Miracle-dz/UniFAR-FTUs huggingface dataset:
Robust Personalisation of 3D Electromechanical Cardiac Models. Application to Heterogeneous and Longitudinal Clinical Databases. (Personnalisation robuste de modèles 3D électromécaniques du coeur. Application à des bases de données cliniques hétérogénes et longitudinales)

Personalised cardiac modeling consists in creating virtual 3D simulations of real clinical cases to help clinicians predict the behaviour of the heart, or better understand some pathologies from the estimated values of biophysical parameters. In this work we first motivate the need for a consistent parameter estimation framework, from a case study were uncertainty in myocardial fibre orientation leads to an uncertainty in estimated parameters which is extremely large compared to their physiological variability. To build a consistent approach to parameter estimation, we then tackle the computational complexity of 3D models. We introduce an original multiscale 0D/3D approach for cardiac models, based on a multiscale coupling to approximate outputs of a 3D model with a reduced "0D" version of the same model. Then we derive from this coupling an efficient multifidelity optimisation algorithm for the 3D model. In a second step, we build more than 140 personalised 3D simulations, in the context of two studies involving the longitudinal analysis of the cardiac function: on one hand the analysis of long-term evolution of cardiomyopathies under therapy, on the other hand the modeling of short-term cardiovascular changes during digestion. Finally we present an algorithm to automatically detect and select observable directions in the parameter space from a set of measurements, and compute consistent population-based priors probabilities in these directions, which can be used to constrain parameter estimation for cases where measurements are missing. This enables consistent parameter estimations in a large databases of 811 cases with the 0D model, and 137 cases of the 3D model.
Dikin ' s Convergence Result for the Affine-Scaling Algorithm

The affine-scaling algorithm is an analogue of Karmarkar's linear programming algorithm that uses affine transformations instead of projective transformations. Although this variant lacks some of the nice properties of Karmarkar's algorithm (for example, it is probably not a polynomial-time algorithm). it nevertheless performs well in computer implementations. It has recently come to the attention of the western mathematical programming community that a Soviet mathematician, I. I. Dikin, proposed the basic affine~scaling algorithm in 1967 and published a proof of convergence in 1974. Dikin's convergence proof assumes only primal nondegeneracy, while all other known proofs require both primal and dual nondegeneracy. Our aim in this paper is to give a clear presentation of Dikin's ideas.
Thermodynamic Basis of Selectivity in the Interactions of Tissue Inhibitors of Metalloproteinases N-domains with Matrix Metalloproteinases-1, -3, and -14*

The four tissue inhibitors of metalloproteinases (TIMPs) are potent inhibitors of the many matrixins (MMPs), except that TIMP1 weakly inhibits some MMPs, including MMP14. The broad-spectrum inhibition of MMPs by TIMPs and their N-domains (NTIMPs) is consistent with the previous isothermal titration calorimetric finding that their interactions are entropy-driven but differ in contributions from solvent and conformational entropy (ΔSsolv, ΔSconf), estimated using heat capacity changes (ΔCp). Selective engineered NTIMPs have potential applications for treating MMP-related diseases, including cancer and cardiomyopathy. Here we report isothermal titration calorimetric studies of the effects of selectivity-modifying mutations in NTIMP1 and NTIMP2 on the thermodynamics of their interactions with MMP1, MMP3, and MMP14. The weak inhibition of MMP14 by NTIMP1 reflects a large conformational entropy penalty for binding. The T98L mutation, peripheral to the NTIMP1 reactive site, enhances binding by increasing ΔSsolv but also reduces ΔSconf. However, the same mutation increases NTIMP1 binding to MMP3 in an interaction that has an unusual positive ΔCp. This indicates a decrease in solvent entropy compensated by increased conformational entropy, possibly reflecting interactions involving alternative conformers. The NTIMP2 mutant, S2D/S4A is a selective MMP1 inhibitor through electrostatic effects of a unique MMP-1 arginine. Asp-2 increases reactive site polarity, reducing ΔCp, but increases conformational entropy to maintain strong binding to MMP1. There is a strong negative correlation between ΔSsolv and ΔSconf for all characterized interactions, but the data for each MMP have characteristic ranges, reflecting intrinsic differences in the structures and dynamics of their free and inhibitor-bound forms.
Processing of digestive vacuoles in Tetrahymena and the effects of dichloroisoproterenol.

