Miracle-dz/UniFAR-FTUs huggingface dataset:
Global analyses of UPF1 binding and function reveal expanded scope of nonsense-mediated mRNA decay

UPF1 is a DNA/RNA helicase with essential roles in nonsense-mediated mRNA decay (NMD) and embryonic development. How UPF1 regulates target abundance and the relationship between NMD and embryogenesis are not well understood. To explore how NMD shapes the embryonic transcriptome, we integrated genome-wide analyses of UPF1 binding locations, NMD-regulated gene expression, and translation in murine embryonic stem cells (mESCs). We identified over 200 direct UPF1 binding targets using crosslinking/immunoprecipitation-sequencing (CLIP-seq) and revealed a repression pathway that involves 3′ UTR binding by UPF1 and translation but is independent of canonical targeting features involving 3′ UTR length and stop codon placement. Interestingly, NMD targeting of this set of mRNAs occurs in other mouse tissues and is conserved in human. We also show, using ribosome footprint profiling, that actively translated upstream open reading frames (uORFs) are enriched in transcription factor mRNAs and predict mRNA repression by NMD, while poorly translated mRNAs escape repression. Together, our results identify novel NMD determinants and targets and provide context for understanding the impact of UPF1 and NMD on the mESC transcriptome.
Gastrointestinal Mucormycosis Mimicking Necrotizing Enterocolitis of Newborn

Like any other pediatric surgeon, Athena is often perplexed by the recalcitrant variety of necrotizing enterocolitis (NEC) in newborn. Despite appropriate therapy, they relentlessly progress to death. These cases are often shelved with a label “fulminant NEC”. [1] The mystery is slowly being unraveled by a recent series of articles on gastrointestinal mucormycosis of neonates (GIMN). GIMN masquerading as NEC is really an eye-opener.
The informational needs of patients with ANCA-associated vasculitis-development of an informational needs questionnaire.

OBJECTIVE The aim of the study was to compare the informational needs of patients with ANCA-associated vasculitis (AAV). METHODS We developed a Vasculitis Informational Needs Questionnaire that was distributed to members of Vasculitis UK (VUK) by mail and registrants of the Vasculitis Clinical Research Consortium (VCRC) online registry with self-reported AAV. Patients were asked to use a 5-point scale (1 = not important, 5 = extremely important) to rank aspects of information in the following domains: disease, investigations, medication, disease management and psychosocial care. The source and preferred method of educational delivery were recorded. RESULTS There were 314 VUK and 273 VCRC respondents. Respondents rated information on diagnosis, prognosis, investigations, treatment and side effects as extremely important. Information on patient support groups and psychosocial care was less important. There was no difference in the ratings of needs based on group, sex, age, disease duration, disease or method of questionnaire delivery. The most-preferred methods of providing information for both groups were by a doctor (with or without written material) or web based; educational courses and compact disc/digital video disc (CD/DVD) were the least-preferred methods. CONCLUSION This study demonstrates that people with AAV seek specific information concerning their disease, treatment regimes and side effects and the results of investigations. Individuals preferred to receive this information from a doctor. Patients with AAV should be treated in a similar manner to patients with other chronic illnesses in which patient education is a fundamental part of care.
Loop Mediated Isothermal Amplification (LAMP) Accurately Detects Malaria DNA from Filter Paper Blood Samples of Low Density Parasitaemias

