Miniaturized peptidomimetics and nano-vesiculation in endothelin types through probable nano-disk formation and structure property relationships of endothelins’ fragments

Endothelins (ETs), which are multi-functional-peptides with potential for antagonist-based-therapy in various physiological-malfunctionings, including cardiovascular, nephrological, oncologic, and diabetic conditions, may produce newer chemical entities and drug leads. The present study deals with molecular-modeling of the ETs’ sub-types, ET-I, II, and III to find the structure property-relationship (SPR) of the ETs, and individual fragments derived from the ET sub-type ET-I. The ETs peptidic tails’ amino acid (AA) sequence’s structural differences and similarities, various dissected fragments of the ET-I, and SPR comparison with the sarafotoxin-6b (SRT-6b), a structurally-related snake-venom, showed points of dissimilarities for their structural specifications, geometric disposition, and physico-chemical properties. The generation of miniaturized (shortened sequence) peptides towards offering peptidomimetic compounds of near- and far-values compared SPR with estimations for log P, hydration energy, and other molecular and quantitative structure activity relationship (QSAR) were based on random and ordered-fragments derived from the original ET-I AA’s sequence, and sequential distance changes in the original ET-I sequence’s chain of 1–21 AA. The feasibility of alternate and bond length parameters-based possible cysteine–cysteine cyclizations, sequence homology, AA’s positional demarcation, and presence/absence of cysteines, homology-based basic non-cysteine and cysteines-AA based cyclization, total structure and fragments end-to-end cyclizations, and geometrical analogy-based miniaturized sequence of the shorter AAs from the original ET-I sequence, together with mutated replacements with naturally constituent AAs of the ETs, and SRT-6 sequences were utilized. The major findings of the fragmented sequences, and sequences at par with the original ETs to provide structures similar to the size, volume and with molecular and electronic properties of electrostatic potential and total charge density distribution, crucial factors in receptor bindings were investigated. The SPRs, molecular properties, and QSAR values were estimated to compare and validate the findings with the known homologous compounds, ET-I, and its known and potent antagonists. The study resulted in leads of smaller and larger sizes of peptide-based compounds which may have prospects as potent antagonist and in future needs their bioactivity evaluations after the synthesis. Moreover, approach to plausible vesiculation of the ETs, and the involved processes and structural requirements, together with the molecular interactions in settling a nano-vesicle of the peptidic structure with a possible mechanism is also suggested.

THE 3-D NUMERICAL SIMULATIONS OF THE SMALL RADIUS ACCRETION DISK FORMATION IN MICROQUASAR CYG X-1. THE CASE OF THE HIGH RESOLUTION GRID IN THE VERTICAL DIRECTION

The present paper is devoted to small radius accretion disk formation in microquasar CYG X-1. The results show that in the case of the strong wind action on a disk the disk radius is about of 20 ÷ 30 per sent of accretor’s Roche lobe radius (it is about of 0.08 of orbital separation) instead of the standard disk radius equal to 80 ÷ 85 per sent of accretor’s Roche lobe radius (the last magnitude is a disk radius equal to 0.22 of orbital separation). In the present paper we try to resolve the problem that is arising in the case of microquasars when we investigate the accretion disk formation in these objects. Indeed, since the microquasars are the massive close binary systems (MCBS) in which the donor is massive stars of O-B class the strong wind is blowing from these stars. In this case the problem is arising: what is the situation in which an accretion disk in microqausars is formed. By the other words, it means what are the processes and the matter that are responsible for an accretion disk formation in microquasars: is this matter from one-point stream only or a disk is formed from the donor’s wind in essential or one is formed from both processes simul- taneously. This question is not idle since one is strong affects on ON-OFF state generations in the precession mechanism model. Since this mechanism is strong depending from the magnitude of the disk centre density and all the parameters affecting on it are very important for calculations. The matter configuration in the vicinity of one-point is one of these parameters that strong affects on ON-OFF state production and disk structure and the central disk density. By this reason we have investigated in the present paper how the disk structure is depending from the wind configuration in the vicinity of one-point.

Combined Intrastromal Implantation of a Semipermeable Hydrogel Membrane in Case of Corneal Graft Failure and Multiple Keratoplasty (Clinical Observation)

