Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of Allele-Specific Therapeutic siRNA in Meesmann Epithelial Corneal Dystrophy

Background Meesmann epithelial corneal dystrophy (MECD) is an inherited eye disorder caused by dominant-negative mutations in either keratins K3 or K12, leading to mechanical fragility of the anterior corneal epithelium, the outermost covering of the eye. Typically, patients suffer from lifelong irritation of the eye and/or photophobia but rarely lose visual acuity; however, some individuals are severely affected, with corneal scarring requiring transplant surgery. At present no treatment exists which addresses the underlying pathology of corneal dystrophy. The aim of this study was to design and assess the efficacy and potency of an allele-specific siRNA approach as a future treatment for MECD. Methods and Findings We studied a family with a consistently severe phenotype where all affected persons were shown to carry heterozygous missense mutation Leu132Pro in the KRT12 gene. Using a cell-culture assay of keratin filament formation, mutation Leu132Pro was shown to be significantly more disruptive than the most common mutation, Arg135Thr, which is associated with typical, mild MECD. A siRNA sequence walk identified a number of potent inhibitors for the mutant allele, which had no appreciable effect on wild-type K12. The most specific and potent inhibitors were shown to completely block mutant K12 protein expression with negligible effect on wild-type K12 or other closely related keratins. Cells transfected with wild-type K12-EGFP construct show a predominantly normal keratin filament formation with only 5% aggregate formation, while transfection with mutant K12-EGFP construct resulted in a significantly higher percentage of keratin aggregates (41.75%; p<0.001 with 95% confidence limits). The lead siRNA inhibitor significantly rescued the ability to form keratin filaments (74.75% of the cells contained normal keratin filaments; p<0.001 with 95% confidence limits). Conclusions This study demonstrates that it is feasible to design highly potent siRNA against mutant alleles with single-nucleotide specificity for future treatment of MECD.
Firm Expansion and Stock Price Momentum

We document a significant and robust connection between firm-level asset changes and return momentum. Momentum profits are large and significant for firms that have experienced large asset expansions or contractions, whereas they otherwise are small and often insignificant. The interaction pattern is not subsumed by previously documented drivers of momentum and shows up in market states where prior literature has documented an absence of momentum profits. Furthermore, we find a positive time series relationship between aggregate asset growth (AG) and return momentum, and the effect of aggregate AG is stronger than that of variables related to business cycles and investor sentiment. While most existing models of firm investment and momentum cannot explain our results, recent real options models appear to hold the most promise.
The Introduction of Technical Debt Tracking in Large Companies

Large software companies need to support continuous and fast delivery of customer value both in the short and long term. However, this can be hindered if both evolution and maintenance of existing systems are hampered by Technical Debt. Although a lot of theoretical work on Technical Debt has been recently produced, its practical management lacks empirical studies. In this paper we investigate the state of practice in several companies in order to understand how they start tracking Technical Debt. We combined different methodologies: we conducted a survey, involving 226 respondents from 15 organizations and a more in-depth multiple case-study in three organizations, where Technical Debt was tracked: we involved 13 interviews and 79 Technical Debt issues analysis. We found that the development time dedicated to manage Technical Debt is substantial (around 25% of the overall development) but not systematic: only a few participants methodically track Technical Debt. By studying the approaches in the companies participating in the case-study, we understood how companies start tracking Technical Debt and what are the initial benefits and challenges. Finally, we propose a Strategic Adoption Model based to define and adopt a dedicated process for tracking Technical Debt
Bp Neural Network-Based Effective Fault Localization

