Electro-mechanical transfection for non-viral primary immune cell engineering

Non-viral approaches to transfection have emerged a viable option for gene transfer. Electro-mechanical transfection involving use of electric fields coupled with high fluid flow rates is a scalable strategy for cell therapy development and manufacturing. Unlike purely electric field-based or mechanical-based delivery methods, the combined effects result in delivery of genetic material at high efficiencies and low toxicity. This study focuses on delivery of reporter mRNA to show electro-mechanical transfection can be used successfully in human T cells. Rapid optimization of delivery to T cells was observed with efficiency over 90% and viability over 80%. Confirmation of optimized electro-mechanical transfection parameters was assessed in multiple use cases including a 50-fold scale up demonstration. Transcriptome and ontology analysis show that delivery, via electro-mechanical transfection, does not result in gene dysregulation. This study demonstrates that non-viral electro-mechanical transfection is an efficient and scalable method for cell and gene therapy engineering and development.

Re-pressurized magma at Mt. Etna, Italy, may feed eruptions for years

Identifying and monitoring the presence of pressurized magma beneath volcanoes allows for improved understanding of internal dynamics and prediction of eruptions. Here we show with time-repeated tomography clear evidence that fresh melts accumulate since 2019 in three reservoirs located at different depths in the central feeding system. In these three volumes, we observe a significant reduction of seismic wave velocity, an anomaly that has endured for almost two years. Reservoir re-pressurization induced seismicity clusters around the pressurized volumes within high fluid pressure compartments. This indicated a sharp change in volcano behavior, with re-pressurization of the central system replacing two-decade-long, flank collapse-dominated dynamics. The volume where the velocities are altered is remarkable in size, suggesting the injection of new melt, and that erupted lava represents only a small percentage. Our findings suggest that ongoing volcanic recrudescence can persist.

Milky pleural effusion in a neonate and approach to investigating chylothorax

Neonatal chylothorax is a rare presentation leading to significant respiratory distress, thus requiring timely diagnosis. A preterm neonate was resuscitated and ventilated, following which she clinically improved but subsequently developed respiratory distress with a right-sided pleural effusion. Interestingly, thoracentesis fluid appeared ‘milky’ with elevated triglycerides and lymphocytes, suggesting chylothorax. As fluid triglyceride level was lower than the established diagnostic criterion for chylothorax (1.24 mmol/L), a high fluid-to-serum triglyceride ratio was used as a surrogate diagnostic marker, later confirmed by lipoprotein electrophoresis. As observed in the index patient, a critically ill neonate would have a lower-than-average fat intake leading to less chylomicron production, thus lower triglyceride levels in chyle than expected, which may still fail to meet the amended cut-off limit. This case highlights the challenges in diagnosing neonatal chylothorax due to the lack of age-specific triglyceride levels in chyle and low oral fat intake in critically ill patients.

An inorganic origin of the “oil-source” rocks carbon substance

On the basis of an inorganic concept of the petroleum origin, the phase relationships of crystalline kerogens of black shales and liquid oil at the physicochemical conditions of a typical geobarotherm on the Texas Gulf Coast are considered. At the conditions of the carbon dioxide (CO2) high fluid pressure, the process of oil transformation into kerogens of varying degrees of “maturity” (retrograde metamorphism) takes place with decreasing temperature and hydrogen pressure. Kerogen generation in black shale rocks occurs by the sequential transition through metastable equilibria of liquid oil and crystalline kerogens (phase “freezing” of oil). The upward migration of hydrocarbons (HC) of oil fluids, clearly recorded in the processes of oil deposit replenishment in oil fields, shifts the oil ↔ kerogen equilibrium towards the formation of kerogen. In addition, with decreasing of the hydrogen chemical potential as a result of the process of high-temperature carboxylation and low-temperature hydration of oil hydrocarbons, the “mature” and “immature” kerogens are formed, respectively. The phase relationships of crystalline black shale kerogens and liquid oil under hypothetical conditions of high fluid pressure of the HC generated in the regime of geodynamic compression of silicate shells of the Earth in the result of the deep alkaline magmatism development. It is substantiated that a falling of hydrogen pressure in rising HC fluids will lead to the transformation of fluid hydrocarbons into liquid oil, and as the HC fluids rise to the surface, the HC ↔oil ↔ kerogen equilibrium will shift towards the formation of oil and kerogen. It is round that both in the geodynamic regime of compression and in the regime of expansion of the mantle and crust, carboxylation and hydration are the main geochemical pathways for the transformation of oil hydrocarbons into kerogen and, therefore, the most powerful geological mechanism for the black shale formations.

