Miracle-dz/UniFAR-FTUs huggingface dataset:
Population Structure, Levels of Selection, and the Evolution of Intracellular Symbionts

Abstract Many obligately intracellular symbionts exhibit a characteristic set of genetic changes that include an increase in substitution rates, loss of many genes, and apparent destabilization of many proteins and structural RNAs. Authors have suggested that these changes are due to increased mutation rates, or, more commonly, decreased effective population size due to population bottlenecks at the symbiont or, perhaps, host level. I propose that the increase in substitution rates and accumulation of deleterious mutations is a consequence of the population structure imposed on the endosymbionts by strict host association, loss of horizontal transmission and potentially conflicting levels of selection. I analyze a population genetic model of endosymbiont evolution, and demonstrate that substitution rates will increase, and the effect of those substitutions on endosymbiont fitness will become more deleterious as horizontal transmission among hosts decreases. Additionally, I find that there is a critical level of horizontal transmission below which natural selection cannot effectively purge deleterious mutations, leading to an expected loss of fitness over time. This critical level varies across loci with the degree of correlation between host and endosymbiont fitness, and may help explain differential retention and loss of certain genes.
Plant mitochondria contain the protein translocase subunits TatB and TatC

ABSTRACT Twin-arginine translocation (Tat) pathways have been well-characterized in bacteria and chloroplasts. Genes encoding a TatC protein are found in almost all plant mitochondrial genomes but to date these have not been extensively investigated. For the first time it could be demonstrated that this mitochondrial-encoded TatC is a functional gene that is translated into a protein in the model plant Arabidopsis thaliana. A TatB-like subunit localized to the inner membrane was also identified that is nuclear-encoded and is essential for plant growth and development, indicating that plants potentially require a Tat pathway for mitochondrial biogenesis. Summary: This paper provides evidence that Arabidopsis thaliana mitochondria contain two subunits of a twin arginine translocation (Tat) pathway, indicating the presence of an active Tat pathway in plants.
Chemical Visualization of Phosphoproteomes on Membrane*

With new discoveries of important roles of phosphorylation on a daily basis, phospho-specific antibodies, as the primary tool for on-membrane detection of phosphoproteins, face enormous challenges. To address an urgent need for convenient and reliable analysis of phosphorylation events, we report a novel strategy for sensitive phosphorylation analysis in the Western blotting format. The chemical reagent, which we termed pIMAGO, is based on a multifunctionalized soluble nanopolymer and is capable of selectively binding to phosphorylated residues independent of amino acid microenvironment, thus offering great promise as a universal tool in biological analyses where the site of phosphorylation is not known or its specific antibody is not available. The specificity and sensitivity of the approach was first examined using a mixture of standard proteins. The method was then applied to monitor phosphorylation changes in in vitro kinase and phosphatase assays. Finally, to demonstrate the unique ability of pIMAGO to measure endogenous phosphorylation, we used it to visualize and determine the differences in phosphorylated proteins that interact with wild-type and kinase dead mutant of Polo-like kinase 1 during mitosis, the results of which were further confirmed by a quantitative phosphoproteomics experiment.
Preoperative Opioid Use Is Associated with Early Revision After Total Knee Arthroplasty: A Study of Male Patients Treated in the Veterans Affairs System

