Miracle-dz/UniFAR-FTUs huggingface dataset:
Circulating Methylated XAF1 DNA Indicates Poor Prognosis for Gastric Cancer

Background Methylated DNA in fluids may be a suitable biomarker for cancer patients. XAF1 has been shown to be frequently down-regulated in human gastric cancer (GC). Here, we investigated if XAF1 methylation in GC could be a useful biomarker. Methods Real-time RT-PCR was used to detect XAF1 mRNA expression; immunohistochemistry and western blot were used to examine XAF1 protein expression in GC tissues (n = 202) and their corresponding para-cancerous histological normal tissues (PCHNTs). Real-time methylation specific-PCR was used to investigate XAF1 promoter methylation in the same panel of GC tissues, their PCHNTs and sera. Results We confirmed frequent XAF1 down-regulation in both mRNA and protein levels in GC tissues as compared to normal controls and PCHNTs. XAF1 hypermethylation was evidenced in 83.2% (168/202) of GC tissues and 27.2% (55/202) of PCHNTs, while no methylation was detected in the 88 normal controls. The methylation level in GC tissues was significantly higher than that in PCHNTs (p<0.05). The hypermethylation of XAF1 significantly correlated with the down-regulation of XAF1 in GC tissues in both mRNA and protein levels (p<0.001 each). Moreover, we detected high frequency of XAF1 methylation (69.8%, 141 out of 202) in the sera DNAs from the same patients, while the sera DNAs from 88 non-tumor controls were negative for XAF1 methylation. The XAF1 methylation in both GC tissues and in the sera could be a good biomarker for diagnosis of GC (AUC = 0.85 for tissue and AUC = 0.91 for sera) and significantly correlated with poorer prognosis (p<0.001). In addition, after-surgery negative-to-positive transition of XAF1 methylation in sera strongly associated with tumor recurrence. Conclusions 1) Dysfunction of XAF1 is frequent and is regulated through XAF1 promoter hypermethylation; 2) Detection of circulating methylated XAF1 DNAs in the serum may be a useful biomarker in diagnosis, evaluating patient’s outcome (prognosis and recurrence) for GC patients.
Scaling Up What Works: Experimental Evidence on External Validity in Kenyan Education

The recent wave of randomized trials in development economics has provoked criticisms regarding external validity. We investigate two concerns – heterogeneity across beneficiaries and implementers – in a randomized trial of contract teachers in Kenyan schools. The intervention, previously shown to raise test scores in NGO-led trials in Western Kenya and parts of India, was replicated across all Kenyan provinces by an NGO and the government. Strong effects of short-term contracts produced in controlled experimental settings are lost in weak public institutions: NGO implementation produces a positive effect on test scores across diverse contexts, while government implementation yields zero effect. The data suggests that the stark contrast in success between the government and NGO arm can be traced back to implementation constraints and political economy forces put in motion as the program went to scale.
High stakes testing and teacher access to professional opportunities: lessons from Indonesia

Abstract High-stakes testing regimes, in which schools are judged on their capacity to attain high student results in national tests, are becoming common in both developed and developing nations, including the United States, Britain and Australia. However, while there has been substantial investigation around the impact of high-stakes testing on curriculum and pedagogy, there has been very little research looking at the impact on teachers’ professional opportunities. The current project used a case study approach to examine the impact a high-stakes national testing programme had on teachers’ access to professional learning and their teaching allocations in four Indonesian public schools. It found that better qualified teachers were allocated to classes that would be sitting for the national examinations, and that these teachers were given much more access to professional learning opportunities than those teaching non-examined year levels. This in turn impacted negatively on the staff morale of less qualified teaching staff and potentially on their career trajectories. Findings suggest that school leaders should be wary of targeting better qualified and/or more experienced staff to year levels sitting for high-stakes tests, as this may lead to staff stratification within schools, limiting opportunities for staff to learn from one another and reducing the morale of less qualified and less experienced staff. They also add support to a substantial body of research that suggests policy-makers should be wary of the flow-on effects of using performance in high-stakes tests as the key means of judging school effectiveness.
Endowments at Birth and Parents' Investments in Children

Do parents invest more in higher quality children, or do they compensate for lower quality by giving more to children with lower endowments? We answer this question in the context of a large-scale iodine supplementation programme in Tanzania. We find that children with higher programme exposure were more likely to receive necessary vaccines and were breastfed for longer. Siblings of treated children were also more likely to be immunised. Fertility behavior and investments at the time of birth were unaffected.
Gain-of-function glutamate receptor interacting protein 1 variants alter GluA2 recycling and surface distribution in patients with autism

