In this article, we consider functions having the properties of both the cumulative distribution function and the quantile function. Due to these characteristics, we term such functions quantile ...cumulative distribution functions. The comparison distribution function defined by Parzen (
1982
) for comparing the probability distributions of two populations is an example of such a function. We discuss some properties of the quantile cumulative distribution function and its usefulness in generating new continuous probability distributions on the unit interval. An overview of some of their applications is also presented to emphasize the importance of the quantile cumulative distribution function.
The interval reliability of a repairable system is the probability that the system is operating at a specified time and will continue to operate for a specified interval of time. This quantity is ...especially important for equipment, which must be working when an emergency situation arises. The present paper discusses the nonparametric estimation of the interval reliability when (i) the data on ‘
n
’ complete cycles of system operation are available, (ii) the data are subject to right censorship, and (iii) the process is observed up to a specified time ‘
T
’. A Simulation study is conducted to assess the performance of the estimators. The proposed method is also illustrated using a compressor failure data.
Over a hundred species of aquatic birds overwinter in Central America's wetlands, providing opportunities for the transmission of influenza A viruses (IAVs). To date, limited IAV surveillance in ...Central America hinders our understanding of the evolution and ecology of IAVs in migratory hosts within the Western Hemisphere. To address this gap, we sequenced the genomes of 68 virus isolates obtained from ducks overwintering along Guatemala's Pacific Coast during 2010 to 2013. High genetic diversity was observed, including 9 hemagglutinin (HA) subtypes, 7 neuraminidase (NA) subtypes, and multiple avian IAV lineages that have been detected at low levels (<1%) in North America. An unusually large number of viruses with the rare H14 subtype were identified (
= 14) over two consecutive seasons, the highest number of H14 viruses ever reported in a single location, providing evidence for a possible H14 source population located outside routinely sampled regions of North America. Viruses from Guatemala were positioned within minor clades divergent from the main North American lineage on phylogenies inferred for the H3, H4, N2, N8, PA, NP, and NS segments. A time-scaled phylogeny indicates that a Eurasian virus PA segment introduced into the Americas in the early 2000s disseminated to Guatemala during ~2007.1 to 2010.4 (95% highest posterior density HPD). Overall, the diversity detected in Guatemala in overwintering ducks highlights the potential role of Central America in the evolution of diverse IAV lineages in the Americas, including divergent variants rarely detected in the United States, and the importance of increasing IAV surveillance throughout Central America.
Recent outbreaks of highly pathogenic H7N3, H5Nx, and H7N8 avian influenza viruses in North America were introduced by migratory birds, underscoring the importance of understanding how wild birds contribute to the dissemination and evolution of IAVs in nature. At least four of the main IAV duck host species in North America migrate through or overwinter within a narrow strip of Central America, providing opportunities for diverse IAV lineages to mix and exchange gene segments. By obtaining whole-genome sequences of 68 IAV isolates collected from migratory waterfowl in Guatemala (2010 to 2013), the largest data set available from Central America to date, we detected extensive viral diversity, including gene variants rarely found in North America and gene segments of Eurasian origin. Our findings highlight the need for increased IAV surveillance across the geographical span of bird migration flyways, including Neotropical regions that have been vastly undersampled to date.
Background
Dual antiplatelet therapy is the current standard of care after acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). We intended to study the pattern of use of ...ticagrelor in patients with acute coronary syndrome undergoing PCI and the effect of switching over to other P2Y12 receptor inhibition on clinical outcomes.
Results
All patients aged > 18 years who had been admitted with acute coronary syndrome and had been provided ticagrelor as the second antiplatelet agent were included as study participants. The primary outcome of the study was the composite outcome of death, recurrent myocardial infarctions, re-intervention, and major bleeding.
We studied 321 patients (54 female patients, 16.82%). The mean age of the patients was 56.65 ± 11.01 years. Ticagrelor was stopped in 76.7% on follow-up. It was stopped in 6.3%, 13.5%, 13.1%, 21.9%, and 45.1% of patients during the first month but after discharge, between first and third months, between 3 and 6 months, between 6 and 12 months, and after 12 months, respectively. In the majority of patients, ticagrelor was replaced by clopidogrel (97.9%). It was stopped according to the physician’s discretion in 79.3% of patients, whereas it was the cost of the drug that made the patient to get swapped to another agent in 18.6%. No difference in the primary composite outcome was observed between the groups where ticagrelor was continued post 12 months and ticagrelor was continued and ticagrelor was switched-over to another agent. Similarly, no difference in death, recurrent myocardial infarctions, re-interventions, or major bleeding manifestations was observed between the two groups.
