Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of the Repeat Domain Structures and Impact of Parkinsonism‐Associated Variations on Structure and Function of all Functional Domains of Leucine‐Rich Repeat Kinase 2 (LRRK2)

Genetic variations of leucine‐rich repeat kinase 2 (LRRK2) are the major cause of dominantly inherited Parkinson disease (PD). LRRK2 protein contains seven predicted domains: a tandem Ras‐like GTPase (ROC) domain and C‐terminal of Roc (COR) domain, a protein kinase domain, and four repeat domains. PD‐causative variations arise in all domains, suggesting that aberrant functioning of any domain can contribute to neurotoxic mechanisms of LRRK2. Determination of the three‐dimensional structure of LRRK2 is one of the best avenues to decipher its neurotoxic mechanism. However, with the exception of the Roc domain, the three‐dimensional structures of the functional domains of LRRK2 have yet to be determined. Based on the known three‐dimensional structures of repeat domains of other proteins, the tandem Roc–COR domains of the Chlorobium tepidum Rab family protein, and the kinase domain of the Dictyostelium discoideum Roco4 protein, we predicted (1) the motifs essential for protein–protein interactions in all domains, (2) the motifs critical for catalysis and substrate recognition in the tandem Roc–COR and kinase domains, and (3) the effects of some PD‐associated missense variations on the neurotoxic action of LRRK2. Results of our analysis provide a conceptual framework for future investigation into the regulation and the neurotoxic mechanism of LRRK2.
Shutoff of host translation by encephalomyocarditis virus infection does not involve cleavage of the eucaryotic initiation factor 4F polypeptide that accompanies poliovirus infection

Studies were conducted to determine whether encephalomyocarditis virus infection causes proteolytic cleavage of any of the polypeptides which comprise eucaryotic initiation factor 4F. Since no such alterations in the components of the initiation factor were detected, these observations confirmed that the mechanisms whereby encephalomyocarditis virus and poliovirus shut off host translation are different.
Staphylococcus aureus requires at least one FtsK/SpoIIIE protein for correct chromosome segregation

Faithful coordination between bacterial cell division and chromosome segregation in rod‐shaped bacteria, such as Escherichia coli and Bacillus subtilis, is dependent on the DNA translocase activity of FtsK/SpoIIIE proteins, which move DNA away from the division site before cytokinesis is completed. However, the role of these proteins in chromosome partitioning has not been well studied in spherical bacteria. Here, it was shown that the two Staphylococcus aureus FtsK/SpoIIIE homologues, SpoIIIE and FtsK, operate in independent pathways to ensure correct chromosome management during cell division. SpoIIIE forms foci at the centre of the closing septum in at least 50% of the cells that are close to complete septum synthesis. FtsK is a multifunctional septal protein with a C‐terminal DNA translocase domain that is not required for correct chromosome management in the presence of SpoIIIE. However, lack of both SpoIIIE and FtsK causes severe nucleoid segregation and morphological defects, showing that the two proteins have partially redundant roles in S. aureus.
The degradation of serum amyloid A protein by activated polymorphonuclear leucocytes: participation of granulocytic elastase.

To determine the role of inflammation in amyloidogenesis, we have studied the degradation of human serum amyloid A (SAA) protein by purified preparations of human blood polymorphonuclear leucocytes (PMN) and monocytes. When both PMN and monocytes were incubated in SAA-containing medium, the concentration of SAA as measured by a competitive anti-AA radioimmunoassay decreased over time. The rate of decrease of SAA was similar for both monocytes and PMN and there were no differences between four patients with amyloidosis and three normal controls. Resting PMN from normal volunteers were able to degrade SAA to smaller acid-soluble peptides within 16 hr while zymosan-activated PMN produced significant degradation within 1 hr (31%–50%). The supernatants from zymosan-treated PMN also caused marked SAA degradation within 1 hr. The following enzyme inhibitors were able to prevent degradation of SAA by PMN supernatants; phenylmethylsulphonyl fluoride, a serine esterase inhibitor; α1 anti-trypsin and soybean trypsin inhibitor; and acetyl-ala-ala-pro-val-chloromethyl ketone, an elastase inhibitor. The ability of a neutral lysosomal enzyme to degrade SAA was further confirmed by showing that purified PMN elastase significantly degraded 125I-SAA. We conclude that PMN contain one or more lysosomal enzymes capable of degrading SAA, an apoprotein of HDL3 serum lipoproteins. Alteration in SAA proteolysis by activated PMN may contribute to the deposition of amyloid fibrils in the tissues of patients with chronic inflammatory disease.
Power-gated FSM synthesis integrating partitioning and state assignment

