A Model of the Influence of Neutral Air Dynamics on the Seasonal Variation in the Low Ionosphere

Recently it has become clear that the phenomena in the ionospheric D-region are determined to a great extent by dynamical processes in the strato-mesosphere D-region. In this respect much attention is paid to the study of the winter anomaly (WA) phenomenon on medium and short radiowaves, in which the meteorological character of the lower ionosphere is most prominent. Significant experimental data about the variations of the electron concentration, N, ion composition, temperature and dynamic regime during WA permit a better understanding of the character of the physical processes in the middle atmosphere. The influence of the neutral wind on the seasonal variation of the electron concentration N for the altitude interval 90 or = z or = 120 km, where the ratio upsilon sub in/omega sub i, of the ion-neutral collision frequency, upsilon sub in and the ion gyrofrequency, omega sub i decreases from 40 to 1 was evaluated. CIRA-72 is used as a model of the zonal wind

Višestruko ometena deca oštećenog sluha u školama u Srbiji

Recently, there has been an impression that in schools for children with impaired hearing there are more and more children who, besides hearing impairment, have one or more additional disabilities. This paper discusses the concept of multiple disabilities in children with impaired hearing and the criteria for classifying these children. Goal of the paper was to study how many multiply disabled children with impaired hearing there are in schools for children with impaired hearing in Serbia and what are the kinds of additional disabilities present in this population. Research was performed in all schools for children with impaired hearing in Serbia. We established that there are 76 pupils in those schools who, besides impaired hearing, have one or more additional disabilities. The paper presents in form of tables and charts the structure of the group of multiply disabled pupils with impaired hearing with respect to demographic variables and type of disability.Poslednjih godina stiče se utisak da je u školama za decu oštećenog sluha sve više dece koja pored oštećenja sluha imaju jednu ili više dodatnih ometenosti. U radu smo razmotrili pojam višestruke ometenosti kod dece oštećenog sluha i kriterijume za razvrstavanje ove dece. Cilj rada je bio da se ispita koliko u školama za decu oštećenog sluha u Srbiji ima višestruko ometene dece oštećenog sluha i koje su vrste dodatnih ometenosti zastupljene u ovoj populaciji. Istraživanje je obavljeno u svim školama za decu oštećenog sluha u Srbiji. Utvrdili smo da se u pomenutim školama nalazi 76 učenika koji pored oštećenja sluha imaju jedno ili više dodatnih oštećenja. U radu je tabelarno i grafički prikazana struktura grupe učenika oštećenog sluha sa višestrukom ometenošću, s obzirom na demografske varijable i tip oštećenja

Composing JSON-based Web APIs

International audienceThe development of Web APIs has become a discipline that companies have to master to succeed in the Web. The so-called API economy is pushing companies to provide access to their data by means of Web APIs, thus requiring web developers to study and integrate such APIs into their applications. The exchange of data with these APIs is usually performed by using JSON, a schemaless data format easy for computers to parse and use. While JSON data is easy to read, its structure is implicit, thus entailing serious problems when integrating APIs coming from di erent vendors. Web developers have therefore to understand the domain behind each API and study how they can be composed. We tackle this issue by presenting an approach able to both discover the domain of JSON-based Web APIs, and identify composition links among them. Our approach allows developers to easily visualize what is behind APIs and how they can be composed to be used in their applications

Population pharmacokinetics-based recommendations for a single delayed or missed dose of nusinersen

Nusinersen is an antisense oligonucleotide approved for the treatment of spinal muscular atrophy. The drug is given intrathecally at 12 mg, beginning with 3 loading doses at 2-week intervals, a fourth loading dose 30 days thereafter, and maintenance doses at 4-month intervals. This population pharmacokinetic model was developed to clarify how to maintain targeted nusinersen exposure after an unforeseen one-time delay or missed dose. Simulations demonstrated that the impact of a one-time delay in dosing or a missed dose on median cerebrospinal fluid exposures depended on duration of interruption and the regimen phase in which it occurred. Delays in loading doses delayed reaching the peak trough concentration by approximately the duration of the interruption. Resumption of the regimen as soon as possible resulted in achieving steady state trough concentration upon completion of the loading phase. A short delay (30-90 days) during the maintenance phase led to prolonged lower median cerebrospinal fluid concentration if all subsequent doses were shifted by the same 4-month interval. However, administration of the delayed dose, followed by the subsequent dose as originally scheduled, rapidly restored trough concentration. If a dose must be delayed, patients should return to the original dosing schedule as soon as possible

Odabir endogene kontrole za imunoblot analizu proteina u sklerotičnim hipokampusima pacijenata sa epilepsijom temporalnog režnja

