Droplet microfluidics for time-resolved serial crystallography.

Serial crystallography requires large numbers of microcrystals and robust strategies to rapidly apply substrates to initiate reactions in time-resolved studies. Here, we report the use of droplet miniaturization for the controlled production of uniform crystals, providing an avenue for controlled substrate addition and synchronous reaction initiation. The approach was evaluated using two enzymatic systems, yielding 3 µm crystals of lysozyme and 2 µm crystals of Pdx1, an Arabidopsis enzyme involved in vitamin B6 biosynthesis. A seeding strategy was used to overcome the improbability of Pdx1 nucleation occurring with diminishing droplet volumes. Convection within droplets was exploited for rapid crystal mixing with ligands. Mixing times of <2 ms were achieved. Droplet microfluidics for crystal size engineering and rapid micromixing can be utilized to advance time-resolved serial crystallography.

Hemodiafiltration: a synergy yet to be convincing.

The desperate attempt to improve mortality, morbidity, quality of life and patient-reported outcomes in patients on hemodialysis has led to multiple attempts to improve the different modes, frequencies, and durations of dialysis sessions in the last few decades. Nothing has been more appealing than the combination of diffusion and convection in the form of hemodiafiltration. Despite the concrete evidence of better clearance of middle weight molecules and better hemodynamic stability, tangible evidence to support the universal adoption is still at a distance. Survival benefits seen in selected groups who are likely to tolerate hemodiafiltration with better vascular access and with lower comorbid burden, need to be extended to real life dialysis patients who are older than the population studied and have significantly higher comorbid burden. Technical demands of initiation hemodiafiltration, the associated costs, and the incremental benefits targeted, along with patient-reported outcomes, need to be explored further before recommending hemodiafiltration as the mode of choice.

Adjuvant convection-enhanced delivery for the treatment of brain tumors.

BACKGROUND: Malignant gliomas are a therapeutic challenge and remain nearly uniformly fatal. While new targeted chemotherapeutic agentsagainst malignant glioma have been developed in vitro, these putative therapeutics have not been translated into successful clinical treatments. The lack of clinical effectiveness can be the result of ineffective biologic strategies, heterogeneous tumor targets and/or the result of poortherapeutic distribution to malignant glioma cells using conventional nervous system delivery modalities (intravascular, cerebrospinal fluid and/orpolymer implantation), and/or ineffective biologic strategies. METHODS: The authors performed a review of the literature for the terms "convection enhanced delivery", "glioblastoma", and "glioma". Selectclinical trials were summarized based on their various biological mechanisms and technological innovation, focusing on more recently publisheddata when possible. RESULTS: We describe the properties, features and landmark clinical trials associated with convection-enhanced delivery for malignant gliomas.We also discuss future trends that will be vital to CED innovation and improvement. CONCLUSION: Efficacy of CED for malignant glioma to date has been mixed, but improvements in technology and therapeutic agents arepromising.

Manipulation of Convection Using Infrared Light Emitted from Human Hands.

Control of convection plays an important role in heat transfer regulation, bio/chemical sensing, phase separation, etc. Current convection controlling systems generally depend on engineered energy sources to drive and manipulate the convection, which brings additional energy consumption into the system. Here the use of human hand as a natural and sustainable infrared (IR) radiation source for the manipulation of liquid convection is demonstrated. The fluid can sense the change of the relative position or the shape of the hand with the formation of different convection patterns. Besides the generation of static complex patterns, dynamic manipulation of convections can also be realized via moving of hand or finger. The use of such sustainable convections to control the movement of a floating "boat" is further achieved. The use of human hands as the natural energy sources provides a promising approach for the manipulation of liquid convection without the need of extra external energy, which may be further utilized for low-cost and intelligent bio/chemical sensing and separation.

Comparison of HVT-ND recombinant and convection-based Newcastle disease vaccination programs in the protection against the genotype VII NDV challenges: an experimental study.