In program debugging, fault localization identifies the exact locations of program faults. Finding these faults using an ad-hoc approach or based only on programmers' intuitive guesswork can be very time consuming. A better way is to use a well-justified method, supported by case studies for its effectiveness, to automatically identify and prioritize suspicious code for an examination of possible fault locations. To do so, we propose the use of a back-propagation (BP) neural network, a machine learning model which has been successfully applied to software risk analysis, cost prediction, and reliability estimation, to help programmers effectively locate program faults. A BP neural network is suitable for learning the input-output relationship from a set of data, such as the inputs and the corresponding outputs of a program. We first train a BP neural network with the coverage data (statement coverage in our case) and the execution result (success or failure) collected from executing a program, and then we use the trained network to compute the suspiciousness of each executable statement, in terms of its likelihood of containing faults. Suspicious code is ranked in descending order based on its suspiciousness. Programmers will examine such code from the top of the rank to identify faults. Four case studies on different programs (the Siemens suite, the Unix suite, grep and gzip) are conducted. Our results suggest that a BP neural network-based fault localization method is effective in locating program faults.
On the Relative Distances of ω Centauri and 47 Tucanae

We present precise optical and near-infrared ground-based photometry of two globular clusters (GCs): ω Cen and 47 Tuc. These photometric catalogs are unbiased in the red giant branch (RGB) region close to the tip. We provide new estimates of the RGB tip (TRGB) magnitudes—mI(TRGB) = 9.84 ± 0.05, ω Cen; mI(TRGB) = 9.46 ± 0.06, 47 Tuc—and use these to determine the relative distances of the two GCs. We find that distance ratios based on different calibrations of the TRGB, the RR Lyrae stars, and kinematic distances agree with each other within 1 σ. Absolute TRGB and RR Lyrae distance moduli agree within 0.10-0.15 mag, while absolute kinematic distance moduli are 0.2-0.3 mag smaller. Absolute distances to 47 Tuc based on the zero-age horizontal branch and on the white dwarf fitting agree within 0.1 mag, but they are 0.1-0.3 mag smaller than TRGB and RR Lyrae distances.
Static Pose Estimation from Depth Images using Random Regression Forests and Hough Voting

Robust and fast algorithms for estimating the pose of a human given an image would have a far reaching impact on many fields in and outside of computer vision. We address the problem using depth data that can be captured inexpensively using consumer depth cameras such as the Kinect sensor. To achieve robustness and speed on a small training dataset, we formulate the pose estimation task within a regression and Hough voting framework. Our approach uses random regression forests to predict joint locations from each pixel and accumulate these predictions with Hough voting. The Hough accumulator images are treated as likelihood distributions where maxima correspond to joint location hypotheses. We demonstrate our approach and compare to the state-ofthe-art on a publicly available dataset.
Confirmation bias in visual attention

This dissertation evaluates the proposal that visual attention is biased towards stimuli that could potentially verify a perceptual hypothesis, compared to stimuli that might falsify it. To do so, I use a visual search task with two, mutually exclusive, coloured targets (e.g., a red p or a blue p). Before each set of searches, one target colour is designated positive, or confirmatory, information and one is designated negative information by requiring affirmative responses or negative responses to one of the two targets (e.g., press Z if the p is red, press M if it is not). The first set of experiments, reported in Chapter 2, showed that confirmatory search patterns were observed for both novel and practiced hypotheses, were observed despite instructions to the contrary, and were mitigated by a search colour-preview. Chapter 3 measured the ocular correlates of the search bias, showing that more fixations indeed go towards confirmatory stimuli, but showed that when stimulus inspections took longer, search became les confirmatory and more efficient. Finally, Chapter 4 demonstrated that confirmatory search did not occur when hypotheses referred to visually heterogeneous stimuli and also did not occur when hypotheses included a negation, suggesting that a visual matching bias underlies confirmatory search. Confirmation bias thus appears to be a side-effect of goal-directed cognition in general, and the present results are discussed in relation to theories likening reasoning to foraging and
Levodopa and executive performance in Parkinson's disease: A randomized study