Conclusion
In patients with acute coronary syndrome who undergo PCI, we observed that early discontinuation of ticagrelor and switching over to other P2Y12 inhibitors after discharge did not affect clinical outcomes.
We consider the system availability behavior of a one-unit repairable system when the failure and the repair times are generated by a stationary dependent sequence of random variables. We obtain the ...general expression for the point availability, and discuss the nature of the availability measure for two time series models: a first-order exponential moving average process and a first-order exponential autoregressive process.
In reliability modelling and analysis of systems, quantile functions play a significant role when the distribution function under consideration does not possess an analytically tractable form, though ...the corresponding quantile function has an explicit form. In the present paper, we propose a quantile-based approach for stress-strength reliability of a system. We also introduce the quantile versions of stress-strength reliability for residual lifetime random variables. The effect of monotone transformations and some characterizations of the proposed measures are discussed. The reliability of multi-component stress-strength systems based on quantiles is also considered.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Surface sediments were collected from the shore and lagoons of Kavaratti, Kadmat and Agatti islands of Lakshadweep Archipelago and analysed for trace element concentration. The sediment contamination ...was assessed on the basis of geochemical, biological hazard and ecological risk indices. Except Cd and Pb, all the other trace elements selected for the study were below the contamination level. Compared to Kadmat, Kavaratti and Agatti were more polluted and the pollution was pronounced in lagoons than shore. Population pressure, untreated sewage, diesel based power generation, shipping and tourism activities contribute to sediment contamination. Statistical analysis revealed the association of trace elements with sedimentary characteristics due to anthropogenic sources.
Abstract
The broadly neutralizing hemagglutinin (BN-HA) stem antibodies represent an universal vaccine prospect. However, our understanding of how these antibodies interact with the influenza virus ...is limited by excluding other immune elements, such as complement, in our experimental systems.
Here, we show that the Fc binding protein of the complement system, C1q, grants BN-HA stem Abs a novel attachment inhibition (AI) and boosts virus neutralization (VN) activity. C1q promotes AI even if added to preformed BN-HA Ab-virion-RBC complexes, pointing at the steric nature of the phenomenon. Most probably by the same mechanism of steric hindrance, C1q also contributes to fusion inhibition. By employing a panel of engineered avidity-reverted anti-BNHA Abs we show that the C1q-mediated VN enhancement is independent of Ab avidity. We also show that C1q’s presence expands the escape viral repertoire beyond the HA stem domain. Among selected viral variants, near-RBS mutations (E156K-Sb, R224I-Ca, S145N-Ca) modulate HA avidity while causing antigenic drift. Expanding our discoveries to SARS-CoV-2, we identified non-RBD anti-SARS-CoV-2 spike Abs which exhibit C1q-VN enhancement. With an increased SARS-CoV-2 spike per viral particle amount, C1q-VN increased concomitantly. Altogether, our results emphasize the general role of C1q in Ab-mediated antiviral activity and viral evolution.
NIH/NIAID intramural funding
Chimeric antigen receptor (CAR)-T cell therapies have adverse side effects such as cytokine release syndrome (CRS) due to on-target off-tumor toxicity. Responses for clinically available CAR-T ...therapies mainly use immunosuppressants for mitigation which lowers their overall functionality. An alternate approach will be to bioengineer cellular regulation that confers high spatiotemporal control over CAR-T cells in vivo to reduce its side effects. The lab has previously developed a protein caging system as a switch for controlling the signalling of CAR. The caging domain binds to CAR and keeps it auto inhibited. The uncaging domain which is under an external control can bind to the caging domain and free the CAR to initiate intracellular signaling. We have tested two strategies for externally controlling the uncaging of CAR by creating a dihydrofolate reductase (DHFR) system and a heat shock promoter (HSP) system. We have developed an in-vitro dimerization dependent fluorescent (ddFP) biosensor that can detect dynamics of the above protein caging system by verifying the expression and binding of the caging and uncaging domains. The results can be used to further optimize the protein caging system and create focused ultrasound (FUS) controllable CAR-T cells.
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