Miracle-dz/UniFAR-FTUs huggingface dataset:
Hearing Faces: How the Infant Brain Matches the Face It Sees with the Speech It Hears

Speech is not a purely auditory signal. From around 2 months of age, infants are able to correctly match the vowel they hear with the appropriate articulating face. However, there is no behavioral evidence of integrated audiovisual perception until 4 months of age, at the earliest, when an illusory percept can be created by the fusion of the auditory stimulus and of the facial cues (McGurk effect). To understand how infants initially match the articulatory movements they see with the sounds they hear, we recorded high-density ERPs in response to auditory vowels that followed a congruent or incongruent silently articulating face in 10-week-old infants. In a first experiment, we determined that auditory–visual integration occurs during the early stages of perception as in adults. The mismatch response was similar in timing and in topography whether the preceding vowels were presented visually or aurally. In the second experiment, we studied audiovisual integration in the linguistic (vowel perception) and nonlinguistic (gender perception) domain. We observed a mismatch response for both types of change at similar latencies. Their topographies were significantly different demonstrating that cross-modal integration of these features is computed in parallel by two different networks. Indeed, brain source modeling revealed that phoneme and gender computations were lateralized toward the left and toward the right hemisphere, respectively, suggesting that each hemisphere possesses an early processing bias. We also observed repetition suppression in temporal regions and repetition enhancement in frontal regions. These results underscore how complex and structured is the human cortical organization which sustains communication from the first weeks of life on.
Palmitoylation of Amyloid Precursor Protein Regulates Amyloidogenic Processing in Lipid Rafts

Brains of patients affected by Alzheimer's disease (AD) contain large deposits of aggregated amyloid β-protein (Aβ). Only a small fraction of the amyloid precursor protein (APP) gives rise to Aβ. Here, we report that ∼10% of APP undergoes a post-translational lipid modification called palmitoylation. We identified the palmitoylation sites in APP at Cys186 and Cys187. Surprisingly, point mutations introduced into these cysteines caused nearly complete ER retention of APP. Thus, either APP palmitoylation or disulfide bridges involving these Cys residues appear to be required for ER exit of APP. In later compartments, palmitoylated APP (palAPP) was specifically enriched in lipid rafts. In vitro BACE1 cleavage assays using cell or mouse brain lipid rafts showed that APP palmitoylation enhanced BACE1-mediated processing of APP. Interestingly, we detected an age-dependent increase in endogenous mouse brain palAPP levels. Overexpression of selected DHHC palmitoyl acyltransferases increased palmitoylation of APP and doubled Aβ production, while two palmitoylation inhibitors reduced palAPP levels and APP processing. We have found previously that acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibition led to impaired APP processing. Here we demonstrate that pharmacological inhibition or genetic inactivation of ACAT decrease lipid raft palAPP levels by up to 76%, likely resulting in impaired APP processing. Together, our results indicate that APP palmitoylation enhances amyloidogenic processing by targeting APP to lipid rafts and enhancing its BACE1-mediated cleavage. Thus, inhibition of palAPP formation by ACAT or specific palmitoylation inhibitors would appear to be a valid strategy for prevention and/or treatment of AD.
Localization Of Accessory Pathways In Wolff Parkinson White Syndrome Using R/S Ratios On Surface Ecgs.

BACKGROUND This study was conducted to establish the accuracy of R/S ratios in localizing accessory pathways in Wolff Parkinson White Syndrome on surface ECGs. METHODS This was a retrospective cross-sectional study from January 2002 till December 2016 conducted at National Institute of Cardiovascular diseases in Karachi, Pakistan. The sample included 157 patients with manifesting Wolff Parkinson White (WPW) Syndrome on a 12-lead surface ECG. As per the inclusion criteria, patients who had persistent or intermittent pre-excitation on surface ECG and had undergone electrophysiological study (EP) were included in the sample. Individuals with both successful and unsuccessful ablation procedures were included. RESULTS The sample consisted of 62.4% males (n=98) and 37.6% females (n=59) with mean age being 35.36±12.44. Accessory pathways (APs) were identified on the left side in majority of the patients with 54.1% (n=85) while right sided pathways were seen in 42.1% (n=66). Moreover, the most common accessory pathway amongst the males was Left Anterior (LA) and Left Lateral (LL) with a percentage of 48%, followed by Right Posteroseptal (RPS) at 20.4%. As opposed to this, the most common pathways amongst the females turned out to be RPS at 33.9% followed by LL and LA at 32.2%. Furthermore, the test using ratios were most effective in identifying left sided APs with sensitivity 74.1% and was least sensitive in identifying right sided pathways (sensitivity=40.7%). However, it was highly specific in locating right sided pathways with specificity of 94.6% as opposed to 83.3% in the left side. Furthermore, mid-septum regions had a sensitivity and specificity of 66.7% and 69.6% respectively. CONCLUSIONS This establishes the effectiveness of R/S ratios in determining the location of accessory pathway based on the surface ECG prior to the ablation procedure. Since the younger population is affected more commonly, prolonged exposure to ionizing radiation can cause long term complications therefore, by this means, the duration of exposure can be reduced.
Image Representations and New Domains in Neural Image Captioning

