Irreversible Events Research Articles

Analysis of landscape hierarchy during coarsening and aging in Ising spin glasses

We use record dynamics (RD), a coarse-grained description of the ubiquitous relaxation phenomenology known as "aging", as a diagnostic tool to find universal features that distinguish between the energy landscapes of Ising spin models and the ferromagnet. According to RD, a non-equilibrium system after a quench relies on fluctuations that randomly generate a sequence of irreversible record-sized events (quakes or avalanches) that allow the system to escape ever-higher barriers of meta-stable states within a complex, hierarchical energy landscape. Once these record events allow the system to overcome such barriers, the system relaxes by tumbling into the following meta-stable state that is marginally more stable. Within this framework, a clear distinction can be drawn between the coarsening dynamics of an Ising ferromagnet and the aging of the spin glass, which are often put in the same category. To that end, we interpolate between the spin glass and ferromagnet by varying the admixture $p$ of ferromagnetic over anti-ferromagnetic bonds from the glassy state (at 50% each) to wherever clear ferromagnetic behavior emerges. The accumulation of record events grows logarithmic with time in the glassy regime, with a sharp transition at a specific admixture into the ferromagnetic regime where such activations saturate quickly. We show this effect both for the Edwards-Anderson model on a cubic lattice as well as the Sherrington-Kirkpatrick (mean-field) spin glass. While this transition coincides with a previously observed zero-temperature equilibrium transition in the former, that transition has not yet been described for the latter.

Dislocation-based crack initiation and propagation in single-crystal SrTiO3

Understanding the irreversible deformation (dislocation activation and crack formation) of functional oxides, based on which various advanced electronic devices are fabricated, is critical for the optimal structural design and mechanical reliability. Here, we demonstrate the dislocation-based crack initiation and propagation in a model perovskite, single-crystal SrTiO3, at small scale. Using nanoindentation tests with spherical tips and etch pit study, we identify the sequence of the irreversible deformation events occurred in single-crystal (001) SrTiO3. For a locally stressed volume that is free of pre-existing cracks, the material undergoes the following processes: (1) purely elastic deformation; (2) dislocation activation on primary slip planes that are 45° inclined to the surface; (3) dislocation activation on secondary slip planes perpendicular to the surface; (4) crack initiation by dislocation pile-up; followed by (5) concurrent crack propagation and dislocation multiplication and motion at higher loads. Specifically, we focus on the crack formation caused by the dislocation pile-up beneath the spherical indenter. We also identify the favorable crack propagation planes to be {110} when the (001) surface is indented. These findings in cubic SrTiO3 are believed to be applicable for other ceramic materials with cubic structure.

How does static granular matter re-arrange for different isotropic strain rate?

The question of how soft granular matter, or dense amorphous systems, re-arrange their microstructure under isotropic compression and de-compression, at different strain rates, will be answered by particle simulations of frictionless model systems in a periodic three-dimensional cuboid. Starting compression below jamming, the systems experience the well known jamming transition, with characteristic evolutions of the state variables elastic energy, elastic stress, coordination number, and elastic moduli. For large strain rates, kinetic energy comes into play and the evolution is more dynamic. In contrast, at extremely slow deformation, the system relaxes to hyper-elastic states, with well-defined elastic moduli, in static equilibrium between irreversible (plastic) re-arrangement events, discrete in time. Small, finite strains explore those reversible (elastic) states, before larger strains push the system into new states, by irreversible, sudden re-arrangements of the micro-structure.

An intelligent prenatal screening system for the prediction of Trisomy-21

Down syndrome is caused by a trisomy on chromosome 21 of humans. Children with this disease often have varying degrees of physical-mental problems such as mental retardation, communication skills problems, congenital heart disease, and thyroid disease. Early and accurate genetic disorders detection can lead to corrective action and prevent irreversible events. Therefore, accurate and low-risk diagnostic methods to detect these diseases in the fetal period are essential. In this study, a combined artificial neural network (ANN) and genetic algorithm (GA) were used to predict Down syndrome through the first-trimester screening test. In order to examine the proposed model, sample data were collected on 381 pregnant women referred to a private screening reference laboratory for the first-trimester screening test and NT ultrasound between 11 and 13 weeks of gestation. The proposed model in this study was a feedforward neural network for which its structure and input parameters were determined by (GA). The performance of the created model was also evaluated by utilizing the sensitivity, specificity, and accuracy indicators. The average of 10 times experiments showed that the developed model could accurately identify cases of Down syndrome with a specificity of 99.72%, sensitivity of 90.91%, and a mean square error (MSE) of 0.61%. This study showed that the use of GA in optimizing the structure of the neural network technique could increase the accuracy in diagnosing Down syndrome through the information of first-trimester screening tests. Most importantly, this study contributes to clinical knowledge by helping clinicians to early identify the risk of Down syndrome with a non-invasive and low-cost method.

