Bed load sediment transport is an inherently challenging process to measure within a river, which is further complicated by the typically transient nature of the hydrograph. Here we use laboratory ...experiments to explore how sediment flux under transient—unsteady and intermittent—flow differ from those under steady flow. For a narrow unimodal sediment distribution, we calculated fluid stress and measured sediment flux for a range of hydrograph durations, magnitudes, shapes, and sequences. Within a hydrograph, we find considerable variability in sediment flux for a given stress above the threshold for motion. However, cumulative bed load flux resulting from a flood scales linearly with the integrated excess transport capacity (flow impulse). This scaling indicates that, to first order, flow magnitude, duration, shape, and sequence are only relevant to bed load flux in terms of their contribution to the total flow impulse, in agreement with prior field results. The flood impulse represents a quantitative parameter through which the effects of transient flow on coarse sediment transport may be parsed.
Plain Language Summary
Mountain river floods produced from snowmelt can last months but remain relatively shallow, while floods resulting from storms are often shorter in duration and deeper. These floods have, in a sense, different shapes and sizes determined by their environment and climate. We performed laboratory experiments to understand how these flood shapes and sizes affect the amount of sediment they can move, a key precursor to understanding how rivers and flooding impact the landscapes in which they reside. Our experiments show that if one accounts for the forcing of the flood in a physically based manner, there is no difference between floods of different shapes and sizes in terms of how much sediment they move. We suggest that these results may make floods easier to characterize when modeling landscapes.
Key Points
Laboratory experiments reveal that total bed load flux for a flood is linearly related to the flow impulse (integrated transport capacity)
For an equivalent flow impulse, transient and steady floods transport the same total bed load sediment flux
Components of unsteady floods affect bed load flux in their contribution to the impulse but are otherwise identical for well sorted gravel
Clostridium botulinum is a species of spore-forming anaerobic bacteria defined by the expression of any one or two of seven serologically distinct botulinum neurotoxins (BoNTs) designated BoNT/A-G. ...This Gram-positive bacterium was first identified in 1897 and since then the paralyzing and lethal effects of its toxin have resulted in the recognition of different forms of the intoxication known as food-borne, infant, or wound botulism. Early microbiological and biochemical characterization of C. botulinum isolates revealed that the bacteria within the species had different characteristics and expressed different toxin types. To organize the variable bacterial traits within the species, Group I-IV designations were created. Interestingly, it was observed that isolates within different Groups could express the same toxin type and conversely a single Group could express different toxin types. This discordant phylogeny between the toxin and the host bacteria indicated that horizontal gene transfer of the toxin was responsible for the variation observed within the species. The recent availability of multiple C. botulinum genomic sequences has offered the ability to bioinformatically analyze the locations of the bont genes, the composition of their toxin gene clusters, and the genes flanking these regions to understand their variation. Comparison of the genomic sequences representing multiple serotypes indicates that the bont genes are not in random locations. Instead the analyses revealed specific regions where the toxin genes occur within the genomes representing serotype A, B, C, E, and F C. botulinum strains and C. butyricum type E strains. The genomic analyses have provided evidence of horizontal gene transfer, site-specific insertion, and recombination events. These events have contributed to the variation observed among the neurotoxins, the toxin gene clusters and the bacteria that contain them, and has supported the historical microbiological, and biochemical characterization of the Group classification within the species.
Abstract
Large laser facilities have recently enabled material characterization at the pressures of Earth and Super-Earth cores. However, the temperature of the compressed materials has been largely ...unknown, or solely relied on models and simulations, due to lack of diagnostics under these challenging conditions. Here, we report on temperature, density, pressure, and local structure of copper determined from extended x-ray absorption fine structure and velocimetry up to 1 Terapascal. These results nearly double the highest pressure at which extended x-ray absorption fine structure has been reported in any material. In this work, the copper temperature is unexpectedly found to be much higher than predicted when adjacent to diamond layer(s), demonstrating the important influence of the sample environment on the thermal state of materials; this effect may introduce additional temperature uncertainties in some previous experiments using diamond and provides new guidance for future experimental design.
Many species are extending their leading‐edge (cool) range margins polewards in response to recent climate change. In the present study, we investigated range margin changes at the northern (cool) ...range margins of 1573 southerly‐distributed species from 21 animal groups in Great Britain over the past four decades of climate change, updating previous work. Depending on data availability, range margin changes were examined over two time intervals during the past four decades. For four groups (birds, butterflies, macromoths, and dragonflies and damselflies), there were sufficient data available to examine range margin changes over both time intervals. We found that most taxa shifted their northern range margins polewards and this finding was not greatly influenced by changes in recorder effort. The mean northwards range margin change in the first time interval was 23 km per decade (N = 13 taxonomic groups) and, in the second interval, was 18 km per decade (N = 16 taxonomic groups) during periods when the British climate warmed by 0.21 and 0.28 °C per decade, respectively. For the four taxa examined over both intervals, there was evidence for higher rate of range margin change in the more recent time interval in the two Lepidoptera groups. Our analyses confirm a continued range margin shift polewards in a wide range of taxonomic groups.
