Most diseases disrupt multiple proteins, and drugs treat such diseases by restoring the functions of the disrupted proteins. How drugs restore these functions, however, is often unknown as a drug's ...therapeutic effects are not limited to the proteins that the drug directly targets. Here, we develop the multiscale interactome, a powerful approach to explain disease treatment. We integrate disease-perturbed proteins, drug targets, and biological functions into a multiscale interactome network. We then develop a random walk-based method that captures how drug effects propagate through a hierarchy of biological functions and physical protein-protein interactions. On three key pharmacological tasks, the multiscale interactome predicts drug-disease treatment, identifies proteins and biological functions related to treatment, and predicts genes that alter a treatment's efficacy and adverse reactions. Our results indicate that physical interactions between proteins alone cannot explain treatment since many drugs treat diseases by affecting the biological functions disrupted by the disease rather than directly targeting disease proteins or their regulators. We provide a general framework for explaining treatment, even when drugs seem unrelated to the diseases they are recommended for.
•In inoculum selection, the micronutrients content and the SMA must be considered.•Depending on inoculum attributes, it is not vital to add a trace elements solution.•Concentrations of Zn an Al ...>1000mg·kg−1 negatively affect the inoculum quality.
The production of renewable energy in the form of methane from the anaerobic digestion (AD) of food waste (FW) varies depending on factors such as the quantity and quality of the inoculum. This research evaluated the influence of trace elements (Ca, K, Fe, Zn, Al, Mg, Co, Ni, and Mo) present in inoculum from different sources (wastewater treatment plants (WWTPs): 2 agro-industrial WWTPs and 1 municipal WWTP) on the AD of FW. This study found that the source of the inoculum determines the content of macronutrients and trace elements, which can alter the requirements of the AD process and therefore affect methane production. The inoculum obtained from municipal WWTPs contain potentially inhibitory concentrations of Zn and Al that negatively affect methane production (<70 mL CH4·gVS−1), the hydrolysis constant (<0.19 d−1), and the lag-phase (>7 days). It was also found that high concentrations of trace elements such as Ni (35.2 mg kg−1) and Mo (15.4 mg kg−1) in the inoculum increase methane production (140.7 mL CH4·gVS−1) and hydrolysis constant (>0.18d−1) in addition to presenting short lag-phase (<1 day) in the AD of food waste.
One of the main challenges faced by iris recognition systems is to be able to work with people in motion, where the sensor is at an increasing distance (more than 1 m) from the person. The ultimate ...goal is to make the system less and less intrusive and require less cooperation from the person. When this scenario is implemented using a single static sensor, it will be necessary for the sensor to have a wide field of view and for the system to process a large number of frames per second (fps). In such a scenario, many of the captured eye images will not have adequate quality (contrast or resolution). This paper describes the implementation in an MPSoC (multiprocessor system-on-chip) of an eye image detection system that integrates, in the programmable logic (PL) part, a functional block to evaluate the level of defocus blur of the captured images. In this way, the system will be able to discard images that do not have the required focus quality in the subsequent processing steps. The proposals were successfully designed using Vitis High Level Synthesis (VHLS) and integrated into an eye detection framework capable of processing over 57 fps working with a 16 Mpixel sensor. Using, for validation, an extended version of the CASIA-Iris-distance V4 database, the experimental evaluation shows that the proposed framework is able to successfully discard unfocused eye images. But what is more relevant is that, in a real implementation, this proposal allows discarding up to 97% of out-of-focus eye images, which will not have to be processed by the segmentation and normalised iris pattern extraction blocks.
In the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more severe outcomes are reported in males than in females, including ...hospitalizations and deaths. Animal models can provide an opportunity to mechanistically interrogate causes of sex differences in the pathogenesis of SARS-CoV-2. Adult male and female golden Syrian hamsters (8 to 10 weeks of age) were inoculated intranasally with 10
50% tissue culture infective dose (TCID
) of SARS-CoV-2/USA-WA1/2020 and euthanized at several time points during the acute (i.e., virus actively replicating) and recovery (i.e., after the infectious virus has been cleared) phases of infection. There was no mortality, but infected male hamsters experienced greater morbidity, losing a greater percentage of body mass, developed more extensive pneumonia as noted on chest computed tomography, and recovered more slowly than females. Treatment of male hamsters with estradiol did not alter pulmonary damage. Virus titers in respiratory tissues, including nasal turbinates, trachea, and lungs, and pulmonary cytokine concentrations, including interferon-β (IFN-β) and tumor necrosis factor-α (TNF-α), were comparable between the sexes. However, during the recovery phase of infection, females mounted 2-fold greater IgM, IgG, and IgA responses against the receptor-binding domain of the spike protein (S-RBD) in both plasma and respiratory tissues. Female hamsters also had significantly greater IgG antibodies against whole-inactivated SARS-CoV-2 and mutant S-RBDs as well as virus-neutralizing antibodies in plasma. The development of an animal model to study COVID-19 sex differences will allow for a greater mechanistic understanding of the SARS-CoV-2-associated sex differences seen in the human population.