Parkinson's disease (PD) patients may experience fluctuations in executive performance after oral levodopa (LD). Their relationship with the pharmacokinetic profile of LD and with distinct cognitive processes associated with frontal-basal ganglia circuits is not well understood. In this randomized, double-blind, crossover study we plotted acute cognitive changes in 14 PD patients challenged with faster (immediate-release, IR) versus slower (controlled-release, CR) increases in LD plasma concentrations. We monitored motor status, LD plasma levels, and performance on four tasks of executive function (Wisconsin Card Sorting Test—WCST, Sternberg test, Stroop and Tower of Hanoi), 1 hr before and over +6 hr after IR and CR-LD dose. Analysis of variance demonstrated significant but divergent changes in the Sternberg (6-digit but not 2- and 4-digit) test: improvement after CR-LD and worsening after IR-LD. Marginal improvement (p = .085) was observed with CR-LD in the WCST, while no significant differences were seen for the Stroop or Tower of Hanoi tests. Executive-related performance after LD challenge may differ depending on the LD time-to-peak plasma concentration and specific task demands. A slower rise in LD levels appears to have a more favorable impact on more difficult working memory tests. These results require replication to determine their generalization. (JINS, 2008, 14, 832–841.)
A saliency-based solution for robust off-road obstacle detection

Stereo-based off-road obstacle detection is a complex and still open problem. The challenges are in great extent related to computational cost and noise level. Previous work has shown that visual saliency and voting mechanisms are extremely effective in tackling these issues. This paper proposes a set of extensions to these mechanisms, to further improve the detector's speed-accuracy trade-off as well as its robustness. The observed enhancements are due in part to the adaptive way saliency is accounted for by the detector during the image scanning procedure. Additionally, detector's positive results are in turn used to boost the saliency map itself, thus reinforcing the analysis of relevant regions of the image. To enable detection in highly roughed terrain, the detector's invariance to the robot's posture is also enhanced. Experimental results show that, with the extended detector, denominated of ESalOD, higher levels of robustness, accuracy and computational efficiency are attained.
Activation of MSRV-Type Endogenous Retroviruses during Infectious Mononucleosis and Epstein-Barr Virus Latency: The Missing Link with Multiple Sclerosis?

The etiology of multiple sclerosis (MS) is still unclear. The immuno-pathogenic phenomena leading to neurodegeneration are thought to be triggered by environmental (viral? ) factors operating on predisposing genetic backgrounds. Among the proposed co-factors are the Epstein Barr virus (EBV), and the potentially neuropathogenic HERV-W/MSRV/Syncytin-1 endogenous retroviruses. The ascertained links between EBV and MS are history of late primary infection, possibly leading to infectious mononucleosis (IM), and high titers of pre-onset IgG against EBV nuclear antigens (anti-EBNA IgG). During MS, there is no evidence of MS-specific EBV expression, while a continuous expression of HERV-Ws occurs, paralleling disease behaviour. We found repeatedly extracellular HERV-W/MSRV and MSRV-specific mRNA sequences in MS patients (in blood, spinal fluid, and brain samples), and MRSV presence/load strikingly paralleled MS stages and active/remission phases. Aim of the study was to verify whether HERV-W might be activated in vivo, in hospitalized young adults with IM symptoms, that were analyzed with respect to expression of HERV-W/MSRV transcripts and proteins. Healthy controls were either EBV-negative or latently EBV-infected with/without high titers of anti-EBNA-1 IgG. The results show that activation of HERV-W/MSRV occurs in blood mononuclear cells of IM patients (2Log10 increase of MSRV-type env mRNA accumulation with respect to EBV-negative controls). When healthy controls are stratified for previous EBV infection (high and low, or no anti-EBNA-1 IgG titers), a direct correlation occurs with MSRV mRNA accumulation. Flow cytometry data show increased percentages of cells exposing surface HERV-Wenv protein, that occur differently in specific cell subsets, and in acute disease and past infection. Thus, the data indicate that the two main links between EBV and MS (IM and high anti-EBNA-1-IgG titers) are paralleled by activation of the potentially neuropathogenic HERV-W/MSRV. These novel findings suggest HERV-W/MSRV activation as the missing link between EBV and MS, and may open new avenues of intervention.
Cognitive Functions, Concentration of Endogenous Estradiol, Estrogen Receptor α (ERα) Polymorphism in Postmenopausal Women

