Gravity waves (disturbances to the density structure of the atmosphere whose restoring forces are gravity and buoyancy) comprise the principal form of energy exchange between the lower and upper ...atmosphere. Wave breaking drives the mean upper atmospheric circulation, determining boundary conditions to stratospheric processes, which in turn influence tropospheric weather and climate patterns on various spatial and temporal scales. Despite their recognized importance, very little is known about upper-level gravity wave characteristics. The knowledge gap is mainly due to lack of global, high-resolution observations from currently available satellite observing systems. Consequently, representations ofwave-related processes in global models are crude, highly parameterized, and poorly constrained, limiting the description of various processes influenced by them. Here we highlight, through a series of examples, the unanticipated ability of the Day/Night Band (DNB) on the NOAA/NASA Suomi National Polar-orbiting Partnership environmental satellite to resolve gravity structures near the mesopause via nightglow emissions at unprecedented subkilometric detail. On moonless nights, the Day/Night Band observations provide all-weather viewing of waves as they modulate the nightglow layer located near the mesopause (∼90 km above mean sea level). These waves are launched by a variety of physical mechanisms, ranging from orography to convection, intensifying fronts, and even seismic and volcanic events. Cross-referencing the Day/Night Band imagery with conventional thermal infrared imagery also available helps to discern nightglow structures and in some cases to attribute their sources. The capability stands to advance our basic understanding of a critical yet poorly constrained driver of the atmospheric circulation.
In this paper, we present near‐simultaneous observations of a gravity wave (GW) event in the stratosphere, mesosphere, and ionosphere over the South Central United States and track it from its ...convective source region in the troposphere to the ionosphere, where it appears as a traveling ionospheric disturbance (TID). On 4 April 2014 concentric GW ring patterns were seen at stratospheric heights in close proximity to a convective storm over North Texas in the Atmospheric Infrared Sounder data on board the NASA Aqua satellite. Concentric GWs of similar orientation and epicenter were also observed in mesospheric nightglow measurements of the Day/Night Band of the Visible/Infrared Imaging Radiometer Suite on the Suomi National Polar‐orbiting Partnership satellite. Concentric TIDs were seen in total electron content data derived from ground‐based GPS receivers distributed throughout the U.S. These new multisensor observations of TIDs and atmospheric GWs can provide a unique perspective on ionosphere‐atmosphere coupling.
Key Points
We track concentric GWs from their convective source region in the troposphere to the ionosphere
Gravity wave features are seen nearly simultaneously in stratosphere, mesosphere, and ionosphere
The slant propagation path of the TIDs suggests their source being near the convective storm
The relationships between clonal architecture and functional heterogeneity in acute myeloid leukemia (AML) samples are not yet clear. We used targeted sequencing to track AML subclones identified by ...whole-genome sequencing using a variety of experimental approaches. We found that virtually all AML subclones trafficked from the marrow to the peripheral blood, but some were enriched in specific cell populations. Subclones showed variable engraftment potential in immunodeficient mice. Xenografts were predominantly comprised of a single genetically defined subclone, but there was no predictable relationship between the engrafting subclone and the evolutionary hierarchy of the leukemia. These data demonstrate the importance of integrating genetic and functional data in studies of primary cancer samples, both in xenograft models and in patients.
•AML subclones are discrete, genetically distinct entities in AML samples•AML subclones often have unique functional and morphological properties•Engraftment of AML cells in mice is not defined by evolutionary hierarchy•The AML founding clone is not equivalent to the AML-initiating cell in mice
Klco et al. track acute myeloid leukemia (AML) subclones identified by whole-genome sequencing and find that subclones of AML can correspond to different cellular populations within a single AML sample and can have different functional properties in vitro and in immunodeficient mice.
