Training deep neural density estimators to identify mechanistic models of neural dynamics

Mechanistic modeling in neuroscience aims to explain observed phenomena in terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge with a machine learning tool which uses deep neural density estimators-- trained using model simulations-- to carry out Bayesian inference and retrieve the full space of parameters compatible with raw data or selected data features. Our method is scalable in parameters and data features, and can rapidly analyze new data after initial training. We demonstrate the power and flexibility of our approach on receptive fields, ion channels, and Hodgkin-Huxley models. We also characterize the space of circuit configurations giving rise to rhythmic activity in the crustacean stomatogastric ganglion, and use these results to derive hypotheses for underlying compensation mechanisms. Our approach will help close the gap between data-driven and theory-driven models of neural dynamics

Parameter estimation for biochemical reaction networks using Wasserstein distances

We present a method for estimating parameters in stochastic models of biochemical reaction networks by fitting steady-state distributions using Wasserstein distances. We simulate a reaction network at different parameter settings and train a Gaussian process to learn the Wasserstein distance between observations and the simulator output for all parameters. We then use Bayesian optimization to find parameters minimizing this distance based on the trained Gaussian process. The effectiveness of our method is demonstrated on the three-stage model of gene expression and a genetic feedback loop for which moment-based methods are known to perform poorly. Our method is applicable to any simulator model of stochastic reaction networks, including Brownian Dynamics.Comment: 22 pages, 8 figures. Slight modifications/additions to the text; added new section (Section 4.4) and Appendi

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Limestone used in Islamic religious architecture from Istanbul and Turkish Thrace

Mankind has always used stone as building material to create monuments and other structures throughout histor

İSLAM DİNİ MİMARİSİNDE KİREÇTAŞI: İSTANBUL VE TÜRKİYE TRAKYASINDAN ÖRNEKLER

Bu çalışmada, İstanbul ve Trakya'daki Türk İslam mimarisinde kullanılan kireçtaşının litolojik özellikleri ile taş bozunmalarının değerlendirilmesi ve korunmasıyla ilgili bazı öneriler üzerinde durulmuştur. Makalede, Trakya'da yaygın olarak kullanılan kireçtaşının davranışını karakterize etmek için disiplinlerarası bir yaklaşım sunulmuştur. Araştırmada özellikle başta Doğu Trakya Havza'sında farklı kireçtaşı ocaklarından alınarak geleneksel yapıların yapımında kullanılmış olan yapı taşlarının paleontolojik yapısı incelenerek fosillerin saptanmasıyla eski jeolojik dönemlerdeki yaşam biçimleri incelenmiştir. Günümüzde, kireçtaşlarının ayrışmaya karşı tepkilerinin tam olarak bilinmesi, anıtların korunmasıyla ilgili çalışmalarda en önemli veri olarak değerlendirilmektedir. Ortamdaki karmaşık kimyasal, mineralojik, biyolojik verilere paleontolojik parametrelerin de eklenmesiyle, kültür varlıkları geri dönüşü olmayan bir bozunma sürecine girmektedirlerMankind has always used stone as building material to create monuments and other structures throughout history. Since limestone is one of the most common building materials used for so many centuries, because the availability and easy to work on (Yıldırım, 2007). In general, stone was the most widely used durable material. The deterioration of building stone thus causes causing irreparable loss to our cultural heritage. Besides chemical and physical factors, microorganisms play a major role in rock decay. Cultural property covers a wide diversity of archeological monuments and sites as well as historic buildings and objects deemed to have significance for both the local and the international communities. Islamic architecture encompasses a wide range of both secular and religious styles from the foundation of Islam to the present day, influencing the design and construction of buildings and structures in Islamic culture. Most of these monuments like mosques, caravanserais, palaces, hamams, madrasas and tombs date back to the periods of the Byzantine and Ottomans. The Tertiary porous limestones from quarries in Thrace Basin represent the characteristical stone type used for the construction of the Islamic monuments. The geological dimensions include sediment-fingerprints of vertical sea level fluctuations and lateral coastline change, which result in the coastal zone from internal (mainly the coastal sedimentary budget) forces. The archaeological dimension includes human fingerprints (e.g., archaeological artifacts, faunistic remains from cultural layers). Both dimensions will be addressed through integration of existing data as a result of this paper. The area under consideration comprises a panhandle-like eastern extension of the Thrace Basin in northwest Turkey, where faulting on the south and north margins has deformed and exposed part of the sedimentary strata (Figure 1). Limestone is one of the most commonly found stones in building construction in Turkey is due to its ability to be cut and shaped easily, its "warm" colour and its abundance. Whole structures such as mosques, castles, palaces and fortresses were built only with limestone blocks or limestone pieces combined with other types of stone. Although various types of stones have been used as a building material for at least 10.000 years in Anatolia, carbonate rocks especially limestone had been extensively used as building stone material because of their well quality and availability in İstanbul. In general, limestone is a stone that is composed of calcium carbonate and crystalline limestone, which consists of minerals of calcite and aragonite. They are formed by inorganic chemical precipitation and/or with the contribution of organisms and organic processes (Küçükkaya, 2003). Pure Limestone contains % 56 CaO and % 44 CO2. Many Islamic monuments in İstanbul and Turkish Thrace are seriously in danger by damage and, as a result, are in need of intervention. Stone weathering represents a significant reason of damage. Air pollution as a consequence of the rapid expansion of İstanbul and rising water table in combination with increasing water pollution due to insufficient or leaking sewage system are considered as important weathering factors. The size and type of fossil remnants in sedimentary rocks have been affected to the selection process of well quality stone building material (Turgut, Gökselin, 2000)

