Miracle-dz/UniFAR-FTUs huggingface dataset:
Two variance component model improves genetic prediction in family data sets

Genetic prediction based on either identity by state (IBS) sharing or pedigree information has been investigated extensively using Best Linear Unbiased Prediction (BLUP) methods. Such methods were pioneered in the plant and animal breeding literature and have since been applied to predict human traits with the aim of eventual clinical utility. However, methods to combine IBS sharing and pedigree information for genetic prediction in humans have not been explored. We introduce a two variance component model for genetic prediction: one component for IBS sharing and one for approximate pedigree structure, both estimated using genetic markers. In simulations using real genotypes from CARe and FHS family cohorts, we demonstrate that the two variance component model achieves gains in prediction r2 over standard BLUP at current sample sizes, and we project based on simulations that these gains will continue to hold at larger sample sizes. Accordingly, in analyses of four quantitative phenotypes from CARe and two quantitative phenotypes from FHS, the two variance component model significantly improves prediction r2 in each case, with up to a 20% relative improvement. We also find that standard mixed model association tests can produce inflated test statistics in data sets with related individuals, whereas the two variance component model corrects for inflation. Author Summary Genetic prediction has been well-studied in plant and animal breeding and has generated considerable recent interest in human genetics, both in family data sets and in population cohorts. Many prediction studies are based on the widely used Best Linear Unbiased Prediction (BLUP) approach, which performs a mixed model analysis using a genetic relationship matrix that is either estimated from genotype data—thus measuring identity-by-state (IBS) sharing—or obtained from family pedigree information. We show here that a substantial improvement in prediction accuracy in family data sets can be obtained by jointly modeling both IBS sharing and approximate pedigree structure, both estimated using genetic markers, using separate variance components within a two variance component mixed model. We demonstrate the performance of this model in simulations and real data sets. We also show that previous mixed model association methods suffer from inflated test statistics in family data sets due to their failure to account for the different heritability parameters corresponding to IBS sharing vs. pedigree relatedness. Our two variance component model provides a solution to this problem without compromising statistical power.
Superovulation, fertilization and in vitro embryo development in mice after administration of an inhibin-neutralizing antiserum.

The present study was conducted to investigate the effect of immunoneutralization against endogenous inhibin on oocyte and embryo production in adult and immature mice. At 12:00 h on day 2 of oestrus (day 1 of dioestrus), a single i.p. injection of inhibin antiserum (50, 100, 200 or 400 microl per animal) or equine chorionic gonadotrophin (eCG; 10 or 20 iu per animal) or control goat serum (100 microl per animal) was administered to adult female mice. After 48 h, the mice in each of the three groups were given a single i.p. injection of hCG (10 iu per animal). At 42 h after hCG injection, ova were collected from oviducts and cultured in KSOM solution. Treatments with both inhibin antiserum-hCG and eCG-hCG induced superovulation in all the animals tested. The number of oocytes in animals treated with inhibin antiserum was significantly higher (P < 0.05) compared with the control group, and the number of oocytes ovulated in animals treated with 200 or 400 ml inhibin antiserum was significantly (P < 0.05) higher than that in animals treated with 10 or 20 iu eCG. The superovulated oocytes that were fertilized normally in vivo were able to form blastocysts in vitro. The rate of blastocyst development for animals treated with 50-200 ml inhibin antiserum was significantly (P < 0.05) higher than that of the eCG-treated animals. Irrespective of the day of the oestrous cycle, 200 microl inhibin antiserum administered at 12:00 h on each of 4 days induced superovulation in all the animals tested. The rates of oocyte and embryo production by these animals were significantly (P < 0.05) higher than in the control groups. Furthermore, administration of inhibin antiserum at doses of 50, 100, 200 or 400 ml produced similar results in 26-day-old immature mice. These results indicate that passive immunoneutralization of endogenous inhibin alpha-subunit induces superovulation in immature and adult mice. The superovulated oocytes obtained by administration of inhibin antiserum have normal embryonic developmental competence. Thus, it is concluded that this inhibin antiserum method is a new practical alternative for induction of superovulation in mice instead of the more commonly used eCG-hCG protocol.
Carcinogenic Air Toxics Exposure and Their Cancer-Related Health Impacts in the United States

