Miracle-dz/UniFAR-FTUs huggingface dataset:
The credit assignment problem in cortico‐basal ganglia‐thalamic networks: A review, a problem and a possible solution

The question of how cortico‐basal ganglia‐thalamic (CBGT) pathways use dopaminergic feedback signals to modify future decisions has challenged computational neuroscientists for decades. Reviewing the literature on computational representations of dopaminergic corticostriatal plasticity, we show how the field is converging on a normative, synaptic‐level learning algorithm that elegantly captures both neurophysiological properties of CBGT circuits and behavioral dynamics during reinforcement learning. Unfortunately, the computational studies that have led to this normative algorithmic model have all relied on simplified circuits that use abstracted action‐selection rules. As a result, the application of this corticostriatal plasticity algorithm to a full model of the CBGT pathways immediately fails because the spatiotemporal distance between integration (corticostriatal circuits), action selection (thalamocortical loops) and learning (nigrostriatal circuits) means that the network does not know which synapses should be reinforced to favor previously rewarding actions. We show how observations from neurophysiology, in particular the sustained activation of selected action representations, can provide a simple means of resolving this credit assignment problem in models of CBGT learning. Using a biologically realistic spiking model of the full CBGT circuit, we demonstrate how this solution can allow a network to learn to select optimal targets and to relearn action‐outcome contingencies when the environment changes. This simple illustration highlights how the normative framework for corticostriatal plasticity can be expanded to capture macroscopic network dynamics during learning and decision‐making.
Propofol inhibits migration and induces apoptosis of pancreatic cancer PANC-1 cells through miR-34a-mediated E-cadherin and LOC285194 signals

ABSTRACT Propofol has exhibited potent antitumor activity in pancreatic cancer cells in vitro and in vivo. The study aimed to investigate the anti-tumor mechanisms of propofol on pancreatic cancer PANC-1 cells in vitro. PANC-1 cells were exposure to concentration 20 μg/ml of propofol for 72 h. Long non-coding RNA LOC285194 siRNA LOC285194 siRNA, E-cadherin siRNA and microRNA-34a (miR-34a) inhibitor were used to investigate the effect of propofol on PANC-1 cells. miR-34a and LOC285194 were analyzed by quantitative real-time PCR (qRT-PCR). Pro-apoptotic protein bax, cleaved-caspase-3 and anti-apoptotic protein bcl-2 were analyzed by Western blot. Cell viability and cell apoptosis were detected by MTT and TUNEL staining, respectively. Cell migration was detected by wound-healing assay. The results showed that propofol upregulated miR-34a expression, which, in turn, upregulated LOC285194 expression, resulting in PANC-1 cell apoptosis and growth inhibition. In addition, propofol upregulated miR-34a expression, which, in turn, upregulated E-cadherin expression, resulting in cell migration inhibition. Our research confirmed that propofol-induced cell apoptosis and inhibited cell migration in PANC-1 cells in vitro via promoting miR-34a-dependent LOC285194 and E-cadherin upregulation, respectively.
SYNCHRONIZED MAMMALIAN CELLS IN SUSPENSION CULTURE

High yields of synchronized mammalian cells in suspension culture have been obtained by reversible interference with DNA synthesis through introduction and removal of high concentrations (1 to 25 m ) of thymidine, deoxycytidine, deoxyguanosine or deoxyadenosine at tvo specified intervals tn a double blocking procedure [Puck, Boot sna et al., Exptl. Cell Res. 33, 301 originally suggested to us by Puck. ABSTRACT High yields of synchronized mammalian cells in suspension culture have been obtained by reversible i n te r fe re n ce with DNA synthesis through introduction and removal of high concentrations (1 to 25 mM) of thymidine or deoxycytidine at two specified intervals. Appropriate spacing of blockade and r e l ea s e r e s u l t ed i n s eg r ega t i on · o f t he en t i r e popu l a t i on int o a s ingle pha se of the life cycle . Up on re lease from the second deoxynucleoside blockade, a synchronous wave of cells comprising up to 100 percent of the population underwent mitosis within a period of approximately 4 hours. This
The Changing Face of Nuclear Cardiology: Guiding Cardiovascular Care Toward Molecular Medicine

