Canonical quantization and black hole perturbations

We examine the possibility of a constraint-free quantization of linearized gravity, based on the Teukolsky equation for black hole perturbations. We exhibit a simple quadratic (but complex) Lagrangian for the Teukolsky equation, leading to the interpretation that the elementary excitations (gravitons bound to the Kerr black hole) are unstable.Comment: Contribution to the XIXth Max Born Symposium, Wroclaw. 10 pages, LaTeX, no figure

Feasibility of Batch Reactive Distillation with Equilibrium-Limited Consecutive Reactions in Rectifier, Stripper, or Middle-Vessel Column.

A general overall feasibility methodology of batch reactive distillation of multireaction systems is developed to study all the possible configurations of batch reactive distillation. The general model equations are derived for multireaction system with any number of chemical equilibrium-limited reactions and for any number of components. The present methodology is demonstrated with the detailed study of the transesterification of dimethyl carbonate in two reversible cascade reactions in batch reactive distillation process. Pure methanol is produced as distillate, and pure diethyl carbonate is produced at the bottom simultaneously in middle-vessel column; in each section, continuous feeding of ethanol is necessary. The results of feasibility study are successfully validated by rigorous simulations

EXPERIMENTAL AND NUMERICAL INVESTIGATIONS ON THE STABILITY OF CYLINDRICAL SHELLS

The stability of thin-walled cylindrical shells under axial pressure is investigated. The results of both experiments and numerical simulations are presented. An appropriate finite element model is introduced that accounts not only for geometric imperfections but also for non-linearities. It is found that small geometrical imperfections within a given tolerance range have considerable negative effect on the buckling load compared to perfect geometry. Various post buckling shell shapes are possible, which depend on these imperfections. The experiments and simulations show a very good correlation

EXPERIMENTAL AND NUMERICAL INVESTIGATIONS ON THE STABILITY OF CYLINDRICAL SHELLS

The stability of thin-walled cylindrical shells under axial pressure is investigated. The results of both experiments and numerical simulations are presented. An appropriate finite element model is introduced that accounts not only for geometric imperfections but also for non-linearities. It is found that small geometrical imperfections within a given tolerance range have considerable negative effect on the buckling load compared to perfect geometry. Various post buckling shell shapes are possible, which depend on these imperfections. The experiments and simulations show a very good correlation

Development and characterization of synthetic antibodies binding to the cystic fibrosis conductance regulator

Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel in the apical surface of epithelial cells in the airway and gastrointestinal tract, and mutation of CFTR is the underlying cause of cystic fibrosis. However, the precise molecular details of the structure and function of CFTR in native and disease states remains elusive and cystic fibrosis researchers are hindered by a lack of high specificity, high affinity binding reagents for use in structural and biological studies. Here, we describe a panel of synthetic antigen-binding fragments (Fabs) isolated from a phage-displayed library that are specific for intracellular domains of CFTR that include the nucleotide-binding domains (NBD1 and NBD2), the R-region, and the regulatory insertion loop of NBD1. Binding assays performed under conditions that promote the native fold of the protein demonstrated that all Fabs recognized full-length CFTR. However, only the NBD1-specific Fab recognized denatured CFTR by western blot, suggesting a conformational epitope requirement for the other Fabs. Surface plasmon resonance experiments showed that the R-region Fab binds with high affinity to both the phosphorylated and unphosphorylated R-region. In addition, NMR analysis of bound versus unbound R-region revealed a distinct conformational effect upon Fab binding. We further defined residues involved with antibody recognition using an overlapping peptide array. In summary, we describe methodology complementary to previous hybridoma-based efforts to develop antibody reagents to CFTR, and introduce a synthetic antibody panel to aid structural and biological studies

Dereglarea metabolismului sfingolipidelor: maladia Krabbe

Instituţia Medico-Sanitară Publică Institutul Mamei și Copilului, Centrul Medical Universitar Hamburg-Eppendorf, Hamburg, GermaniaIntroducere. Maladia Krabbe reprezintă o patologie neurodegenerativă determinată genetic de defi ciența enzimei lizozomale galactocerebrozidaza (β-GALC), al cărei rol este esențial în dezvoltarea și maturarea mielinei. Defi citul acesteia este responsabil de acumularea galactozilceramidei, care produce o substanță toxică, numită psychosina, ce afectează substanța albă a sistemului nervos central și periferic. Incidența acestei patologii este estimată în jur de 1 la 100.000 de nașteri, 90% atribuindu-se formei infantile [1], cu mecanismul de transmitere autosomal recesiv. Se cunosc peste 75 de mutații în gena GALC care pot provoca maladia Krabbe, însă corelarea genotip–fenotip până în prezent ramâne o provocare [3]. Singura excepție o prezintă ”deleția 30-kb” în gena GALC în stare homozigotă, care rezultă cu activitate nulă a enzimei β-GALC și este predictivă pentru debutul infantilă–precoce al maladiei [6]. Ținând cont de vârsta de debut, se cunosc 4 forme clinice ale bolii Krabbe: infantilă, infantilă-tardivă, juvenilă și forma adultă. Tratamentul acestei patologii se rezumă la transplantul de celule stem (HSCT), eficacitatea căruia este demonstrată doar în perioada presimptomatică