Public health protection from air pollution can be achieved more effectively by shifting from a single-pollutant approach to a multi-pollutant approach. To develop such multi-pollutant approaches, identifying which air pollutants are present most frequently is essential. This study aims to determine the frequently found carcinogenic air toxics or hazardous air pollutants (HAPs) combinations across the United States as well as to analyze the health impacts of developing cancer due to exposure to these HAPs. To identify the most commonly found carcinogenic air toxics combinations, we first identified HAPs with cancer risk greater than one in a million in more than 5% of the census tracts across the United States, based on the National-Scale Air Toxics Assessment (NATA) by the U.S. EPA for year 2005. We then calculated the frequencies of their two-component (binary), and three-component (ternary) combinations. To quantify the cancer-related health impacts, we focused on the 10 most frequently found HAPs with national average cancer risk greater than one in a million. Their cancer-related health impacts were calculated by converting lifetime cancer risk reported in NATA 2005 to years of healthy life lost or Disability-Adjusted Life Years (DALYs). We found that the most frequently found air toxics with cancer risk greater than one in a million are formaldehyde, carbon tetrachloride, acetaldehyde, and benzene. The most frequently occurring binary pairs and ternary mixtures are the various combinations of these four air toxics. Analysis of urban and rural HAPs did not reveal significant differences in the top combinations of these chemicals. The cumulative annual cancer-related health impacts of inhaling the top 10 carcinogenic air toxics included was about 1,600 DALYs in the United States or 0.6 DALYs per 100,000 people. Formaldehyde and benzene together contribute nearly 60 percent of the total cancer-related health impacts. Our study shows that although there are many carcinogenic air toxics, only a few of them affect public health significantly at the national level in the United States, based on the frequency of occurrence of air toxics mixtures and cancer-related public health impacts. Future research is needed on their joint toxicity and cumulative health impacts.
Interplay between MEK-ERK signaling, cyclin D1, and cyclin-dependent kinase 5 regulates cell cycle reentry and apoptosis of neurons

A novel mechanism is described by which neurons reenter the cell cycle, which leads to their apoptosis: β-amyloid peptide activates the MEK-ERK pathway aberrantly, resulting in expression of cyclin D1 and cell death. Cyclin D1, in turn, prevents the activation of neuronal CDK5, which is important for neuronal survival.
Increased release of dopamine in the striata of young adults with hearing impairment and its relevance for the social defeat hypothesis of schizophrenia.

IMPORTANCE An increased risk for psychosis is observed in people with hearing impairment. According to the social defeat hypothesis, the long-term experience of exclusion leads to enhanced baseline activity and/or sensitization of the dopamine system and puts the individual at increased risk for psychosis. OBJECTIVE To investigate whether young adults with severe hearing impairment (SHI) experience more feelings of social defeat, show greater dopamine release in response to dexamphetamine, and report a stronger subjective reaction to this substance than normal-hearing young adults and to examine whether dopamine release is associated with both self-reported social exclusion and dexamphetamine-induced psychotic experiences. DESIGN, SETTING, AND PARTICIPANTS A sample of 19 participants with SHI and 19 smoking-, age-, and sex-matched healthy controls underwent single-photon emission computed tomography with iodine 123-labeled iodobenzamide as a radiotracer before and after an amphetamine challenge at an academic hospital. EXPOSURES Dexamphetamine sulfate (0.3 mg/kg) administered intravenously. MAIN OUTCOMES AND MEASURES Baseline D2/3 receptor binding and endogenous dopamine release. RESULTS The participants with SHI reported experiencing more feelings of social defeat (U=109, z=-2.09, P=.04) and loneliness (U=87.5, z=-2.72, P=<.001) than did healthy controls, but they did not differ from healthy controls with regard to baseline psychotic symptoms (U=156.5, z=-0.70, P=.48). There were no significant group differences in baseline D2/3 receptor binding. However, repeated-measures multivariate analysis of covariance with age (in months) and tobacco smoking (in pack-years) as covariates showed that there was a greater amphetamine-induced striatal dopamine release among the participants with SHI than among the healthy controls (F1,34=4.55, P=.04). After amphetamine administration, the participants with SHI reported more changes in affect than the healthy controls, but not a greater increase in psychotic symptoms. Likewise, reports of social exclusion and an increase in psychotic symptoms were not associated with dopamine release. CONCLUSIONS AND RELEVANCE Our study presents preliminary evidence of dopamine sensitization in a socially excluded group of people with hearing impairment. If replicated by future studies in other excluded groups, this finding may have major implications for our understanding of the underlying mechanism and for prevention of psychotic disorders.
Role of monocytes in the expansion of human activated natural killer cells.