Universal features of annealing and aging in compaction of granular piles

This paper links the nonequilibrium glassy relaxation behavior of otherwise athermal granular materials to those of thermally activated glasses. Thus, it demonstrates a much wider universality among complex glassy materials out of equilibrium. Our three-dimensional molecular dynamics simulations, fully incorporating friction and inelastic collisions, are designed to reproduce experimental behavior of tapped granular piles. A simple theory based on a dynamics of records explains why the typical phenomenology of annealing and aging after a quench should extend to such granular matter, activated by taps, beyond the more familiar realm of polymers, colloids, and magnetic materials that all exhibit thermal fluctuations.

Characteristics of online medical care consultation for pregnant women during the COVID-19 outbreak: cross-sectional study

ObjectivesThis study described the needs of pregnant women and the contents of online obstetric consultation in representative areas with various severity of the epidemic in China.DesignThis was a cross- sectional...

Тенденції трансформації Бреттон-Вудських організацій у глобальному просторі

The article highlights the historical aspects and preconditions for the creation of the International Monetary Fund (the IMF) and the World Bank, which since 1944 have been the most influential international financial organizations and have played the role of the world's largest creditors. The essence of the transformations of their activity caused by the phenomena of the new economic reality is revealed. The solution to the problems of financial stability on a global scale in the postwar period by the United States and the newly created the IMF was to peg national currencies to the US dollar in the Fund's arbitration. The events related to the crisis of the Bretton Woods system of single fixed exchange rates and the irreversible disruptions in the world circulation of oil and its derivatives in the 1970s were important reasons for changing the principles of the world monetary and financial system towards the introduction of free exchange. At the same time, due to the intensification of domestic trade and investment, there were abrupt outpacing transformations of the economies of the south-eastern part of the Asian continent. Following the irreversible events involving the collapse of the socialist camp, support for reform programs in transition economies has been added to the IMF's targets. The activities of the World Bank under the impact of these total changes were also significantly renewed. Further, the IMF and the World Bank began to work more closely, integrating anti-crisis approaches and measures, while remaining a universally recognized instrument of stabilization in the global dimension. The activities of the Bretton Woods organizations are aimed at assisting the governments of developing countries in implementing market economic policies to protect the rights of all forms of ownership, modernize institutional structures, achieve financial balance, and improve the social situation of all segments of the population. It is concluded that in order to ensure sustainable development, the strategic renewal of the IMF and the World Bank provides for the expansion of quotas to support structural reform programs, improve the allocation of credit and financial resources, support opportunities to meet the needs of socio-economic systems, develop human capital and efforts for solving macroeconomic problems, etc. The directions of impact of these international financial institutions on solving actual problems concerning climate change, displays of corruption, overcoming inequality, resistance to threats of destabilization, struggle against a pandemic of a coronavirus disease of COVID-19 are defined.

Pathogenic germline variants are associated with poor survival in stage III/IV melanoma patients

