Miracle-dz/UniFAR-FTUs huggingface dataset:
System dynamics: What’s in it for healthcare simulation modelers

In the past decade there has been an explosion in the use of system dynamics modeling in healthcare. Despite this, the approach is still far less well known than discrete-event simulation in the mainstream Operations Research community. This paper contains an introduction to system dynamics, illustrated by several examples in the field of healthcare, and discusses some of the possible reasons for the growth in the popularity of this approach for healthcare modeling.
Molecular mobility and nucleocytoplasmic flux in hepatoma cells

Fluorescence microphotolysis (photobleaching) was used to measure, in single polyethylene glycol-induced polykaryons of hepatoma tissue culture cells, nucleocytoplasmic flux and intracellular mobility for a series of dextrans ranging in molecular mass from 3 to 150 kD and for bovine serum albumin. For the dextrans, the cytoplasmic and the nucleoplasmic translational diffusion coefficients amounted to approximately 9 and approximately 15%, respectively, of the value in dilute buffer. The diffusion coefficients depended inversely on molecular radius, suggesting that diffusion was dominated by viscosity effects. By application of the Stokes-Einstein equation, cytoplasmic and nucleoplasmic viscosities were derived to be 6.6 and 8.1 cP, respectively, at 23 degrees C. Between 10 and 37 degrees C nucleoplasmic diffusion coefficients increased by approximately 45-85%, whereas cytoplasmic diffusion coefficients were virtually independent of temperature. In contrast to that of the dextrans, diffusion of bovine serum albumin was more restricted. In the cytoplasm the diffusion coefficient was approximately 1.5% of the value in dilute buffer; in the nucleus albumin was largely immobile. This indicated that albumin mobility is dominated by association with immobile cellular structures. Nucleocytoplasmic flux of dextrans depended inversely on molecular mass with an exclusion limit between 17 and 41 kD. This agrees with previous measurements on primary hepatocytes (Peters, R., 1984, EMBO [Eur. Mol. Biol. Organ.] J. 3:1831-1836), suggesting that in both cell types the nuclear envelope has properties of a molecular sieve with a functional pore radius of approximately 55 A.
Joint estimation of thresholds in a bi-threshold verification problem

Veriﬁcation problems are usually posted as a 2-class problem and the objective is to verify if an observation belongs to a class, say, A or its complement A’. However, we ﬁnd that in a computer-assisted language learning application, because of the relatively low reliability of phoneme veriﬁcation — with an equal-error-rate of more than 30% — a system built on conventional phoneme ver-iﬁcation algorithm needs to be improved. In this paper, we propose to cast the problem as a 3-class veriﬁcation problem with the addition of an “in-between” class besides A and A’. As a result, there are two thresholds to be designed in such a system. Although one may determine the two thresholds independently, better performance can be obtained by a joint estimation of these thresholds by allowing small deviation from the speciﬁed false acceptance and false rejection rates. This paper describes a cost-based approach to do that. Furthermore, issues such as per-phoneme thresholds vs. phoneme-class thresholds, and the use of bagging technique to improve the stability of thresholds are investigated. Experimental results on a kids’ corpus show that cost-based thresholds and bagging improve veriﬁcation performance.
"Social Opium" as a Social Mechanism : A Sociological Analysis of the Vicissitudes of the Fukushima Power Plant-based Town

People seek for the better, whatever that “better” means. Rarely do they seek for the worse, at least not on their conscious level. They want to enjoy amenities and a higher quality of life, material or otherwise. A similar inclination holds at the level of local government as well as at the national level. In 2010, the Shanghai World Expo took place, whose slogan was “better city, better life. ” In 2011, the Chinese government formed a new five-year plan (2011−2015) aimed at achieving the better life. Almost all countries have always sought a better world (Popper, 1984). However, seeking for the better may result in the worse, perhaps as an unintended consequence of social action (Boudon, 1982) at an individual or collective level. The present paper attempts to formulate such a social mechanism, which I call “social opium,” by referring to the local township government located adjacent to the Fukushima Nuclear Power Plant that was damaged severely by a massive earthquake and ensuing tsunami on March 11, 2011.
Breteau Index threshold levels indicating risk for dengue transmission in areas with low Aedes infestation

