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The phosphatidylinositol 3-kinase (PI3K)/Akt pathway integrates environmental clues to regulate cell growth and survival. We showed previously that depriving cells of a single essential amino acid rapidly and reversibly arrests purine synthesis. Here we demonstrate that amino acids via mammalian target of rapamycin 2 and IκB kinase regulate Akt activity and Akt association and phosphorylation of transketolase (TKT), a key enzyme of the nonoxidative pentose phosphate pathway (PPP). Akt phosphorylates TKT on Thr382, markedly enhancing enzyme activity and increasing carbon flow through the nonoxidative PPP, thereby increasing purine synthesis. Mice fed a lysine-deficient diet for 2 days show decreased Akt activity, TKT activity, and purine synthesis in multiple organs. These results provide a mechanism whereby Akt coordinates amino acid availability with glucose utilization, purine synthesis, and RNA and DNA synthesis.
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Aminoácidos/fisiologia , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas c-akt/metabolismo , Purinas/biossíntese , Transcetolase/metabolismo , Sequência de Aminoácidos , Animais , Sequência Conservada , Células HeLa , Humanos , Quinase I-kappa B/metabolismo , Masculino , Alvo Mecanístico do Complexo 2 de Rapamicina , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Complexos Multiproteicos/metabolismo , Oxirredução , Fosforribosil Pirofosfato/biossíntese , Fosforilação , Serina-Treonina Quinases TOR/metabolismoRESUMO
Obstacle detection is an essential task for the autonomous navigation by robots. The task becomes more complex in a dynamic and cluttered environment. In this context, the RGB-D camera sensor is one of the most common devices that provides a quick and reasonable estimation of the environment in the form of RGB and depth images. This work proposes an efficient obstacle detection and tracking method using depth images to facilitate quick dynamic obstacle detection. To achieve early detection of dynamic obstacles and stable estimation of their states, as in previous methods, we applied a u-depth map for obstacle detection. Unlike existing methods, the present method provides dynamic thresholding facilities on the u-depth map to detect obstacles more accurately. Here, we propose a restricted v-depth map technique, using post-processing after the u-depth map processing to obtain a better prediction of the obstacle dimension. We also propose a new algorithm to track obstacles until they are within the field of view (FOV). We evaluate the performance of the proposed system on different kinds of data sets. The proposed method outperformed the vision-based state-of-the-art (SoA) methods in terms of state estimation of dynamic obstacles and execution time.
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Procedimentos Cirúrgicos Robóticos , Robótica , Algoritmos , Robótica/métodosRESUMO
Background and Objectives: The elicitation of a host's immune−inflammatory responses to overcome oral bacterial biofilm challenges is mediated by numerous cytokines. We explored the role of three such cytokines, viz. interleukin (IL)-17, 18 and 21, by measuring their levels in the gingival crevicular fluid (GCF) of Indian individuals with healthy gingiva, chronic gingivitis, or chronic periodontitis. Materials and Method: Ninety systemically healthy individuals were enrolled in the study on the basis of predefined criteria and were categorized into three groups of 30 participants each. Groups A, B and C were composed of a control group with healthy gingiva, subjects with chronic gingivitis and subjects with chronic periodontitis, respectively. The periodontal disease status was assessed on the basis of a subject's gingival index, probing pocket depth, clinical attachment loss and radiographic evidence of bone loss. After the complete history-taking and identification of gingival sulcus/pocket depth areas for GCF collection, a sample was collected from each subject in all groups for an estimation of the cytokine levels using ELISA. Statistical analysis was performed using SPSS v 21.0. Intergroup comparisons were conducted using a post hoc Tukey's test. A value of p < 0.05 was considered to be statistically significant. Results: The mean IL-17, 18 and 21 concentrations in pg/mL was the greatest for Group C (99.67 ± 18.85, 144.61 ± 20.83 and 69.67 ± 12.46, respectively), followed by Group B (19.27 ± 2.78, 22.27 ± 2.43 and 22.74 ± 1.43, respectively) and finally by Group A (healthy control; 11.56 ± 0.99, 17.94 ± 1.24 and 12.83 ± 1.21 respectively). A statistically significant difference in the mean concentrations of two interleukins (IL-17 and IL-18) was observed between Groups A and C and also between Groups B and C. A statistically significant difference in the mean concentrations of IL-21 was observed between Groups B and C. Conclusions: Within the limitations of the present study, the findings revealed that the GCF levels of IL-17, IL-18 and IL-21 rose and correlated well with the severity of the disease. Thus, these cytokines present in GCF have the potential to be considered as biomarkers for periodontal tissue destruction. IL-21 in particular appears to be a promising biomarker for differentiating between gingivitis and periodontitis.
