Our current knowledge of cosmic star-formation history during the first two billion years (corresponding to redshift z > 3) is mainly based on galaxies identified in rest-frame ultraviolet light
. ...However, this population of galaxies is known to under-represent the most massive galaxies, which have rich dust content and/or old stellar populations. This raises the questions of the true abundance of massive galaxies and the star-formation-rate density in the early Universe. Although several massive galaxies that are invisible in the ultraviolet have recently been confirmed at early epochs
, most of them are extreme starburst galaxies with star-formation rates exceeding 1,000 solar masses per year, suggesting that they are unlikely to represent the bulk population of massive galaxies. Here we report submillimetre (wavelength 870 micrometres) detections of 39 massive star-forming galaxies at z > 3, which are unseen in the spectral region from the deepest ultraviolet to the near-infrared. With a space density of about 2 × 10
per cubic megaparsec (two orders of magnitude higher than extreme starbursts
) and star-formation rates of 200 solar masses per year, these galaxies represent the bulk population of massive galaxies that has been missed from previous surveys. They contribute a total star-formation-rate density ten times larger than that of equivalently massive ultraviolet-bright galaxies at z > 3. Residing in the most massive dark matter haloes at their redshifts, they are probably the progenitors of the largest present-day galaxies in massive groups and clusters. Such a high abundance of massive and dusty galaxies in the early Universe challenges our understanding of massive-galaxy formation.
Summary
Background
Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti‐viral therapy affects ...survival after HCC diagnosis.
Methods
This was an international multicentre cohort study of 2518 HBV‐related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti‐viral therapy and cirrhosis on patients' risk of death.
Results
Approximately, 48% of patients received anti‐viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti‐viral therapy would have been indicated for >60% of the patients not on anti‐viral therapy based on American criteria. Patients with cirrhosis had lower 5‐year survival (34% vs 46%; P < 0.001) while patients receiving anti‐viral therapy had increased 5‐year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti‐viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001).
Conclusions
Anti‐viral therapy improved overall survival in patients with HBV‐related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti‐viral therapy in HBV‐related HCC and better linkage‐to‐care for HBV patients are needed.
The identification of high-redshift, massive galaxies with old stellar populations may pose challenges to some models of galaxy formation. However, to securely classify a galaxy as quiescent, it is ...necessary to exclude significant ongoing star formation, something that can be challenging to achieve at high redshifts. In this Letter, we analyze deep ALMA/870 m and SCUBA-2/450 m imaging of the claimed "post-starburst" galaxy ZF 20115 at z = 3.717 that exhibits a strong Balmer break and absorption lines. The rest-frame far-infrared imaging identifies a luminous starburst 0 4 0 1 (∼3 kpc in projection) from the position of the ultraviolet/optical emission and is consistent with lying at the redshift of ZF 20115. The star-forming component, with an obscured star formation rate of , is undetected in the rest-frame ultraviolet but contributes significantly to the lower angular resolution photometry at rest-frame wavelengths 3500 . This contribution from the obscured starburst, especially in the Spitzer/IRAC wavebands, significantly complicates the determination of a reliable stellar mass for the ZF 20015 system, and we conclude that this source does not pose a challenge to current models of galaxy formation. The multi-wavelength observations of ZF 20115 unveil a complex system with an intricate and spatially varying star formation history. ZF 20115 demonstrates that understanding high-redshift obscured starbursts will only be possible with multi-wavelength studies that include high-resolution observations, available with the James Webb Space Telescope, at mid-infrared wavelengths.
There are considerable challenges in directly targeting the mutant p53 protein, given the large heterogeneity of p53 mutations in the clinic. An alternative approach is to exploit the altered fitness ...of cells imposed by loss-of-wild-type p53. Here we identify niclosamide through a HTS screen for compounds selectively killing p53-deficient cells. Niclosamide impairs the growth of p53-deficient cells and of p53 mutant patient-derived ovarian xenografts. Metabolome profiling reveals that niclosamide induces mitochondrial uncoupling, which renders mutant p53 cells susceptible to mitochondrial-dependent apoptosis through preferential accumulation of arachidonic acid (AA), and represents a first-in-class inhibitor of p53 mutant tumors. Wild-type p53 evades the cytotoxicity by promoting the transcriptional induction of two key lipid oxygenation genes, ALOX5 and ALOX12B, which catalyzes the dioxygenation and breakdown of AA. Therefore, we propose a new paradigm for targeting cancers defective in the p53 pathway, by exploiting their vulnerability to niclosamide-induced mitochondrial uncoupling.
