Achievement of Target Gain Larger than Unity in an Inertial Fusion Experiment.

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment.

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.

A simple explanation for declining temperature sensitivity with warming.

Recently, multiple studies have reported declining phenological sensitivities (∆ days per ℃) with higher temperatures. Such observations have been used to suggest climate change is reshaping biological processes, with major implications for forecasts of future change. Here, we show that these results may simply be the outcome of using linear models to estimate nonlinear temperature responses, specifically for events that occur after a cumulative thermal threshold is met-a common model for many biological events. Corrections for the nonlinearity of temperature responses consistently remove the apparent decline. Our results show that rising temperatures combined with linear estimates based on calendar time produce the observations of declining sensitivity-without any shift in the underlying biology. Current methods may thus undermine efforts to identify when and how warming will reshape biological processes.

New Measures for Research on Men Who Have Sex with Men and for At-Risk Heterosexuals: Tools to Study Links Between Structural Interventions or Large-Scale Social Change and HIV Risk Behaviors, Service Use, and Infection.

Large-scale structural interventions and "Big Events" like revolutions, wars and major disasters can affect HIV transmission by changing the sizes of at-risk populations, making high-risk behaviors more or less likely, or changing contexts in which risk occurs. This paper describes new measures to investigate hypothesized pathways that could connect macro-social changes to subsequent HIV transmission. We developed a "menu" of novel scales and indexes on topics including norms about sex and drug injecting under different conditions, experiencing denial of dignity, agreement with cultural themes about what actions are needed for survival or resistance, solidarity and other issues. We interviewed 298 at-risk heterosexuals and 256 men who have sex with men in New York City about these measures and possible validators for them. Most measures showed evidence of criterion validity (absolute magnitude of Pearson's r ≥ 0.20) and reliability (Cronbach's alpha ≥ 0.70). These measures can be (cautiously) used to understand how macro-changes affect HIV and other risk. Many can also be used to understand risk contexts and dynamics in more normal situations. Additional efforts to improve and to replicate the validation of these measures should be conducted.

A pulsed-air model of blue whale B call vocalizations.

Blue whale sound production has been thought to occur by Helmholtz resonance via air flowing from the lungs into the upper respiratory spaces. This implies that the frequency of blue whale vocalizations might be directly proportional to the size of their sound-producing organs. Here we present a sound production mechanism where the fundamental and overtone frequencies of blue whale B calls can be well modeled using a series of short-duration (<1 s) wavelets. We propose that the likely source of these wavelets are pneumatic pulses caused by opening and closing of respiratory valves during air recirculation between the lungs and laryngeal sac. This vocal production model is similar to those proposed for humpback whales, where valve open/closure and vocal fold oscillation is passively driven by airflow between the lungs and upper respiratory spaces, and implies call frequencies could be actively changed by the animal to center fundamental tones at different frequency bands during the call series.

Genetic basis of octanoic acid resistance in Drosophila sechellia: functional analysis of a fine-mapped region.

Drosophila sechellia is a species of fruit fly endemic to the Seychelles islands. Unlike its generalist sister species, D. sechellia has evolved to be a specialist on the host plant Morinda citrifolia. This specialization is interesting because the plant's fruit contains secondary defence compounds, primarily octanoic acid (OA), that are lethal to most other Drosophilids. Although ecological and behavioural adaptations to this toxic fruit are known, the genetic basis for evolutionary changes in OA resistance is not. Prior work showed that a genomic region on chromosome 3R containing 18 genes has the greatest contribution to differences in OA resistance between D. sechellia and D. simulans. To determine which gene(s) in this region might be involved in the evolutionary change in OA resistance, we knocked down expression of each gene in this region in D. melanogaster with RNA interference (RNAi) (i) ubiquitously throughout development, (ii) during only the adult stage and (iii) within specific tissues. We identified three neighbouring genes in the Osiris family, Osiris 6 (Osi6), Osi7 and Osi8, that led to decreased OA resistance when ubiquitously knocked down. Tissue-specific RNAi, however, showed that decreasing expression of Osi6 and Osi7 specifically in the fat body and/or salivary glands increased OA resistance. Gene expression analyses of Osi6 and Osi7 revealed that while standing levels of expression are higher in D. sechellia, Osi6 expression is significantly downregulated in salivary glands in response to OA exposure, suggesting that evolved tissue-specific environmental plasticity of Osi6 expression may be responsible for OA resistance in D. sechellia.

Recent and future warm extreme events and high-mountain slope stability.