We examine the possibility that recent promising results in automatic caption generation are due primarily to language models. By varying image representation quality produced by a convolutional neural network, we find that a state-of-the-art neural captioning algorithm is able to produce quality captions even when provided with surprisingly poor image representations. We replicate this result in a new, fine-grained, transfer learned captioning domain, consisting of 66K recipe image/title pairs. We also provide some experiments regarding the appropriateness of datasets for automatic captioning, and find that having multiple captions per image is beneficial, but not an absolute requirement.
The wake of imagination

A test strip of the type which is dipped into a liquid such as urine for indicating by color information with respect to the liquid. The test strip has a transparent backing on one side of which is located a color-reaction paper with a fastening layer situated between the paper and the backing for fastening the paper to the backing. The fastening layer is opaque and non-reflecting with respect to light, so that while light can pass freely through the backing it will reflected by the color-reaction paper without passing through the backing. The test strip is moved perpendicularly across an optical axis along which light is directed with the light traveling first through the transparent backing and then being reflected by the color-reaction paper. Signals are generated from the light passing through the backing and the light reflected by the color-reaction paper, with the timing of the signal from the reflected light being controlled by the signal from the light which has passed through the transparent backing. The signal from the light which has traveled through the backing is utilized to initiate a time interval after which the signal from the reflected light is generated so as to assure that the operation of the structure providing the signal from the reflected light takes place when the color-reaction paper intersects the optical axis.
LinkBench: a database benchmark based on the Facebook social graph

Database benchmarks are an important tool for database researchers and practitioners that ease the process of making informed comparisons between different database hardware, software and configurations. Large scale web services such as social networks are a major and growing database application area, but currently there are few benchmarks that accurately model web service workloads. In this paper we present a new synthetic benchmark called LinkBench. LinkBench is based on traces from production databases that store "social graph" data at Facebook, a major social network. We characterize the data and query workload in many dimensions, and use the insights gained to construct a realistic synthetic benchmark. LinkBench provides a realistic and challenging test for persistent storage of social and web service data, filling a gap in the available tools for researchers, developers and administrators.
It's Never Too LATE: A New Look at Local Average Treatment Effects with or Without Defiers

In heterogeneous treatment effect models with endogeneity, identification of the LATE typically relies on the availability of an exogenous instrument monotonically related to treatment participation. We demonstrate that a strictly weaker local monotonicity condition identifies the LATEs on compliers and on defiers. We propose simple estimators that are potentially more efficient than 2SLS, even under circumstances where 2SLS is consistent. Additionally, when easing local monotonicity to local stochastic monotonicity, our identification results still apply to subsets of compliers and defiers. Finally, we provide an empirical application, rejoining the endeavor of estimating returns to education using the quarter of birth instrument.
Hypofractionated High-Dose Irradiation with Positron Emission Tomography Data for the Treatment of Glioblastoma Multiforme

This research paper presents clinical outcomes of hypofractionated high-dose irradiation by intensity-modulated radiation therapy (Hypo-IMRT) with 11C-methionine positron emission tomography (MET-PET) data for the treatment of glioblastoma multiforme (GBM). A total of 45 patients with GBM were treated with Hypo-IMRT after surgery. Gross tumor volume (GTV) was defined as the area of enhanced lesion on MRI, including MET-PET avid region; clinical target volume (CTV) was the area with 5 mm margin surrounding the GTV; planning target volume (PTV) was the area with 15 mm margin surrounding the CTV, including MET-PET moderate region. Hypo-IMRT was performed in 8 fractions; planning the dose for GTV was escalated to 68 Gy and that for CTV was escalated to 56 Gy, while keeping the dose delivered to the PTV at 40 Gy. Concomitant and adjuvant TMZ chemotherapy was administered. At a median follow-up of 18.7 months, median overall survival (OS) was 20.0 months, and median progression-free survival was 13.0 months. The 1- and 2-year OS rates were 71.2% and 26.3%, respectively. Adjuvant TMZ chemotherapy was significantly predictive of OS on multivariate analysis. Late toxicity included 7 cases of Grade 3-4 radiation necrosis. Hypo-IMRT with MET-PET data appeared to result in favorable survival outcomes for patients with GBM.
Reducing Preconception Risks Among African American Women with Conversational Agent Technology

