Powerful Option Research Articles

Next Generation Immuno-Oncology Strategies: Unleashing NK Cells Activity.

In recent years, immunotherapy has become a powerful therapeutic option against multiple malignancies. The unique capacity of natural killer (NK) cells to attack cancer cells without antigen specificity makes them an optimal immunotherapeutic tool for targeting tumors. Several approaches are currently being pursued to maximize the anti-tumor properties of NK cells in the clinic, including the development of NK cell expansion protocols for adoptive transfer, the establishment of a favorable microenvironment for NK cell activity, the redirection of NK cell activity against tumor cells, and the blockage of inhibitory mechanisms that constrain NK cell function. We here summarize the recent strategies in NK cell-based immunotherapies and discuss the requirement to further optimize these approaches for enhancement of the clinical outcome of NK cell-based immunotherapy targeting tumors.

The role and value of inter-seasonal grid-scale energy storage in net zero electricity systems

Grid-scale inter-seasonal energy storage and its ability to balance power demand and the supply of renewable energy may prove vital to decarbonise the broader energy system. Whilst there is a focus on techno-economic analysis and battery storage, there is a relative paucity of work on grid-scale energy storage on the system level with the required temporal resolution. Here, we evaluate the potential of power-to-gas-to-power as inter-seasonal energy storage technology. Our results suggest that inter-seasonal energy storage can reduce curtailment of renewable energy, and overcapacity of intermittent renewable power. Importantly, grid scale energy storage assumes a critical role especially when the technology options for dispatchable power are limited. It appears that neither high CAPEX nor low round-trip efficiency preclude the value of the technology per se, however the rate of charge and discharge of the technology emerges as key technical characteristic. This study emphasises the rising importance of balancing seasonality in energy systems characterised by a high penetration of renewable energy, and prompts questions regarding sector integration and resilient decision-making toward a zero-carbon economy.

Cancer: Can CRISPR Become a Game Changer?

Recent development in CRISPR technologies has emerged as a powerful tool for genome editing, which can become a powerful diagnostic and therapeutic option for cancer patients. While literature search demonstrates some successes in this dimension in animal models and phase-I human trials, still the promised panacea has shortcomings in terms of off-target mutations (OTMs), minimal efficiency, and tailoring individualised interventions. While there is a promise for the future, although the CRISPR technology still has to climb up the ladder in terms of improvements with more enhanced efficiency tools for delivering the payload into cell and reducing the off-target mutations. Key Words: CRISPR, Oncology, Off-target mutations (OTMs), Genome editing, 3-D cell cultures.

Incidence and Predictors of Valgus Tibiotalar Tilt after Progressive Collapsing Foot Deformity Reconstruction using Subtalar Fusion

