The Noether\u2013Lefschetz locus of surfaces in toric threefolds

The Noether-Lefschetz theorem asserts that any curve in a very general surface (Formula presented.) in (Formula presented.) of degree (Formula presented.) is a restriction of a surface in the ambient space, that is, the Picard number of (Formula presented.) is (Formula presented.). We proved previously that under some conditions, which replace the condition (Formula presented.), a very general surface in a simplicial toric threefold (Formula presented.) (with orbifold singularities) has the same Picard number as (Formula presented.). Here we define the Noether-Lefschetz loci of quasi-smooth surfaces in (Formula presented.) in a linear system of a Cartier ample divisor with respect to a (Formula presented.)-regular, respectively 0-regular, ample Cartier divisor, and give bounds on their codimensions. We also study the components of the Noether-Lefschetz loci which contain a line, defined as a rational curve which is minimal in a suitable sense

Duplication of clostridial binding domains for enhanced macromolecular delivery into neurons

Neurological diseases constitute a quarter of global disease burden and are expected to rise worldwide with the ageing of human populations. There is an increasing need to develop new molecular systems which can deliver drugs specifically into neurons, non-dividing cells meant to last a human lifetime. Neuronal drug delivery must rely on agents which can recognise neurons with high specificity and affinity. Here we used a recently introduced ‘stapling’ system to prepare macromolecules carrying duplicated binding domains from the clostridial family of neurotoxins. We engineered individual parts of clostridial neurotoxins separately and combined them using a strong alpha-helical bundle. We show that combining two identical binding domains of tetanus and botulinum type D neurotoxins, in a sterically defined way by protein stapling, allows enhanced intracellular delivery of molecules into neurons. We also engineered a botulinum neurotoxin type C variant with a duplicated binding domain which increased enzymatic delivery compared to the native type C toxin. We conclude that duplication of the binding parts of tetanus or botulinum neurotoxins will allow production of high avidity agents which could deliver imaging reagents and large therapeutic enzymes into neurons with superior efficiency

\u3cem\u3eRPGRIP1\u3c/em\u3e and Cone-Rod Dystrophy in Dogs

Cone–rod dystrophies (crd) represent a group of progressive inherited blinding diseases characterized by primary dysfunction and loss of cone photoreceptors accompanying or preceding rod death. Recessive crd type 1 was described in dogs associated with an RPGRIP1 exon 2 mutation, but with lack of complete concordance between genotype and phenotype. This review highlights role of the RPGRIP1, a component of complex protein networks, and its function in the primary cilium, and discusses the potential mechanisms of genotype–phenotype discordance observed in dogs with the RPGRIP1 mutation

АРТРОПЛАСТИКА ТАЗОБЕДРЕННОГО СУСТАВА ПРИ ДЕСТРУКТИВНО-ДИСТРОФИЧЕСКИХ ПОРАЖЕНИЯХ

Introduction. Hip arthroplasty is considered to be the most effective method providing social and household reintegration for destructive-dystrophic lesions. Goal of the study is to improve the results of surgical treatment using the technology of arthroplasty in patients with decompensated forms of destructive-dystrophic hip joint lesions. Material and methods. It was an open prospective, randomized study carried out on the base of traumatology and ortopaedics department of the Bashkir State Medical University including 710 patients with decompensated destructivedystrophic hip joint lesions. All patients (n=710, of which 6.1% were female) depending on the diacritic approach were divided into groups: the control group included (n=406) patients with hip joint trauma who were provided a conventional range of diagnostic and treatment procedures; the experimental group (n=304) included patients who had a range of diagnostics and treatment of destructive-dystrophic lesions of hip joints based on assessment of the connective tissue phase state. Results. Biometric indicators of stance and walking phase firmly improved in all groups 3 years after arthroplasty (p<0.05). Comparative analysis of arthroplasty results in the research groups showed effectiveness of the developed concept to surgically treat destructive and dystrophic lesions of hip joint on the basis of the system approach in the form of improved parameters of the components of the local and systemic level by 2.38% and 2.3% for osteoarthrosis (p<0.05), by 1.61% and 1.84% for aseptic necrosis of femoral head (p>0.05), by 5.62% and 4.37% for post-traumatic damage of hip joint (p<0.05). Conclusion. Analysis of short-term and long-term results of arthroplasty showed high efficiency of the developed concept of surgical treatment and monitoring of connective tissue phase state at destructive-dystrophic lesions of hip joints based on the system approach in the form of reduced pain syndrome, improvement of functional possibilities and patients life quality.Введение. Эндопротезирование тазобедренного сустава (ТБС) считается наиболее эффективным методом, обеспечивающим социальную и бытовую реинтеграцию при деструктивно-дистрофических поражениях.Цель исследования: улучшить результаты хирургического лечения по технологии артропластики пациентов с декомпенсированными формами деструктивно-дистрофических поражений ТБС.Материалы и методы. На клинических базах кафедры травматологии и ортопедии Башкирского государственного медицинского университета проведено открытое проспективное рандомизированное исследование, включающее 710 пациентов с декомпенсированными деструктивно-дистрофическими поражениями ТБС. Все пациенты (n=710, из них 61,97% женщин), в зависимости от диагностических подходов, были разделены на группы: контрольную группу составили (n=406) пациенты с поражением ТБС, которым проводился традиционный комплекс диагностических и лечебных процедур; исследуемая группа (n=304) включала пациентов, которым проводились комплексная диагностика и лечение деструктивно-дистрофических поражений ТБС на основе оценки фазового состояния соединительной ткани.Результаты. Показатели биометрии фаз опоры и ходьбы достоверно улучшились во всех группах через три года после артропластики (р<0,05). Сравнительный анализ результатов артропластики в группах показал эффективность разработанной концепции хирургического лечения при поражениях ТБС на основе системного подхода в виде улучшения показателей компонент локального и системного уровня на 2,38 и 2,3% при остеоартрозе (р<0,05), на 1,61 и 1,84% при асептическом некрозе головки бедра (р>0,05), на 5,62 и 4,37% при посттравматических поражениях ТБС (р<0,05).Заключение. Анализ ближайших и отдаленных результатов артропластики показал высокую эффективность разработанной концепции хирургического лечения и мониторинга фазового состояния соединительной ткани при деструктивно-дистрофических поражениях ТБС на основе системного подхода в виде уменьшения болевого синдрома, улучшения функциональных возможностей и качества жизни пациентов.

