Cosmic-ray proton and helium spectra have been measured with the balloon-borne Cosmic Ray Energetics And Mass experiment flown for 42 days in Antarctica in the 2004-2005 austral summer season. ...High-energy cosmic-ray data were collected at an average altitude of ~38.5 km with an average atmospheric overburden of ~3.9 g cm--2. Individual elements are clearly separated with a charge resolution of ~0.15 e (in charge units) and ~0.2 e for protons and helium nuclei, respectively. The measured spectra at the top of the atmosphere are represented by power laws with a spectral index of --2.66 ? 0.02 for protons from 2.5 TeV to 250 TeV and --2.58 ? 0.02 for helium nuclei from 630 GeV nucleon--1 to 63 TeV nucleon--1. They are harder than previous measurements at a few tens of GeV nucleon--1. The helium flux is higher than that expected from the extrapolation of the power law fitted to the lower-energy data. The relative abundance of protons to helium nuclei is 9.1 ? 0.5 for the range from 2.5 TeV nucleon--1 to 63 TeV nucleon--1. This ratio is considerably smaller than the previous measurements at a few tens of GeV nucleon--1.
Summary
Patient education and behavioural interventions for self‐management of type 2 diabetes mellitus (T2DM) are effective but place demands on manpower resources. This systematic review aimed to ...investigate the effectiveness of smartphone technologies (STs) for improving glycaemic control among T2DM patients. CENTRAL, MEDLINE, Embase, CINAHL and ScienceDirect were searched through December 2016. Randomized controlled trials comparing STs with usual diabetes care among T2DM patients and reporting change in glycated haemoglobin (HbA1c) level were included. Seventeen trials (2,225 participants) were included. There was a significant reduction in HbA1c (pooled weighted mean difference: −0.51%; 95% confidence interval: −0.71% to −0.30%; p < 0.001), favouring ST intervention. The pooled weighted mean difference was −0.83% in patients with T2DM <8.5 years and −0.22% in patients with T2DM ≥8.5 years, with significant subgroup difference (p = 0.007). No subgroup differences were found among different follow‐up durations, trial locations, patients' age, healthcare provider contract time, baseline body mass index and baseline HbA1c. Compared with usual diabetes care, STs improved glycaemic control among T2DM patients, especially for patients at earlier disease stages (duration of diagnosis <8.5 years). STs could be a complement or alternative to labour‐intensive patient education and behavioural interventions, but more studies on up‐to‐date technologies are needed.
Analysis of hematopoietic stem cell function in nonhuman primates provides insights that are relevant for human biology and therapeutic strategies. In this study, we applied quantitative genetic ...barcoding to track the clonal output of transplanted autologous rhesus macaque hematopoietic stem and progenitor cells over a time period of up to 9.5 months. We found that unilineage short-term progenitors reconstituted myeloid and lymphoid lineages at 1 month but were supplanted over time by multilineage clones, initially myeloid restricted, then myeloid-B clones, and then stable myeloid-B-T multilineage, long-term repopulating clones. Surprisingly, reconstitution of the natural killer (NK) cell lineage, and particularly the major CD16+/CD56− peripheral blood NK compartment, showed limited clonal overlap with T, B, or myeloid lineages, and therefore appears to be ontologically distinct. Thus, in addition to providing insights into clonal behavior over time, our analysis suggests an unexpected paradigm for the relationship between NK cells and other hematopoietic lineages in primates.
Display omitted
•The output of individual primate HSPCs can be clonally tracked in vivo•Unilineage, bilineage, and multilineage clones can be mapped posttransplantation•Primate myeloid and B cells are more closely related than B and T cells•The dominant blood fraction of NK cells forms a unique hematopoietic lineage
Quantitative tracking of rhesus macaque hematopoiesis at a single-cell level by genetic cellular barcoding highlights a distinct origin for the dominant peripheral blood natural killer cell lineage.
We present new measurements of the energy spectra of cosmic-ray (CR) nuclei from the second flight of the balloon-borne experiment Cosmic-Ray Energetics And Mass (CREAM). The instrument included ...different particle detectors to provide redundant charge identification and measure the energy of CRs up to several hundred TeV. The measured individual energy spectra of C, O, Ne, Mg, Si, and Fe are presented up to ~1014 eV. The spectral shape looks nearly the same for these primary elements and it can be fitted to an E -2.66 +/- 0.04 power law in energy. Moreover, a new measurement of the absolute intensity of nitrogen in the 100-800 GeV/n energy range with smaller errors than previous observations, clearly indicates a hardening of the spectrum at high energy. The relative abundance of N/O at the top of the atmosphere is measured to be 0.080 +/- 0.025 (stat.)+/-0.025 (sys.) at ~800 GeV/n, in good agreement with a recent result from the first CREAM flight.