Background: Systems and tools are needed to identify and mitigate preconception health (PCH) risks, particularly for African American (AA) women, given persistent health disparities. We developed and tested “Gabby,” an online preconception conversational agent system. Methods: One hundred nongravid AA women 18–34 years of age were screened for over 100 PCH risks and randomized to the Gabby or control group. The Gabby group interacted with the system for up to six months; the control group received a letter indicating their health risks with a recommendation to talk with their clinician. The numbers, proportions, and types of risks were compared between groups. Results: There were 23.7 (SD 5.9) risks identified per participant. Eighty-five percent (77 of 91) provided 6 month follow up data. The Gabby group had greater reductions in the number (8.3 vs. 5.5 risks, P < .05) and the proportion (27.8% vs 20.5%, P < 0.01) of risks compared to controls. The Gabby group averaged 63.7 minutes of interaction time. Seventy-eight percent reported that it “was easy to talk to Gabby” and 64% used information from Gabby to improve their health. Conclusion: Gabby was significantly associated with preconception risk reduction. More research is needed to determine if Gabby can benefit higher risk populations and if risk reduction is clinically significant.
Correction of the ΔF508 Mutation in the Cystic Fibrosis Transmembrane Conductance Regulator Gene by Zinc-Finger Nuclease Homology-Directed Repair

Abstract The use of zinc-finger nucleases (ZFNs) to permanently and precisely modify the human genome offers a potential alternative to cDNA-based gene therapy. The ΔF508 mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene is observed in ∼70% of patients with cystic fibrosis (CF) and is a candidate for ZFN-mediated repair. Here, we report the modular design and synthesis of a pair of ZFNs that can create a double-stranded break (DSB) 203 bp upstream of the ΔF508 lesion, resulting in a nonhomologous end-joining (NHEJ) frequency of 7.8%. In spite of this relatively long distance between the DSB and the ΔF508 mutation, homology-directed repair (HDR) could be detected when using a DNA donor containing part of the wild-type (WT) CFTR. The ZFN target half-sites in CFTR are separated by a 4-bp spacer, but efficient cleavage of synthetic targets with either a 4- or 6-bp spacer was observed in vitro. These ZFNs may be suitable for a genome-editing strategy using a partial cDNA sequence-containing exons 10–24 of CFTR to restore CFTR function to cells containing not only the ΔF508 mutation but also potentially any mutation in or downstream of exon 10.
Return to work after coronary revascularization procedures and a patient’s job satisfaction: A prospective study

ObjectivesResearch into work reintegration following invasive cardiac procedures is limited. The aim of this prospective study was to explore predictors of job satisfaction among cardiac patients who have returned to work after cardiac rehabilitation (CR). Material and MethodsThe study population consisted of 90 cardiac patients who have recently been treated with coronary angioplasty or heart surgery. They were evaluated during their CR and 12 months after the discharge using validated self-report questionnaires measuring job satisfaction, work stress-related factors, emotional distress and illness perception. Information on socio-demographic, medical and occupational factors has also been collected.ResultsAfter adjusting for demographic, occupational and medical variables, baseline job satisfaction (p < 0.001), depression (p < 0.01) and ambition (p < 0.05) turned out to be independent, significant predictors of job satisfaction following return to work (RTW). Patients who had a partial RTW were more satisfied with their job than those who had a full RTW, controlling for baseline job satisfaction.ConclusionsThese findings recommend an early assessment of patients’ psychosocial work environment and emotional distress, with particular emphasis on job satisfaction and depressive symptoms, in order to promote satisfying and healthy RTW after cardiac interventions.
Temperature compensation and temperature sensation in the circadian clock