Skleroza hipokampusa je najčešći neuropatološki nalaz kod epilepsije temporalnog režnja. Pored morfoloških promena odlikuju ga i promene nivoa različitih proteina u ćeliji. Imunoblot je nezamenjiva metoda za određivanje nivoa proteina i podrazumeva normalizaciju u odnosu na endogenu kontrolu (kontrolu jednakog nanošenja uzorka). Za tu svrhu se koriste proteini za koje se smatra da imaju stabilnu ekspresiju koja najmanje varira u ispitivanim uslovima, tretmanima i patofiziološkim stanjima. Ipak u nekim patofiziološkim stanjima se i ekspresija tradicionalno korišćenih endogenih kontrola menja, 1 što može dovesti do prikupljanja netačnih podataka i pogrešnog tumačenja rezultata. Cilj ovog rada je bio da se ispita stabilnost najčešće korišćenih endogenih kontrola i izabere najstabilnija koja će se koristiti za normalizaciju pri poređenju nivoa ciljnih proteina hipokampusa obolelih od epilepsije i neurološki intaktnih kontrola. Imunoblotom su detektovani β-aktin, α-tubulin, TATA-vezujući protein i gliceraldehid3-fosfat dehidrogenaza u tkivnim ekstraktima hipokampusa 9 pacijenata i 7 kontrola, i NormFinder softverom2 određene unutargrupna i međugrupna varijabilnost. Pokazano je da nivo strukturnih proteina β-aktina i α-tubulina najmanje varira u ispitivanim uslovima te se mogu koristiti za poređenje nivoa proteina u sklerotičnim i intaktnim hipokampusima. Rezultati upućuju da je odabir endogenih kontrola važan preduslov za dobijanje tačnih i pouzdanih podataka imunoblot metodom

The importance of copper in pathology of mesial temporal lobe epilepsy

More and more studies are identifying the regulation of metal homeostasis as one of the key points of central nervous system’s well-being. Epilepsy is a particularly interesting neurological condition when viewed in terms of the correlation between the amount of metals and the development of a seizure. This lecture will present contribution of our group to the field of metal biology in epilepsy by mapping brain metals in sclerotic hippocampus resected from drug resistant mesial temporal lobe epilepsy (mTLE) patients as surgical therapeutic approach. Direct insight into this epileptogenic area, by two powerful techniques, optical emission and mass spectrometry, has led us to investigation of copper turnover. Namely, among the examined metals, we found the deficiency of copper in sclerotic hippocampus on two levels: (i) in whole structure (ii) and locally in the areas of neuronal loss, with significant correlation between copper concentration and neuron density. Furthermore, analysis of copper metalloproteins showed: (i) significant increase or decrease in levels of protein that is participating in copper transport into the cell (CTR1) depending on the degree of hippocampal neuronal loss; (ii) and lower activity of an enzyme in which copper is part of the active site, cytochrome c oxidase, in sclerotic hippocampi of patients compared to control tissue. In our further investigations it remained to be determined whether changes in copper concentrations and copper metalloproteins are causal to pathology of mTLE or they represent epiphenomenon

BioDMET: a physiologically based pharmacokinetic simulation tool for assessing proposed solutions to complex biological problems

We developed a detailed, whole-body physiologically based pharmacokinetic (PBPK) modeling tool for calculating the distribution of pharmaceutical agents in the various tissues and organs of a human or animal as a function of time. Ordinary differential equations (ODEs) represent the circulation of body fluids through organs and tissues at the macroscopic level, and the biological transport mechanisms and biotransformations within cells and their organelles at the molecular scale. Each major organ in the body is modeled as composed of one or more tissues. Tissues are made up of cells and fluid spaces. The model accounts for the circulation of arterial and venous blood as well as lymph. Since its development was fueled by the need to accurately predict the pharmacokinetic properties of imaging agents, BioDMET is more complex than most PBPK models. The anatomical details of the model are important for the imaging simulation endpoints. Model complexity has also been crucial for quickly adapting the tool to different problems without the need to generate a new model for every problem. When simpler models are preferred, the non-critical compartments can be dynamically collapsed to reduce unnecessary complexity. BioDMET has been used for imaging feasibility calculations in oncology, neurology, cardiology, and diabetes. For this purpose, the time concentration data generated by the model is inputted into a physics-based image simulator to establish imageability criteria. These are then used to define agent and physiology property ranges required for successful imaging. BioDMET has lately been adapted to aid the development of antimicrobial therapeutics. Given a range of built-in features and its inherent flexibility to customization, the model can be used to study a variety of pharmacokinetic and pharmacodynamic problems such as the effects of inter-individual differences and disease-states on drug pharmacokinetics and pharmacodynamics, dosing optimization, and inter-species scaling. While developing a tool to aid imaging agent and drug development, we aimed at accelerating the acceptance and broad use of PBPK modeling by providing a free mechanistic PBPK software that is user friendly, easy to adapt to a wide range of problems even by non-programmers, provided with ready-to-use parameterized models and benchmarking data collected from the peer-reviewed literature