Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 57,822 bioRxiv papers from 266,142 authors.
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9 downloads physiology
In spite of all the efforts on deciphering such spinning process of spiders, the underlying mechanism currently is yet to be fully revealed. In this research, we designed a novel approach to quantitatively estimate the overall concentration change of spider silk along the progression of liquid-to-solid silk transition from the gland silk. As a prior characterization, we first studied the influence of silking-rate, ranged from 1.5 to 8.0 m/min, on spun fiber diameters as well as fiber strengths. Furthermore, the liquid contents of silk in the sac and the silk fibers leaving the spinneret were investigated by thermogravimetric analysis (TGA) and by estimating the ratio of collected dried silk to the weight loss of spider, respectively. The strength of spun silk fiber showed in the range of 7.5 - 8.5 g/denier; while, the fiber diameter of 0.7 - 1.1 deniers for spun silk first increased then decreased with take-up speed of winder. The results showed that the percentage liquid content of silk stored in the major ampullate sac (50.0 wt%) was lower than that of silk leaving the spinnerets (80.9 - 96.1 wt%), indicating a liquid supplying mechanism might be involved during the spinning process. Thus, a hypothesis of liquid coating on the outer surface of the silk thread served as a lubrication layer to reduce the silking resistance in spinning spigot of spider was proposed. In addition, we speculated the spigot serves as a valve-like regulator that controls not only the fiber diameter but also the lubrication layer. These findings provide understanding in physiological function of the spider spinning process and could further shed some light on future biomimetic development of silk material fabrication.
9 downloads neuroscience
Information integration is fundamental to many aspects of human behavior, and yet its neural mechanism remains to be understood. For example, during face-to-face communication we know that the brain integrates the auditory and visual inputs but we do not yet understand where and how such integration mechanisms support speech comprehension. Here we show that two independent mechanisms forge audiovisual representations for speech comprehension in different brain regions. With a novel information theoretic measure, we found that theta (3-7 Hz) oscillations in the posterior superior temporal gyrus/sulcus (pSTG/S) code speech information that is common (i.e. redundant) to the auditory and visual inputs whereas the same oscillations in left motor and inferior temporal cortex code synergistic information between the same inputs. Importantly, redundant coding in the left pSTG/S and synergistic coding in the left motor cortex predict behavior - i.e. speech comprehension performance. Our findings therefore demonstrate that processes classically described as integration effectively reflect independent mechanisms that occur in different brain regions to support audiovisual speech comprehension.
9 downloads neuroscience
Axon guidance requires interactions between extracellular signaling molecules and transmembrane receptors, but how appropriate context-dependent decisions are coordinated outside the cell remains unclear. Here we show that the transmembrane glycoprotein Dystroglycan interacts with a changing set of environmental cues that regulate the trajectories of extending axons throughout the brain and spinal cord. Dystroglycan operates primarily as an extracellular scaffold during axon guidance, as it functions non-cell autonomously and does not require signaling through its intracellular domain. We identify the transmembrane receptor Celsr3/Adgrc3 as a binding partner for Dystroglycan, and show that this interaction is critical for specific axon guidance events in vivo. These findings establish Dystroglycan as a multifunctional scaffold that coordinates extracellular matrix proteins, secreted cues, and transmembrane receptors to regulate axon guidance.
9 downloads pathology
Background: In patients with clinically localized prostate cancer receiving external beam radiation therapy, studies have shown information from prostate biopsy cores can be predictive of clinical outcomes. Recent work from our institution compared several biopsy findings in low- and intermediate-risk patients and found a subset of patients who were more likely to fail treatment. This indicates patients in these groups may benefit from further risk stratification prior to initiation of therapy. Furthermore, findings on pre-treatment prostate MRI independently predict PSA relapse after external beam radiation therapy. Comparing MRI and pathological data may help to accurately further risk stratify patients. Our purpose is to determine if there is a correlation between the poor prognostic factors demonstrated on prostate biopsy cores and selected findings on prostate MRI. Methods: Intermediate risk prostate cancer patients with 1.5 and 3.0 Tesla MRI scans of the prostate performed from 2007-2011 were selected for a retrospective cohort study. Cases were reviewed by two body-trained radiologists who were blinded to clinical patient information. Reader consensus was obtained at the time of reading regarding presence of extracapsular extension, seminal vesicle invasion, and disease in each sextant by T2 and ADC imaging, including a dominant nodule. Results were analyzed for correlation between these findings on MRI and compared with results of prostate biopsy cores, including maximum involvement of any biopsy core (MIBC), percentage of cancer volume (PCV) and percent positive biopsy cores (PPBC). Results: The absolute presence of a dominant nodule on MRI was statistically significantly correlated with elevated PCV and PPBC applying the t-test for equality of means, with p-values of 0.019 and 0.006 respectively. PSA, Gleason score, and MIBC were not found to be correlated with dominant nodule on MRI. Conclusions: There is a strong positive correlation between MRI findings of a dominant nodule and prognostic biopsy findings of elevated PPBC and PCV.