Radiation sensitivity varies greatly between tissues. The transcription factor p53 mediates the response to radiation; however, the abundance of p53 protein does not correlate well with the extent of ...radiosensitivity across tissues. Given recent studies showing that the temporal dynamics of p53 influence the fate of cultured cells in response to irradiation, we set out to determine the dynamic behavior of p53 and its impact on radiation sensitivity in vivo. We find that radiosensitive tissues show prolonged p53 signaling after radiation, while more resistant tissues show transient p53 activation. Sustaining p53 using a small molecule (NMI801) that inhibits Mdm2, a negative regulator of p53, reduced viability in cell culture and suppressed tumor growth. Our work proposes a mechanism for the control of radiation sensitivity and suggests tools to alter the dynamics of p53 to enhance tumor clearance. Similar approaches can be used to enhance killing of cancer cells or reduce toxicity in normal tissues following genotoxic therapies.
High resolution scanning electron microscope digital image correlation (SEM DIC) was performed in situ during uniaxial loading on Ti-6Al-4V rolled titanium plate to determine the dependence of strain ...localization on microstructure and microtexture. Individual grains with preferred orientation for basal slip exhibited plastic localization along basal planes before macroscopic yielding. With additional strain, but still below macroscopic yielding, pyramidal and prismatic plastic activity was observed as slip bands transmitting across many grains and entire microtextured regions (MTRs). The localization of long range plastic strain occurred within MTRs that allowed for slip transmission across grains with low angle boundaries. The rolled titanium plate material having strong 0001 and101¯0texture components showed pyramidal and prismatic type slip extending across entire MTRs at strains well below macroscopic yielding. These strain localization processes occur much earlier in straining and over lengthscales much longer than observed with conventional slip offset imaging. The implications for properties are discussed.
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Many antibiotics lack activity against Gram-negative bacteria because they cannot permeate the outer membrane or suffer from efflux and, in the case of β-lactams, are degraded by β-lactamases. ...Herein, we describe the synthesis and studies of a dual drug conjugate (1) of a siderophore linked to a cephalosporin with an attached oxazolidinone. The cephalosporin component of 1 is rapidly hydrolyzed by purified ADC-1 β-lactamase to release the oxazolidinone. Conjugate 1 is active against clinical isolates of Acinetobacter baumannii as well as strains producing large amounts of ADC-1 β-lactamase. Overall, the results are consistent with siderophore-mediated active uptake, inherent activity of the delivered dual drug, and in the presence of β-lactamases, intracellular release of the oxazolidinone upon cleavage of the cephalosporin to allow the freed oxazolidinone to inactivate its target. The ultimate result demonstrates that Gram-positive oxazolidinone antibiotics can be made to be effective against Gram-negative bacteria by β-lactamase triggered release.
This systematic review examines the incidence and prevalence of traumatic spinal cord injury (SCI) in different countries worldwide and their trends over time. The literature search of the studies ...published between 1950 and 2012 captured 1,871 articles of which 64 articles on incidence and 13 articles on prevalence fulfilled the inclusion and exclusion criteria. The global incidence of SCI varied from 8.0 to 246.0 cases per million inhabitants per year. The global prevalence varied from 236.0 to 1,298.0 per million inhabitants. In addition to regional differences regarding the prevalence rates of SCI across the globe, there has been a trend towards increasing prevalence rates over the last decades. Our results suggest a relatively broad variation of incidence and prevalence rates of SCI among distinctive geographic regions. These results emphasize the need for further studies on incidence and prevalence of SCI, and for international standards and guidelines for reporting on SCI.
We explore the effect of randomized treatment, comparing intensive to standard glucose-lowering strategies on major cardiovascular outcomes, death, and severe adverse events in older versus younger ...participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.
Participants with type 2 diabetes (n = 10,251) with a mean age of 62 years, a median duration of diabetes of 10 years, and a median A1C of 8.1% (65 mmol/mol) were randomized to treatment strategies targeting either A1C <6.0% (42 mmol/mol) or 7.0-7.9% (53-63 mmol/mol) and followed for a mean of 3.7 years. Outcomes were analyzed within subgroups defined by baseline age (<65 vs. ≥65 years).