Chronic leg and foot wounds represent an increasing burden to healthcare systems as the age of the population increases. The deep dermal tissues of all chronic wounds harbour microorganisms, however, ...the precise interaction between microbes in the wounds and impaired healing is unknown. With regard to antibiotic therapy, there is a lack of evidence concerning its effectiveness, optimal regimens or clinical indications for treatment. Despite this lack of evidence, antibiotics are frequently a feature of the management of chronic wounds and these patients receive significantly more antibiotic prescriptions (both systemic and topical) than age and sex-matched patients. Current guidelines for antibiotic prescribing for such wounds are often based on expert opinion rather than scientific fact and may present difficulties in interpretation and implementation to the clinician. Although the increasing prevalence of antibiotic resistance is widely recognized, the relationships between antibiotic resistance, chronic wound microbiology and rationales for antibiotic therapy have yet to be determined. This review discusses the role of microbes in chronic wounds from a clinical perspective with particular focus on the occurrence of bacteria and their impact on such wounds. The evidence and role of antibiotics in the treatment of such wounds are outlined and current practice of antibiotic usage for chronic wounds in the primary care setting described. The implications of antibiotic usage with regard to antibiotic resistance are also considered.
The current standard of care in the neoadjuvant setting for high-risk HER2-positive (HER2 +) breast cancer is to combine systemic chemotherapy with dual HER2 blockade, trastuzumab and pertuzumab. ...Targeted therapies have significantly improved outcomes for patients with HER2-positive breast cancer. To improve treatment-associated toxicity, chemotherapy-sparing approaches are currently being investigated. Trastuzumab deruxtecan (T-DXd) is an HER2-directed antibody-drug-conjugate (ADC) with promising results in the metastatic setting for HER2-positive breast cancer. The SHAMROCK study investigates neoadjuvant T-DXd in early stage HER2-positive breast cancer, using pathological complete response (pCR) rate as the primary endpoint.
This is a phase II open-label, single arm, adaptive multi-centre trial of T-DXd in the neoadjuvant setting in stage 2-3 HER2-positive breast cancer. Eligible patients will receive 5.4 mg/kg of T-DXd intravenously every 3 weeks for up to 6 cycles. A repeat biopsy will performed after 2 cycles for the RNA disruption index (RDI) score assessment. According to their likelihood of pCR, as determined by the RDI score, patients will either undergo 4 or 6 cycles of T-DXd prior to imaging. Patients with imaging complete response (iCR) after either 4 or 6 cycles will proceed to surgery. Patients who do not achieve iCR will either undergo further systemic therapy or proceed to surgery.
The SHAMROCK study is a chemotherapy-sparing approach to curative intent treatment, investigating neoadjuvant T-DXd. We hypothesise that neoadjuvant T-DXd will have a high pCR rate and be associated low toxicity in early stage HER2-positive breast cancer.
EudraCT Number: 2022-002485-32; ClinicalTrials.gov identifier: NCT05710666; Cancer Trials Ireland study number: CTRIAL-IE 22-01.
Activity-dependent transcription influences neuronal connectivity, but the roles and mechanisms of inactivation of activity-dependent genes have remained poorly understood. Genome-wide analyses in ...the mouse cerebellum revealed that the nucleosome remodeling and deacetylase (NuRD) complex deposits the histone variant H2A.z at promoters of activity-dependent genes, thereby triggering their inactivation. Purification of translating messenger RNAs from synchronously developing granule neurons (Sync-TRAP) showed that conditional knockout of the core NuRD subunit Chd4 impairs inactivation of activity-dependent genes when neurons undergo dendrite pruning. Chd4 knockout or expression of NuRD-regulated activity genes impairs dendrite pruning. Imaging of behaving mice revealed hyperresponsivity of granule neurons to sensorimotor stimuli upon Chd4 knockout. Our findings define an epigenetic mechanism that inactivates activity-dependent transcription and regulates dendrite patterning and sensorimotor encoding in the brain.
Many species are predicted to shift their ranges to higher latitudes and altitudes in response to climate warming. This study presents evidence for 37 species of nonmigratory British dragonflies and ...damselflies shifting northwards at their range margins over the past 40 years, seemingly as a result of climate change. This response by an exemplar group of insects associated with fresh water, parallels polewards range changes observed in terrestrial invertebrates and other taxa.
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