Newcastle disease virus (NDV) belongs to the Avulavirus genus and Paramyxoviridae family virus that causes acute, highly infectious Newcastle disease in poultry. The two proteins of haemagglutinin neuraminidase (HN) and fusion (F) are key virulence factors with an important role in its immunogenicity. Genotype VII NDV is still among the most serious viral hazards to the poultry industry worldwide. In this study, a commercial vector vaccine (HVT-NDV) was evaluated compared to the conventional vaccination strategy against Iranian genotype VII. This experiment showed that the group receiving the conventional vaccination strategy had higher antibodies, fewer clinical signs, and lower viral loads in tracheal swabs and feces. Also, two vaccine groups showed significant difference, which could have resulted from two extra vaccine doses in the conventional group. However, except for antibody levels in commercial chickens in the Iran new-generation vaccine, this difference was minor. Further, both groups showed 100% protection in the challenge study. Despite the phylogenetic gap between the NDV-F gene placed in the vector vaccine and the challenge virus (genotypes I and VII, respectively), the rHVT-NDV vaccine offered strong clinical protection and decreased challenge virus shedding considerably.

Magnetic Resonance Imaging-Aided SmartFlow Convection Delivery of DNX-2401: A Pilot, Prospective Case Series.

BACKGROUND: The Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects (CAPTIVE) study is a phase II clinical trial testing the efficacy of a recombinant adenovirus DNX-2401 combined with the immune checkpoint inhibitor pembrolizumab. Here, we report the first patients in this study who underwent viral delivery through real-time magnetic resonance imaging (MRI) stereotaxis-guided SmartFlow convection delivery of DNX-2401. METHODS: Patients who underwent real-time MRI-guided DNX-2401 delivery through the SmartFlow convection catheter were prospectively followed. RESULTS: Precise catheter placement was achieved in all patients treated, and no adverse events were noted. Average radial error from target was 0.9 mm. Average procedural time was 3 hours 16 minutes and was comparable to other convection-enhanced delivery techniques. In 2 patients, delivery of DNX-2401 was visualized as >1 cm maximal diameter of T1 hypointensity infusate on MRI obtained immediately after completion of viral infusion. These patients exhibited partial response based on Response Assessment in Neuro-Oncology assessment. The remaining patient showed <1 cm maximal diameter of infusate on immediate postinfusion MRI and showed disease progression on subsequent MRI. CONCLUSIONS: Our pilot case series supports compatibility of the SmartFlow system with oncolytic adenovirus delivery and provides the basis for future validation studies.

Chronic intermittent convection-enhanced delivery of vigabatrin to the bilateral subthalamic nucleus in an acute rat seizure model.

Targeted intracerebral drug delivery is an attractive experimental approach for the treatment of drug-resistant epilepsies. In this regard, the subthalamic nucleus (STN) represents a focus-independent target involved in the remote modulation and propagation of seizure activity. Indeed, acute and chronic pharmacological inhibition of the STN with vigabatrin (VGB), an irreversible inhibitor of GABA transaminase, has been shown to produce antiseizure effects. This effect, however, is lost over time as tolerance develops with chronic, continuous intracerebral pharmacotherapy. Here we investigated the antiseizure effects of chronic intermittent intra-STN convection-enhanced delivery of VGB in an acute rat seizure model focusing on circumventing tolerance development and preventing adverse effects. Timed intravenous pentylenetetrazol (PTZ) seizure threshold testing was conducted before and after implantation of subcutaneous drug pumps and bilateral intra-STN cannulas. Drug pumps infused vehicle or VGB twice daily (0.4 µg) or once weekly (2.5 µg, 5 µg) over three weeks. Putative adverse effects were evaluated and found to be prevented by intermittent compared to previous continuous VGB delivery. Clonic seizure thresholds were more clearly raised by intra-STN VGB compared to myoclonic twitch. Both twice daily and once weekly intra-STN VGB significantly elevated clonic seizure thresholds depending on dose and time point, with responder rates of up to 100% observed at tolerable doses. However, tolerance could not be completely avoided, as tolerance rates of 40-75% were observed with chronic VGB treatment. Results indicate that the extent of tolerance development after intermittent intra-STN VGB delivery varies depending on infusion dose and regimen.