Background The goal of this study was to investigate the relationship between cognitive functions and the level of endogenous estradiol in postmenopausal women, according to which estrogen receptor α (ERα) polymorphism the woman carries. Material/Methods The study group consisted of 210 women. The inclusion criteria were: minimum 2 years after the last menstruation, FSH concentration 30 U/ml, and no dementia signs on Montreal Cognitive Assessment (MoCA). A computerized battery of Central Nervous System Vital Signs (CNS VS) test was used to diagnose cognitive functions. Genotyping of the ERα polymorphism was performed using a polymerase chain reaction and restriction enzymes (PCR-RFLP). Blood plasma was tested for FSH and estradiol (E2). Statistical analysis was performed using STATISTICA software. Results A relationship was confirmed between standard scores for 3 cognitive functions: general memory, verbal memory, and processing speed, and the XbaI polymorphism in the women in the study. In the group of women with genotype TT PvuII, significant positive relationships were observed between the concentration of E2 and the standard scores of 3 cognitive functions: general memory, verbal memory, and processing speed. In the group of women with genotype TC PvuII, significant negative correlations were found between the concentration of E2 and the standard scores of 4 cognitive functions: NCI, general memory, verbal memory, and processing speed. Conclusions ERα polymorphism exerted an effect on the interaction between the concentration of estradiol and the results for cognitive functions. The concentration of estradiol did not depend on Xba1 and PvuII polymorphisms. The results for cognitive functions depended on which Xba1 polymorphism the woman carried.
Activation and Habituation of the Cingulate Cortex during Emotion Processing in Healthy Controls, Borderline, and Schizotypal Personality Disorder

Disturbances in emotional functioning are central features of the clinical profiles of both borderline and schizotypal personality disorder (BPD and SPD, respectively). BPD is characterized by a high sensitivity to emotional stimuli and unusually strong and long-lasting reactions, indicative of impaired habituation to emotional stimuli (Linehan, 1993). Previous research suggests that SPD patients demonstrate limbic hyper-reactivity to unpleasant stimuli, at least initially, but intact habituation to repeated presentation of unpleasant stimuli (Hazlett et al., 2012). The cingulate cortex supports various aspects of emotion processing and regulation, and abnormalities of this region have been related to emotion dysfunction in SPD and BPD (Koenigsberg, Fan, et al., 2009; Modinos, Ormel, & Aleman, 2010). However, findings of functional cingulate abnormalities in the context of emotion processing have been inconsistent in BPD and limited in SPD. The current study utilized event-related functional magnetic resonance imaging (fMRI) in three groups, BPD patients, SPD patients, and healthy control individuals, during a task involving an intermixed series of unpleasant, neutral, and pleasant pictures, each presented twice within their respective trial. This approach permitted the examination of reactivity to emotional stimuli and habituation of emotional responses within the cingulate. Blood-oxygen-level dependent response values were obtained within the manually delineated anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) and compared across groups. Compared to healthy controls and SPD patients, BPD patients exhibited significantly greater activity in the ACC during the presentation of neutral pictures. Heightened activity in the BPD group persisted across the initial and repeated presentations of neutral pictures. On the other hand, SPD patients exhibited greater activity in the ACC compared to healthy controls and BPD patients during the initial presentation of unpleasant pictures, but activity normalized when the pictures were repeated. The two patient groups demonstrated heightened ACC activation,
Long-term outcome in patients receiving permanent pacemaker implantation for atrioventricular block