The digestive-lysosomal system in Tetrahymena has been extensively studied; however, the various vacuole stages and the existence of a required processing period prior to defecation have not been clearly defined. In this study the presence of such a required processing period and the rate of DV defecation in Tetrahymena thermophila were determined. Like the cycle in Paramecium, a digestive cycle in Tetrahymena consisted of two periods: the processing period was 45 min and the defecation period was approximately 2 h, making the complete cycle approximately 3 h. During the defecation period vacuole egestion followed the kinetics of a first-order rate reaction and had a rate constant of 0.0187/min and a t1/2 of 37 min (82 min into the cycle). Using the naphthol AS-TR phosphate-hexazotized rosanilin method to visualize acid phosphatase activity at the light microscopic level, DVs became positive beginning at 10 min. The number of positive DVs increased to a maximum of 13% when DVs were 20-min old and declined to 5-7% beyond 30 min. Although dichloroisoproterenol (DCI) has been reported by others to stimulate vacuole defecation, we found it inhibited the defecation rate. The extent of inhibition depended on the age of the DVs when exposed to DCI. Vacuole formation was completely blocked in cells preexposed to 40 microM DCI for only 10 min; however, upon further exposure, cells could recover from this inhibition. The time required for complete recovery increased with increasing DCI concentrations. If DCI was given to cells simultaneously with latex beads, it was found to exert a dose-dependent inhibitory effect on DV formation. (ABSTRACT TRUNCATED AT 250 WORDS)
Aristotle, Autism, and Applied Behavior Analysis

This essay asks and answers the question: Is it possible for children with autism to live a good life, to flourish? The notion of a good life that is used is borrowed from Aristotle. Initially, the answer is no. Left to their own devises, children with autism do not flourish. However, unbeknownst to the public, a significant percentage of children with autism can and do flourish when properly treated with the ‘new’ science of Applied Behavior Analysis.
Diagnosis of prosthetic heart valve thrombosis. The respective values of transthoracic and transoesophageal Doppler echocardiography.

Early diagnosis of acute prosthetic thrombosis remains a challenge. In 20 patients with 23 thrombosed cardiac valves, we evaluated the respective value of transthoracic (TTE) and transoesophageal (TEE) Doppler echocardiography. According to the presence or absence of prosthetic obstruction by continuous-wave Doppler, prostheses were separated into two groups. Group 1 included nine thrombosed prostheses (8 mitral, 1 aortic) with severe obstruction. All patients presented with severe symptoms of heart failure. Transthoracic Doppler echocardiography allowed immediate diagnosis of prosthetic thrombosis, even in critically ill patients, showing (1) eccentric transprosthetic colour flow jets in all eight mitral prostheses, (2) severe obstruction on Doppler examination (mean gradient = 18 to 36 mmHg in eight mitral prostheses, and 69 mmHg in one aortic valve), and (3) direct echocardiographic evidence of thrombosis (i.e. thrombus or abnormal disc or leaflet motion) in four patients. All nine patients were immediately treated by surgery (n = 8) or fibrinolysis (n = 1) on the basis of TTE results only. TEE allowed better visualization of thrombus and restricted leaflet or disc motion, but had little influence on patient management. Group 2 included 14 thrombosed prostheses (10 mitral, 4 aortic) with mild or absent obstruction. In three patients with massive mitral prosthetic thrombosis, an associated minimal thrombosis of a prosthetic aortic valve was found at surgery, but was detected neither by TTE, nor by TEE. The 11 remaining patients with isolated partial mitral (n = 10) or aortic (n = 1) thrombosis. Clinical presentation was fever, cerebral embolism, or mild dyspnoea, but no heart failure. TTE was normal in all. (ABSTRACT TRUNCATED AT 250 WORDS)
Why is the special structure of the language important for Chinese spoken language processing? - examples on spoken document retrieval, segmentation and summarization

