Miracle-dz/UniFAR-FTUs huggingface dataset:
14-3-3 Proteins Reduce Cell-to-Cell Transfer and Propagation of Pathogenic α-Synuclein

α-Synuclein (αsyn) is the key protein that forms neuronal aggregates in the neurodegenerative disorders Parkinson's disease (PD) and dementia with Lewy bodies. Recent evidence points to the prion-like spread of αsyn from one brain region to another. Propagation of αsyn is likely dependent on release, uptake, and misfolding. Under normal circumstances, this highly expressed brain protein functions normally without promoting pathology, yet the underlying endogenous mechanisms that prevent αsyn spread are not understood. 14-3-3 proteins are highly expressed brain proteins that have chaperone function and regulate protein trafficking. In this study, we investigated the potential role of the 14-3-3 proteins in the regulation of αsyn spread using two models of αsyn spread. In a paracrine αsyn model, 14-3-3θ promoted release of αsyn complexed with 14-3-3θ. Despite higher amounts of released αsyn, extracellular αsyn showed reduced oligomerization and seeding capability, reduced internalization, and reduced toxicity in primary mixed-gender mouse neurons. 14-3-3 inhibition reduced the amount of αsyn released, yet released αsyn was more toxic and demonstrated increased oligomerization, seeding capability, and internalization. In the preformed fibril model, 14-3-3 θ reduced αsyn aggregation and neuronal death, whereas 14-3-3 inhibition enhanced αsyn aggregation and neuronal death in primary mouse neurons. 14-3-3s blocked αsyn spread to distal chamber neurons not exposed directly to fibrils in multichamber, microfluidic devices. These findings point to 14-3-3s as a direct regulator of αsyn propagation, and suggest that dysfunction of 14-3-3 function may promote αsyn pathology in PD and related synucleinopathies. SIGNIFICANCE STATEMENT Transfer of misfolded aggregates of α-synuclein from one brain region to another is implicated in the pathogenesis of Parkinson's disease and other synucleinopathies. This process is dependent on active release, internalization, and misfolding of α-synuclein. 14-3-3 proteins are highly expressed chaperone proteins that interact with α-synuclein and regulate protein trafficking. We used two different models in which toxicity is associated with cell-to-cell transfer of α-synuclein to test whether 14-3-3s impact α-synuclein toxicity. We demonstrate that 14-3-3θ reduces α-synuclein transfer and toxicity by inhibiting oligomerization, seeding capability, and internalization of α-synuclein, whereas 14-3-3 inhibition accelerates the transfer and toxicity of α-synuclein in these models. Dysfunction of 14-3-3 function may be a critical mechanism by which α-synuclein propagation occurs in disease.
Dynamic Scheduling for Progressive Large-Scale Visualization

The ever-increasing compute capacity of high-performance systems enables scientists to simulate physical phenomena with a high spatial and temporal accuracy. Thus, the simulation output can yield dataset sizes of many terabytes. An efficient analysis and visualization process becomes very difficult especially for explorative scenarios where users continuously change input parameters. Using a distributed rendering pipeline may relieve the visualization frontend considerably but is often not sufficient. Therefore, we additionally propose a progressive data streaming and rendering approach. The main contribution of our method is the importance-guided order of data processing for block structured datasets. This requires a dynamic scheduling of data chunks on the parallel post-processing system which has been implemented by using an R-Tree. In this paper, we demonstrate the efficiency of our implementation for view-dependent feature extraction with varying viewpoints.
APPD: Adaptive and Precise Pupil Boundary Detection using Entropy of Contour Gradients.

