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Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources 1 . Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds 2 , 3 . Here we report experiments at the Korea Superconducting Tokamak Advanced Research 4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors. A magnetic confinement regime established at the Korea Superconducting Tokamak Advanced Research device enables the generation of plasmas over 10 8  kelvin for 20 seconds with the aid of fast ions without plasma edge instabilities or impurity accumulation.

Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a possible association between BD and the gene encoding phospholipase Cγ1 ( PLCG1 ), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain ( Plcg1 f/f ; CaMKII ) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1 -deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca 2+ /calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1 f/f ; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.

Material pitting from cavitation bubble collapse is investigated numerically including two-way fluid–structure interaction (FSI). A hybrid numerical approach which links an incompressible boundary element method (BEM) solver and a compressible finite difference flow solver is applied to capture non-spherical bubble dynamics efficiently and accurately. The flow codes solve the fluid dynamics while intimately coupling the solution with a finite element structure code to enable simulation of the full FSI. During bubble collapse high impulsive pressures result from the impact of the bubble re-entrant jet on the material surface and from the collapse of the remaining bubble ring. A pit forms on the material surface when the impulsive pressure is large enough to result in high equivalent stresses exceeding the material yield stress. The results depend on bubble dynamics parameters such as the size of the bubble at its maximum volume, the bubble standoff distance from the material wall, and the pressure driving the bubble collapse. The effects of these parameters on the re-entrant jet, the following bubble ring collapse pressure, and the generated material pit characteristics are investigated.

Research over the past quarter century has identified cyclin D-dependent kinases, CDK4 and CDK6, as the major oncogenic drivers among members of the CDK superfamily. CDK4/6 are rendered hyperactive in the majority of human cancers through a multitude of genomic alterations. Sustained activation of these protein kinases provides cancer cells with the power to enter the cell cycle continuously by triggering G1-S-phase transitions and dramatically shortening the duration of the G1 phase. It has also become clear, however, that CDK4/6 effectively counter cancer cell-intrinsic tumor suppression mechanisms, senescence and apoptosis, which must be overcome during cell transformation and kept at bay throughout all stages of tumorigenesis. As a central ‘node’ in cellular signaling networks, cyclin D-dependent kinases sense a plethora of mitogenic signals to orchestrate specific transcriptional programs. As the complexity of the cellular signaling network regulated by these oncogenic kinases unfolds, much remains to be learned about its architecture, its dynamics and the consequences of its perturbation.

Unidirectional electric current flow, such as that found in a diode, is essential for modern electronics. It usually occurs at asymmetric interfaces such as p-n junctions or metal/semiconductor interfaces with Schottky barriers. We report on a diode effect associated with the direction of bulk electric polarization in BiFeO3: a ferroelectric with a small optical gap edge of approximately 2.2 electron volts. We found that bulk electric conduction in ferroelectric monodomain BiFeO3 crystals is highly nonlinear and unidirectional. This diode effect switches its direction when the electric polarization is flipped by an external voltage. A substantial visible-light photovoltaic effect is observed in BiFeO3 diode structures. These results should improve understanding of charge conduction mechanisms in leaky ferroelectrics and advance the design of switchable devices combining ferroelectric, electronic, and optical functionalities.

Although a large amount of acoustic indicators have already been proposed in the literature to evaluate the hypokinetic dysarthria of people with Parkinson's Disease, the goal of this work is to identify and interpret new reliable and complementary articulatory biomarkers that could be applied to predict/evaluate Parkinson's Disease from a diadochokinetic test, contributing to the possibility of a further multidimensional analysis of the speech of parkinsonian patients. The new biomarkers proposed are based on the kinetic behaviour of the envelope trace, which is directly linked with the articulatory dysfunctions introduced by the disease since the early stages. The interest of these new articulatory indicators stands on their easiness of identification and interpretation, and their potential to be translated into computer based automatic methods to screen the disease from the speech. Throughout this paper, the accuracy provided by these acoustic kinetic biomarkers is compared with the one obtained with a baseline system based on speaker identification techniques. Results show accuracies around 85% that are in line with those obtained with the complex state of the art speaker recognition techniques, but with an easier physical interpretation, which open the possibility to be transferred to a clinical setting.