9 downloads neuroscience
Previous studies in humans interested in inhibitory synaptic activity at the level of the primary motor cortex (M1) have frequently used an electrophysiological technique call short intracortical inhibition (SICI). This technique consists of two subsequent pulses with transcranial magnetic stimulation (TMS), of which the first pulse (S1) has been argued to target local inhibitory connections, reducing corticospinal output generated by the second pulse (S2). However, the reduction of corticospinal output is not seen in every tested subject, sometimes S1 even increased corticospinal output. Thus there seems to be more occurring than just the targeting of local inhibitory connections by S1, indicating that the mechanisms of SICI are not fully understood. In the present study, in 18 healthy young subjects we applied a method allowing to segregate corticospinal volleys with different conduction times and investigated the effect of S1 on the excitation of these volleys. Our results revealed three major findings, which can be summarized as follows: i) S1 acted not only locally at the level of M1, but produced corticospinal activity which may influence corticospinal output by S2 at the spinal level; ii) there was not only reduced excitation of corticospinal volleys by S1, but also an increased excitation of corticospinal volleys with longer conduction times; iii) at the level of M1, S1 indeed targeted preferentially inhibitory synaptic connections, and these reduced corticospinal excitation of the fastest conduction corticospinal volleys. Our results indicate that underlying mechanisms in studies applying SICI should be interpreted with caution.
9 downloads microbiology
Objective: Experiments were designed to compare the expressions of IL-1 TNF-α P-selectin mRNA by porcine endothelial cells after vein thrombosis. Methods: IVC under the renal vein of 20 porcines were ligated to induce thrombosis modes. These thrombosed veins were divided into three groups:group A-one day after thrombosis, group B-four days after thrombosis and group C-seven days after thrombosis. The other pigs were given the shame operation as a contro group (group D). The mRNA levels of IL-1?TNF-α and P-selectin expressed by porcine endothelial cells in three groups were analy sed by semi quantitative RT-PCR. Endothelial cells were harvested with collagenase?. Results: The purity of endothelial cells harvested was 99.42 ±0.07. The expression of IL-1 was detained only in group A while TNF-αreached its peak in group B(P <0.05) and P-selectin increased gradually with the days passing by(P <0.05). Conclusion: Endothelial cells are not only the target cells of inflammatory mediators, but also can express a variety of active factors to promote venous thrombosis. Expression of TNF-α mRNA is increased gradually in the early period of vein thrombosis while P-selectin in the acute period; IL-1 mRNA was transiently expressed only in the early stage of thrombosis.
9 downloads evolutionary biology
We introduce a multi-factorial, multi-level approach to build and explore evolutionary scenarios of complex protein networks. EvoKEN combines a unique formalism for integrating multiple types of data associated with network molecular components and knowledge extraction techniques for detecting cohesive/anomalous evolutionary processes. We analyzed known human pathway maps and identified perturbations or specializations at the local topology level that reveal important evolutionary and functional aspects of these cellular systems.