Glutamate receptor interacting protein 1 (GRIP1) is a neuronal scaffolding protein that interacts directly with the C termini of glutamate receptors 2/3 (GluA2/3) via its PDZ domains 4 to 6 (PDZ4–6). We found an association (P < 0.05) of a SNP within the PDZ4-6 genomic region with autism by genotyping autistic patients (n = 480) and matched controls (n = 480). Parallel sequencing identified five rare missense variants within or near PDZ4–6 only in the autism cohort, resulting in a higher cumulative mutation load (P = 0.032). Two variants correlated with a more severe deficit in reciprocal social interaction in affected sibling pairs from proband families. These variants were associated with altered interactions with GluA2/3 and faster recycling and increased surface distribution of GluA2 in neurons, suggesting gain-of-function because GRIP1/2 deficiency showed opposite phenotypes. Grip1/2 knockout mice exhibited increased sociability and impaired prepulse inhibition. These results support a role for GRIP in social behavior and implicate GRIP1 variants in modulating autistic phenotype.
Emotional Power of Music in Patients with Memory Disorders Clinical Implications of Cognitive Neuroscience

By adapting methods of cognitive psychology to neuropsychology, we examined memory and familiarity abilities in music in relation to emotion. First we present data illustrating how the emotional content of stimuli influences memory for music. Second, we discuss recent findings obtained in patients with two different brain disorders (medically intractable epilepsy and Alzheimer’s disease) that show relatively spared memory performance for music, despite severe verbal memory disorders. Studies on musical memory and its relation to emotion open up paths for new strategies in cognitive rehabilitation and reinstate the importance of examining interactions between cognitive and clinical neurosciences. Numerous behavioral data suggest that music can be well remembered even years after it was first heard (for a discussion about the specificity of memory for music, see the paper by Schulkind 35 in this volume). Moreover, neuropsychological data show that, under certain circumstances, musical memory can be relatively spared even in patients with severe cognitive impairment. Several explanations can be proposed to account for this finding: The preservation of music abilities may result, at leastinpart,fromthefactthatthecerebralsubstrate for music memory is largely distributed and thus is less likely to be impaired by brain damage. It seems also plausible that the strong emotional power of music enhances the encod
The Insanity Defense, Public Anger, and the Potential Impact on Attributions of Responsibility and Punishment

Research indicates that the general public perceives the insanity defense negatively and inaccurately despite the infrequency with which it is pled and the realities often surrounding those who plead the defense. The negative and inaccurate perception of the insanity defense, combined with the potentially increased punitive judgments the defense elicits, suggests that emotion may play a role in perception of the insanity defense. In particular, the psychological literature on anger may contain answers to reactions toward the insanity defense. The current research explored the role of anger on punitive judgments toward a defendant pleading not guilty by reason of insanity (NGRI). Punitive judgment was assessed by measuring participants' perceptions of controllability (the extent to which the defendant's actions were perceived as preventable and controllable), punishment worthiness (the degree to which the defendant's actions were seen as intentional and perceptions of blameworthiness, punishment-worthiness, recklessness, and future recklessness), plea fairness, verdict fairness, verdict, and verdict certainty. In both studies, mock jurors read case vignettes in which a defendant pled NGRI. In Study One, potential jurors considered a plea and verdict of NGRI to be less fair than a plea and verdict of self-defense. In Study Two, participants in the medication non-compliance group felt more anger, after reading the vignettes, than participants in the prior history group. Additionally, anger was able to predict verdict to a statistically significant degree. Overall, the current research suggests that anger does play a role in negative perceptions of the insanity defense. Thus, it is important to further explore the role of emotions in insanity defense bias and effective bias reduction tools and strategies. v DEDICATION This dissertation is dedicated to those whom I rely on for support. Thank you for always believing in me.
Second-Best Institutions

The focus of policy reform in developing countries has moved from getting prices right to getting institutions right, and accordingly countries are increasingly being advised to move towards "best-practice" institutions. This paper argues that appropriate institutions for developing countries are instead "second-best" institutions -- those that take into account context-specific market and government failures that cannot be removed in short order. Such institutions will often diverge greatly from best practice. The argument is illustrated using examples from four areas: contract enforcement, entrepreneurship, trade openness, and macroeconomic stability.
Neurobiological Correlates of EMDR Monitoring – An EEG Study