Category: Ankle; Ankle Arthritis; Hindfoot; Midfoot/Forefoot; Other Introduction/Purpose: Subtalar fusion is a powerful option for correcting hindfoot deformity in progressive collapsing foot deformity (PCFD). Despite successful correction through subtalar fusion, the development of valgus tibiotalar tilt at the ankle joint has been documented as a significant complication. This can be detrimental since abnormal forces on the ankle joint can induce cartilage wear and subsequent ankle arthritis over time. However, the incidence of valgus tilt of the ankle following subtalar fusion for PCFD reconstruction has not been extensively studied, and little is known about its etiological factors. The purpose of this study was to define the incidence of valgus tibiotalar tilt after subtalar fusion for PCFD reconstruction, and to determine if any demographic and radiographic parameters predict which patients develop this complication. Methods: This study reviewed 59 patients (median age: 59 years) who underwent PCFD reconstruction with subtalar fusion and had pre-and postoperative weightbearing anteroposterior radiographs of the ankle in the registry. Patients with a tibiotalar tilt prior to surgery were excluded. On standard weightbearing radiographs, the talonavicular coverage angle, talo-1st metatarsal angle, calcaneal pitch, and hindfoot moment arm (HMA), and medial distal tibial angle were measured. Weightbearing computed tomography (WBCT) was used to determine the presence of preoperative sinus tarsi or calcaneofibular bony impingement. A radiologist evaluated the superficial and deep deltoid ligaments using magnetic resonance imaging (MRI). Postoperative valgus tibiotalar tilt was defined as tilt >2 degrees. Univariate regression analysis was used to identify the factors associated with development of postoperative valgus tibiotalar tilt. These factors included age, gender, BMI, as well as concomitant procedures, radiographic parameters, lateral bony impingement on WBCT, and deltoid ligament status on MRI. Results: A total of 17 patients (28.8%) developed postoperative valgus tibiotalar tilt at a mean of 7.7 (range, 2-31) months. Eight (47.1%) of the 17 patients developed valgus tibiotalar tilt (mean talar tilt of 5.3 degrees, range: 4-8) on postoperative weightbearing within 3 months. In bivariate analysis, male gender and preoperative HMA were significantly associated with development of valgus tibiotalar tilt (Table 1). Univariate logistic regression demonstrated that preoperative HMA was associated with postoperative valgus tibiotalar tilt (odds ratio 1.06, P = .026), with a 6% increase in risk per millimeter of increased HMA. Deltoid ligament status on MRI and concomitant procedures on other joints including fusion did not correlate with postoperative valgus tibiotalar tilt. Conclusion: The incidence of valgus tibiotalar tilt after subtalar fusion in PCFD reconstruction was 28.8% in this study. Preoperative valgus hindfoot alignment rather than the condition of the deltoid ligament was a significant predictor of postoperative valgus tibiotalar tilt. Our findings indicate that surgeons should be cognizant of patients with a greater degree of hindfoot valgus and of their propensity to develop a valgus ankle deformity. Additionally, our relatively high incidence of valgus tibiotalar tilt suggests that weightbearing ankle radiographs should be included in the initial and subsequent follow-up of PCFD patients with hindfoot valgus treated with subtalar fusions.

Pricing and Hedging Bond Power Exchange Options in a Stochastic String Term-Structure Model

We study power exchange options written on zero-coupon bonds under a stochastic string term-structure framework. Closed-form expressions for pricing and hedging bond power exchange options are obtained and, as particular cases, the corresponding expressions for call power options and constant underlying elasticity in strikes (CUES) options. Sufficient conditions for the equivalence of the European and the American versions of bond power exchange options are provided and the put-call parity relation for European bond power exchange options is established. Finally, we consider several applications of our results including duration and convexity measures for bond power exchange options, pricing extendable/accelerable maturity zero-coupon bonds, options to price a zero-coupon bond off of a shifted term-structure, and options on interest rates and rate spreads. In particular, we show that standard formulas for interest rate caplets and floorlets in a LIBOR market model can be obtained as special cases of bond power exchange options under a stochastic string term-structure model.

Synthetic Reagents for Enzyme‐Catalyzed Methylation

AbstractLate‐stage methylation is a key technology in the development of pharmaceutical compounds. Methyltransferase biocatalysis may provide powerful options to insert methyl groups into complex molecules with high regio‐ and chemoselectivity. The challenge of a large‐scale application of methyltransferases is their dependence on S‐adenosylmethionine (SAM) as a stoichiometric, and thus exceedingly expensive co‐substrate. As a solution to this problem, we and others have explored the use of methyl halides as reagents for the in situ regeneration of SAM. However, the need to handle volatile electrophiles, such as methyl iodide (MeI), may also hamper applications at scale. As a more practical solution, we have now developed an enzyme‐catalyzed process for the regeneration of SAM with methyl toluene sulfonate. Herein, we describe enzymes from the thiopurine methyltransferase family that accept sulfate‐ and sulfonate‐based methyl donors to convert S‐adenosylhomocysteine into SAM with efficiencies that rival MeI‐based reactions.

Synthetic Reagents for Enzyme‐Catalyzed Methylation

Late-stage methylation is a key technology in the development of pharmaceutical compounds. Methyltransferase biocatalysis may provide powerful options to insert methyl groups into complex molecules with high regio- and chemoselectivity. The challenge of a large-scale application of methyltransferases is their dependence on S-adenosylmethionine (SAM) as a stoichiometric, and thus exceedingly expensive co-substrate. As a solution to this problem, we and others have explored the use of methyl halides as reagents for the in situ regeneration of SAM. However, the need to handle volatile electrophiles, such as methyl iodide (MeI), may also hamper applications at scale. As a more practical solution, we have now developed an enzyme-catalyzed process for the regeneration of SAM with methyl toluene sulfonate. Herein, we describe enzymes from the thiopurine methyltransferase family that accept sulfate- and sulfonate-based methyl donors to convert S-adenosylhomocysteine into SAM with efficiencies that rival MeI-based reactions.