Patients with late stage resected cutaneous melanoma have poor overall survival (OS) and experience irreversible adverse events from systemic therapy. There is a clinical need to identify biomarkers to predict outcome. Performing germline/tumour whole-exome sequencing of 44 stage III/IV melanoma patients we identified pathogenic germline mutations in CDKN2A, CDK4, ATM, POLH, MRE11A, RECQL4 and XPC, affecting 7/44 patients. These mutations were associated with poor OS (p = 0.0082). We confirmed our findings in The Cancer Genome Atlas (TCGA) human skin cutaneous melanoma cohort where we identified pathogenic variants in 40/455 patients (p = 0.0203). Combining these cohorts (n = 499) further strengthened these findings showing germline carriers had worse OS (p = 0.0009). Additionally, we determined whether tumour mutation burden (TMB) or BRAF status were prognostic markers of survival. Low TMB rate (< 20 Mut/Mb; p = 0.0034) and BRAF p.V600 mutation (p = 0.0355) were associated with worse progression-free survival. Combining these biomarkers indicated that V600 mutant patients had significantly lower TMB (p = 0.0155). This was confirmed in the TCGA (n = 443, p = 0.0007). Integrative analysis showed germline mutation status conferred the highest risk (HR 5.2, 95% CI 1.72–15.7). Stage IV (HR 2.5, 0.74–8.6) and low TMB (HR 2.3, 0.57–9.4) were similar, whereas BRAF V600 status was the weakest prognostic biomarker (HR 1.5, 95% CI 0.44–5.2).

Pediatric spinal cord infarction following a minor trauma: a case report.

Pediatric spinal cord infarction is a rare entity that presents a diagnostic challenge at the emergency department. Ischemic spinal cord infarction can occur in the setting of trauma, cardiovascular malformation, or postoperatively. We report a case of anterior spinal artery infarction following seemingly minor trauma in an otherwise healthy 14-year-old male. A 14-year-old male presented with unprovoked sudden-onset stabbing back pain earlier that day. The patient then demonstrated bilateral lower extremities weakness while at the emergency department. After extensive diagnostic workup, the patient was diagnosed with anterior spinal artery territory infarction involving the thoracic spinal cord. Minor trauma to the thoracic spinal cord was detected on imaging and was believed to be the culprit of this event. Given the rarity of spinal cord ischemia, a high index of suspicion and extensive workup of patients presenting with clinical weakness are needed for accurate diagnosis and to avoid the eventual poor outcome. With so few reports in the literature regarding spinal cord ischemia in the pediatric population, accurate diagnosis is often delayed until after irreversible events have already taken place. Our case report of anterior spinal artery distribution thoracic cord infarct following a minor trauma was diagnosed by axial thin-slice DWI MRI with an otherwise negative workup.

FORC signatures and switching-field distributions of dipolar coupled nanowire-based hysterons

Analysis of first-order reversal curves (FORCs) is a powerful tool to probe irreversible switching events in nanomagnet assemblies. As in essence switching events are related to the intrinsic properties of the constituents and their interactions, the resulting FORC diagrams contain much information that can be cross-linked and complex to deconvolute. In order to quantify the relevant parameters that drive the FORC diagrams of arrays of perpendicularly magnetized nanomagnets, we present step-by-step simulations of assemblies of hysterons to determine the specific signatures related to different known inputs. While we explored the consequences of dipolar interactions using either mean field or magnetostatic approaches, we completed by taking the hysteron switching field distribution (SFD) as either normal or lognormal. We demonstrated that the transition between FORC diagrams composed of an isolated interaction field distribution (IFD) and a wishbone shape operates via the SFD deviation, σHsw, in the presence of a weakly dispersed interaction field. In the presence of a magnetostatic interaction field, the IFD profile is peaked and a coercive field distribution (CFD) sums to the IFD as σHsw increases. A transition between IFD + CFD and wishbone shapes is clearly demonstrated as a function of the interaction field deviation σHint. In addition, we demonstrate that whatever the considered cases, σHswcan be quantitatively extracted from the FORC diagrams within an error inferior to 10%. These findings are of interest for dipolar coupled perpendicularly magnetized nanomagnets, as in assemblies of magnetic nanowires and nanopillars, as well as bit patterned media.

Optimal number of faces for fast self-folding kirigami

There is an increasing body of research studying how to obtain 3D structures at the microscale from the spontaneous folding of planar templates, using thermal fluctuations as the driving force. Here, combining numerical simulations and analytical calculations, we show that the total folding time of a regular pyramid is a non-monotonic function of the number of faces (N), with a minimum for five faces. The motion of each face is consistent with a Brownian process and folding occurs through a sequence of irreversible binding events between faces. The first one is well-described by a first-passage process in 2D, with a characteristic time that decays with N. By contrast, the subsequent binding events are first-passage processes in 1D and the time of the last one grows logarithmically with N. It is the interplay between these two different sets of events that explains the non-monotonic behavior. Implications in the self-folding of more complex structures are discussed.