Eye tracking spreads through a vast area of applications from ophthalmology, assistive technologies to gaming and virtual reality. Precisely detecting the pupil's contour and center is the very first step in many of these tasks, hence needs to be performed accurately. Although detection of pupil is a simple problem when it is entirely visible; occlusions and oblique view angles complicate the solution. In this study, we propose APPD, an adaptive and precise pupil boundary detection method that is able to infer whether entire pupil is in clearly visible by a heuristic that estimates the shape of a contour in a computationally efficient way. Thus, a faster detection is performed with the assumption of no occlusions. If the heuristic fails, a more comprehensive search among extracted image features is executed to maintain accuracy. Furthermore, the algorithm can find out if there is no pupil as an helpful information for many applications. We provide a dataset containing 3904 high resolution eye images collected from 12 subjects and perform an extensive set of experiments to obtain quantitative results in terms of accuracy, localization and timing. The proposed method outperforms three other state of the art algorithms and has an average execution time $\sim$5 ms in single-thread on a standard laptop computer for 720p images.
Trends and Complications of Vulvar Reconstruction After Vulvectomy: A Study of a Nationwide Cohort

Objectives The objective of this study was to determine complications associated with primary closure compared with reconstruction after vulvar excision and predisposing factors to these complications. Methods Patients undergoing vulvar excision with or without reconstruction from 2011 to 2015 were abstracted from the National Surgical Quality Improvement Program database. Common Procedural Terminology codes were used to characterize surgical procedures as vulvar excision alone or vulvar excision with reconstruction. Patient characteristics and 30-day outcomes were used to compare the 2 procedures. Descriptive and univariate statistics were performed. Adjusted odds ratios and confidence intervals were calculated using a logistic regression model to control for potential confounders. Two-sided &agr; with P < 0.05 was designated as significant. Results A total of 2698 patients were identified; 78 (2.9%) underwent reconstruction. There were no differences in age, race, body mass index, diabetes, hypertension, tobacco use, heart failure, renal failure, or functional status between the 2 groups. American Society of Anesthesiologists class 3 and 4 patients and those with disseminated cancer were more likely to undergo reconstruction (both P < 0.001). On univariate analysis, reconstruction was associated with increased risk of readmission, surgical site infection, pulmonary complications, urinary tract infection, transfusion, deep venous thrombosis, sepsis, septic shock, unplanned reoperation, longer hospital stay, need for skilled nursing or subacute rehab on discharge, and death within 30 days. On logistic regression analysis, disseminated cancer, American Society of Anesthesiologists classes 3 and 4 and reconstruction remained significant risk factors for readmission and any postoperative complication. Conclusions Patients undergoing vulvar excision with reconstruction are at increased risk for readmission and postoperative complications compared with those undergoing excision alone. Careful patient selection and efforts to optimize surgical readiness are needed to improve outcomes. Long-term data could help determine if these 30-day outcomes are a reliable measure of surgical quality in vulvar surgery.
KeyDrown: Eliminating Software-Based Keystroke Timing Side-Channel Attacks

Besides cryptographic secrets, software-based side-channel attacks also leak sensitive user input. The most accurate attacks exploit cache timings or interrupt information to monitor keystroke timings and subsequently infer typed words and sentences. These attacks have also been demonstrated in JavaScript embedded in websites by a remote attacker. We extend the state-of-the-art with a new interrupt-based attack and the first Prime+ Probe attack on kernel interrupt handlers. Previously proposed countermeasures fail to prevent software-based keystroke timing attacks as they do not protect keystroke processing through the entire software stack. We close this gap with KeyDrown, a new defense mechanism against software-based keystroke timing attacks. KeyDrown injects a large number of fake keystrokes in the kernel, making the keystroke interrupt density uniform over time, i.e., independent of the real keystrokes. All keystrokes, including fake keystrokes, are carefully propagated through the shared library to make them indistinguishable by exploiting the specific properties of software-based side channels. We show that attackers cannot distinguish fake keystrokes from real keystrokes anymore and we evaluate KeyDrown on a commodity notebook as well as on Android smartphones. We show that KeyDrown eliminates any advantage an attacker can gain from using software-based side-channel attacks.
The effects of temperature on the development, fecundity and mortality of Eretmocerus warrae: is Eretmocerus warrae better adapted to high temperatures than Encarsia formosa?

