Network motifs, such as the feed-forward loop (FFL), introduce a range of complex behaviors to transcriptional regulatory networks, yet such properties are typically determined from their isolated ...study. We characterize the effects of crosstalk on FFL dynamics by modeling the cross regulation between two different FFLs and evaluate the extent to which these patterns occur in vivo. Analytical modeling suggests that crosstalk should overwhelmingly affect individual protein-expression dynamics. Counter to this expectation we find that entire FFLs are more likely than expected to resist the effects of crosstalk (≈20% for one crosstalk interaction) and remain dynamically modular. The likelihood that cross-linked FFLs are dynamically correlated increases monotonically with additional crosstalk, but is independent of the specific regulation type or connectivity of the interactions. Just one additional regulatory interaction is sufficient to drive the FFL dynamics to a statistically different state. Despite the potential for modularity between sparsely connected network motifs, Escherichia coli (E. coli) appears to favor crosstalk wherein at least one of the cross-linked FFLs remains modular. A gene ontology analysis reveals that stress response processes are significantly overrepresented in the cross-linked motifs found within E. coli. Although the daunting complexity of biological networks affects the dynamical properties of individual network motifs, some resist and remain modular, seemingly insulated from extrinsic perturbations—an intriguing possibility for nature to consistently and reliably provide certain network functionalities wherever the need arise.
De-identification of electronic health records (EHR) is a vital step toward advancing health informatics research and maximizing the use of available data. It is a two-step process where step one is ...the identification of protected health information (PHI), and step two is replacing such PHI with surrogates. Despite the recent advances in automatic de-identification of EHR, significant obstacles remain if the abundant health data available are to be used to the full potential. Accuracy in de-identification could be considered a necessary, but not sufficient condition for the use of EHR without individual patient consent. We present here a comprehensive review of the progress to date, both the impressive successes in achieving high accuracy and the significant risks and challenges that remain. To best of our knowledge, this is the first paper to present a complete picture of end-to-end automatic de-identification. We review 18 recently published automatic de-identification systems -designed to de-identify EHR in the form of free text- to show the advancements made in improving the overall accuracy of the system, and in identifying individual PHI. We argue that despite the improvements in accuracy there remain challenges in surrogate generation and replacements of identified PHIs, and the risks posed to patient protection and privacy.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
The SARS-CoV-2 virus is responsible for the novel coronavirus disease 2019 (COVID-19), which has spread to populations throughout the continental United States. Most state and local ...governments have adopted some level of “social distancing” policy, but infections have continued to spread despite these efforts. Absent a vaccine, authorities have few other tools by which to mitigate further spread of the virus. This begs the question of how effective social policy really is at reducing new infections that, left alone, could potentially overwhelm the existing hospitalization capacity of many states. We developed a mathematical model that captures correlations between some state-level “social distancing” policies and infection kinetics for all U.S. states, and use it to illustrate the link between social policy decisions, disease dynamics, and an effective reproduction number that changes over time, for case studies of Massachusetts, New Jersey, and Washington states. In general, our findings indicate that the potential for second waves of infection, which result after reopening states without an increase to immunity, can be mitigated by a return of social distancing policies as soon as possible after the waves are detected.
The effects of the atmospheric oxygen concentration on the physical and chemical ignition behavior of biodiesel and diesel fuel blends were investigated using an optically accessible constant-volume ...combustion chamber (600 °C and 20 bar) equipped with a light-duty diesel injector. High-speed imaging was used to measure the transient cone angle and penetration length of the liquid spray jet as it developed within the chamber. Structural fluctuations of the developing spray jets were suggested to be a function of injector pin movement, with their frequency and amplitude being functions of the fuel viscosity and density. Physical and chemical ignition delay was analyzed through detection of excited formaldehyde and hydroxide chemiluminescence using a system of optical filters and photomultiplier tubes. Although biodiesel produced slightly longer physical ignition delays as a result of an extended atomization and evaporation process, its chemical ignition delay was much shorter than that of diesel, which is attributed to the long-chain hydrocarbon fuel structure and fuel oxygen availability. From an engine control and performance standpoint, the short ignition delay and robust heat release profile of biodiesel produced under simulated low-temperature combustion operating conditions demonstrates the compatibility of biodiesel for use in next-generation compression ignition engines.
