Miracle-dz/UniFAR-FTUs huggingface dataset:
The default modes of reading: modulation of posterior cingulate and medial prefrontal cortex connectivity associated with comprehension and task focus while reading

Reading is a fundamental human capacity and yet it can easily be derailed by the simple act of mind-wandering. A large-scale brain network, referred to as the default mode network (DMN), has been shown to be involved in both mind-wandering and reading, raising the question as to how the same neural system could be implicated in processes with both costs and benefits to narrative comprehension. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to explore whether the intrinsic functional connectivity of the two key midline hubs of the DMN—the posterior cingulate cortex (PCC) and anterior medial prefrontal cortex (aMPFC)—was predictive of individual differences in reading comprehension and task focus recorded outside of the scanner. Worse comprehension was associated with greater functional connectivity between the PCC and a region of the ventral striatum. Better comprehension was associated with greater functional connectivity with a region of the right insula. By contrast reports of increasing task focus were associated with functional connectivity from the aMPFC to clusters in the PCC, the left parietal and temporal cortex, and the cerebellum. Our results suggest that the DMN has both costs (such as poor comprehension) and benefits to reading (such as an on-task focus) because its midline core can couple its activity with other regions to form distinct functional communities that allow seemingly opposing mental states to occur. This flexible coupling allows the DMN to participate in cognitive states that complement the act of reading as well as others that do not.
Presence of Cathepsin B in the Human Pancreatic Secretory Pathway and Its Role in Trypsinogen Activation during Hereditary Pancreatitis*

The lysosomal cysteine protease cathepsin B is thought to play a central role in intrapancreatic trypsinogen activation and the onset of experimental pancreatitis. Recent in vitro studies have suggested that this mechanism might be of pathophysiological relevance in hereditary pancreatitis, a human inborn disorder associated with mutations in the cationic trypsinogen gene. In the present study evidence is presented that cathepsin B is abundantly present in the secretory compartment of the human exocrine pancreas, as judged by immunogold electron microscopy. Moreover, pro-cathepsin B and mature cathepsin B are both secreted together with trypsinogen and active trypsin into the pancreatic juice of patients with sporadic pancreatitis or hereditary pancreatitis. Finally, cathepsin B- catalyzed activation of recombinant human cationic trypsinogen with hereditary pancreatitis-associated mutations N29I, N29T, or R122H were characterized. In contrast to a previous report, cathepsin B-mediated activation of wild type and all three mutant trypsinogen forms was essentially identical under a wide range of experimental conditions. These observations confirm the presence of active cathepsin B in the human pancreatic secretory pathway and are consistent with the notion that cathepsin B-mediated trypsinogen activation might play a pathogenic role in human pancreatitis. On the other hand, the results clearly demonstrate that hereditary pancreatitis-associated mutations do not lead to increased or decreased trypsinogen activation by cathepsin B. Therefore, mutation-dependent alterations in cathepsin B-induced trypsinogen activation are not the cause of hereditary pancreatitis.
Formin‐mediated actin polymerization promotes Salmonella invasion

Salmonella invade host cells using Type 3 secreted effectors, which modulate host cellular targets to promote actin rearrangements at the cell surface that drive bacterial uptake. The Arp2/3 complex contributes to Salmonella invasion but is not essential, indicating other actin regulatory factors are involved. Here, we show a novel role for FHOD1, a formin family member, in Salmonella invasion. FHOD1 and Arp2/3 occupy distinct microdomains at the invasion site and control distinct aspects of membrane protrusion formation. FHOD1 is phosphorylated during infection and this modification is required for promoting bacterial uptake by host cells. ROCK II, but not ROCK I, is recruited to the invasion site and is required for FHOD1 phosphorylation and for Salmonella invasion. Together, our studies revealan important phospho‐dependent FHOD1 actin polymerization pathway in Salmonella invasion.
Incidental memory for faces in children with different genetic subtypes of Prader-Willi syndrome

Abstract The present study examined the effects of genetic subtype on social memory in children (7–16 years) with Prader–Willi syndrome (PWS). Visual event-related potentials (ERPs) during a passive viewing task were used to compare incidental memory traces for repeated vs single presentations of previously unfamiliar social (faces) and nonsocial (houses) images in 15 children with the deletion subtype and 13 children with maternal uniparental disomy (mUPD). While all participants perceived faces as different from houses (N170 responses), repeated faces elicited more positive ERP amplitudes (‘old/new’ effect, 250–500ms) only in children with the deletion subtype. Conversely, the mUPD group demonstrated reduced amplitudes suggestive of habituation to the repeated faces. ERP responses to repeated vs single house images did not differ in either group. The results suggest that faces hold different motivational value for individuals with the deletion vs mUPD subtype of PWS and could contribute to the explanation of subtype differences in the psychiatric symptoms, including autism symptomatology.
Unbiased MMSE-Based Noise Power Estimation With Low Complexity and Low Tracking Delay