Background Eye Movement Desensitization and Reprocessing (EMDR) is a recognized first-line treatment for psychological trauma. However its neurobiological bases have yet to be fully disclosed. Methods Electroencephalography (EEG) was used to fully monitor neuronal activation throughout EMDR sessions including the autobiographical script. Ten patients with major psychological trauma were investigated during their first EMDR session (T0) and during the last one performed after processing the index trauma (T1). Neuropsychological tests were administered at the same time. Comparisons were performed between EEGs of patients at T0 and T1 and between EEGs of patients and 10 controls who underwent the same EMDR procedure at T0. Connectivity analyses were carried out by lagged phase synchronization. Results During bilateral ocular stimulation (BS) of EMDR sessions EEG showed a significantly higher activity on the orbito-frontal, prefrontal and anterior cingulate cortex in patients at T0 shifting towards left temporo-occipital regions at T1. A similar trend was found for autobiographical script with a higher firing in fronto-temporal limbic regions at T0 moving to right temporo-occipital cortex at T1. The comparisons between patients and controls confirmed the maximal activation in the limbic cortex of patients occurring before trauma processing. Connectivity analysis showed decreased pair-wise interactions between prefrontal and cingulate cortex during BS in patients as compared to controls and between fusiform gyrus and visual cortex during script listening in patients at T1 as compared to T0. These changes correlated significantly with those occurring in neuropsychological tests. Conclusions The ground-breaking methodology enabled our study to image for the first time the specific activations associated with the therapeutic actions typical of EMDR protocol. The findings suggest that traumatic events are processed at cognitive level following successful EMDR therapy, thus supporting the evidence of distinct neurobiological patterns of brain activations during BS associated with a significant relief from negative emotional experiences.
Study on the complexity of reservoir parameters inversionin partially saturated porous media

The main purpose of this paper is to further clarify the complexity of the inversion method by using Niche Genetic Algorithms (NGA) to inverse the petrophysical property parameters. The improved BISQ model, presented in our earlier work, is chosen for the forward model in NGA. In this paper, the relationship between the sample number of the given wave response data and the inversion results, such as the precision and stability, is detailedly discussed by means of numerical experiments. It is found that, with respect to the data examined, the precision of inversion results is mostly satisfied when the sample number of given data is chosen as N=5. The simulation results also show that the inversion results of the porosity are most stable, which relative error is less than 1.17% at all cases.
Independent Mechanisms Target SMCHD1 to Trimethylated Histone H3 Lysine 9-Modified Chromatin and the Inactive X Chromosome

ABSTRACT The chromosomal protein SMCHD1 plays an important role in epigenetic silencing at diverse loci, including the inactive X chromosome, imprinted genes, and the facioscapulohumeral muscular dystrophy locus. Although homology with canonical SMC family proteins suggests a role in chromosome organization, the mechanisms underlying SMCHD1 function and target site selection remain poorly understood. Here we show that SMCHD1 forms an active GHKL-ATPase homodimer, contrasting with canonical SMC complexes, which exist as tripartite ring structures. Electron microscopy analysis demonstrates that SMCHD1 homodimers structurally resemble prokaryotic condensins. We further show that the principal mechanism for chromatin loading of SMCHD1 involves an LRIF1-mediated interaction with HP1γ at trimethylated histone H3 lysine 9 (H3K9me3)-modified chromatin sites on the chromosome arms. A parallel pathway accounts for chromatin loading at a minority of sites, notably the inactive X chromosome. Together, our results provide key insights into SMCHD1 function and target site selection.
Single pulse excimer laser nanostructuring of thin silicon films: Nanosharp cones formation and a heat transfer problem

We present analytical and computer modeling along with an experiment on the formation of sharp conical tips on monocrystalline silicon thin films, silicon-on-insulator, subjected to irradiation by single 25 ns pulses from a KrF excimer laser focused into a spot several micrometers in diameter. These fabricated structures have heights of about 1 μm and apical radii of curvature of several tens of nanometers. We offer a simplified analytical model for the formation of these structures. The computer simulation includes two-dimensional time-dependant heat transfer and phase transformations in Si films on SiO2 substrates that result from the laser irradiation (the Stefan problem). It is shown that upon irradiation and initial melting, the liquid/solid interface remains mainly parallel to the surface of the film. After the laser pulse, the molten material self-cools and resolidifies. The solid/liquid interface moves predominately laterally toward the center of the irradiated spot, forming an almost vertical fro.
The Biogeography of Putative Microbial Antibiotic Production

Understanding patterns in the distribution and abundance of functional traits across a landscape is of fundamental importance to ecology. Mapping these distributions is particularly challenging for species-rich groups with sparse trait measurement coverage, such as flowering plants, insects, and microorganisms. Here, we use likelihood-based character reconstruction to infer and analyze the spatial distribution of unmeasured traits. We apply this framework to a microbial dataset comprised of 11,732 ketosynthase alpha gene sequences extracted from 144 soil samples from three continents to document the spatial distribution of putative microbial polyketide antibiotic production. Antibiotic production is a key competitive strategy for soil microbial survival and performance. Additionally, novel antibiotic discovery is highly relevant to human health, making natural antibiotic production by soil microorganisms a major target for bioprospecting. Our comparison of trait-based biogeographical patterns to patterns based on taxonomy and phylogeny is relevant to our basic understanding of microbial biogeography as well as the pressing need for new antibiotics.
Progress and promise in understanding the genetic basis of common diseases

