Mechanism of shaping membrane nanostructures of endoplasmic reticulum

Recent advances in super-resolution microscopy revealed the previously unknown nanoscopic level of organization of endoplasmic reticulum (ER), one of the most vital intracellular organelles. Membrane nanostructures of 10- to 100-nm intrinsic length scales, which include ER tubular matrices, ER sheet nanoholes, internal membranes of ER exit sites (ERES), and ER transport intermediates, were discovered and imaged in considerable detail, but the physical factors determining their unique geometrical features remained unknown. Here, we proposed and computationally substantiated a common concept for mechanisms of all ER nanostructures based on the membrane intrinsic curvature as a primary factor shaping the membrane and ultra-low membrane tensions as modulators of the membrane configurations. We computationally revealed a common structural motif underlying most of the nanostructures. We predicted the existence of a discrete series of equilibrium configurations of ER tubular matrices and recovered the one corresponding to the observations and favored by ultra-low tensions. We modeled the nanohole formation as resulting from a spontaneous collapse of elements of the ER tubular network adjacent to the ER sheet edge and calculated the nanohole dimensions. We proposed the ERES membrane to have a shape of a super flexible membrane bead chain, which acquires random walk configurations unless an ultra-low tension converts it into a straight conformation of a transport intermediate. The adequacy of the proposed concept is supported by a close qualitative and quantitative similarity between the predicted and observed configurations of all four ER nanostructures.

Ellipticity and discrete series

We explain by elementary means why the existence of a discrete series representation of a real reductive group G implies the existence of a compact Cartan subgroup of G. The presented approach has the potential to generalize to real spherical spaces.

Invariant measures on nilpotent orbits associated with holomorphic discrete series

Let G R G_\mathbb R be a real form of a complex, semisimple Lie group G G . Assume G R G_\mathbb R has holomorphic discrete series. Let W \mathcal W be a nilpotent coadjoint G R G_\mathbb R -orbit contained in the wave front set of a holomorphic discrete series. We prove a limit formula, expressing the canonical measure on W \mathcal W as a limit of canonical measures on semisimple coadjoint orbits, where the parameter of orbits varies over the positive chamber defined by the Borel subalgebra associated with holomorphic discrete series.

PHARMACOTHERAPY OF SYSTEMIC AUTOIMMUNE DISEASES IN CONDITIONS OF THE COVID-19 PANDEMIC: INNOVATIVE EXPERIMENTAL STUDY

The article presents the results of an innovative experimental study of pharmacotherapy of systemic autoimmune diseases in a pandemic of coronavirus infection is a timely and socially oriented way. The methodology of conducting a content analysis based on the theoretical principles of pharmaceutical and medical law and its components. Author used the method of drug selection developed by the Department of Medical and Pharmaceutical Law, General and Clinical Pharmacy of the Kharkiv Medical Academy of Postgraduate Education. Content analysis was performed by dosage forms by grouping them using the Sturgess formula, followed by the construction of discrete series of variations and distribution polygon. Received data made possible to state, that in some circumstances, doctors have a choice of both drugs and dosage forms. However, the data obtained show a lack of balance between supply and demand for patients and physicians. The analysis allows to obtain a complete description of the balance of "supply and demand" between the range and types of dosage forms of drugs INN Silymarin ATC code A05BA03, that approved for use.

ASSESSMENT OF THE STATE OF THE ORGANIZATION OF CIRCULATION AND THE AVAILABILITY OF MEDICINES FOR DIFFERENT CATEGORIES OF PATIENTS AT THE LEVEL OF OBSTETRIC UNITS

Introduction. In the context of the coronavirus infection pandemic, the relevance of increasing the level of availability of medicines for various categories of patients in primary care is becoming crucial. The aim of the work was to process the state of the organization of circulation and the availability of medicines for various clinical and pharmacological groups of patients at the level of obstetric points. Materials and methods. To assess the organization of circulation and the availability of medicines of various clinical-pharmacological, nomenclature-legal and classification-legal groups, a conditional indicator was used – the conditional availability of medicines, calculated using content analysis. To conduct a content analysis, the organization of the regional primary network of medical care was studied; a list of obstetric points was compiled according to a quantitative indicator by grouping using the Sturges formula, followed by the construction of discrete series of variations and a distribution polygon. Results and discussion. Noted that obstetric centers perform socially oriented tasks to increase the level of organization of circulation and the availability of medicines for all contingents of the population on the principles of medical and pharmaceutical law, as the basis of state policy to minimize risks in the organization of pharmaceutical business. According to our own developed methods using content analysis, the structuring of the primary health care with a network of obstetric points at the regional level was carried out and it was established for the overwhelming majority of districts a low, above low and medium level of conditional availability of drugs for patients. Conclusions. The organization of circulation and the availability of drugs for various contingents of the population in the studied regional primary health care network is at the following level: unsatisfactory (for three districts); low (for five districts); higher than low (twelve districts); medium (for five districts); above average (for one district) satisfactory (for one district). Based on the results obtained, it can be concluded that the insufficient number of obstetric points in the regional primary health care unit is an obstacle to the timely provision of the population with high quality, effective and affordable drugs.

On counting cuspidal automorphic representations for GSp(4)

We find the number s k ⁢ ( p , Ω ) s_{k}(p,\Omega) of cuspidal automorphic representations of GSp ⁢ ( 4 , A Q ) \mathrm{GSp}(4,\mathbb{A}_{\mathbb{Q}}) with trivial central character such that the archimedean component is a holomorphic discrete series representation of weight k ≥ 3 k\geq 3 , and the non-archimedean component at 𝑝 is an Iwahori-spherical representation of type Ω and unramified otherwise. Using the automorphic Plancherel density theorem, we show how a limit version of our formula for s k ⁢ ( p , Ω ) s_{k}(p,\Omega) generalizes to the vector-valued case and a finite number of ramified places.

Rodier type theorem for generalized principal series

Given a regular supercuspidal representation $$\rho $$ ρ of the Levi subgroup M of a standard parabolic subgroup $$P=MN$$ P = M N in a connected reductive group G defined over a non-archimedean local field F, we serve you a Rodier type structure theorem which provides us a geometrical parametrization of the set $$JH(Ind^G_P(\rho ))$$ J H ( I n d P G ( ρ ) ) of Jordan–Hölder constituents of the Harish-Chandra parabolic induction representation $$Ind^G_P(\rho )$$ I n d P G ( ρ ) , vastly generalizing Rodier structure theorem for $$P=B=TU$$ P = B = T U Borel subgroup of a connected split reductive group about 40 years ago. Our novel contribution is to overcome the essential difficulty that the relative Weyl group $$W_M=N_G(M)/M$$ W M = N G ( M ) / M is not a coxeter group in general, as opposed to the well-known fact that the Weyl group $$W_T=N_G(T)/T$$ W T = N G ( T ) / T is a coxeter group. Along the way, we sort out all regular discrete series/tempered/generic representations for arbitrary G, generalizing Tadić’s work on regular discrete series representation for split $$(G)Sp_{2n}$$ ( G ) S p 2 n and $$SO_{2n+1}$$ S O 2 n + 1 , and also providing a new simple proof of Casselman–Shahidi’s theorem on generalized injectivity conjecture for regular generalized principal series. Indeed, such a beautiful structure theorem also holds for finite central covering groups.