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Lithium-ion batteries offer the highest energy density of any currently available portable energy storage technology. By using different anode materials, these batteries could have an even greater energy density. One material, tin, has a theoretical lithium capacity (994 mAh/g) over three-times higher than commercial carbon anode materials. Unfortunately, to achieve this high capacity, bulk tin undergoes a large volume expansion, and the material pulverizes during cycling, giving a rapid capacity fade. To mitigate this issue, tin must be scaled down to the nano-level to take advantage of unique micromechanics at the nanoscale. Synthesis techniques for Sn nanoparticle anodes are costly and overly complicated for commercial production. A novel one-step process for producing carbon-coated Sn nanoparticles via spark plasma erosion (SPE) shows great promise as a simple, inexpensive production method. The SPE method, characterization of the resulting particles, and their high-capacity reversible electrochemical performance as anodes are described. With only a 10% addition of these novel SPE carbon-coated Sn particles, one anode composition demonstrated a reversible capacity of ~460 mAh/g, achieving the theoretical capacity of that particular electrode formulation. These SPE carbon-coated Sn nanoparticles are drop-in ready for present commercial lithium-ion anode processing and would provide a ~10% increase in the total capacity of current commercial lithium-ion cells.

To better understand the dynamics of avian populations and their role in population trends, we require an in‐depth understanding of the factors influencing the survival of adults and juveniles. However, assessing survival in juveniles is often challenging, especially in small, migratory species where individuals typically disperse from the study area and are not available for recapture in subsequent years. Bobolinks (Dolichonyx oryzivorus) are a long‐distance migrant that exhibits natal philopatry in at least one population, allowing for more comprehensive juvenile survival analyses than in many other long‐distance avian migrants. Using a 17‐yr dataset from two sites representing a Vermont population of Bobolinks, we used Program MARK to assess factors influencing apparent juvenile survival, including factors related to nesting timing, nest attempt number, the philopatric behaviors of relatives, body mass, brood size, and agricultural management scheme. Our top models indicated that nest attempt number and whether or not a nest mate also survived and returned to breed locally were important factors explaining variation in apparent survival in juvenile Bobolinks. Specifically, juveniles from first nest attempts that fledged earlier in the season, with siblings that did not survive and return to breed locally, showed higher apparent survival. Factors such as site and the philopatric behavior of females associated with nests also appeared in top‐ranking models, while factors such as body mass and brood size did not. These results indicate the importance of providing high‐quality breeding habitat to birds early in the season when juvenile survival is greatest and indicate that individuals may be utilizing inbreeding avoidance strategies. These results provide new insight into the ecological and agricultural management factors influencing survival in migratory species that use managed habitats and underscore the importance of integrating juvenile survival data into current management schemes to better support this and other declining species.

Economic uncertainty in the rare earth (RE) permanent magnet marketplace, as well as in an expanding electric drive vehicle market that favors permanent magnet alternating current synchronous drive motors, motivated renewed research in RE-free permanent magnets like “alnico,” an Al-Ni-Co-Fe alloy. Thus, high-pressure, gas-atomized isotropic type-8H pre-alloyed alnico powder was compression molded with a clean burn - out binder to near-final shape and sintered to density >99% of cast alnico 8 (full density of 7.3 g/cm 3 ). To produce aligned sintered alnico magnets for improved energy product and magnetic remanence, uniaxial stress was attempted to promote controlled grain growth, avoiding directional solidification that provides alignment in alnico 9. Successful development of solid-state powder processing may enable anisotropically aligned alnico magnets with enhanced energy density to be mass-produced.

Since the mid-1980s, our understanding of avian reproductive strategies has shifted as new molecular technologies have revealed how common promiscuity is in many monogamous avian species. However, the prevalence and importance of extra-pair paternity in polygynous species is less well studied. We used microsatellite loci from related icterid species to identify the extra-pair paternity rate in a polygynous population of Bobolinks (Dolichonyx oryzivorus) that bred in the Champlain Valley of Vermont from 2002 to 2018. We assigned paternity for 120 nestlings and found that 42% of nestlings were sired by extra-pair males. These results highlight the importance of extra-pair paternity in the reproductive behavior of Bobolinks that breed in agricultural habitats.

Since the mid-1980s, our understanding of avian reproductive strategies has shifted as new molecular technologies have revealed how common promiscuity is in many monogamous avian species. However, the prevalence and importance of extra-pair paternity in polygynous species is less well studied. We used microsatellite loci from related icterid species to identify the extra-pair paternity rate in a polygynous population of Bobolinks (Dolichonyx oryzivorus) that bred in the Champlain Valley of Vermont from 2002 to 2018. We assigned paternity for 120 nestlings and found that 42% of nestlings were sired by extra-pair males. These results highlight the importance of extra-pair paternity in the reproductive behavior of Bobolinks that breed in agricultural habitats. Received 29 March 2020. Accepted I October 2021.