Among the power-aware circuit synthesis techniques that have been proposed so far, power-gating has traditionally been the most effective way to lower power. In this approach, power reduction is achieved by shutting off the power supply to some portions of the logic block which are not active. So, we have to partition the design into two or more power islands. Suitable Finite State Machine partitioning and encoding reduces the power dissipation also in power-gating method. In this paper we have presented the state partitioning and state encoding strategy targeting low power Finite State Machine (FSM) decomposition based on Genetic Algorithmic approach. Our strategy has been validated using commercial FSM synthesis tool. All the previous works dealt with only FSM partitioning but did not consider state encoding together. This is the first ever approach considering FSM partitioning and state encoding together in power-gating technique. Experimental result shows that up to 78% power saving can be achieved.
Surface plasmon resonance analysis of the binding of high‐risk mucosal HPV E6 oncoproteins to the PDZ1 domain of the tight junction protein MAGI‐1

The E6 oncoproteins from high‐risk mucosal human papillomavirus (HPV) induce cervical cancer via two major activities, the binding and the degradation of the p53 protein and PDZ domain‐containing proteins. Human MAGI‐1 is a multi‐PDZ domain protein implicated into protein complex assembly at cell–cell contacts. High‐risk mucosal HPV E6 proteins interact with the PDZ1 domain of MAGI‐1 via a C‐terminal consensus binding motif. Here, we developed a medium throughput protocol to accurately measure by surface plasmon resonance affinity constants of protein domains binding to peptidic sequences produced as recombinant fusions to the glutathione‐S‐transferase (GST). This approach was applied to measure the binding of MAGI‐1 PDZ1 to the C‐termini of viral or cellular proteins. Both high‐risk mucosal HPV E6 C‐terminal peptides and cellular partners of MAGI‐1 PDZ1 bind to MAGI‐1 PDZ1 with comparable dissociation constants in the micromolar range. MAGI‐1 PDZ1 shows a preference for C‐termini with a valine at position 0 and a negative charge at position −3, confirming previous studies performed with HPV18 E6. A detailed combined analysis via site‐directed mutagenesis of the HPV16 C‐terminal peptide and PDZ1 indicated that interactions mediated by charged residues upstream the PDZ‐binding motif strongly contribute to binding selectivity of this interaction. In addition, our work highlighted the K499 residue of MAGI‐1 as a novel determinant of binding specificity. Finally, we showed that MAGI‐1 PDZ1 also binds to the C‐termini of LPP and Tax proteins, which were already known to bind to PDZ proteins but not to MAGI‐1. Copyright © 2010 John Wiley & Sons, Ltd.
No Pharmacokinetic Effect of Retaining the Infusion Site up to Four Days During Continuous Subcutaneous Insulin Infusion Therapy

This study was designed to investigate whether the indwelling time of the needle during continuous subcutaneous insulin infusion (CSII) could contribute to one of the main problems with subcutaneous insulin administration, that is the day‐to‐day intra‐patient variation in absorption. The effect on insulin kinetics after a bolus dose was investigated at different time intervals up to 4 days after insertion of an indwelling catheter in situ for CSII therapy. Nine insulin‐dependent diabetic patients treated with pump (Nordisk Infuser; Velosulin 100 U ml−1) took part in the study. The evening before day 1 of the investigation a needle connected to the pump with a polyethylene catheter was inserted subcutaneously on the abdominal wall where it remained throughout the investigation. There were no significant differences in blood glucose or plasma free insulin profiles between days 1, 3, and 5. The intra‐patient coefficient of variation of free insulin was 38% at basal and 19% at post‐bolus state. We conclude that during CSII it is acceptable from a pharmacokinetic point of view to retain the infusion site for up to 4 days.
Provider-Consumer Anomaly Detection for Healthcare Systems

