Miracle-dz/UniFAR-FTUs huggingface dataset:
Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection

Innate immune cells detect pathogens via pattern recognition receptors (PRRs), which signal for initiation of immune responses to infection. Studies with Dectin-1, a PRR for fungi, have defined a novel innate signaling pathway involving Syk kinase and the adaptor CARD9, which is critical for inducing Th17 responses to fungal infection. We show that another C-type lectin, Dectin-2, also signals via Syk and CARD9, and contributes to dendritic cell (DC) activation by fungal particles. Unlike Dectin-1, Dectin-2 couples to Syk indirectly, through association with the FcRγ chain. In a model of Candida albicans infection, blockade of Dectin-2 did not affect innate immune resistance but abrogated Candida-specific T cell production of IL-17 and, in combination with the absence of Dectin-1, decreased Th1 responses to the organism. Thus, Dectin-2 constitutes a major fungal PRR that can couple to the Syk–CARD9 innate signaling pathway to activate DCs and regulate adaptive immune responses to fungal infection.
Studies in Astronomical Time Series Analysis. V. Bayesian Blocks, a New Method to Analyze Structure in Photon Counting Data

I describe a new time-domain algorithm for detecting localized structures (bursts), revealing pulse shapes, and generally characterizing intensity variations. The input is raw counting data, in any of three forms: time-tagged photon events (TTE), binned counts, or time-to-spill (TTS) data. The output is the most probable segmentation of the observation into time intervals during which the photon arrival rate is perceptibly constant, i.e., has no statistically significant variations. The idea is not that the source is deemed to have this discontinuous, piecewise constant form, rather that such an approximate and generic model is often useful. Since the analysis is based on Bayesian statistics, I call the resulting structures Bayesian blocks. Unlike most, this method does not stipulate time bins—instead the data determine a piecewise constant representation. Therefore the analysis procedure itself does not impose a lower limit to the timescale on which variability can be detected. Locations, amplitudes, and rise and decay times of pulses within a time series can be estimated independent of any pulse-shape model—but only if they do not overlap too much, as deconvolution is not incorporated. The Bayesian blocks method is demonstrated by analyzing pulse structure in BATSE γ-ray data.
The Thatcher Illusion Reveals Orientation Dependence in Brain Regions Involved in Processing Facial Expressions

Although the processing of facial identity is known to be sensitive to the orientation of the face, it is less clear whether orientation sensitivity extends to the processing of facial expressions. To address this issue, we used functional MRI (fMRI) to measure the neural response to the Thatcher illusion. This illusion involves a local inversion of the eyes and mouth in a smiling face—when the face is upright, the inverted features make it appear grotesque, but when the face is inverted, the inversion is no longer apparent. Using an fMRI-adaptation paradigm, we found a release from adaptation in the superior temporal sulcus—a region directly linked to the processing of facial expressions—when the images were upright and they changed from a normal to a Thatcherized configuration. However, this release from adaptation was not evident when the faces were inverted. These results show that regions involved in processing facial expressions display a pronounced orientation sensitivity.
Agreeing to cross: How drivers and pedestrians communicate

The contribution of this paper is twofold. The first is a novel dataset for studying behaviors of traffic participants while crossing. Our dataset contains more than 650 samples of pedestrian behaviors in various street configurations and weather conditions. These examples were selected from approx. 240 hours of driving in the city, suburban and rural roads. The second contribution is an analysis of our data from the point of view of joint attention. We identify what types of non-verbal communication cues road users use at the point of crossing, their responses, and under what circumstances the crossing event takes place. It was found that in more than 90% of the cases pedestrians gaze at the approaching cars prior to crossing in non-signalized crosswalks. The crossing action, however, depends on additional factors such as time to collision, explicit driver's reaction or structure of the crosswalk.
Improved Efficacy of a Pegylated Interferon-α-2a Stepwise Optimization Treatment Strategy in the Treatment of Hepatitis B e Antigen-positive Chronic Hepatitis B Patients

