label-free technologies for enhanced serotype-independent characterization of key properties and stability profiles of rAAV5 samples.

A finite element method for Allen–Cahn equation on deforming surface

The paper studies an Allen–Cahn-type equation defined on a time-dependent surface as a model of phase separation with order–disorder transition in a thin material layer. By a formal inner–outer expansion, it is shown that the limiting behavior of the solution is a geodesic mean curvature type flow in reference coordinates. A geometrically unfitted finite element method, known as a trace FEM, is considered for the numerical solution of the equation. The paper provides full stability analysis and convergence analysis that accounts for interpolation errors and an approximate recovery of the geometry.