A facile synthesis of a metal oxide (ZrO2) coating on the surface of high voltage type Li2CoPO4F cathode material using the conventional solution method is reported in this study. The Li2CoPO4F is ...prepared by a two step solid state method, followed by the application of wet coating containing various amounts of ZrO2. Among the samples, the 5 wt% ZrO2 coated Li2CoPO4F material shows the best performance with an initial discharge capacity of up to 144 mA h g−1 within the voltage range of 2–5.2 V vs Li at 10 mA g−1. Moreover, this ZrO2 coated cell demonstrates an enhanced capacity retention which is two times higher than that of the uncoated sample. The reversible extraction–insertion of one lithium unit from Li2CoPO4F is successfully carried out in a controlled environment, where the electrolyte decomposition is reduced using a highly durable ZrO2 coating. The nanosized coating over the Li2CoPO4F surface helps to attain a higher discharge capacity even at high current rates. As a consequence, the cell delivers a capacity of 104 mA h g−1 at a high current rate of 100 mA g−1.
► A highly durable ZrO2 coating was applied to 5 V class cathode material Li2CoPO4F. ► The 5 wt% ZrO2 coated sample exhibited highest discharge capacity of 144 mA h g−1. ► 5 wt% samples exhibited higher capacities at 10–500 mA g−1 current rates. ► The durability of Li2CoPO4F increased to 70% after coating even at 100 mA g−1 rate.
Last year, HIV surpassed other pathogens to become the world's leading infectious cause of adult death. More than 90% of deaths occur in poor countries, yet new antiretroviral therapies have only led ...to a drop in AIDS deaths in industrialised countries. The main objections to the use of these agents in less-developed countries have been their high cost and the lack of health infrastructure necessary to use them. We have shown that it is possible to carry out an HIV treatment programme in a poor community in rural Haiti, the poorest country in the western hemisphere. Relying on an already existing tuberculosis-control infrastructure, we have been able to provide directly observed therapy with highly-active antiretroviral therapy (HAART) to about 60 patients with advanced HIV disease. Inclusion criteria and clinical follow-up were based on basic laboratory data available in most rural clinics. Serious side-effects have been rare and readily managed by community-health workers and clinic staff. We discuss objections to the widespread use of HAART, and suggest that directly-observed therapy of chronic infectious disease with multidrug regimens can be highly effective in settings of great privation as long as there is sustained commitment to uninterrupted care that is free to the patient.
Adherence to medical treatment following a kidney transplant is particularly challenging during adolescence and young adulthood.
There is increasing evidence of the benefits of the use of computer ...and mobile technology (labelled as eHealth hereafter) including serious gaming and gamification in many clinical areas. We aimed to conduct a systematic review of such interventions designed to improve self-management skills, treatment adherence and clinical outcomes in young kidney transplant recipients aged 16 to 30 years.
The Cochrane Library, MEDLINE, EMBASE, PsychINFO, SCOPUS and CINAHL databases were searched for studies published between 01 January 1990 and 20 October 2020. Articles were short-listed by two independent reviewers based on pre-defined inclusion/exclusion criteria. Reference lists were screened and authors of published conference abstracts contacted. Two reviewers independently appraised selected articles, systematically extracted data and assessed the quality of individual studies (CASP and SORT). Thematic analysis was used for evidence synthesis; quantitative meta-analysis was not possible.
A total of 1098 unique records were identified. Short-listing identified four eligible studies, all randomized controlled trials (n = 266 participants). Trials mainly focused on mHealth applications or electronic pill dispensers (mostly for patients >18 years old). Most studies reported on clinical outcome measures. All showed improved adherence but there were no differences in the number of rejections. Study quality was low for all four studies.
The findings of this review suggest that eHealth interventions can improve treatment adherence and clinical outcomes for young kidney transplant patients. More robust and high-quality studies are now needed to validate these findings. Future studies should also extend beyond short-term outcomes, and consider cost of implementation. The review was registered with PROSPERO (CRD42017062469).
•Treatment adherence is challenging in young kidney transplant patients.•eHealth can support adherence during this major life transition.•More high-quality RCTs should be designed to validate digital self-management approaches.
High–molecular weight kininogen (HK) circulates in plasma as a complex with zymogen prekallikrein (PK). HK is both a substrate and a cofactor for activated plasma kallikrein, and the principal ...exosite interactions occur between PK N-terminal apple domains and the C-terminal D6 domain of HK.
To determine the structure of the complex formed between PK apple domains and an HKD6 fragment and compare this with the coagulation factor XI (FXI)-HK complex.
We produced recombinant FXI and PK heavy chains (HCs) spanning all 4 apple domains. We cocrystallized PKHC (and subsequently FXIHC) with a 31-amino acid synthetic peptide spanning HK residues Ser565-Lys595 and determined the crystal structure. We also analyzed the full-length FXI-HK complex in solution using hydrogen deuterium exchange mass spectrometry.
The 2.3Å PKHC-HK peptide crystal structure revealed that the HKD6 sequence WIPDIQ (Trp569-Gln574) binds to the apple 1 domain and HK FNPISDFPDT (Phe582-Thr591) binds to the apple 2 domain with a flexible intervening sequence resulting in a bent double conformation. A second 3.2Å FXIHC-HK peptide crystal structure revealed a similar interaction with the apple 2 domain but an alternate, straightened conformation of the HK peptide where residues LSFN (Leu579-Asn583) interacts with a unique pocket formed between the apple 2 and 3 domains. HDX-MS of full length FXI-HK complex in solution confirmed interactions with both apple 2 and apple 3.