Background: Opioid use is endemic in the U.S. and is associated with morbidity and mortality. The impact of long-term opioid use on joint-replacement outcomes remains unknown. We tested the hypothesis that use of opioids is associated with adverse outcomes after total knee arthroplasty (TKA). Methods: We performed a retrospective analysis of patients who had had TKA within the U.S. Veterans Affairs (VA) system over a 6-year period and had been followed for 1 year postoperatively. The length of time for which an opioid had been prescribed and the morphine equivalent dose were calculated for each patient. Patients for whom opioids had been prescribed for >3 months in the year prior to the TKA were assigned to the long-term opioid group. A natural language processing-based machine-learning classifier was developed to classify revisions due to infectious and non-infectious causes on the basis of the postoperative note. Survival curves for the time to knee revision or manipulation were used to compare the long-term opioid group with the patients who did not take opioids long-term. Hazard and odds ratios for knee revision and manipulation were obtained as well. Results: Of 32,636 patients (94.4% male; mean age [and standard deviation], 64.45 ± 9.41 years) who underwent TKA, 12,772 (39.1%) were in the long-term opioid group and 734 (2.2%) had a revision within a year after the TKA. Chronic kidney disease, diabetes, and long-term opioid use were associated with revision within 1 year—with odds ratios (95% confidence intervals [CIs]) of 1.76 (1.37 to 2.22), 1.11 (0.93 to 1.31), and 1.40 (1.19 to 1.64), respectively—and were also the leading factors associated with a revision at any time after the index TKA—with odds ratios (95% CIs) of 1.61 (1.34 to 1.92), 1.21 (1.08 to 1.36), and 1.28 (1.15 to 1.43), respectively. Long-term opioid use had a hazard ratio of 1.19 (95% CI = 1.10 to 0.24) in the analysis of its relationship with knee revision, but the hazard was not significant in the analysis of its association with knee manipulation. The accuracy of the text classifier was 0.94, with the area under the receiver operating characteristic curve being 0.99. There was no association between long-term use of opioids and the specific cause for knee revision. Conclusions: Long-term opioid use prior to TKA was associated with an increased risk of knee revision during the first year after TKA among predominantly male patients treated in the VA system. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Comparison of the Intelligent Techniques for Data Mining in Spam Detection to Computer Networks

Anomalies in computer networks has increased in the last decades and raised concern to create techniques to identify the unusual traffic patterns. This research aims to use data mining techniques in order to correctly identify these anomalies. Weka is a collection of machine learning algorithms for data mining tasks which was used to identify and analyze the anomalies of a data set called SPAMBASE in order to improve this environment.
Low loss multimode polymer shuffling optical waveguide for high-density optical circuit

To realize free optical wiring patterns on printed circuit boards (PCBs), polymer shuffling optical waveguides are fabricated, in which both crossing and curved core structures are combined. The obtained GI polymer shuffling waveguides show low insertion loss independent of the crossing angle and core size. The GI-core polymer shuffling waveguide is a key device for low loss and high density on-board optical wiring.
Interaction between cytochrome c2 and the photosynthetic reaction center from Rhodobacter sphaeroides: effects of charge-modifying mutations on binding and electron transfer.

The electrostatic interactions governing binding and electron transfer from cytochrome c(2) (cyt c(2)) to the reaction center (RC) from the photosynthetic bacteria Rhodobacter sphaeroides were studied by using site-directed mutagenesis to change the charges of residues on the RC surface. Charge-reversing mutations (acid --> Lys) decreased the binding affinity for cyt c(2). Dissociation constants, K(D) (0.3--250 microM), were largest for mutations of Asp M184 and nearby acid residues, identifying the main region for electrostatic interaction with cyt c(2). The second-order rate constants, k(2) (1--17 x 10(8) M(-1) s(-1)), increased with increasing binding affinity (log k(2) vs log 1/K(D) had a slope of approximately 0.4), indicating a transition state structurally related to the final complex. In contrast, first-order electron transfer rates, k(e), for the bound cyt did not change significantly (<3-fold), indicating that electron tunneling pathways were unchanged by mutation. Charge-neutralizing mutations (acid --> amide) showed changes in binding free energies of approximately 1/2 the free energy changes due to the corresponding charge-reversing mutations, suggesting that the charges in the docked complex remain well solvated. Charge-enhancing mutations (amide --> acid) produced free energy changes of the same magnitude (but opposite sign) as changes due to the charge-neutralizing mutations in the same region, indicating a diffuse electrostatic potential due to cyt c(2). A two-domain model is proposed, consisting of an electrostatic docking domain with charged surfaces separated by a water layer and a hydrophobic tunneling domain with atomic contacts that provide an efficient pathway for electron transfer.
Nonuniform pulse intervals and nonuniform frequency steps for managing radar ambiguity properties