Synthesis and characterization of 1,4-chalcogenesters bearing 5-membered heterocycles

Treatment of 1,4-(SeSiMe3)2-C6H4 (1) with two equiv of ClC(O)R (2) (a, R = 2-cC4H3O; b, R = 2-cC4H3S; c, R = 3-cC4H3S) produced the corresponding phenylene carboselenolates 1,4-(SeC(O)R)2-C6H4 (3a–c), while the reaction of 1,4-(SLi)2-C6H4 (4) with ClC(O)R (2) in a 1:2 molar ratio gave phenylene carbothiolates 1,4-(SC(O)R)2-C6H4 (5a–c). Compounds 3a–c and 5a–c were characterized by elemental analysis, NMR (1H, 13C{1H}, 77Se{1H}) and IR spectroscopy. The molecular structures of 3a–c and 5a–c in the solid state were determined by single-crystal X-ray structure analysis. The carbochalcogenato groups and the heteroatoms of the 5-membered rings are in an anti-arrangement with respect to each other. Cyclic voltammetry measurements show irreversible reduction processes for the 5-membered heterocyclic redox moiety in which reduction of these compounds lead to decomposition of the original compounds to unidentified species and show redox potentials between 1480 and 1580 mV for 3a-c and 1470−1490 mV for 5a-c, relative to the FcH/FcH+ redox couple. Also, thioester-functionalized systems 5a-c show significantly higher reduction potentials as compared to selenoesters 3a-c, reflecting the minor electron-donating effect of the sulfur atoms. The molecular electronic structures of the title compounds were additionally investigated by DFT calculations, revealing different degrees of HOMO-LUMO energy gaps within the series of 3a–c and 5a–c, due to a lowering in LUMO energy, depending on the nature of the heterocyclic ring. The calculations showed that the HOMO and LUMO are mainly located on the selenoester/thioester functionalized heterocyclic. The phase transition temperatures and enthalpies of the title compounds were detected by differential scanning calorimetry (DSC) analysis and the phases are confirmed by polarizing optical microscopy (POM). The mesomorphic investigation shows that compound 5a only exhibits enantiotropic smectic B (SmB) mesophase. In contrast, the other compounds do not show mesomorphic behavior, but simply changes from the solid crystalline state to the isotropic liquid. Biological activity of the compounds was evaluated using cytotoxicity assay on different cancer cell lines. Only compound 3c showed selective cytotoxic effect against MDA-231 and PC-3 cancer cell lines. The synthesis and characterization of phenylene carboselenolates 1,4-(SeC(O)R)2-C6H4 (3a–c) and phenylene carbothiolates 1,4-(SC(O)R)2-C6H4 (5a–c) were discussed. The solid state structures of the six compounds are reported. Electrochemical investigations show irreversible redox events. DFT calculations reveal different HOMO-LUMO gaps depending on the aryl substituent pattern. In addition, the liquid crystalline properties and the bioactivity test were carried out too.

Clinical outcomes of sacral neuromodulation in non-neurogenic, non-obstructive dysuria: A 5-year retrospective, multicentre study in China.

