Miracle-dz/UniFAR-FTUs huggingface dataset:
Biophysical Basis for Three Distinct Dynamical Mechanisms of Action Potential Initiation

Transduction of graded synaptic input into trains of all-or-none action potentials (spikes) is a crucial step in neural coding. Hodgkin identified three classes of neurons with qualitatively different analog-to-digital transduction properties. Despite widespread use of this classification scheme, a generalizable explanation of its biophysical basis has not been described. We recorded from spinal sensory neurons representing each class and reproduced their transduction properties in a minimal model. With phase plane and bifurcation analysis, each class of excitability was shown to derive from distinct spike initiating dynamics. Excitability could be converted between all three classes by varying single parameters; moreover, several parameters, when varied one at a time, had functionally equivalent effects on excitability. From this, we conclude that the spike-initiating dynamics associated with each of Hodgkin's classes represent different outcomes in a nonlinear competition between oppositely directed, kinetically mismatched currents. Class 1 excitability occurs through a saddle node on invariant circle bifurcation when net current at perithreshold potentials is inward (depolarizing) at steady state. Class 2 excitability occurs through a Hopf bifurcation when, despite net current being outward (hyperpolarizing) at steady state, spike initiation occurs because inward current activates faster than outward current. Class 3 excitability occurs through a quasi-separatrix crossing when fast-activating inward current overpowers slow-activating outward current during a stimulus transient, although slow-activating outward current dominates during constant stimulation. Experiments confirmed that different classes of spinal lamina I neurons express the subthreshold currents predicted by our simulations and, further, that those currents are necessary for the excitability in each cell class. Thus, our results demonstrate that all three classes of excitability arise from a continuum in the direction and magnitude of subthreshold currents. Through detailed analysis of the spike-initiating process, we have explained a fundamental link between biophysical properties and qualitative differences in how neurons encode sensory input.
Osmolyte‐induced conformational changes in the Hsp90 molecular chaperone

Osmolytes are small molecules that play a central role in cellular homeostasis and the stress response by maintaining protein thermodynamic stability at controlled levels. The underlying physical chemistry that describes how different osmolytes impact folding free energy is well understood, however little is known about their influence on other crucial aspects of protein behavior, such as native‐state conformational changes. Here we investigate this issue with the Hsp90 molecular chaperone, a large dimeric protein that populates a complex conformational equilibrium. Using small angle X‐ray scattering we observe dramatic osmolyte‐dependent structural changes within the native ensemble. The degree to which different osmolytes affect the Hsp90 conformation strongly correlates with thermodynamic metrics of their influence on stability. This observation suggests that the well‐established osmolyte principles that govern stability also apply to large‐scale conformational changes, a proposition that is corroborated by structure‐based fitting of the scattering data, surface area comparisons and m‐value analysis. This approach shows how osmolytes affect a highly cooperative open/closed structural transition between two conformations that differ by a domain‐domain interaction. Hsp90 adopts an additional ligand‐specific conformation in the presence of ATP and we find that osmolytes do not significantly affect this conformational change. Together, these results extend the scope of osmolytes by suggesting that they can maintain protein conformational heterogeneity at controlled levels using similar underlying principles that allow them to maintain protein stability; however the relative impact of osmolytes on different structural states can vary significantly.
Towards Intrusion Detection for Encrypted Networks

Traditionally, network-based Intrusion Detection Systems (NIDS) monitor network traffic for signs of malicious activities. However, with the growing use of Virtual Private Networks (VPNs) that encrypt network traffic, the NIDS can no longer analyse the encrypted data. This essentially negates any protection offered by the NIDS. Although the encrypted traffic can be decrypted at a network gateway for analysis, this compromises on data confidentiality. In this paper, we propose a detection framework which allows a traditional NIDS to continue functioning, without compromising the confidentiality afforded by the VPN. Our approach uses Shamir's secret-sharing scheme and randomised network proxies to enable detection of malicious activities in encrypted channels. Additionally, this approach is able to detect any malicious attempts to forge network traffic with the intention of evading detection. Our experiments show that the probability of a successful evasion is low, at about 0.98% in the worst case. We implement our approach in a prototype and present some preliminary results. Overall, the proposed approach is able to consistently detect intrusions and does not introduce any additional false positives.
Distinctions Of The Multiresolution Model Of Surface For Regularly Distributed Data