AbstractCurrent pegylated interferon-&agr; (PEG-IFN) treatment for chronic hepatitis B (CHB) e-antigen (HBeAg)-positive patients are suboptimal, and effective ways of improving PEG-IFN treatment efficacy are needed.This retrospective cohort study compared the efficacy of a PEG-IFN stepwise optimization treatment (PEG-IFN SOT) strategy with that of a 48-week PEG-IFN standard therapy (PEG-IFN ST) in HBeAg-positive CHB patients.A total of 110 patients were included in our study. Of these, 70 received the PEG-IFN SOT and 40 received the PEG-IFN ST (control group). We based the decision whether to add adefovir and/or extend the PEG-IFN–based treatment to 96 weeks on the patients’ 12-week or 24-week early virological response (12W EVR, at least a 2 log10 reduction in HBV DNA copies/mL at week 12; 24W EVR, at least 1 log10 reduction in HBsAg IU/mL or HBsAg <1500 IU/mL at week 24) and their 48-week partial response (48W PR, 1.0 ⩽HBeAg ⩽10.0 S/CO or HBeAg >10.0 S/CO but HBsAg <1000 IU/mL). The HBeAg seroconversion rate 24 weeks post-PEG-IFN treatment was significantly higher in the PEG-IFN SOT than the PEG-IFN ST group (50% vs 22.5%, P = 0.005). The HBsAg clearance rates in the PEG-IFN SOT and ST groups were 10% and 0% (P = 0.04), respectively. Receiving PEG-IFN SOT (OR = 0.26, P = 0.01), ALT × ULN at baseline (OR = 0.74, P = 0.003), and achieving 12 and 24W EVR (OR = 0.29, P = 0.03) were independent factors associated with HBeAg seroconversion.PEG-IFN SOT is a promising strategy for achieving high rates of serological response in HBeAg-positive CHB patients.
The Rodney L. White Center for Financial Research a No-arbitrage Approach to Range-based Estimation of Return Covariances and Correlations *

We extend range-based volatility estimation to the multivariate case. In particular, we propose a range-based covariance estimator motivated by a key financial economic consideration, the absence of arbitrage, in addition to statistical considerations. We show that this estimator is highly efficient yet robust to market microstructure noise arising from bid-ask bounce and asynchronous trading. as well as seminar participants at the University of Pennsylvania and at CIRANO for insightful discussions and comments. Clara Vega provided outstanding research assistance.
Polymerase chain reaction in the detection of an ‘outbreak’ of asymptomatic viral infections in a community birth cohort in south India

SUMMARY Asymptomatic enteric infections are important where sequelae or protection from subsequent illness is an outcome measure. The use of reverse transcription–polymerase chain reaction (RT–PCR) to identify asymptomatic enteric infections in a birth cohort followed for rotaviral infections in a south Indian urban slum is reported. Of 1191 non-diarrhoeal samples from 371 children collected in May–June 2003, 22 (1·9%) were positive by ELISA. A total of 147 (40·6%) of 362 samples tested by VP6 RT–PCR were positive. In those samples that could be typed, a high diversity of G types including G1, G2, G4, G8, G9 and G10, and a high proportion (34·4%) of mixed infections were detected. Noroviruses were identified in 6/28 (21·4%) samples tested. The identification of infections undetectable by conventional techniques indicates the importance of the use of sensitive diagnostic techniques in research studies. Asymptomatically infected children may also act as a source of infection for other susceptible hosts.
Homeodomain Interacting Protein Kinase 2 Regulates Postnatal Development of Enteric Dopaminergic Neurons and Glia via BMP Signaling