We used Breteau Indices to – retrospectively – predict dengue transmission. The presence of one house block (on average about 50 houses) with a Breteau Index ≥4 in a neighbourhood (a block plus the surrounding blocks in a radius of 100 m) predicted transmission at the latter level with 81.8% sensitivity and 73.3% specificity during the first month of the Havana 2001 dengue outbreak. This result corroborates the external validity of this threshold, at least in situations with low infestations levels.
Wisdom of crowds algorithm for stock market predictions

In this paper we present a mathematical model for collaborative filtering implementation in stock market predictions. In popular literature collaborative filtering, also known as Wisdom of Crowds, assumes that group has a greater knowledge than the individual while each individual can improve groups performance by its specific information input. There are commercially available tools for collaborative stock market predictions and patent protected web-based software solutions. Mathematics that lies behind those algorithms is not disclosed in the literature, so the presented model and algorithmic implementation are the main contributions of this work.
Tracking Multiple Colored Blobs with a Moving Camera

This paper concerns a method for tracking multiple blobs exhibiting certain color distributions in images acquired by a possibly moving camera. The method encompasses a collection of techniques that enable modeling and detecting the blobs possessing the desired color distribution(s), as well as inferring their temporal association across image sequences. Appropriately colored blobs are detected with a Bayesian classifier, which is bootstrapped with a small set of training data. Then, an online iterative training procedure is employed to refine the classifier using additional training images. Online adaptation of color probabilities is used to enable the classifier to cope with illumination changes. Tracking over time is realized through a novel technique, which can handle multiple colored blobs. Such blobs may move in complex trajectories and occlude each other in the field of view of a possibly moving camera, while their number may vary over time. A prototype implementation of the developed system running on a conventional Pentium IV processor at 2.5 GHz operates on 320/spl times/240 live video in real time (30Hz). It is worth pointing out that currently, the cycle time of the tracker is determined by the maximum acquisition frame rate that is supported by our IEEE 1394 camera, rather than the latency introduced by the computational overhead for tracking blobs.
Nebivolol Reverses Endothelial Dysfunction in Essential Hypertension: A Randomized, Double-Blind, Crossover Study

Background—Vascular endothelial dysfunction may predict future atherosclerosis. Hence, an antihypertensive agent that reverses endothelial dysfunction and lowers blood pressure might improve the prognosis of patients with hypertension. We hypothesized that nebivolol, a vasodilating &bgr;-blocker, could improve endothelial dysfunction. We tested this hypothesis by comparing the effects of nebivolol and atenolol on endothelial function. Methods and Results—Twelve hypertensive patients with a mean ambulatory blood pressure of 154±7/97±10 mm Hg were randomized after a 2-week placebo run-in period (baseline) in a double-blind, crossover fashion to 8-week treatment periods with either 5 mg of nebivolol with 2.5 mg of bendrofluazide or 50 mg of atenolol with 2.5 mg of bendrofluazide. Forearm venous occlusion plethysmography and intra-arterial infusions of acetylcholine and NG-monomethyl-l-arginine (L-NMMA) were used to assess stimulated and basal endothelium-dependent nitric oxide release, respectively. Sodium nitroprusside was used as an endothelium-independent control. Nebivolol/bendrofluazide and atenolol/bendrofluazide each lowered the clinic blood pressure to the same extent (132±7/82±6 and 132±9/83±8 mm Hg, respectively;P <0.001 from baseline). The vasodilatory response to acetylcholine was significantly increased with nebivolol/bendrofluazide (maximum percentage change in forearm blood flow [mean±SEM], 435±27%, P <0.001) but not with atenolol/bendrofluazide. Similarly, the endothelium-dependent vasoconstrictive response to L-NMMA was significantly improved only with nebivolol treatment (percentage change in forearm blood flow, −54±5%;P <0.001). The response to sodium nitroprusside was not different between treatments, suggesting that the endothelium-independent pathway was unaffected. Conclusions—Nebivolol/bendrofluazide increased both stimulated and basal endothelial nitric oxide release, whereas for the same degree of blood pressure control, atenolol/bendrofluazide had no effect on nitric oxide bioactivity. Thus, nebivolol may offer additional vascular protection in treating hypertension.
Invasive Streptococcus pneumoniae isolates from Argentinian children: serotypes, families of pneumococcal surface protein A (PspA) and genetic diversity