"Floating Catalytic Foam" with prominent heat-induced convection for the effective photocatalytic removal of antibiotics.

Immobilized photocatalysts represent a promising candidate for the wastewater treatments due to their good reusability, high stability and low eco-risk. Mass transfer within the immobilized catalytic bed is a crucial process that determines the contacting, adsorption, and degradation kinetics in the photodegradation. In this study, a floating catalytic foam (FCF) with a prominent pumping effect was designed to promote mass transfer. The polyurethane foam immobilized with rGO/TiO2/ultrathin-g-C3N4 photocatalyst (PRTCN) was prepared by a simple dip-coating and Uv-light aging process. It was found that the hydrophilic-hydrophobic interfaces could not only contribute to the floating of the catalyst but also establish a temperature gradient across the floating immobilized catalyst. In addition, the temperature gradient induced convection could serve as a built-in pump to effectively promote the diffusion and adsorption of target antibiotic molecules during the photocatalytic process. Therefore, the PRTCN demonstrated a high photodegradation and mineralization efficiency with excellent reusability and anti-interference capability. Moreover, the photodegradation mechanism and the intermediates' toxicity of norfloxacin were detailly investigated by ultra-high resolution electrospray time-of-flight mass spectrometry, density functional theory simulation and ECOSAR estimation. This work proposed a facile and sustainable strategy to enhance the mass transfer problem on immobilized photocatalysts, which could promote the application of the immobilized photocatalysts in the real water-treatment scenarios.

Design and Characterization of Pressure Monitoring and Insertion system for Intraparenchymal Convection Enhanced Delivery.

Neurological disorders are a significant societal and economic burden. Common pharmacological therapies often can only manage symptoms and have limited efficacy. Intraparenchymal convection enhanced delivery (IP CED) is a neurosurgical technique for direct brain delivery of therapeutics. Currently, the main applications of IP CED are targeted chemotherapy for glioblastoma and gene therapy. While IP CED has advantages over systemic approaches, its benefits can be drastically reduced by inadequate coverage as low as 21% of target anatomy, excessive infusion durations greater than 2 hours, and off-target effects. Addressing the limitations of IP CED requires thorough investigation and optimization of the relevant fluid dynamic and operational parameters. In this work, we present the design, fabrication, and characterization of low-cost, open-source, and fully automated CED cannula insertion control and pressure-monitoring systems. Using these automated CED control systems, we investigate the effects of pressure, insertion velocity, and flow rates on several outcome variables, including reflux, volume distribution, and infusion cloud morphology during CED infusions in brain phantoms.Clinical Relevance- CED pressure properties may be able to implicate reflux incidents and could provide clinicians with valuable, real-time information regarding ongoing infusions without the need for costly medical imaging modalities.

Uniformly convergent extended cubic B-spline collocation method for two parameters singularly perturbed time-delayed convection-diffusion problems.

This work proposes a uniformly convergent numerical scheme to solve singularly perturbed parabolic problems of large time delay with two small parameters. The approach uses implicit Euler and the exponentially fitted extended cubic B-spline for time and space derivatives respectively. Extended cubic B-splines have advantages over classical B-splines. This is because for a given value of the free parameter [Formula: see text] the solution obtained by the extended B-spline is better than the solution obtained by the classical B-spline. To confirm the correspondence of the numerical methods with the theoretical results, numerical examples are presented. The present numerical technique converges uniformly, leading to the current study of being more efficient.

Long-lasting antiseizure effects of chronic intrasubthalamic convection-enhanced delivery of valproate.