BACKGROUND Eretmocerus warrae (Hymenoptera: Aphelinidae) is a parasitoid of the glasshouse whitefly, Trialeurodes vaporariorum (Hemiptera: Aleyrodidae). Here, we compare its potential as a biological control agent at high temperatures to that of Encarsia formosa (Hymenoptera: Aphelinidae), a wasp which is widely sold for control of T. vaporariorum. RESULTS Eretmocerus warrae attained the highest estimated developmental rate at 31.4 °C and the maximum oviposition rate at 30.5 °C. Developmental times of E. warrae at fluctuating temperatures that simulate night-day patterns were similar to those predicted based on constant temperatures. Above the optimum temperature, E. warrae tolerated higher constant temperatures than En. formosa during development and as adults. Using a ramping temperature approach, the critical thermal maximum for adult E. warrae was significantly higher than that of adult En. formosa. CONCLUSION Eretmocerus warrae is better adapted to high temperatures than En. formosa, and could therefore be a complementary or superior biological control agent during summer months in hot regions. © 2018 Society of Chemical Industry.
PointAO - Improved Ambient Occlusion for Point-based Visualization

The visualization of large amounts of particles, glyphs, and other point-based data plays an important role in many ﬁelds of science, among them ﬂow mechanics, molecular dynamics, and medical imaging. The proper perception of spatial structures and spatial relations in the data is crucial to the understanding. To accommodate this aspect, we utilize and improve an existing ambient occlusion approach, originally tailored towards line rendering and extend the approach to be applicable to point-based visualizations
Perception-Aware Uncertainty Glyphs in the 3D Vector Fields

We often cannot avoid value uncertainties when curating raw data to obtain a ﬁnal visualization image. Although numerous studies maintain the importance of uncertainty visualization, there lack a standard means of depicting the information, especially in 3D ﬂow visualization tasks. We introduce a novel glyph design referred to as the disk-tailed arrow which shows the trends and uncertainties in 3D vector ﬁelds concisely. The proposed design includes a glyph shape and modeling strategies which map statistical information to visual cues. Our scheme is devised so that the user can perceive 3D uncertainty information effectively. We also present a case study of the application of the proposed glyph to an actual ﬂow dataset as an assessment.
Porcine Epidemic Diarrhoea Virus in Italy: Disease spread and the role of transportation

Abstract Porcine Epidemic Diarrhoea Virus (PEDV) causes watery diarrhoea, dehydration, and a high mortality rate among suckling pigs. Recently, PEDV had a large negative economic impact on the swine industries in Asia and North America. In 2014, PEDV re‐emerged in many European countries, but most countries only reported a few sporadic cases. Here, we report the epidemic wave that occurred in Italy from 2015 to 2017. During this time, PEDV was detected by real‐time PCR in 438 farms located mainly in the high‐density pig production area in Northern Italy. Most of the outbreaks were in farrow‐to‐finish, farrow‐to‐wean and finisher farms. Clinical signs were observed mainly in suckling and fattening animals, while mortality rates were higher in piglets, reaching 50%. A sequence analysis showed that a PEDV strain, similar to the OH851 S‐INDEL strain isolated in the USA in January 2014, was responsible for the outbreaks in Italy in 2015 and 2016. However, from January 2017, a recombinant variant strain, containing a portion of the Swine Enteric Coronavirus in the S1 gene, spread and almost completely outcompeted the previous nonrecombinant strain. In total, 14.1% of the environmental swabs collected from trucks at slaughterhouses after animals were unloaded tested positive for PEDV before the trucks were cleaned and disinfected, and 46% remained positive after cleaning and disinfection processes were performed. Moreover, environmental swabs indicated that 17.3% of the empty trucks arriving at the farms to load animals were PEDV‐positive. This study indicates that trucks can have an important role in the spread of PEDV in Italy.
RESEARCH ARTICLE Stem Cells, Tissue Engineering, Development, and Cancer In the setting of (cid:2) -cell stress, the pancreatic duct gland transcriptome shows characteristics of an activated regenerative response

