78 research outputs found
Divining Siraya: Sources of language and authority in documentation and revitalisation
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Nonlinear temperature response of lake ice breakup
A uniquely comprehensive set of four decades of ice breakup data from 196 Swedish lakes covering 13degrees of latitude (55.7degrees N to 68.4degrees N) shows the relationship between the timing of lake ice breakup and air temperature to be an arc cosine function. The nonlinearity inherent in this relationship results in marked differences in the response of the timing of lake ice breakup to changes in air temperature between colder and warmer geographical regions, and between colder and warmer time periods. The spatial and temporal patterns are mutually consistent, suggesting that climate change impacts on the timing of lake ice breakup will vary along a temperature gradient. This has potentially important ramifications for the employment of lake ice phenologies as climate indicators and for the future behavior of lacustrine ecosystem
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Thrombocytopenia Is Associated with Acute Respiratory Distress Syndrome Mortality: An International Study
Background: Early detection of the Acute Respiratory Distress Syndrome (ARDS) has the potential to improvethe prognosis of critically ill patients admitted to the intensive care unit (ICU). However, no reliable biomarkers are currently available for accurate early detection of ARDS in patients with predisposing conditions. Objectives: This study examined risk factors and biomarkers for ARDS development and mortality in two prospective cohort studies. Methods: We examined clinical risk factors for ARDS in a cohort of 178 patients in Beijing, China who were admitted to the ICU and were at high risk for ARDS. Identified biomarkers were then replicated in a second cohort of1,878 patients in Boston, USA. Results: Of 178 patients recruited from participating hospitals in Beijing, 75 developed ARDS. After multivariate adjustment, sepsis (odds ratio [OR]:5.58, 95% CI: 1.70–18.3), pulmonary injury (OR: 3.22; 95% CI: 1.60–6.47), and thrombocytopenia, defined as platelet count <80×103/µL, (OR: 2.67; 95% CI: 1.27–5.62)were significantly associated with increased risk of developing ARDS. Thrombocytopenia was also associated with increased mortality in patients who developed ARDS (adjusted hazard ratio [AHR]: 1.38, 95% CI: 1.07–1.57) but not in those who did not develop ARDS(AHR: 1.25, 95% CI: 0.96–1.62). The presence of both thrombocytopenia and ARDS substantially increased 60-daymortality. Sensitivity analyses showed that a platelet count of <100×103/µLin combination with ARDS provide the highest prognostic value for mortality. These associations were replicated in the cohort of US patients. Conclusions: This study of ICU patients in both China and US showed that thrombocytopenia is associated with an increased risk of ARDS and platelet count in combination with ARDS had a high predictive value for patient mortality
The short coiled-coil domain-containing protein UNC-69 cooperates with UNC-76 to regulate axonal outgrowth and normal presynaptic organization in Caenorhabditis elegans
BACKGROUND: The nematode Caenorhabditis elegans has been used extensively to identify the genetic requirements for proper nervous system development and function. Key to this process is the direction of vesicles to the growing axons and dendrites, which is required for growth-cone extension and synapse formation in the developing neurons. The contribution and mechanism of membrane traffic in neuronal development are not fully understood, however. RESULTS: We show that the C. elegans gene unc-69 is required for axon outgrowth, guidance, fasciculation and normal presynaptic organization. We identify UNC-69 as an evolutionarily conserved 108-amino-acid protein with a short coiled-coil domain. UNC-69 interacts physically with UNC-76, mutations in which produce similar defects to loss of unc-69 function. In addition, a weak reduction-of-function allele, unc-69(ju69), preferentially causes mislocalization of the synaptic vesicle marker synaptobrevin. UNC-69 and UNC-76 colocalize as puncta in neuronal processes and cooperate to regulate axon extension and synapse formation. The chicken UNC-69 homolog is highly expressed in the developing central nervous system, and its inactivation by RNA interference leads to axon guidance defects. CONCLUSION: We have identified a novel protein complex, composed of UNC-69 and UNC-76, which promotes axonal growth and normal presynaptic organization in C. elegans. As both proteins are conserved through evolution, we suggest that the mammalian homologs of UNC-69 and UNC-76 (SCOCO and FEZ, respectively) may function similarly