Radionuclide imaging of myocardial perfusion, function, and viability has been established for decades and remains a robust, evidence-based and broadly available means for clinical workup and therapeutic guidance in ischemic heart disease. Yet, powerful alternative modalities have emerged for this purpose, and their growth has resulted in increasing competition. But the potential of the tracer principle goes beyond the assessment of physiology and function, toward the interrogation of biology and molecular pathways. This is a unique selling point of radionuclide imaging, which has been underrecognized in cardiovascular medicine until recently. Now, molecular imaging methods for the detection of myocardial infiltration, device infection, and cardiovascular inflammation are successfully gaining clinical acceptance. This is further strengthened by the symbiotic quest of cardiac imaging and therapy for an increasing implementation of molecule-targeted procedures, in which specific therapeutic interventions require specific diagnostic guidance toward the most suitable candidates. This review will summarize the current advent of clinical cardiovascular molecular imaging and highlight its transformative contribution to the evolution of cardiovascular therapy beyond mechanical interventions and broad blockbuster medication, toward a future of novel, individualized molecule-targeted and molecular imaging–guided therapies.
A human-origin probiotic cocktail ameliorates aging-related leaky gut and inflammation via modulating microbiota-taurine-tight junction axis.

Inflammation is a major risk factor of morbidity and mortality in older adults. Although its precise etiology is unknown, low-grade inflammation in older adults is commonly associated with increased intestinal epithelial permeability (leaky gut) and abnormal (dysbiotic) gut microbiota. The increasing older population and lack of treatments to reduce aging-related microbiota dysbiosis, leaky gut and inflammation culminates on a rise in aging-related comorbidities, constituting a significant public health concern. Here we demonstrate that a human-origin probiotic cocktail containing 5-Lactobacillus and 5 Enterococcus strains isolated from healthy infant's gut prevents high-fat diet (HFD)-induced microbiota dysbiosis, leaky gut, inflammation, metabolic dysfunctions and physical function decline in older mice. Probiotic-modulated gut microbiota primarily reduced leaky gut by increasing tight junctions, which in turn reduced inflammation. Mechanistically, probiotics modulated microbiota in a way to increases bile salt hydrolase activity, which in turn increased taurine abundance in the gut that stimulated tight junctions and suppressed gut leakiness. Further, in Caenorhabditis elegans, taurine increased life span, reduced adiposity and leaky gut, and enhanced physical function. The results suggest that such probiotic therapies could prevent or treat aging-related leaky gut and inflammation in elderly.
CHAID Algoritması ile Balık Eti Tüketimini Etkileyen Faktörlerin İncelenmesi

Inthis study, factors affecting the monthly fishmeat consumption was investigated in the survey administered to 384 people with CHAID algorithm central district of Bingol province. The dependent variable used is in fishmeat consumption. The independent variables are age, education level, occupation, number of households, vehiclenership, place of residence, income, expenses, food expenses and monthly fish consumption. Determination factor (R 2 ), corrected determination coefficient and correlation coefficient were used to determine the effect of the model and factors affecting fish consumption by creating a regression tree. Factors affecting fishmeat consumption are; monthly fish expenditure (P <0.01), city of residence time (P <0.01), total monthly expenditure (P <0.01), car ownership (P <0.01), the number of households (P <0.01), total monthly income (P <0.01) and job (P <0.01). The determination coefficient (%) and the corrected determination coefficient (%) were calculated as 70.06 and 69.74, respectively, while a strong and positive correlation (r = 0.837) was found between observed and estimated fishing consumptions. On average, the most fishing consumptions are; Total monthly income was obtained from the subgroup of individuals whose monthly fish expenditure was BH> 240 TL and whose household number was more than 3 persons. Household income was found to be more in fluential on economic factors and household number of people in fish consumption. According to these results, lowering fish prices, raising the education level of consumers and increasing the number of households will be reflected positively in fish consumption.
Lipid Nanoparticles As A Skin Wound Healing Drug Delivery System: Discoveries And Advances.