We have studied the mechanisms underlying expansion of recombinant interleukin-2 (rIL-2)-stimulated natural killer (NK) cells in vitro. A population of NK cells expressing the CD56+/CD3-phenotype (98.9% +/- 0.42%) was obtained from normal human peripheral blood mononuclear cells (PBMNC) by fluorescence-activated cell sorting (FACS). Culture of NK cells in media containing rIL-2 (1,000 U/mL) for 18 days resulted in a population of activated NK cells (ANK) with significantly enhanced cytotoxicity, but only 2.6 +/- 0.56-fold expansion of cell number compared with the starting NK population. Culture of starting NK populations and autologous PBMNC in a Transwell system (Costar, Cambridge, MA), providing separation of the two cell populations by a 0.4-microns pore membrane, resulted in a dose-dependent increase in fold expansion of ANK (expansion = 19.9 +/- 4.0-fold; P < .001; n = 22) significantly greater than that observed when NK were cultured alone. Further experiments using the Transwell system showed that the stimulatory effect of autologous PBMNC on ANK progenitor proliferation resides in the CD14+ monocyte fraction (maximal expansion = 14.5 +/- 1.5-fold; n = 17) and not in the CD5+ T-lymphocyte or CD19+ B-lymphocyte fractions. Direct coculture of purified NK and autologous monocytes in the same compartment, thus permitting cell-cell contact, resulted in significantly greater expansion of the ANK population (30.6 +/- 4.7-fold expansion, P < .001; n = 10) than that observed when NK and monocytes were separated by the Transwell membrane. Finally, depletion of PBMNC of cells bearing CD5 and CD8 by panning on antibody-coated plastic flasks resulted in a starting cell population enriched for NK progenitors and for monocytes. Cultures of this resultant population for 18 days in the presence of rIL-2 yielded an ANK population similar to that obtained when CD56+/CD3- cells obtained by FACS were cocultured with autologous monocytes. These results suggest that proliferation of ANK requires autologous monocytes and is in part mediated by humoral factors, but is enhanced when NK and monocytes are in direct cell-cell contact. Depletion of cells bearing CD5 and CD8 from PBMNC is a single efficient method for obtaining a starting population capable of producing large numbers of ANK in culture that may lead to new therapeutic uses for the ANK population.
Adolescents' information-creating behavior embedded in digital Media practice using scratch

This study explores the ways adolescents create information collaboratively in the digital environment. In spite of the current widespread practice of information creation by young people, little research exists to illuminate how youth are engaged in creative information behavior or how they make participatory contributions to the changing information world. The purposefully selected sample includes teenagers who actively produce and share information projects, such as online school magazines, an information‐sharing website in Wiki, and a digital media library, using Scratch—a graphical programming language developed by MIT Media Lab. Qualitative data were collected through group and individual interviews informed by Dervin's Sense‐Making Methodology. The data analysis technique included directed qualitative content analysis with Atlas.ti. Findings reveal the process of information creation, including content development, organization, and presentation of information, as well as noticeable patterns by youth such as visualizing, remixing, tinkering, and gaining a sense of empowerment. This study extends our knowledge of the creative aspects of information behavior.
Efficacy of tomato concentrates in mouse models of dyslipidemia and cancer

