Data-driven discovery of stochastic dynamical equations of collective motion.

Coarse-grained descriptions of collective motion of flocking systems are often derived for the macroscopic or the thermodynamic limit. However, the size of many real flocks falls within 'mesoscopic' scales (10 to 100 individuals), where stochasticity arising from the finite flock sizes is important. Previous studies on mesoscopic models have typically focused on non-spatial models. Developing mesoscopic scale equations, typically in the form of stochastic differential equations, can be challenging even for the simplest of the collective motion models that explicitly account for space. To address this gap, here, we take a novel data-driven equation learning approach to construct the stochastic mesoscopic descriptions of a simple, spatial, self-propelled particle (SPP) model of collective motion. In the spatial model, a focal individual can interact withkrandomly chosen neighbours within an interaction radius. We considerk = 1 (called stochastic pairwise interactions),k = 2 (stochastic ternary interactions), andkequalling all available neighbours within the interaction radius (equivalent to Vicsek-like local averaging). For the stochastic pairwise interaction model, the data-driven mesoscopic equations reveal that the collective order is driven by a multiplicative noise term (hence termed, noise-induced flocking). In contrast, for higher order interactions (k > 1), including Vicsek-like averaging interactions, models yield collective order driven by a combination of deterministic and stochastic forces. We find that the relation between the parameters of the mesoscopic equations describing the dynamics and the population size are sensitive to the density and to the interaction radius, exhibiting deviations from mean-field theoretical expectations. We provide semi-analytic arguments potentially explaining these observed deviations. In summary, our study emphasises the importance of mesoscopic descriptions of flocking systems and demonstrates the potential of the data-driven equation discovery methods for complex systems studies.

Randomness in the choice of neighbours promotes cohesion in mobile animal groups.

Classic computational models of collective motion suggest that simple local averaging rules can promote many observed group-level patterns. Recent studies, however, suggest that rules simpler than local averaging may be at play in real organisms; for example, fish stochastically align towards only one randomly chosen neighbour and yet the schools are highly polarized. Here, we ask-how do organisms maintain group cohesion? Using a spatially explicit model, inspired from empirical investigations, we show that group cohesion can be achieved in finite groups even when organisms randomly choose only one neighbour to interact with. Cohesion is maintained even in the absence of local averaging that requires interactions with many neighbours. Furthermore, we show that choosing a neighbour randomly is a better way to achieve cohesion than interacting with just its closest neighbour. To understand how cohesion emerges from these random pairwise interactions, we turn to a graph-theoretic analysis of the underlying dynamic interaction networks. We find that randomness in choosing a neighbour gives rise to well-connected networks that essentially cause the groups to stay cohesive. We compare our findings with the canonical averaging models (analogous to the Vicsek model). In summary, we argue that randomness in the choice of interacting neighbours plays a crucial role in achieving cohesion.

Full Mouth Rehabilitation by Implant Supported Fixed Prosthesis.

The purpose of this study is to report a case of full-mouth rehabilitation on six endosseous implants loaded following the standard procedure. It was decided to insert six implants in the maxillary and six implants in the mandibular arch in a patient with no systemic disease. The surgery was performed with the patient under local anesthesia with lignocaine and 1:100,000 adrenaline. Implant stability was sufficient (35 N/cm measured with a torque spring) for all 12 implants. An impression is taken in the open tray with a silicone impression material. Vertical dimension for rest and occlusion was checked with wax occlusal rims placed in the mouth. Interocclusal records were made with the metal framework in place. The final restoration was realized with ceramic layering completed. Good impressions and meticulous attention to detail are crucial for a successful implant-supported fixed prosthesis.

Anisogamy selects for male-biased care in self-consistent games with synchronous matings.

We reexamine the influential parental investment hypothesis proposed by Trivers for the causal relationship between anisogamy and widespread female-biased parental care. We build self-consistent versions of Maynard Smith's simple evolutionary game between males and females over parental care, and incorporate consequences of anisogamy for gamete production and its trade-off with parental care, and for patterns of mate limitation. As male mating opportunities are limited by females, frequency-dependent selection acts on male strategies. Assuming synchrony of matings in the population, our analytical models find either symmetric sex roles or male-biased care as an evolutionarily stable strategy (ESS), in contrast to Trivers' hypothesis. We simulate evolution in asynchronously mating populations and find that diverse parental roles, including female care, can be ESS depending on the parameters. When caring males can also remate, or when females can increase the clutch size by deserting, there is stronger selection for male-biased care. Hence, we argue that the mating-caring trade-off for males is neither a necessary consequence of anisogamy nor sufficient to select for female-biased care. Instead, the factors excluded from our models-costly competitive traits, sexual selection, and partial parentage-may be necessary for the parental investment hypothesis to work.

Assessment of computer-controlled local anesthetic delivery system for pain control during restorative procedures: A randomized controlled trial.