Recently, it has been proposed to estimate the noise power spectral density by means of minimum mean-square error (MMSE) optimal estimation. We show that the resulting estimator can be interpreted as a voice activity detector (VAD)-based noise power estimator, where the noise power is updated only when speech absence is signaled, compensated with a required bias compensation. We show that the bias compensation is unnecessary when we replace the VAD by a soft speech presence probability (SPP) with fixed priors. Choosing fixed priors also has the benefit of decoupling the noise power estimator from subsequent steps in a speech enhancement framework, such as the estimation of the speech power and the estimation of the clean speech. We show that the proposed speech presence probability (SPP) approach maintains the quick noise tracking performance of the bias compensated minimum mean-square error (MMSE)-based approach while exhibiting less overestimation of the spectral noise power and an even lower computational complexity.
Computer-aided diagnosis for classifying benign versus malignant thyroid nodules based on ultrasound images: A comparison with radiologist-based assessments.

PURPOSE To develop a semiautomated computer-aided diagnosis (cad) system for thyroid cancer using two-dimensional ultrasound images that can be used to yield a second opinion in the clinic to differentiate malignant and benign lesions. METHODS A total of 118 ultrasound images that included axial and longitudinal images from patients with biopsy-confirmed malignant (n = 30) and benign (n = 29) nodules were collected. Thyroid cad software was developed to extract quantitative features from these images based on thyroid nodule segmentation in which adaptive diffusion flow for active contours was used. Various features, including histogram, intensity differences, elliptical fit, gray-level co-occurrence matrixes, and gray-level run-length matrixes, were evaluated for each region imaged. Based on these imaging features, a support vector machine (SVM) classifier was used to differentiate benign and malignant nodules. Leave-one-out cross-validation with sequential forward feature selection was performed to evaluate the overall accuracy of this method. Additionally, analyses with contingency tables and receiver operating characteristic (ROC) curves were performed to compare the performance of cad with visual inspection by expert radiologists based on established gold standards. RESULTS Most univariate features for this proposed cad system attained accuracies that ranged from 78.0% to 83.1%. When optimal SVM parameters that were established using a grid search method with features that radiologists use for visual inspection were employed, the authors could attain rates of accuracy that ranged from 72.9% to 84.7%. Using leave-one-out cross-validation results in a multivariate analysis of various features, the highest accuracy achieved using the proposed cad system was 98.3%, whereas visual inspection by radiologists reached 94.9% accuracy. To obtain the highest accuracies, "axial ratio" and "max probability" in axial images were most frequently included in the optimal feature sets for the authors' proposed cad system, while "shape" and "calcification" in longitudinal images were most frequently included in the optimal feature sets for visual inspection by radiologists. The computed areas under curves in the ROC analysis were 0.986 and 0.979 for the proposed cad system and visual inspection by radiologists, respectively; no significant difference was detected between these groups. CONCLUSIONS The use of thyroid cad to differentiate malignant from benign lesions shows accuracy similar to that obtained via visual inspection by radiologists. Thyroid cad might be considered a viable way to generate a second opinion for radiologists in clinical practice.
Sequence Kernel Association Test of Multiple Continuous Phenotypes

Genetic studies often collect multiple correlated traits, which could be analyzed jointly to increase power by aggregating multiple weak effects and provide additional insights into the etiology of complex human diseases. Existing methods for multiple trait association tests have primarily focused on common variants. There is a surprising dearth of published methods for testing the association of rare variants with multiple correlated traits. In this paper, we extend the commonly used sequence kernel association test (SKAT) for single‐trait analysis to test for the joint association of rare variant sets with multiple traits. We investigate the performance of the proposed method through extensive simulation studies. We further illustrate its usefulness with application to the analysis of diabetes‐related traits in the Atherosclerosis Risk in Communities (ARIC) Study. We identified an exome‐wide significant rare variant set in the gene YAP1 worthy of further investigations.
Promising Practices in Employer Health and Productivity Management Efforts: Findings From a Benchmarking Study

Objective: To identify key success factors related to employer-based health and productivity management (HPM) programs. Methods: Data regarding promising practices in HPM were gathered via literature review, discussions with subject matter experts, online inventory, and site visits. Results: Promising practices in HPM include 1) integrating HPM programs into the organization’s operations; 2) simultaneously addressing individual, environmental, policy, and cultural factors affecting health and productivity; 3) targeting several health issues; 4) tailoring programs to address specific needs; 5) attaining high participation; 6) rigorously evaluating programs; and 7) communicating successful outcomes to key stakeholders. Conclusion: Increased efforts should be directed at disseminating the experiences of promising practices. However, more research is needed in this area, so that additional public and private funding is made available for applied research in “real-life” business settings. Finally, employers should be provided effective tools and resources to support their HPM efforts.
Possible linkages of late‐Holocene drought in the North American midcontinent to Pacific Decadal Oscillation and solar activity