Anomaly detection is an important task that has been widely applied to different scenarios. In particular, its application in public healthcare is a crucial management task that can improve the quality of the health services and avoid loss of huge amounts of money. In this work we propose and evaluate, in a real scenario, a method for anomaly detection in healthcare based on a provider-consumer model. Our method is divided into two phases. In the first phase it assigns anomaly scores to the cities (consumers) as a function of their demand, then, in the second phase, it transfers the scores from cities to hospitals (providers). We applied the method to a real database from the Brazilian public healthcare that records medical procedures which cost more than $8.5 billion from 2008 to 2012, and demonstrated our method's ability to find potentially fraudulent hospitals. The method is being adopted by the Brazilian government for selecting anomalous hospitals to be investigated. Our main contributions are (i) a simple and effective method for anomaly detection in healthcare; (ii) our method does not require information about the providers nor medical rules; (iii) the analysis from the consumer perspective allows the detection of anomalies that could not be detected with traditional methods; and (iv) we applied the method to a real database and performed a detailed validation.
The Computerized Test of Information Processing (CTIP) by Tom Tombaugh

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Optimisation d'opérateurs arithmétiques matériels à base d'approximations polynomiales

This article presents a method for the optimisation of hardware arithmetic operators dedicated to function evaluation using polynomial approximations. Using recent tools, the method reduces the size of the polynomial coefficients and the intermediate values while keeping the total error bounded (approximation and evaluation). It leads to small and fast operators with a good numerical quality. The method is illustrated on several examples implemented on FPGA circuits.
Impact of Anthropogenic CO2 on the CaCO3 System in the Oceans

Rising atmospheric carbon dioxide (CO2) concentrations over the past two centuries have led to greater CO2 uptake by the oceans. This acidification process has changed the saturation state ofthe oceans with respect to calcium carbonate (CaCO3) particles. Here we estimate the in situ CaCO3 dissolution rates for the global oceans from total alkalinity and chlorofluorocarbon data, and we also discuss the future impacts of anthropogenic CO2 on CaCO3 shell–forming species. CaCO3 dissolution rates, ranging from 0.003 to 1.2 micromoles per kilogram per year, are observed beginning near the aragonite saturation horizon. The total water column CaCO3 dissolution rate for the global oceans is approximately 0.5 ± 0.2 petagrams of CaCO3-C per year, which is approximately 45 to 65% of the export production of CaCO3.
A hybrid Honey Bees Mating Optimization algorithm for the Probabilistic Traveling Salesman Problem

The Probabilistic Traveling Salesman Problem is a variation of the classic Traveling Salesman Problem and one of the most significant stochastic routing problems. In this paper, a new hybrid algorithmic nature inspired approach based on Honey Bees Mating Optimization (HBMO), Greedy Randomized Adaptive Search Procedure (GRASP) and Expanding Neighborhood Search Strategy (ENS) is proposed for the solution of the Probabilistic Traveling Salesman Problem. The proposed algorithm has two additional main innovative features compared to other Honey Bees Mating Optimization algorithms that concern the crossover operator and the workers. The proposed algorithm is tested on a numerous benchmark problems from TSPLIB with very satisfactory results. Comparisons with the classic GRASP algorithm, the Particle Swarm Optimization (PSO) algorithm and with a Tabu Search algorithm are also presented. Also, a comparison is performed with the results of a number of implementations of the Ant Colony Optimization algorithm from the literature and in 6 out of 10 cases the proposed algorithm gives a new best solution.
Regional lung volume changes during high-frequency oscillatory ventilation*