In a quest to improve air quality, many experts are supportive of using hydrogen as the fuel of the future. More recently, two other key objectives of several nations have been instrumental in ...accelerating development for an alternative fuel, independence from foreign oil and securing renewable, affordable energy sources.
Most experts suggest that hydrogen as an alternative fuel has the elements to address all three of these concerns. In its purest form there are zero emissions, the supply is endless and production may use a variety of energy sources, including renewable.
The purpose of this paper is to explore and understand the challenges related to moving to a hydrogen-fueled economy. The efforts of some countries and leaders in the automotive sector are reviewed as they strive to develop the technology and find possible answers to production, storage and distribution challenges.
There are many opinions on how best to proceed. Some favor moving directly to a hydrogen infrastructure, while others advocate transitioning by using hydrogen fuel cell technology. While the problems of migrating to hydrogen are complex, there is no doubt that hydrogen is the energy source for the 21st century.
A collection consisting of the images of 774 live moth individuals, each moth belonging to one of 35 different UK species, was analysed to determine if data mining techniques could be used ...effectively for automatic species identification. Feature vectors were extracted from each of the moth images and the machine learning toolkit WEKA was used to classify the moths by species using the feature vectors. Whereas a previous analysis of this image dataset reported in the literature A. Watson, M. O’Neill, I. Kitching, Automated identification of live moths (Macrolepidoptera) using Digital Automated Identification System (DAISY), Systematics and Biodiversity 1 (3) (2004) 287–300. required that each moth’s least worn wing region be highlighted manually for each image, WEKA was able to achieve a greater level of accuracy (85%) using support vector machines without manual specification of a region of interest at all. This paper describes the features that were extracted from the images, and the various experiments using different classifiers and datasets that were performed. The results show that data mining can be usefully applied to the problem of automatic species identification of live specimens in the field.
The global burden of peripheral artery disease Eid, Mark A.; Mehta, Kunal; Barnes, J. Aaron ...
Journal of vascular surgery,
April 2023, 2023-04-00, 20230401, Letnik:
77, Številka:
4
Journal Article
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Previous efforts to characterize the burden of peripheral artery disease (PAD) have focused on national populations. A need for a more detailed analysis of how PAD impacts the global population has ...been identified. Our objective was to study in greater detail the global burden of PAD, including its impact on mortality, over the past three decades.
Using data and models from the Global Burden of Diseases, Injuries and Risk Factors Study, we estimated the prevalence, years of life lost, years lived with disability and disability-adjusted life-years (a measure accounting for incurred morbidity and mortality), attributable to PAD. We analyzed results over time and stratified by sex, age, and sociodemographic index (SDI) group. We compared PAD with other atherosclerosis-related conditions and assessed the contribution of risk factors to PAD disability-adjusted life-years.
We observed a 72% increase in the global prevalence of PAD from an estimated 65,764,499 persons in 1990 to 113,443,016 in 2019. Prevalence per 100,000 persons increased 13% and the prevalence per 100,000 age-standardized decreased 22%. Similar patterns were seen for years of live lost, mortality, years lived with disability, and disability-adjusted life-years. The prevalence and disability were higher among women, whereas mortality and years of life lost were higher among men. Disease burden increased with increasing SDI. These increases in PAD were in contrast with global trends for the overall burden of ischemic heart disease and ischemic stroke, which had decreasing prevalence and disease-related mortality over the same time frame. Overall, only approximately 55% of PAD disease burden could be attributed to identified risk factors, with tobacco use, diabetes, and hypertension being the three major contributors in all SDI groups.
The global prevalence and mortality associated with PAD has increased substantially, in contrast with other forms of ischemic cardiovascular disease. Globally, there is a growing need for vascular surgical resources to manage PAD, as well as public health efforts to address risk factors for this increasing health threat.