Paleorecords are key for evaluating the long‐term patterns and controls of drought. We analyzed calcite in annually laminated sediments from a Minnesota lake for oxygen‐isotopic composition (δ18O). The δ18O record of the past ∼3100 years reveals that droughts of greater severity and duration than during the 20th century occurred repeatedly, especially prior to 300 AD. Drought variability was anomalously low during the 20th century; ∼90% of the variability values during the last 3100 years were greater than the 20th‐century average. δ18O is strongly correlated with the index of the Pacific Decadal Oscillation (PDO) during the past 100 years, and periodicities of the late‐Holocene δ18O record are similar to those of the PDO. Furthermore, time series of δ18O and atmospheric Δ14C are generally coherent after 700 AD. Both the Pacific climate and solar irradiance probably played a role in drought occurrence, but their effects were non‐stationary through the late Holocene.
A Tumor-Activatable Theranostic Nanomedicine Platform for NIR Fluorescence-Guided Surgery and Combinatorial Phototherapy

Fluorescence image-guided surgery combined with intraoperative therapeutic modalities has great potential for intraoperative detection of oncologic targets and eradication of unresectable cancer residues. Therefore, we have developed an activatable theranostic nanoplatform that can be used concurrently for two purposes: (1) tumor delineation with real-time near infrared (NIR) fluorescence signal during surgery, and (2) intraoperative targeted treatment to further eliminate unresected disease sites by non-toxic phototherapy. Methods: The developed nanoplatform is based on a single agent, silicon naphthalocyanine (SiNc), encapsulated in biodegradable PEG-PCL (poly (ethylene glycol)-b-poly(ɛ-caprolactone)) nanoparticles. It is engineered to be non-fluorescent initially via dense SiNc packing within the nanoparticle's hydrophobic core, with NIR fluorescence activation after accumulation at the tumor site. The activatable nanoplatform was evaluated in vitro and in two different murine cancer models, including an ovarian intraperitoneal metastasis-mimicking model. Furthermore, fluorescence image-guided surgery mediated by this nanoplatform was performed on the employed animal models using a Fluobeam® 800 imaging system. Finally, the phototherapeutic efficacy of the developed nanoplatform was demonstrated in vivo. Results: Our in vitro data suggest that the intracellular environment of cancer cells is capable of compromising the integrity of self-assembled nanoparticles and thus causes disruption of the tight dye packing inside the hydrophobic cores and activation of the NIR fluorescence. Animal studies demonstrated accumulation of activatable nanoparticles at the tumor site following systemic administration, as well as release and fluorescence recovery of SiNc from the polymeric carrier. It was also validated that the developed nanoparticles are compatible with the intraoperative imaging system Fluobeam® 800, and nanoparticle-mediated image-guided surgery provides successful resection of cancer tumors. Finally, in vivo studies revealed that combinatorial phototherapy mediated by the nanoparticles could efficiently eradicate chemoresistant ovarian cancer tumors. Conclusion: The revealed properties of the activatable nanoplatform make it highly promising for further application in clinical image-guided surgery and combined phototherapy, facilitating a potential translation to clinical studies.
Can We Translate Letters?

Current statistical machine translation systems handle the translation process as the transformation of a string of symbols into another string of symbols. Normally the symbols dealt with are the words in different languages, sometimes with some additional information included, like morphological data. In this work we try to push the approach to the limit, working not on the level of words, but treating both the source and target sentences as a string of letters. We try to find out if a nearly unmodified state-of-the-art translation system is able to cope with the problem and whether it is capable to further generalize translation rules, for example at the level of word suffixes and translation of unseen words. Experiments are carried out for the translation of Catalan to Spanish.
Modeling and predicting competitive sorption of organic compounds in soil