9 downloads genetics
A plausible explanation for statistical epistasis revealed in genome wide association analyses is the presence of high order linkage disequilibrium (LD) between the genotyped markers tested for interactions and unobserved functional polymorphisms. Based on findings in experimental data, it has been suggested that high order LD might be a common explanation for statistical epistasis inferred between local polymorphisms in the same genomic region. Here, we empirically evaluate how prevalent high order LD is between local, as well as distal, polymorphisms in the genome. This could provide insights into whether we should account for this when interpreting results from genome wide scans for statistical epistasis. An extensive and strong genome wide high order LD was revealed between pairs of markers on the high density 250k SNP-chip and individual markers revealed by whole genome sequencing in the A. thaliana 1001-genomes collection. The high order LD was found to be more prevalent in smaller populations, but present also in samples including several hundred individuals. An empirical example illustrates that high order LD might be an even greater challenge in cases when the genetic architecture is more complex than the common assumption of bi-allelic loci. The example shows how significant statistical epistasis is detected for a pair of markers in high order LD with a complex multi allelic locus. Overall, our study illustrates the importance of considering also other explanations than functional genetic interactions when genome wide statistical epistasis is detected, in particular when the results are obtained in small populations of inbred individuals.
9 downloads genetics
Whole genome duplications have played an important role in the evolution of angiosperms. These events often occur through hybridization between closely related species, resulting in an allopolyploid with multiple subgenomes. With the availability of affordable genotyping and a reference genome to locate markers, breeders of allopolyploids now have the opportunity to manipulate subgenomes independently. This also presents a unique opportunity to investigate epistatic interactions between homeologous orthologs across subgenomes. We present a statistical framework for partitioning genetic variance to the subgenomes of an allopolyploid, predicting breeding values for each subgenome, and determining the importance of inter-genomic epistasis. We demonstrate using an allohexaploid wheat breeding population evaluated in Ithaca, NY and an important wheat dataset previously shown to demonstrate non-additive genetic variance. Subgenome covariance matrices were constructed and used to calculate subgenome interaction covariance matrices across subgenomes for variance component estimation and genomic prediction. We propose a method to extract population structure from all subgenomes at once before covariances are calculated to reduce collinearity between subgenome estimates. Variance parameter estimation was shown to be reliable for additive subgenome effects, but was less reliable for subgenome interaction components. Predictive ability was equivalent to current genomic prediction methods. Including only inter-genomic interactions resulted in the same increase in accuracy as modeling all pairwise marker interactions. Thus, we provide a new tool for breeders of allopolyploid crops to characterize the genetic architecture of existing populations, determine breeding goals, and develop new strategies for selection of additive effects and fixation of inter-genomic epistasis.
9 downloads neuroscience
Resent studies found that sleep is essential to helping maintain mood, memory and cognitive performance. Sleep is a dynamic activity, when we sleep we pass throw different state in a cyclic way, wherein key processes for sustaining a healthy condition and overall well-being take place. It is very important that these cycles are maintained for healthy body function in awake state. Because of that, it is paramount to develop tools that can help to detect and classify these states. In this work, we analyzed the EEG signals from 17 subjects. By estimating Shannon's entropy, MPR statistical complexity and the Fisher information measure over the signals we show that it is possible to quantify and classify the sleep stages. Thus, information theory-based measures allow us to characterize the underlying dynamics of EEG time series, identifying the different sleep stages and most importantly define potential electrophysiological biomarkers able to distinguish between pathological and normal conditions.
9 downloads physiology
Animals are naturally surrounded by a variety of microorganisms with which they constantly interact. Among these microbes, some live closely associated with a host and form its microbiota. These communities are now extensively studied, owing to their contributions to shaping various aspects of animal physiology. One of these commensal species, Lactobacillus plantarum, and in particular the L.p.WJL strain, has been shown to promote the growth of Drosophila larvae upon nutrient scarcity, allowing earlier metamorphosis and adult emergence compared to axenic individuals. As for many insects, conditions surrounding the post-embryonic development dictate key Drosophila adult life history traits, and adjusting developmental timing according to the environment is essential for adult fitness. The growth acceleration induced by L.p.WJL occurs in a context of poor nutrition and we wondered if this could adversely impact the fitness of Drosophila adults. Here we show that the L.p.WJL-mediated acceleration of growth is not deleterious; adults emerging after an accelerated development are as fit as their axenic siblings. Additionally, L.p.WJL presence even leads to a lifespan extension in nutritionally challenged males. These results demonstrate that L.p.WJL is a beneficial partner for Drosophila melanogaster through its entire life cycle. This commensal bacteria allows the earlier emergence and longer survival of fit and fertile individuals and might represent one of the factors contributing to the ecological success of Drosophila.