Background Loop mediated isothermal amplification (LAMP) provides an opportunity for improved, field-friendly detection of malaria infections in endemic areas. However data on the diagnostic accuracy of LAMP for active case detection, particularly low-density parasitaemias, are lacking. We therefore evaluated the performance of a new LAMP kit compared with PCR using DNA from filter paper blood spots. Methods and Findings Samples from 865 fever patients and 465 asymptomatic individuals collected in Zanzibar were analysed for Pan (all species) and Pf (P. falciparum) DNA with the Loopamp MALARIA Pan/Pf kit. Samples were amplified at 65°C for 40 minutes in a real-time turbidimeter and results were compared with nested PCR. Samples with discordant results between LAMP and nested PCR were analysed with real-time PCR. The real-time PCR corrected nested PCR result was defined as gold standard. Among the 117 (13.5%) PCR detected P. falciparum infections from fever patients (mean parasite density 7491/µL, range 6–782,400) 115, 115 and 111 were positive by Pan-LAMP, Pf-LAMP and nested PCR, respectively. The sensitivities were 98.3% (95%CI 94–99.8) for both Pan and Pf-LAMP. Among the 54 (11.6%) PCR positive samples from asymptomatic individuals (mean parasite density 10/µL, range 0–4972) Pf-LAMP had a sensitivity of 92.7% (95%CI 80.1–98.5) for detection of the 41 P. falciparum infections. Pan-LAMP had sensitivities of 97% (95%CI 84.2–99.9) and 76.9% (95%CI 46.2–95) for detection of P. falciparum and P. malariae, respectively. The specificities for both Pan and Pf-LAMP were 100% (95%CI 99.1–100) in both study groups. Conclusion Both components of the Loopamp MALARIA Pan/Pf detection kit revealed high diagnostic accuracy for parasite detection among fever patients and importantly also among asymptomatic individuals of low parasite densities from minute blood volumes preserved on filter paper. These data support LAMPs potential role for improved detection of low-density malaria infections in pre-elimination settings.
Factors of Professional Learning Community Implementation and Effect on Student Achievement

ABSTRACT Professional learning communities (PLCs) promote collaboration among school personnel in an effort to stimulate student learning. Using data obtained from a larger statewide initiative in Missouri, the current study examined data from 181 schools (102 elementary schools, 32 middle schools, 41 high schools, and 6 other schools, average of 428.76 students) to determine (a) the factors that can be used to assess the effects of PLCs, (b) how well PLCs relate to student achievement, and (c) the extent to which teams differentially implement the factors. An exploratory factor analysis and confirmatory factor analyses resulted in two broader constructs that represented PLC attributes, collaborative leadership process and data-driven systems for learning, both of which correlated with student achievement and together provided unique variance in mathematics beyond school variables and achievement scores from before the PLC began. Directions for future research and implications for practice are discussed.
Leveling the Informational Playing Field

This study uses experimental data to compare the information generated by professional and nonprofessional investors when both groups receive access to the same financial disclosures. We also manipulate the disclosure level for both subject groups. Using the method developed by Barron, Kim, Lim and Stevens (1998), we then analyze the information contained in stock price forecasts that were made by the experimental subjects. Professionals on average inferred more information than nonprofessionals. The higher level of disclosure did not affect the information possessed by the professional investors. However, we find that a higher level of disclosure is associated with more private information being produced (or inferred) by nonprofessional investors. As a result, these subjects realized a significant improvement in the accuracy of their mean forecasts relative to their individual forecasts. This finding suggests that the enhanced capacity of firms to widely disclose information to all market participants via the Internet, together with the SEC's new “Fair Disclosure (FD)” regulation, has the potential to produce a significant increase in privately inferred information for on‐line nonprofessionals, potentially resulting in the aggregation of more diverse information into share prices.
Role and Functional Domain of Hepatitis B Virus X Protein in Regulating HBV Transcription and Replication in Vitro and in Vivo

The role of hepatitis B virus (HBV) X protein (HBx) in the regulation of HBV replication remains controversial. In the present study, the role of HBx in regulating HBV replication was initially investigated in both HepG2 and Huh7 in vitro cell lines with a transient transfection system. Next, the regions of HBx responsible for transcriptional transactivation and promotion of HBV replication were mapped in an HBV replication mouse model by in vivo transfection of a series of HBx expression plasmids. In an in vitro setting, HBx deficiency had little effect on HBV replication in Huh7 cells, but impaired HBV replication in HepG2 cells. In an in vivo setting, HBx had a strong enhancing effect on HBV transcription and replication. For the C-terminal two-thirds of the protein (amino acids [aa] 51 to 154) was required for this function of HBx, and the regions spanning aa 52 to 72 and 88 to 154 were found to be important for the stimulatory function of HBx on HBV replication. In conclusion, the role of HBx in HBV replication regulation is affected by host cell type, and HBx has an important role in stimulating HBV transcription and replication in hepatocytes in vivo. Further, the transcriptional transactivation function of HBx may be crucial for its stimulatory effect on HBV transcription and replication.
Dopaminergic Modulation of Mitral Cells and Odor Responses in the Zebrafish Olfactory Bulb