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Periodontite Crônica , Gengivite , Biomarcadores/análise , Citocinas/análise , Líquido do Sulco Gengival/química , Humanos , Interleucina-17/análise , Interleucina-18 , Perda da Inserção PeriodontalRESUMO
Using a system of two FitzHugh-Nagumo units, we demonstrate the occurrence of riddled basins of attraction in delay-coupled systems as the coupling between the units is increased. We characterize riddled basins using the uncertainty exponent which is a measure of the dimensions of the basin boundary. Additionally, we show that the phase space can be partitioned into pure and mixed regions, where initial conditions in the pure regions certainly avoid the generation of extreme events, while initial conditions in the mixed region may or may not exhibit such events. This implies that any tiny perturbation of initial conditions in the mixed region could yield the emergence of extreme events because the latter state possesses a riddled basin of attraction.
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We study numerically the dynamics of a network of all-to-all-coupled, identical sub-networks consisting of diffusively coupled, non-identical FitzHugh-Nagumo oscillators. For a large range of within- and between-network couplings, the network exhibits a variety of dynamical behaviors, previously described for single, uncoupled networks. We identify a region in parameter space in which the interplay of within- and between-network couplings allows for a richer dynamical behavior than can be observed for a single sub-network. Adjoining this atypical region, our network of networks exhibits transitions to multistability. We elucidate bifurcations governing the transitions between the various dynamics when crossing this region and discuss how varying the couplings affects the effective structure of our network of networks. Our findings indicate that reducing a network of networks to a single (but bigger) network might not be accurate enough to properly understand the complexity of its dynamics.
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Multifunctional ZnFe2O4 nanoparticles were successfully synthesized via thermolysis of Fe-oleate and Zn-oleate precursors. Monodisperse, single phase ZnFe2O4 nanoparticles with an average particle size of â¼22 nm, exhibiting green emission (λmaxâ¼ 480 nm) and ferromagnetism at room temperature (saturation magnetization of 48.46 emu gm(-1)) have been formed by this novel approach. By appropriate surface functionalization, these materials have been converted into smart carriers of hydrophobic (water insoluble) drug molecule-curcumin and hydrophilic (water soluble) drug molecule-daunorubicin. The in vitro cytotoxicity of both the hydrophobic and hydrophilic drug loaded ZnFe2O4 nanoparticles was studied using the conventional MTT assay which revealed that the drug loaded nanoparticles induce significant death of the carcinoma cells (HeLa). Interestingly, this appears to be a significant development towards the capability of surface functionalized multifunctional ZnFe2O4 nanoparticles as carriers for both water soluble and insoluble drugs for anti-cancer therapy.
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Understanding of nanoparticle-membrane interactions is useful for various applications of nanoparticles like drug delivery and imaging. Here we report on the studies of interaction between hydrophilic charged polymer coated semiconductor quantum dot nanoparticles with model lipid membranes. Atomic force microscopy and X-ray reflectivity measurements suggest that cationic nanoparticles bind and penetrate bilayers of zwitterionic lipids. Penetration and binding depend on the extent of lipid packing and result in the disruption of the lipid bilayer accompanied by enhanced lipid diffusion. On the other hand, anionic nanoparticles show minimal membrane binding although, curiously, their interaction leads to reduction in lipid diffusivity. It is suggested that the enhanced binding of cationic QDs at higher lipid packing can be understood in terms of the effective surface potential of the bilayers which is tunable through membrane lipid packing. Our results bring forth the subtle interplay of membrane lipid packing and electrostatics which determine nanoparticle binding and penetration of model membranes with further implications for real cell membranes.