Trophic factor signaling is important for the migration, differentiation, and survival of enteric neurons during development. The mechanisms that regulate the maturation of enteric neurons in postnatal life, however, are poorly understood. Here, we show that transcriptional cofactor HIPK2 (homeodomain interacting protein kinase 2) is required for the maturation of enteric neurons and for regulating gliogenesis during postnatal development. Mice lacking HIPK2 display a spectrum of gastrointestinal (GI) phenotypes, including distention of colon and slowed GI transit time. Although loss of HIPK2 does not affect the enteric neurons in prenatal development, a progressive loss of enteric neurons occurs during postnatal life in Hipk2−/− mutant mice that preferentially affects the dopaminergic population of neurons in the caudal region of the intestine. The mechanism by which HIPK2 regulates postnatal enteric neuron development appears to involve the response of enteric neurons to bone morphogenetic proteins (BMPs). Specifically, compared to wild type mice, a larger proportion of enteric neurons in Hipk2−/− mutants have an abnormally high level of phosphorylated Smad1/5/8. Consistent with the ability of BMP signaling to promote gliogenesis, Hipk2−/− mutants show a significant increase in glia in the enteric nervous system. In addition, numbers of autophagosomes are increased in enteric neurons in Hipk2−/− mutants, and synaptic maturation is arrested. These results reveal a new role for HIPK2 as an important transcriptional cofactor that regulates the BMP signaling pathway in the maintenance of enteric neurons and glia, and further suggest that HIPK2 and its associated signaling mechanisms may be therapeutically altered to promote postnatal neuronal maturation.
Landscape-Scale Controls on Aboveground Forest Carbon Stocks on the Osa Peninsula, Costa Rica

Tropical forests store large amounts of carbon in tree biomass, although the environmental controls on forest carbon stocks remain poorly resolved. Emerging airborne remote sensing techniques offer a powerful approach to understand how aboveground carbon density (ACD) varies across tropical landscapes. In this study, we evaluate the accuracy of the Carnegie Airborne Observatory (CAO) Light Detection and Ranging (LiDAR) system to detect top-of-canopy tree height (TCH) and ACD across the Osa Peninsula, Costa Rica. LiDAR and field-estimated TCH and ACD were highly correlated across a wide range of forest ages and types. Top-of-canopy height (TCH) reached 67 m, and ACD surpassed 225 Mg C ha-1, indicating both that airborne CAO LiDAR-based estimates of ACD are accurate in tall, high-biomass forests and that the Osa Peninsula harbors some of the most carbon-rich forests in the Neotropics. We also examined the relative influence of lithologic, topoedaphic and climatic factors on regional patterns in ACD, which are known to influence ACD by regulating forest productivity and turnover. Analyses revealed a spatially nested set of factors controlling ACD patterns, with geologic variation explaining up to 16% of the mapped ACD variation at the regional scale, while local variation in topographic slope explained an additional 18%. Lithologic and topoedaphic factors also explained more ACD variation at 30-m than at 100-m spatial resolution, suggesting that environmental filtering depends on the spatial scale of terrain variation. Our result indicate that patterns in ACD are partially controlled by spatial variation in geologic history and geomorphic processes underpinning topographic diversity across landscapes. ACD also exhibited spatial autocorrelation, which may reflect biological processes that influence ACD, such as the assembly of species or phenotypes across the landscape, but additional research is needed to resolve how abiotic and biotic factors contribute to ACD variation across high biomass, high diversity tropical landscapes.
A Possible Link Between Parathyroid Hormone Secretion and Local Regulation of GABA in Human Parathyroid Adenomas.

CONTEXT γ-Aminobutyric acid-B receptor 1 (GABABR1) forms a heterodimeric complex with calcium-sensing receptor (CaSR) in human brain tissue. However, the expression and implication of GABABR1 in human parathyroid adenoma has not yet been examined. OBJECTIVE The objective of the study was to examine a possible link between GABABR1 and PTH secretion in human parathyroid adenoma Design and Methods: Sixty-five patients who underwent parathyroidectomy for primary hyperparathyroidism (PHPT) and 29 control patients with normal parathyroid glands were retrospectively included. All patients diagnosed with PHPT had parathyroid adenomas. We evaluated the protein expression of GABABR1, glutamic acid decarboxylase 65/67 (GAD65/67), and various factors proposed as regulators of PTH secretion including CaSR, vitamin D receptor (VDR), CYP24A1, CYP27B1, fibroblast growth factor, and α-klotho in parathyroid tissues from patients with parathyroid adenomas using immunohistochemistry. RESULTS Expressions of CaSR, GABABR1, and VDR were significantly lower in PHPT patients than in control subjects (P < .001 for CaSR and GABABR1; P = .006 for VDR). Protein expression of GAD65/67, which indicates local production and regulation of GABAergic pathway, was significantly increased in PHPT (P < .001). There were no significant differences in CYP24A1, CYP27B1, fibroblast growth factor, and α-klotho expression between the two groups. Expression of GAD65/67 was significantly correlated with VDR, CYP24A1, CYP27B1, and α-klotho in PHPT (all P < .01) but not in the control groups. CaSR expression was positively associated with serum phosphorus level (r = 0.274, P = .029) and GAD65/67 was negatively correlated with serum PTH level (r = -0.342, P = .005). CONCLUSIONS Local production and action of GABA may be regulated in human parathyroid adenomas. This suggests a possible link between PTH secretion and local regulation of GABA in parathyroid adenomas.
A software method to extend tonal levels and widen tonal range of CCD sensor images

