Miracle-dz/UniFAR-FTUs huggingface dataset:
A Study of Reverse Causation: Examining the Associations of Perfluorooctanoic Acid Serum Levels with Two Outcomes

Background: Impaired kidney function and earlier menopause were associated with perfluorooctanoic acid (PFOA) serum levels in previous cross-sectional studies. Reverse causation, whereby health outcomes increase serum PFOA, may underlie these associations. Objective: We compared measured (subject to reverse causation) versus modeled (unaffected by reverse causation) serum PFOA in association with these outcomes to examine the possible role of reverse causation in these associations. Methods: In cross-sectional analyses, we analyzed PFOA in relation to self-reported menopause among women (n = 9,192) 30–65 years old and in relation to kidney function among adults > 20 years old (n = 29,499) in a highly exposed Mid-Ohio Valley cohort. Estimated glomerular filtration rate (eGFR, a marker of kidney function) and serum PFOA concentration were measured in blood samples collected during 2005–2006. Retrospective year-specific serum PFOA estimates were modeled independently of measured PFOA based on residential history and plant emissions. Using measured and modeled PFOA in 2005 or 2006 (predictor variables), cross-sectional associations were assessed for eGFR and menopause (yes/no). We also analyzed measured PFOA (dependent variable) in relation to the number of years since menopause. Results: Menopause and eGFR were significantly associated with measured (trend tests: p = 0.013, p = 0.0005, respectively) but not with modeled serum PFOA (p = 0.50, p = 0.76, respectively). Measured PFOA levels increased for the first 7 years after menopause (trend test, p < 0.0001), providing further evidence that the observed association between measured PFOA and menopause is subject to reverse causation for this outcome. Conclusion: Our results support the conjecture that in previous studies, earlier menopause and reduced kidney function are the causes rather than the results of increased measured serum PFOA. These results suggest caution in using biomarkers in cross-sectional studies. Citation: Dhingra R, Winquist A, Darrow LA, Klein M, Steenland K. 2017. A study of reverse causation: examining the associations of perfluorooctanoic acid serum levels with two outcomes. Environ Health Perspect 125:416–421; http://dx.doi. org/10.1289/EHP273
Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells

In Hodgkin's disease (HD), the Hodgkin and Reed-Sternberg (HRS) cells represent only a minute population in the diseased tissue. The investigation of lineage derivation and clonal origin of these cells has yielded conflicting results. We have analyzed HRS cells micromanipulated from infiltrated tissue sections of 10 primary HD patients for rearranged V genes, extending a previous study. Clonally related rearrangements were found in nine cases, indicating that HRS cells represent a dominant clone of B lineage-derived cells in at least a large fraction of cases of HD. Rearranged VH genes from HRS cells carried a high load of somatic mutation, indicating that HRS cells are derived from germinal center (GC) cells or their progeny. Stop codons in some in-frame V gene rearrangements suggest that the HRS cell precursors reside inside GCs, have acquired crippling mutations that prevent antigenic selection, but escape apoptosis through some transforming event.
Specificity of Salt Marsh Diazotrophs for Vegetation Zones and Plant Hosts: Results from a North American marsh

Salt marshes located on the east coast of temperate North America are highly productive, typically nitrogen-limited, and support diverse assemblages of free-living nitrogen fixing (diazotrophic) bacteria. This article reviews and analyzes data from North Inlet estuary (SC, USA), addressing diazotroph assemblage structure and the influence of plant host and environmental conditions on the assemblage. The North Inlet estuary is a salt marsh ecosystem in which anthropogenic influences are minimal and the distributions of diazotrophs are governed by the natural biota and dynamics of the system. Denaturing gradient gel electrophoresis fingerprinting and phylogenetic analyses of recovered sequences demonstrated that the distributions of some diazotrophs reflect plant host specificity and that diazotroph assemblages distributed across marsh gradients are also heavily influenced by edaphic conditions. Broadly distributed diazotrophs that are capable of maintaining populations under all environmental conditions spanning such gradients are also present in these assemblages. Statistical analyses indicate that the structures of diazotroph assemblages in different vegetation zones are significantly (p < 0.01) different. New data presented here demonstrate the heterogeneity of salt marsh rhizosphere microenvironments, and corroborate previous findings from different plant hosts growing at several locations within this estuary. The data from these collected works support the hypothesis that the biogeography of microorganisms is non-random and these biogeographic patterns are predictable.
Enhancement of gene targeting in human cells by intranuclear permeation of the Saccharomyces cerevisiae Rad52 protein