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Compostos de Cádmio/química , Lipídeos de Membrana/química , Membranas Artificiais , Nanopartículas/química , Polímeros/química , Compostos de Selênio/química , Eletricidade Estática , Sulfetos/química , Compostos de Zinco/química , Sítios de Ligação , Modelos Moleculares , Pontos QuânticosRESUMO
BACKGROUND: Most patients presenting with symptoms of esophageal cancer (EC) have advanced disease. Even with resection, the cure rate is extremely low due to local recurrence and metastatic disease. Early detection and effective therapeutic intervention are essential to improve survival. AIMS: This study tested the hypothesis that the presence of EC modulates concentrations of specific plasma proteins and peptides, potentially allowing discrimination between EC and controls based on mass spectrometric analysis of the respective plasma proteomes. METHODS: Blood samples from 79 esophageal cancer patients and 40 age-matched normal subjects were processed to plasma, and protein/peptide sub-fractions were isolated using HIC8 or WAX-derivatized superparamagnetic beads. Triplicate matrix-assisted laser desorption time-of-flight mass spectra were acquired for specific plasma fractions from each subject. RESULTS: HIC8 and WAX-derivatized plasma eluates yielded 79 and 77 candidate features, respectively, and a Random Forest algorithm identified a subset of features whose peak intensities allowed discrimination between cancer patients and controls. Areas under the curve in receiver operating characteristic curves for HIC8 spectra were 0.88 and 0.83 for WAX spectra. The combined feature set discriminated EC from control plasma with 79 % sensitivity and 79 % specificity, with positive and negative test likelihood ratios of >14 and 0.17, respectively. CONCLUSIONS: These data lay the foundation for the development of a clinically useful test for esophageal cancer based on statistical analysis of proteomic spectra of patient plasma samples. This approach will be validated by analysis of larger patient cohorts, development of cancer-specific classifiers, and assessment of racial origin imbalances.
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Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Esofágicas/sangue , Proteômica/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
Cells must increase synthesis of purine nucleotides/deoxynucleotides before or during S-phase. We found that rates of purine synthesis via the de novo and salvage pathways increased 5.0- and 3.3-fold respectively, as cells progressed from mid-G1-phase to early S-phase. The increased purine synthesis could be attributed to a 3.2-fold increase in intracellular PRPP (5-phosphoribosyl-α-1-pyrophosphate), a rate-limiting substrate for de novo and salvage purine synthesis. PRPP can be produced by the oxidative and non-oxidative pentose phosphate pathways, and we found a 3.1-fold increase in flow through the non-oxidative pathway, with no change in oxidative pathway activity. Non-oxidative pentose phosphate pathway enzymes showed no change in activity, but PRPP synthetase is regulated by phosphate, and we found that phosphate uptake and total intracellular phosphate concentration increased significantly between mid-G1-phase and early S-phase. Over the same time period, PRPP synthetase activity increased 2.5-fold when assayed in the absence of added phosphate, making enzyme activity dependent on cellular phosphate at the time of extraction. We conclude that purine synthesis increases as cells progress from G1- to S-phase, and that the increase is from heightened PRPP synthetase activity due to increased intracellular phosphate.