Chronic wounds are a remarkable cause of morbidity, requiring long-time treatments with significant impact on quality of life and high costs for public health. Although there are a variety of topical skin preparations commercially available, they have several limitations that frequently impair wound healing, such as drug instability, toxicity, limited time of action and ineffective skin permeation. In recent years, researchers have focused on the development of new effective treatments for wound healing and frequently appeal for nanometric drug delivery systems to overcome such obstacles. In dermatology, lipid nanoparticles (LNP) have received great attention of researchers due to its great functionalities, greater adhesion to the skin and film formation, enabling the hydration and maintenance of skin integrity, as well as presents a more effective penetration through the skin barrier. This review provides an update on topical formulations based on Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) as wound healing treatments. Both SLN and NLC are able to increase solubility and stability of active pharmaceutical ingredients, and to increase skin penetration compared to the free drugs. Additionally, SLN and NLC can increase pharmacological activity, increase the release profile of the drugs, promote synergistic effects and improve the sensory properties of the final formulation. Topical dosage forms containing nanoparticles have been extensively evaluated for wound healing activity, mainly the dressings, films and scaffolds. Therefore, lipid nanoparticles have contributed to improve wound healing therapies, including when incorporated into other dosage forms, with better efficacy and lesser adverse effects than conventional formulations.
Resting state networks of the canine brain under sevoflurane anaesthesia

Resting-state functional Magnetic Resonance Imaging (rs-fMRI) has become an established technique in humans and reliably determines several resting state networks (RSNs) simultaneously. Limited data exist about RSN in dogs. The aim of this study was to investigate the RSNs in 10 healthy beagle dogs using a 3 tesla MRI scanner and subsequently perform group-level independent component analysis (ICA) to identify functionally connected brain networks. Rs-fMRI sequences were performed under steady state sevoflurane inhalation anaesthesia. Anaesthetic depth was titrated to the minimum level needed for immobilisation and mechanical ventilation of the patient. This required a sevoflurane MAC between 0.8 to 1.2. Group-level ICA dimensionality of 20 components revealed distributed sensory, motor and higher-order networks in the dogs’ brain. We identified in total 7 RSNs (default mode, primary and higher order visual, auditory, two putative motor-somatosensory and one putative somatosensory), which are common to other mammals including humans. Identified RSN are remarkably similar to those identified in awake dogs. This study proves the feasibility of rs-fMRI in anesthetized dogs and describes several RSNs, which may set the basis for investigating pathophysiological characteristics of various canine brain diseases.
Crystal Contact Engineering Enables Efficient Capture and Purification of an Oxidoreductase by Technical Crystallization

Technical crystallization is an attractive method to purify recombinant proteins. However, it is rarely applied due to the limited crystallizability of many proteins. To overcome this limitation, single amino acid exchanges are rationally introduced to enhance intermolecular interactions at the crystal contacts of the industrially relevant biocatalyst Lactobacillus brevis alcohol dehydrogenase (LbADH). The wildtype (WT) and the best crystallizing and enzymatically active LbADH mutants K32A, D54F, Q126H, and T102E are produced with Escherichia coli and subsequently crystallized from cell lysate in stirred mL‐crystallizers. Notwithstanding the high host cell protein (HCP) concentrations in the lysate, all mutants crystallize significantly faster than the WT. Combinations of mutations result in double mutants with faster crystallization kinetics than the respective single mutants, demonstrating a synergetic effect. The almost entire depletion of the soluble LbADH fraction at crystallization equilibrium is observed, proving high yields. The HCP concentration is reduced to below 0.5% after crystal dissolution and recrystallization, and thus a 100‐fold HCP reduction is achieved after two successive crystallization steps. The combination of fast kinetics, high yields, and high target protein purity highlights the potential of crystal contact engineering to transform technical crystallization into an efficient protein capture and purification step in biotechnological downstream processes.
Consequences of drought severity for tropical live oak (Quercus oleoides) in Mesoamerica.