As one of important outcomes of the past decades of researches on sensor arrays for digital cameras, the manufacturers of sensor array technology have responded to the necessity and importance of obtaining an optimal fill factor, which has great impact on collection of incident photons on the sensor, with hardware solution e.g. by introducing microlenses. However it is still impossible to make a fill factor of 100% due to the physical limitations in practical development and manufacturing of digital camera. This has been a bottle neck problem for improving dynamic range and tonal levels for digital cameras e.g. CCD cameras. In this paper we propose a software method to not only widen the recordable dynamic range of a captured image by a CCD camera but also extend its tonal levels. In the method we estimate the fill factor and by a resampling process a virtual fill factor of 100% is achieved where a CCD image is rearranged to a new grid of virtual subpixels. A statistical framework including local learning model and Bayesian inference is used for estimating new sub-pixel intensity values. The highest probability of sub-pixels intensity values in each resampled pixel area is used to estimate the pixel intensity values of the new image. The results show that in comparison to the methods of histogram equalization and image contrast enhancement, which are generally used for improving the displayable dynamic range on only one image, the tonal levels and dynamic range of the image is extended and widen significantly and respectively.
Perinatal predictors of respiratory symptoms and lung function at a young adult age

A longitudinal cohort of 2,957 babies, born in 1975–1978, was used to investigate whether perinatal factors predict respiratory morbidity at a young adult age. In 1997, the presence of asthmatic (wheeze, nocturnal dyspnoea) and bronchitic (cough, phlegm, dyspnoea grade 3) symptoms and the level of lung function was determined in this cohort. The independent association between smoking during pregnancy, being first-born, birth weight and respiratory symptoms and lung function at young adult age was investigated using multiple regression models, taking other potential risk factors into account. Of 1,568 responders, 608 (39%, aged 18–22 yrs) had at least one respiratory symptom. The young adults who had a mother that smoked during pregnancy had a significantly lower level of lung function than their nonintra-uterine exposed peers (regression coefficient (B) (standard error): peak expiratory flow (PEF) −0.257 (0.131) L·s−1; forced expiratory flow when 25% of the forced vital capacity has been exhaled (FEF25) −0.290 (0.129) L·s−1), although they were not at increased risk of having respiratory symptoms. Young adults who were first-born had better levels of lung function (B (se): forced expiratory volume in one second (FEV1) 0.090 (0.042) L) and were less likely to have asthmatic symptoms (odds ratio (95% confidence interval): 0.58 (0.35–0.95)) than those not first-born. Low birth weight (FEV1 −0.013 (0.004) L for a reduction of 100 g) was also predictive of reduced achieved levels of lung function at young adult age, independent of other potential risk factors, e.g. current smoking habits or familial predisposition. This study adds to the knowledge of the role of perinatal factors, such as smoking during pregnancy, as important predictors of respiratory morbidity.
Pragmatic Failure and Referential Ambiguity When Attorneys Ask Child Witnesses “Do You Know/Remember” Questions

