The need and prospects for improved fusion reactors

Conceptual fusion reactor studies over the past 10–15 yr have projected systems that may be too large, complex, and costly to be of commercial interest. One main direction for improved fusion reactors points toward smaller, higher-power-density approaches. First-order economic issues (i.e., unit direct cost and cost of electricity) are used to support the need for more compact fusion reactors. The results of a number of recent conceptual designs of reversed-field pinch, spheromak, and tokamak fusion reactors are summarized as examples of more compact approaches. While a focus has been placed on increasing the fusion-power-core mass power density beyond the minimum economic threshold of 100–200 kWe/tonne, other means by which the overall attractiveness of fusion as a long-term energy source are also addressed.Nomenclature a Plasma minor radius at outboard equatorial plane (m) - A Plasma aspect ratioR _T /a - AC Annual charges ($/yr) - b Plasma minor radius in vertical direction (m) - B Magentic field at plasma or blanket (T) - B _c Magnetic field at the coil (T) - B Toroidal magnetic field (T) - B Poloidal magnetic field (T) - BOP Balance of plant - C Coil - COE Cost of electricity (mills/kWeh) - CRFPR Compact RFP reactor - CT Compact torus (FRC or spheromak) - c _FPC Unit cost of fusion power core ($/kg) - DC Direct cost ($) - DZP Dense Z-pinch - E Escalation rate (1/yr) - EDC Escalation during construction ($) - ET Elongated tokamak - F Annual fuel charges ($/yr) - FC Component of UDC not strongly dependent or FPC size ($/kWe) - FW First wall - FPC Fusion power core - f _Aux Fraction of gross electric power recirculated to BOP - f ₁ (IC+IDC+EDC)/DC - f ₂ (O&M + SCR + F)/AC - IC Indirect cost ($) - IDC Interest during construction ($) - I _w Neutron first-wall loading (MW/m²) - i Toroidal plasma current (MA) - j Plasma current density, I/a² - k _B Boltzmann constant, 1.602(10)^–16 (J/keV) - LWR Light-water (fission) reactor - MPD Mass power density 1000P_E/M_FPC (kWe/tonne) - M _N Blanket energy multiplication of 14.1-MeV neutron energy - M _FPC Mass of fusion power core (tonne) - n Plasma density (m^–3) or toroidal MHD mode number - O&M Annual operating and maintenance cost ($/yr) - p _f Plant availability factor - PFD Poloidal field dominated (CTs, RFP, DZP) - P Construction time (yr) - P_TH Thermal power (MWt) - P _E Net electric power (1-)P _ET (MWe) - P_ET Total gross electric power (MWe) - p_f Fusion power (MW) - q Tokamak safety factor (B /B _gq )(a/R _T ) - q _e EngineeringQ value, 1/e - R _T Major toroidal radius (m) - RFP Reversed-field pinch - RPE Reactor plant equipment (Account 22) - S Shield - SCR Annual spare component cost ($/yr) - SSR Second stability region for the tokamak - S/T/H Stellarator/torsatron/heliotron - ST Spherical tokamak or spherical torus - T Plasma temperature (keV) - TDC Total direct cost ($) - TOC Total overnight cost ($) - UDC Unit direct cost,TDC/10 ³ P _E ($/kWe) - V _p Plasma volume (m³) - W _p Plasma energy (GJ) - W _B Magnetic field energy (GJ) - Magnetic utilization efficiency, 2nk_BT/(B ²/2₀) - ₀ Permeability of free space, 4(10)^–7 H/m - XE Plasma confinement efficiency, a²/4_E - _e Plasma energy confinement time - _p Overall plant efficiency, _TH(1-) - _TH Thermal conversion efficiency - _FPC AverageFPC mass density (tonne/m³) - Plasma vertical elongation factor,b/a - Thickness of allFPC engineering structure surround plasma (m) - Total recirculating power fraction, (P _ET-P _E)/P _ET, or inverse aspect ratioa/R _T This work was performed under the auspices of USDOE, Office of Fusion Energy.     

An Overview of Next-Generation Androgen Receptor-Targeted Therapeutics in Development for the Treatment of Prostate Cancer

Traditional endocrine therapy for prostate cancer (PCa) has been directed at suppression of the androgen receptor (AR) signaling axis since Huggins et al. discovered that diethylstilbestrol (DES; an estrogen) produced chemical castration and PCa tumor regression. Androgen deprivation therapy (ADT) still remains the first-line PCa therapy. Insufficiency of ADT over time leads to castration-resistant PCa (CRPC) in which the AR axis is still active, despite castrate levels of circulating androgens. Despite the approval and use of multiple generations of competitive AR antagonists (antiandrogens), antiandrogen resistance emerges rapidly in CRPC due to several mechanisms, mostly converging in the AR axis. Recent evidence from multiple groups have defined noncompetitive or noncanonical direct binding sites on AR that can be targeted to inhibit the AR axis. This review discusses new developments in the PCa treatment paradigm that includes the next-generation molecules to noncanonical sites, proteolysis targeting chimera (PROTAC), or noncanonical N-terminal domain (NTD)-binding of selective AR degraders (SARDs). A few lead compounds targeting each of these novel noncanonical sites or with SARD activity are discussed. Many of these ligands are still in preclinical development, and a few early clinical leads have emerged, but successful late-stage clinical data are still lacking. The breadth and diversity of targets provide hope that optimized noncanonical inhibitors and/or SARDs will be able to overcome antiandrogen-resistant CRPC.     