PspA is an antigenically variable virulence factor of Streptococcus pneumoniae that inhibits complement deposition and is a potential candidate for human vaccines. Of 64 published strains 96% are in PspA families 1 and 2; optimal protection is family-specific. Effective development of a PspA-containing vaccine requires more information about the PspA family of strains in parts of the world where the vaccine is most needed. In these studies we observed that of 149 isolates (of 19 capsular types) from Argentina, 54·4% were family 1, 41·6% were family 2 and 4·0% expressed both family 1 and family 2 PspAs. Box typing revealed the Argentinian strains to be from at least 10 clonally related groups.
mRNA Targeting to Endoplasmic Reticulum Precedes Ago Protein Interaction and MicroRNA (miRNA)-mediated Translation Repression in Mammalian Cells*

Background: miRNA, Ago2, and target messages are enriched on ER in metazoan cells. Results: Polysome association of newly formed mRNA precedes Ago2 binding on ER membrane and its translation repression. Conclusion: miRNA repression process is compartmentalized in mammalian cells, and polysome association of mRNA happens before the repression. Significance: This work provides a detailed understanding of the miRNA-mediated gene repression and mRNA compartmentalization in mammalian cells. MicroRNA (miRNA) binds to the 3′-UTR of its target mRNAs to repress protein synthesis. Extensive research was done to understand the mechanism of miRNA-mediated repression in animal cells. Considering the progress in understanding the mechanism, information about the subcellular sites of miRNA-mediated repression is surprisingly limited. In this study, using an inducible expression system for an miRNA target message, we have delineated how a target mRNA passes through polysome association and Ago2 interaction steps on rough endoplasmic reticulum (ER) before the miRNA-mediated repression sets in. From this study, de novo formed target mRNA localization to the ER-bound polysomes manifested as the earliest event, which is followed by Ago2 micro-ribonucleoprotein binding, and translation repression of target message. Compartmentalization of this process to rough ER membrane ensures enrichment of miRNA-targeted messages and micro-ribonucleoprotein components on ER upon reaching a steady state.
Clustering and Detection of Hub in a Complex Networks via the Laplacian Matrix

In clustering (also known as unsuper- vised learning and class discovery), the classes are unknown a priori and need to be identied from the unsupervised data. The cluster analysis is concerned about estimating the number of classes and assigning each observation to a certain class. In this article we discuss a method for clustering via the Laplacian ma- trix. Also, based on a similar argument, we suggest a method for detecting hubs in a complex networks.
Long-term potentiation and activity-dependent retinotopic sharpening in the regenerating retinotectal projection of goldfish: common sensitive period and sensitivity to NMDA blockers

The regenerating retinotectal projection in goldfish goes through an activity-driven refinement that appears to involve the elimination of inappropriate branches from early arbors. Retinotopically appropriate branches may be stabilized because the normally correlated firing of neighboring ganglion cells causes summation of their postsynaptic responses and increases their effectiveness by a Hebbian mechanism. In this study, I report that the regenerating projection has an increased capacity for long-term potentiation (LTP) that may be related to the activity-driven sharpening. In the normal projection, field potentials, reflecting currents from EPSPs elicited by optic nerve shock, are large (greater than 4 mV) and very stable. In newly regenerated projections, field potentials are initially small (less than 1 mV), but a train of 20 stimuli at 0.1 Hz results in a large (100–200%) increase in amplitude that is stable for at least 8 hr, and in 3 cases overnight. The capacity for potentiation is greatest from 20 to 40 d postcrush, the time just after arrival of the optic fibers, and during the period of retinotopic sharpening. A greater-than-normal capacity for potentiation persists for many months. Topical application of NMDA receptor blockers AP5 or AP7 at 25 microM prevents potentiation without decrementing ongoing responses. The closely related agent AP6, which is not an NMDA receptor blocker, does not prevent potentiation. In addition, infusion of the NMDA receptor blockers AP5 or AP7 into the tectal ventricle (4 microliters/d of 500 microM solution) for 2–3 weeks during regeneration prevented retinotopic sharpening, as assessed by electrophysiological mapping. At each tectal point, responsive areas in the visual field were enlarged to 28 degrees vs 11–12 degrees in control regenerates and normals. This was comparable to data from fish regenerating with activity blocked with intraocular tetrodotoxin or synchronized by stroboscopic illumination and indicates uncorrected errors in targeting of regenerated arbors (Schmidt, 1985). The results support the involvement of NMDA receptors in sharpening and suggest that the initial step in stabilizing appropriate branches may be a long- lasting increase in synaptic gain.
Discovering Emerging Topics from WWW