9 downloads epidemiology
Background: There are sparse data in Africa on the association between HIV infection and deaths from underlying medical conditions. Using records from the Chris Hani Baragwanath Hospital (CHBH) in Soweto, South Africa, we determined mortality from medical conditions associated with HIV. Methods: From January 2006 to December 2009 AB collected data on 15,725 deaths including age, sex, day of admittance and death, HIV status, ART initiation and CD4+ cell counts and reviewed the underlying cause of death using medical notes. Conditions known to be associated with HIV were cases; conditions not associated with HIV were controls. We calculate the HIV odds-ratios for cases relative to controls and HIV-attributable deaths as the fraction of those with each condition, the disease-attributable fraction (DA), and as the fraction of all deaths, the population-attributable fraction (PAF). Interpretation: The high prevalence of HIV among those that died in the medical wards at the CHBH, especially in those below the age of 50 years, demonstrates the impact of the HIV-epidemic on adult mortality and hospital services and the extent to which early antiretroviral treatment would have reduced the burden of both. Of the deaths included in the analysis the prevalence of HIV was 61% and the prevalence of AIDS related conditions was 69%. The HIV-attributable fraction was 36% in the whole sample and 60% in those that were HIV-positive. Cryptococcosis, Kaposis sarcoma and Pneumocystis jeroveci are highly predictive of HIV while TB, gastroenteritis and anaemia are very strongly associated with HIV. The greatest number of deaths attributable to HIV was among those dying of TB or of other respiratory conditions.
9 downloads neuroscience
Neurodegenerative disorders are characterized by a progressive loss of brain function. Improved precision in mapping the altered brain pathways can provide a deep understanding of the trajectory of decline. We propose a tractometry workflow for conducting group statistical analyses of pointwise microstructural measures along white matter fasciculi to identify patterns of abnormalities associated with disease. We combined state-of-the-art tools including fiber registration, tract simplification and fiber matching for accurate point-wise statistical analyses across populations. We test the utility of this method by identifying group differences between Parkinson's disease (PD) patients and healthy controls. We find statistically significant group differences in diffusion MRI derived measures along the anterior thalamic radiations (ATR), corticospinal tract (CST) and regions of the corpus callosum (CC). These pathways are essential for motor control systems within cortico-cortical and cortico-subcortical brain networks. Moreover, the reported pathological changes were not widespread but rather localized along several tracts. Point-wise tract analyses may therefore offer an advantage in anatomical specificity over traditional methods that assess mean microstructural measures across large regions of interest.
9 downloads cell biology
Cholesterol is one of the most essential lipids in eukaryotic cell membranes. However, acute and selective manipulation of membrane cholesterol remains challenging. Here, we report that graphene nanoflakes (GNFs) insert into the plasma membrane and directly interact with cholesterol, resulting in acute cholesterol enrichment - and thus structural and functional changes. Using two representative cell preparations, we explore the utility of GNFs in modifying cell communication pathways sensitive to membrane cholesterol. In fibroblasts, GNFs enhance ATP-induced intracellular Ca2+-release by allosteric facilitation of P2Y receptors, a subtype of G protein-coupled receptors, in a cholesterol-dependent manner. In neurons, which possess higher membrane cholesterol levels than most cell types, GNFs further increase cholesterol. Consequently, GNFs change membrane fluidity, especially at synaptic boutons, and potentiate neurotransmitter release by accelerating synaptic vesicle turnover. Together, our results provide a molecular explanation for graphene's cellular impacts and demonstrate its potential for membrane-oriented engineering of cell signaling.
9 downloads genetics
Patients admitted to an intensive care unit (ICU) are subjected to a high burden of stress, rendering them prone to develop stress-related psychopathology. Dysregulation of inflammation and, more specifically, upregulation of inflammatory markers such as C-reactive protein (CRP) is potentially key in development of post-ICU psychopathology. To investigate the effects of state-independent CRP on symptoms of post-traumatic stress disorder (PTSD) and depression after ICU admission, we analysed the three leading single nucleotide polymorphisms (SNPs) of loci most strongly associated with blood CRP levels (i.e. rs2794520, rs4420638, and rs1183910) in an ICU survivor cohort. Genetic association was estimated by linear and logistical regression models of individual SNPs and genetic risk score (GRS) profiling. Mendelian Randomization (MR) was used to investigate potential causal relationships. Single-SNP analyses were non-significant for both quantitative and binary trait analyses after correction for multiple testing. In addition, GRS results were non-significant and explained little variance in psychopathology. Moreover, MR analysis did not reveal any causality and MR-Egger regression showed no evidence of pleiotropic effects (p-pleiotropy > 0.05). Furthermore, estimation of causality between these loci and other psychiatric disorders was similarly non-significant. In conclusion, by applying a range of statistical models we demonstrate that the strongest plasma CRP-influencing genetic loci are not associated with post-ICU PTSD and depressive symptoms. Our findings add to an expanding body of literature on the absence of associations between trait CRP and neuropsychiatric phenotypes.