The alternate conformations and exosite binding of the HKD6 peptide likely reflects the diverging relationship of HK to the functions of PK and FXI.
•Factor XI (FXI) and prekallikrein (PK) form key exosite interactions with the D6 domain of high–molecular weight kininogen (HK).•Structures of FXI and PK heavy chain (HC) complexed to an HKD6 peptide reveal exosite interactions.•Both FXIHC and PKHC interact with the HK582-591 sequence FNPISDFPDT via the apple 2 domain.•PKHC has a second exosite in the apple 1 domain, whereas FXIHC utilizes an apple 2/3 domain pocket.
Deconstructing pancreas developmental biology Benitez, Cecil M; Goodyer, William R; Kim, Seung K
Cold Spring Harbor perspectives in biology,
06/2012, Volume:
4, Issue:
6
Journal Article
Peer reviewed
Open access
The relentless nature and increasing prevalence of human pancreatic diseases, in particular, diabetes mellitus and adenocarcinoma, has motivated further understanding of pancreas organogenesis. The ...pancreas is a multifunctional organ whose epithelial cells govern a diversity of physiologically vital endocrine and exocrine functions. The mechanisms governing the birth, differentiation, morphogenesis, growth, maturation, and maintenance of the endocrine and exocrine components in the pancreas have been discovered recently with increasing tempo. This includes recent studies unveiling mechanisms permitting unexpected flexibility in the developmental potential of immature and mature pancreatic cell subsets, including the ability to interconvert fates. In this article, we describe how classical cell biology, genetic analysis, lineage tracing, and embryological investigations are being complemented by powerful modern methods including epigenetic analysis, time-lapse imaging, and flow cytometry-based cell purification to dissect fundamental processes of pancreas development.
Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not ...known.
We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15.
A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval CI, 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003).
Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).
Accelerated life test sampling plans (ALTSPs) provide information quickly on the lifetime distribution of products by testing them at higher-than-usual stress level to induce early failures and ...reduce the testing efforts. In the traditional design of ALTSPs for Weibull distribution, it is assumed that the shape parameter remains constant over all stress levels. This paper extends the existing design of ALTSPs to Weibull distribution with a nonconstant shape parameter and presents two types of ALTSPs; time-censored and failure-censored. Optimum ALTSPs which satisfy the producer’s and consumer’s risk requirements and minimize the asymptotic variance of the test statistic for deciding the lot acceptability are obtained. The properties of the proposed ALTSPs and the effects of errors in pre-estimate of the design parameters are also investigated.
Background and Objective
Interleukin‐6 (IL‐6) is a powerful stimulator of osteoclast differentiation and bone resorption. Production of IL‐6 is modulated by polymorphisms, and higher levels of this ...cytokine are found locally in patients with chronic periodontitis. In this study we performed a modern approach – Complete physical mapping of the IL6 gene – to identify the polymorphisms associated with chronic periodontitis in a southern Brazilian population sample.
Material and Methods
One‐hundred and nine individuals of both genders (mean age: 41.5 ± 8.5 years) were divided into a study group (56 participants with periodontitis) and a control group (53 individuals without periodontitis). After collection and purification of DNA, nine tag single nucleotide polymorphisms (SNPs; rs1524107, rs2069835, rs2069837, rs2069838, rs2069840, rs2069842, rs2069843, rs2069845 and rs2069849) covering the entire gene were selected according to the information available on the International HapMap Project website and evaluated using real‐time PCR.
Results
Differences in the distribution of the following parameters were statistically significant between study and control groups: number of teeth (p = 0.030); probing depth (p < 0.001); clinical attachment level (p < 0.001); gingival index (p < 0.001); plaque index (p = 0.003); calculus index (p < 0.001); and dental mobility (p < 0.001). It was found that marker rs2069837 (located in intron 2 of IL6) under G dominant was associated with protection against chronic periodontitis in a Brazilian population in the presence of clinical variables, such as visible plaque, dentist visit frequency and dental floss use, and was suggested for the first time as a marker of susceptibility to chronic periodontitis.
Conclusion
Complete physical mapping of IL6 (using tag SNPs) was carried out for the first time, unveiling allele G of polymorphism rs2069837 (located in the second intron of IL6) as a suggestive marker of protection against chronic periodontitis in a Brazilian population.
We present the analysis of the binary-microlensing event OGLE-2014-BLG-0289. The event light curve exhibits five very unusual peaks, four of which were produced by caustic crossings and the other by ...a cusp approach. It is found that the quintuple-peak features of the light curve provide tight constraints on the source trajectory, enabling us to precisely and accurately measure the microlensing parallax π E . Furthermore, the three resolved caustics allow us to measure the angular Einstein radius θ E . From the combination of π E and θ E , the physical lens parameters are uniquely determined. It is found that the lens is a binary composed of two M dwarfs with masses M 1 = 0.52 0.04 M and M 2 = 0.42 0.03 M separated in projection by a = 6.4 0.5 au . The lens is located in the disk with a distance of D L = 3.3 0.3 kpc . The reason for the absence of a lensing signal in the Spitzer data is that the time of observation corresponds to the flat region of the light curve.
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