Finite Hilbert stability of (bi)canonical curves

We prove that a generic canonically or bicanonically embedded smooth curve has semistable m-th Hilbert points for all m. We also prove that a generic bicanonically embedded smooth curve has stable m-th Hilbert points for all m \geq 3. In the canonical case, this is accomplished by proving finite Hilbert semistability of special singular curves with G_m-action, namely the canonically embedded balanced ribbon and the canonically embedded balanced double A_{2k+1}-curve. In the bicanonical case, we prove finite Hilbert stability of special hyperelliptic curves, namely Wiman curves. Finally, we give examples of canonically embedded smooth curves whose m-th Hilbert points are non-semistable for low values of m, but become semistable past a definite threshold. (This paper subsumes the previous submission and arXiv:1110.5960).Comment: To appear in Inventiones Mathematicae, 2012. The final publication is available at http://www.springerlink.co

Features of type 2 diabetes mellitus and its pharmacotherapy in outpatients

Background. Type 2 diabetes mellitus (DM) remains the most common type of DM and is associat-ed with disabling complications, reduced quality of life and reduced life expectancy. Satisfactory control of carbohydrate metabolism remains the key way to manage them. Aim. To perform a retrospective analysis of carbohydrate metabolism (in terms of glycated hemoglobin – HbA1c), the prevalence of complications, and features of hypoglycemic and concomitant therapy in patients with type 2 DM. Materials and methods. The analysis of sex and age characteristics, achieved level of HbA1c, diabetes complications, sugar-reducing and concomitant therapy according to the data of outpatient records of the patients who are on dispensary registration with an endocrinologist in the Endocrinology Department of the Consultative and Diagnostic Polyclinic of the Tomsk Regional Clinical Hospital in Tomsk was carried out. Results. 546 outpatient medical records of patients with type 2 DM were analysed, among which there were 39.6% men (n=216) with a history of type 2 DM 8.0 years [3.0; 13.0] , median age 64.0 years [54.5; 71.0] and 60.4% women (n=330), history of type 2 DM 10.0 years [5.0; 15.0], median age 70.0 years [63.0; 75.0]. The achieved HbA1c level in men was 7.6% [6.3; 9.0] and in women 7.4% [6.4; 9.1]. 19.4% of men and 13.6% of women had an aggravated history of type 2 DM. According to the history, 6.5% of men (n=14) and 3% of women (n=10) with type 2 DM had a history of stroke, and myocardial infarction 12% (n=26) and 1.5% (n=5), respectively. Among the analysed outpatient records of type 2 DM patients, 18.5% of men (n=40) and 12.4% of women (n=41) were found to have diabetic nephropathy. Diabetic retinopathy was reported in 9.3% (n=20) of men and 4.2% (n=14) of women. Diabetic macroangiopathies were detected in 29.6% (n=64) of males and 9.7% (n=32) of females. Among other chronic complications of DM, diabetic neuroosteoarthropathy was recorded in 1% (n=2) of males and 3% (n=10) of females, diabetic polyneuropathy in 25% (n=54) and 21.5% (n=71), respectively. Diabetic foot was diagnosed in 1.9% (n=4) of men and 1.8% (n=6) of women. Among comorbid pathology, obesity was diagnosed in 45.4% (n=88) of men and 69.1% (n=228) of women, dyslipidaemia in 10.2% (n=22) and 10.6% (n=35) respectively, hypertension in 39.8% (n=86) and 32.6% (n=108) of cases. The diagnosis of non-alcoholic fatty liver disease was verified in 3.7% of men (n=7) and 1.8% of women (n=6), chronic heart failure in 7.4% of men (n=16) and 2.4% of women (n=8) registered for type 2 DM. According to the analysed outpatient records, 4.1% (n=23) of patients received diet therapy, 48.3% (n=263) received monotherapy and 47.6% (n=260) received combination therapy for type 2 DM. Metformin was the most commonly used monotherapy for type 2 DM 36.1% (n=197), followed by insulin 6.9% (n=38), sulfonylurea derivatives – 2.7% (n=15). Combination of metformin and dipeptidyl peptidase-4 inhibitors (13.9%) was the most commonly used combination therapy. Conclusion. Analysis of the current situation in the diabetology service will help to identify weaknesses and strengths, which is necessary to optimise existing therapeutic approaches in accordance with current clinical recommendations

Preparation of polyclonal and monoclonal anti-idiotypic antibodies against morphine-specific immunoglobulins

The preparation and study of anti-idiotypic (secondary) antibodies (Ab2) against monoclonal primary antibodies (Ab1) specific to biologically active molecules with a known structure is of great scientific and practical importance. Due to partial antigenic similarity of Ab2 and the initial antigen structures, these antibodies can be the basis of the vaccine, if the antigen usage is not possible, or is limited by law. In particular, one may create Ab2-based preparations, designed for immunization, in order to prevent and treat the drug addiction. The value of Ab2 properties increases even more if Ab1, used to obtain them, recognize different parts of the antigen molecule, which makes it possible to obtain second-generation antibodies with a wide range of specificity. In this work, the morphine-like polyclonal and monoclonal Ab2 were obtained. In each case, as the first-generation immunoglobulins for immunization, we used two murine monoclonal antibodies (mAbs) specific to different morphine derivatives: 3K11 antibodies to 3-0-carboxymethyl (CMM) and 2-p-carboxyphenylazomethyl (FAM) derivatives, as well as 6G1 antibodies to 6-hemisuccinyl derivative (GSM). After immunization of the horse with Ab1 and development of immune response, three pools of specific polyclonal antibodies were isolated from the animal blood serum: horse anti-species antibodies to the total mouse immunoglobulins (HAM); horse anti-idiotypic antibodies against 3K11 antibodies (HAM-K11), and against 6G1 antibodies (HAM-G1). In parallel, immunization of mice with 3K11 and 6G1 antibodies and fusion of obtained lymphocytes with Sp2/0 mouse myeloma cells by the Milstein-Köhler method resulted in three producers of anti-idiotypic antibodies: a clone producing mouse monoclonal Ab2 specific for mAb-6G1 (AIG1), as well as clones producing anti-mAb-3K11 antibodies (AI-K11A and AI-K11B). The physico-chemical and antigenic properties of all the Ab2 obtained were characterized. It was shown that the horse anti-idiotypic immunoglobulins not only belong to different classes, but are also polyvalent, while all monoclonal Ab2 obtained are represented by IgM immunoglobulins, being also strictly specific to the corresponding first-generation antibodies. Subsequently, the morphine-like properties of the first domestic polyclonal and monoclonal Ab2 obtained in the work will be investigated in a cellular model. Likewise, we shall study their ability to induce Ab3 as well as morphine-specific Ab1