In two Costa Rican and three Honduran sites that vary in rainfall and soil properties, we used natural isotopes, a soil water balance model and broad-scale climate-based drought indices to study shifts in water use with ontogeny from seedlings to mature tropical live oak (Quercus oleoides) trees. Water use patterns help to explain persistence of this broadly distributed species in Mesoamerica and to evaluate likely threats of on-going climate changes. At the end of the dry season, soil δ18 O profiles can be described by one-phase exponential decay curves. Minimum values reflect geographic origins of the last significant rain event, and curvature is inversely related to canopy closure, demonstrating its role in controlling topsoil evaporation. Partitioning of soil water sources for transpiration was analyzed with a mixing model. In the Costa Rican sites, in a relatively dry year, saplings and mature trees took up water from the upper soil. In a relatively wet year in the Honduran sites, we observed deeper water extraction. In all sites, soil storage dampens extreme variation in water availability. The size-dependence of water uptake with larger stems exploiting deeper layers is translated into variation in bulk leaf δ13 C-based water use efficiency (WUE) with the exception of mature trees. From 1932-2015, drought severity was evaluated with the Standardized Precipitation Evapotranspiration Index (SPEI) concurrently with simulations of the soil water balance model. Drought occurrence increased, regardless of the time period averaged across 6, 12 or 24 months. All ontogenetic stages in all populations experienced frequent water limitation. We found evidence for linear trends toward aridification with increases of return periods of drought for October SPEI-24 declining from 42 to 6 yr in Costa Rica and from 21 to 7 yr in Honduras and recent occurrence of multiyear droughts from 2013 to 2016. October SPEI-12 and SPEI-24 were significantly related to the Oceanic Niño Indices demonstrating that local inter-annual variations in drought severity in Mesoamerica are modulated by large-scale climate forces. Drought severity in the near-term future depends on the extent to which the Pacific will adopt a more La Niña-like vs. a more El Niño-like state under on-going climatic changes.
Pituitary Adenylate Cyclase-Activating Polypeptide Prevents Mortality Caused by Septic Peritonitis in Mice

The purpose of this study was to investigate whether pituitary adenylate cyclase-activating polypeptide (PACAP) prevents mortality due to sepsis in mice. Mice were given PACAP at designated time points before or after cecal ligation and puncture (CLP), and organ injury and mortality were investigated. Serum inflammatory and anti-inflammatory cytokine levels were assessed after CLP. Plasma corticosterone and adrenocorticotropic hormone levels were also measured. Isolated tissue macrophages (Mfs) were incubated with or without PACAP, and production of cytokines was measured. Activation of NF-κB was investigated in tissue Mfs isolated from CLP animal in the presence and absence PACAP in vitro. PACAP treatment significantly prevented acute lung injury and mortality after CLP. Plasma endotoxin levels and bacterial load were not different between PACAP-treated and nontreated groups. Increased serum TNF-α and HMGB1 levels in animals treated with vehicle were significantly blunted in PACAP-treated animals after CLP. Furthermore, serum IL-10 levels were significantly greater in the PACAP-treated group compared with the vehicle group. Production of HMGB1 and TNF-α by isolated hepatic Mfs was significantly inhibited in the presence of PACAP, whereas production of IL-10 by isolated hepatic Mfs and interstitial lung Mfs was significantly increased. Plasma corticosterone and adrenocorticotropic hormone levels were significantly greater in the animals treated with PACAP compared with vehicle after CLP. Activation of NF-κB was significantly inhibited by PACAP in the hepatic Mfs compared with other tissue Mfs. PACAP prevents mortality due to septic peritonitis by inhibiting inflammation via NF-κB activation and possible effects on the brain.
MESH-BASED SOIL LIQUEFACTION ANALYSIS FOR EMERGENCY RESPONSE–CASE STUDY OF THE MEINONG EARTHQUAKE IN TAIWAN