Visfatin (also known as pre-B cell colony-enhancing factor or PBEF) is a novel adipocytokine that is highly expressed in visceral fat and upregulated in obesity and type 2 diabetes mellitus. Visfatin ...binds to and activates the insulin receptor (IR), thereby exerting insulin-mimetic effects in various cell lines. IR has been detected in osteoblasts, which is consistent with the role of insulin as an important osteotropic hormone. This study investigated the actions of visfatin on human primary osteoblasts. The expression and tyrosine phosphorylation of IR, IR substrate-1 (IRS-1), and IRS-2 were determined by immunoprecipitation and immunoblotting. Cell proliferation was determined by measuring (3)Hthymidine incorporation and cell number. Glucose uptake was determined by measuring 2-(3)Hdeoxyglucose incorporation. Real-time quantitative reverse-transcription polymerase chain reaction (PCR) was used for determining alkaline phosphatase (ALP), osteocalcin, and type I collagen mRNA expression. Enzyme-linked immunosorbent assay and radioimmunoassay were used for measuring ALP activity, osteocalcin secretion, and type I collagen production. We found that visfatin induced tyrosine phosphorylation of IR, IRS-1, and IRS-2. Moreover, the effects of visfatin - glucose uptake, proliferation, and type I collagen enhancement of cultured human osteoblast-like cells - bore a close resemblance to those of insulin and were inhibited by hydroxy-2-naphthalenylmethylphosphonic acid tris-acetoxymethyl ester, a specific inhibitor of IR tyrosine kinase activity. We also unexpectedly found that visfatin downregulated osteocalcin secretion from human osteoblast-like cells. These data indicate that the regulation of glucose uptake, proliferation, and type I collagen production by visfatin in human osteoblasts involves IR phosphorylation, the same signal-transduction pathway used by insulin.
A set of 184 recombinant inbred lines (RILs) derived from soybean vars. Kefeng No.1 x Nannong 1138-2 was used to construct a genetic linkage map. The two parents exhibit contrasting characteristics ...for most of the traits that were mapped. Using restricted fragment length polymorphisms (RFLPs), simple sequence repeats (SSRs) and expressed sequence tags (ESTs), we mapped 452 markers onto 21 linkage groups and covered 3595.9 cM of the soybean genome. All of the linkage groups except linkage group F were consistent with those of the consensus map of Cregan et al. (1999). Linkage group F was divided into two linkage groups, F1 and F2. The map consisted of 189 RFLPs, 219 SSRs, 40 ESTs, three R gene loci and one phenotype marker. Ten agronomic traits-days to flowering, days to maturity, plant height, number of nodes on main stem, lodging, number of pods per node, protein content, oil content, 100-seed weight, and plot yield-were studied. Using winqtlcart, we detected 63 quantitative trait loci (QTLs) that had LOD>3 for nine of the agronomic traits (only exception being seed oil content) and mapped these on 12 linkage groups. Most of the QTLs were clustered, especially on groups B1 and C2. Some QTLs were mapped to the same loci. This pleiotropism was common for most of the QTLs, and one QTL could influence at most five traits. Seven EST markers were found to be linked closely with or located at the same loci as the QTLs. EST marker GmKF059a, encoding a repressor protein and mapped on group C2, accounted for about 20% of the total variation of days to flowering, plant height, lodging and nodes on the main stem, respectively.