The introduction of exogenous DNA in human somatic cells results in a frequency of random integration at least 100-fold higher than gene targeting (GT), posing a seemingly insurmountable limitation for gene therapy applications. We previously reported that, in human cells, the stable over-expression of the Saccharomyces cerevisiae Rad52 gene (yRAD52), which plays the major role in yeast homologous recombination (HR), caused an up to 37-fold increase in the frequency of GT, indicating that yRAD52 interacts with the double-strand break repair pathway(s) of human cells favoring homologous integration. In the present study, we tested the effect of the yRad52 protein by delivering it directly to the human cells. To this purpose, we fused the yRAD52 cDNA to the arginine-rich domain of the TAT protein of HIV (tat11) that is known to permeate the cell membranes. We observed that a recombinant yRad52tat11 fusion protein produced in Escherichia coli, which maintains its ability to bind single-stranded DNA (ssDNA), enters the cells and the nuclei, where it is able to increase both intrachromosomal recombination and GT up to 63- and 50-fold, respectively. Moreover, the non-homologous plasmid DNA integration decreased by 4-fold. yRAD52tat11 proteins carrying point mutations in the ssDNA binding domain caused a lower or nil increase in recombination proficiency. Thus, the yRad52tat11 could be instrumental to increase GT in human cells and a ‘protein delivery approach’ offers a new tool for developing novel strategies for genome modification and gene therapy applications.
Feature Engineering for Activity Recognition from Wrist-worn Motion Sensors

With their integrated sensors, wrist-worn devices, such as smart watches, provide an ideal platform for human activity recognition. Particularly, the inertial sensors, such as accelerometer and gyroscope can efficiently capture the wrist and arm movements of the users. In this paper, we investigate the use of accelerometer sensor for recognizing thirteen different activities. Particularly, we analyse how different sets of features extracted from acceleration readings perform in activity recognition. We categorize the set of features into three classes: motion related features, orientation-related features and rotation-related features and we analyse the recognition performance using motion, orientation and rotation information both alone and in combination. We utilize a dataset collected from 10 participants and use different classification algorithms in the analysis. The results show that using orientation features achieve the highest accuracies when used alone and in combination with other sensors. Moreover, using only raw acceleration performs slightly better than using linear acceleration and similar compared with gyroscope.
Proline Modulates the Trypanosoma cruzi Resistance to Reactive Oxygen Species and Drugs through a Novel D, L-Proline Transporter

Trypanosoma cruzi, the etiological agent of Chagas' disease, has a metabolism largely based on the consumption of glucose and proline. This amino acid is essential for host cells infection and intracellular differentiation. In this work we identified a proline transporter (TcAAAP069) by yeasts complementation assays and overexpression in Trypanosoma cruzi epimastigotes. TcAAAP069 is mono-specific for proline but presents an unusual feature; the lack of stereospecificity, because it is competitively inhibited by the D- enantiomer. Parasites overexpressing TcAAAP069 have an increased intracellular proline concentration, 2.6-fold higher than controls, as a consequence of a higher proline transport rate. Furthermore, augmented proline concentration correlates with an improved resistance to trypanocidal drugs and also to reactive oxygen species including hydrogen peroxide and nitric oxide, emulating natural physiological situations. The IC50s for nifurtimox, benznidazole, H2O2 and NO. were 125%, 68%, 44% and 112% higher than controls, respectively. Finally, proline metabolism generates a higher concentration (48%) of ATP in TcAAAP069 parasites. Since proline participates on essential energy pathways, stress and drug resistance responses, these results provide a novel target for the development of new drugs for the treatments for Chagas' disease.
Goldilocks: a race and transaction-aware java runtime