Susceptibility to common human diseases is influenced by both genetic and environmental factors. The explosive growth of genetic data, and the knowledge that it is generating, are transforming our biological understanding of these diseases. In this review, we describe the technological and analytical advances that have enabled genome-wide association studies to be successful in identifying a large number of genetic variants robustly associated with common disease. We examine the biological insights that these genetic associations are beginning to produce, from functional mechanisms involving individual genes to biological pathways linking associated genes, and the identification of functional annotations, some of which are cell-type-specific, enriched in disease associations. Although most efforts have focused on identifying and interpreting genetic variants that are irrefutably associated with disease, it is increasingly clear that—even at large sample sizes—these represent only the tip of the iceberg of genetic signal, motivating polygenic analyses that consider the effects of genetic variants throughout the genome, including modest effects that are not individually statistically significant. As data from an increasingly large number of diseases and traits are analysed, pleiotropic effects (defined as genetic loci affecting multiple phenotypes) can help integrate our biological understanding. Looking forward, the next generation of population-scale data resources, linking genomic information with health outcomes, will lead to another step-change in our ability to understand, and treat, common diseases.
Semi-Nonparametric Modeling and Estimation of First-Price Auction Models with Auction-Specific Heterogeneity

In this paper we extend and generalize the semi-nonparametric modeling and sieve estimation approach of Bierens and Song (2011a) for independently and identically distributed first-price auctions to firstprice auction models with observed auction-specific heterogeneity. The latter will be incorporated via a linear model for the log values with unknown error distribution. This distribution will be modeled seminonparametrically similar to the approach in Bierens (2011). It will be shown that the semi-nonparametric conditional value distribution involved can be estimated consistently by minimizing the integrated square distance between the empirical characteristic function of the actual bids and the simulated bids, together with the auction-specific covariates, via an integrated conditional moment criterion.
The Role of Thalamic Population Synchrony in the Emergence of Cortical Feature Selectivity

In a wide range of studies, the emergence of orientation selectivity in primary visual cortex has been attributed to a complex interaction between feed-forward thalamic input and inhibitory mechanisms at the level of cortex. Although it is well known that layer 4 cortical neurons are highly sensitive to the timing of thalamic inputs, the role of the stimulus-driven timing of thalamic inputs in cortical orientation selectivity is not well understood. Here we show that the synchronization of thalamic firing contributes directly to the orientation tuned responses of primary visual cortex in a way that optimizes the stimulus information per cortical spike. From the recorded responses of geniculate X-cells in the anesthetized cat, we synthesized thalamic sub-populations that would likely serve as the synaptic input to a common layer 4 cortical neuron based on anatomical constraints. We used this synchronized input as the driving input to an integrate-and-fire model of cortical responses and demonstrated that the tuning properties match closely to those measured in primary visual cortex. By modulating the overall level of synchronization at the preferred orientation, we show that efficiency of information transmission in the cortex is maximized for levels of synchronization which match those reported in thalamic recordings in response to naturalistic stimuli, a property which is relatively invariant to the orientation tuning width. These findings indicate evidence for a more prominent role of the feed-forward thalamic input in cortical feature selectivity based on thalamic synchronization.
Interventional Audiology to Address Hearing Health Care Disparities: Oyendo Bien Pilot Study

Abstract Interventional audiology, specifically community-based outreach, can connect people with the hearing health care system. Community-based participatory research methods were applied in two phases of research to: (1) investigate the needs of families affected by hearing loss in a rural Arizona community on the U.S.–Mexico border; and (2) evaluate an outreach program on hearing health. The needs assessment included interviews with persons with hearing loss and focus groups with family members and the greater community. The needs assessment revealed that despite perceived severity of hearing loss, help-seeking for audiologic care was limited due to barriers, stigma, and low self-efficacy. Results informed development of a community-based pilot study conducted as part of an academic-community partnership between audiology, public health, and community health workers of a federally qualified health center. An outreach program, Oyendo Bien (hearing wellness), a 5-week, Spanish-language health education program for older adults (n = 21) incorporated communication strategies and behavioral change techniques. Postprogram focus groups revealed increased self-efficacy and decreased stigma. After 1 year, 7 of 9 participants with hearing loss contacted for follow-up had sought some form of hearing-related health care. Future research should further investigate interventional audiology approaches to address health disparities.