Large-scale wind power grid modelling and stability evaluation using stochastic approaches

With the global demand to increase the level of low-carbon renewable energy resources (RERs) for electric power generation, dwindling fossil fuel reserves, and concerns that fossil fuel emissions are leading to climate change with possibly disastrous consequences, research is underway to discover the probable large-scale usage of RERs that will not be integrated into an existing power grid. A large-scale RER power grid is anticipated to run independently and be stable and dependable, like a traditional system. Wind power generation is no longer negligible. Wind energy is one of the most established renewable power options for ensuring RE self-sufficiency, but it's also one of the ficklest (RERs). Wind power generation is predicted to rise quickly in the next years owing to interest in renewable energy to counteract global warming. National or regional RE power networks are the subjects of growing study. The issue is the grid's stability and dependability. Wind farms' production variability, intermittency, and load mismatch can damage grid voltage stability. In answer to this difficulty, a large-scale wind power system was modeled using a stochastic methodology, and the results were analyzed using the Lyapunov technique, matrix exponential, and Hurwitz criteria to determine the future stability of a 100% RE grid.

Complex networks, an innovative methodology for functional zoning in forest management

Forest management planning requires a permanent collection of data on the distribution, composition, and structure of the stands that conform a woodland. These data serve as the basis for suggesting the most appropriate management scheme according to the natural resource conditions and management objectives. It is common for the collected databases’ structure and dimension to hinder their analysis using traditional descriptive techniques. Therefore, alternative methodologies are required to facilitate both the exploration of data properties and their collective behavior. We used complex networks analysis to identify distribution patterns of topographic, biological, and productive conditions of a managed forest, suggesting its functional zoning. The forest was considered a graph consisting of nodes and edges; the stands served as nodes and interactions between them as edges. Degree, clustering coefficient, triangles, and modularity were used as segregation and connectivity metrics to evaluate forest properties and allocate stands to five predefined potential forest uses (zones). The clustering coefficient metric provided the better graph partition, allowing to obtain the best alternatives for zoning the forest in conservation areas, areas with potential for timber production, and carbon storage. Proposing forest functional zoning through complex network theory is a powerful methodological option to represent the spatial and nonspatial interactions among the relevant attributes defining a forest ecosystem condition.

Nonparametric Option Pricing with Generalized Entropic Estimators

We propose a family of nonparametric estimators for an option price that require only the use of underlying return data, but can also easily incorporate information from observed option prices. Each estimator comes from a risk-neutral measure minimizing generalized entropy according to a different Cressie–Read discrepancy. We apply our method to price S&P 500 options and the cross-section of individual equity options, using distinct amounts of option data in the estimation. Estimators incorporating mild nonlinearities produce optimal pricing accuracy within the Cressie–Read family and outperform several benchmarks such as Black–Scholes and different GARCH option pricing models. Overall, we provide a powerful option pricing technique suitable for scenarios of limited option data availability.

Detection of the Atherosclerotic PCSK9 gene Inhibitors Through in silico Method to Improve Targeted Therapy

The PCSK9 is one of the most important marks for the evolution of therapeutic agents for atherosclerosis because its interaction with low-density lipoprotein receptors causes atherosclerosis. Protein-ligand interactions help us to understand the true mechanism of pharmacological action. This study seeks to identify the most powerful suppression options for PCSK9. Initially, the reported ACE inhibitors were included in pharmacophore modeling using PharmaGist. Next, ZINCPHARMER was used to screen the selected model against a ZINC database to identify putative drug candidates docked to the target protein to understand the interactions. The 10 best pharmacological candidates for PCSK9 with a binding energy of 9.8-8.2 kcal mol-1 were identified by molecular docking and their pharmacokinetic properties and oral bioavailability were evaluated. The (S) severalplant obtained chemicals have been discovered, including anti-hypersensitive drugs such as “Canadine, Hesperetin, and Labetalol”. According to Biochemistry, these compounds formed a stable “protein-ligand” complex. The (S) canadine PCSK9 complex had the lowest RMSD and was the most stable. Future in vitro studies could identify (S) canadin as a promising atherosclerosis inhibitor for the evolution of novel PCSK9 inhibitors.