During the last years the conception of the multiresolution model (MRM) of surface was developed for representation of the geometric objects with continuous level of detail (LOD). The basic idea of this model is the storing of the triangulations with different LODs in the directed acyclic graph (DAG) structure. The model is created at the preprocessing step and provides extracting of the consistent triangulation with continuous LOD from DAG in real time. The sample algorithms for the creation of MRM for arbitrary surface triangulation are described in [1]. The algorithm for DAG creation is time and memory consuming. The regularity of data allows to increase the performance of MRM significantly. In that case no complex refinement/decimation algorithms are needed for DAG creation. Memory overhead is also decreased compared with the arbitrary data memory overhead. Also, we managed to represent extracted triangulation as a single generalized triangle-strip. We used this approach of DAG creation and LOD extraction in two applications: one for real-time rendering of the regular terrain and the other for adaptive representation of the surface in 3DStudioMax footprint simulation plug-in. The algorithm may be used in different areas where significant reduction of primitives without any noticeable loss of quality is required, e.g., computer graphics (real-time rendering, games), GIS or physical modeling (intensive calculations on meshes with huge number of primitives), etc.
MCORE: a context‐sensitive recommendation system for the mobile Web

Abstract: Recommendation systems for the mobile Web have focused on endorsing particular types of content to users. Today, mobile service providers have a more direct recommendation channel, namely the short messaging service. Therefore, mobile service providers should consider both the timing and context of recommendation messages (push messages) that are sent to users. Mobile service providers can learn context‐specific user preferences by analysing mobile Web use logs and user responses to push messages. In this paper, we present a context‐sensitive recommendation system that can be used to select the optimal context in which to send recommendation messages. We call this system the mobile context recommender system (MCORE). We compared user responses to push messages delivered in and out of suitable contexts as determined by MCORE. The precision of push messages delivered within a suitable context was higher than that of messages delivered outside of one.
Prognosis of Children With HIV-1 Infection Starting Antiretroviral Therapy in Southern Africa: A Collaborative Analysis of Treatment Programs

Background: Prognostic models for children starting antiretroviral therapy (ART) in Africa are lacking. We developed models to estimate the probability of death during the first year receiving ART in Southern Africa. Methods: We analyzed data from children ⩽10 years of age who started ART in Malawi, South Africa, Zambia or Zimbabwe from 2004 to 2010. Children lost to follow up or transferred were excluded. The primary outcome was all-cause mortality in the first year of ART. We used Weibull survival models to construct 2 prognostic models: 1 with CD4%, age, World Health Organization clinical stage, weight-for-age z-score (WAZ) and anemia and the other without CD4%, because it is not routinely measured in many programs. We used multiple imputation to account for missing data. Results: Among 12,655 children, 877 (6.9%) died in the first year of ART. We excluded 1780 children who were lost to follow up/transferred from main analyses; 10,875 children were therefore included. With the CD4% model probability of death at 1 year ranged from 1.8% [95% confidence interval (CI): 1.5–2.3] in children 5–10 years with CD4% ≥10%, World Health Organization stage I/II, WAZ ≥−2 and without severe anemia to 46.3% (95% CI: 38.2–55.2) in children <1 year with CD4% <5%, stage III/IV, WAZ< −3 and severe anemia. The corresponding range for the model without CD4% was 2.2% (95% CI: 1.8–2.7) to 33.4% (95% CI: 28.2–39.3). Agreement between predicted and observed mortality was good (C-statistics = 0.753 and 0.745 for models with and without CD4%, respectively). Conclusions: These models may be useful to counsel children/caregivers, for program planning and to assess program outcomes after allowing for differences in patient disease severity characteristics.
Towards a 'Europe of flows'? : discourse, power and space in the development of a transnational high-speed rail line in the European Union

The aim of this thesis is to contribute to the understanding of European integration through a focus on the politics surrounding transnational high-speed rail infrastructure. Although it has been argued that a discourse on the creation of a ‘Europe of Flows’ has become dominant in policy development, the spatial conflicts that this type of infrastructure involves and the wide array of political actors concerned cast doubts on the smooth development of such a space. The thesis aim is pursued through a critical approach that considers policy problems as socially constructed, seeks to reveal the power struggles in policy-making, and places space at the centre of the study of politics. Thus, an analytical framework that combines discourse analysis, social and political theories of power and a spatially-nuanced approach informed by human geography debates on scale and relationality was adopted and applied to the case of a cross-border and EU-relevant high-speed rail line in the Spanish Basque Country. The case study first demonstrates the existence of a hegemonic discourse on transport infrastructure development, which accommodated a variety of concerns according to different scalar frames and was produced and reproduced in state, private sector and mainstream media discursive arenas. Proponents of an alternative construction based on the notion of proximity unsuccessfully struggled to challenge the former from other, minor arenas. Although those actors practicing the hegemonic discourse supported the high-speed rail line, the continuing prevalence of nation-state actors and power arenas largely prevented the timely development of a truly trans-European link, in spite of the efforts of both EU institutions and several transnational networks of association. Overall, the thesis illustrates how transnational high-speed rail infrastructure policy-making shapes, rather than a frictionless ‘Europe of Flows’, a hybrid European space that results from complex struggles for discursive hegemony and effective influence in the policy process.
Dietary Intake of Lignans and Risk of Esophageal and Gastric Adenocarcinoma: A Cohort Study in Sweden