“Do you know” and “Do you remember” (DYK/R) questions explicitly ask whether one knows or remembers some information while implicitly asking for that information. This study examined how 4- to 9-year-old (N = 104) children testifying in child sexual abuse cases responded to DYK/R wh- (who, what, where, why, how, and which) and yes/no questions. When asked DYK/R questions containing an implicit wh- question requesting information, children often provided unelaborated “yes” responses. Attorneys’ follow-up questions suggested that children usually misunderstood the pragmatics of the questions. When DYK/R questions contained an implicit yes/no question, unelaborated “yes” or “no” responses could be responding to the explicit or the implicit questions resulting in referentially ambiguous responses. Children often provided referentially ambiguous responses and attorneys usually failed to disambiguate children’s answers. Although pragmatic failure following DYK/R wh- questions decreased with age, the likelihood of referential ambiguity following DYK/R yes/no questions did not. The results highlight the risks of serious miscommunications caused by pragmatic misunderstanding and referential ambiguity when children testify.
Antiremodeling Effect of Long-Term Exercise Training in Patients With Stable Chronic Heart Failure: Results of the Exercise in Left Ventricular Dysfunction and Chronic Heart Failure (ELVD-CHF) Trial

Background—The effects of exercise training (ET) on left ventricular (LV) remodeling in chronic heart failure are not definitively established, and the safety of ET in these patients is still debated. Methods and Results—This multicenter study investigated the long-term effect of moderate ET on LV remodeling, work capacity, and quality of life (QoL) in 90 patients with stable chronic heart failure caused by LV systolic dysfunction, randomized to a 6-month ET program (T, n=45) or a control group (C, n=45). All patients underwent resting echocardiography, a cardiopulmonary exercise test, 6-minute walking test, and QoL assessment at entry and after 6 months. At entry, end-diastolic (EDV) and end-systolic (ESV) volume, ejection fraction, work capacity, peak &OV0312;o2, and walking distance were similar in the 2 groups. After 6 months, LV volumes diminished in T (EDV, from 142±26 to 135±26 mL/m2, P <0.006; ESV, from 107±24 to 97±24 mL/m2, P <0.05) but increased in C (EDV, from 147±41 to 156±42 mL/m2, P <0.01; ESV, from 110±34 to 118±34 mL/m2, P <0.01). Ejection fraction improved in T (P <0.001) but was unchanged in C (P =NS). Significant improvement in work capacity (P <0.001), peak &OV0312;o2 (P <0.006), walking distance (P <0.001), and QoL (P <0.01) was observed in T but not in C (P =NS). T showed a trend toward fewer (P =0.05) hospital readmissions for worsening dyspnea in the absence of other adverse cardiac events. Conclusions—In stable chronic heart failure, long-term moderate ET has no detrimental effect on LV volumes and function; rather, it attenuates abnormal remodeling. Furthermore, ET is safe and effective in improving exercise tolerance and QoL.
The Effect of Motivation on Movement: A Study of Bradykinesia in Parkinson’s Disease

Background Bradykinesia is a cardinal feature of Parkinson’s disease (PD). Despite its disabling impact, the precise cause of this symptom remains elusive. Recent thinking suggests that bradykinesia may be more than simply a manifestation of motor slowness, and may in part reflect a specific deficit in the operation of motivational vigour in the striatum. In this paper we test the hypothesis that movement time in PD can be modulated by the specific nature of the motivational salience of possible action-outcomes. Methodology/Principal Findings We developed a novel movement time paradigm involving winnable rewards and avoidable painful electrical stimuli. The faster the subjects performed an action the more likely they were to win money (in appetitive blocks) or to avoid a painful shock (in aversive blocks). We compared PD patients when OFF dopaminergic medication with controls. Our key finding is that PD patients OFF dopaminergic medication move faster to avoid aversive outcomes (painful electric shocks) than to reap rewarding outcomes (winning money) and, unlike controls, do not speed up in the current trial having failed to win money in the previous one. We also demonstrate that sensitivity to distracting stimuli is valence specific. Conclusions/Significance We suggest this pattern of results can be explained in terms of low dopamine levels in the Parkinsonian state leading to an insensitivity to appetitive outcomes, and thus an inability to modulate movement speed in the face of rewards. By comparison, sensitivity to aversive stimuli is relatively spared. Our findings point to a rarely described property of bradykinesia in PD, namely its selective regulation by everyday outcomes.