In the olfactory bulb, the modulatory neurotransmitter dopamine (DA) is coexpressed with GABA by local interneurons, but its role in odor processing remains obscure. We examined functions of DA mediated by D2-like receptors in the olfactory bulb of adult zebrafish by pharmacology, whole-cell recordings, calcium imaging, and optogenetics. Bath application of DA had no detectable effect on odorant-evoked sensory input. DA directly hyperpolarized mitral cells (MCs) via D2-like receptors and slightly increased their response gain. Consistent with this effect on input–output functions of MCs, small odorant responses were suppressed, whereas strong responses were enhanced in the presence of DA. These effects increased the root-mean-square contrast of population activity patterns but did not reduce their correlations. Optical stimulation of interneurons expressing channelrhodopsin-2 evoked fast GABAergic inhibitory currents in mitral cells but failed to activate D2 receptor-mediated currents when stimuli were short. Prolonged stimulus trains, however, activated a slow hyperpolarizing current that was blocked by an antagonist of D2-like receptors. GABA and DA are therefore both released from interneurons by electrical activity and hyperpolarize MCs, but D2-dependent dopaminergic effects occur on slower timescales. Additional effects of DA may be mediated by D1-like receptors. These results indicate that DA acts on D2-like receptors via asynchronous release and/or volume transmission and implicate DA in the slow adaptation of circuit function. The shift of the membrane potential away from spike threshold could adapt mitral cells to background input without compromising their sensitivity.
A Neural Mechanism Underlying Memory Failure in Older Adults

Older adults have reduced memory, primarily for recall, but also for recognition (Craik and McDowd, 1987), particularly for unfamiliar faces (Bartlett et al., 1989). Behavioral studies have shown that age-related memory declines are due in part to distraction from impaired inhibition of task-irrelevant input during encoding (Healey et al., 2008). Functional magnetic resonance imaging (fMRI) has been used to uncover the sources of memory deficits associated with aging. To date, this work has focused on successful encoding, while the neural correlates of unsuccessful encoding are unknown. Here, we provide novel evidence of a neural mechanism underlying memory failures exclusively affecting older adults. Whereas both younger and older adults showed reduced activation of brain regions important for encoding (e.g., hippocampus) during unsuccessful encoding, only older adults showed increased activity in brain regions mediating distraction (e.g., auditory cortex) and in left prefrontal cortex. Further, these regions were functionally connected with medial parietal areas, previously identified as default mode regions (Raichle and Snyder, 2007), which may reflect environmental monitoring. Our results suggest that increased distraction from task-irrelevant input (auditory in this case), associated with the unfamiliar and noisy fMRI environment, may increase environmental monitoring. This in turn could hinder suppression of default mode processing, resulting in memory failures in older adults. These findings provide novel evidence of a brain mechanism underlying the behavioral evidence that impaired inhibition of extraneous input during encoding leads to memory failure in older adults and may have implications for the ubiquitous use of fMRI for investigating neurocognitive aging.
Early Release of HMGB1 may Aggravate Neuronal Damage after Transient Focal Ischemia in Diabetic Rat Brain