Urban street trees provide many environmental, social, and economic benefits for our cities. This research explored the role of street trees in Melbourne, Australia, in cooling the urban microclimate and improving human thermal comfort (HTC). Three east–west (E–W) oriented streets were studied in two contrasting street canyon forms (deep and shallow) and between contrasting tree canopy covers (high and low). These streets were instrumented with multiple microclimate monitoring stations to continuously measure air temperature, humidity, solar radiation, wind speed and mean radiant temperature so as to calculate the Universal Thermal Climate Index (UTCI) from May 2011 to June 2013, focusing on summertime conditions and heat events. Street trees supported average daytime cooling during heat events in the shallow canyon by around 0.2 to 0.6 °C and up to 0.9 °C during mid-morning (9:00–10:00). Maximum daytime cooling reached 1.5 °C in the shallow canyon. The influence of street tree canopies in the deep canyon was masked by the shading effect of the tall buildings. Trees were very effective at reducing daytime UTCI in summer largely through a reduction in mean radiant temperature from shade, lowering thermal stress from very strong (UTCI > 38 °C) down to strong (UTCI > 32 °C). The influence of street trees on canyon air temperature and HTC was highly localized and variable, depending on tree cover, geometry, and prevailing meteorological conditions. The cooling benefit of street tree canopies increases as street canyon geometry shallows and broadens. This should be recognized in the strategic placement, density of planting, and species selection of street trees.

The UK Medical Research Council’s widely used guidance for developing and evaluating complex interventions has been replaced by a new framework, commissioned jointly by the Medical Research Council and the National Institute for Health Research, which takes account of recent developments in theory and methods and the need to maximise the efficiency, use, and impact of research.

New treatment options are needed for patients with multiple myeloma that is refractory to proteasome inhibitors and immunomodulatory drugs. We assessed daratumumab, a novel CD38-targeted monoclonal antibody, in patients with refractory multiple myeloma. In this open-label, multicentre, phase 2 trial done in Canada, Spain, and the USA, patients (age ≥18 years) with multiple myeloma who were previously treated with at least three lines of therapy (including proteasome inhibitors and immunomodulatory drugs), or were refractory to both proteasome inhibitors and immunomodulatory drugs, were randomly allocated in a 1:1 ratio to receive intravenous daratumumab 8 mg/kg or 16 mg/kg in part 1 stage 1 of the study, to decide the dose for further assessment in part 2. Patients received 8 mg/kg every 4 weeks, or 16 mg/kg per week for 8 weeks (cycles 1 and 2), then every 2 weeks for 16 weeks (cycles 3–6), and then every 4 weeks thereafter (cycle 7 and higher). The allocation schedule was computer-generated and randomisation, with permuted blocks, was done centrally with an interactive web response system. In part 1 stage 2 and part 2, patients received 16 mg/kg dosed as in part 1 stage 1. The primary endpoint was overall response rate (partial response [PR] + very good PR + complete response [CR] + stringent CR). All patients who received at least one dose of daratumumab were included in the analysis. The trial is registered with ClinicalTrials.gov, number NCT01985126. The study is ongoing. In part 1 stage 1 of the study, 18 patients were randomly allocated to the 8 mg/kg group and 16 to the 16 mg/kg group. Findings are reported for the 106 patients who received daratumumab 16 mg/kg in parts 1 and 2. Patients received a median of five previous lines of therapy (range 2–14). 85 (80%) patients had previously received autologous stem cell transplantation, 101 (95%) were refractory to the most recent proteasome inhibitors and immunomodulatory drugs used, and 103 (97%) were refractory to the last line of therapy. Overall responses were noted in 31 patients (29·2%, 95% CI 20·8–38·9)—three (2·8%, 0·6–8·0) had a stringent CR, ten (9·4%, 4·6–16·7) had a very good PR, and 18 (17·0%, 10·4–25·5) had a PR. The median time to first response was 1·0 month (range 0·9–5·6). Median duration of response was 7·4 months (95% CI 5·5–not estimable) and progression-free survival was 3·7 months (95% CI 2·8–4·6). The 12-month overall survival was 64·8% (95% CI 51·2–75·5) and, at a subsequent cutoff, median overall survival was 17·5 months (95% CI 13·7–not estimable). Daratumumab was well tolerated; fatigue (42 [40%] patients) and anaemia (35 [33%]) of any grade were the most common adverse events. No drug-related adverse events led to treatment discontinuation. Daratumumab monotherapy showed encouraging efficacy in heavily pretreated and refractory patients with multiple myeloma, with a favourable safety profile in this population of patients. Janssen Research & Development.