Background. . Local anesthesia is given to decrease pain perception during dental treatments, but it may itself be a reason for pain and aggravate the dental fear. Computer-controlled local anesthetic delivery system (CCLADS) is one of the alternatives for decreasing the patients' pain during local anesthesia. This study compared the time required for the recovery from anesthesia, pain/discomfort during injection and pain/discomfort 24 hours after administering local anesthesia with CCLADS, a standard self-aspirating syringe and a conventional disposable 2-mL syringe. Methods. The study was conducted on 90 subjects (an age group of 20-40 years), who suffered from sensitivity during cavity preparation. They were randomly divided into three groups of 30 individuals each to receive intraligamentary anesthesia (2% lignocaine with 1:80,000 adrenaline) using either of the three techniques: CCLADS, a standard self-aspirating syringe, or a conventional disposable 2-mL syringe. The onset of anesthesia, time required for recovery from anesthesia (in minutes), pain/discomfort during injection and pain/discomfort 24 hours after administering local anesthesia were recorded. Results. The time required for the onset of anesthesia and recovery from anesthesia was shorter with CCLADS (4.83±2.31 and 34.2±1.895, respectively) as compared to the standard self-aspirating group (10.83±1.90 and 43.5±7.581, respectively) and the conventional group (11.00±2.03 and 43.5±6.453, respectively) (P<0.001). The patients in the CCLADS group experienced no pain during local anesthesia administration as compared to the patients in the self-aspirating and conventional groups. The CCLADS and self-aspirating groups showed lower pain response as compared to the conventional group for pain after 24 hours. Conclusion. CCLADS can be an effective and pain-free alternative to conventional local anesthetic procedures.

Porous Zero-Mode Waveguides for Picogram-Level DNA Capture.

We have recently shown that nanopore zero-mode waveguides are effective tools for capturing picogram levels of long DNA fragments for single-molecule DNA sequencing. Despite these key advantages, the manufacturing of large arrays is not practical due to the need for serial nanopore fabrication. To overcome this challenge, we have developed an approach for the wafer-scale fabrication of waveguide arrays on low-cost porous membranes, which are deposited using molecular-layer deposition. The membrane at each waveguide base contains a network of serpentine pores that allows for efficient electrophoretic DNA capture at picogram levels while eliminating the need for prohibitive serial pore milling. Here, we show that the loading efficiency of these porous waveguides is up to 2 orders of magnitude greater than their nanopore predecessors. This new device facilitates the scaling-up of the process, greatly reducing the cost and effort of manufacturing. Furthermore, the porous zero-mode waveguides can be used for applications that benefit from low-input single-molecule real-time sequencing.

Comparative Evaluation of Conventional and Accelerated Castings on Marginal Fit and Surface Roughness.

AIMS: The aim of this study was to evaluate the marginal fit and surface roughness of complete cast crowns made by a conventional and an accelerated casting technique. SETTINGS AND DESIGN: This study was divided into three parts. In Part I, the marginal fit of full metal crowns made by both casting techniques in the vertical direction was checked, in Part II, the fit of sectional metal crowns in the horizontal direction made by both casting techniques was checked, and in Part III, the surface roughness of disc-shaped metal plate specimens made by both casting techniques was checked. MATERIALS AND METHODS: A conventional technique was compared with an accelerated technique. In Part I of the study, the marginal fit of the full metal crowns as well as in Part II, the horizontal fit of sectional metal crowns made by both casting techniques was determined, and in Part III, the surface roughness of castings made with the same techniques was compared. STATISTICAL ANALYSIS USED: The results of the t-test and independent sample test do not indicate statistically significant differences in the marginal discrepancy detected between the two casting techniques. RESULTS: For the marginal discrepancy and surface roughness, crowns fabricated with the accelerated technique were significantly different from those fabricated with the conventional technique. CONCLUSIONS: Accelerated casting technique showed quite satisfactory results, but the conventional technique was superior in terms of marginal fit and surface roughness.

Length-independent DNA packing into nanopore zero-mode waveguides for low-input DNA sequencing.

Compared with conventional methods, single-molecule real-time (SMRT) DNA sequencing exhibits longer read lengths than conventional methods, less GC bias, and the ability to read DNA base modifications. However, reading DNA sequence from sub-nanogram quantities is impractical owing to inefficient delivery of DNA molecules into the confines of zero-mode waveguides-zeptolitre optical cavities in which DNA sequencing proceeds. Here, we show that the efficiency of voltage-induced DNA loading into waveguides equipped with nanopores at their floors is five orders of magnitude greater than existing methods. In addition, we find that DNA loading is nearly length-independent, unlike diffusive loading, which is biased towards shorter fragments. We demonstrate here loading and proof-of-principle four-colour sequence readout of a polymerase-bound 20,000-base-pair-long DNA template within seconds from a sub-nanogram input quantity, a step towards low-input DNA sequencing and mammalian epigenomic mapping of native DNA samples.