9 downloads ecology
1. Estimates of age-specific mortality are regularly used in ecology, evolution, and conservation research. However, existing methods to estimate mortality from re-sighting records of marked individuals fail at estimating mortality of males for species with male natal dispersal due to the uncertainty surrounding disappearances of adult males from study populations. 2. Here, we develop a mortality model that imputes dispersal state (i.e., died or left) for uncertain male records as a latent state jointly with the coefficients of a parametric mortality model in a Bayesian hierarchical framework. To check the performance of our model, we first conduct a simulation study. We then apply our model to a long-term data set for African lions. Using these data, we further scrutinise the mortality estimates derived from our model by incrementally reducing the level of uncertainty in the male records. We achieve this by taking advantage of an expert's intuition on the likely fate of each uncertain male record. 3. We find that our new model produces accurate mortality parameters for simulated data of varying sample sizes and proportions of uncertain male records. From the empirical study we learned that our model provides similar mortality estimates for different levels of uncertainty in male records. However, a sensitivity of the mortality estimates to varying uncertainty is, as can be expected, detectable. 4. We conclude that our model provides a solution to the challenge of estimating male mortality in species with data-deficiency for males due to natal dispersal. Given the utility of sex-specific mortality estimates in biological and conservation research and the virtual ubiquity of sex-biased dispersal, our model will be useful to a wide variety of applications.
9 downloads developmental biology
Organ size and pattern results from the integration of two positional information systems. One global, encoded by the Hox genes, links organ type with position along the main body axis. Within specific organs, local information is conveyed by signaling molecules that regulate organ growth and pattern. The mesothoracic (T2) wing and the metathoracic (T3) haltere of Drosophila represent a paradigmatic example of this coordination. The Hox gene Ultrabithorax (Ubx), expressed in the developing T3, selects haltere identity by, among other processes, modulating the production and signaling efficiency of Dpp, a BMP2-like molecule that acts as a major regulator of size and pattern. Still, the mechanisms of the Hox-signal integration even in this well-studied system, are incomplete. Here we have investigated this issue by studying the expression and function of the Six3 transcription factor optix during the development of the Drosophila wing and haltere development. We find that in both organs Dpp defines the expression domain of optix through repression, and that the specific position of this domain in wing and haltere seems to reflect the differential signaling profile among these organs. We show that optix expression in wing and haltere primordia is conserved beyond Drosophila in other higher diptera. Despite the similar expression pattern, optix plays different roles in wing and haltere. In the wing, optix is required for the growth of the most anterior/proximal region (the marginal cell) and for the correct formation of sensory structures along the proximal anterior wing margin. In contrast, in the haltere optix is necessary for the suppression of sensory bristles without any noticeable effect on organ growth. Therefore, optix shows an organ-specific function. Beyond dipterans, optix expression in the anterior wing has been shown also in butterflies. We propose that the ancestral role of optix might have been structural in the anterior wing. Once expressed in the wing, optix expression had been re-deployed for wing spot formation in other parts of the wing of Heliconius butterflies.