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Ciclo Celular/fisiologia , Fosfatos/fisiologia , Fosforribosil Pirofosfato/fisiologia , Purinas/biossíntese , Ribose-Fosfato Pirofosfoquinase/metabolismo , Animais , Células COS , Chlorocebus aethiops , Células HCT116 , HumanosRESUMO
Three Pt(II)-bis(quinolinyl) complexes with varying electron densities were synthesized, structurally characterized and used for photocatalytic hydrogen production under different conditions. All the complexes were found to be active for hydrogen production giving a maximum turnover number (TON) of 1230 surpassing the conventionally used Pt-terpyridyl complexes.
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Background: This study aimed to compare the effectiveness of laser-assisted periodontal therapy (LAPT) with conventional scaling and root planing (CSRP) in the treatment of periodontal disease. The objective was to assess the outcomes of these two treatments on a sample of 30 patients in each group. Materials and Methods: In this study, a total of 60 patients diagnosed with periodontal disease were divided into two groups: the LAPT group and the CSRP group, with 30 patients in each group. The LAPT group received periodontal treatment using laser therapy, while the SRP group underwent traditional SRP. The patients were evaluated for periodontal parameters, including probing depth and clinical attachment level before and after the treatments. Results: After the treatment interventions, both the LAPT group and the CSRP group showed significant improvements in periodontal health. The mean reduction in probing depth was 2.5 mm in the LAPT group and 2.2 mm in the SRP group. In addition, the clinical attachment level increased by 2.8 mm in the LAPT group and 2.5 mm in the SRP group. Statistical analysis using the paired t-test demonstrated a P-value of less than 0.05, indicating the significance of these improvements in both groups. Conclusion: This study suggests that both LAP and CSRP are effective in improving periodontal health in patients with periodontal disease.
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Glutathione (GSH) and oxidized glutathione (GSSG) control cellular function and efficiency of anticancer therapy. Reliable detection of cellular GSH/GSSG is challenging due to their ultralow concentration (typically femtomolar concentrations) and interference by other thiol-based molecules. Here, we report a "turn-off" surface enhanced Raman scattering (SERS)-based approach for reliable detection of cellular GSH and GSSG. This approach exploits GSH-induced replacement of a Raman probe from the surface of γ-Fe2O3-Au followed by Ag growth around γ-Fe2O3-Au that generates electromagnetic hot spots at the junction between Au and Ag where the Raman probe is localized. The magnetic component of the hybrid nanoparticle concentrates the cellular GSH, and the Au/Ag-based plasmonic component provides electromagnetic hot spots for sensitive SERS. This approach is able to monitor GSH level during photothermal cancer therapy.
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Glutationa/análise , Nanopartículas de Magnetita/química , Nanocompostos/química , Animais , Células CHO , Cricetulus , Células HeLa , Humanos , Oxirredução , Tamanho da Partícula , Análise Espectral Raman , Propriedades de SuperfícieRESUMO
Multivalency of nanoparticle and associated cooperative binding with biological interface is an important aspect in the development of nanoparticle based bioimaging probes. However, the preparation of such a nanobioconjugate with a controlled number of biomolecules per nanoparticle, typically between 1 and 100, is challenging. Here we report a generalized two-step bioconjugation method to prepare nanobioconjugates with a varied average number of biomolecules between 1 to 100 per nanoparticle that can be applied to different nanoparticles and biomolecules. Following this approach we have successfully synthesized quantum dot (QD) based bioconjugates with controlled average numbers of glucose or folate and found their number-dependent interaction with proteins and cells. We propose a method for exploiting the nanoparticle multivalency effect toward various biological interactions and preparing such nanobioconjugates for best performance.