Objective: High Mobility Group Box 1 (HMGB1) released extracellularly from necrotic cells evokes delayed inflammatory processes via interaction with the Receptor for Advanced Glycation End Products (RAGE) or Toll-like Receptors (TLR) in postischemic brain. The diabetic state (DM) aggravated cerebral ischemic injury following the stroke in rats. Therefore, we examined the behavior of HMGB1 and the expression of RAGE in non-DM and DM rat brain after middle cerebral artery occlusion followed by reperfusion (MCAO/Re). Methods: Diabetes was induced by a single injection of streptozotocin in male Sprague Dawley rats (DM group). MCAO/ Re was performed in non-DM and DM rats (ischemic groups) using a standard intraluminal procedure, and postischemic neurological deficits. Both brain infarction and edema were evaluated at various times after reperfusion. Control non-DM and DM rats underwent sham operation using the same manipulation, but without insertion of the occlusion filament. The behavior of HMGB1 and the expression of its receptors in the rat brain were examined using immunohistochemical and western blot analyses. Results: In sham-operated DM rat brain, immunoreactivity of HMGB1, which was localized in the neuronal nuclei of the cortex, was markedly increased compared with that in non-DM shamoperated rat brain. In the ischemic groups, the DM state aggravated MCAO/Re-induced neurological deficits and cerebral injury assessed by the infarction volume. Enhancement of translocation of HMGB1 from the nucleus to the cytoplasm induced by MCAO/ Re was markedly accelerated in the penumbral region of DM rat cortex. Immunoblot analysis revealed that the ischemia-induced increase in the release of HMGB1 into the cerebrospinal fluid and plasma was also enhanced in DM rats. Moreover, the expression of RAGE was upregulated in the brains of DM ischemic and control rats. Conclusions: The early release of HMGB1 and the expression of its receptors may be involved in the aggravation of neuronal damage caused by transient cerebral ischemia in DM rats. Therefore, it is important to inhibit the HMGB1 released in response to ischemia during the treatment of postischemic injury in diabetic patients.
Psychology and Child Protection: Promoting Widespread Improvement in Practice

The contribution of psychology to knowledge on child protection is substantial. This article reviews this contribution and suggests opportunities for psychology to contribute more, choosing 3 selected areas: (a) interviewing children to assess child maltreatment, (b) the well-being of children involved with the child protection system, and (c) evidence-based practices to ameliorate the effects of child maltreatment among children involved with the child protection system. Across these areas, psychology has contributed both to the knowledge base and to available assessment and intervention methods. However, in each area, the effect on usual child protection practice has been limited. Psychology has an opportunity to broaden its contribution through research and systems intervention aimed at extending gains in these areas throughout the child protection field.
SDN orchestration of OpenFlow and GMPLS flexi-grid networks with a stateful hierarchical PCE [invited]

New and emerging use cases, such as the interconnection of geographically remote data centers, are drawing attention to the need for provisioning end-to-end connectivity services spanning multiple and heterogeneous network domains. This heterogeneity is due not only to the data transmission and switching technology (the so-called data plane) but also to the deployed control plane, which may be used within each domain to automate the setup and recovery of such services, dynamically. The choice of a control plane is affected by factors such as availability, maturity, operator's preference, and the ability to satisfy a list of functional requirements. Given the current developments around OpenFlow and software-defined networking (SDN) along with the need to account for existing deployments based on GMPLS, the problem of heterogeneous control plane interworking needs to be solved. The retained solution must equally address the specific issues of multidomain networks, such as limited domain topology visibility, given the scalability and confidentiality constraints that characterize them. In this setting, we propose a functional and protocol architecture for such interworking, based on the key concepts of network abstraction and overarching control, implemented in terms of a hierarchical stateful path computation element (PCE), which provides the orchestration and coordination layer. In the proposed architecture, the PCEP and BGP-LS protocols are extended to support OpenFlow addresses and datapath identifiers, unifying both GMPLS and OpenFlow domains. The solution is deployed in an experimental testbed and validated. Although the main scope of the approach is the interworking of OpenFlow and GMPLS, the same approach can be directly applied to a wide range of multidomain scenarios, with either homogeneous or heterogeneous control technologies.
Vanishing point attracts gaze in free-viewing and visual search tasks