The number of large slope failures in some high-mountain regions such as the European Alps has increased during the past two to three decades. There is concern that recent climate change is driving this increase in slope failures, thus possibly further exacerbating the hazard in the future. Although the effects of a gradual temperature rise on glaciers and permafrost have been extensively studied, the impacts of short-term, unusually warm temperature increases on slope stability in high mountains remain largely unexplored. We describe several large slope failures in rock and ice in recent years in Alaska, New Zealand and the European Alps, and analyse weather patterns in the days and weeks before the failures. Although we did not find one general temperature pattern, all the failures were preceded by unusually warm periods; some happened immediately after temperatures suddenly dropped to freezing. We assessed the frequency of warm extremes in the future by analysing eight regional climate models from the recently completed European Union programme ENSEMBLES for the central Swiss Alps. The models show an increase in the higher frequency of high-temperature events for the period 2001-2050 compared with a 1951-2000 reference period. Warm events lasting 5, 10 and 30 days are projected to increase by about 1.5-4 times by 2050 and in some models by up to 10 times. Warm extremes can trigger large landslides in temperature-sensitive high mountains by enhancing the production of water by melt of snow and ice, and by rapid thaw. Although these processes reduce slope strength, they must be considered within the local geological, glaciological and topographic context of a slope.

National Ignition Facility laser performance status.

The National Ignition Facility (NIF) is the world's largest laser system. It contains a 192 beam neodymium glass laser that is designed to deliver 1.8 MJ at 500 TW at 351 nm in order to achieve energy gain (ignition) in a deuterium-tritium nuclear fusion target. To meet this goal, laser design criteria include the ability to generate pulses of up to 1.8 MJ total energy, with peak power of 500 TW and temporal pulse shapes spanning 2 orders of magnitude at the third harmonic (351 nm or 3omega) of the laser wavelength. The focal-spot fluence distribution of these pulses is carefully controlled, through a combination of special optics in the 1omega (1053 nm) portion of the laser (continuous phase plates), smoothing by spectral dispersion, and the overlapping of multiple beams with orthogonal polarization (polarization smoothing). We report performance qualification tests of the first eight beams of the NIF laser. Measurements are reported at both 1omega and 3omega, both with and without focal-spot conditioning. When scaled to full 192 beam operation, these results demonstrate, to the best of our knowledge for the first time, that the NIF will meet its laser performance design criteria, and that the NIF can simultaneously meet the temporal pulse shaping, focal-spot conditioning, and peak power requirements for two candidate indirect drive ignition designs.

Effect of multiple wavelengths on laser-induced damage in KH(2-x)DxPO4 crystals.

Laser-induced damage is a key factor that constrains the ways in which optical materials are used in high-power laser systems. We study the size and density of bulk laser-induced damage sites formed during frequency tripling in a DKDP crystal. The characteristics of the damage sites formed during tripling, for which 1053, 526, and 351 nm light is simultaneously present, are compared to those of damage sites formed by 351 nm light alone. The fluence of each wavelength is calculated as a function of depth with a full 4D(x,y,z,t) frequency conversion code and compared with measured damage density and size distributions. The density of damage is found to be governed predominantly by 351 nm light with some lesser, though nonnegligible, contribution from 526 nm light. The 1053 nm light does not appear to contribute to the damage density. The morphology of the damage sites, however, is seen to be relatively insensitive to wavelength and to depend only on total fluence of all wavelengths present. The strong and negligible wavelength dependences of initiation density and damage morphology, respectively, indicate that the dominant energy deposition mechanism varies during the damaging pulse.

Latissimus dorsi tendon transfer for massive rotator cuff tears: a cadaveric study.

Certain massive defects of the rotator cuff tendinous insertion cannot be repaired primarily to the greater tuberosity. If restoration of strength is an important treatment goal to the patient, then a tendon transfer may be considered. Ten cadaver shoulders were dissected to define the anatomy of the latissimus dorsi tendon (LDT) and its distance relationship to the axillary and radial nerves with the arm in various positions. The axillary nerve lies superior to the LDT insertion, and the radial nerve passes medial and inferior to the LDT insertion. With the arm internally rotated and the shoulder flexed, the distances from the axillary and radial nerves to the LDT insertion were 2.3 cm and 2.8 cm, respectively. With the arm internally rotated and the shoulder abducted, the distances from the axillary and radial nerves to the LDT insertion were 1.8 cm and 2.0 cm, respectively. Understanding specific anatomic relationships is one of the factors contributing to the safety of the LDT transfer procedure with respect to nerve injury.

The association of the dopamine D4 receptor gene (DRD4) and the serotonin transporter promoter gene (5-HTTLPR) with temperament in 12-month-old infants.