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Glicoproteínas/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Nanotecnologia/métodos , Aminas/química , Transporte Biológico , Ácido Fólico/química , Glucose/química , Glicina/química , Células HeLa , Humanos , Ligação Proteica , Pontos QuânticosRESUMO
Background: The risk factors for ectopic pregnancy are on the rise. Despite the progress (availability of serum ßhCG, USG and MRI), there are diagnostic and therapeutic challenges in the management. Up to 50% of ectopic pregnancies go undetected. Furthermore, cases seen as emergency with hemodynamic instability need urgent intervention with simultaneous arrangement of transport, blood transfusion and at times multidisciplinary team involvement. This is more challenging in a setting where resources are limited. Objective: To evaluate the outcome of women presenting with uncommon ectopic pregnancies as life-threatening emergency. Challenges encountered in diagnosis, pre-operative evaluation, decision for surgery and the procedure are presented. Patients and Methods: This is a series of twelve cases of uncommon ectopic pregnancies belonging to eight different types. These were managed under the first author during the period 2001 to 2019. Subjects were analyzed retrospectively. Results: Diagnostic dilemma was faced in majority of the cases even with the use of ultrasonography. All the conceptions were spontaneous. Emergency surgical interventions were made on the basis of clinical evaluation. Five cases presented with massive hemoperitoneum. Blood transfusion was needed in nine cases. There was no mortality. One woman (case 4), with abdominal pregnancy, went home with a live baby, after the second laparotomy. Conclusion: Uncommon ectopic pregnancies are life-threatening conditions. Clinical acumen and an alert mind are of superior value in diagnosis. Investigations are supportive. Early diagnosis and intervention are lifesaving.
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We present our agent-based CoronAvirus Lifelong Modelling and Simulation (CALMS) model that aspires to predict the lifelong impacts of Covid-19 on the health and economy of a population. CALMS considers individual characteristics as well as comorbidities in calculating the risk of infection and severe disease. We conduct two sets of experiments aiming at demonstrating the validity and capabilities of CALMS. We run simulations retrospectively and validate the model outputs against hospitalisations, ICU admissions and fatalities in a UK population for the period between March and September 2020. We then run simulations for the lifetime of the cohort applying a variety of targeted intervention strategies and compare their effectiveness against the baseline scenario where no intervention is applied. Four scenarios are simulated with targeted vaccination programmes and periodic lockdowns. Vaccinations are targeted first at individuals based on their age and second at vulnerable individuals based on their health status. Periodic lockdowns, triggered by hospitalisations, are tested with and without vaccination programme in place. Our results demonstrate that periodic lockdowns achieve reductions in hospitalisations, ICU admissions and fatalities of 6-8% compared to the baseline scenario, with an associated intervention cost of £173 million per 1,000 people and targeted vaccination programmes achieve reductions in hospitalisations, ICU admissions and fatalities of 89-90%, compared to the baseline scenario, with an associated intervention cost of £51,924 per 1,000 people. We conclude that periodic lockdowns alone are ineffective at reducing health-related outputs over the long-term and that vaccination programmes which target only the clinically vulnerable are sufficient in providing healthcare protection for the population as a whole.
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COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis , Hospitalização , Humanos , Estudos Retrospectivos , VacinaçãoRESUMO
BACKGROUND & AIMS: Infection with Helicobacter pylori represses expression of the gastric H, K-adenosine triphosphatase alpha-subunit (HKalpha), which could contribute to transient hypochlorhydria. CagL, a pilus protein component of the H pylori type IV secretion system, binds to the integrin alpha(5)beta1 to mediate translocation of virulence factors into the host cell and initiate signaling. alpha(5)beta1 binds a disintegrin and metalloprotease (ADAM) 17, a metalloenzyme that catalyzes ectodomain shedding of receptor tyrosine kinase ligands. We investigated whether H pylori-induced repression of HKalpha is mediated by CagL activation of ADAM17 and release of heparin-binding epidermal growth factor (HB-EGF). METHODS: HKalpha promoter and ADAM17 activity were measured in AGS gastric epithelial cells transfected with HKalpha promoter-reporter constructs or ADAM17-specific small interfering RNAs and infected with H pylori. HB-EGF secretion was measured by enzyme-linked immunosorbent assay analysis, and ADAM17 interaction with integrins was investigated by coimmunoprecipitation analyses. RESULTS: Infection of AGS cells with wild-type H pylori or an H pylori cagL-deficient isogenic mutant that also contained a wild-type version of cagL (P12DeltacagL/cagL) repressed HKalpha promoter-Luc reporter activity and stimulated ADAM17 activity. Both responses were inhibited by point mutations in the nuclear factor-kappaB binding site of HKalpha or by infection with P12DeltacagL. Small interfering RNA-mediated silencing of ADAM17 in AGS cells inhibited the repression of wild-type HKalpha promoter and reduced ADAM17 activity and HB-EGF production, compared to controls. Coimmunoprecipitation studies of AGS lysates showed that wild-type H pylori disrupted ADAM17-alpha5beta1 complexes. CONCLUSIONS: During acute H pylori infection, CagL dissociates ADAM17 from the integrin alpha(5)beta1 and activates ADAM17-dependent, nuclear factor-kappaB-mediated repression of HKalpha. This might contribute to transient hypochlorhydria in patients with H pylori infection.