Discovering emerging topics from WWW has been attracting attention of business professionals, especially marketing researchers. For this purpose, WWW can be a valuable source of information because it reflects the dynamics of human society. In this paper we aim at revealing the structure of WWW by using "KeyGraph," a visualization method of hidden structure behind data, for understanding emerging topics.
Effect of unilateral hearing loss on the speech-evoked auditory brainstem response in the presence of noise

Effect of unilateral hearing loss on the speech-evoked auditory brainstem response in the presence of noise" Abstract: Speech-evoked auditory brainstem responses (ABRs) were acquired in quiet and in the presence of noise at two study sessions to investigate 1) test-retest variability and 2) subcortical representation of speech stimuli. Participants were adults with normal hearing in both ears who listened monaurally and adults with unilateral deafness. Results indicate consistency in responses across sessions and several differences between hearing groups for magnitudes of discrete components.
Gating-Dependent Mechanisms for Flecainide Action in SCN5A-Linked Arrhythmia Syndromes

Background—Mutations in the cardiac sodium (Na) channel gene (SCN5A) give rise to the congenital long-QT syndrome (LQT3) and the Brugada syndrome. Na channel blockade by antiarrhythmic drugs improves the QT interval prolongation in LQT3 but worsens the Brugada syndrome ST-segment elevation. Although Na channel blockade has been proposed as a treatment for LQT3, flecainide also evokes “Brugada-like” ST-segment elevation in LQT3 patients. Here, we examine how Na channel inactivation gating defects in LQT3 and Brugada syndrome elicit proarrhythmic sensitivity to flecainide. Methods and Results—We measured whole-cell Na current (INa) from tsA-201 cells transfected with &Dgr;KPQ, a LQT3 mutation, and 1795insD, a mutation that provokes both the LQT3 and Brugada syndromes. The 1795insD and &Dgr;KPQ channels both exhibited modified inactivation gating (from the closed state), thus potentiating tonic INa block. Flecainide (1 &mgr;mol/L) tonic block was only 16.8±3.0% for wild type but was 58.0±6.0% for 1795insD (P <0.01) and 39.4±8.0% (P <0.05) for &Dgr;KPQ. In addition, the 1795insD mutation delayed recovery from inactivation by enhancing intermediate inactivation, with a 4-fold delay in recovery from use-dependent flecainide block. Conclusions—We have linked 2 inactivation gating defects (“closed-state” fast inactivation and intermediate inactivation) to flecainide sensitivity in patients carrying LQT3 and Brugada syndrome mutations. These results provide a mechanistic rationale for predicting proarrhythmic sensitivity to flecainide based on the identification of specific SCN5A inactivation gating defects.
Protective Efficacy of Newcastle Disease Virus Expressing Soluble Trimeric Hemagglutinin against Highly Pathogenic H5N1 Influenza in Chickens and Mice