Objective: To investigate regional lung volume changes occurring during an inflation–deflation maneuver using high-frequency oscillatory ventilation. Design: Prospective animal trial. Setting: Animal research laboratory. Subjects: Six Yorkshire swine. Interventions: Electrical impedance tomography was used to quantify regional ventilation during high-frequency oscillatory ventilation. The electrical impedance tomography-derived center of ventilation was used to describe the distribution of regional ventilation, whereas spectral analysis was used to describe regional ventilation-induced impedance changes. Lung injury was induced using surfactant lavage. Animals were transitioned to high-frequency oscillatory ventilation and a slow inflation–deflation maneuver was performed by changing mean airway pressure by 5 cm H2O every 15 mins to a maximum mean airway pressure of 40 cm H2O. Measurements and Main Results: The induction of lung injury was associated with a significant shift of the center of ventilation toward nondependent areas and an increase in shunt fraction (p < .001). During the following inflation–deflation maneuver using high-frequency oscillatory ventilation, inflation was associated with a shift of the center of ventilation from nondependent to dependent areas. Center of ventilation was significantly correlated with the shunt fraction (p < .001). Analyzing different lung layers along the gravitational axis separately, nondependent lung areas showed significantly decreased regional ventilation-induced impedance changes at higher pressures, suggesting overdistension, whereas dependent lung areas showed increased impedance changes, suggesting recruitment. The reverse was observed during deflation (all p < .05). Conclusions: The center of ventilation during high-frequency oscillatory ventilation correlated with oxygenating efficiency as measured by the shunt fraction. Lung recruitment during high-frequency oscillatory ventilation produced a significant shift of regional ventilation toward dependent areas of the lung and led to overdistension of nondependent areas.
Evaluation of position of maxillary impacted canine and its effect on adjacent teeth - A correlation study between panoramic radiography and cone beam computed tomography

Aims and Objective: The present study was undertaken to evaluate the usefulness of panoramic radiograph in determining labiopalatal position of MIPC and its effect on permanent teeth by assessing the mesiodistal position of MIPC on panoramic radiograph and by correlating it with 3D position on CBCT. Methods: The designed study was a cross-sectional study enrolling total 60 patients of either sex with 76 impacted maxillary canines. Patients were divided into 2 groups based on age criteria i.e age groups: ? 15 years and >15 years. Evaluation of MIPC in both groups was done by digital panoramic radiograph and subjects were subjected to CBCT imaging for exact localization of MIPC and detection of root resorption of permanent incisors. The sector location on panoramic radiographs was compared with the labiopalatal position of impacted maxillary canines on CBCT. The statistical correlation between panoramic and CBCT findings was examined using the Pearsons Chi-square test. Results: Most of the positions of MIPC were labial (35%), followed by palatal (34%) and mid-alveolus (30%). Labial MIPC on CBCT were more frequent in sectors 1, 2 and 3 and palatal MIPC were more frequent in sector 4 and 5 on panoramic radiographs. Distribution of mid-alveolus canines showed great variation with most of them located in sector 1 and 5. Root resorption of permanent incisors (28.94%) was observed in sectors 3, 4 and 5. Conclusions: The present study recommended that labiopalatal position of MIPC and resorption of permanent incisors might be predicted using sector location on panoramic radiography.
Reducing Mismatch in Training of DNN-Based Glottal Excitation Models in a Statistical Parametric Text-to-Speech System

Neural network-based models that generate glottal excitation waveforms from acoustic features have been found to give improved quality in statistical parametric speech synthesis. Until now, however, these models have been trained separately from the acoustic model. This creates mismatch between training and synthesis, as the synthesized acoustic features used for the excitation model input differ from the original inputs, with which the model was trained on. Furthermore, due to the errors in predicting the vocal tract ﬁlter, the original excitation waveforms do not provide perfect reconstruction of the speech waveform even if predicted without error. To address these issues and to make the excitation model more robust against errors in acoustic modeling, this paper proposes two modiﬁca-tions to the excitation model training scheme. First, the excitation model is trained in a connected manner, with inputs generated by the acoustic model. Second, the target glottal wave-forms are re-estimated by performing glottal inverse ﬁltering with the predicted vocal tract ﬁlters. The results show that both of these modiﬁcations improve performance measured in MSE and MFCC distortion, and slightly improve the subjective quality of the synthetic speech.
CONTRACTILE PROPERTIES OF A HIGH-FREQUENCY MUSCLE FROM A CRUSTACEAN - MECHANICAL POWER OUTPUT

