Tm-Doped Fiber Lasers: Fundamentals and Power Scaling Moulton, P.F.; Rines, G.A.; Slobodtchikov, E.V. ...
IEEE journal of selected topics in quantum electronics,
2009-Jan., 2009-01-00, 20090101, Letnik:
15, Številka:
1
Journal Article
Recenzirano
We describe fundamental measurements of the properties of thulium (Tm)-doped silica and power scaling studies of fiber lasers based on the material. Data on the high-lying Tm:silica energy levels, ...the first taken to our knowledge, indicate that pumping at 790 nm is unlikely to lead to fiber darkening via multiphoton excitation. Measurement of the cross-relaxation dynamics produces an estimate that, at the doping levels used, as much as 80% of the decay of the Tm level pumped is due to cross relaxation. Using a fiber having a 25-mum-diameter, 0.08 numerical aperture (NA) core, we observed fiber laser efficiencies as high as 64.5% and output powers of 300 W (around 2040 nm) for 500 W of launched pump power, with a nearly diffraction-limited beam. At these efficiencies, the cross-relaxation process was producing 1.8 laser photons per pump photon. We generated 885 W from a multimode laser using a 35-mum, 0.2-NA core fiber and set a new record for Tm-doped fiber laser continuous-wave power.
Infection with the opportunistic enteric pathogen Clostridium difficile is an increasingly common clinical complication that follows antibiotic treatment-induced gut microbiota perturbation. Innate ...lymphoid cells (ILCs) are early responders to enteric pathogens; however, their role during C. difficile infection is undefined. To identify immune pathways that mediate recovery from C. difficile infection, we challenged C57BL/6, Rag1−/− (which lack T and B cells), and Rag2−/−Il2rg−/− (Ragγc−/−) mice (which additionally lack ILCs) with C. difficile. In contrast to Rag1−/− mice, ILC-deficient Ragγc−/− mice rapidly succumbed to infection. Rag1−/− but not Ragγc−/− mice upregulate expression of ILC1- or ILC3-associated proteins following C. difficile infection. Protection against infection was restored by transferring ILCs into Ragγc−/− mice. While ILC3s made a minor contribution to resistance, loss of IFN-γ or T-bet-expressing ILC1s in Rag1−/− mice increased susceptibility to C. difficile. These data demonstrate a critical role for ILC1s in defense against C. difficile.
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•Recovery from acute C. difficile infection is independent of adaptive immunity•Lack of innate lymphoid cells leads to mortality following C. difficile infection•Transfer of ILCs into susceptible hosts restores protection against C. difficile•Type-1 ILCs mediate IFN-γ-dependent protection against C. difficile
C. difficile pathogenicity is determined by strain virulence, interactions with commensal bacteria, and the host’s inflammatory response to intestinal epithelial damage. Abt et al. demonstrate that type-1 and type-3 innate lymphoid cells function in concert and coordinate early host responses to provide initial resistance against C. difficile infection.
Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) ...protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis anterior (vulnerable) muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo.
Hip fractures in the older person lead to an increased risk of mortality, poorer quality of life and increased morbidity. Benzodiazepine (BNZ) use is associated with increased hip fracture rate, ...consequently Z-drugs are fast becoming the physician's hypnotic prescription of choice yet data on their use is limited. We compared the risk of hip fracture associated with Z-drugs and BNZ medications, respectively, and examined if this risk varied with longer-term use.
We carried out a systematic review of the literature and meta-analysis. MEDLINE and SCOPUS were searched to identify studies involving BNZ or Z-drugs and the risk of hip fracture up to May 2015. Each included study was quality-assessed. A pooled relative risk of hip fracture was calculated using the generic inverse variance method, with a random effects model, with the length of hypnotic usage as a subgroup. Both BNZ, and Z-drug use respectively, were significantly associated with an increased risk of hip fracture (RR = 1.52, 95% CI 1.37-1.68; and RR = 1.90, 95% CI 1.68-2.13). Short-term use of BNZ and Z-drugs respectively, was also associated with the greatest risk of hip fracture (RR = 2.40, 95% CI 1.88-3.05 and RR = 2.39, 95% CI 1.74-3.29).
There is strong evidence that both BNZ and Z-drugs are associated with an increased risk of hip fracture in the older person, and there is little difference between their respective risks. Patients newly prescribed these medicines are at the greatest risk of hip fracture. Clinicians and policy makers need to consider the increased risk of fallings and hip fracture particularly amongst new users of these medications.
Trust the Text Sinclair, John
2004, 20040731, 2004-07-31
eBook
John Sinclair is one of the major figures in applied linguistics and his work is essential study for students. This accessible book collects in one volume Sinclair's key papers on written discourse ...structure, lexis patterns, phraseology, corpus analysis, lexicography and linguistic theory from the 1990s. All the papers have been edited and updated for this book. The clear and accessible introduction helps students to navigate his key themes and arguments, making the volume an ideal companion for those coming to Sinclair's more recent writings for the first time.
' ... the book contains valuable insights from which both discourse analysts and corpus linguistics will benefit.' - BaaL News
Abstract This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between ...mouse and human in placental cell types and genes controlling placental development. There are, however, substantive differences, including a different mode of implantation, a prominent yolk sac placenta, and fewer placental hormones in the mouse. Crucially, trophoblast invasion is very limited in the mouse and transformation of uterine arteries depends on maternal factors. The mouse also has a short gestation and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial, there is no trophoblast invasion of uterine vessels, and the immunology of pregnancy may be quite different. We conclude that continued research on non-human primates is needed to clarify embryonic–endometrial interactions. The interstitial implantation of human is unusual, but the initial interaction between trophoblast and endometrium is similar in macaques and baboons, as is the subsequent lacunar stage. The absence of interstitial trophoblast cells in the monkey is an important difference from human placentation. However, there is a strong resemblance in the way spiral arteries are invaded and transformed in the macaque, baboon and human. Non-human primates are therefore important models for understanding the dysfunction that has been linked to pre-eclampsia and fetal growth restriction. Models that are likely to be established in the wake of comparative genomics include the marmoset, tree shrew, hedgehog tenrec and nine-banded armadillo.
It remains unclear how and why autoimmunity occurs. Here we show evidence for a previously unrecognized and possibly general mechanism of autoimmunity. This new finding was discovered serendipitously ...using material from patients with inflammatory vascular disease caused by antineutrophil cytoplasmic autoantibodies (ANCA) with specificity for proteinase-3 (PR-3). Such patients harbor not only antibodies to the autoantigen (PR-3), but also antibodies to a peptide translated from the antisense DNA strand of PR-3 (complementary PR-3, cPR-3) or to a mimic of this peptide. Immunization of mice with the middle region of cPR-3 resulted in production of antibodies not only to cPR-3, but also to the immunogen's sense peptide counterpart, PR-3. Both human and mouse antibodies to PR-3 and cPR-3 bound to each other, indicating idiotypic relationships. These findings indicate that autoimmunity can be initiated through an immune response against a peptide that is antisense or complementary to the autoantigen, which then induces anti-idiotypic antibodies (autoantibodies) that cross-react with the autoantigen.
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