Interplay between different forms of power and meritocratic considerations shapes fairness perceptions

Power imbalance often leads to unequal allocations. However, it remains largely unknown how different forms of power and meritocratic considerations interact to shape fairness perceptions. Using modified Ultimatum Games, we examined how two power forms—decision power and availability of attractive outside option—affect bargaining behavior and fairness perceptions, and how meritocratic considerations are incorporated into the fairness perceptions of powerful and powerless individuals. We identified an asymmetric power effect: having increased decision power or attractive outside options independently increased self-advantageous allocations and self-serving fairness perceptions, whereas the combined lack of both power forms led to self-disadvantageous allocations but had no influence on fairness perceptions. The power effect on fairness perceptions became symmetric when power was obtained through a meritocratic process (procedural justice). In contrast, relative contributions to resource production (distributive justice) did not moderate power effects. We provide causal evidence that the powerful, but not the powerless, strive to minimize cognitive dissonance between behavior and fairness perceptions by interpreting fairness in self-serving ways. This study contributes novel insights into the interplay between different power forms, the asymmetry of power effects, the moderating role of procedural justice, and the mediating role of behavior in the power-driven adjustment of fairness perceptions.

Sea Water Converted into Usable and Emergency Drinkable Water

Abstract: Water could be very important for all residing beings. It covers almost 70% of earths surface. Even alevin though the principal part of earth is included via way of means of water, there's extreme scarcity of consuming water in maximum of the international locations throughout the world. Safe consuming water is crucial for all kinds of lifestyles alevin though it does now no longer offer any calories. Desalination of sea water seems as an answer for this problem. Advanced desalination technology which are carried out to seawater and brackish water show to be powerful options in a whole lot of situations. This take a look at in particular makes a speciality of upcoming traits in current desalination technology and emphasizing the alternatives supplied via way of means of them. Desalination is a way wherein the extra salts are eliminated from sea water or brackish water changing it into secure potable or usable water. Desalination techniques are labelled into thermal procedures and membrane procedures. In this bankruptcy we speak approximately special thermal procedures like multistage flash distillation, a couple of impact distillation, vapour compression evaporation, cogeneration and sun water desalination Keywords: Water management project, Desalination, Salt remova

Efficient and Robust Combinatorial Option Pricing Algorithms on the Trinomial Lattice for Polynomial and Barrier Options

Options can be priced by the lattice model, the results of which converge to the theoretical option value as the lattice’s number of time steps n approaches infinity. The time complexity of a common dynamic programming pricing approach on the lattice is slow (at least O n 2 ), and a large n is required to obtain accurate option values. Although O n -time combinatorial pricing algorithms have been developed for the classical binomial lattice, significantly oscillating convergence behavior makes them impractical. The flexibility of trinomial lattices can be leveraged to reduce the oscillation, but there are as yet no linear-time algorithms on trinomial lattices. We develop O n -time combinatorial pricing algorithms for polynomial options that cannot be analytically priced. The commonly traded plain vanilla and power options are degenerated cases of polynomial options. Barrier options that cannot be stably priced by the binomial lattice can be stably priced by our O n -time algorithm on a trinomial lattice. Numerical experiments demonstrate the efficiency and accuracy of our O n -time trinomial lattice algorithms.

Policy options for offshore wind power in Vietnam

This study assesses key barriers to offshore wind power (OWP) development in Vietnam and policy options for the development of the sector. A survey of 39 experts from government agencies, research institutions, industry, and civil society plus 22 follow-up interviews were conducted over January–September 2021, coupled with a broader analysis of key barriers and policy options. The analysis finds that an underdeveloped policy environment, incomplete procedures, and infrastructure and supply chain immaturity are key current barriers to OWP development in Vietnam. Recommended policy measures include: 1) setting a clear vision and ambitious target for OWP development, 2) adopting a renewable portfolio standard while charting the way for a move from feed-in tariffs to reverse auctions, 3) clarifying that OWP project developers are to self-connect to onshore grids, and 4) developing a streamlined leasing and licensing process within an integrated overall electricity and marine policy. If enabled by well-designed policy, OWP has the potential to play a key role in Vietnam’s emission reduction and energy availability efforts.