Ultrasmall Glutathione-Protected Gold Nanoclusters as Next Generation Radiotherapy Sensitizers with High Tumor Uptake and High Renal Clearance
Radiotherapy is often the most straightforward first line cancer treatment
for solid tumors. While it is highly effective against tumors, there is also
collateral damage to healthy proximal tissues especially with high doses. The
use of radiosensitizers is an effective way to boost the killing efficacy of
radiotherapy against the tumor while drastically limiting the received dose and
reducing the possible damage to normal tissues. Here, we report the design and
application of a good radiosensitizer by using ultrasmall gold nanoclusters
with a naturally occurring peptide (e.g., glutathione or GSH) as the protecting
shell. The GSH coated gold nanoclusters can escape the RES absorption, leading
to a good tumor uptake (8.1% ID/g at 24 h post injection). As a result, the
as-designed Au nanoclusters led to a strong enhancement for radiotherapy, as
well as a negligible damage to normal tissues. After the treatment, the
ultrasmall gold nanoclusters can be efficiently cleared by the kidney, thereby
avoiding potential long term side effects caused by the accumulation of gold
atoms in the body. Our data suggest that the ultrasmall peptide protected Au
nanoclusters are a promising radiosensitizer for cancer radiotherapy.Comment: 15 Pages, 6 Figures, Scientific Reports 5, 201
Experimental observation of gain in a resonantly pumped Pr3+-doped chalcogenide glass mid-infrared fibre amplifier notwithstanding the signal excited-state absorption
We demonstrate a maximum gain of 4.6 dB at a signal wavelength of 5.28 μm in a 4.1 μm resonantly pumped Pr3+- doped selenide-based chalcogenide glass fibre amplifier of length 109 mm, as well as a new signal excited-stated absorption (ESA) at signal wavelengths around 5.5 μm. This work is to the best of our knowledge is the first experimental demonstration of gain at mid-infrared (MIR) wavelengths in a Pr3+-doped chalcogenide fibre amplifier. The signal ESA of Pr3+ ions is attributed to the transition 3H6→(3F4, 3F3) after the pump ESA (3H5→3H6) at a pump wavelength of 4.1 μm, which absorbs the MIR signal at wavelengths of 5.37, 5.51 and 5.57 μm, and so spoils the amplifier’s performance at these wavelengths. Thus, this signal ESA should be suppressed in a resonantly pumped Pr3+-doped chalcogenide fibre amplifier
Genotype-predicted tetrahydrobiopterin (BH4)-responsiveness and molecular genetics in Croatian patients with phenylalanine hydroxylase (PAH) deficiency
a b s t r a c t Specific mutations in the gene encoding phenylalanine hydroxylase (PAH), located on chromosome 12q22-24.1, are linked to tetrahydrobiopterin (BH 4 ; sapropterin)-responsive phenylketonuria (PKU). Diagnosis is usually done through the newborn screening for PKU, followed by a BH 4 loading test. So far, more than 60 mutant alleles, presenting with a substantial residual PAH activity (average $47%), were identified in more than 500 patients worldwide. We investigated the predictive value of BH 4 -responsive PAH mutations in Croatian population. From a group of 127 PKU patients, 62 were selected (based on the genotype) as potentially BH 4 -responsive and 39 loaded with BH 4 (20 mg/kg). The overall frequency of BH 4 -responsiveness (>30% blood phenylalanine reduction within 24 h) was 36% (14 out of 39 patients with 23 different genotypes), significantly less than expected. The best responders were patients with mild hyperphenylalaninemia (4/4; 100%), followed by mild PKU (8/9; 89%), and classical PKU (2/26; 8%). The most common BH 4 -responsive genotypes were p.E390G/p.R408W and p.P281L/ p.E390G. These genotypes correspond for approximately >30% residual PAH activity. The p.E390G mutation was 100% associated with BH 4 -responsiveness, regardless of the second allele (p.R408W, p.P281L, p.F55Lfs, p.L249P). With regard to the predicted relative PAH activity of recombinantly expressed mutant alleles, there was a significant (p < 0.002) difference between BH 4 -responders and non-responders. In a general Croatian PKU population, disease-causing mutations were identified on 226 alleles (99%). There were 35 different mutations: 21 missense, 8 splice site, 3 nonsense, 2 single nucleotide deletions
Transcriptome analysis reveals dynamic changes in coxsackievirus A16 infected HEK 293T cells
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