High intake of phytoestrogen lignans has been found to be associated with decreased risk of esophageal adenocarcinoma in our previous population-based case–control study in Sweden. To further evaluate this possible association, we tested the hypothesis of an inverse association between dietary lignan intake and risk of esophageal and gastric adenocarcinoma using a prospective design. In a population-based cohort study in Sweden, 81,670 participants who were cancer-free at baseline were followed up during 1998 to 2009. All participants completed a 96-item food frequency questionnaire (FFQ), which was used to assess dietary exposure to lignans (secoisolariciresinol, matairesinol, lariciresinol, pinoresinol, medioresinol, and syringaresinol). All cases of esophageal, gastroesophageal junctional, and gastric adenocarcinoma were identified through linkage to the Swedish Cancer Register. Cox proportional hazard models were used to estimate HRs and 95% confidence intervals (CI), with adjustment for potential confounding factors. During an average follow-up of 9.9 years, a total of 211 cases were identified, including 83 cases of esophageal or junctional adenocarcinoma, and 128 cases of gastric adenocarcinoma. There was no statistically significant association between dietary intake of lignans and any of the studied adenocarcinomas. Compared with participants in the lowest quartile of lignan intake, the adjusted HR of the highest quartile was 0.96 (95% CI, 0.46–2.00; Ptrend = 0.70) for adenocarcinoma of the esophagus or gastroesophageal junction, and 0.89 (95% CI, 0.52–1.55: Ptrend = 0.78) for gastric adenocarcinoma. No clear support for a protective role of dietary intake of lignans in the development of esophageal or gastric adenocarcinoma was found. Cancer Epidemiol Biomarkers Prev; 22(2); 308–12. ©2012 AACR.
Mesh-based Monte Carlo method in time-domain widefield fluorescence molecular tomography

Abstract. We evaluated the potential of mesh-based Monte Carlo (MC) method for widefield time-gated fluorescence molecular tomography, aiming to improve accuracy in both shape discretization and photon transport modeling in preclinical settings. An optimized software platform was developed utilizing multithreading and distributed parallel computing to achieve efficient calculation. We validated the proposed algorithm and software by both simulations and in vivo studies. The results establish that the optimized mesh-based Monte Carlo (mMC) method is a computationally efficient solution for optical tomography studies in terms of both calculation time and memory utilization. The open source code, as part of a new release of mMC, is publicly available at http://mcx.sourceforge. net/mmc/.
Adjustment and Assessment of the Measurements of Low and High Sampling Frequencies of GPS Real-Time Monitoring of Structural Movement

Global Positioning System (GPS) structural health monitoring data collection is one of the important systems in structure movement monitoring. However, GPS measurement error and noise limit the application of such systems. Many attempts have been made to adjust GPS measurements and eliminate their errors. Comparing common nonlinear methods used in the adjustment of GPS positioning for the monitoring of structures is the main objective of this study. Nonlinear Adaptive-Recursive Least Square (RLS), extended Kalman filter (EKF), and wavelet principal component analysis (WPCA) are presented and applied to improve the quality of GPS time series observations. Two real monitoring observation systems for the Mansoura railway and long-span Yonghe bridges are utilized to examine suitable methods used to assess bridge behavior under different load conditions. From the analysis of the results, it is concluded that the wavelet principal component is the best method to smooth low and high GPS sampling frequency observations. The evaluation of the bridges reveals the ability of the GPS systems to detect the behavior and damage of structures in both the time and frequency domains.
A Tree-Based μ TESLA Broadcast Authentication for Sensor Networks

Broadcast authentication is a critical security service in sensor networks; it allows a sender to broadcast messages to multiple nodes in an authenticated way. μTESLA and multi-level μTESLA have been proposed to provide such service for sensor networks. However, none of these techniques are scalable in terms of the number of senders. Though multi-level μTESLA schemes can scale up to large sensor networks (in terms of receivers), they either use substantial bandwidth and storage at sensor nodes, or require significant resources at senders to deal with DOS attacks. This paper presents efficient techniques to support a potentially large number of broadcast senders using μTESLA instances as building blocks. The proposed techniques are immune to the DOS attacks. This paper also provides two approaches, a revocation tree based scheme and a proactive distribution based scheme, to revoke the broadcast authentication capability from compromised senders. The proposed techniques are implemented, and evaluated through simulation on TinyOS. The analysis and experiment show that our techniques are efficient and practical, and can achieve better performance than the previous ap-
Tilastollinen järkeily ja oppilasarviointi suomalaisen kasvatustieteen historiassa Ian Hackingin tieteenfilosofian näkökulmasta