Biflavonoid-Induced Disruption of Hydrogen Bonds Leads to Amyloid-β Disaggregation

Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, we further sought to investigate the structural basis of the Aβ disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of Aβ fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of Aβ fibril via the π–π interactions. Moreover, docking scores correlate well with the ThT EC₅₀ values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in Aβ fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of Aβ fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of Aβ fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer’s disease.     

A Newly Developed Synbiotic Yogurt Prevents Diabetes by Improving the Microbiome–Intestine–Pancreas Axis

The prevalence of type 2 diabetes mellitus (T2D) is increasing worldwide, and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be beneficial for T2D prevention. However, microbiome modulators that are effective, safe, affordable, and able to be administered daily are not yet available. Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced T2D in mice. We compared the effects of our synbiotic yogurt to those of a commercially available yogurt (control yogurt). Interestingly, we found that the feeding of the synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls. Surprisingly, the control yogurt exacerbated diabetes progression. Synbiotic yogurt beneficially modulated the gut microbiota composition compared to milk, while the control yogurt negatively modulated it by significantly increasing the abundance of detrimental bacteria such as Proteobacteria and Enterobacteriaceae. In addition, the synbiotic yogurt protected pancreatic islet morphology compared to the milk control, while the control yogurt demonstrated worse effects on islets. These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a therapeutic to prevent diabetes progression.     

Electron Microscopy Imaging Applications of Room Temperature Ionic Liquids in the Biological Field: A Review

For biological imaging using electron microscopy (EM), the use of room-temperature ionic liquids (RTILs) has been proposed as an alternative to traditional lengthy preparation methods. With their low vapor pressures and conductivity, RTILs can be applied onto hard-to-image soft and/or wet samples without dehydration – allowing for a more representative, hydrated state of material and opening the possibility for visualization of in situ physiological processes using conventional EM systems. However, RTILs have yet to be utilized to their full potential by microscopists and microbiologists alike. To this end, this review aims to provide a comprehensive summary of biological applications of RTILs for EM to bridge the RTIL, in situ microscopy, and biological communities. We outline future research avenues for the use of RTILs for the EM observation of biological samples, notably i) RTIL selection and optimization, ii) applications for live cell processes and iii) electron beam and ionic liquid interaction studies.     

Collaborative test of determination of iodine value in fish oils. 1. Reaction time and carbon tetrachloride or cyclohexane as solvents

Twenty-two laboratories participated in a collaborative test to determine the iodine value (IV) of eight samples of fish oil (four with IV<150, four with IV>150) with either carbon tetrachloride (AOCS Official Method Cd 1–25) or cyclohexane (AOCS Recommended Practice Cd 1b-87) as solvent and either 1 or 2 h of reaction time. Laboratories received coded duplicate samples (hidden duplicates) and carried out duplicate determinations on each oil by each solvent-time combination (open duplicates). Replacing carbon tetrachloride with cyclohexane resulted in a lower IV (P<0.001). The decrease averaged 1.6 IV units for low-IV oils and 3.8 IV units for high-IV oils; this difference in response of 2.2 IV units between low- and high-IV oils was significant (P<0.001). Increasing the reaction time had a relatively small effect (0.34±0.18). There was no interaction of reaction time with solvent or oil type. Cyclohexane caused emulsions, which made it difficult to titrate residual iodine and thus increased the variability of the determination. The repeatability standard deviations (s _r ), based on hidden duplicates, for 1-h reaction time with carbon tetrachloride and cyclohexane were 2.17 and 3.35, respectively. The corresponding reproducibility standard deviations were 2.73 and 4.53.     

Monoterpene concentrations in fresh,senescent, and decaying foliage of singleleaf pinyon (Pinus monophylla Torr. & Frem.: Pinaceae) from the western Great Basin

Senescent foliage from pines is potentially a large contributor to the total monoterpene content of the litter layer, and the availability of these compounds as phytotoxins may result from release of these compounds into the vapor phase. In order to determine the fate of several monoterpene hydrocarbons in the natural environment, we examined their concentrations in fresh, senescent, and decaying needles from 32 single-leaf pinyon pine (Pinus monophylla Torr. & Frem.: Pinaceae) trees growing at two different locations. Total monoterpene content was highest in the fresh needles (mean=5.6 ± 2.2 mg/g extracted air dry weight), but also remained relatively high in senescent needles (mean=3.6 ±1.8 mg/g extracted air dry weight), either still attached to the tree or forming the freshest layer of understory litter. Decaying needles within a dark decomposing layer of litter material 5–20 cm from the surface were found to contain much lower amounts of total monoterpenes (average: =0.12 ±0.06 mg/g extracted air dry weight). Further investigation of the fate of these compounds in the pinyon understory is required to determine if these hydrocarbons are indeed exerting phytotoxic characteristics.     

The Synthesis and Antitumor Activity of the Sodium Salt and Copper (II) Complex of N-[(Trimethylamineboryl)-Carbonyl]-L-Phenylalanine Methyl Ester

Sodium N-[(trimethylamineboryl)-carbonyl]-L-phenylalanine 2 and {N-[(trimethylamineboryl)-carbonyl]-L-phenylalanyl- carbxylato}-bis-{N-[(trimethylaminebryl)-carbonyl]-L-phenylalanine} dicopper (II) 3 were successfully synthesized. The agents blocked L(1210) leukemic cell DNA and RNA syntheses by inhibiting multiple enzyme activities for nucleic acid synthesis, e.g. PRPP amido transferase, IMP dehydrogenase, DNA polymerase alpha, thymidine kinase, and TMP kinase. The copper (II) complex 3 demonstrated improved ability to inhibit L(1210) partially purified DNA topoisomerase II compared to the parent compound while the sodium salt was inactive at 100 muM.