Significance Circadian clocks in animals, plants, and fungi possess the remarkable property of temperature compensation: the clock has a temperature-insensitive period, while retaining the ability to synchronize to temperature cycles. The conservation of temperature compensation across clades means it is likely critical to the function of circadian clocks. Temperature compensation also places the circadian clock in contrast to other biological pathways, which generally have temperature-sensitive time scales. However, the mechanism of temperature compensation remains unknown. We present a general scheme by which a circadian oscillator can be temperature-compensated while still synchronizing to environmental temperature cycles. In particular, we give experimental evidence that the circadian clock consists of a temperature-insensitive core oscillator coupled to a specific adaptive temperature signaling pathway. All known circadian clocks have an endogenous period that is remarkably insensitive to temperature, a property known as temperature compensation, while at the same time being readily entrained by a diurnal temperature oscillation. Although temperature compensation and entrainment are defining features of circadian clocks, their mechanisms remain poorly understood. Most models presume that multiple steps in the circadian cycle are temperature-dependent, thus facilitating temperature entrainment, but then insist that the effect of changes around the cycle sums to zero to enforce temperature compensation. An alternative theory proposes that the circadian oscillator evolved from an adaptive temperature sensor: a gene circuit that responds only to temperature changes. This theory implies that temperature changes should linearly rescale the amplitudes of clock component oscillations but leave phase relationships and shapes unchanged. We show using timeless luciferase reporter measurements and Western blots against TIMELESS protein that this prediction is satisfied by the Drosophila circadian clock. We also review evidence for pathways that couple temperature to the circadian clock, and show previously unidentified evidence for coupling between the Drosophila clock and the heat-shock pathway.
Fingerprinting of poultry isolates of Enterococcus cecorum using three molecular typing methods

Enterococcus cecorum is an emerging challenge to the broiler industry. The organism has been implicated in septicemia, spondylitis, arthritis, and osteomyelitis in commercial broilers and broiler breeders, which lead to economic losses attributed to increased mortality and culling rates, decreased average processing weights, and increased feed conversion ratios. The current study evaluated the genetic variability of 30 clinical isolates of E. cecorum from outbreaks in Pennsylvania, using 3 molecular typing methods, namely, pulsed-field gel electrophoresis (PFGE), randomly amplified polymorphic DNA analysis, and enterobacterial repetitive intergenic consensus–PCR (polymerase chain reaction), in order to understand their genetic relatedness and to identify possible pathogenic clones. The study revealed the existence of genotypic polymorphism among E. cecorum associated with clinical disease. Of the 3 typing methods used, PFGE analysis demonstrated higher genetic variability of E. cecorum isolates compared to PCR-based methods. Also, each molecular typing method was evaluated in terms of typeability, discriminatory power, and reproducibility for application of these typing methods in fingerprinting of E. cecorum in future reference. Pulsed-field gel electrophoresis provided the most reliable results with greater discriminatory power and higher reproducibility compared to the 2 PCR-based methods.
Evolution of opsins and phototransduction

Opsins are the universal photoreceptor molecules of all visual systems in the animal kingdom. They can change their conformation from a resting state to a signalling state upon light absorption, which activates the G protein, thereby resulting in a signalling cascade that produces physiological responses. This process of capturing a photon and transforming it into a physiological response is known as phototransduction. Recent cloning techniques have revealed the rich and diverse nature of these molecules, found in organisms ranging from jellyfish to humans, functioning in visual and non-visual phototransduction systems and photoisomerases. Here we describe the diversity of these proteins and their role in phototransduction. Then we explore the molecular properties of opsins, by analysing site-directed mutants, strategically designed by phylogenetic comparison. This site-directed mutant approach led us to identify many key features in the evolution of the photoreceptor molecules. In particular, we will discuss the evolution of the counterion, the reduction of agonist binding to the receptor, and the molecular properties that characterize rod opsins apart from cone opsins. We will show how the advances in molecular biology and biophysics have given us insights into how evolution works at the molecular level.
Reproductive factors and familial predisposition for breast cancer by age 50 years. A case-control-family study for assessing main effects and possible gene-environment interaction.

BACKGROUND The effect of environmental/lifestyle factors on breast cancer risk may be modified by genetic predisposition. METHODS In a population-based case-control-family study performed in Germany including 706 cases by age 50 years, 1381 population, and 252 sister controls, we investigated main effects for environmental/lifestyle factors and genetic susceptibility and gene-environment interaction (G x E). Different surrogate measures for genetic predisposition using pedigree information were used: first-degree family history of breast or ovarian cancer; and gene carrier probability using a genetic model based on rare dominant genes. Possible G x E interaction was studied by (1) logistic regression using cases and population controls including an interaction term; (2) comparing results using sister controls and population controls; (3) case-only analysis with logistic regression and (4) a mixture logistic model. RESULTS Familial predisposition showed the strongest main effect and the estimated gene carrier probability gave the best fit. High parity and longer duration of breastfeeding reduced breast cancer risk significantly, a history of abortions increased risk and age at menarche showed no significant effect. We found significant G x E interaction between parity and genetic susceptibility using different surrogate measures. In women most likely to have a high genetic susceptibility, high parity was less protective. Later age at menarche was protective in women with a positive family history. No evidence for G x E interaction was found for breastfeeding and abortion. CONCLUSIONS These findings corroborate results from other studies and provide further evidence that the magnitude of protection from parity is reduced in women most likely to have a genetic risk in spite of the limitations of using surrogate genetic measures.