We previously reported that adding freeze‐dried tomato powder from transgenic plants expressing the apolipoprotein A‐I mimetic peptide 6F at 2.2% by weight to a Western diet (WD) ameliorated dyslipidemia and atherosclerosis in mice. The same dose in a human would require three cups of tomato powder three times daily. To reduce the volume, we sought a method to concentrate 6F. Remarkably, extracting the transgenic freeze‐dried tomato overnight in ethyl acetate with 5% acetic acid resulted in a 37‐fold reduction in the amount of transgenic tomato needed for biologic activity. In a mouse model of dyslipidemia, adding 0.06% by weight of the tomato concentrate expressing the 6F peptide (Tg6F) to a WD significantly reduced plasma total cholesterol and triglycerides (P < 0.0065). In a mouse model of colon cancer metastatic to the lungs, adding 0.06% of Tg6F, but not a control tomato concentrate (EV), to standard mouse chow reduced tumor‐associated neutrophils by 94 ± 1.1% (P = 0.0052), and reduced tumor burden by two‐thirds (P = 0.0371). Adding 0.06% of either EV or Tg6F by weight to standard mouse chow significantly reduced tumor burden in a mouse model of ovarian cancer; however, Tg6F was significantly more effective (35% reduction for EV vs. 53% reduction for Tg6F; P = 0.0069). Providing the same dose of tomato concentrate to humans would require only two tablespoons three times daily making this a practical approach for testing oral apoA‐I mimetic therapy in the treatment of dyslipidemia and cancer.
Basis pursuit based algorithm for intra-voxel recovering information in DW-MRI

In this work, we applied the basis pursuit (BP) methodology for recovering the intra-voxel information in diffusion weighted MR images (DW-MRI). We compare the proposed BP approach with the diffusion basis function estimation (DBFE) algorithm. DBFE approach was previously applied to recover intra-voxel diffusion information in brain DW-MRI. The intra-voxel information is recovered at voxels that contain axon fiber crosses or bifurcations by means of a linear combination of a known diffusion functions. We state the DBFE solution in the signal decomposition context, i.e., the measured DW-MRI signal is decomposed as a linear combination of signals that belongs to a base of diffusion functions (BDF). In such a BDF, each signal is an M-dimensional vector, where each component indicates the water diffusion coefficient in a known three-dimensional orientation. In this work, we analyze and compare the solution given by DBFE method with the BP methodology. The BP methodology is used in order to select the set of base signals (which are taken from a dictionary) that best explain a given arbitrary signal. Moreover, solution strategies used in the BP and DBFE algorithm are compared and discussed. Examples in synthetic and real images are shown in order to demonstrate the performance of the compared methods.
Discovering graphical Granger causality using the truncating lasso penalty

Motivation: Components of biological systems interact with each other in order to carry out vital cell functions. Such information can be used to improve estimation and inference, and to obtain better insights into the underlying cellular mechanisms. Discovering regulatory interactions among genes is therefore an important problem in systems biology. Whole-genome expression data over time provides an opportunity to determine how the expression levels of genes are affected by changes in transcription levels of other genes, and can therefore be used to discover regulatory interactions among genes. Results: In this article, we propose a novel penalization method, called truncating lasso, for estimation of causal relationships from time-course gene expression data. The proposed penalty can correctly determine the order of the underlying time series, and improves the performance of the lasso-type estimators. Moreover, the resulting estimate provides information on the time lag between activation of transcription factors and their effects on regulated genes. We provide an efficient algorithm for estimation of model parameters, and show that the proposed method can consistently discover causal relationships in the large p, small n setting. The performance of the proposed model is evaluated favorably in simulated, as well as real, data examples. Availability: The proposed truncating lasso method is implemented in the R-package ‘grangerTlasso’ and is freely available at http://www.stat.lsa.umich.edu/∼shojaie/ Contact: shojaie@umich.edu
Loss of a c-Hras-1 AlÃ-eleand Aggressive Human Primary Breast Carcinomas 1