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Proteínas ADAM/fisiologia , Helicobacter pylori/fisiologia , ATPase Trocadora de Sódio-Potássio/genética , Estômago/enzimologia , Proteína ADAM17 , Repressão Enzimática , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Humanos , Integrina beta1/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Oligopeptídeos/fisiologia , Regiões Promotoras Genéticas , ATPase Trocadora de Sódio-Potássio/biossínteseRESUMO
BACKGROUND AND AIMS: Helicobacter pylori infection of gastric mucosa causes gastritis and transient hypochlorhydria, which may provoke emergence of a mucosal precancer phenotype; H pylori strains containing a cag pathogenicity island (PAI) augment cancer risk. Acid secretion is mediated by the catalytic alpha subunit of parietal cell H,K-ATPase (HKalpha). In AGS gastric epithelial cells, H pylori induces nuclear factor-kappaB (NF-kappaB) binding to and repression of transfected HKalpha promoter activity. This study sought to identify bacterial genes involved in HKalpha repression and to assess their impact on acid secretion. METHODS AND RESULTS: AGS cells transfected with an HKalpha promoter construct or human gastric body biopsies were infected with wild-type (wt) or isogenic mutant (IM) H pylori strains. AGS cell HKalpha promoter activity, and biopsy HKalpha mRNA, protein and H(+) secretory activity were measured by luminometry, reverse transcription-PCR, immunoblotting and extracellular acidification, respectively. Wt H pylori and DeltavacA, DeltaureA, Deltaslt and DeltaflaA IM strains repressed HKalpha promoter activity by approximately 50%, a DeltacagA IM strain repressed HKalpha by approximately 33%, and DeltacagE, DeltacagM and DeltacagL IM strains elicited no HKalpha repression. Wt H pylori-infected biopsies had markedly reduced HKalpha mRNA and protein compared with IM strain infections or mock-infected controls. Histamine-stimulated, SCH28080-sensitive biopsy acid secretion was significantly inhibited by wt but not by DeltacagL IM H pylori infection compared with vehicle-only controls. CONCLUSIONS: It is concluded that H pylori cag PAI gene products CagE, CagM, CagL and, possibly, CagA are mechanistically involved in repression of HKalpha transcription. Further, acute H pylori infection of human gastric mucosa downregulates parietal cell H,K-ATPase expression, significantly inhibiting acid secretion.
