Progress and challenges in modelling country-level HIV/AIDS epidemics: the UNAIDS Estimation and Projection Package 2007

The UNAIDS Estimation and Projection Package (EPP) was developed to aid in country-level estimation and short-term projection of HIV/AIDS epidemics. This paper describes advances reflected in the most recent update of this tool (EPP 2007), and identifies key issues that remain to be addressed in future versions. The major change to EPP 2007 is the addition of uncertainty estimation for generalised epidemics using the technique of Bayesian melding, but many additional changes have been made to improve the user interface and efficiency of the package. This paper describes the interface for uncertainty analysis, changes to the user interface for calibration procedures and other user interface changes to improve EPP’s utility in different settings. While formal uncertainty assessment remains an unresolved challenge in low-level and concentrated epidemics, the Bayesian melding approach has been applied to provide analysts in these settings with a visual depiction of the range of models that may be consistent with their data. In fitting the model to countries with longer-running epidemics in sub-Saharan Africa, a number of limitations have been identified in the current model with respect to accommodating behaviour change and accurately replicating certain observed epidemic patterns. This paper discusses these issues along with their implications for future changes to EPP and to the underlying UNAIDS Reference Group model

МЕХАНІЗМ ФІНАНСОВОГО КОНТРОЛЮ ЗА РОЗПОДІЛОМ БЮДЖЕТНИХ КОШТІВ ЗАЛЕЖНО ВІД РЕЗУЛЬТАТІВ НАУКОВОЇ ДІЯЛЬНОСТІ ЗАКЛАДУ ВИЩОЇ ОСВІТИ

The article proposes a mechanism for financial control over the allocation of budget funds, depending on the results of the scientific activity of a higher education institution (HEI) and its structure, which includes: the purpose and objectives of the mechanism; objects and entities of the mechanism; the basic principles on which the mechanism is based; types of ensuring the implementation of the mechanism; impact levers and tools for implementing the mechanism; methodological approaches to the evaluation of the results of scientific activity; measures of financial control over the allocation of budgetary funds. The concept of «mechanism of financial control over the allocation of budgetary resources depending on the results of scientific activity of a higher education institution» is introduced, which proposes to understand the system of measures and methods of influence of state financial control on the activity of higher education institutions in order to increase the efficiency of spending of budgetary funds by deciding on financing. HEI based on the results of scientific research. It is stated that the main directions of ensuring the functioning of the mechanism of financial control over the allocation of budget funds, depending on the results of scientific activity of the institution of higher education are: legal, regulatory and information. The main levers of influence on the functioning of the proposed mechanism have been systematized: licensing of a specialty, which will be used for the preparation of applicants for higher education; accreditation of educational programs in specialties; state certification of HEI depending on the results of scientific activity; allocation of budgetary funds depending on the results of the state certification of the HEI. The instruments of implementation of the mechanism of financial control over the allocation of budget funds, depending on the results of the scientific activity of the HEI include: financial control; state financial audit; IT audit. The mechanism of carrying out an IT audit of the results of the scientific activity of HEI is proposed by searching for information on the results of the scientific activity of employees and comparing it with the information of the HEI, submitted in the application for state certification in the part of carrying out scientific (scientific and technical) activity.Запропоновано механізм фінансового контролю за розподілом бюджетних коштів залежно від результатів наукової діяльності закладу вищої освіти (ЗВО) і його структуру, яка включає: мету і завдання механізму; об’єкти і суб’єкти механізму; основні принцип, на яких ґрунтується механізм; види забезпечення реалізації механізму; важелі впливу та інструменти реалізації механізму; методичні підходи до оцінювання результатів наукової діяльності; заходи фінансового контролю за розподілом бюджетних коштів. Введено поняття «механізм фінансового контролю за розподілом бюджетних коштів залежно від результатів наукової діяльності закладу вищої освіти», під яким пропонуємо розуміти систему заходів і методів впливу державного фінансового контролю на діяльність закладів вищої освіти з метою підвищення ефективності витрачання бюджетних коштів шляхом ухвалення рішення про фінансування ЗВО на основі результатів проведених наукових досліджень. Зазначено, що основними напрямами забезпечення функціонування механізму фінансового контролю за розподілом бюджетних коштів залежно від результатів наукової діяльності закладу вищої освіти є: правовий, нормативний та інформаційний. Систематизовано основні важелі впливу на функціонування запропонованого механізму: ліцензування спеціальності, за якою буде проводитись підготовка здобувачів вищої освіти; акредитація освітніх програм за спеціальностями; державна атестація ЗВО залежно від результатів наукової діяльності; розподіл бюджетних коштів залежно від результатів державної атестації ЗВО. До інструментів реалізації механізму фінансового контролю за розподілом бюджетних коштів залежно від результатів наукової діяльності ЗВО віднесено: фінансовий контроль; державний фінансовий аудит; ІТ-аудит. Запропоновано механізм проведення ІТ-аудиту результатів наукової діяльності ЗВО шляхом пошуку інформації про результати наукової діяльності працівників та її порівняння з інформацією ЗВО, поданою у заявці на проходження державної атестації в частині провадження ним наукової (науково-технічної) діяльності