PC. In the setting of (cid:2) -cell stress, the pancreatic duct gland transcriptome shows characteristics of an activated regenerative response. Am J Physiol Gastrointest Liver Physiol 315: G848–G854, 2018. pancreatic duct gland (PDG) compartment has been proposed as a potential stem cell niche based on its coiled tubular structure embedded in mesenchyme, its proliferation and expansion in response to pancreatic injury, and the fact that it contains endocrine and exocrine epithelial cells. Little is known of the molecular signature of the PDG compartment in either a quiescent state or the potentially activated state during (cid:2) -cell stress characteristic of diabetes. To address this, we performed RNA sequencing on RNA obtained from PDGs of wild-type vs. prediabetic HIP rats, a model of type 2 diabetes. The transcriptome of the PDG compartment, compared with a library of 84 tissue types, placed PDGs midpoint between the exocrine and endocrine pancreas and closely related to seminiferous tubules, consistent with a role as a stem cell niche for the exocrine and endocrine pancreas. Standard differential expression analysis (permissive threshold P (cid:3) 0.005) identiﬁed 245 genes differentially expressed in PDGs from HIP rats vs. WT rats, with overrepresentation of transcripts involved in acute inﬂammatory responses, regulation of cell proliferation, and tissue development, while pathway analysis pointed to enrichment of cell movement-related pathways. In conclusion, the transcriptome of the PDG compartment is consistent with a pancreatic stem cell niche that is activated by ongoing (cid:2) -cell stress signals. The documented PDG transcriptome provides potential candidates to be exploited for lineage tracing studies of this as yet little investigated compartment. study) were normalized jointly using quantile normalization, and MDS plots were generated to organize samples in a two-dimensional space, based on the expression of the top 1,000 most variable genes. Differential expression analysis was performed to compare HIP and WT samples, using the edgeR package and setting the P value threshold of 0.005. Gene ontology and pathway analysis were per- formed using DAVID (http://david.abcc.ncifcrf.gov/) and Ingenuity Pathway Analysis (ingenuity.org).
Self-Reported Lifetime Violence Exposure and Self-Compassion Associated With Satisfaction of Life in Historically Black College and University Students

In the United States, approximately 25% of minors have witnessed a violent act, specifically physical assault. African Americans from under-served backgrounds are more likely than other racial and ethnic groups to be exposed to traumatic events. However, there is scant literature examining violence exposure, SC, and life satisfaction collectively, specifically in an African American college sample. The current study sought to determine the associations among violence exposure, SC components, and life satisfaction in an African American college sample. The current sample was comprised of 356 participants (80% female) with a mean age of 20.23 (SD = 1.70). Eighty-eight participants (25%) reported being exposed to violence in their lifetime. Employing logistic regression, we determined violence exposed individuals were less likely to report high satisfaction of life than their non-exposed counterparts (OR = 0.58, 95% CIs = 0.33, 1.00). Individuals with high level of self-kindness were approximately two times more likely to have higher satisfaction of life (OR = 2.48; CI = 1.52, 4.05) compared to their low level self-kindness counterparts and in the presence of demographic covariates. These findings may educate and increase awareness of the impacts of traumatic events. This education could lead to the implementation of interventions to build upon overall well-being in order increase life satisfaction in college students.
Ancient convergent losses of Paraoxonase 1 yield potential risks for modern marine mammals

Adaptive conflicts with the modern world Mammals evolved in terrestrial environments. Those that now live in the marine environment have had to adapt to the particular selective pressures that this environment imposes. Meyer et al. surveyed the genomes of several marine mammal species to identify regions of convergent change. Multiple losses of the Paraoxonase 1 gene are evident in marine mammals, likely resulting from remodeling of lipid metabolism or antioxidant networks. The multiple occurrences of this loss of function across taxa indicate an evolutionary benefit. However, Paraoxonase 1 is the primary mammalian defense against organophosphorus toxicity. Marine mammals may be at a great disadvantage in the Anthropocene if run-off of this agricultural product into the marine environment continues. Science, this issue p. 591 Convergent loss of Paraoxonase 1 may leave marine mammals unable to metabolize organophosphates. Mammals diversified by colonizing drastically different environments, with each transition yielding numerous molecular changes, including losses of protein function. Though not initially deleterious, these losses could subsequently carry deleterious pleiotropic consequences. We have used phylogenetic methods to identify convergent functional losses across independent marine mammal lineages. In one extreme case, Paraoxonase 1 (PON1) accrued lesions in all marine lineages, while remaining intact in all terrestrial mammals. These lesions coincide with PON1 enzymatic activity loss in marine species’ blood plasma. This convergent loss is likely explained by parallel shifts in marine ancestors’ lipid metabolism and/or bloodstream oxidative environment affecting PON1’s role in fatty acid oxidation. PON1 loss also eliminates marine mammals’ main defense against neurotoxicity from specific man-made organophosphorus compounds, implying potential risks in modern environments.
Biomaterials for intervertebral disc regeneration: Current status and looming challenges

