Iterative methods based on splittings for stochastic automata networks

Cataloged from PDF version of article.This paper presents iterative methods based on splittings (Jacobi, Gauss-Seidel, Successive Over Relaxation) and their block versions for Stochastic Automata Networks (SANs). These methods prove to be better than the power method that has been used to solve SANs until recently. With the help of three examples we show that the time it takes to solve a system modeled as a SAN is still substantial and it does not seem to be possible to solve systems with tens of millions of states on standard desktop workstations with the current state of technology. However, the SAN methodology enables one to solve much larger models than those could be solved by explicitly storing the global generator in the core of a target architecture especially if the generator is reasonably dense. (C) 1998 Elsevier Science B.V. All rights reserved

Putative Roles for Peptidylarginine Deiminases in COVID-19

Peptidylarginine deiminases (PADs) are a family of calcium-regulated enzymes that are phylogenetically conserved and cause post-translational deimination/citrullination, contributing to protein moonlighting in health and disease. PADs are implicated in a range of inflammatory and autoimmune conditions, in the regulation of extracellular vesicle (EV) release, and their roles in infection and immunomodulation are known to some extent, including in viral infections. In the current study we describe putative roles for PADs in COVID-19, based on in silico analysis of BioProject transcriptome data (PRJNA615032 BioProject), including lung biopsies from healthy volunteers and SARS-CoV-2-infected patients, as well as SARS-CoV-2-infected, and mock human bronchial epithelial NHBE and adenocarcinoma alveolar basal epithelial A549 cell lines. In addition, BioProject Data PRJNA631753, analysing patients tissue biopsy data (n = 5), was utilised. We report a high individual variation observed for all PADI isozymes in the patients’ tissue biopsies, including lung, in response to SARS-CoV-2 infection, while PADI2 and PADI4 mRNA showed most variability in lung tissue specifically. The other tissues assessed were heart, kidney, marrow, bowel, jejunum, skin and fat, which all varied with respect to mRNA levels for the different PADI isozymes. In vitro lung epithelial and adenocarcinoma alveolar cell models revealed that PADI1, PADI2 and PADI4 mRNA levels were elevated, but PADI3 and PADI6 mRNA levels were reduced in SARS-CoV-2-infected NHBE cells. In A549 cells, PADI2 mRNA was elevated, PADI3 and PADI6 mRNA was downregulated, and no effect was observed on the PADI4 or PADI6 mRNA levels in infected cells, compared with control mock cells. Our findings indicate a link between PADI expression changes, including modulation of PADI2 and PADI4, particularly in lung tissue, in response to SARS-CoV-2 infection. PADI isozyme 1–6 expression in other organ biopsies also reveals putative links to COVID-19 symptoms, including vascular, cardiac and cutaneous responses, kidney injury and stroke. KEGG and GO pathway analysis furthermore identified links between PADs and inflammatory pathways, in particular between PAD4 and viral infections, as well as identifying links for PADs with a range of comorbidities. The analysis presented here highlights roles for PADs in-host responses to SARS-CoV-2, and their potential as therapeutic targets in COVID-19

The Role of CDK4 in the Pathogenesis of Pancreatic Cancer.

Pancreatic cancer (PC) continues to have the lowest overall survival and the lack of effective early diagnosis. Cyclin-dependent kinase 4 (CDK4) plays a fundamental role in the orderly progression of the cell cycle, binding to cyclin D to promote the progression through the G1/2 transition. The inhibition of CDK4/6 has therefore gained substantial interest in the hope of new and effective therapeutics in multiple cancers, such as advanced metastatic breast cancer. While the use of these agents is encouraging, their potential is yet to be fully explored. In this study we used the GLOBOCAN database to understand the most recent epidemiology of PC, Human Protein Atlas and KEGG to highlight the role, prevalence, and significance on patient survival of CDK4 in PC. We found that CDK4 cannot be used as prognostic in PC and no significant differences were observed between CDK4 expression and the patient's clinical status, though larger studies, especially concerning CDK4 protein expressions, are required for a more thorough understanding. The use of CDK4/6 inhibitors in PC is still in clinical trials. However, due to only modest improvements observed in the use of single-agent therapies, efforts have focused on combinatorial approaches

Free-space optical communication employing subcarrier modulation and spatial diversity in atmospheric turbulence channel

An expression for the bit error rate of a multiple subcarrier intensity-modulated atmospheric optical communication system employing spatial diversity is derived. Spatial diversity is used to mitigate scintillation caused by atmospheric turbulence, which is assumed to obey lognormal distribution. Optimal but complex maximum ratio, equal gain combining (EGC) and relatively simple selection combining spatial diversity techniques in a clear atmosphere are considered. Each subcarrier is modulated using binary phase shift keying. Laser irradiance is subsequently modulated by a subcarrier signal, and a direct detection PIN receiver is employed (i.e. intensity modulation/direction detection). At a subcarrier level, coherent demodulation is used to extract the transmitted data/information. The performance of on–off-keying is also presented and compared with the subcarrier intensity modulation under the same atmospheric conditions

The Hasse norm principle in global function fields

Let $L$ be a finite extension of $\mathbb{F}_q(t)$. We calculate the proportion of polynomials of degree $d$ in $\mathbb{F}_q[t]$ that are everywhere locally norms from $L/\mathbb{F}_q(t)$ which fail to be global norms from $L/\mathbb{F}_q(t)$

microRNA expression in acute myeloid leukaemia: New targets for therapy?