Men experience more severe outcomes from coronavirus disease 2019 (COVID-19) than women. Golden Syrian hamsters were used to explore sex differences in the pathogenesis of a human isolate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After inoculation, male hamsters experienced greater sickness, developed more severe lung pathology, and recovered more slowly than females. Sex differences in disease could not be reversed by estradiol treatment in males and were not explained by either virus replication kinetics or the concentrations of inflammatory cytokines in the lungs. During the recovery period, antiviral antibody responses in the respiratory tract and plasma, including to newly emerging SARS-CoV-2 variants, were greater in female than in male hamsters. Greater lung pathology during the acute phase combined with lower antiviral antibody responses during the recovery phase of infection in males than in females illustrate the utility of golden Syrian hamsters as a model to explore sex differences in the pathogenesis of SARS-CoV-2 and vaccine-induced immunity and protection.
Real-time embedded eye detection system Ruiz-Beltrán, Camilo A.; Romero-Garcés, Adrián; González, Martín ...
Expert systems with applications,
05/2022, Letnik:
194
Journal Article
Recenzirano
Odprti dostop
The detection of a person’s eyes is a basic task in applications as important as iris recognition in biometric identification or fatigue detection in driving assistance systems. Current commercial ...and research systems use software frameworks that require a dedicated computer, whose power consumption, size and price are significantly large. This paper presents a hardware-based embedded solution for eye detection in real-time. From an algorithmic point-of-view, the popular Viola–Jones approach has been redesigned to enable highly parallel, single-pass image-processing implementation. Synthesized and implemented in an All-Programmable System-on-Chip (AP SoC), this proposal allows us to process more than 88 frames per second (fps), taking the classifier less than 2 ms per image. Experimental validation has been successfully addressed in an iris recognition system that works with walking subjects. In this case, the prototype module includes a CMOS digital imaging sensor providing 16 Mpixels images, and it outputs a stream of detected eyes as 640 × 480 images. Experiments for determining the accuracy of the proposed system in terms of eye detection are performed in the CASIA-Iris-distance V4 database. Significantly, they show that the accuracy in terms of eye detection is 100%.
•A single-pass image-processing redesign of the Viola–Jones approach is proposed.•The classifier core can process more than 750 fps.•An accuracy rate of 100% is obtained using the CASIA-Iris-distance V4 database.•The proposal is integrated into a framework for iris identification on motion.
The displacement of a sprint kayak can be described by a one-dimensional mathematical model, which, in its simplest case, is analogous to the free-fall problem with quadratic drag and constant ...propulsion. To describe realistic cases, it is necessary to introduce a propulsion capable of reproducing the characteristics of the kayak stroke, including periodicity, average force and effects of stroke frequency, among others. Addressing the problem in terms of a Fourier series allows us to separate the equation into two parts, one of which is equivalent to the constant propulsion case and results in an asymptotic expression, while the second accounts for the periodic contributions. This approach allows us to solve several cases of interest: to propose a quadrature rule for the asymptotic part that allows fast estimations; to compare results with the literature; and finally to propose a general mathematical method for this problem which could help to understand some key strategies in the kayak race.
The carrier envelope phase (CEP) is a crucial parameter for a few-cycle laser pulse since it substantially determines the laser waveform. Stepping forward from infrared to extreme ultraviolet (EUV) ...pulses, we propose a strategy to directly characterize the CEP of an isolated attosecond pulse (IAP) by numerically simulating the tunneling ionization of a hydrogen atom in a combined IAP and phase-stabilized circularly polarized IR laser pulse. The fine modulations of the combined laser fields, due to the variation of the CEP of the IAP, are exponentially enlarged onto the distinct time-dependent tunneling ionization rate. Electrons released at different time with distinct tunneling ionization rates are angularly streaked to different directions. By measuring the resulting photoelectron momentum distribution, the CEP of the IAP can be retrieved. The characterization of the CEP of an IAP will open the possibility of capturing sub-EUV-cycle dynamics.