Monolithic polymeric porous superhydrophobic material with pneumatic plastron stabilization for functionally durable drag reduction in blood-contacting biomedical applications

Superhydrophobic (SHP) surfaces can provide substantial reductions in flow drag forces and reduce blood damage in cardiovascular medical devices. However, strategies for functional durability are necessary, as many SHP surfaces have low durability under abrasion or strong fluid jetting or eventually lose their air plastron and slip-flow capabilities due to plastron gas dissolution, high fluid pressure, or fouling. Here, we present a functional material that extends the functional durability of superhydrophobic slip flow. Facile modification of a porous superhydrophobic polytetrafluoroethylene (PTFE, Teflon) foam produced suitable surface structures to enable fluid slip flow and resist protein fouling. Its monolithic nature offered abrasion durability, while its porosity allowed pressurized air to be supplied to resist fluid impalement and to replenish the air plastron lost to the fluid through dissolution. Active pore pressure control could resist high fluid pressures and turbulent flow conditions across a wide range of applied pressures. The pneumatically stabilized material yielded large drag reductions (up to 50%) even with protein fouling, as demonstrated from high-speed water jetting and closed loop pressure drop tests. Coupled with its high hemocompatibility and impaired protein adsorption, this easily fabricated material can be viable for incorporation into blood-contacting medical devices.

Medicinal treatment of multiple renal calculi (Hisat-E-Kulyah) and bilateral ureteric calculi (Hisat-E-Halib) by Unani Pharmacopoeial formulations – A Case Study

Hisat-e-Kulyah (nephrolithiasis) is one of the most common urological diseases affecting approximately 15 % population worldwide and about 2.3% population of India. It results from a complex process of several physicochemical events including supersaturation, nucleation, growth, aggregation and retention with the kidney. A kidney stone is a hard crystalline mineral material formed within the kidney or urinary tract. Various dietary, non-dietary and urinary risk factors contribute to their formation. High fluid intake and adopting healthy lifestyle measures are some of the cost-effective measures in preventing renal stones. The present paper deals with a case study was conducted on a 13 years old male having multiple calculi (8-10) in left kidney and bilateral ureteric stones, were treated with Qurs-e-Kaknaj, Qurs Kushta Hajrul Yahood, Sharbat-e-Bazoori Motadil. The efficacy of the drugs was assessed based on subjective and objective parameters. Ultrasonography (USG) of the abdomen was performed at baseline and after treatment of 1 month. The follow-up observation was 1 week and the duration of the study was 4 weeks. The clinical improved response was excellent and significant after 7 days of treatment. USG finding was suggestive of the absence of any calculus in the left kidney and ureter after 1 month of Unani treatment without any surgical intervention. The formulations were found to be safe, effective and to prevent urinary supersaturation of lithogenic substances.

Modelling of crustal composition and Moho depths and their Implications toward seismogenesis in the Kumaon–Garhwal Himalaya

We image the lateral variations in the Moho depths and average crustal composition across the Kumaon–Garhwal (KG) Himalaya, through the H–K stacking of 1400 radial PRFs from 42 three-component broadband stations. The modelled Moho depth, average crustal Vp/Vs, and Poisson’s ratio estimates vary from 28.3 to 52.9 km, 1.59 to 2.13 and 0.17 to 0.36, respectively, in the KG Himalaya. We map three NS to NNE trending transverse zones of significant thinning of mafic crust, which are interspaced by zones of thickening of felsic crust. These mapped transverse zones bend toward the north to form a NE dipping zone of maximum changes in Moho depths, below the region between Munsiari and Vaikrita thrusts. The 1991 Mw6.6 Uttarakashi and 1999 Mw6.4 Chamoli earthquakes have occurred on the main Himalayan thrust (MHT), lying just above the mapped zone of maximum changes in Moho depths. Modelled large values of average crustal Vp/Vs (> 1.85) could be attributed to the high fluid (metamorphic fluids) pressure associated with the mid-crustal MHT. Additionally, the serpentinization of the lowermost crust resulted from the continent–continent Himalayan collision process could also contribute to the increase of the average crustal Vp/Vs ratio in the region.

High fluid intelligence is characterized by flexible allocation of attentional resources: Evidence from EEG

Recently, the integrated control hypothesis (Lu et al., 2020) was proposed to explain the relationship between fluid intelligence (Gf) and attentional resource allocation. This hypothesis suggested that individuals with higher Gf tend to flexibly and adaptively allocate their limited resources according to the task type and task difficulty rather than simply exert more or fewer resources in any conditions. To examine this hypothesis, the present study used electroencephalogram (EEG) indicators (i.e., frontal theta-ERS and parietal-occipital alpha-ERD) as the measurement of participants’ resource allocation during the exploration task and exploitation task with different difficulties. The results found that higher Gf individuals tend to allocate fewer resources in all difficulty levels in the exploitation task compared to average Gf participants. In contrast, in the exploration task, higher Gf participants would allocate more resources in the medium- and high-difficulty levels than average Gf participants, but this phenomenon was only found in males. These findings provided supportive evidence for the integrated control hypothesis that flexible and adaptive attentional control ability are important characteristics of human intelligence.