Several structural scene cues such as gist, layout, horizontal line, openness, and depth have been shown to guide scene perception (e.g., Oliva & Torralba, 2001); Ross & Oliva, 2009). Here, to investigate whether vanishing point (VP) plays a significant role in gaze guidance, we ran two experiments. In the first one, we recorded fixations of 10 observers (six male, four female; mean age 22; SD = 0.84) freely viewing 532 images, out of which 319 had a VP (shuffled presentation; each image for 4 s). We found that the average number of fixations at a local region (80 × 80 pixels) centered at the VP is significantly higher than the average fixations at random locations (t test; n = 319; p < 0.001). To address the confounding factor of saliency, we learned a combined model of bottom-up saliency and VP. The AUC (area under curve) score of our model (0.85; SD = 0.01) is significantly higher than the base saliency model (e.g., 0.8 using attention for information maximization (AIM) model by Bruce & Tsotsos, 2005, t test; p = 3.14e-16) and the VP-only model (0.64, t test; p < 0.001). In the second experiment, we asked 14 subjects (10 male, four female; mean age 23.07, SD = 1.26) to search for a target character (T or L) placed randomly on a 3 × 3 imaginary grid overlaid on top of an image. Subjects reported their answers by pressing one of the two keys. Stimuli consisted of 270 color images (180 with a single VP, 90 without). The target happened with equal probability inside each cell (15 times L, 15 times T). We found that subjects were significantly faster (and more accurate) when the target appeared inside the cell containing the VP compared to cells without the VP (median across 14 subjects 1.34 s vs. 1.96 s; Wilcoxon rank-sum test; p = 0.0014). These findings support the hypothesis that vanishing point, similar to face, text (Cerf, Frady, & Koch, 2009), and gaze direction Borji, Parks, & Itti, 2014) guides attention in free-viewing and visual search tasks.
BINNING IN GAUSSIAN KERNEL REGULARIZATION

Gaussian kernel regularization is widely used in the machine learning literature and has proved successful in many empirical experiments. The periodic version of Gaussian kernel regularization has been shown to be minimax rate optimal in estimating functions in any finite order Sobolev space. However, for a data set with n points, the computation complexity of the Gaussian kernel regularization method is of order O(n). In this paper we propose to use binning to reduce the computation of Gaussian kernel regularization in both regression and classification. For periodic Gaussian kernel regression, we show that the binned estimator achieves the same minimax rates as the unbinned estimator, but the computation is reduced to O(m) with m as the number of bins. To achieve the minimax rate in the kth order Sobolev space, m needs to be in the order of O(kn), which makes the binned estimator computation of order O(n) for k = 1, and even less for larger k. Our simulations show that the binned estimator (binning 120 data points into 20 bins in our simulation) provides almost the same accuracy with only 0.4% of computation time. For classification, binning with L2-loss Gaussian kernel regularization and Gaussian kernel Support Vector Machines is tested in a polar cloud detection problem.
General Strain Theory and Racial Insurgency: Assessing the Role of Legitimate Coping

While General Strain Theory (GST) recognizes the broad range of legitimate and illegitimate coping behaviors people adopt in reaction to strain, tests of the theory focus almost exclusively on criminal coping. We advance the theory by articulating the role of legitimate coping in the GST process. We test the theory’s assumptions that strain increases both legitimate and illegitimate coping and that negative emotions more strongly increase illegitimate coping. We also draw on recent work by Agnew and expect that these coping strategies co-occur rather than being mutually exclusive. We investigate these hypotheses in relation to black insurgency, specifically nonviolent civil-rights protest (legitimate coping) and rioting (illegitimate coping). Using data from a large 1968 survey of blacks, multivariate findings are consistent with the theory’s expectations regarding the role of legitimate coping. More broadly, our results echo calls to extend the boundaries of the discipline beyond traditional conceptualizations of “crime. ”
Exploring Everyday Energy Usage Practices in Australian Households: A Qualitative Analysis

In recent years, energy conservation research has identified a number of household actions that have the potential to drive significant reductions in carbon emissions in the near-term, without requiring substantial changes to householders’ lifestyles or imposing significant financial costs. In this qualitative study, we investigate the potential of some of these actions for behavioral modification by asking householders to reveal the reasons why they perform (or fail to perform) such actions. As part of a telephone survey, a sample of customers (n = 1541) from an Australian energy retailer were asked about their reasons for engaging in specific energy usage practices in one of five household domains: laundry, kitchen, bathroom, space heating/cooling or general appliance usage. Qualitative analyses of participants’ open-ended responses revealed that practices in the laundry and kitchen appear to hold the greatest promise for behavioral change, whereas practices in the shower may be more challenging to modify. Integrating our findings with current psychological and sociological knowledge, we present a range of possibilities for future behavior change interventions at the practice-level.