AbstractA permanent pacemaker (PPM) with dual chamber pacing (DDD) offers atrioventricular synchronization for patients with atrioventricular block (AVB). Single lead atrial synchronous ventricular pacing mode (VDD) is an alternative, but there are concerns about its efficacy and risk of atrial undersensing. Whether VDD can be a good alternative in patients with AVB remains unknown. The aim of the present study was to compare the long-term risk of mortality of VDD with DDD pacing.A total of 207 patients undergoing PPM implantations for AVB with VDD mode were enrolled from 2000 to 2013. Another 828 age- and sex-matched patients undergoing DDD implantations during the same period of time were selected as the control group in a 1 to 4 ratio. The study endpoint was mortality.A total of 1035 patients (64.3% male) were followed up for 46.5 ± 43.2 months. The mean ages were 75.0 years for VDD, and 74.9 years for DDD. The Kaplan–Meier survival analysis showed no significant difference in long-term survival between the VDD and DDD groups (log-rank P = 0.313). After adjustment for baseline characteristics, the VDD and DDD groups had a similar long-term prognosis with an adjusted hazard ratio of 0.875 (P = 0.445). Further analyses for the risk of cardiovascular and noncardiovascular deaths also showed no significant differences between the 2 groups.The long-term prognosis of VDD mode is comparable to that of DDD mode. Single lead VDD can be considered as an alternative choice in patients with AVB without sinus nodal dysfunction.
Compression and Filtering of Random Signals under Constraint of Variable Memory

We study a new technique for optimal data compression subject to conditions of causality and different types of memory. The technique is based on the assumption that some information about compressed data can be obtained from a solution of the associated problem without constraints of causality and memory. This allows us to consider two separate problem related to compression and de- compression subject to those constraints. Their solutions are given and the analysis of the associated errors is provided. Keywords—stochastic signals, optimization problems in signal processing.
Posterior features for template-based ASR

This paper investigates the use of phoneme class conditional probabilities as features (posterior features) for template-based ASR. Using 75 words and 600 words task-independent and speaker-independent setup on Phonebook database, we investigate the use of different posterior distribution estimators, different distance measures that are better suited for posterior distributions, and different training data. The reported experiments clearly demonstrate that posterior features are always superior, and generalize better than other classical acoustic features (at the cost of training a posterior distribution estimator).
Physiopucks

In this article, we evaluate b-Reactable, a digital music instrument that combines implicit physiology-based interaction through EEG and ECG, and explicit gestural interaction for sound generation and control. This multimodality is embodied in tangible objects named physiopucks, which are driven by biosignals. We hypothesize that multimodality increases users’ motivation in a musical task, compared to the use of a gesture-only tabletop system (the Reactable). We compared motivational aspects in dyads collaborating in three experimental groups (N = 56): the Physio group (one physiology- and one gesture-based user), the Sham group (one prerecorded physiology- and one gesture-based user), and the Control group (two gesture users). Between-group comparisons showed that motivation dimensions of Confidence and Satisfaction were higher in b-Reactable than in the gesture-only tangible interface, and that fake physiology-based feedback significantly reduced these effects. Our study also shows the potential of combined implicit and explicit interaction modes in multiuser HCI scenarios.
Evolutionary robotics-a children's game

The authors explore the concept of development without programming by children. Especially, they look at the case of developing robot control systems. The evolutionary robotics approach has shown that in some cases, given a mathematically described fitness function, it is possible to achieve an automatic development of robot controllers. However, it is questionable how one is to construct the mathematical fitness function. So they applied an interactive genetic algorithm to the problem of developing robot controllers and achieved and evolutionary robotics approach that allows children without any programming knowledge to develop controller for LEGO robots. They used neural networks as robot controllers, and found that combining the interactive genetic algorithm with a kind of reinforcement learning-development at the evolutionary time scale combined with life-time development-reduces the development time drastically. Hence, they overcome one of the major drawbacks of the interactive genetic algorithm, namely the development time.
Makespan Minimization in Job Shops: A Linear Time Approximation Scheme

In this paper we present a linear time approximation scheme for the job shop scheduling problem with a fixed number of machines and fixed number of operations per job. This improves on the previously best $2+\epsilon$, $\epsilon > 0$, approximation algorithm for the problem by Shmoys, Stein, and Wein [SIAM J. Comput. , 23 (1994), pp. 617--632]. Our approximation scheme is very general and it can be extended to the case of job shop scheduling problems with release and delivery times, multistage job shops, dag job shops, and preemptive variants of most of these problems.