The effect of covering faces on face identification is recently garnering interest amid the COVID-19 pandemic. Here, we investigated how face identification performance was affected by two types of ...face disguise: sunglasses and face masks. Observers studied a series of faces; then judged whether a series of test faces, comprising studied and novel faces, had been studied before or not. Face stimuli were presented either without coverings (full faces), wearing sunglasses covering the upper region (eyes, eyebrows), or wearing surgical masks covering the lower region (nose, mouth, chin). We found that sunglasses led to larger reductions in sensitivity (d') to face identity than face masks did, while both disguises increased the tendency to report faces as studied before, a bias that was absent for full faces. In addition, faces disguised during either study or test only (i.e. study disguised faces, test with full faces; and vice versa) led to further reductions in sensitivity from both studying and testing with disguised faces, suggesting that congruence between study and test is crucial for memory retrieval. These findings implied that the upper region of the face, including the eye-region features, is more diagnostic for holistic face-identity processing than the lower face region.
The effects of mass transfer on the electrocatalytic reduction of CO2 on a polycrystalline Cu rotating cylinder electrode were investigated. When the rotation rate was increased, the current ...efficiency toward CO2 reduction products decreased while that for the hydrogen evolution reaction increased. Furthermore, the product selectivity switched from CH4 to CO as the rotation rate was increased. This observation is generally inconsistent with the widely reported dependence of the electrocatalytic CO2 reduction on interfacial pH and CO2 concentration. As increasing the rotation rate improves mass transfer of species to and from the electrode surface, the interfacial pH becomes closer to the bulk pH while the interfacial concentration of CO2 at the electrode surface increases. However, increasing the rotation rate significantly decreased the CO2 reduction activity for constant current electrochemical CO2 reduction despite the increased availability of CO2 at the electrode surface. As the changes in interfacial pH and CO2 concentration with rotation rate cannot adequately explain the results, it is instead suggested that the enhanced mass transfer of dissolved CO away from the electrode surface at high rotation rates is the main reason behind the observed effects. We propose that this enhanced mass transfer of CO away from the electrode surface decreases the surface coverage of COads (due to the equilibrium between COads and dissolved CO at the electrode-electrolyte interface) and limits the further reduction of COads to hydrocarbons.
A generalized refined theory including surface effects is developed for functionally graded ultra-thin films with different surface properties. The classical generalized shear deformable theory is ...adopted to model the film bulk, while the bulk stresses along the surfaces of the bulk substrate are required to satisfy the surface balance equations of the continuum surface elasticity. As a result, the shape function also shows size-dependence on the film thickness. Since the film is non-homogeneous through the thickness, the state space method and approximate laminate model are employed to derive the variation of shape function through the thickness direction. A simply supported thin film in cylindrical bending is considered as an example to illustrate the application of the present theory. By comparing to the Kirchhoff plate theory including surface effects, the necessity of the present theory for FGM thin films is solidly validated. It is established that the present FGM thin films exhibit significant size-dependence when the thickness approaches to micro-scale. As the gradient index changes, the extent of size-dependence varies accordingly.
A general, global theory is developed for nano-scaled functionally graded films considering surface effects. In addition to the Kirchhoff hypothesis of the classical thin plate theory, the surface ...layers of the film are modeled by the continuum theory of surface elasticity. Bulk stresses on the surfaces are required to satisfy the surface balance conditions involving surface stresses. Unlike the classical plate theory, the bulk transverse normal stress is preserved here. By incorporating the surface energies into the principle of minimum potential energy, a series of non-classical governing differential equations which include intrinsic length scales are derived. To illustrate application of the theory, a simply supported nano-scaled film in cylindrical bending is investigated. Numerical examples are presented to clarify the effects of surface energies on the bending behavior of FGM films, whose effective elastic moduli are predicted using the Mori–Tanaka method. Finally, the nature of intrinsic length scales, and the effects of gradient index and aspect ratio on the displacements are discussed.
The effect of uniform lighting on face identity processing is little understood, despite its potential influence on our ability to recognize faces. Here, we investigated how changes in uniform ...lighting level affected face identification performance during face memory tests. Observers were tasked with learning a series of faces, followed by a memory test where observers judged whether the faces presented were studied before or novel. Face stimuli were presented under uniform bright or dim illuminations, and lighting across the face learning and the memory test sessions could be the same ("congruent") or different ("incongruent"). This led to four experimental conditions: (1) Bright/Dim (learning bright faces, testing on dim faces); (2) Bright/Bright; (3) Dim/Bright; and (4) Dim/Dim. Our results revealed that incongruent lighting levels across sessions (Bright/Dim and Dim/Bright) significantly reduced sensitivity (
) to faces and introduced conservative biases compared to congruent lighting levels (Bright/Bright and Dim/Dim). No significant differences in performance were detected between the congruent lighting conditions (Bright/Bright vs. Dim/Dim) and between the incongruent lighting conditions (Bright/Dim vs. Dim/Bright). Thus, incongruent lighting deteriorated performance in face identification. These findings implied that the level of uniform lighting should be considered in an illumination-specific face representation and potential applications such as eyewitness testimony.
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