BACKGROUNDManagement of non-neurogenic, non-obstructive dysuria represents one of the most challenging dilemmas in urological practice. The main clinical symptom is the increase in residual urine. Voiding dysfunction is the main cause of dysuria or urinary retention, mainly due to the decrease in bladder contraction (the decrease in contraction amplitude or duration) or the increase in outflow tract resistance. Sacral neuromodulation (SNM) has been used for > 10 years to treat many kinds of lower urinary tract dysfunction. It has become increasingly popular in China in recent years. Consequently, studies focusing on non-neurogenic, non-obstructive dysuria patients treated by SNM are highly desirable.AIMTo assess the outcome of two-stage SNM in non-neurogenic, non-obstructive dysuria.METHODSClinical data of 54 patients (26 men, 28 women) with non-neurogenic, non-obstructive dysuria treated by SNM from January 2012 to December 2016 in ten medical centers in China were retrospectively analyzed. All patients received two or more conservative treatments. The voiding diary, urgency score, and quality of life score before operation, after implantation of tined lead in stage I (test period), and during short-term follow-up (latest follow-up) after implantation of the implanted pulse generator in stage II were compared to observe symptom improvements.RESULTSAmong the 54 study patients, eight refused to implant an implanted pulse generator because of the unsatisfactory effect, and 46 chose to embed the implanted pulse generator at the end of stage I. The conversion rate of stage I to stage II was 85.2%. The average follow-up time was 18.6 mo. There were significant differences between baseline (before stage I) and the test period (after stage I) in residual urine, voiding frequency, average voiding amount, maximum voiding amount, nocturia, urgency score, and quality of life score. The residual urine and urgency score between the test period and the latest follow-up time (after stage II) were also significantly different. No significant differences were observed for other parameters. No wound infection, electrode breakage, or other irreversible adverse events occurred.CONCLUSIONSNM is effective for patients with non-neurogenic, non-obstructive dysuria showing a poor response to traditional treatment. The duration of continuous stimulation may be positively correlated with the improvement of residual urine.

Tradeoffs between costly capacity investment and risk of regime shift

There is mounting evidence that increasing natural resource exploitation (e.g., fossil fuel extraction and consumption) could trigger irreversible dramatic ecological events like global warming. While capacity investment costs and the possibility to produce at full capacity are two factors that critically affect the exploitation rate, little is known about their effect on management. I generalize standard models of pollution control under the threat of dramatic regime shifts to investigate how optimal management changes with both factors. My analysis reveals that accounting for such factors gives rise to investment and emissions policies that challenge conventional wisdom. For instance, I find that under reasonable conditions, an exogenous threat of a doomsday event induces a cautious management strategy. Using parameters estimated from climatic data, my analysis shows that raising the discount rate can induce lower emissions, highlighting the complex interplay between the threat and both factors.

Long-lasting, irreversible and late-onset immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs): A real-world data analysis.

e15095 Background: ICIs are effective in many tumors, but can cause severe irAEs, with potential long-term impact. Description of irAEs in literature is often insufficient, especially in terms of irAEs duration, and in terms of incidence of late-onset events. Namely, duration of irAEs and proportion of patients (pts) with toxicity still ongoing at data cut-off were not specified in 52 (89.6%) of 58 publications of trials leading to ICIs approval by US FDA and/or EMA up to August 2019. Real-world data are urgently needed to integrate this information. Methods: We retrieved the medical charts of all pts affected by lung cancer (LC) and melanoma (Mel) treated consecutively with approved ICIs at the Centre Hospitalier Universitaire Vaudoise (CHUV) from Jan 2012 to Dec 2019. We collected the following data: treatment setting, ICIs received, duration of each treatment, incidence of any irAEs of grade (G) ≥ 2 (according to CTCAE v5.0), time to onset and duration of irAEs. Pts with follow-up (FU) ≤ 28 days were excluded. Results: 345 pts were included (166 LC, 179 Mel), for a total of 455 ICIs treatment lines. 33 pts (7%, all with Mel) were treated in the adjuvant setting, while all the others were treated for advanced disease. 228 pts (50%) received anti-PD1, 43 (9%) anti-PD-L1, 56 (12%) anti-CTLA-4, 100 (22%) ICI-ICI combinations and 28 (6%) ICI–chemotherapy combinations. Median FU was 369 days (range 29-2903). Median duration of treatment was 71 days (range 1-1625). 196 pts (57%) experienced at least 1 G≥2 irAE for a total of 277 irAEs (22% skin, 18% gastro-intentinal [GI], 13% pneumonitis, 12% thyroid disorders, 11% hyphophisitis and 8% hepatitis). With 122/277 (44%) irAEs still on-going at our data cut-off, median duration of irAEs was 98 days; 104/277 irAEs (37%) lasted more than 6 month, of them 89% were considered irreversible. Out of 76 pts still on ICIs treatment at 6 months, incidence of G≥2 irAE with onset after 6 months was 51% (26% pneumonitis, 26% endocrine disorders, 15% skin disorders, 8% hepatitis and GI). Out of 32 pts still on ICIs treatment at 12 months, incidence of G≥2 irAE with onset after 12 months was 41% (38% pneumonitis, 23% endocrine and 15% skin disorders, 8% hepatitis and GI). Conclusions: Our real-world analysis shows that long-lasting and late-onset irAEs represent an important issue during ICIs treatment. A better description of toxicities in clinical trials is needed to allow a proper evaluation of treatment value and the impact on patients' quality of life.