Systemic antibiotic prophylaxis does not affect infectious complications in 1 pediatric burn injury: a meta-analysis

In pediatric burns the use of systemic antibiotic prophylaxis is a standard procedure in some burn centers, though its beneficial effect on the infectious complications is debated. The present meta-analysis aimed at determining whether systemic antibiotic prophylaxis prevents infectious complications in pediatric patients with burn injuries. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to August 2019. We included 6 studies, in which event rates of infectious complications were reported in children with burn injuries receiving or not receiving systemic antibiotic prophylaxis. We found that the overall odds ratio (OR) of developing an infection (including local and systemic) was not different between the groups (OR = 1.35; 95% CI, 0.44, 4.18). The chances for systemic infectious complications alone were also not different between antibiotic-treated and non-treated patients (OR = 0.74; 95% CI, 0.38, 1.45). Based on the age, affected total body surface area, and country income level, we did not find any subgroup that benefited from the prophylaxis. Our findings provide quantitative evidence for the inefficacy of systemic antibiotic prophylaxis in preventing infections in pediatric burns. To validate our conclusion, multinational, randomized trials in a diverse population of children with burn injuries are warranted

Распространенность болезни Помпе у пациентов с идиопатической гиперкреатинкиназемией и слабостью поясно-конечностных мышц (анализ 3076 случаев)*

.Проведен проспективный скрининг дефицита фермента кислой α-глюкозидазы (GAA) европейской когорты пациентов с гиперкреатинкиназемией (гиперКК) и / или слабостью поясно-конечностных мышц (СПКМ) неустановленной этиологии с помощью метода сухого пятна крови (dry blood spot, DBS).Материалы и методы. Образцы DBS были собраны у 3076 взрослых пациентов, проходивших обследование в 7 немецких и британских нервно-мышечных центрах. Все образцы были исследованы на дефицит GAA методом флуорометрии. При выявлении пониженной ферментативной активности определяли наличие мутации гена GAA.Результаты. Из 3076 образцов DBS в 232 (7,6 %) случаях обнаружена низкая ферментативная активность GAA. У 55 (24 %) из 232 пациентов наблюдали изолированную гиперКК, а у 176 (76 %) – гиперКК и СПКМ. При комбинации 2 признаков у 94 % больных активность GAA была снижена. Мутационный анализ выявил мутации гена GAA у 74 (2,4 %) пациентов, при этом 70 больных были гетерозиготными по распространенной мутации сайта сплайсинга гена GAA c.-32-13T>G. У пациентов с подтвержденной болезнью Помпе основной симптомокомплекс состоял из СПКМ (85,3 %) в сочетании с дыхательной недостаточностью (61 %). У 12,0 % больных наблюдали изолированную гиперКК, а у 2,7 % – гиперКК и дыхательную недостаточность.Заключение. В большой когорте пациентов с гиперКК и / или СПКМ  распространенность болезни Помпе с поздним началом составляет 2,4 %, что требует проведения целевого скрининга активности GAA у пациентов с гиперКК и / или СПКМнеустановленной этиологии

Diagnosing mucopolysaccharidosis IVA

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity. Diagnosis can be challenging and requires agreement of clinical, radiographic, and laboratory findings. A group of biochemical genetics laboratory directors and clinicians involved in the diagnosis of MPS IVA, convened by BioMarin Pharmaceutical Inc., met to develop recommendations for diagnosis. The following conclusions were reached. Due to the wide variation and subtleties of radiographic findings, imaging of multiple body regions is recommended. Urinary glycosaminoglycan analysis is particularly problematic for MPS IVA and it is strongly recommended to proceed to enzyme activity testing even if urine appears normal when there is clinical suspicion of MPS IVA. Enzyme activity testing of GALNS is essential in diagnosing MPS IVA. Additional analyses to confirm sample integrity and rule out MPS IVB, multiple sulfatase deficiency, and mucolipidoses types II/III are critical as part of enzyme activity testing. Leukocytes or cultured dermal fibroblasts are strongly recommended for enzyme activity testing to confirm screening results. Molecular testing may also be used to confirm the diagnosis in many patients. However, two known or probable causative mutations may not be identified in all cases of MPS IVA. A diagnostic testing algorithm is presented which attempts to streamline this complex testing process