Binary systems consisting of 1,2‐dichlorobenzene (12DCB) + competitor were investigated over a range of concentrations of competitor in three natural sorbents with distinct characteristics. Two models, the ideal adsorbed solution theory (IAST) and the potential theory (Polanyi‐based multisolute model), widely used in the prediction of multisolute sorption equilibrium from single‐solute data, were used to simulate competitive sorption in our systems. The goal was to determine which multisolute model best represented the experimentally obtained multisolute data in natural sorbents of varied properties. Results suggested that for the sorbents and sorbates studied, the IAST model provided much better results. On average, the IAST model provided lower errors (23%) than the potential model (45%). The effect of competitor structure on the degree of competition was also investigated to identify any relationships between competition and structure using molecular descriptors. The competitors chlorobenzene, naphthalene, 1,4‐dichlorobenzene, 1,2,4‐trichlorobenzene all showed very similar degrees of competition, while benzene, phenanthrene, and pyrene were the least effective competitors toward 12DCB across all sorbents. Different sorption sites or sorption mechanisms might be involved in the sorption of these molecules leading to a lack of competitive behavior. A significant relationship between competitor structure and the degree of competition was observed at environmentally relevant sorbed competitor concentrations for the soil containing the highest fraction of hard carbon (Forbes soil). Environ. Toxicol. Chem. 2010;29:2676–2684. © 2010 SETAC
Q Fever Pneumonia: Virulence of Coxiella burnetii Pathovars in a Murine Model of Aerosol Infection

ABSTRACT Q fever is a worldwide zoonosis caused by Coxiella burnetii, a strictly intracellular bacterium that is a potential bioweapon. Humans usually acquires Q fever after inhalation of dust infected by subclinical animals. We used an aerosol exposure apparatus to challenge immunocompetent (BALB/c) and severe combined immunodeficient (SCID) mice with two different strains (strain Nine Mile and strain Q 212) of C. burnetii at two different inocula. Pathological lesions and dissemination of the bacteria were related to the size of the inoculum. SCID mice showed major pulmonary lesions, whereas similarly infected BALB/c mice were more able to eliminate the bacteria. Pathological differences were found between the strains, with Nine Mile showing more severe histological lesions and quantified spread of bacteria. Our animal model could provide a new tool for the study of acute Q fever pneumonia, the development of Q fever in immunodeficient hosts, and the differentiation of pathogenicity among C. burnetii isolates.
Imaging dislocation cores – the way forward

Although the sub-angstrom resolution of the modern transmission electron microscope (TEM) has made major contributions to defect structure analysis in many fields (such as oxides, interfaces, nanoparticles and superconductors) it has yielded little direct information on the core structure of dislocations. We suggest that “forbidden reflection” lattice images recorded in an ultra-high vacuum TEM in projections normal to the dislocation line could provide interpretable images of cores at atomic resolution. These could answer crucial questions, such as the nature of kinks, core reconstruction and periodicity, the nature of obstacles, and help distinguish obstacle theories of kink motion from the secondary Peierls–valley Hirth–Lothe theory. We give experimental forbidden reflection images and a new image obtained from silicon under UHV conditions with atomically smooth surfaces, whose preparation did not anneal out all dislocations. We also show experimental coherent nanodiffraction patterns and scanning transmission electron microscope (STEM) images recorded with the beam parallel to the core, so that core reconstruction can be expected to introduce a “half-order” Laue zone ring. We discuss the contribution that energy-loss spectroscopy from dislocation cores can be expected to make if a nanoprobe beam is used.
Survival in primary pulmonary hypertension. Validation of a prognostic equation.

BACKGROUND The prognosis of patients with primary pulmonary hypertension (PPH) remains a major problem for the planning and assessment of therapeutic interventions. The objectives of this study were (1) to characterize mortality in a Mexican population of patients with PPH and to investigate factors associated with survival and (2) to test the applicability in this population of the prognostic equation proposed by the US National Institutes of Health study on PPH. METHODS AND RESULTS A dynamic cohort of patients with PPH at our institution were enrolled between June 1977 and August 1991 and prospectively followed at regular intervals through September 1992. Measurements at diagnosis included hemodynamic and pulmonary function variables in addition to information on demographic data and medical history. The response to vasodilator treatment was also analyzed. The estimated median survival of the group was 4.04 years (95% confidence interval, 2.98 to 5.08 years). Variables associated with poor survival (univariate analysis) included an elevated mean right atrial pressure, a decreased cardiac index, and a decreased mixed venous PO2. A reduced forced vital capacity and the absence of vasodilator treatment were also associated with poor survival. A multivariate Cox proportional-hazards regression analysis was used to assess the adjusted hazard ratios, hence the relative contributions of the variables controlling for confounding. Reduced forced vital capacity and cardiac index and increased right atrial pressure were still significantly associated as risk factors for survival in patients with PPH. Survival as computed by the equation correlated with real survival of PPH patients with positive predictive values of 87%, 91%, and 89% at 1, 2, and 3 years, respectively. The equation, however, was relatively unable to predict deaths in our population, in part because of the strict limits of poor prognosis. CONCLUSIONS Mortality in PPH is largely associated with hemodynamic variables that assess right ventricular function. The proposed prognostic equation had a high sensitivity and a relatively low specificity to predict survival in our PPH population. To improve this specificity it may be necessary to increase the limits of poor prognosis as defined by the equation.