Introduction: penetrating keratoplasty (PK) is an effective method for the surgical treatment of corneal failure and its layers and low visual acuity. It is well-known that the graft degrades over time, it is associated with “chronic immune destruction”. Rekeratoplasty is conducted in case of rapid decrease of transplant functions, but even with multiple rekeratoplasty iterations, the result can be unstable.Patient and methods. Patient D., 42 years old, complaints to low vision of left eye — arm movement 10 cm on face. Both eyes have been previously surgically operated for the last 10 years. Two iterations of an artificial iris transplantation in combination with IOL implantation, and Ahmed drainage implantation and five rekeratoplasty on the left eye were conducted. Corneal graft failure with transplant thickness — 802 μm. The patient suffers from Mediterranean fever and polyarthritis. We conducted a course of conservative therapy, which increased visual acuity to 0.05. Then we performed a surgical procedure for hybrid type of keratotransplantation. The following procedures were gradually conducted: mechanical removal of epithelium, femto-laser formation in a recipient’s replaceable corneal disk formation with 500 μm thick and a diameter of 7.0 mm, removal of disk, femto-laser formation of a central penetrating hole with a diameter of 3 mm opposite the artificial pupil, placing of the hydrogel graft 60 μm thick on the bottom of the bed. Hydrogel graft was covered by a donor corneal graft, which was fixed by interrupted sutures and soft contact lens.Results: Visual acuity of the left eye after 1 day after keratoplasty — 0.2; after 1 month — 0.3, the transplant was transparent; after 4 months — 0.4 with complex correction — 0.7, the transplant was transparent, the thickness of the donor disc — 275 μm.Conclusion. After multiple rekeratoplasty iterations the presented method of combined keratotransplantation allows to obtain a non-permanent effective result. At the same time, the polymer metabolism is preserved, since it has a circulation with the front camera. The case requires further observation.

Accretion bursts in magnetized gas-dust protoplanetary disks

Aims. Accretion bursts triggered by the magnetorotational instability (MRI) in the innermost disk regions were studied for protoplanetary gas-dust disks that formed from prestellar cores of a various mass Mcore and mass-to-magnetic flux ratio λ. Methods. Numerical magnetohydrodynamics simulations in the thin-disk limit were employed to study the long-term (~1.0 Myr) evolution of protoplanetary disks with an adaptive turbulent α-parameter, which explicitly depends on the strength of the magnetic field and ionization fraction in the disk. The numerical models also feature the co-evolution of gas and dust, including the back-reaction of dust on gas and dust growth. Results. A dead zone with a low ionization fraction of x≲10−13 and temperature on the order of several hundred Kelvin forms in the inner disk soon after its formation, extending from several to several tens of astronomical units depending on the model. The dead zone features pronounced dust rings that are formed due to the concentration of grown dust particles in the local pressure maxima. Thermal ionization of alkaline metals in the dead zone trigger the MRI and associated accretion burst, which is characterized by a sharp rise, small-scale variability in the active phase, and fast decline once the inner MRI-active region is depleted of matter. The burst occurrence frequency is highest in the initial stages of disk formation and is driven by gravitational instability (GI), but it declines with diminishing disk mass-loading from the infalling envelope. There is a causal link between the initial burst activity and the strength of GI in the disk fueled by mass infall from the envelope. We find that the MRI-driven burst phenomenon occurs for λ = 2–10, but diminishes in models with Mcore ≲ M⊙, suggesting a lower limit on the stellar mass for which the MRI-triggered burst can occur. Conclusions. The MRI-triggered bursts occur for a wide range of mass-to-magnetic flux ratios and initial cloud core masses. The burst occurrence frequency is highest in the initial disk formation stage and reduces as the disk evolves from a gravitationally unstable to a viscous-dominated state. The MRI-triggered bursts are intrinsically connected with the dust rings in the inner disk regions, and both can be a manifestation of the same phenomenon, that is to say the formation of a dead zone.

Angular momentum profiles of Class 0 protostellar envelopes

Context. Understanding the initial properties of star forming material and how they affect the star formation process is a key question. The infalling gas must redistribute most of its initial angular momentum inherited from prestellar cores before reaching the central stellar embryo. Disk formation has been naturally considered as a possible solution to this “angular momentum problem”. However, how the initial angular momentum of protostellar cores is distributed and evolves during the main accretion phase and the beginning of disk formation has largely remained unconstrained up to now. Aims. In the framework of the IRAM CALYPSO survey, we obtained observations of the dense gas kinematics that we used to quantify the amount and distribution of specific angular momentum at all scales in collapsing-rotating Class 0 protostellar envelopes. Methods. We used the high dynamic range C18O (2−1) and N2H+ (1−0) datasets to produce centroid velocity maps and probe the rotational motions in the sample of 12 envelopes from scales ~50 to ~5000 au. Results. We identify differential rotation motions at scales ≲1600 au in 11 out of the 12 protostellar envelopes of our sample by measuring the velocity gradient along the equatorial axis, which we fit with a power-law model v ∝ rα. This suggests that coherent motions dominate the kinematics in the inner protostellar envelopes. The radial distributions of specific angular momentum in the CALYPSO sample suggest the following two distinct regimes within protostellar envelopes: the specific angular momentum decreases as j ∝ r1.6±0.2 down to ~1600 au and then tends to become relatively constant around ~6 × 10−4 km s−1 pc down to ~50 au. Conclusions. The values of specific angular momentum measured in the inner Class 0 envelopes suggest that material directly involved in the star formation process (<1600 au) has a specific angular momentum on the same order of magnitude as what is inferred in small T-Tauri disks. Thus, disk formation appears to be a direct consequence of angular momentum conservation during the collapse. Our analysis reveals a dispersion of the directions of velocity gradients at envelope scales >1600 au, suggesting that these gradients may not be directly related to rotational motions of the envelopes. We conclude that the specific angular momentum observed at these scales could find its origin in other mechanisms, such as core-forming motions (infall, turbulence), or trace an imprint of the initial conditions for the formation of protostellar cores.