Intracerebral drug delivery is an experimental approach for the treatment of drug-resistant epilepsies that allows for pharmacological intervention in targeted brain regions. Previous studies have shown that targeted pharmacological inhibition of the subthalamic nucleus (STN) via modulators of the GABAergic system produces antiseizure effects. However, with chronic treatment, antiseizure effects are lost as tolerance develops. Here, we report that chronic intrasubthalamic microinfusion of valproate (VPA), an antiseizure medication known for its wide range of mechanisms of action, can produce long-lasting antiseizure effects over three weeks in rats. In the intravenous pentylenetetrazole seizure-threshold test, seizure thresholds were determined before and during chronic VPA application (480 µg/d, 720 µg/d, 960 µg/d) to the bilateral STN. Results indicate a dose-dependent variation in VPA-induced antiseizure effects with mean increases in seizure threshold of up to 33%, and individual increases of up to 150%. The lowest VPA dose showed a complete lack of tolerance development with long-lasting antiseizure effects. Behavioral testing with all doses revealed few, acceptable adverse effects. VPA concentrations were high in STN and low in plasma and liver. In vitro electrophysiology with bath applied VPA revealed a reduction in spontaneous firing rate, increased background membrane potential, decreased input resistance and a significant reduction in peak NMDA, but not AMPA, receptor currents in STN neurons. Our results suggest an advantage of VPA over purely GABAergic modulators in preventing tolerance development with chronic intrasubthalamic drug delivery and provide first mechanistic insights in intracerebral pharmacotherapy targeting the STN.

Environmental energy enhanced solar-driven evaporator with spontaneous internal convection for highly efficient water purification.

Solar-driven interfacial evaporation for water purification is limited by the structural design of the solar evaporator and, more importantly, by the inability to separate the water from volatile organic compounds (VOCs) present in the water source. Here, we report a three-dimensional (3D) bifunctional evaporator based on N-doped carbon (CoNC/CF), which enables the separation of fresh water from VOCs by activating PMS during the evaporation process with a VOC removal rate of 99%. There is abundant van der Waals interaction between peroxymonosulfate (PMS) and CoNC/CF, and pyrrolic N is confirmed as the active site for binding phenol, thus contributing to the separation of phenol from water. With the advantageous features of sufficient light absorption, adequate water storage capacity, and spontaneous internal convection flow on its top surface, the 3D evaporator achieves a high evaporation rate under one sun (1 kW/m2) at 3.16 kg/m2/h. More notably, through careful structural design, additional energy from the environment and water can be utilized. With such a high evaporation rate and satisfactory purification performance, this work is expected to provide a promising platform for wastewater treatment.

An overview of oxygen transport in plants: diffusion and convection.

The movement of gases within plants is crucial for species that live in flood-prone areas with limited soil oxygen. These plants adapt to hypoxia/anoxia not by using oxygen more efficiently, but by ensuring a steady oxygen supply to their cells. Wetland plants typically form gas-filled spaces (aerenchyma) in their tissues, providing a low-resistance pathway for gas movement between shoots and roots, especially when the shoots are above water, and the roots are submerged. Oxygen movement in plant roots is mainly through diffusion. However, in certain species, such as emergent and floating-leaved plants, pressurized flows can also facilitate the movement of gases within their stems and rhizomes. Three types of pressurized (convective) flows have been identified: humidity-induced pressurization (positive pressure), thermal osmosis (positive pressure with air flow against the heat gradient), and venturi-induced suction (negative pressure) caused by wind passing over broken culms. A clear diel variation in pressurized flows exists, with higher pressures and flows during the day and negligible pressures and flows during the night. This article discusses some key aspects of these mechanisms for oxygen movement.

PNOC015: Repeated convection-enhanced delivery of MTX110 (aqueous panobinostat) in children with newly diagnosed diffuse intrinsic pontine glioma.