Asymmetric Interest Rate Effects for the UK Real Economy

Recent literature has uncovered asymmetries in the response of real output to monetary policy variables. Nevertheless, it remains unclear whether such asymmetries relate to different responses to monetary policy or to the business cycle. This paper uses nonlinear models to examine the issues in the context of interest rate effects on quarterly UK GDP growth. Strong evidence of nonlinearity is found, with asymmetry relating to the business cycle through lagged GDP regimes and interest rate changes. The results suggest that interest rate effects on GDP are larger when either lagged growth has been high or when interest rates have substantially increased in the past. However, the inclusion of interest rate regimes without taking account of GDP regimes yields an unsatisfactory model.monetary policy, business cycle asymmetries, smooth transition models, forecasting

Dexmedetomidine modifies uterine contractions in pregnancy terms of rats

PubMedID: 23716894Objectives: The present study was aimed at determining the effective doses of Dexmedetomidine (Dex) involved in amplitude of contraction-force and frequency of uterine rings in pregnancy terms of rats. All experiments involving animal subjects were carried out with the approval of animal care and use Ethical Committee of Cukurova University. Experiments were performed on female Albino-Wistar rats (200-260 g; n = 40). Materials and Methods: Uterine rings from pregnant rats were placed in organ bath with Krebs and calcium ion (Ca 2+ )-free solutions to record and exposed to serially increasing log10 concentrations of Dex. Results: In Krebs solution, while Dex caused an increase in the spontaneous contraction-forces in all pregnancy terms of rats in a significant dose-dependent manner, it led to a decrease in contraction-frequency in late-pregnancy term of rats. In Ca2+ -free, the spontaneous contraction-force decreased in late-pregnancy term and increased in early and middle-pregnancy terms. In addition, while Dex increased the contraction-frequency in early and middle-pregnancy terms, it decreased in late-pregnancy term in a dose-dependent manner. Statistical Analysis Used: The data were subjected to one-way analysis of variance. Repeated measures were employed for comparison of several group means through the Tukey post-hoc test (SPSS 10.00 Inc., Chicago, Ill, USA). P < 0.05 was considered statistically significant. Conclusions: This study suggested that Dex might differently alter the spontaneous contraction-forces and contraction-frequencies of uterine rings in all pregnancy terms of rats in Krebs and Ca 2+ -free solutions

Dimensional approach to obsessive-compulsive disorder: Dimensional obsessive-compulsive scale with Turkish psychometric properties

Objective: The Dimensional Obsessive Compulsive Scale (DOCS) is a measurement tool that examines the severity of thematically distinct symptom domains of obsessive compulsive disorder (OCD). In this study we assess psychometric properties of the Turkish version of DOCS. Methods: Ninety-six patients who presented consecutively to the Dişkapi Yildirim Beyazit Teaching and Research Hospital outpatient unit and who were diagnosed with OCD according to the DSM-IV-TR criteria were enrolled in the study. The DOCS, Yale-Brown Obsessive Compulsive Scale (YBOCS), and Padua Inventory (PI) were completed by the participants. Internal consistency was estimated using Cronbach's Alpha values and item-total correlations. Principal component analyses with Varimax rotation were used to assess latent factor structure . Results: Explanatory Factor Analyses (EFA) revealed a 4-factor solution for the DOCS. Chronbach's alpha values for the whole scale, "contamination" sub-scale, "responsibility" sub-scale, "unacceptable thoughts", and "symmetry" sub-scales were 0.874, 0.932, 0.933, 0.948, 0.921, respectively. There was a high correlation between It has been determined that there is high correlations between both total scores and sub-scales scores of DOCS, YBOCS and PI. Conclusions: Internal consistencies were high good for the total scale and very high perfect for the sub-scales. The factor structure and the contents of the factors were perfectly in line with the original scale (i.e. 4 factor). Positive correlations between DOCS, its sub-scales, and similar OCD scales suggest that the DOCS accurately measures the structures it claims to assess. Thus the DOCS Turkish version can measure dimensional obsessive compulsive symptoms among the Turkish speaking OCD population. © 2018 Turkish Association of Nervous and Mental Health