Summary Background Although repeat radiation treatment has been shown to palliate pain in patients with bone metastases from multiple primary origin sites, data for the best possible dose ...fractionation schedules are lacking. We aimed to assess two dose fractionation schedules in patients with painful bone metastases needing repeat radiation therapy. Methods We did a multicentre, non-blinded, randomised, controlled trial in nine countries worldwide. We enrolled patients 18 years or older who had radiologically confirmed, painful (ie, pain measured as ≥2 points using the Brief Pain Inventory) bone metastases, had received previous radiation therapy, and were taking a stable dose and schedule of pain-relieving drugs (if prescribed). Patients were randomly assigned (1:1) to receive either 8 Gy in a single fraction or 20 Gy in multiple fractions by a central computer-generated allocation sequence using dynamic minimisation to conceal assignment, stratified by previous radiation fraction schedule, response to initial radiation, and treatment centre. Patients, caregivers, and investigators were not masked to treatment allocation. The primary endpoint was overall pain response at 2 months, which was defined as the sum of complete and partial pain responses to treatment, assessed using both Brief Pain Inventory scores and changes in analgesic consumption. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00080912. Findings Between Jan 7, 2004, and May 24, 2012, we randomly assigned 425 patients to each treatment group. 19 (4%) patients in the 8 Gy group and 12 (3%) in the 20 Gy group were found to be ineligible after randomisation, and 140 (33%) and 132 (31%) patients, respectively, were not assessable at 2 months and were counted as missing data in the intention-to-treat analysis. In the intention-to-treat population, 118 (28%) patients allocated to 8 Gy treatment and 135 (32%) allocated to 20 Gy treatment had an overall pain response to treatment (p=0·21; response difference of 4·00% upper limit of the 95% CI 9·2, less than the prespecified non-inferiority margin of 10%). In the per-protocol population, 116 (45%) of 258 patients and 134 (51%) of 263 patients, respectively, had an overall pain response to treatment (p=0·17; response difference 6·00% upper limit of the 95% CI 13·2, greater than the prespecified non-inferiority margin of 10%). The most frequently reported acute radiation-related toxicities at 14 days were lack of appetite (201 56% of 358 assessable patients who received 8 Gy vs 229 66% of 349 assessable patients who received 20 Gy; p=0·011) and diarrhoea (81 23% of 357 vs 108 31% of 349; p=0·018). Pathological fractures occurred in 30 (7%) of 425 patients assigned to 8 Gy and 20 (5%) of 425 assigned to 20 Gy (odds ratio OR 1·54, 95% CI 0·85–2·75; p=0·15), and spinal cord or cauda equina compressions were reported in seven (2%) of 425 versus two (<1%) of 425, respectively (OR 3·54, 95% CI 0·73–17·15; p=0·094). Interpretation In patients with painful bone metastases requiring repeat radiation therapy, treatment with 8 Gy in a single fraction seems to be non-inferior and less toxic than 20 Gy in multiple fractions; however, as findings were not robust in a per-protocol analysis, trade-offs between efficacy and toxicity might exist. Funding Canadian Cancer Society Research Institute, US National Cancer Institute, Cancer Council Australia, Royal Adelaide Hospital, Dutch Cancer Society, and Assistance Publique-Hôpitaux de Paris.
The crystal structure and magnetoresponsive properties of Fe-doped MnCoGe alloys have been investigated using x-ray diffraction (XRD) and magnetic measurements. By alloying the Fe-containing ...isostructure compounds into MnCoGe, a magnetostructural transition from paramagnetic austenite to ferromagnetic martensite with large magnetization difference can be realized in a temperature window between the Curie temperatures of the austenite and martensite, resulting in a magnetic-field-induced martensitic transformation and large magnetic-entropy changes. A structural and magnetic phase diagram of Fe-doped MnCoGe alloys is presented.
► Isostructural alloying can manipulate structural stability of Fe-doped MnCoGe alloys. ► A magnetostructural transition was realized in a temperature window between TCA and TCM. ► The remarkable magnetoresponsive properties in Fe-doped MnCoGe alloys were found. ► A structural and magnetic phase diagram of Fe-doped MnCoGe alloys was proposed.
Synthetic control over pore size and pore connectivity is the crowning achievement for porous metal-organic frameworks (MOFs). The same level of control has not been achieved for molecular crystals, ...which are not defined by strong, directional intermolecular coordination bonds. Hence, molecular crystallization is inherently less controllable than framework crystallization, and there are fewer examples of 'reticular synthesis', in which multiple building blocks can be assembled according to a common assembly motif. Here we apply a chiral recognition strategy to a new family of tubular covalent cages to create both 1D porous nanotubes and 3D diamondoid pillared porous networks. The diamondoid networks are analogous to MOFs prepared from tetrahedral metal nodes and linear ditopic organic linkers. The crystal structures can be rationalized by computational lattice-energy searches, which provide an in silico screening method to evaluate candidate molecular building blocks. These results are a blueprint for applying the 'node and strut' principles of reticular synthesis to molecular crystals.
Protons and helium nuclei are the most abundant components of the cosmic radiation. Precise measurements of their fluxes are needed to understand the acceleration and subsequent propagation of cosmic ...rays in our Galaxy. We report precision measurements of the proton and helium spectra in the rigidity range 1 gigavolt to 1.2 teravolts performed by the satellite-borne experiment PAMELA (payload for antimatter matter exploration and light-nuclei astrophysics). We find that the spectral shapes of these two species are different and cannot be described well by a single power law. These data challenge the current paradigm of cosmic-ray acceleration in supernova remnants followed by diffusive propagation in the Galaxy. More complex processes of acceleration and propagation of cosmic rays are required to explain the spectral structures observed in our data.