BACKGROUND: The objective of this study was to determine the safety, tolerability, and distribution of MTX110 (aqueous panobinostat) delivered by convection-enhanced delivery (CED) in patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) who completed focal radiation therapy (RT). METHODS: Patients with DIPG (2-21 years) were enrolled after RT. CED of MTX110 combined with gadoteridol was completed across 7 dose levels (DL) (30-90 µM; volumes ranging from 3 mL to 2 consecutive doses of 6 mL). An accelerated dose escalation design was used. Distribution of infusate was monitored with real-time MR imaging. Repeat CED was performed every 4-8 weeks. Quality-of-life (QoL) assessments were obtained at baseline, every 3 months on therapy, and end of therapy. RESULTS: Between May 2018 and March 2020, 7 patients who received a total of 48 CED infusions, were enrolled (median age 8 years, range 5-21). Three patients experienced dose-limited toxicities. Four grade 3 treatment-related adverse events were observed. Most toxicities were transient new or worsening neurologic function. Median overall survival (OS) was 26.1 months (95% confidence interval: 14.8-not reached). Progression-free survival was 4-14 months (median, 7). Cumulative percentage of tumor coverage for combined CED infusions per patient ranged from 35.6% to 81.0%. Increased CED infusions were negatively associated with self-reported QoL assessments. CONCLUSION: Repeat CED of MTX110 with real-time imaging with gadoteridol is tolerable for patients with DIPG. Median OS of 26.1 months compares favorably with historical data for children with DIPG. The results support further investigation of this strategy in a larger cohort.

Fourth-order multiple-relaxation-time lattice Boltzmann model and equivalent finite-difference scheme for one-dimensional convection-diffusion equations.

In this paper, we first develop a fourth-order multiple-relaxation-time lattice Boltzmann (MRT-LB) model for the one-dimensional convection-diffusion equation (CDE) with the constant velocity and diffusion coefficient, where the D1Q3 (three discrete velocities in one-dimensional space) lattice structure is used. We also perform the Chapman-Enskog analysis to recover the CDE from the MRT-LB model. Then an explicit four-level finite-difference (FLFD) scheme is derived from the developed MRT-LB model for the CDE. Through the Taylor expansion, the truncation error of the FLFD scheme is obtained, and at the diffusive scaling, the FLFD scheme can achieve the fourth-order accuracy in space. After that, we present a stability analysis and derive the same stability condition for the MRT-LB model and FLFD scheme. Finally, we perform some numerical experiments to test the MRT-LB model and FLFD scheme, and the numerical results show that they have a fourth-order convergence rate in space, which is consistent with our theoretical analysis.

Thermal responses induced by nitrogen and forced convection based partial-body cryostimulation.

Partial Body Cryostimulation (PBC) involves a very cold air flow directed to the body of subjects with minimal clothing. PBC is performed in a rapid timeframe, inside an on-purposed designed cryo-cabin. Recently, cryo-cabins have been built with different energy systems, however a validation study on relative thermal responses is missing. This study was aimed at comparing thermal responses following a PBC in an electrically powered cryo-cabin based on forced convection or into a standard nitrogen-fueled cryo-cabin. In a randomized crossover fashion, thirty-six subjects (F=20; M=16) underwent both cryo-exposures lasting 150 s each. Thermal responses were assessed before and immediately after completing each PBC session. Mixed model analysis of variance revealed a significantly colder temperature after electric PBC in all the body regions (except for the thighs) with respect to a standard nitrogen based PBC (F: 16.4 ± 1.4 vs 18 ± 5.8 °C; M: 16.4 ± 1.7 vs 20.9 ± 4 °C). Moreover, a significant lower thermal discomfort was perceived at the end of electric PBC as compared to that one felt following standard PBC. For the first time, the safety and thermo-effectiveness of an electric cryo-cabin based on forced convection was ensured. This methodology can be viable for practitioners of PBC and clinicians.

A practical design equation for accurate quantification of CRRT filter design factors and convection effects.