The Chinese language is not only spoken by the largest population in the world, but quite different from many western languages with a very special structure. It is not alphabetic: large number of Chinese characters are ideographic symbols and pronounced as monosyllables. The open vocabulary nature, the flexible wording structure and the tone behavior are also good examples within the special structure. It is believed that better results and performance will be obtainable in developing Chinese spoken language processing technologies, if this special structure can be taken into account. In this paper, a set of “feature units” for Chinese spoken language processing is identified, and the retrieval, segmentation and summarization of Chinese spoken documents are taken as examples in analyzing the use of such “feature units”. Experimental results indicate that by careful considerations of the special structure and proper choice of the “feature units”, significantly better performance can be achieved.
Comparative Preclinical Pharmacokinetic and Metabolic Studies of the Combretastatin Prodrugs Combretastatin A4 Phosphate and A1 Phosphate

Purpose: Combretastatin A4 phosphate (CA4P) and its structural analog, combretastatin A1 phosphate (CA1P), are soluble prodrugs capable of interacting with tubulin and causing rapid vascular shutdown within tumors. CA4P has completed Phase I clinical trials, but recent preclinical studies have shown that CA1P displays a greater antitumor effect than the combretastatin A4 (CA4) analog at equal doses. The aim of this study, therefore, is to compare pharmacokinetics and metabolism of the two compounds to determine whether pharmacokinetics plays a role in their differential activity. Experimental Design: NMRI mice bearing MAC29 tumors received injection with either CA4P or CA1P at a therapeutic dose of 150 mg·kg−1, and profiles of both compounds and their metabolites analyzed by a sensitive and specific liquid chromatography/mass spectroscopy method. Results: The metabolic profile of both compounds is complex, with up to 14 metabolites being detected for combretastatin A1 (CA1) in the plasma. Many of these metabolites have been identified by liquid chromatography/mass spectroscopy. Initial studies, however, focused on the active components CA4 and CA1, where plasma and tumor areas under the curve were 18.4 and 60.1 μg·h·ml−1 for CA4, and 10.4 and 13.1 μg·h·ml−1 for CA1, respectively. In vitro metabolic comparisons of the two compounds strongly suggest that CA1 is metabolized to a more reactive species than the CA4. Conclusions: Although in vitro studies suggest that variable rates of tumor-specific prodrug dephosphorylation may explain these differences in pharmacokinetics profiles, the improved antitumor activity and altered pharmacokinetic profile of CA1 may be due to the formation of a more reactive metabolite.
Angiotensin-(1-7)-Mediated Signaling in Cardiomyocytes

The Renin-Angiotensin System (RAS) acts at multiple targets and has its synthesis machinery present in different tissues, including the heart. Actually, it is well known that besides Ang II, the RAS has other active peptides. Of particular interest is the heptapeptide Ang-(1-7) that has been shown to exert cardioprotective effects. In this way, great compilations about Ang-(1-7) actions in the heart have been presented in the literature. However, much less information is available concerning the Ang-(1-7) actions directly in cardiomyocytes. In this paper, we show the actual knowledge about Ang-(1-7)-mediated signaling in cardiac cells more specifically we provide a brief overview of ACE2/Ang-(1-7)/Mas axis; and highlight the discoveries made in cardiomyocyte physiology through the use of genetic approaches. Finally, we discuss the protective signaling induced by Ang-(1-7) in cardiomyocytes and point molecular determinants of these effects.
Risk Factors for Ductal, Lobular, and Mixed Ductal-Lobular Breast Cancer in a Screening Population