Shear Bands in Monolithic Metallic Glasses: Experiment, Theory, and Modeling

For applications, metallic glasses need to retain their high strength over enhanced strain ranges. However, many metallic glasses show catastrophic failure, even in or close to the end of the regime that conventionally has been thought to be elastic. Recent observations of irreversible events at low strains shed some doubt on this nomenclature. In fact, these observations indicate that although the macroscopic response indicates elastic behavior, the microscopic processes might at least partially be irreversible and time-dependent. In that respect, shear bands as the result of shear localization and as the cause of shear softening play a decisive role with respect to the performance of metallic glasses under mechanical load. We are aiming at understanding the correlations between glass structure, glass properties and the thermomechanical history of the glass including the shear bands on one hand and the plastic yielding on the other hand. Various attempts have been made to explain or model the response of metallic glasses to externally applied shear stresses. Hypotheses have been put forward concerning the impact of materials parameters or structural aspects that might favor homogeneous plastic flow. Additionally, scenarios have been suggested for the early stages of anelastic and plastic deformation as well as for the transition to localization and shear band formation/activation. We present a focused viewpoint both from theory and modelling as well as an experimental perspective set on the structure and properties of glasses under shear, with a special focus on shear banding. We discuss the impact of the local structure of glasses (that depend on the synthesis and processing path-way) in terms of their medium range order. The impact of chemical composition (including microalloying effects) on kinetic properties of shear bands and elasto-plastic properties (Poisson's ratio and three-point bending) is evaluated. These aspects have seen relatively sparse coverage, but are of far-reaching consequences concerning the properties of glasses under mechanical stress. These aspects can reveal new insight into the underlying dominant mechanisms and, equally important, allow also to infer about the early stages of strain localization and to analyze the impact of structural heterogeneity or processing conditions on plastic yielding.

A new 3D model for genotoxicity assessment: EpiSkin™ Micronucleus Assay.

The European Regulation on Cosmetics (no. 1223/2009) has prohibited the use of animals in safety testing since March 2009 for ingredients used in cosmetics. Irreversible events at the chromosome level (clastogenesis and aneugenesis) are commonly evaluated by scoring either micronuclei or chromosome aberrations using cell-based genotoxicity assays. Like most in vitro genotoxicity assays, the 2D in vitro micronucleus assay exhibits a poor specificity and does not mimic the dermal route. To address these limitations, the current project aims to develop and validate a 3D micronucleus assay using the EpiSkin™ model. This project is scientifically supported by the Cosmetics Europe Genotoxicity Task Force. In a first step, two key criteria for the development of micronucleus assay, namely, the sufficient yield of cells from the EpiSkin™ model and an acceptable proliferation rate of the basal layer, were assessed and demonstrated. Subsequently, six chemicals (vinblastine, n-ethylnitrosourea, β-butyrolactone, 2-acetylaminofluorene, 2,4-dichlorophenoland d-limonene) were evaluated in the EpiSkin™ Micronucleus Assay. At least two independent experiments using 48- and 72-h incubations were performed for each chemical. Results showed good inter-experimental reproducibility, as well as the correct identification of all six tested chemicals. The metabolism of 2-acetylaminofluorene on the EpiSkin™ model was also investigated and confirmed by the formation of an intermediate metabolite (2-aminofluorene). These preliminary results from the EpiSkin™ Micronucleus Assay indicate that it is a promising in vitro assay for assessing genotoxicity. The availability and suitability of this test method contribute significantly to the development of non-animal testing methods in China and its impact on the worldwide field.

Quantum Artificial Intelligence: A “precautionary” U.S. approach?