The theory of nonuniform or irregular sampling has many new application areas. With pulsed radar, a classic example of nonuniform sampling is staggered PRF which provides aid for MTI or Doppler processing. For example with a conventional surveillance radar, PRF is often too low for decent Doppler analysis due to operational requirement of unambiguous range. This paper discusses a nonuniform sampling scheme that guarantees a desired unambiguous measurement. The approach is applied to two experiments. First, staggering a sequence of PRIs provides desired unambiguous Doppler. Second, range ambiguity is solved correspondingly with a stepped frequency waveform. Of course, one can achieve these by utilizing conventional uniform sampling but with considerably higher number of samples. Results with real pulsed radar recordings prove the applicability of the sampling scheme.
Integration of information about cardiovascular risk factors: how do highly motivated women in a lifestyle intervention programme act and react?

Objective - To understand the experience of being at risk and of participating in health interventions. How is information about risk factors handled on an individual level with respect to feeling, thinking and doing? Design - Tape-recorded, open interviews, written out and analysed using a descriptive/analytical method. Setting - Selected women who had participated in a lifestyle intervention programme aimed at reducing risk factors for cardiovascular disease in Strömstad, a community of 10 000 inhabitants on the west coast of Sweden. Subjects - Eight women in the most active group who had had some contact with the project during the whole period 1985-94. Main outcome measures - The creation of core concepts as a result of close text reading through codes and categories. Results - Three core concepts in relation to the handling of risk factors were identified: there is no one but yourself to rely on, resisting invasion, and living with incompatibility, based respectively on the subjects' self-efficacy and self-awareness, their ways of maintaining a good life and their trying to understand the risk-factor concept. Conclusion - Risk-factor-oriented health interventions focus on disease and create uncertainty as to the relationship between the concepts of risk and disease. The powerful health resources demonstrated by the women in this study to counterbalance the risk pre-occupation suggest changing to health-oriented interventions that focus on individual health resources.
On the influence of the forgetting factor of the RLS adaptive filter in system identification

The overall performance of the recursive least-squares (RLS) algorithm is governed by the forgetting factor. The value of this parameter leads to a compromise between low misadjustment and stability on the one hand, and fast convergence rate and tracking on the other hand. In this paper, we analyze another important phenomenon that has to be considered when choosing the value of the forgetting factor. Considering a system identification setup, there is a “leakage” of the system noise into the output of the adaptive filter. This process is highly influenced by the value of the forgetting factor but it also depends on the length of the adaptive filter. Simulations performed in an echo cancellation configuration prove these theoretical findings.
Melatonin attenuates decrease of protein phosphatase 2A subunit B in ischemic brain injury

Abstract: Melatonin is an antioxidant that has neuroprotective functions in ischemic brain injury. Protein phosphatase 2A (PP2A) is a serine and threonine phosphatase that modulates cell metabolism and cell survival. This study investigated whether melatonin modulates PP2A subunit B in focal cerebral ischemia and glutamate toxicity‐induced neuronal cell death in a rat model. Middle cerebral artery occlusion (MCAO) was performed to induce permanent cerebral ischemic injury. Adult male rats were treated with vehicle or melatonin (5 mg/kg) prior to MCAO, and cerebral cortex tissues were collected 24 hr after MCAO. A proteomic approach elucidated the decrease in PP2A subunit B in MCAO‐operated animals. Melatonin treatment attenuated injury‐induced reductions in PP2A subunit B levels. Western blot analyses indicated that melatonin prevents injury‐induced decrease in PP2A subunit B levels. In neuronal cells, glutamate toxicity induced a lowering of PP2A subunit B, while melatonin treatment attenuated the glutamate exposure‐induced decreases in PP2A subunit B. These results suggest that the maintenance of PP2A subunit B by melatonin in ischemic injury is critical to the neuroprotective function of melatonin during neuronal cell damage.
Host B7x Promotes Pulmonary Metastasis of Breast Cancer