Ru(II)–polybipyridine complexes are efficient oxidizers and charge-transfer agents. Combined with semiconductor quantum dots (QDs) they show promising potential for solar energy conversion. Using ...density functional theory (DFT) and time-dependent DFT (TD-DFT), we study the ground- and excited-state properties of PbSe and ZnO QDs functionalized by Ru(II)–trisbipyridine derivatives. The calculated binding energies elucidate that the most stable QD–complex structures occur through binding of the complex in a bridging mode, when the carboxylate group of the complex is bound to the two metal ions on the QD surface. However, independent of the attachment and the type and size of the QD, the complex introduces unoccupied molecular orbitals near the edge of the conduction band of the QD, while occupied orbitals localized on Ru(II) are deep inside the QDs’ valence band. Such an energy alignment of the complex’s and QD’s orbitals makes the hole transfer from the photoexcited QD to the complex energetically unfavorable but supports a scenario of electron and energy transfer from the photoexcited complex to the QD. For small 1 nm PbSe and ZnO QDs, the lowest absorption peak originates from the complex and is well-separated from the next peak associated with the QD transitions, thus providing well-controlled excitation of either the QD or the complex. For PbSe QDs 2 nm in size and larger, however, the first absorption peak belongs to the QD transitions, while the next peak in the absorption spectra originates from both the QD’s and the complex’s transitions. The overlap between complex’s and QD’s optical transitions tends to hinder controllable excitation and regulated charge-transfer processes in experimental probes.
High‐grade serous carcinoma (HGSC) is the most common and fatal form of ovarian cancer. While most tumours are highly sensitive to cytoreductive surgery and platinum‐ and taxane‐based chemotherapy, ...the majority of patients experience recurrence of treatment‐resistant tumours. The clonal origin and mutational adaptations associated with recurrent disease are poorly understood. We performed whole exome sequencing on tumour cells harvested from ascites at three time points (primary, first recurrence, and second recurrence) for three HGSC patients receiving standard treatment. Somatic point mutations and small insertions and deletions were identified by comparison to constitutional DNA. The clonal structure and evolution of tumours were inferred from patterns of mutant allele frequencies. TP53 mutations were predominant in all patients at all time points, consistent with the known founder role of this gene. Tumours from all three patients also harboured mutations associated with cell cycle checkpoint function and Golgi vesicle trafficking. There was convergence of germline and somatic variants within the DNA repair, ECM, cell cycle control, and Golgi vesicle pathways. The vast majority of somatic variants found in recurrent tumours were present in primary tumours. Our findings highlight both known and novel pathways that are commonly mutated in HGSC. Moreover, they provide the first evidence at single nucleotide resolution that recurrent HGSC arises from multiple clones present in the primary tumour with negligible accumulation of new mutations during standard treatment.
Proteins search along the DNA for targets, such as transcription initiation sequences, according to one-dimensional diffusion, which is interrupted by micro- and macro-hopping events and ...intersegmental transfers that occur under close packing conditions.
A one-dimensional diffusion-reaction model in the form of difference-differential equations is proposed to analyze the nonequilibrium protein sliding kinetics along a segment of bacterial DNA. A renormalization approach is used to derive an expression for the mean first-passage time to arrive at sites downstream of the origin from the occupation probabilities given by the individual transport equations. Monte Carlo simulations are employed to assess the validity of the proposed approach, and all results are interpreted within the context of bacterial transcription.
Mean first-passage times decrease with increasing reaction rates, indicating that, on average, surviving proteins more rapidly locate downstream targets than their reaction-free counterparts, but at the price of increasing rarity. Two qualitatively different screening regimes are identified according to whether the search process operates under "small" or "large" values for the dissociation rate of the protein-DNA complex. Lower bounds are placed on the overall search time for varying reactive conditions. Good agreement with experimental estimates requires the reaction rate reside near the transition between both screening regimes, suggesting that biology balances a need for rapid searches against maximum exploration during each round of the sliding phase.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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