Trends in Aortic Occlusion and How to Minimize the Risk of Complications in REBOA

Resuscitative endovascular balloon occlusion of the aorta (REBOA) increases proximal aortic pressure in order to maintain central organ perfusion pressure, and simultaneously regulates distal arterial flow by endovascular aortic occlusion, which is applied during subdiaphragmatic hemorrhage. This article briefly introduces the history of REBOA and discusses its potential effectiveness and harmfulness. The article also mentions the technical aspects of REBOA, and reconsiders the term “REBOA” and “resuscitation.” The risks of aortic occlusion and ischemia-reperfusion injury have not been fully elucidated. It is hoped that REBOA can be used appropriately as a powerful option for the resuscitation of hemorrhagic patients and save the lives of as many patients as possible. The Society of Diagnostic and Interventional Radiology in Emergency, Critical Care, and Trauma will publish continuous medical education articles on REBOA.

Fabric‐Based Wearable Self‐Powered Asymmetric Supercapacitor Comprising Lead‐Free Perovskite Piezoelectrodes

AbstractThe demand for flexible supercapacitor sustaining green energy can go a long way in mitigating the issue of no power source in wearable electronics. Herein, a novel strategy is used to develop a self‐charging supercapacitor using lead‐free perovskites as piezoelectrodes and polyvinyl alcohol‐potassium hydroxide (PVA‐KOH) film as ionogelled electrolyte. This approach is unique as the existing conventional self‐powered devices are based only on piezoelectric electrolytes. The all‐solid‐state supercapacitor is asymmetric, with nickel stannate (NiSnO3) acting as the positrode and ferrous stannate (FeSnO3) as the negatrode. These materials are non‐toxic, environment‐friendly, and bio‐compatible, making them suitable for wearable electronics. The value of specific capacitance of FeSnO3 is 2853 F g–1, the highest among the perovskite‐based electrodes. The self‐charging characteristics of the fabricated supercapacitor are analyzed by bending, twisting, and subjecting it to compressive forces of varying magnitude. A maximum voltage of 266 mV is recorded through the self‐charging phenomenon. All these tests approve that the fabricated perovskite‐based supercapacitor is highly flexible, robust, stable, and has considerable electrochemical and self‐charging potential. The present study focuses on understanding the piezoelectric effect in self‐charging supercapacitors and offering a viable power option for self‐powered wearable devices in the future.

Tech-Economic Assessment of Power Transmission Options for Large-Scale Offshore Wind Farms in China

China is taking initiative in energy transition to cope with the long-term controversy of its enormous energy consumption, aiming to use less carbon. Wind power, especially offshore wind energy, has become a prevailing alternative due to its low carbon emissions, renewability, competitiveness, and operation security. The layout of a transmission channel is a key consideration in marine project implementation. This paper investigates the technical characteristics, application status, and viable advantages of a conventional AC transmission, voltage source converter-based high-voltage direct current (VSC-HVDC) transmission, gas-insulated line (GIL) transmission, and hybrid HVDC transmission. A component-resolved evaluation model was proposed to estimate the costs to be incurred of four electrical transmission options for offshore wind power along the coast of Eastern China, with technical feasibility and economical considerations. Cost comparisons and component sensitivity analyses were developed with different transmission distances and capacities. Results suggest HVAC transmission and VSC-HVDC are the preferable solutions for present offshore wind farm development in Eastern China, and the economic potential of the hybrid HVDC makes it feasible for future deployment. Some conclusions can be applied in disparate regions across the globe.