Quantum Computing (QC) and Quantum Artificial Intelligence (QAI) are two powerful new technologies whose potential impacts are just starting to be appreciated. As important as they are likely to be, their implications are still little known. This article's purpose is an attempt to provide a policy space within which to begin fill that void.It presents a non-technical introduction to the concept of quantum mechanics in general, to the unique characteristics of sub-atomic particles, to quantum applications, and to QC and QAI in particular. The development of fully functioning quantum information technologies is in its early stages, but is being pursued aggressively. One of the most salient of these is Quantum Artificial Intelligence (QAI) – a fusion of QC and AI -- which some see as potentially threatening. There is little in established telecommunications or information policies to inform our approach to its capabilities.The article notes some of the challenges to development of quantum-based information technologies and considers the scope of global competition to the U.S. in this field, especially from China. It reviews the treatment of “Quantum Information Science” in U.S. policy. It describes the current policy environment and the range of new measures which might be available, if needed, to incorporate QAI into an overall information policy regime.In conclusion the article reviews the debate over adoption of the “precautionary principle” for QAI, an approach to policy when it must deal with weakly understood causes of potentially catastrophic or irreversible events. It sets out the arguments pro and con, and in the absence of an immediate resolution proposes adoption of a policy space in which stakeholders can address their salient concerns, without materially impairing technological progress and commercial viability.

Hyperspectrally Compressed Ultrafast Photography.

The spatial, temporal, and spectral information in optical imaging play a crucial role in exploring the unknown world and unencrypting natural mysteries. However, the existing optical imaging techniques can only acquire the spatiotemporal or spatiospectral information of the object with the single-shot method. Here, we develop a hyperspectrally compressed ultrafast photography (HCUP) that can simultaneously record the spatial, temporal, and spectral information of the object. In our HCUP, the spatial resolution is 1.26 lp/mm in the horizontal direction and 1.41 lp/mm in the vertical direction, the temporal frame interval is 2ps, and the spectral frame interval is 1.72nm. Moreover, HCUP operates with receive-only and single-shot modes, and therefore it overcomes the technical limitation of active illumination and can measure the nonrepetitive or irreversible transient events. Using our HCUP, we successfully measure the spatiotemporal-spatiospectral intensity evolution of the chirped picosecond laser pulse and the photoluminescence dynamics. This Letter extends the optical imaging from three- to four-dimensional information, which has an important scientific significance in both fundamental research and applied science.

Molecular signature of different lesion types in the brain white matter of patients with progressive multiple sclerosis

To identify pathogenetic markers and potential drivers of different lesion types in the white matter (WM) of patients with progressive multiple sclerosis (PMS), we sequenced RNA from 73 different WM areas. Compared to 25 WM controls, 6713 out of 18,609 genes were significantly differentially expressed in MS tissues (FDR < 0.05). A computational systems medicine analysis was performed to describe the MS lesion endophenotypes. The cellular source of specific molecules was examined by RNAscope, immunohistochemistry, and immunofluorescence. To examine common lesion specific mechanisms, we performed de novo network enrichment based on shared differentially expressed genes (DEGs), and found TGFβ-R2 as a central hub. RNAscope revealed astrocytes as the cellular source of TGFβ-R2 in remyelinating lesions. Since lesion-specific unique DEGs were more common than shared signatures, we examined lesion-specific pathways and de novo networks enriched with unique DEGs. Such network analysis indicated classic inflammatory responses in active lesions; catabolic and heat shock protein responses in inactive lesions; neuronal/axonal specific processes in chronic active lesions. In remyelinating lesions, de novo analyses identified axonal transport responses and adaptive immune markers, which was also supported by the most heterogeneous immunoglobulin gene expression. The signature of the normal-appearing white matter (NAWM) was more similar to control WM than to lesions: only 465 DEGs differentiated NAWM from controls, and 16 were unique. The upregulated marker CD26/DPP4 was expressed by microglia in the NAWM but by mononuclear cells in active lesions, which may indicate a special subset of microglia before the lesion develops, but also emphasizes that omics related to MS lesions should be interpreted in the context of different lesions types. While chronic active lesions were the most distinct from control WM based on the highest number of unique DEGs (n = 2213), remyelinating lesions had the highest gene expression levels, and the most different molecular map from chronic active lesions. This may suggest that these two lesion types represent two ends of the spectrum of lesion evolution in PMS. The profound changes in chronic active lesions, the predominance of synaptic/neural/axonal signatures coupled with minor inflammation may indicate end-stage irreversible molecular events responsible for this less treatable phase.