Catalytic alkylation of C–H bonds is achieved via homolysis of N–H bonds of N -alkyl amides through proton-coupled electron transfer. Functionalizing unactivated aliphatic C–H bonds In two separate reports, Robert Knowles and colleagues, and John Chu and Tomislav Rovis report the selective homolysis of selected amidyl N–H bonds through a photocatalytic proton-coupled electron-transfer process. The resulting radical enables C–H abstraction and radical alkylation at the unactivated 5 position on the aliphatic chain of the N -alkyl amide. As this method does not rely on pre-activation of the amidyl N–H bond or the use of haloamides, it offers a potentially simpler solution than previous approaches to radical amidyls. Additionally, the subsequent 1,5-hydrogen-atom transfer offers a route to selective C–C bond formation in the presence of alkyl amides. Despite advances in hydrogen atom transfer (HAT) catalysis 1 , 2 , 3 , 4 , 5 , there are currently no molecular HAT catalysts that are capable of homolysing the strong nitrogen–hydrogen (N–H) bonds of N- alkyl amides. The motivation to develop amide homolysis protocols stems from the utility of the resultant amidyl radicals, which are involved in various synthetically useful transformations, including olefin amination 6 , 7 , 8 , 9 , 10 , 11 and directed carbon–hydrogen (C–H) bond functionalization 12 , 13 , 14 , 15 , 16 . In the latter process—a subset of the classical Hofmann–Löffler–Freytag reaction—amidyl radicals remove hydrogen atoms from unactivated aliphatic C–H bonds 17 , 18 , 19 , 20 , 21 . Although powerful, these transformations typically require oxidative N- prefunctionalization of the amide starting materials to achieve efficient amidyl generation. Moreover, because these N -activating groups are often incorporated into the final products, these methods are generally not amenable to the direct construction of carbon–carbon (C–C) bonds. Here we report an approach that overcomes these limitations by homolysing the N–H bonds of N -alkyl amides via proton-coupled electron transfer. In this protocol, an excited-state iridium photocatalyst and a weak phosphate base cooperatively serve to remove both a proton and an electron from an amide substrate in a concerted elementary step. The resultant amidyl radical intermediates are shown to promote subsequent C–H abstraction and radical alkylation steps. This C–H alkylation represents a catalytic variant of the Hofmann–Löffler–Freytag reaction, using simple, unfunctionalized amides to direct the formation of new C–C bonds. Given the prevalence of amides in pharmaceuticals and natural products, we anticipate that this method will simplify the synthesis and structural elaboration of amine-containing targets. Moreover, this study demonstrates that concerted proton-coupled electron transfer can enable homolytic activation of common organic functional groups that are energetically inaccessible using traditional HAT-based approaches.

We survey a representative sample of U.S. individuals about how well leading academic theories describe their financial beliefs and decisions. We find substantial support for many factors hypothesized to affect portfolio equity share, particularly background risk, investment horizon, rare disasters, transactional factors, and fixed costs of stock market participation. Individuals tend to believe that past mutual fund performance is a good signal of stock-picking skill, actively managed funds do not suffer from diseconomies of scale, value stocks are safer and do not have higher expected returns, and high-momentum stocks are riskier and do have higher expected returns.

The annual modulation signal observed by the DAMA experiment is a long-standing question in the community of dark matter direct detection. This necessitates an independent verification of its existence using the same detection technique. The COSINE-100 experiment has been operating with 106 kg of low-background NaI(Tl) detectors providing interesting checks on the DAMA signal. However, due to higher backgrounds in the NaI(Tl) crystals used in COSINE-100 relative to those used for DAMA, it was difficult to reach final conclusions. Since the start of COSINE-100 data taking in 2016, we also have initiated a program to develop ultra-pure NaI(Tl) crystals for COSINE-200, the next phase of the experiment. The program includes efforts of raw powder purification, ultra-pure NaI(Tl) crystal growth, and detector assembly techniques. After extensive research and development of NaI(Tl) crystal growth, we have successfully grown a few small-size (0.61–0.78 kg) thallium-doped crystals with high radio-purity. A high light yield has been achieved by improvements of our detector assembly technique. Here we report the ultra-pure NaI(Tl) detector developments at the Institute for Basic Science, Korea. The technique developed here will be applied to the production of NaI(Tl) detectors for the COSINE-200 experiment.