The mechanical power output during oscillatory contraction was determined for the flagellum abductor muscle of the crab Carcinus maenas using the work loop technique. Measurements were made at 10 Hz, which is the normal operating frequency of the muscle. The temperature was 15 °C. Increasing the number of stimuli per cycle (given at an interstimulus interval of 3.3 ms) decreased the number of cycles required to reach a work plateau and increased the work per cycle at the plateau to a maximum at 4­5 stimuli per cycle. The maximum mechanical power output was 9.7 W kg-1 muscle (about 26 W kg-1 myofibril). The optimum strain for work output (5.7 %) was close to the estimated muscle strain in vivo (5.2 %).
Efficacy of BAL5788, a Prodrug of Cephalosporin BAL9141, in a Mouse Model of Acute Pneumococcal Pneumonia

ABSTRACT BAL5788 is a water-soluble prodrug of BAL9141, a new broad-spectrum cephalosporin with high levels of in vitro activity against methicillin- and vancomycin-resistant staphylococci and penicillin-resistant streptococci. In plasma BAL5788 is rapidly converted to BAL9141. We studied the activity of BAL5788 in a mouse model of acute pneumococcal pneumonia. Leukopenic female Swiss albino mice were challenged intratracheally with 107 CFU of clinical Streptococcus pneumoniae strains P-52181 (Pens Cros Ctxs), P-15986 (Penr Cros Ctxs), P-40422 (Penr Cror Ctxr), and P-40984 (Penr Cror Ctxr). Infected mice received subcutaneous (s.c.) injections of BAL5788 or ceftriaxone starting 3 h after pneumococcal challenge. Uninfected nonleukopenic mice received single s.c. doses of BAL5788 to determine the BAL9141 concentration-time profiles in serum and lungs. Untreated control mice died within 5 days postinfection. Ten-day cumulative survival rates for infected mice receiving BAL5788 (total daily doses of BAL9141 equivalents, 2.1 to 75 mg/kg of body weight) ranged from 57 to 100%, whereas with ceftriaxone (total daily doses, 10 to 400 mg/kg), the survival rates varied between 13 and 100%. In mice infected with P-15986, the survival rates achieved with BAL5788 (BAL9141 equivalent, 8.4 mg/kg) and those achieved with ceftriaxone (50 mg/kg) were significantly different (93 versus 13%; P < 0.0001) in favor of BAL5788; the outcomes of the trials with all other strains were not significantly different between the two antibiotics, but markedly lower doses of BAL5788 than ceftriaxone were required to obtain similar survival rates. Pharmacokinetic data showed that BAL9141 was effective against the four pneumococcal strains tested at very low values of the time above the MIC (T > MIC), which ranged from 9 to 18% of the dosing interval, whereas the values of T > MICs for ceftriaxone ranged from 30 to 50% of the dosing interval.
Single-ended 6T sub-threshold SRAM with horizontal local bit-lines

This study presents a novel SRAM architecture focused on minimizing area utilization for sub- and near-threshold operation in ultra-low power applications. This new architecture utilizes a modified 6T SRAM cell, introduces horizontal bit-lines, mitigates half-select disturb, and supports bit-interleaving. The proposed design's stability was thoroughly tested in the presence of process, temperature, and voltage variations and compared to the standard 6T and traditional 8T cells. A 32kb SRAM block implementing the proposed architecture was designed, simulated, and compared to a traditional 8T SRAM cell block. The results show that the proposed design has lower power consumption than the 8T SRAM block, comparable read performance, and better write performance. This was all achieved while only having a 10% increase in area per bit over the conventional 6T thin-cell layout.