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Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Pulmonary hypertension is a complex and progressive condition that is either idiopathic or heritable, or associated with one or multiple health conditions, with or without congenital or acquired cardiovascular disease. Recent developments have tremendously increased the armamentarium of diagnostic and therapeutic approaches in children and young adults with pulmonary hypertension that is still associated with a high morbidity and mortality. These modalities include non-invasive imaging, pharmacotherapy, interventional and surgical procedures, and supportive measures. The optimal, tailored diagnostic and therapeutic strategies for pulmonary hypertension in the young are rapidly evolving but still face enormous challenges: Healthcare providers need to take the patient’s age, development, disease state, and family concerns into account when initiating advanced diagnostics and treatment. Therefore, there is a need for guidance on core and advanced medical training in paediatric pulmonary hypertension. The Association for European Paediatric and Congenital Cardiology working group “pulmonary hypertension, heart failure and transplantation” has produced this document as an expert consensus statement; however, all recommendations must be considered and applied in the context of the local and national infrastructure and legal regulations.
Cognitive impairment is a core feature of major depressive disorder (MDD). Cognitive remediation may improve cognition in MDD, yet so far, the underlying neural mechanisms are unclear. This study investigated changes in intrinsic neural activity in MDD after a cognitive remediation trial.
In a longitudinal design, 20 patients with MDD and pronounced cognitive deficits and 18 healthy controls (HC) were examined using resting-state functional magnetic resonance imaging. MDD patients received structured cognitive remediation therapy (CRT) over 5 weeks. The whole-brain fractional amplitude of low-frequency fluctuations was computed before the first and after the last training session. Univariate methods were used to address regionally-specific effects, and a multivariate data analysis strategy was employed to investigate functional network strength (FNS).
MDD patients significantly improved in cognitive function after CRT. Baseline comparisons revealed increased right caudate activity and reduced activity in the left frontal cortex, parietal lobule, insula, and precuneus in MDD compared to HC. In patients, reduced FNS was found in a bilateral prefrontal system at baseline (p < 0.05, uncorrected). In MDD, intrinsic neural activity increased in right inferior frontal gyrus after CRT (p < 0.05, small volume corrected). Left inferior parietal lobule, left insula, left precuneus, and right caudate activity showed associations with cognitive improvement (p < 0.05, uncorrected). Prefrontal network strength increased in patients after CRT, but this increase was not associated with improved cognitive performance.
Our findings support the role of intrinsic neural activity of the prefrontal cortex as a possible mediator of cognitive improvement following CRT in MDD.
It is a truth universally acknowledged that every ambitious twenty-first century trade agreement is in want of a chapter on electronic commerce. One of the most politically sensitive and technically challenging issues is personal privacy, including cross-border transfer of information by electronic means, use and location of computing facilities, and personal information protection. States are learning to solve the problem of state responsibility for something that does not respect their borders while still allowing twenty-first century commerce to develop. A comparison of the Canada–European Union Comprehensive Economic and Trade Agreement (CETA) and the Trans-Pacific Partnership (TPP) allows us to see the evolution of the issues thought necessary for an e-commerce chapter, since both include Canada, and to see the differing priorities of the US and the EU, since they are each signatory to one of the agreements, but not of the other. I conclude by seeking generalizations about why we see a mix of aspirational and obligatory provisions in free trade agreements. I suggest that the reasons are that governments are learning how to work with each other in a new domain, and learning about the trade implications of these issues.
Returning genomic research results to family members raises complex questions. Genomic research on life-limiting conditions such as cancer, and research involving storage and reanalysis of data and specimens long into the future, makes these questions pressing. This author group, funded by an NIH grant, published consensus recommendations presenting a framework. This follow-up paper offers concrete guidance and tools for implementation. The group collected and analyzed relevant documents and guidance, including tools from the Clinical Sequencing Exploratory Research (CSER) Consortium. The authors then negotiated a consensus toolkit of processes and documents. That toolkit offers sample consent and notification documents plus decision flow-charts to address return of results to family of living and deceased participants, in adult and pediatric research. Core concerns are eliciting participant preferences on sharing results with family and on choice of a representative to make decisions about sharing after participant death.
State-owned enterprises (SOEs) are a major force in the Chinese economy and a growing presence in international trade and investment. The challenge to the WTO legal regime is commercial, given the size of SOEs and their share of Chinese output, and political, given worries that trade and investment by SOEs may be driven by public policy goals. And both challenges may be exacerbated by the murky world of Chinese SOEs. In this article, I first review whether Chinese SOEs are a problem for the WTO, and whether more sunshine on their operations might be a useful discipline. I then ask what we know about SOEs inside the WTO, including in the Trade Policy Review Mechanism. Since the answer is, not much, I consider whether mega-regional trade negotiations offer a better approach. My answer being negative, I finally consider whether an attempt to negotiate a WTO Reference Paper on SOEs might help. I conclude that transparency is likely to be a better discipline on the spillovers associated with SOEs than a search for binding rules, while also helping everyone better understand the efficiency effects.