B7x (B7-H4 or B7S1) is an inhibitory member of the B7 family of T cell costimulation. It is expressed in low levels in healthy peripheral tissues, such as the lung epithelium, but is overexpressed in a variety of human cancers with negative clinical associations, including metastasis. However, the function of B7x in the context of cancer, whether expressed on cancer cells or on surrounding “host” tissues, has not been elucidated in vivo. We used the 4T1 metastatic breast cancer model and B7x knockout (B7x −/−) mice to investigate the effect of host tissue–expressed B7x on cancer. We found that 4T1 cells were B7x negative in vitro and in vivo, and B7x−/− mice had significantly fewer lung 4T1 tumor nodules than did wild-type mice. Furthermore, B7x−/− mice showed significantly enhanced survival and a memory response to tumor rechallenge. Mechanistic studies revealed that the presence of B7x correlated with reduced general and tumor-specific T cell cytokine responses, as well as with an increased infiltration of immunosuppressive cells, including tumor-associated neutrophils, macrophages, and regulatory T cells, into tumor-bearing lungs. Importantly, tumor-associated neutrophils strongly bound B7x protein and inhibited the proliferation of both CD4 and CD8 T cells. These results suggest that host B7x may enable metastasizing cancer cells to escape local antitumor immune responses through interactions with the innate and adaptive immune systems. Thus, targeting the B7x pathway holds much promise for improving the efficacy of immunotherapy for metastatic cancer.
Effective adaptive virtual queue: a stabilising active queue management algorithm for improving responsiveness and robustness

Adaptive virtual queue (AVQ) algorithm is an effective method aiming to achieve low loss, low delay and high-link utilisation at the link. However, it is difficult to guarantee fast response, strong robustness and good trade-off over a wide range of network dynamics. The authors propose a stabilising active queue management (AQM) algorithm – effective-AVQ, as an extension of AVQ, to improve the responsiveness and robustness of the transmission control protocol (TCP)/AQM system. Specifically, a proportional integral derivative (PID) neuron is introduced to tune the virtual link capacity dynamically. Also we derive the parameter self-tuning mechanism for the PID neuron from the Hebbian learning rule and gradient descent approach. The stability condition of the closed-loop system is presented based on the time-delay control theory. The performance of effective-AVQ is validated in the NS2 platform. Simulation results demonstrate that effective-AVQ outperforms AVQ in terms of steady-state and transient performance. It achieves fast response, expected link utilisation, low queue size and small delay jitter, being robust against dynamic network changes.
Expression of genes for non-collagenous proteins during embryonic bone formation.

In situ hybridization has been used to localize RNAs for a variety of non-collagenous proteins during embryogenesis of the mouse, with particular reference to bone formation. Transcripts of the Sparc (osteonectin) gene are first detected around 14.5d post coitum (p.c.) in the periosteal layer around the cartilage model of long bones and in membrane bone in the head. By 15.5d p.c. transcripts are seen in hypertrophic cartilage and later in cells within the bone closely associated with new matrix. By contrast, RNA for 2ar (osteopontin) is not seen in the periosteal layer but is confined to cells in the marrow region. TIMP (tissue inhibitor of metalloproteinase) transcripts show a very similar distribution to those for Sparc.
Burden of Stroke in Italy: An Economic Model Highlights Savings Arising from Reduced Disability following Thrombolysis