This study examined the association between two common polymorphisms, the dopamine D4 receptor (DRD4) gene and the serotonin transporter promoter (5-HTTLPR) gene and temperament in 61 infants aged 12 months. Twenty-two infants had a least one copy of the 6-8 repeat DRD4 alleles (L-DRD4) and 39 had two copies of the 2-5 repeat allele (S-DRD4). Twenty infants were homozygous for the short form (s/s) of 5-HTTLPR while 41 were either heterozygous for the short and the long form (l/s) or were homozygous for the long form (l/l). The infants were observed in a series of standard temperament episodes that elicited fear, anger, pleasure, interest, and activity. L-DRD4 infants showed less interest in a structured block play situation and more activity in a free play situation. They also displayed less anger in an episode of mild physical restraint. Infants with s/s 5-HTTLPR showed less fearful distress to stranger approach and less pleasure in a structured play situation than infants with l/l or l/s 5-HTTLPR. Duration of looking during block play was affected by a significant interaction between DRD4 and 5-HTTLPR. Shortest duration of looking was associated with the L-DRD4 and s/s 5-HTTLPR genotypes. The implications and limitations of these findings are discussed.

DRD4 related to infant attention and information processing: a developmental link to ADHD?

The dopamine D4 receptor (DRD4) exon III polymorphism has generated interest because of its association with attention deficit hyperactivity disorder (ADHD), with an increased frequency of the seven-repeat allele being reported in children with ADHD. Deficits in sustained attention and information processing characterize ADHD, and individual differences in these functions are apparent from infancy. We found that in a structured play situation and on an information-processing task, 1-year-old infants with the 7-DRD4 allele showed less sustained attention and novelty preference than do infants without the 7-DRD4 allele. There was also a significant interaction between DRD4 and the serotonin transporter promoter (5-HTTLPR) gene on a measure of sustained attention. Our results provide evidence for a possible developmental link between DRD4 and ADHD via early sustained attention and information processing. It also points to the importance of considering the influence of more than one gene in studies of behavior.

Mental representation, severe psychopathology, and the therapeutic process.

Mental representation is a central construct in psychological development. A method for assessing the developmental level of representation of self and significant figures is described, and changes in the developmental level of these representations are reported in a sample of forty seriously disturbed, treatment-resistant adolescents and young adults in intensive, psychoanalytically oriented inpatient treatment lasting more than a year. Increased differentiation-relatedness of descriptions of self and significant figures (mother, father, and therapist) was significantly correlated with improved clinical functioning. Over the course of treatment, representations moved from descriptions of self and significant figures dominated by polarization and splitting to representations involving the emergence and consolidation of object constancy. Improved clinical functioning was correlated with more positive descriptions of self, mother, and therapist and, paradoxically, with more negative descriptions of father. Two prototypical case studies of these self- and significant-figure descriptions are presented, one for a borderline patient and one for a schizophrenic. Intense negative affect, predominantly anger, and a relative preservation of self-reflexivity are typical of the self- and object representations of borderline individuals, but representations in schizophrenic individuals are characterized by affective muting and marked disturbance in reflexive self-awareness. The assessment of cognitive-affective schemas of self and significant others provides a method for investigating therapeutic change and for identifying important differences among various forms of psychopathology.

Modeling of frequency doubling and tripling with measured crystal spatial refractive-index nonuniformities.

Efficient frequency doubling and tripling are critical to the successful operation of inertial confinement fusion laser systems such as the National Ignition Facility currently being constructed at the Lawrence Livermore National Laboratory and the Omega laser at the Laboratory for Laser Energetics. High-frequency conversion efficiency is strongly dependent on attainment of the phase-matching condition. In an ideal converter crystal, one can obtain the phase-matching condition throughout by angle tuning or temperature tuning of the crystal as a whole. In real crystals, imperfections in the crystal structure prohibit the attainment of phase matching at all locations in the crystal. We have modeled frequency doubling and tripling with a quantitative measure of this departure from phase matching in real crystals. This measure is obtained from interferometry of KDP and KD*P crystals at two orthogonal light polarizations.

Social adjustment of adolescents at risk for schizophrenia: the Jerusalem Infant Development Study.