Topological String Amplitudes, Complete Intersection Calabi-Yau Spaces and Threshold Corrections

We present the most complete list of mirror pairs of Calabi-Yau complete intersections in toric ambient varieties and develop the methods to solve the topological string and to calculate higher genus amplitudes on these compact Calabi-Yau spaces. These symplectic invariants are used to remove redundancies in examples. The construction of the B-model propagators leads to compatibility conditions, which constrain multi-parameter mirror maps. For K3 fibered Calabi-Yau spaces without reducible fibers we find closed formulas for all genus contributions in the fiber direction from the geometry of the fibration. If the heterotic dual to this geometry is known, the higher genus invariants can be identified with the degeneracies of BPS states contributing to gravitational threshold corrections and all genus checks on string duality in the perturbative regime are accomplished. We find, however, that the BPS degeneracies do not uniquely fix the non-perturbative completion of the heterotic string. For these geometries we can write the topological partition function in terms of the Donaldson-Thomas invariants and we perform a non-trivial check of S-duality in topological strings. We further investigate transitions via collapsing D5 del Pezzo surfaces and the occurrence of free Z2 quotients that lead to a new class of heterotic duals.Comment: 117 pages, 1 Postscript figur

Consensus recommendation for mouse models of ocular hypertension to study aqueous humor outflow and its mechanisms

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings

Hip Arthroplasty of the Destructive-Dystrophic Lesions

Introduction. Hip arthroplasty is considered to be the most effective method providing social and household reintegration for destructive-dystrophic lesions. Goal of the study is to improve the results of surgical treatment using the technology of arthroplasty in patients with decompensated forms of destructive-dystrophic hip joint lesions. Material and methods. It was an open prospective, randomized study carried out on the base of traumatology and ortopaedics department of the Bashkir State Medical University including 710 patients with decompensated destructivedystrophic hip joint lesions. All patients (n=710, of which 6.1% were female) depending on the diacritic approach were divided into groups: the control group included (n=406) patients with hip joint trauma who were provided a conventional range of diagnostic and treatment procedures; the experimental group (n=304) included patients who had a range of diagnostics and treatment of destructive-dystrophic lesions of hip joints based on assessment of the connective tissue phase state. Results. Biometric indicators of stance and walking phase firmly improved in all groups 3 years after arthroplasty (p<0.05). Comparative analysis of arthroplasty results in the research groups showed effectiveness of the developed concept to surgically treat destructive and dystrophic lesions of hip joint on the basis of the system approach in the form of improved parameters of the components of the local and systemic level by 2.38% and 2.3% for osteoarthrosis (p<0.05), by 1.61% and 1.84% for aseptic necrosis of femoral head (p>0.05), by 5.62% and 4.37% for post-traumatic damage of hip joint (p<0.05). Conclusion. Analysis of short-term and long-term results of arthroplasty showed high efficiency of the developed concept of surgical treatment and monitoring of connective tissue phase state at destructive-dystrophic lesions of hip joints based on the system approach in the form of reduced pain syndrome, improvement of functional possibilities and patients life quality