Many urban areas in Taiwan are located in the alluvial deposit with high ground water level which is prone to soil liquefaction endangering buildings, transportation and lifeline systems under strong ground shaking. An extensive database of engineering boreholes from the governmental agency and private sectors is established for soil liquefaction analysis. An automatic processing module producing the shake map and soil liquefaction map in a 500m × 500m mesh is developed in this study. The Meinong earthquake (ML=6.6) in 2016 caused 117 death and wide-range soil liquefaction was chosen as a case study to verified the performance of the methodology. Incorporated with the actual distribution of ground motion and the borehole data in corresponding grids is capable of providing a superior evaluation of liquefaction potential comparing to traditional approach subjected to a uniform excitation. The analytical results of liquefaction potential and induced settlement are generally consistent with the field observations except for some areas without borehole data. Majority of the buildings settled obviously as a result of soil liquefaction are seated in the medium liquefaction potential region as the analysis disclosed. This study provided the prompt and reliable information to the commander for decision making in the practical emergency operation.
SEISMIC RETROFIT OF OLD BRIDGES WITH SEISMIC ISOLATION

A standard highway bridge has usually multi simple spans supported over piers by elastomeric bearings in Turkey. The bearings usually do not provide a positive connection but in contact with girder and pier by only gravitational forces. In this study, a model test bridge of about 1⁄2 scale have been shaken under low to moderate earth quakes to determine the change in response of the bridge with different seismic isolation configurations. Three configurations of bearings are elastomeric bearings, lead core bearings and ball rubber bearings. The bridges supported with lead rubber or ball rubber bearings’ deck displacements are dampened out in a short period of time compared to the tests of bridges with elastomeric bearings as expected. The seismic retrofit goals can be defined for the old bridges based on the target structural response in terms of displacements and forces.
Explaining Democratic Models in the Swiss Global Justice Movement: A Qualitative Comparative Analysis

The democratic practices implemented by the global justice movement in internal decision-making processes vary sensibly from one movement organization to another as well as from one country to another. Some organizations defend an assembleary democratic model (characterized by a weak search for consensus and a decision-making mode that aims to include all the participants), other put forward an associational model (weak search for consensus and strong delegation of power in the hands of a restricted committee), still others stress a deliberative representative model (strong search for consensus and strong delegation of power), and, finally, certain organizations follow a deliberative participative model (strong search for consensus and weak delegation of power). This paper focuses on the possible explanations of these differences in the case of the Swiss global justice movement. In particular, the impact of the structural characteristics of the organizations, the ideological cleavage upon which rests their political mobilization, the tradition of contention in which they are embedded, and the historical period in which they became active will be tested by means of an original dataset gathered in a current research project (DEMOS, Democracy in Europe and the Mobilization of Society, 6 th EU FP) which includes 35 Swiss organizations that participate to the mobilization of the global justice movement. These data include standardized information on decision-making rules of these organizations. Given the limited number of cases, the empirical tests will be carried using Qualitative Comparative Analyses (QCA), which are particularly suited for the study of small samples. Moreover, a particular procedure will be proposed for the resolution of conflicting cases.
Prevalence of Self-medication and Drug use behaviour among Housewives in an Urban Slum area, Visakhapatnam

Introduction: Popping pills without a doctor's prescription, even if the ailment is minor, could have serious repercussions. Self-medication is defined as "The use of drugs to treat self-diagnosed disorders or symptoms, or the intermittent or continued use of a prescribed drug for chronic or recurrent disease or symptoms". Objectives: To study the prevalence of self-medication and drug use behaviour among housewives in an urban slum area, Visakhapatnam city. Materials and Methods: A community based, cross sectional descriptive study was done among 147 housewives residing in an urban slum area during the month of May, 2015. A pretested, structured interview schedule was used to collect data. Data was analysed using MS Excel and Epi Info 7. Results: Mean age of the study population was 33.19 + 6.91 years. Majority of the housewives had education up to primary level. About 58.5% practiced self-medication. Analgesics were the most commonly used self-medicated drugs. Only 62.5% of the participants had the habit of checking for expiry date before taking drugs. Conclusions: Though self-medication if promoted by WHO because of affordability and inaccessibility of health services in developing world, benefits must be weighed against adverse effects.