Tuberculous meningitis (TB meningitis) is the most severe form of tuberculosis (TB), requiring 12 months of multidrug treatment for cure, and is associated with high morbidity and mortality. ...High-dose rifampin (35 mg/kg/d) is safe and improves the bactericidal activity of the standard-dose (10 mg/kg/d) rifampin-containing TB regimen in pulmonary TB. However, there are conflicting clinical data regarding its benefit for TB meningitis, where outcomes may also be associated with intracerebral inflammation. We conducted cross-species studies in mice and rabbits, demonstrating that an intensified high-dose rifampin-containing regimen has significantly improved bactericidal activity for TB meningitis over the first-line, standard-dose rifampin regimen, without an increase in intracerebral inflammation. Positron emission tomography in live animals demonstrated spatially compartmentalized, lesion-specific pathology, with postmortem analyses showing discordant brain tissue and cerebrospinal fluid rifampin levels and inflammatory markers. Longitudinal multimodal imaging in the same cohort of animals during TB treatment as well as imaging studies in two cohorts of TB patients demonstrated that spatiotemporal changes in localized blood-brain barrier disruption in TB meningitis are an important driver of rifampin brain exposure. These data provide unique insights into the mechanisms underlying high-dose rifampin in TB meningitis with important implications for developing new antibiotic treatments for infections.
Despite numerous advances in tuberculosis (TB) drug development, long treatment durations have led to the emergence of multidrug resistance, which poses a major hurdle to global TB control. ...Shortening treatment time therefore remains a top priority. Host-directed therapies that promote bacterial clearance and/or lung health may improve the efficacy and treatment duration of tuberculosis antibiotics. We recently discovered that inhibition of the integrated stress response, which is abnormally activated in tuberculosis and associated with necrotic granuloma formation, reduced bacterial numbers and lung inflammation in mice. Here, we evaluated the impact of the integrated stress response (ISR) inhibitor ISRIB, administered as an adjunct to standard tuberculosis antibiotics, on bacterial clearance, relapse, and lung pathology in a mouse model of tuberculosis. Throughout the course of treatment, ISRIB robustly lowered bacterial burdens compared to the burdens with standard TB therapy alone and accelerated the time to sterility in mice, as demonstrated by significantly reduced relapse rates after 4 months of treatment. In addition, mice receiving adjunctive ISRIB tended to have reduced lung necrosis and inflammation. Together, our findings identify the ISR pathway as a promising therapeutic target with the potential to shorten TB treatment durations and improve lung health.
Necrosis of lung lesions is a hallmark of tuberculosis (TB) that promotes bacterial growth, dissemination, and transmission. This process is driven by the persistent hyperactivation of the integrated stress response (ISR) pathway. Here, we show that adjunctive ISR inhibition during standard antibiotic therapy accelerates bacterial clearance and reduces immunopathology in a clinically relevant mouse model of TB, suggesting that host-directed therapies that de-escalate these pathological stress responses may shorten TB treatment durations. Our findings present an important conceptual advance toward overcoming the challenge of improving TB therapy and lowering the global burden of disease.
Urban systems present hierarchical structures at many different scales. These are observed as administrative regional delimitations which are the outcome of complex geographical, political and ...historical processes which leave almost indelible footprints on infrastructure such as the street network. In this work, we uncover a set of hierarchies in Britain at different scales using percolation theory on the street network and on its intersections which are the primary points of interaction and urban agglomeration. At the larger scales, the observed hierarchical structures can be interpreted as regional fractures of Britain, observed in various forms, from natural boundaries, such as National Parks, to regional divisions based on social class and wealth such as the well-known North–South divide. At smaller scales, cities are generated through recursive percolations on each of the emerging regional clusters. We examine the evolution of the morphology of the system as a whole, by measuring the fractal dimension of the clusters at each distance threshold in the percolation. We observe that this reaches a maximum plateau at a specific distance. The clusters defined at this distance threshold are in excellent correspondence with the boundaries of cities recovered from satellite images, and from previous methods using population density.
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