A biomaterial‐based strategy is employed to regenerate the degenerated intervertebral disc, which is considered a major generator of neck and back pain. Although encouraging enhancements in the anatomy and kinematics of the degenerative disc have been gained by biomaterials with various formulations in animals, the number of biomaterials tested in humans is rare. At present, most studies that involve the use of newly developed biomaterials focus on regeneration of the degenerative disc, but not pain relief. In this review, we summarise the current state of the art in the field of biomaterial‐based regeneration or repair for the nucleus pulposus, annulus fibrosus, and total disc transplantation in animals and humans, and we then provide essential suggestions for the development and clinical translation of biomaterials for disc regeneration. It is important for researchers to consider the commonly neglected issues instead of concentrating solely on biomaterial development and fabrication.
Untreated Sleep Apnea: An Analysis of Administrative Data to Identify Risk Factors for Early Nonadherence.

STUDY OBJECTIVES Discontinuation of positive airway pressure (PAP) treatment for obstructive sleep apnea (OSA) is widely reported, but research has not adequately addressed nonadherence with diagnostic testing for sleep disorders and initiation of PAP. This study sought to identify drivers of nonadherence with diagnostic sleep testing and PAP treatment initiation among patients preauthorized for these services. METHODS This observational cohort study used preauthorization records from a sleep management program and administrative medical claims from a large commercial health insurer. Participants included adults preauthorized for sleep testing and a subset in whom OSA was diagnosed and who were preauthorized for PAP treatment. Outcome measures were nonadherence with diagnostic sleep testing and PAP treatment initiation, identified as lack of a claim for a preauthorized service within 3 months of preauthorization of that service. Risk factors for nonadherence included patient demographics, prescribing factors, signs and symptoms of OSA, comorbidities, and prior health service utilization. RESULTS Of 51,749 patients preauthorized for diagnostic testing, 23.5% did not undergo testing. Among 19,968 patients preauthorized for PAP treatment, 11.1% did not initiate treatment. Testing and treatment ordered by primary care providers, residence outside the Midwest region, and two or fewer office visits within 6 months before preauthorization were strong predictors of nonadherence. Apnea-hypopnea index score < 30 events/h was also a strong predictor of nonadherence with treatment initiation. CONCLUSIONS This study adds to existing knowledge about risk factors for nonadherence with sleep testing and treatment initiation following preauthorization. Health plans and providers should develop strategies to better engage patients with higher risk of nonadherence.
Kinome analyses of inflammatory responses to swine barn dust extract in human bronchial epithelial and monocyte cell lines

Exacerbated inflammation upon persistent barn organic dust exposure is a key contributor to the pathogenesis of lung inflammation and lung function decline. Barn dust constituents and the mechanisms contributing to the exacerbated inflammation are not clearly known. We set out to understand the inflammatory effects of Swine Barn Dust Extracts (SBDE) on human lung epithelial (BEAS2B) and macrophage (THP-1 monocyte derived) cell lines on a kinome array to determine phosphorylation events in the inflammatory signaling pathways. Upon identifying events unique to SBDE or those induced by innate immune ligands in each cell line, we validated the signaling pathway activation by transcriptional analyses of downstream inflammatory cytokines. Our findings indicate that SBDE-mediated pro-inflammatory effects are predominantly due to the induction of neutrophilic chemokine IL-8. Differentially phosphorylated peptides implicated in IL-8 induction in BEAS2B cell line include, TLR2, 4, 5, 7, 8, 9, PKC, MAP kinases (p38, JNK), inflammasomes (NLRP1, NLRP3), NF-κB and AP-1. In the THP-1 cell line, in addition to the aforementioned peptides, peptides corresponding to RIG-I-like receptors (RIG-I, MDA5) were found. This is the first report to demonstrate the application of a kinome array to delineate key inflammatory signaling pathways activated upon SBDE exposure in vitro.