The exon-skipping oligonucleotide, KitStop, depletes tissue-resident mast cells in vivo to ameliorate anaphylaxis

Abstract Anaphylaxis represents the most extreme, life-threatening form of allergic disease and is often an emergency requiring immediate intervention. It occurs following cross-linking of the high-affinity IgE receptor (FcɛRI) on the surface of mast cells by allergen-IgE complexes; however, non-IgE-mediated and idiopathic mast cell activation also contribute. Causes include environmental allergens, foods, venoms, and medications. In addition, some people with mastocytosis have repeated anaphylactic episodes during normal daily activities with no exposure to these triggers. While acute therapy consists primarily of epinephrine and supportive care, chronic therapy relies heavily on desensitization to the inciting allergen—a time-consuming and sometimes unsuccessful process. Desensitization also requires identification of the trigger which is not always possible. Here, we report the use of an exon-skipping oligonucleotide, previously termed KitStop, to safely reduce the severity of anaphylaxis via mast cell depopulation in tissues. KitStop administration results in the integration of a premature stop codon within the mRNA transcript of the Kit receptor—a receptor tyrosine kinase found primarily on mast cells and whose gain-of-function mutation can result in systemic mastocytosis. After either local or systemic KitStop treatment, mice had significantly reduced mast cell numbers in the skin, peritoneum, and lungs. In addition, KitStop-treated mice had a significantly diminished anaphylactic response in a model of passive systemic anaphylaxis. These data demonstrate that KitStop has the potential to serve as a powerful treatment option for patients that experience anaphylaxis, including idiopathic anaphylaxis. Research was supported by the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID), Award Number R01AI143985 (G.C.), Department of Molecular Biomedical Sciences, College of Veterinary Medicine, start-up funds (G.C.), NCSU Center for Human Health and the Environment NIH P30ES025128 (G.C.), Institutional National Research Service Award from the Office of the Director of National Institutes of Health, NIH T32OD011130 (B.H., D.S.).

Strategically Substituted Agmatine Analogs Reduce Neuropathic Pain and Show Improved Pharmacokinetics Compared to Agmatine

Chronic pain remains a serious issue, affecting millions in the United States. Opioids serve as the most powerful therapeutic option but show limited efficacy in neuropathic pain and consequential side‐effects, such as tolerance, addiction, and respiratory depression. Development of novel drugs to treat pain, though, continues to stagnate. Additionally, in conditions in which opioids are required, adjuvants to reduce opioid‐induced neuroplasticity is critical. Agmatine has been shown to reduce neuropathic pain behavior and opioid tolerance, but use remains limited due to potentially reduced CNS penetration due to its hydrophilicity. Therefore, we have developed a series of agmatine‐based compounds that exhibit greater lipophilicity while exhibiting equivalent pharmacological responses (Figure 1). The goal of this study was to assess differences in pharmacokinetics and dynamics of 4 of these strategically substituted agmatines (SSAs). Our hypothesis is that these compounds will have an increased plasma half‐life and CNS distribution compared to agmatine, with equivalent reductions in neuropathic pain and opioid tolerance.Analysis of the pharmacokinetics in rat plasma was done using serial sampling via jugular catheter. All in vivo experiments were reviewed and approved by the University of Minnesota IACUC and the ACURO of the Department of Defense. After intravenous administration, the SSAs exhibit 2‐phase distribution and elimination and have an increased elimination half‐life over agmatine (9 minutes), with SSA3 and SSA4 showing the longest (Table 1). This increased half‐life aligns with the increased lipophilicity of these compounds. Additionally, SSA2 and SSA4 show large volumes of distribution, suggesting increased CNS distribution.To test the impact of these compounds in vivo, we induced neuropathic pain by performing spared nerve injury (SNI). SNI drives robust tactile hypersensitivity measured using the von Frey assay in the ipsilateral hind‐paw, with the contralateral paw serving as a non‐injured control. Following intravenous administration, SSA2‐4 reduced SNI‐induced hypersensitivity at similar doses to agmatine, showing equivalent pharmacological activity. Additionally, after chronic morphine treatment alongside co‐treatment with SSA1 and SSA2, opioid reduction in the warm water (52.5°C) tail flick response was preserved, representing a prevention of opioid tolerance. In conclusion, these chemical alterations to agmatine are able to improve pharmacokinetic parameters while maintaining the pharmacological reduction in neuropathic pain and opioid tolerance, suggesting potential as novel therapeutics to replace opioids in pain treatment.