OBJECTIVE: To better understand whether poor social adjustment, a core characteristic of schizophrenic illness, may also be an indicator of vulnerability in young people who are at genetic risk for schizophrenia, but who do not have schizophrenia. METHOD: Between 1992 and 1996, 27 Israeli adolescents with a schizophrenic parent, 29 adolescents with no mentally ill parent, and 30 adolescents with a parent having a nonschizophrenic mental disorder were assessed on multiple domains of social adjustment measured using the Social Adjustment Inventory for Children and Adolescents and the Youth Self-Report. RESULTS: Young people with a schizophrenic parent showed poor peer engagement, particularly heterosexual engagement, and social problems characterized by immaturity and unpopularity with peers. These social adjustment difficulties in youths at risk for schizophrenia could not be attributed solely to the presence of early-onset mental disorders, although problems were greater in those with disorders in the schizophrenia spectrum. Young people whose parents had other disorders showed different patterns of social maladjustment characterized by difficult, conflictual relationships with peers and family. CONCLUSION: Adolescents at risk for schizophrenia have social deficits that extend beyond early-onset psychopathology and that may reflect vulnerability to schizophrenic disorder.

HIV prevention research: accomplishments and challenges for the third decade of AIDS.

The past 2 decades have taught us that HIV prevention can work. We now have evidence from places as diverse as Senegal, Thailand, Uganda, and Australia that concerted HIV prevention efforts at the national level have resulted in the maintenance of low seroprevalence rates where they otherwise would have been expected to rise. We are beginning to observe declining rates of HIV prevalence and incidence in places and populations with historically high rates--for example, injection drug users in New York City. This trend points to the long-term impact of prevention efforts in those communities. The best of these efforts have been based on sound scientific research. As we move into the third decade of the AIDS epidemic, it is important to restate principles, acknowledge advances, and identify challenges and future directions in HIV prevention research.

Economic deprivation and AIDS incidence in Massachusetts.

OBJECTIVES: This study quantified AIDS incidence in Massachusetts in relation to economic deprivation. METHODS: Using 1990 census block-group data, 1990 census population counts, and AIDS surveillance registry data for the years 1988 through 1994, we generated yearly and cumulative AIDS incidence data for the state of Massachusetts stratified by sex and by neighborhood measures of economic position for the total, Black, Hispanic, and White populations. RESULTS: Incidence of AIDS increased with economic deprivation, with the magnitude of these trends varying by both race/ethnicity and sex. The cumulative incidence of AIDS in the total population was nearly 7 times higher among persons in block-groups where 40% or more of the population was below the poverty line (362 per 100,000) than among persons in block-groups where less than 2% of the population was below poverty (53 per 100,000). CONCLUSIONS: Observing patterns of disease burden in relation to neighborhood levels of economic well-being elucidates further the role of poverty as a population-level determinant of disease burden. Public health agencies and researchers can use readily available census data to describe neighborhood-level socioeconomic conditions. Such knowledge expands options for disease prevention and increases the visibility of economic inequality as an underlying cause of AIDS.

Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells.

Embryonic stem (ES) cells are clonal cell lines derived from the inner cell mass of the developing blastocyst that can proliferate extensively in vitro and are capable of adopting all the cell fates in a developing embryo. Clinical interest in the use of ES cells has been stimulated by studies showing that isolated human cells with ES properties from the inner cell mass or developing germ cells can provide a source of somatic precursors. Previous studies have defined in vitro conditions for promoting the development of specific somatic fates, specifically, hematopoietic, mesodermal, and neurectodermal. In this study, we present a method for obtaining dopaminergic (DA) and serotonergic neurons in high yield from mouse ES cells in vitro. Furthermore, we demonstrate that the ES cells can be obtained in unlimited numbers and that these neuron types are generated efficiently. We generated CNS progenitor populations from ES cells, expanded these cells and promoted their differentiation into dopaminergic and serotonergic neurons in the presence of mitogen and specific signaling molecules. The differentiation and maturation of neuronal cells was completed after mitogen withdrawal from the growth medium. This experimental system provides a powerful tool for analyzing the molecular mechanisms controlling the functions of these neurons in vitro and in vivo, and potentially for understanding and treating neurodegenerative and psychiatric diseases.

Transplanted CNS stem cells form functional synapses in vivo.

An understanding of developmental mechanisms and new cell therapies can be achieved by transplantation into the nervous system. Multipotential stem cells have been isolated from the foetal and adult central nervous system (CNS). Immortalized and primary precursor cells integrate into the developing brain generating both neurons and glia as defined by immunological and morphological criteria. Here we show for the first time that in vitro-expanded CNS precursors, upon transplantation into the brains of rats, form electrically active and functionally connected neurons. These neurons exhibit spontaneous and evoked postsynaptic events and respond to focal glutamate application. Donor cells were grafted into the foetal hippocampus, and the amplitude and frequency of spontaneous synaptic events were monitored in the grafted cells in area CA1 for the first month of postnatal life. The formation of synapses onto grafted neurons indicates that grafted CNS stem cells can be used to study synaptic development in vivo and has important implications for clinical cell replacement therapies.