Nanohybrids as Protein-Polymer Conjugate Multimodal Therapeutics

Protein therapeutic formulations are being widely explored as multifunctional nanotherapeutics. Challenges in ensuring susceptibility and efficacy of nanoformulation still prevail owing to various interactions with biological fluids before reaching the target site. Smart polymers with the capability of masking drugs, ease of chemical modification, and multi-stimuli responsiveness can assist controlled delivery. An active moiety like therapeutic protein has started to be known as an important biological formulation with a diverse medicinal prospect. The delivery of proteins and peptides with high target specificity has however been tedious, due to their tendency to aggregate formation in different environmental conditions. Proteins due to high chemical reactivity and poor bioavailability are being researched widely in the field of nanomedicine. Clinically, multiple nano-based formulations have been explored for delivering protein with different carrier systems. A biocompatible and non-toxic polymer-based delivery system serves to tailor the polymer or drug better. Polymers not only aid delivery to the target site but are also responsible for proper stearic orientation of proteins thus protecting them from internal hindrances. Polymers have been shown to conjugate with proteins through covalent linkage rendering stability and enhancing therapeutic efficacy prominently when dealing with the systemic route. Here, we present the recent developments in polymer-protein/drug-linked systems. We aim to address questions by assessing the properties of the conjugate system and optimized delivery approaches. Since thorough characterization is the key aspect for technology to enter into the market, correlating laboratory research with commercially available formulations will also be presented in this review. By examining characteristics including morphology, surface properties, and functionalization, we will expand different hybrid applications from a biomaterial stance applied in in vivo complex biological conditions. Further, we explore understanding related to design criteria and strategies for polymer-protein smart nanomedicines with their potential prophylactic theranostic applications. Overall, we intend to highlight protein-drug delivery through multifunctional smart polymers.

Structural Evidences for Present-day Compressive Tectonics at the St. Peter and St. Paul Archipelago (Equatorial Atlantic Ocean)

This paper discusses the tectonics of the St. Peter and St. Paul Archipelago (SPSPA) in the Equato-rial Atlantic Ocean, based on the joint-system geometry which show a North-South shorten-ing/transpressional uplift tectonism, is active leading to exhumation of the sub-oceanic mantle. These islets are the summits of a sigmoidal submarine ridge formed by mantle ultramafic rocks. The ridge is crossed by the principal transform deformation zone of the northern transform fault of the St. Paul Multifault System. The South flank ridge exposes serpentinized mantle perido-tites, while the North flank exposes strongly deformed/fractured ultramylonites, recording duc-tile and brittle deformation at lithospheric conditions. The SPSPA show multiple joint systems cutting mylonitic foliation of the exposed rocks, forming three main families: high-angle paral-lel joints of tectonic origin, serpentinization-related joints with random direction and load-release low-angle parallel joints. The tectonic joints show an average direction of N31°E and N28°W, forming a conjugate system with a N1ºW compression axes, coherent with a trans-pressive stress field. Accordingly, the earthquakes focal mechanism close to the islets also shows N-S compression. The previously reported active uplift with an average rate of 1.5 mm/year and the directions of the joint system here reported agreeing with a present-day active N-S compres-sive field at a high angle with the direction of the transform fault.

A Novel Quinoxaline-Rhodamine Conjugate for a Simple and Efficient Detection of Hydrogen Sulphate Ion

This work presents the development of a quinoxaline and rhodamine conjugate system that acts as a colorimetric chemosensor for hydrogen sulfate (HSO4−) ions in methanol media. This sensor has been characterized both theoretically and experimentally. The detection limits for HSO4− are small as 0.71 µM and 3.8 µM for the absorption and emission experiments, respectively. The effectiveness of the probe in recognizing HSO4− both in gel and solid phase is evaluated as well. Thus, this works presents a simple strategy to detect the environmental HSO4− pollutant event at tiny concentrations.