Background The consequences of stroke must be assessed not only in terms of incidence and mortality rates, but also in terms of disability, which may persist long after the acute phase. Thrombolysis, if timely administered, can effectively reduce post-stroke disability. Aims The economic model presented herein aims to evaluate, in eligible patients, the effects of alteplase on post-stroke disability and related costs over three-years. Methods The economic analysis was developed on the basis of four key components: clinical outcomes from international trials, economic consequences extracted from cost of illness studies, regulatory data from national and international agencies, and national epidemiological data. A population-level model estimated the difference in disability costs between patients treated with standard care versus those receiving thrombolytic therapy within 4×5 h of acute ischemic stroke. The analysis covered 36 months from discharge. Results Reduced costs related to post-stroke disability were observed in treated patients compared with those receiving standard care (control). The overall savings were ¢2330×15 per average patient: ¢1445×81 during the first 18 months, ¢362×25 between 18 and 24 months, and ¢522×09 in the 24–36 months period. The overall savings on 3174 Italian treated patients in 2013 were ¢7 395 907 over three-years. Conclusion Our study reveals that performing thrombolytic therapy in eligible patients improves economic outcomes compared with patients receiving standard care. This model is useful for decision makers, both within and outside of the Italian national context, as a tool to assess the cost-effectiveness of thrombolysis in both short- and long-term period.
Towards formalisation of situation-specific computations in pervasive computing environments

We have categorised the characteristics and the content of pervasive computing environments (PCEs), and demonstrated why a non-dynamic approach to knowledge conceptualisation in PCEs does not fulfil the expectations we may have from them. Consequently, we have proposed a formalised computational model, the FCM, for knowledge representation and reasoning in PCEs which, secures the delivery of situation and domain specific services to their users. The proposed model is a user centric model, materialised as a software engineering solution, which uses the computations generated from the FCM, stores them within software architectural components, which in turn can be deployed using modern software technologies. The model has also been inspired by the Semantic Web (SW) vision and provision of SW technologies. Therefore, the FCM creates a semantically rich situation-specific PCE based on SWRL-enabled OWL ontologies that allows reasoning about the situation in a PCE and delivers situation specific service. The proposed FCM model has been illustrated through the example of remote patient monitoring in the healthcare domain. Numerous software applications generated from the FCM have been deployed using Integrated Development Environments and OWL-API.
Fibrin nanoconstructs: a novel processing method and their use as controlled delivery agents

Fibrin nanoconstructs (FNCs) were prepared through a modified water-in-oil emulsification–diffusion route without the use of any surfactants, resulting in a high yield synthesis of fibrin nanotubes (FNTs) and fibrin nanoparticles (FNPs). The fibrin nanoconstructs formed an aligned structure with self-assembled nanotubes with closed heads that eventually formed spherical nanoparticles of size ∼250 nm. The nanotubes were typically ∼700 nm long and 150–300 nm in diameter, with a wall thickness of ∼50 nm and pore diameter of about 150–250 nm. These constructs showed high stability against aggregation indicated by a zeta potential of −44 mV and an excellent temperature stability upto 200 °C. Furthermore, they were found to be enzymatically degradable, thereby precluding any long term toxicity effects. These unique fibrin nanostructures were analyzed for their ability to deliver tacrolimus, an immunosuppressive drug that is used widely to prevent the initial phase of tissue rejection during allogenic transplantation surgeries. Upon conjugation with tacrolimus, a drug encapsulation efficiency of 66% was achieved, with the in vitro release studies in PBS depicting a sustained and complete drug release over a period of one week at the physiological pH of 7.4. At a more acidic pH, the drug release was very slow, suggesting their potential for oral–intestinal drug administration as well. The in vivo drug absorption rates analyzed in Sprague Dawley rats further confirmed the sustained release pattern of tacrolimus for both oral and parenteral delivery routes. The novel fibrin nanoconstructs developed using a green chemistry approach thus proved to be excellent biodegradable nanocarriers for oral as well as parenteral administrations, with remarkable potential also for delivering specific growth factors in tissue engineering scaffolds.