Data races often result in unexpected and erroneous behavior. In addition to causing data corruption and leading programs to crash, the presence of data races complicates the semantics of an execution which might no longer be sequentially consistent. Motivated by these observations, we have designed and implemented a Java runtime system that monitors program executions and throws a DataRaceException when a data race is about to occur. Analogous to other runtime exceptions, the DataRaceException provides two key benefits. First, accesses causing race conditions are interruptedand handled before they cause errors that may be difficult to diagnose later. Second, if no DataRaceException is thrown in an execution, it is guaranteed to be sequentially consistent. This strong guarantee helps to rule out many concurrency-related possibilities as the cause of erroneous behavior. When a DataRaceException is caught, the operation, thread, or program causing it can be terminated gracefully. Alternatively, the DataRaceException can serve as a conflict-detection mechanism inoptimistic uses of concurrency. We start with the definition of data-race-free executions in the Java memory model. We generalize this definition to executions that use transactions in addition to locks and volatile variables for synchronization. We present a precise and efficient algorithm for dynamically verifying that an execution is free of data races. This algorithm generalizes the Goldilocks algorithm for data-race detectionby handling transactions and providing the ability to distinguish between read and write accesses. We have implemented our algorithm and the DataRaceException in the Kaffe Java Virtual Machine. We have evaluated our system on a variety of publicly available Java benchmarks and a few microbenchmarks that combine lock-based and transaction-based synchronization. Our experiments indicate that our implementation has reasonable overhead. Therefore, we believe that inaddition to being a debugging tool, the DataRaceException may be a viable mechanism to enforce the safety of executions of multithreaded Java programs.
Pulsed laser ablation (PLA) of ultra-hard structures : generation of damage-tolerant freeform surfaces for advanced machining applications

This thesis covers the laser generation of novel micro-cutting arrays in ultra-hard super-abrasive composites (e.g. polycrystalline diamond, PCD and polycrystalline cubic boron nitride, PCBN). Pulsed laser ablation (PLA) has been used to manufacture repeatable patterns of micro cutting/abrasive edges onto micro structurally different PCD/PCBN composites. The analysis on the influence of microstructural factors of the composite materials in the use of laser ablation technology has been carried out via a novel technique (Focused Ion Beam/High Resolution Transmission Electron Microscopy/Electron Energy Loss Spectroscopy) to identify the allotropic changes occurring in the composite as a consequence of PLA allowing the laser ablated PCD/PCBN surfaces to be characterized and the nanometric changes evaluated. The wear/failure characteristics/progression of the ultra-hard laser generated micro cutting/abrasive arrays has been studied in wear tests of Silicon Dioxide workpiece shafts and the influence of the microstructural factors in the wear properties of the super-abrasive micro cutting edges has been found. Opposing to these highly-engineered micro cutting/abrasive arrays, conventional electroplated abrasive pads containing diamond and CBN abrasives respectively have been chosen as benchmarks and tested under the same conditions. Contact profiling, Optical Microscopy and Environmental Scanning Electron Microscopy have been employed for the characterization of the abrasive arrays/electroplated tools before/during/after the wear/cutting tests. In the PCD abrasive micro-arrays, the type of grain and binder percentage proved to affect the wear performances due to the different extents of compressive stresses occurring at the grain boundaries. Mixed grained PCD arrays performed 25% better than fine grained arrays. All of the PCD laser manufactured arrays showed an increase up to 60% in the tool life when compared to the benchmarked pads. As for the PCBN abrasive micro-arrays, the laser manufactured arrays proved to perform 50% better than the electroplated ones in terms of wear resistance. This eThesis was first deposited on 6 November 2014.
Developmental regulation of skull morphology II: ontogenetic dynamics of covariance