Single-molecule mechanics of protein-labelled DNA handles.

DNA handles are often used as spacers and linkers in single-molecule experiments to isolate and tether RNAs, proteins, enzymes and ribozymes, amongst other biomolecules, between surface-modified beads for nanomechanical investigations. Custom DNA handles with varying lengths and chemical end-modifications are readily and reliably synthesized en masse, enabling force spectroscopic measurements with well-defined and long-lasting mechanical characteristics under physiological conditions over a large range of applied forces. Although these chemically tagged DNA handles are widely used, their further individual modification with protein receptors is less common and would allow for additional flexibility in grabbing biomolecules for mechanical measurements. In-depth information on reliable protocols for the synthesis of these DNA-protein hybrids and on their mechanical characteristics under varying physiological conditions are lacking in literature. Here, optical tweezers are used to investigate different protein-labelled DNA handles in a microfluidic environment under different physiological conditions. Digoxigenin (DIG)-dsDNA-biotin handles of varying sizes (1000, 3034 and 4056 bp) were conjugated with streptavidin or neutravidin proteins. The DIG-modified ends of these hybrids were bound to surface-modified polystyrene (anti-DIG) beads. Using different physiological buffers, optical force measurements showed consistent mechanical characteristics with long dissociation times. These protein-modified DNA hybrids were also interconnected in situ with other tethered biotinylated DNA molecules. Electron-multiplying CCD (EMCCD) imaging control experiments revealed that quantum dot-streptavidin conjugates at the end of DNA handles remain freely accessible. The experiments presented here demonstrate that handles produced with our protein-DNA labelling procedure are excellent candidates for grasping single molecules exposing tags suitable for molecular recognition in time-critical molecular motor studies.

Tipping off endothelial tubes: nitric oxide drives tip cells.

Angiogenesis, the formation of new blood vessels from pre-existing vessels, is a complex process that warrants cell migration, proliferation, tip cell formation, ring formation, and finally tube formation. Angiogenesis is initiated by a single leader endothelial cell called "tip cell," followed by vessel elongation by "stalk cells." Tip cells are characterized by their long filopodial extensions and expression of vascular endothelial growth factor receptor-2 and endocan. Although nitric oxide (NO) is an important modulator of angiogenesis, its role in angiogenic sprouting and specifically in tip cell formation is poorly understood. The present study tested the role of endothelial nitric oxide synthase (eNOS)/NO/cyclic GMP (cGMP) signaling in tip cell formation. In primary endothelial cell culture, about 40% of the tip cells showed characteristic sub-cellular localization of eNOS toward the anterior progressive end of the tip cells, and eNOS became phosphorylated at serine 1177. Loss of eNOS suppressed tip cell formation. Live cell NO imaging demonstrated approximately 35% more NO in tip cells compared with stalk cells. Tip cells showed increased level of cGMP relative to stalk cells. Further, the dissection of NO downstream signaling using pharmacological inhibitors and inducers indicates that NO uses the sGC/cGMP pathway in tip cells to lead angiogenesis. Taken together, the present study confirms that eNOS/NO/cGMP signaling defines the direction of tip cell migration and thereby initiates new blood vessel formation.

Nitric oxide protects endothelium from cadmium mediated leakiness.

Cadmium targets the vascular endothelium causing endothelial dysfunction and leakiness of endothelial barrier. Nitric oxide plays a major role in mediating endothelial functions including angiogenesis, migration and permeability. The present study investigates the nitric oxide effects on cadmium induced endothelial leakiness. Results of ex vivo and in vitro permeability assays showed that even a sub-lethal dose of cadmium chloride (1 µM) was sufficient to induce leakiness of endothelial cells. Cadmium drastically altered the actin polymerisation pattern and membrane tension of these cells compared to controls. Addition of nitric oxide donor Spermine NONOate (SP) significantly blunted cadmium-mediated effects and recover endothelial cells integrity. Cadmium-induced cytoskeletal rearrangements and membrane leakiness are associated with the low nitric oxide availability and high reactive oxygen species generation. In brief, we show the protective role of nitric oxide against cadmium-mediated endothelial leakiness.

Simultaneous determination of metoprolol succinate and amlodipine besylate in pharmaceutical dosage form by HPLC.

A simple, precise, specific and accurate reverse phase HPLC method has been developed for the simultaneous determination of metoprolol succinate (MS) and amlodipine besylate (AB) in tablet dosage form. The chromatographic separation was achieved on Hypersil BDS cyano (250 mm x 4.6 mm, 5 microm) column using PDA detector. The mobile phase consisting of buffer (aqueous triethylamine pH 3) and acetonitrile in the ratio of 85:15 (v/v) at a flow rate of 1.0 mL/min was used. The method was validated according to the ICH guidelines with respect to specificity, linearity, accuracy, precision and robustness.