Immunosurveillance of cancer requires the presentation of peptide antigens on major histocompatibility complex class I (MHC-I) molecules 1 – 5 . Current approaches to profiling of MHC-I-associated peptides, collectively known as the immunopeptidome, are limited to in vitro investigation or bulk tumour lysates, which limits our understanding of cancer-specific patterns of antigen presentation in vivo 6 . To overcome these limitations, we engineered an inducible affinity tag into the mouse MHC-I gene ( H2-K1 ) and targeted this allele to the Kras LSL-G12D/+ Trp53 fl/fl mouse model (KP/K b Strep) 7 . This approach enabled us to precisely isolate MHC-I peptides from autochthonous pancreatic ductal adenocarcinoma and from lung adenocarcinoma (LUAD) in vivo. In addition, we profiled the LUAD immunopeptidome from the alveolar type 2 cell of origin up to late-stage disease. Differential peptide presentation in LUAD was not predictable by mRNA expression or translation efficiency and is probably driven by post-translational mechanisms. Vaccination with peptides presented by LUAD in vivo induced CD8 + T cell responses in naive mice and tumour-bearing mice. Many peptides specific to LUAD, including immunogenic peptides, exhibited minimal expression of the cognate mRNA, which prompts the reconsideration of antigen prediction pipelines that triage peptides according to transcript abundance 8 . Beyond cancer, the K b Strep allele is compatible with other Cre-driver lines to explore antigen presentation in vivo in the pursuit of understanding basic immunology, infectious disease and autoimmunity. A newly developed genetically engineered mouse model enables the analysis of specific antigen presentation in vivo, providing insights into the tumour immunopeptidome and cancer progression.

Middle East respiratory syndrome (MERS) coronavirus causes a highly fatal lower-respiratory tract infection. There are as yet no licensed MERS vaccines or therapeutics. This study (WRAIR-2274) assessed the safety, tolerability, and immunogenicity of the GLS-5300 MERS coronavirus DNA vaccine in healthy adults. This study was a phase 1, open-label, single-arm, dose-escalation study of GLS-5300 done at the Walter Reed Army Institute for Research Clinical Trials Center (Silver Spring, MD, USA). We enrolled healthy adults aged 18–50 years; exclusion criteria included previous infection or treatment of MERS. Eligible participants were enrolled sequentially using a dose-escalation protocol to receive 0·67 mg, 2 mg, or 6 mg GLS-5300 administered by trained clinical site staff via a single intramuscular 1 mL injection at each vaccination at baseline, week 4, and week 12 followed immediately by co-localised intramuscular electroporation. Enrolment into the higher dose groups occurred after a safety monitoring committee reviewed the data following vaccination of the first five participants at the previous lower dose in each group. The primary outcome of the study was safety, assessed in all participants who received at least one study treatment and for whom post-dose study data were available, during the vaccination period with follow-up through to 48 weeks after dose 3. Safety was measured by the incidence of adverse events; administration site reactions and pain; and changes in safety laboratory parameters. The secondary outcome was immunogenicity. This trial is registered at ClinicalTrials.gov (number NCT02670187) and is completed. Between Feb 17 and July 22, 2016, we enrolled 75 individuals and allocated 25 each to 0·67 mg, 2 mg, or 6 mg GLS-5300. No vaccine-associated serious adverse events were reported. The most common adverse events were injection-site reactions, reported in 70 participants (93%) of 75. Overall, 73 participants (97%) of 75 reported at least one solicited adverse event; the most common systemic symptoms were headache (five [20%] with 0·67 mg, 11 [44%] with 2 mg, and seven [28%] with 6 mg), and malaise or fatigue (five [20%] with 0·67 mg, seven [28%] with 2 mg, and two [8%] with 6 mg). The most common local solicited symptoms were administration site pain (23 [92%] with all three doses) and tenderness (21 [84%] with all three doses). Most solicited symptoms were reported as mild (19 [76%] with 0·67 mg, 20 [80%] with 2 mg, and 17 [68%] with 6 mg) and were self-limiting. Unsolicited symptoms were reported for 56 participants (75%) of 75 and were deemed treatment-related for 26 (35%). The most common unsolicited adverse events were infections, occurring in 27 participants (36%); six (8%) were deemed possibly related to study treatment. There were no laboratory abnormalities of grade 3 or higher that were related to study treatment; laboratory abnormalities were uncommon, except for 15 increases in creatine phosphokinase in 14 participants (three participants in the 0·67 mg group, three in the 2 mg group, and seven in the 6 mg group). Of these 15 increases, five (33%) were deemed possibly related to study treatment (one in the 2 mg group and four in the 6 mg group). Seroconversion measured by S1-ELISA occurred in 59 (86%) of 69 participants and 61 (94%) of 65 participants after two and three vaccinations, respectively. Neutralising antibodies were detected in 34 (50%) of 68 participants. T-cell responses were detected in 47 (71%) of 66 participants after two vaccinations and in 44 (76%) of 58 participants after three vaccinations. There were no differences in immune responses between dose groups after 6 weeks. At week 60, vaccine-induced humoral and cellular responses were detected in 51 (77%) of 66 participants and 42 (64%) of 66, respectively. The GLS-5300 MERS coronavirus vaccine was well tolerated with no vaccine-associated serious adverse events. Immune responses were dose-independent, detected in more than 85% of participants after two vaccinations, and durable through 1 year of follow-up. The data support further development of the GLS-5300 vaccine, including additional studies to test the efficacy of GLS-5300 in a region endemic for MERS coronavirus. US Department of the Army and GeneOne Life Science.