SUMMARY Canalization may play a critical role in molding patterns of integration when variability is regulated by the balance between processes that generate and remove variation. Under these conditions, the interaction among those processes may produce a dynamic structure of integration even when the level of variability is constant. To determine whether the constancy of variance in skull shape throughout most of postnatal growth results from a balance between processes generating and removing variation, we compare covariance structures from age to age in two rodent species, cotton rats (Sigmodon fulviventer) and house mice (Mus musculus domesticus). We assess the overall similarity of covariance matrices by the matrix correlation, and compare the structures of covariance matrices using common subspace analysis, a method related to common principal components (PCs) analysis but suited to cases in which variation is so nearly spherical that PCs are ambiguous. We find significant differences from age to age in covariance structure and the more effectively canalized ones tend to be least stable in covariance structure. We find no evidence that canalization gradually and preferentially removes deviations arising early in development as we might expect if canalization results from compensatory differential growth. Our results suggest that (co)variation patterns are continually restructured by processes that equilibrate variance, and thus that canalization plays a critical role in molding patterns of integration.
Sociodemographics, referral patterns, and Internet use for decision-making in microsurgical breast reconstruction.

BACKGROUND Increasing numbers of patients are choosing to undergo microsurgical breast reconstruction. Currently, no information is available about the sociodemographic profile, referral patterns, or decision-making process of women who choose this reconstructive modality. METHODS All women who underwent breast reconstruction at a single institution between 2004 and 2007 were surveyed regarding demographic information, referral patterns, and decision-making processes. For data analysis, the cohort was separated by reconstructive method: nonmicrosurgical reconstruction (i.e., implant, latissimus, and pedicled transverse rectus abdominis musculocutaneous flaps) or microsurgical reconstruction (i.e., free transverse rectus abdominis musculocutaneous, deep inferior epigastric artery perforator, superficial inferior epigastric artery, and superior gluteal artery perforator flaps). RESULTS Overall, 332 women were surveyed, with a response rate of 77 percent. Patients who underwent microsurgical reconstruction were more likely to be 40 to 49 years old (p = 0.014), whereas nonmicrosurgical patients were clustered at the extremes of age. Microsurgery patients self-referred to a reconstructive surgeon, whereas other patients were sent by surgical oncologists (p < 0.001). The Internet was an important decision-making aid to help microsurgery patients identify their reconstructive modality (p < 0.001). Compared with nonmicrosurgical counterparts, microsurgery patients were independent decision-makers and more active in choosing their reconstructive procedure (p = 0.001). CONCLUSIONS Microsurgical breast reconstruction is highly sought after by a subset of patients with breast cancer. These patients are independent decision-makers in their health care choices. They use the Internet to learn about breast reconstruction techniques and are more likely to self-refer to a reconstructive surgeon. It remains unclear how many patients would choose microsurgical reconstruction if offered more widely or if awareness of the procedure were greater.
Evaluation of Statistical Treatments of Left-Censored Environmental Data using Coincident Uncensored Data Sets : I . Summary Statistics

The main classes of statistical treatment of below-detection limit (left-censored) environmental data for the determination of basic statistics that have been used in the literature are substitution methods, maximum likelihood, regression on order statistics (ROS), and nonparametric techniques. These treatments, along with using all instrument-generated data (even those below detection), were evaluated by examining data sets in which the true values of the censored data were known. It was found that for data sets with less than 70% censored data, the best technique overall for determination of summary statistics was the nonparametric Kaplan–Meier technique.ROSandthetwosubstitutionmethodsofassigningonehalf the detection limit value to censored data or assigning a random number between zero and the detection limit to censored data were adequate alternatives. The use of these two substitutionmethods,however, requiresathoroughunderstanding of how the laboratory censored the data. The technique of employing all instrument-generated datasincluding numbers below the detection limitswas found to be less adequate than the above techniques. At high degrees of censoring (greater than 70% censored data), no technique provided good estimates of summary statistics. Maximum likelihood techniques were found to be far inferior to all other treatments except substituting zero or the detection limit value to censored data.
Long-term effects of mild traumatic brain injury on cognitive performance