Considering the increasing clinical need for continuous renal replacement therapy (CRRT), further improvement in therapeutic efficacy has become an important focus for researchers. Here, we designed nine CRRT filters with various combinations of hollow fiber packing density (PD) and housing shape (effective hollow fiber length (L) and inner housing diameter (D) ratio (L/D ratio)) to evaluate the clearance of middle molecular uremic toxins (MMs) via simulation of an in vitro continuous veno-venous hemodialysis treatment model. We also used Doppler ultrasonography to measure the maximum internal filtration flow rate (QIF-Max) as an aid; this approach facilitated an exploration of the impacts of various design factors on convection effects, while revealing the mechanisms influencing MM removal performance. Furthermore, we constructed a multiple linear regression model of design factors and QIF-Max, then conducted experimental verification. Finally, we proposed an accurate and practical design equation to quantify the design factors influencing CRRT filters and convection effects: QIF-Max=4.749×ND2+2.293×LD-34.775, where N/D2 and L/D affect QIF-Max by 15.0% and 85.0%, respectively. This design equation was able to effectively quantify the convection effects of CRRT filters with different design factors, thereby predicting MM removal performance; this convenient design equation can support the development of CRRT-related products.

Influence of Geometric Parameters on the Charging process of PCM in Semi-circular thermal storages for energy management.

The limitation of intermittent and irregular supply of the solar energy systems can be compensated through utilization of thermal energy storage systems. The design of an efficient latent heat thermal energy storage system plays a huge role in determining the overall performance. Therefore, this study aims to investigate the effect of geometric parameters such as thermal charger interspacing and inclination angle on the charging performance of a PCM (phase change material) inside a semi-circular enclosure with two charging sources (renewable heat sources). A numerical analysis is performed using the enthalpy-porosity method. The system performance is assessed in terms of dimensionless flow parameters such as Fourier number, Rayleigh number, and Stefan number. The study shows that the variation of Rayleigh number significantly influences the natural convection in the fluid zone of a PCM. An increase of Rayleigh number from 1e4 to 5e5 reduced the overall melting time by more than half. In addition, the thermal charger interspacing and inclination angle both showed considerable effect on the flow physics which can cause significant expedition/delay of the melting process.

Impact of human body shape on forced convection heat transfer.

Predicting human thermal comfort and safety requires quantitative knowledge of the convective heat transfer between the body and its surrounding. So far, convective heat transfer coefficient correlations have been based only upon measurements or simulations of the average body shape of an adult. To address this knowledge gap, here we quantify the impact of adult human body shape on forced convection. To do this, we generated fifty three-dimensional human body meshes covering 1st to 99th percentile variation in height and body mass index (BMI) of the USA adult population. We developed a coupled turbulent flow and convective heat transfer simulation and benchmarked it in the 0.5 to 2.5 m·s-1 air speed range against prior literature. We computed the overall heat transfer coefficients, hoverall, for the manikins for representative airflow with 2 m·s-1 uniform speed and 5% turbulence intensity. We found that hoverall varied only between 19.9 and 23.2 W·m-2 K-1. Within this small range, the height of the manikins had negligible impact while an increase in the BMI led to a nearly linear decrease of the hoverall. Evaluation of the local coefficients revealed that those also nearly linearly decreased with BMI, which correlated to an inversely proportional local area (i.e., cross-sectional dimension) increase. Since even the most considerable difference that exists between 1st and 99th percentile BMI manikins is less than 15% of hoverall of the average manikin, it can be concluded that the impact of the human body shape on the convective heat transfer is minor.

Coupling radiative, conductive and convective heat-transfers in a single Monte Carlo algorithm: A general theoretical framework for linear situations.

It was recently shown that radiation, conduction and convection can be combined within a single Monte Carlo algorithm and that such an algorithm immediately benefits from state-of-the-art computer-graphics advances when dealing with complex geometries. The theoretical foundations that make this coupling possible are fully exposed for the first time, supporting the intuitive pictures of continuous thermal paths that run through the different physics at work. First, the theoretical frameworks of propagators and Green's functions are used to demonstrate that a coupled model involving different physical phenomena can be probabilized. Second, they are extended and made operational using the Feynman-Kac theory and stochastic processes. Finally, the theoretical framework is supported by a new proposal for an approximation of coupled Brownian trajectories compatible with the algorithmic design required by ray-tracing acceleration techniques in highly refined geometry.