Recent studies have shown that short non-coding RNAs, known as microRNAs (miRNAs) and their dysregulation, are implicated in the pathogenesis of acute myeloid leukaemia (AML). This is due to their role in the control of gene expression in a variety of molecular pathways. Therapies involving miRNA suppression and replacement have been developed. The normalisation of expression and the subsequent impact on AML cells have been investigated for some miRNAs, demonstrating their potential to act as therapeutic targets. Focussing on miRs with therapeutic potential, we have reviewed those that have a significant impact on the aberrant biological processes associated with AML, and crucially, impact leukaemic stem cell survival. We describe six miRNAs in preclinical trials (miR-21, miR-29b, miR-126, miR-181a, miR-223 and miR-196b) and two miRNAs that are in clinical trials (miR-29 and miR-155). However none have been used to treat AML patients and greater efforts are needed to develop miRNA therapies that could benefit AML patients in the future

MIMO free-space optical communication employing subcarrier intensity modulation in atmospheric turbulence channels

In this paper, we analyse the error performance of transmitter/receiver array free-space optical (FSO) communication system employing binary phase shift keying (BPSK) subcarrier intensity modulation (SIM) in clear but turbulent atmospheric channel. Subcarrier modulation is employed to eliminate the need for adaptive threshold detector. Direct detection is employed at the receiver and each subcarrier is subsequently demodulated coherently. The effect of irradiance fading is mitigated with an array of lasers and photodetectors. The received signals are linearly combined using the optimal maximum ratio combining (MRC), the equal gain combining (EGC) and the selection combining (SelC). The bit error rate (BER) equations are derived considering additive white Gaussian noise and log normal intensity fluctuations. This work is part of the EU COST actions and EU projects

Heavy Anionic Complex Creates a Unique Water Structure at a Soft Charged Interface

Ion hydration and interfacial water play crucial roles in numerous phenomena ranging from biological to industrial systems. Although biologically relevant (and mostly smaller) ions have been studied extensively in this context, very little experimental data exist about molecular scale behavior of heavy ions and their complexes at interfaces, especially under technologically significant conditions. It has recently been shown that PtCl62- complexes adsorb at positively charged interfaces in a two-step process that cannot fit into well-known empirical trends, such as Hofmeister series. Here, a combined vibrational sum frequency generation and molecular dynamics study reveals that a unique interfacial water structure is connected to this peculiar adsorption behavior. A novel sub-ensemble analysis of MD simulation results show that after adsorption, PtCl62- complexes partially retain their first and second hydration spheres, and it is possible to identify three different types of water molecules around them based on their orientational structures and hydrogen bonding strengths. These results have important implications for relating interfacial water structure and hydration enthalpy to the general understanding of specific ion effects. This in turn influences interpretation of heavy metal ion distribution across and reactivity within, liquid interfaces

CHARACTERIZATION OF CYLINDROCARPON-LIKE ANAMORPHS CAUSING ROOT AND BASAL ROT OF APRICOT AND IN VITRO ACTIVITIES OF SOME FUNGICIDES

Four apricot nurseries were surveyed in Hatay province in Turkey to evaluate the phytosanitary status of the nursery plant material. Endophytic and potential pathogenic fungi were identified in plants and 12 Cylindrocarpon-like anamorph isolates were detected in the root system and basal stems of analyzed rootstocks. Based on partial sequencing ITS, three different  Cylindrocarpon-like anamorph species were identified as Dactylonectria torresensis (6 isolates), Dactylonectria novozelandica (3 isolates) and Neonectria candida (3 isolates). Pathogenicity tests were conducted under greenhouse conditions which showed that all three Cylindrocarpon-like anamorph species, were identified as pathogens. ADt12 (D. torresensis) isolate, obtained from the survey area, have been tested in vitro for its sensitivity to several fungicides (thiophanate-methyl (70%), fluazinam (500g/L), fludioxonil (230g/L), and boscalid (26.7%)+pyraclostrobin (6.7%)). It was determined that ADt12 isolate was highly sensitive to fludioxonil and fluazinam, and sensitive to thiophanate-methyl and boscalid+pyraclostrobin as a result of probit analysis of EC50 values

The inventory of problems-29 is a cross‑culturally valid symptom validity test: Initial validation in a Turkish community sample

Because the actuarial evidence base for symptom validity tests (SVTs) is developed in a specific population, it is unclear whether their clinical utility is transferable to a population with different demographic characteristics. To address this, we report here the validation study of a recently developed free-standing SVT, the Inventory of Problems-29 (IOP-29), in a Turkish community sample. We employed a mixed design with a simulation paradigm: The Turkish IOP–29 was presented to the same participants (N = 125; 53.6% female; age range: 19–53) three times in an online format, with instructions to respond honestly (HON), randomly (RND), and attempt to feign a psychiatric disorder (SIM) based on different vignettes. In the SIM condition, participants were presented with one of three scripts instructing them to feign either schizophrenia (SIM-SCZ), depression (SIM-DEP), or posttraumatic stress disorder (SIM-PTSD). As predicted, the Turkish IOP–29 is effective in discriminating between credible and noncredible presentations and equally sensitive to feigning of different psychiatric disorders: The standard cutoff (FDS ≥ .50) is uniformly sensitive (90.2% to 92.9%) and yields a specificity of 88%. Random responding produces FDS scores more similar to those of noncredible presentations, and the random responding score (RRS) has incremental validity in distinguishing random responding from feigned and honest responding. Our findings reveal that the classification accuracy of the IOP–29 is stable across administration languages, feigned clinical constructs, and geographic regions. Validation of the Turkish IOP–29 will be a valuable addition to the limited availability of SVTs in Turkish. We discuss limitations and future directions