9 downloads microbiology
Lipoate is an essential cofactor for key enzymes of oxidative and one-carbon metabolism. It is covalently attached to E2 subunits of dehydrogenase (DH) complexes and the GcvH subunit of the glycine cleavage system. Bacillus subtilis possess two protein lipoylation pathways: biosynthesis and scavenging. The former requires octanoylation of GcvH, amidotransfer of the octanoate to E2s, and insertion of sulfur atoms. Lipoate scavenging is mediated by a lipoate ligase (LplJ), that catalizes a classical two-step ATP-dependent reaction. Although these pathways were thought to be redundant, a ΔlipL mutant, unable to transfer the octanoyl group from GcvH to the E2s during lipoate synthesis, showed growth defects in minimal media even when supplemented with this cofactor, despite the presence of a functional LplJ. In this study we demonstrated that LipL is essential to modify E2 subunits of branched chain ketoacid and pyruvate DH during lipoate scavenging. LipL must be functional and it is not forming a complex with LplJ, which suggests that these enzymes might be acting sequentially. We also show that the E2 subunit of oxoglutarate DH is a good donor for LipL amidotransfer reaction. The essential role of LipL during lipoate utilization relies on the strict substrate specificity of LplJ, determined by charge complementarity between the ligase and the lipoylable subunits. LplJ does not recognize E2 subunits without a negatively charged residue in key positions of the target protein, and thus LipL is required to transfer the lipoate to them. This model of lipoate scavenging seems widespread among Gram-positive bacteria.
9 downloads genetics
In this study, we perform a full genome-wide association study (GWAS) to identify statistically significantly associated single nucleotide polymorphisms (SNPs) with three red blood cell (RBC) components and follow it with two independent PheWASs to examine associations between phenotypic data (case-control status of diagnoses or disease), significant SNPs, and RBC component levels. We first identified associations between the three RBC components: mean platelet volume (MPV), mean corpuscular volume (MCV), and platelet counts (PC), and the genotypes of approximately 500,000 SNPs on the Illumina Infimum DNA Human OmniExpress-24 BeadChip using a single cohort of 4,700 Northern Nevadans. Twenty-one SNPs in five major genomic regions were found to be statistically significantly associated with MPV, two regions with MCV, and one region with PC, with p<5x10-8. Twenty-nine SNPs and nine chromosomal regions were identified in 30 previous GWASs, with effect sizes of similar magnitude and direction as found in our cohort. The two strongest associations were SNP rs1354034 with MPV (p=2.4x10-13) and rs855791 with MCV (p=5.2x10-12).We then examined possible associations between these significant SNPs and incidence of 1,488 phenotype groups mapped from International Classification of Disease version 9 and 10 (ICD9 and ICD10) codes collected in the extensive electronic health record (EHR) database associated with Healthy Nevada Project consented participants. Further leveraging data collected in the EHR, we performed an additional PheWAS to identify associations between continuous red blood cell (RBC) component measures and incidence of specific diagnoses. The first PheWAS illuminated whether SNPs associated with RBC components in our cohort were linked with other hematologic phenotypic diagnoses or diagnoses of other nature. Although no SNPs from our GWAS were identified as strongly associated to other phenotypic components, a number of associations were identified with p-values ranging between 1x10-3 and 1x10-4 with traits such as respiratory failure, sleep disorders, hypoglycemia, hyperglyceridemia, GERD and IBS. The second PheWAS examined possible phenotypic predictors of abnormal RBC component measures: a number of hematologic phenotypes such as thrombocytopenia, anemias, hemoglobinopathies, and pancytopenia were found to be strongly associated to RBC component measures; additional phenotypes such as (morbid) obesity, malaise and fatigue, alcoholism, and cirrhosis were also identified to be possible predictors of RBC component measures.
9 downloads neuroscience
Peripheral nerve interfaces show promise in making prosthetic limbs more biomimetic and ultimately more intuitive and useful for patients. However, approaches to assess these emerging technologies are limited in their scope and the insight they provide. When outfitting a prosthesis with a new feedback system it would be helpful to quantify its physiological correspondence, i.e. how well the experimental feedback mimics the perceived feedback in an intact limb. Here we present an approach to quantify physiological correspondence using a modified crossmodal congruency task. We trained 60 able-bodied subjects to control a bypass prosthesis under different feedback conditions and training durations. We find that the crossmodal congruency effect (CCE) score is sensitive to changes in feedback modality (multi-way ANOVA; F(2,48) = 6.02, p<0.05). After extended training, the CCE score increased as the spatial separation between expected and perceived feedback decreased (unpaired t-test, p<0.05). We present a model that can quantitatively estimate physiological correspondence given the CCE result and the measured spatial separation of the feedback. This quantification approach gives researchers a tool to assess an aspect of emerging augmented feedback systems that is not measurable with current motor assessments.
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