Monoaminergic Orchestration of Motor Programs in a Complex C. elegans Behavior

Monoamines provide chemical codes of behavioral states. However, the neural mechanisms of monoaminergic orchestration of behavior are poorly understood. Touch elicits an escape response in Caenorhabditis elegans where the animal moves backward and turns to change its direction of locomotion. We show that the tyramine receptor SER-2 acts through a $G\alpha_o$ pathway to inhibit neurotransmitter release from GABAergic motor neurons that synapse onto ventral body wall muscles. Extrasynaptic activation of SER-2 facilitates ventral body wall muscle contraction, contributing to the tight ventral turn that allows the animal to navigate away from a threatening stimulus. Tyramine temporally coordinates the different phases of the escape response through the synaptic activation of the fast-acting ionotropic receptor, LGC-55, and extrasynaptic activation of the slow-acting metabotropic receptor, SER-2. Our studies show, at the level of single cells, how a sensory input recruits the action of a monoamine to change neural circuit properties and orchestrate a compound motor sequence.Physic

The balance of Polo-like kinase 1 in tumorigenesis

Polo-like kinase 1 (Plk1) belongs to a family of conserved serine/threonine kinases with a polo-box domain, which have similar but non-overlapping functions in the cell cycle progression. Plk1 plays a key role to ensure the normal mitosis. Interestingly, overexpression of Plk1 is associated with tumor development and could serve as a prognostic marker for many cancers. Due to Plk1 overexpression, several Plk1 inhibitors have been developed and tested for the cancer treatment. However, in a recent study, it has been suggested that down-regulation of Plk1 could also induce aneuploidy and tumor formation in vivo. Therefore, a normal level of Plk1 is important for mitosis. And caution should be taken when Plk1 inhibitors are used in the clinical trial and their side effects including tumorigenesis should be carefully evaluated

A conserved neuropeptide system links head and body motor circuits to enable adaptive behavior

Neuromodulators promote adaptive behaviors that are often complex and involve concerted activity changes across circuits that are often not physically connected. It is not well understood how neuromodulatory systems accomplish these tasks. Here, we show that the Caenorhabditis elegans NLP-12 neuropeptide system shapes responses to food availability by modulating the activity of head and body wall motor neurons through alternate G-protein coupled receptor (GPCR) targets, CKR-1 and CKR-2. We show ckr-2 deletion reduces body bend depth during movement under basal conditions. We demonstrate CKR-1 is a functional NLP-12 receptor and define its expression in the nervous system. In contrast to basal locomotion, biased CKR-1 GPCR stimulation of head motor neurons promotes turning during local searching. Deletion of ckr-1 reduces head neuron activity and diminishes turning while specific ckr-1 overexpression or head neuron activation promote turning. Thus, our studies suggest locomotor responses to changing food availability are regulated through conditional NLP-12 stimulation of head or body wall motor circuits

Co-option of neurotransmitter signaling for inter-organismal communication in C. elegans

Biogenic amine neurotransmitters play a central role in metazoan biology, and both their chemical structures and cognate receptors are evolutionarily conserved. Their primary roles are in cell-to-cell signaling, as biogenic amines are not normally recruited for communication between separate individuals. Here, we show that in the nematode C. elegans, a neurotransmitter-sensing G protein-coupled receptor, TYRA-2, is required for avoidance responses to osas#9, an ascaroside pheromone that incorporates the neurotransmitter, octopamine. Neuronal ablation, cell-specific genetic rescue, and calcium imaging show that tyra-2 expression in the nociceptive neuron, ASH, is necessary and sufficient to induce osas#9 avoidance. Ectopic expression in the AWA neuron, which is generally associated with attractive responses, reverses the response to osas#9, resulting in attraction instead of avoidance behavior, confirming that TYRA-2 partakes in the sensing of osas#9. The TYRA-2/osas#9 signaling system represents an inter-organismal communication channel that evolved via co-option of a neurotransmitter and its cognate receptor

A Conserved Neuropeptide System Links Head and Body Motor Circuits to Enable Adaptive Behavior

Neuromodulators promote adaptive behaviors that are often complex and involve concerted activity changes across circuits that are often not physically connected. It is not well understood how neuromodulatory systems accomplish these tasks. Here, we show that the Caenorhabditis elegans NLP-12 neuropeptide system shapes responses to food availability by modulating the activity of head and body wall motor neurons through alternate G-protein coupled receptor (GPCR) targets, CKR-1 and CKR-2. We show ckr-2 deletion reduces body bend depth during movement under basal conditions. We demonstrate CKR-1 is a functional NLP-12 receptor and define its expression in the nervous system. In contrast to basal locomotion, biased CKR-1 GPCR stimulation of head motor neurons promotes turning during local searching. Deletion of ckr-1 reduces head neuron activity and diminishes turning while specific ckr-1 overexpression or head neuron activation promote turning. Thus, our studies suggest locomotor responses to changing food availability are regulated through conditional NLP-12 stimulation of head or body wall motor circuits

Rapid Scaling Up of Insecticide-Treated Bed Net Coverage in Africa and Its Relationship with Development Assistance for Health: A Systematic Synthesis of Supply, Distribution, and Household Survey Data

Stephen Lim and colleagues use several sources of data to estimate the changes in distribution of insecticide-treated bed nets across Africa between 2000 and 2008, and to analyze the link between development assistance and net coverage