Seismicity of the Northern Volcanic Zone of Iceland

A half century of monitoring of the Northern Volcanic Zone of Iceland, a branch of the North America—Eurasia plate boundary, shows that the seismicity is very unevenly distributed, both in time and space. The four central volcanoes at the boundary, Þeistareykir, Krafla, Fremrinámar, and Askja, show persistent but very low-level seismicity, spatially coinciding with their high-temperature geothermal systems. On their rift structures, on the other hand, seismicity is almost absent, except during rifting episodes. Krafla went through a rifting episode in 1975–1984 with inflation, interrupted by 20 diking events with extensive rifting, eruptive activity, and intense seismicity along an 80 km long section of the rift. During inflation periods, the seismicity was contained within the caldera of the volcano, reflecting the inflation level of the magma chamber. Diking events were marked by seismicity propagating away from the volcano into the fissure swarms to the south or north of the volcano, accompanied by rapid deflation of the caldera magma chamber. These events lasted from 1 day to 3 months, and the dike length varied between 1 and 60 km. The area around the Askja volcano is the only section of the Northern Volcanic Zone that shows persistent moderate seismicity. The largest events are located between fissure swarms of adjacent volcanic systems. Detailed relative locations of hypocenters reveal a system of vertical strike-slip faults, forming a conjugate system consistent with minimum principal stress in the direction of spreading across the plate boundary. A diking event into the lower crust was identified in the adjacent fissure swarm at Upptyppingar in 2007–2008. Four nests of anomalously deep earthquakes (10–34 km) have been identified in the Askja region, apparently associated with the movements of magma well below the brittle-ductile transition. Several processes have been pointed out as possible causes of earthquakes in the deformation zone around the plate boundary. These include inflation and deflation of central volcanoes, intrusion of propagating dikes, both laterally and vertically, strike-slip faulting on conjugate fault systems between overlapping fissure swarms, migration of magma in the lower, ductile crust, and geothermal heat mining.

Consecutive ruptures on a complex conjugate fault system during the 2018 Gulf of Alaska earthquake

We developed a flexible finite-fault inversion method for teleseismic P waveforms to obtain a detailed rupture process of a complex multiple-fault earthquake. We estimate the distribution of potency-rate density tensors on an assumed model plane to clarify rupture evolution processes, including variations of fault geometry. We applied our method to the 23 January 2018 Gulf of Alaska earthquake by representing slip on a projected horizontal model plane at a depth of 33.6 km to fit the distribution of aftershocks occurring within one week of the mainshock. The obtained source model, which successfully explained the complex teleseismic P waveforms, shows that the 2018 earthquake ruptured a conjugate system of N-S and E-W faults. The spatiotemporal rupture evolution indicates irregular rupture behavior involving a multiple-shock sequence, which is likely associated with discontinuities in the fault geometry that originated from E-W sea-floor fracture zones and N-S plate-bending faults.

A doxorubicin–platinum conjugate system: impacts on PI3K/AKT actuation and apoptosis in breast cancer cells

In recent years, the development of a nano-conjugate system for drug delivery applications has gained attention among researchers.

Oxidation Assisted Fabrication of Sterculia Gum/Protein Hybrid Hydrogel Networks through Schiff Base Formation: Characterization and Swelling Kinetic Studies

Polysaccharide/protein hybrid conjugate system becomes an emerging system with integrated characteristics of protein as well as polysaccharide to be exploited for recent advancements in biomedical sectors. Present study is an attempt to fabricate a sterculia gum/gelatin hybrid hydrophilic network system via Schiff base formation using oxidative route at ambient conditions. This route transforms hydrogel synthesis through green mode without employing any crosslinking systems so as to minimize the toxicity issues associated. Fabricated Schiff base based gel systems have been characterized by FT-IR, powdered XRD, FESEM and EDX to confirm the inclusion of new characteristics, morphological changes and functionalization. Oxidation of natural gum drastically alter the physico-chemical behaviour of the gum as confirmed by powdered XRD by incorporating crystalline nature of oxidized sterculia gum as compared to the native sterculia gum and the Schiff base formed. The changes observed are due to the chemical modification of sterculia gum during Schiff base formation. Further the swelling capacity of oxidized sterculia gum and crosslinked network formed is also modulated and was less as compared to native sterculia gum and gelatin. This article also elaborates the mechanistic changes which take place during oxidative route of hydrogel formation in various segments of sterculia gum during oxidation and Schiff base formation.

Point control of a differential-difference system with distributed parameters on the graph

The article considers the problem of point control of the differential-difference equation with distributed parameters on the graph in the class of summable functions. The differential- difference system is closely related to the evolutionary differential system and moreover the properties of the differential system are preserved. This connection is established by the universal method of semi-discretization in a time variable for a differential system, which provides an effective tool in order to find conditions for unique solvability and continuity on the initial data for the differential-difference system. For this differential-difference system, a special case of the optimal control problem is studied: the problem of point control action on the controlled differential-difference system is considered by the control, concentrated at all internal nodes of the graph. At the same time, the restrictive set of permissible controls is set by the means of conditions depending on the nature of the applied tasks. In this case, the controls are concentrated at the end points of the edges adjacent to each inner node of the graph. This is a characteristic feature of the study presented, quite often used in practice when building a mechanism for managing the processes of transportation of different kinds of masses over network media. The study essentially uses the conjugate state of the system and the conjugate system for a differential-difference system — obtained ratios that determine optimal point control. The obtained results underlie the analysis of optimal control problems for differential systems with distributed parameters on the graph, which have interesting analogies with multi-phase problems of multidimensional hydrodynamics.