Background Highly pathogenic avian influenza virus (HPAIV) causes a highly contagious often fatal disease in poultry, resulting in significant economic losses in the poultry industry. HPAIV H5N1 also poses a major public health threat as it can be transmitted directly from infected poultry to humans. One effective way to combat avian influenza with pandemic potential is through the vaccination of poultry. Several live vaccines based on attenuated Newcastle disease virus (NDV) that express influenza hemagglutinin (HA) have been developed to protect chickens or mammalian species against HPAIV. However, the zoonotic potential of NDV raises safety concerns regarding the use of live NDV recombinants, as the incorporation of a heterologous attachment protein may result in the generation of NDV with altered tropism and/or pathogenicity. Methodology/Principal Findings In the present study we generated recombinant NDVs expressing either full length, membrane-anchored HA of the H5 subtype (NDV-H5) or a soluble trimeric form thereof (NDV-sH53). A single intramuscular immunization with NDV-sH53 or NDV-H5 fully protected chickens against disease after a lethal challenge with H5N1 and reduced levels of virus shedding in tracheal and cloacal swabs. NDV-sH53 was less protective than NDV-H5 (50% vs 80% protection) when administered via the respiratory tract. The NDV-sH53 was ineffective in mice, regardless of whether administered oculonasally or intramuscularly. In this species, NDV-H5 induced protective immunity against HPAIV H5N1, but only after oculonasal administration, despite the poor H5-specific serum antibody response it elicited. Conclusions/Significance Although NDV expressing membrane anchored H5 in general provided better protection than its counterpart expressing soluble H5, chickens could be fully protected against a lethal challenge with H5N1 by using the latter NDV vector. This study thus provides proof of concept for the use of recombinant vector vaccines expressing a soluble form of a heterologous viral membrane protein. Such vectors may be advantageous as they preclude the incorporation of heterologous membrane proteins into the viral vector particles.
Quantification of excess risk for diabetes for those born in times of hunger, in an entire population of a nation, across a century

Based on a unique dataset comprising all 325,000 Austrian patients that were under pharmaceutical treatment for diabetes during 2006 and 2007, we measured the excess risk of developing diabetes triggered by undernourishment in early life. We studied the percentage of all diabetes patients in the total population specifically for each year of birth, from 1917 to 2007. We found a massive excess risk of diabetes in people born during the times of the three major famines and immediately after, which occurred in Austria in the 20th century: 1918–1919, 1938, and 1946–1947. Depending on the region, there was an up to 40% higher chance of having diabetes when born in 1919–1921, compared with 1918 or 1922, where age-specific typical diabetes ratios are observed. The excess risk for diabetes was practically absent in those provinces of Austria that were less affected by the famines. We show that diabetes rates exhibit nontrivial, age-specific sex differences, and correlate with the economic wealth of the region. Our results might be of relevance for establishing higher awareness in the health system for those born in high-risk years, and underline the importance of ensuring sufficient nutrition in prenatal and early stages of life.
Application of Gene Shaving and Mixture Models to Cluster Microarray Gene Expression Data

Researchers are frequently faced with the analysis of microarray data of a relatively large number of genes using a small number of tissue samples. We examine the application of two statistical methods for clustering such microarray expression data: EMMIX-GENE and GeneClust. EMMIX-GENE is a mixture-model based clustering approach, designed primarily to cluster tissue samples on the basis of the genes. GeneClust is an implementation of the gene shaving methodology, motivated by research to identify distinct sets of genes for which variation in expression could be related to a biological property of the tissue samples. We illustrate the use of these two methods in the analysis of Affymetrix oligonucleotide arrays of well-known data sets from colon tissue samples with and without tumors, and of tumor tissue samples from patients with leukemia. Although the two approaches have been developed from different perspectives, the results demonstrate a clear correspondence between gene clusters produced by GeneClust and EMMIX-GENE for the colon tissue data. It is demonstrated, for the case of ribosomal proteins and smooth muscle genes in the colon data set, that both methods can classify genes into co-regulated families. It is further demonstrated that tissue types (tumor and normal) can be separated on the basis of subtle distributed patterns of genes. Application to the leukemia tissue data produces a division of tissues corresponding closely to the external classification, acute myeloid meukemia (AML) and acute lymphoblastic leukemia (ALL), for both methods. In addition, we also identify genes specific for the subgroup of ALL-Tcell samples. Overall, we find that the gene shaving method produces gene clusters at great speed; allows variable cluster sizes and can incorporate partial or full supervision; and finds clusters of genes in which the gene expression varies greatly over the tissue samples while maintaining a high level of coherence between the gene expression profiles. The intent of the EMMIX-GENE method is to cluster the tissue samples. It performs a filtering step that results in a subset of relevant genes, followed by gene clustering, and then tissue clustering, and is favorable in its accuracy of ranking the clusters produced.