PREPARATION AND PROPERTIES OF MURINE ANTI-IDIOTYPIC MONOCLONAL ANTIBODIES RECOGNIZING PRIMARY RABBIT POLYCLONAL ANTIBODIES AGAINST MORPHINE DERIVATIVES

Anti-idiotypic antibodies (Ab2), according to the network theory of Jerne, are second-generation immunoglobulins that are produced against the idiotype of an antibody to a specific antigen. Despite the large number of works devoted to the study of the properties of these proteins, their role in the regulation of the immune system is not fully known. It may consist in maintaining or blocking a minimal immune response to the antigen. The study of Ab2 is of great practical and scientific importance. The special properties of Ab2, namely, the ability to partially reproduce the structure of the primary antigen and, upon immunization, induce the appearance of tertiary antibodies, which, like first-generation antibodies, can bind to the antigen, have found application in the development of Ab2-based vaccines, in particular, for the treatment of tumors. In view of the presence of a number of limitations on research related to psychoactive substances, the development of Ab2- based vaccines against drug addiction also seems promising. To example, anti-idiotypic antibodies obtained for this purpose possessing a cocaine-like structure are described in the literature. In this work, murine monoclonal anti-idiotypic antibodies (mAb2) mimicking the structure of various morphine derivatives were obtained. Rabbit polyclonal antibodies to the 6-hemisuccinyl derivative of morphine conjugated with bovine serum albumin isolated by affinity chromatography were used as primary antibodies for immunization. Four hybridoma clones were obtained as a result of the fusion of immunized mice lymphocytes with mouse Sp2/0 mouse myeloma cells by the Milstein-Köhler method. After growth in animals, mAb2 produced by hybridoma cells were affinity purified. We investigated the physicochemical and antigenic properties of the isolated antibodies. It was shown that the obtained mAb2 differ in immunological specificity, competing in different degree with morphine derivatives for binding to first-generation antibodies. We tested the possibility of using the obtained mAb2 as antigen analogues in the solid-phase enzyme-linked immunosorbent assay to determine the titer of primary antibodies against morphine in the blood serum of laboratory animals immunized with morphine derivatives. Based on the obtained anti-idiotypic antibodies, it is proposed to develop test systems to determine the serum opiate-specific antibodies in people after specific vaccination for therapeutic or prophylactic purposes to avoid the use of drugs as antigens immobilized on the solid phase in the analysis

Mitochondrial respiratory states and rate

As the knowledge base and importance of mitochondrial physiology to human health expands, the necessity for harmonizing the terminologyconcerning mitochondrial respiratory states and rates has become increasingly apparent. Thechemiosmotic theoryestablishes the mechanism of energy transformationandcoupling in oxidative phosphorylation. Theunifying concept of the protonmotive force providestheframeworkfordeveloping a consistent theoretical foundation ofmitochondrial physiology and bioenergetics.We followguidelines of the International Union of Pure and Applied Chemistry(IUPAC)onterminology inphysical chemistry, extended by considerationsofopen systems and thermodynamicsof irreversible processes.Theconcept-driven constructive terminology incorporates the meaning of each quantity and alignsconcepts and symbols withthe nomenclature of classicalbioenergetics. We endeavour to provide a balanced view ofmitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes.Uniform standards for evaluation of respiratory states and rates will ultimatelycontribute to reproducibility between laboratories and thussupport the development of databases of mitochondrial respiratory function in species, tissues, and cells.Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Coincidence Tests of a Compton Telescope Based on Continuous LaBr3 Crystals and SiPMs for Dose Monitoring in Hadron Therapy

International audienceIn hadron therapy, a proton or carbon ion beam interacts with the tissue and prompt gamma rays are emitted from the excited nuclei that can be employed for dose monitoring. A Compton telescope makes it possible to locate the origin of these photons, allowing an indirect estimation of the delivered dose. The telescope prototype being developed at IFIC-Valencia within the ENVISION project will consist of three detector layers. Each layer will be composed of a continuous LaBr3 crystal coupled to four Silicon Photomultiplier (SiPM) arrays. Coincidence tests have been carried out with a first layer of a 16 mm × 18 mm × 5 mm LaBr3 crystal coupled to a 16 mm × 18 mm SiPM array and a second layer of a 12 mm × 12 mm × 5 mm LYSO crystal coupled to another 16 mm × 18 mm SiPM array. The test system is read out by two SPIROC1 boards working in time coincidence. First data have been taken and the results demonstrate the feasibility of operating the system