Private standards are increasing in number, and they affect trade, but their status in the WTO remains problematic. Standards-takers are typically countries with little bargaining power, who cannot affect their terms of trade, and, thus, even if they possess domestic antitrust laws, will find it hard to persuade standard-setters to take account of their interests. Our concern is to bring more of these standards within the normative framework of the trade regime – that is, we worry that these private forms of social order can conflict with the fundamental norms of transparency and non-discrimination. The WTO membership has consumed itself in endless discussions regarding mundane, legalistic issues, and has not moved at all towards addressing the real concerns of developing countries. We discuss one aspect of the problem: How reclusive should the WTO allow product standards to be? We argue that the WTO should adopt a ‘Reference Paper’ that would encourage its members to apply WTO rules for adopting those standards that already come under the aegis of the WTO to private standards. In the absence of centralized enforcement, utopia in the WTO legal paradigm, transparency disciplines imposed on standard-setters is the best the WTO could offer to those who are negatively affected by private standards.
The debate about how to manage individual research results and incidental findings in genetic and genomic research has focused primarily on what information, if any, to offer back to research participants. However, increasing controversy surrounds the question of whether researchers have any responsibility to offer a participant’s results (defined here to include both individual research results and incidental findings) to the participant’s relatives, including after the participant’s death. This question arises in multiple contexts, including when researchers discover a result with potentially important health implications for genetic relatives, when a participant’s relatives ask a researcher whether any research results about the participant have implications for their own health or reproductive planning, when a participant’s relative asks whether any of the participant’s results have implications for a child’s health, and when the participant is deceased and the participant’s relatives seek information about the participant’s genetic results in order to address their own health or reproductive concerns.
Heterogeneous system integration is one of the key topics for future system integration. Scaling of System on Chip (SoC) alone does not address today's requirements of smart electronic systems in terms of performance, functionality, miniaturization, low production cost and time to market.
The traditional microelectronic packaging will more and more convert into complex sys-tem integration. ‘More than Moore’ will be required due to tighter integration of system level components at the package level. This trend leads to advanced System in Package solutions (SiP) which require the synergy and a combination of wafer level and board integration technologies and which are rapidly evolving from a specialty technology used in a narrow set of applications to a high volume technology with wide ranging impact on electronics markets especially due to the high volume and very cost competitive consumer and communication market. Advanced SiP approaches explore the third dimension which results in complex system architectures that also require, beside new technologies and improved materials, adequate system design tools and reli-ability models. One of the most promising technology approaches is 3D packaging which in-volves a set of different integration approaches including stacked packages, silicon interposer with Through Silicon Vias (TSV) and embedding technologies. The paper highlights future sys-tem and potential technical solutions.
Nasal inspiration is important for maintaining the internal milieu of the lung, since ambient air is conditioned to nearly alveolar conditions (body temperature and fullysaturated with water vapour) upon reaching the nasopharynx. This literature review of the existing in vivo, in vitro and computational studies on transport phenomena that take place within the human nasal cavity summarizes the current knowledge on air-conditioning characteristics of the human nose.
From a 45ks Chandra observation of V42G Oph we have obtained high-resolution X-ray spectra at moderate signal-to-noise, and a, good quality, uninterrupted lightcurve. The spectra are reasonably fit with a cooling flow model, similar to EX Hya and U Gem. Our analysis of the Chandra and additional X-ray/optical lightcurves reveals a persistent modulation at 4.2 hr from 1988 to 2003, likely the white dwarf spin period indicating an intermediate polar nature for V426 Oph.
The crystal structure of the FMN-binding domain
of human NADPH-cytochrome P450 reductase (P450R-FMN), a
key component in the cytochrome P450 monooxygenase system,
has been determined to 1.93 Å resolution and shown
to be very similar both to the global fold in solution
(Barsukov I et al., 1997, J Biomol NMR 10:63–75)
and to the corresponding domain in the 2.6 Å crystal
structure of intact rat P450R (Wang M et al., 1997, Proc
Nat Acad Sci USA 94:8411–8416). The crystal
structure of P450R-FMN reported here confirms the overall
similarity of its α-β-α architecture to that
of the bacterial flavodoxins, but reveals differences in
the position, number, and length of the helices relative
to the central β-sheet. The marked similarity between
P450R-FMN and flavodoxins in the interactions between the
FMN and the protein, indicate a striking evolutionary conservation
of the FMN binding site. The P450R-FMN molecule has an
unusual surface charge distribution, leading to a very
strong dipole, which may be involved in docking cytochrome
P450 into place for electron transfer near the FMN. Several
acidic residues near the FMN are identified by mutagenesis
experiments to be important for electron transfer to P4502D6
and to cytochrome c, a clear indication of the
part of the molecular surface that is likely to be involved
in substrate binding. Somewhat different parts are found
to be involved in binding cytochrome P450 and cytochrome