Although a proportion of individuals report chronic cognitive difficulties after mild traumatic brain injury (mTBI), results from behavioral testing have been inconsistent. In fact, the variability inherent to the mTBI population may be masking subtle cognitive deficits. We hypothesized that this variability could be reduced by accounting for post-concussion syndrome (PCS) in the sample. Thirty-six participants with mTBI (>1 year post-injury) and 36 non-head injured controls performed information processing speed (Paced Visual Serial Addition Task, PVSAT) and working memory (n-Back) tasks. Both groups were split by PCS diagnosis (4 groups, all n = 18), with categorization of controls based on symptom report. Participants with mTBI and persistent PCS had significantly greater error rates on both the n-Back and PVSAT, at every difficulty level except 0-Back (used as a test of performance validity). There was no difference between any of the other groups. Therefore, a cognitive deficit can be observed in mTBI participants, even 1 year after injury. Correlations between cognitive performance and symptoms were only observed for mTBI participants, with worse performance correlating with lower sleep quality, in addition to a medium effect size association (falling short of statistical significance) with higher PCS symptoms, post-traumatic stress disorder (PTSD), and anxiety. These results suggest that the reduction in cognitive performance is not due to greater symptom report itself, but is associated to some extent with the initial injury. Furthermore, the results validate the utility of our participant grouping, and demonstrate its potential to reduce the variability observed in previous studies.
Effect of training focused on executive functions (attention, inhibition, and working memory) in preschoolers exhibiting ADHD symptoms

The development of early intervention strategies for children with symptoms of Attention Deficit Hyperactivity Disorder (ADHD) is important because it provides an opportunity to prevent severe problems in the future. The main purpose of this investigation was to determine the efficacy of a group training for the control of attention, working memory and impulsive behaviors, involving 5-year-old children with ADHD symptoms. Twenty-six children with ADHD symptoms and 26 with typical development were randomly divided in two conditions. Thirteen children in each group were assigned to the training condition and the other to the business as usual condition (normal class activity). Children who participated in the intervention showed an improvement in the tasks measuring their control of attention, impulsive behavior, and working memory. Moreover, children with typical development who attended the training also improved their competencies. The results confirm the importance of an early intervention for preschool-age children with ADHD symptoms.
NatB Domain-Containing CRA-1 Antagonizes Hydrolase ACER-1 Linking Acetyl-CoA Metabolism to the Initiation of Recombination during C. elegans Meiosis

The formation of DNA double-strand breaks (DSBs) must take place during meiosis to ensure the formation of crossovers, which are required for accurate chromosome segregation, therefore avoiding aneuploidy. However, DSB formation must be tightly regulated to maintain genomic integrity. How this regulation operates in the context of different chromatin architectures and accessibility, and how it is linked to metabolic pathways, is not understood. We show here that global histone acetylation levels undergo changes throughout meiotic progression. Moreover, perturbations to global histone acetylation levels are accompanied by changes in the frequency of DSB formation in C. elegans. We provide evidence that the regulation of histone acetylation requires CRA-1, a NatB domain-containing protein homologous to human NAA25, which controls the levels of acetyl-Coenzyme A (acetyl-CoA) by antagonizing ACER-1, a previously unknown and conserved acetyl-CoA hydrolase. CRA-1 is in turn negatively regulated by XND-1, an AT-hook containing protein. We propose that this newly defined protein network links acetyl-CoA metabolism to meiotic DSB formation via modulation of global histone acetylation.