Background: Biological distinctions between histologic subtypes of breast cancer suggest etiologic differences, although few studies have been powered to examine such differences. We compared associations between several factors and risk of ductal, lobular, and mixed ductal-lobular breast cancers. Methods: We used risk factor data from the Breast Cancer Surveillance Consortium for 3,331,744 mammograms on 1,211,238 women, including 19,119 women diagnosed with invasive breast cancer following mammography (n = 14,818 ductal, 1,602 lobular, and 1,601 mixed ductal-lobular). Histologic subtype–specific risk factor associations were evaluated using Cox regression. Results: Significant positive associations with family history and breast density were similar across subtypes. Hormone therapy use was associated with increased risk of all subtypes, but was most strongly associated with lobular cancer [hazard ratio (HR) = 1.46; 95% confidence interval (CI), 1.25-1.70]. Relative to nulliparous women, parous women had lower risk of ductal and mixed but not lobular cancers (HR = 0.80; 95% CI, 0.76-0.84; HR = 0.79; 95% CI, 0.68-0.93; HR = 0.96; 95% CI, 0.81-1.15, respectively). Late age at first birth was associated with increased risk of all subtypes. Conclusions: Similarities in risk factor associations with ductal, lobular, and mixed breast cancer subtypes were more pronounced than differences. Distinctions between subtype-specific associations were limited to analyses of hormone therapy use and reproductive history. Impact: The results of this study indicate that the strongest risk factors for breast cancer overall (that is, family history and breast density) are not histologic subtype specific. Additional studies are needed to better characterize subtype-specific associations with genetic, hormonal, and nonhormonal factors. Cancer Epidemiol Biomarkers Prev; 19(6); 1643–54. ©2010 AACR.
Knocking down of the KCC2 in rat hippocampal neurons increases intracellular chloride concentration and compromises neuronal survival

Non‐technical summary ‘To be, or not to be’– thousands of neurons are facing this Shakespearean question in the brains of patients suffering from epilepsy or the consequences of a brain traumatism or stroke. The destiny of neurons in damaged brain depends on tiny equilibrium between pro‐survival and pro‐death signalling. Numerous studies have shown that the activity of the neuronal potassium chloride co‐transporter KCC2 strongly decreases during a pathology. However, it remained unclear whether the change of the KCC2 function protects neurons or contributes to neuronal death. Here, using cultures of hippocampal neurons, we show that experimental silencing of endogenous KCC2 using an RNA interference approach or a dominant negative mutant reduces neuronal resistance to toxic insults. In contrast, the artificial gain of KCC2 function in the same neurons protects them from death. This finding highlights KCC2 as a molecule that plays a critical role in the destiny of neurons under toxic conditions and opens new avenues for the development of neuroprotective therapy.
Teachers’ code-switching in bilingual classrooms: exploring pedagogical and sociocultural functions

ABSTRACT The pedagogical and sociocultural functions of teachers’ code-switching are an important factor in achieving the dual goals of content learning and language learning in bilingual programmes. This paper reports on an ethnographic case study investigating how and why teachers switched between languages in tertiary bilingual classrooms in Indonesia, where the main language of instruction was English. Data on code-switching were gathered in three classrooms over one semester, employing classroom observation with video and audio recording, semi-structured teacher interviews with some stimulated recall, and a focus group discussion. Transcripts of classroom interaction were examined using both an Interactional Sociolinguistics (IS) perspective and functional categories of code-switching. Teacher reflections were studied, and analysis indicated that teachers’ code-switching was frequently used to support students to gain understanding of unfamiliar concepts, where the pedagogical focus was on the subject matter more than on language. It also involved managing students’ behaviour and engaging in interpersonal and affective interactions with students. The teachers’ code-switching thus frequently functioned as translanguaging in that it occurred as an intentional strategy for teaching in these bilingual classrooms, integrating the two languages in order to achieve better communication and engagement in learning.
The combination of intravitreal bevacizumab and phacoemulsification surgery in patients with cataract and coexisting diabetic macular edema.