The article discusses the significance of statistical methods for the development of pupil evaluation in Finland. Until the 1940s Finnish pupil evaluation was largely uncoordinated and left to the consideration of individual teachers. After World War II pupil evaluation gradually turned into a more standardized, scientific form in which statistical methods played significant part. The special focus in this article is on the epistemological foundations of statistical reasoning which are discussed in the light of Ian Hacking’s philosophy of the human sciences. First, the article discusses the historical formation of the epistemological foundations of statistics and proceeds to show how these have become intertwined with rationalized curriculum planning and evaluation. Furthermore, the consequences of the statistical implications of the bell curve in pupil assessment are discussed. With these case analyses, the article shows how statistical methods can provide ramifications for what is considered as objective, rational and fair in pupil assessment. In addition, this also changes the actual practices of student evaluation.
XMatch: A language for satisfaction-based selection of Grid services

Grid systems enable the sharing of a large number of geographically-dispersed resources among different communities of users. They require a mapping functionality for the association of users requests expressed in terms of requirements and preferences to actual resources. This functionality should deal with a potentially high number of similar resources and with the diversity of the perceived satisfactions of users. We propose XMatch, a query language enabling the expression of the user request in terms of the expected satisfaction over XML-based representation of available resources. This language offers a compact way for users to express their preferences for Grid resources and enable the maximization of the global preference.
Plasma cell-free DNA for predicting outcomes of patients with HBV-related acute-on-chronic liver failure: a pilot study.

OBJECTIVE Cell-free DNA (cfDNA) was shown to be a prognostic marker for diverse pathological states in the Intense Care Unit, but little is known of the role of cfDNA in HBV-related acute-on-chronic liver failure (ACLF). We hypothesize that cfDNA can also be a promising prognostic as well as a diagnostic marker in patients with HBV-related ACLF. METHODS Thirty-eight patients with HBV-related ACLF admitted in the Intense Care Unit were enrolled in the study. The patients were divided, according to the improvement of liver function at discharge, into favorable prognosis group (group 1, n=17) and poor prognosis group (group 2, n=19). Plasma samples were collected from each patient at hospitalization and at discharge to measure cfDNA by real-time quantitative PCR. MELD score was calculated at the same time points. RESULTS The average level of cfDNA of group 1 was lower than that of group 2 both at the time of hospitalization (P=0.044) and at discharge (P<0.001). There was no difference in MELD score between the two groups at hospitalization. Significant correlations were found of cfDNA levels with the MELD score, TBIL, CRE and INR both at hospitalization (γ=0.662, P<0.001; γ=0.356, P=0.033; γ=0.360, P=0.031; γ=0.570, P<0.001, respectively) and at discharge (γ=0.854, P<0.001; γ=0.821, P<0.001; γ=0.650, P<0.001; γ=0.638, P<0.001, respectively). The ROC curve showed that cfDNA level at discharge was optimal in diagnosing ACLF with an area under curve (AUC) value of 0.96, followed by δcfDNA (AUC value of 0.923) and cfDNA level at hospitalization (AUC value of 0.667). The MELD scores had an AUC value of only 0.545 at the time of hospitalization. CONCLUSION cfDNA may serve as a promising prognostic and diagnostic marker for predicting in-hospital prognosis of HBV-related ACLF within 2 to 8 weeks.
Size at birth, weight gain in infancy and childhood, and adult blood pressure in 5 low- and middle-income-country cohorts: when does weight gain matter?123

Background: Promoting catch-up growth in malnourished children has health benefits, but recent evidence suggests that accelerated child weight gain increases adult chronic disease risk. Objective: We aimed to determine how birth weight (BW) and weight gain to midchildhood relate to blood pressure (BP) in young adults. Design: We pooled data from birth cohorts in Brazil, Guatemala, India, the Philippines, and South Africa. We used conditional weight (CW), a residual of current weight regressed on prior weights, to represent deviations from expected weight gain from 0 to 12, 12 to 24, 24 to 48 mo, and 48 mo to adulthood. Adult BP and risk of prehypertension or hypertension (P/HTN) were modeled before and after adjustment for adult body mass index (BMI) and height. Interactions of CWs with small size-for-gestational age (SGA) at birth were tested. Results: Higher CWs were associated with increased BP and odds of P/HTN, with coefficients proportional to the contribution of each CW to adult BMI. Adjusted for adult height and BMI, no child CW was associated with adult BP, but 1 SD of BW was related to a 0.5-mm Hg lower systolic BP and a 9% lower odds of P/HTN. BW and CW associations with systolic BP and P/HTN were not different between adults born SGA and those with normal BW, but higher CW at 48 mo was associated with higher diastolic BP in those born SGA. Conclusions: Greater weight gain at any age relates to elevated adult BP, but faster weight gains in infancy and young childhood do not pose a higher risk than do gains at other ages.