Older and younger ACCORD participants achieved similar intensive-arm A1C levels and between-arm A1C differences. Within the older subgroup, similar hazards of the cardiovascular primary outcome and total mortality were observed in the two arms. While there was no intervention effect on cardiovascular mortality in the older subgroup, there was an increased risk in the intensive arm for the younger subgroup (older hazard ratio HR = 0.97; younger HR = 1.71; P = 0.03). Regardless of intervention arm, the older subgroup experienced higher annualized rates of severe hypoglycemia (4.45% intensive and 1.36% standard) than the younger subgroup (2.45% intensive and 0.80% standard).
Intensive glucose lowering increased the risk of cardiovascular disease and total mortality in younger participants, whereas it had a neutral effect in older participants. The intensive to standard relative risk of severe hypoglycemia was similar in both age subgroups, with higher absolute rates in older participants within both treatment arms.
Breast cancer brain metastases (BCBM) are a challenging consequence of advanced BC. Nanoparticle agents, including liposomes, have shown enhanced delivery to solid tumors and brain. We compared ...pharmacokinetics (PK) and efficacy of PEGylated liposomal doxorubicin (PLD) with non-liposomal doxorubicin (NonL-doxo) in an intracranial model of BC.
Athymic mice were inoculated intracerebrally with MDA-MB-231-BR-luciferase-expressing cells. Tumor-bearing mice were administered PLD or NonL-doxo at 6 mg/kg IV × 1 and were euthanized prior to and 0.083, 1, 3, 6, 24, 72 and 96 h post-treatment. Samples were processed to measure sum total doxorubicin via HPLC. PLD and NonL-doxo were administered IV weekly as single agents (6 mg/kg) or in combination (4.5 mg/kg) with the PARP inhibitor, ABT-888, PO 25 mg/kg/day. Efficacy was assessed by survival and bioluminescence.
Treatment with PLD resulted in approximately 1,500-fold higher plasma and 20-fold higher intracranial tumor sum total doxorubicin AUC compared with NonL-doxo. PLD was detected at 96 h; NonL-doxo was undetectable after 24 h in plasma and tumor. Median survival of PLD-treated animals was 32 days (d, CI 31-38), which was significantly longer than controls (26d CI 25-28; p = 0.0012) or NonL-doxo treatment (23.5d CI 18-28, p = 0.0002). Combination treatment with PLD/ABT-888 yielded improved survival compared to NonL-doxo/ABT-888 (35d CI 31-38 versus 29.5d CI 25-34; p = 0.006).
PLD provides both PK and efficacy advantage over NonL-doxo in the treatment of an in vivo model of BCBM. The results provide preclinical rationale to translate findings into early phase trials of PLD, with or without ABT-888, for patients with BCBM.
The literature suggests that stroke is a major risk factor for falls, but there is a lack of prospective, controlled studies which quantify fall-risk after stroke. The purpose of this study was to ...compare the rates, location and predictors among individuals recently discharged home from stroke rehabilitation to age and sex matched controls.
A sample of 80 people with stroke and 90 controls received baseline assessments of balance, mobility and balance confidence. Falls were recorded prospectively over 13 months for both groups. Group differences in fall rates and contribution of clinical measures to falls were determined using negative binomial regression. Fall location was compared between groups using χ(2) statistics. The rate of falls for individuals with stroke was 1.77 times the rate for the control group. People with stroke were more likely to fall at home. Poorer balance (Berg Balance Scale) was associated with greater falls for both stroke and control groups (incidence rate ratio IRR: 0.908 and IRR: 0.877 respectively). A faster Timed Up and Go Test was associated with greater falls for the stroke group (IRR: 0.955) while better walking endurance (Six Minute Walk Test) was associated with greater falls for the controls (IRR: 1.004). Balance confidence was not an independent predictor in either group.
Individuals recently discharged home are at greater risk of falling than individuals without stroke. Attention to home environment is warranted. Balance function can predict falls for both people with stroke and age and sex matched controls. Increased mobility may increase exposure to fall opportunities.
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