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Ácido Gástrico/metabolismo , Mucosa Gástrica/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/genética , Infecções por Helicobacter/metabolismo , Helicobacter pylori/patogenicidade , Bombas de Próton/metabolismo , Adulto , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Mucosa Gástrica/microbiologia , Genes Bacterianos , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Técnicas de Cultura de Tecidos , Células Tumorais Cultivadas , Virulência/genética , Adulto JovemRESUMO
We have developed a reversible, biocompatible, "self-programmed" PLGA [poly(lactic-co-glycolic acid)] nanoparticle-based optical biosensor capable of sensing and continuous monitoring of glucose above the physiologically relevant threshold value (100-125 mg/dL) as well as "on-demand" insulin delivery via an "On-Off" technique. We have carefully surface engineered the PLGA nanoparticle using amino dextran-fluorescein (A-DexFl) and amino-phenyl boronic acid (A-PBA) to exploit the binding affinity of boronic acids with that of cis-1,2 diols of dextran/glucose. Initially, the dextran chains wrap the nanoparticle surface due to its high affinity toward A-PBA (Kb = 6.1 × 106 M-1). The close proximity of the fluorophores with that of A-PBA quenches the fluorescence, resulting in an "Off" state. On the addition of glucose, it competes with A-DexFl to bind with A-PBA. Above a certain threshold concentration of glucose, the binding affinity overcomes (Kb = 6.3 × 107 M-1) the dextran-A-PBA binding. This opens-up the wrapped A-DexFl chains from the nanoparticle surface and results in an increased distance between the fluorophore and A-PBA, triggering the "On" state. The activation of the On-Off state can be finely tuned in the desired range of physiologically relevant glucose concentrations by varying the ligand ratios on the PLGA surface. The nanoparticle core has also been used as an insulin reservoir to trigger the drug release in the "On" state. We have obtained â¼53% encapsulation efficiency and â¼20% loading efficiency for insulin loading. Once the glucose concentration falls beyond the detection range, the dextran chains collapse on the nanoparticle surface with a suspension in drug release. The process is solely controlled by the competition and multivalent binding affinity between glucose, A-DexFl, and A-PBA, which allows it to be "self-programmed" and "self-regulated" with continuous monitoring up to 8-10 cycles over a 72 h time period. A sustained drug release has been found with â¼70% of released drug over a period of 72 h, although this release is insignificant in the absence of glucose. Several control experiments have been performed to optimize the sensor design.
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Insulina , Nanopartículas , Glicemia , Automonitorização da Glicemia , GlucoseRESUMO
Node counting on a graph is subject to some fundamental theoretical limitations, yet a solution to such problems is necessary in many applications of graph theory to real-world systems, such as collective robotics and distributed sensor networks. Thus several stochastic and naïve deterministic algorithms for distributed graph size estimation or calculation have been provided. Here we present a deterministic and distributed algorithm that allows every node of a connected graph to determine the graph size in finite time, if an upper bound on the graph size is provided. The algorithm consists in the iterative aggregation of information in local hubs which then broadcast it throughout the whole graph. The proposed node-counting algorithm is on average more efficient in terms of node memory and communication cost than its previous deterministic counterpart for node counting, and appears comparable or more efficient in terms of average-case time complexity. As well as node counting, the algorithm is more broadly applicable to problems such as summation over graphs, quorum sensing, and spontaneous hierarchy creation.
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Algoritmos , Memória , Percepção de QuorumRESUMO
To effectively perform collective monitoring of dynamic environments, a robot swarm needs to adapt to changes by processing the latest information and discarding outdated beliefs. We show that in a swarm composed of robots relying on local sensing, adaptation is better achieved if the robots have a shorter rather than longer communication range. This result is in contrast with the widespread belief that more communication links always improve the information exchange on a network. We tasked robots with reaching agreement on the best option currently available in their operating environment. We propose a variety of behaviors composed of reactive rules to process environmental and social information. Our study focuses on simple behaviors based on the voter model-a well-known minimal protocol to regulate social interactions-that can be implemented in minimalistic machines. Although different from each other, all behaviors confirm the general result: The ability of the swarm to adapt improves when robots have fewer communication links. The average number of links per robot reduces when the individual communication range or the robot density decreases. The analysis of the swarm dynamics via mean-field models suggests that our results generalize to other systems based on the voter model. Model predictions are confirmed by results of multiagent simulations and experiments with 50 Kilobot robots. Limiting the communication to a local neighborhood is a cheap decentralized solution to allow robot swarms to adapt to previously unknown information that is locally observed by a minority of the robots.