PURPOSE The aim of this study was to assess the efficacy of phacoemulsification combined with intravitreal (i.v.t.) bevacizumab injection in diabetics with clinically significant macular edema (CSME) and cataract. METHODS This retrospective study included diabetic patients with cataract and CSME who underwent phacoemulsification and intraocular lens implantation with a 2.5-mg bevacizumab i.v. t injection (ivBe) (15 eyes) or without ivBe (controls, 14 eyes). Best-corrected visual acuity (BCVA), central macular thickness (CMT) measured by optic coherence tomography (OCT), and adverse events were recorded. RESULTS In the ivBe group, the OCT images demonstrated that CMT (mean +/- standard deviation [SD]) decreased significantly from 466 +/- 105 at baseline to 333 +/- 107, 313 +/- 138 and 333 +/- 111 microm at 4, 8, and 12 weeks, respectively, after treatment (P < 0.05). The visual acuity in logMAR (mean +/- SD) improved significantly from 1.66 +/- 0.39 at baseline to 1.30 +/- 0.50, 1.15 +/- 0.42, 0.99 +/- 0.48, and 1.03+/- 0.44 at 1, 4, 8, and 12 weeks, respectively, after treatment (P < 0.05). However, in the control group, the CMT changed insignificantly from 443 +/- 109 at baseline to 463 +/- 106, 425 +/- 128, and 421 +/- 119 microm at 4, 8 and 12 weeks, respectively after treatment (P > 0.05). The visual acuity in logMAR improved insignificantly from 1.63 +/- 0.42 at baseline to 1.43 +/- 0.53, and 1.39 +/- 0.43 at 1, and 4 weeks (P > 0.05) and significantly to 1.24 +/- 0.45 and 1.18 +/- 0.44 at 8 and 12 weeks, respectively, after treatment (P < 0.05). None of the patients in both groups experienced injection- or surgery-related complications or any obvious systemic adverse events. CONCLUSIONS The short-term results suggest that phacoemulsification with i.v. t. bevacizumab safely reduces macular edema and improves visual acuity for cataract and CSME in diabetics.
Reactive Criminal Thinking as a Consequence of Low Self-Control and Prior Offending

ABSTRACT The purpose of this study was to determine if low self-control and prior serious offending serve as antecedents to reactive criminal thinking. Cross-lagged correlations between low self-control and serious offending were examined in 5,427 male and female members of the National Longitudinal Study of Adolescent Health (Add Health) in an effort to determine their effect on subsequent reactive criminal thinking. Results from a five-equation path analysis showed that the two cross-lagged relationships were equally predictive of reactive criminal thinking. These findings suggest that reactive criminal thinking may have its roots in low self-control and prior serious offending.
NetScale: scalable time-stepped hybrid simulation of large IP networks

This paper presents a scalable time-stepped hybrid simulation algorithm which is well adapted to the simulation of large IP networks (up to one million of competing ows and network elements), while tracking reactive traffic behaviour and packet-level phenomena e.g. timeout trigger or packet burstiness. This simulation paradigm allows one to gain several orders of magnitude of computation time compared to traditional discrete event simulation approaches. The accuracy of this simulation method is evaluated by comparison to other simulation methodologies. Examples of large scale network simulations are also presented.
A Procedure for Alternate Test Feature Design and Selection

This paper is a practical illustration of the adoption of alternate tests based upon the judicious selection of the set of parameters to be considered for design as well as to be observed subsequently. The notion of signatures is introduced, and their ability to predict design accuracy is analyzed. The application is demonstrated for an RF LNA circuit.
Analysis of SSR dynamics in chloroplast genomes of Brassicaceae family

Simple sequence repeats (SSRs) are present abundantly in most eukaryotic genomes. They affect several cellular processes like chromatin organization, regulation of gene activity, DNA repair, DNA recombination, etc. Though considerable data exists on using nuclear SSRs to infer phylogenetic relationships, the potential of chloroplast microsatellites (cpSSR), in this regard, remains largely unexplored. In the present study we probe various nucleotide repeat motifs (NRMs) / types of SSRs present in chloroplast genomes (cpDNA) of 12 species belonging to Brassicaceae family. NRMs show a non-random distribution in coding and non-coding compartments of cpDNA. As expected, trinucleotide repeats are more common in coding regions while other repeat motifs are prominent in non-coding DNA. Total numbers of SSRs in coding region show little variation between species while considerable variation is exhibited by SSRs in non-coding regions. Finally, we have designed universal primers that yield polymorphic amplicons from all 12 species. Our analysis also suggests that amplicon length polymorphism shows no significant relationship with sequence based phylogeny of SSRs in cpDNA of Brassicaceae family.