The human I l-ruv protooncogene was shown to be expressed in 16 of 22 invasive ductal carcinomas of the breast. The Kand N-ros protoon cogenes were either not expressed or expressed at low levels. No ampli fication or rearrangement of the three ras genes was detected among the 104 breast carcinoma DNAs tested. These results indicate that the overexpression of H-ras in human breast tumors is not correlated with alteration of the protooncogene. In addition, we did not find any point mutation at the codon 12 of the I l-ru.vor K-ras protooncogenes in 32 and 64, respectively, tumor DNAs examined. However, in tumor DNAs from 14 of 51 patients, heterozygous for I l-ra.v-l related /fumi II restriction fragments, one alÃ-elewas lost. This alÃ-eleloss did not alter rus M, 21,000 protein expression. Correlation with clinicopathological data showed, however, that the loss of one \\-ru\-\ alÃ-elein breast carcinoma DNAs is significantly linked to histolÃ3gica! Grade III tumors, the lack of estrogen and/or progesterone receptors, and the subsequent occurrence of distal metastasis. Our results thus indicate that the loss of one H-ros1 alÃ-elecorrelates with the most aggressive primary carcinomas of the breast.
Diversity and Abundance of Uncultured Cytophaga-Like Bacteria in the Delaware Estuary

ABSTRACT The Cytophaga-Flavobacterium group is known to be abundant in aquatic ecosystems and to have a potentially unique role in the utilization of organic material. However, relatively little is known about the diversity and abundance of uncultured members of this bacterial group, in part because they are underrepresented in clone libraries of 16S rRNA genes. To circumvent a suspected bias in PCR, a primer set was designed to amplify 16S rRNA genes from the Cytophaga-Flavobacterium group and was used to construct a library of these genes from the Delaware Estuary. This library had several novel Cytophaga-like 16S rRNA genes, of which about 40% could be grouped together into two clusters (DE clusters 1 and 2) defined by sequences initially observed only in the Delaware library; the other 16S rRNA genes were classified into an additional four clades containing sequences from other environments. An oligonucleotide probe was designed for the cluster with the most clones (DE cluster 2) and was used in fluorescence in situ hybridization assays. Bacteria in DE cluster 2 accounted for about 10% of the total prokaryotic abundance in the Delaware Estuary and in a depth profile of the Chukchi Sea (Arctic Ocean). The presence of DE cluster 2 in the Arctic Ocean was confirmed by results from 16S rRNA clone libraries. The contribution of this cluster to the total bacterial biomass is probably larger than is indicated by the abundance of its members, because the average cell volume of bacteria in DE cluster 2 was larger than those of other bacteria and prokaryotes in the Delaware Estuary and Chukchi Sea. DE cluster 2 may be one of the more abundant bacterial groups in the Delaware Estuary and possibly other marine environments.
Dispersion-Adaptive First–Last Fit Spectrum Allocation Scheme for Elastic Optical Networks

The quality-of-transmission (QoT) degradation due to the dispersion effect in longer lightpaths is higher than that of shorter lightpaths in a dispersion uncompensated network. To overcome this shortcoming, this letter proposes a dispersion-adaptive first-last fit spectrum allocation scheme for elastic optical networks to decrease the call blocking in the network. The proposed scheme assigns longer lightpath requests from the smallest indexed spectrum slot, where the dispersion effect is less, and shorter lightpath requests from the largest indexed spectrum slot, where the dispersion effect is more. As a result, a less robust modulation technique is used to maintain the QoT threshold level for the longer lightpath requests, and hence a lower number of spectrum slots are required for lightpath establishment. Simulation results show that the proposed scheme outperforms the conventional scheme in terms of blocking probability and contiguous aligned available slot ratio.