Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans

The regulation of cell migration is essential to animal development and physiology. Heparan sulfate proteoglycans shape the interactions of morphogens and guidance cues with their respective receptors to elicit appropriate cellular responses. Heparan sulfate proteoglycans consist of a protein core with attached heparan sulfate glycosaminoglycan chains, which are synthesized by glycosyltransferases of the exostosin (EXT) family. Abnormal HS chain synthesis results in pleiotropic consequences, including abnormal development and tumor formation. In humans, mutations in either of the exostosin genes EXT1 and EXT2 lead to osteosarcomas or multiple exostoses. Complete loss of any of the exostosin glycosyltransferases in mouse, fish, flies and worms leads to drastic morphogenetic defects and embryonic lethality. Here we identify and study previously unavailable viable hypomorphic mutations in the two C. elegans exostosin glycosyltransferases genes, rib-1 and rib-2. These partial loss-of-function mutations lead to a severe reduction of HS levels and result in profound but specific developmental defects, including abnormal cell and axonal migrations. We find that the expression pattern of the HS copolymerase is dynamic during embryonic and larval morphogenesis, and is sustained throughout life in specific cell types, consistent with HSPGs playing both developmental and post-developmental roles. Cell-type specific expression of the HS copolymerase shows that HS elongation is required in both the migrating neuron and neighboring cells to coordinate migration guidance. Our findings provide insights into general principles underlying HSPG function in development.
Combined Impact of NBTI Aging and Process Variations on Noise Margins of Flip-Flops

The estimation of dependable noise margins in digital cells is increasingly significant as nano-scale CMOS technology is facing true reliability issues. On one hand, a major concern comes from circuit aging mechanisms, such as NBTI, which degrade the reliability of circuit operation over time. On the other hand, variability in technology parameters results in affecting reliability. The impact of such phenomena is particularly related to the noise margins in the memory elements of a design, since a wrong stored logic value results in an upset of the system state. This work quantifies and compares the joint effect of process variations and of NBTI aging over the years on the real noise margins of several flip-flop cells. The huge amount of transistor level Monte Carlo simulations produced both nominal (i.e. average) values and associated standard deviations of the noise margins of the selected flip-flops. A possible concept of utilization of the acquired noise margin data is also reported.
T-Cell Activation Marker Expression on Tumor-Infiltrating Lymphocytes As Prognostic Factor in Cutaneous Malignant Melanoma

The central role of T cells in antitumor immunity is well established. However, tumor progression, often seen in the presence of substantial lymphocytic infiltration, suggests that these T cells are not capable of mounting an effective immune response to control tumor growth. Evidence has accumulated that T lymphocytes infiltrating human neoplasms are functionally defective, incompletely activated, or anergic. Therefore, when characterizing the immune competent cells within lymphoid infiltrates of tumors, it is important to assess their activation state. We investigated the expression of two T-cell activation markers, interleukin 2 receptor α (CD25) and OX40 (CD134), by immunohistochemistry in primary cutaneous melanoma samples of 76 patients and analyzed it in relation to tumor stage and tumor progression (>5 years follow-up), as well as to patients’ survival. We found that the degree of infiltration by CD25+ and intratumoral OX40+ lymphocytes showed a tendency to decrease in thicker melanomas. The frequency of samples with high numbers of peritumoral CD25+ and OX40+ cells was significantly lower (P = 0.0009 and P = 0.0087, respectively) in melanomas developing distant visceral metastases, compared with nonmetastatic or lymph node metastatic tumors. For both activation markers studied, high peritumoral densities were associated with longer survival by univariate analysis (P = 0.0028 and P = 0.0255 for CD25 and OX40, respectively), whereas peritumoral OX40+ lymphocyte infiltration had an impact on survival also in multivariate analysis (P = 0.035). The results suggest that the presence of lymphocytes expressing the T-cell activation markers CD25 or OX40 shows correlation with tumor progression as well as with patients’ survival in cutaneous malignant melanoma.
Exploring Inflammatory Asthma Phenotypes: Proteomic Signatures in Serum and Induced Sputum

Asthma drug responses may differ due to inflammatory mechanisms triggered by the immune cells in the pulmonary microenvironment. Thus, asthma phenotyping based on the local inflammatory profile may aid in treatment definition and the identification of new therapeutic targets. Here, we investigated protein profiles of induced sputum and serum from asthma patients classified into eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma, according to inflammatory phenotypes. Proteomic analyses were performed using an ultra-performance liquid chromatography (ultra-HPLC) system coupled to the Q Exactive Hybrid Quadrupole Orbitrap Mass Spectrometer. Fifty-two (52) proteins showed significant differences in induced sputum among the groups, while only 12 were altered in patients’ sera. Five proteins in the induced sputum were able to discriminate all phenotypic groups, while four proteins in the serum could differentiate all except the neutrophilic from the paucigranulocytic inflammatory pattern. This is the first report on comparative proteomics of inflammatory asthma phenotypes in both sputum and serum samples. We have identified a potential five-biomarker panel that may be able to discriminate all four inflammatory phenotypes in sputum. These findings not only provide insights into potential therapeutic targets but also emphasize the potential for personalized treatment approaches in asthma management.
Postnatal corneal transparency, keratocyte cell cycle exit and expression of ALDH1A1.

PURPOSE Recent studies have shown that rabbit corneal keratocytes abundantly express two water-soluble proteins, transketolase (TKT) and aldehyde dehydrogenase class 1A1 (ALDH1A1), in vivo and that these proteins may contribute to corneal transparency at the cellular level. The purpose of this study was to determine the relationship between the expression of these proteins and the development of postnatal corneal transparency. METHODS Rabbits 1 day to 42 days of postnatal age were evaluated by in vivo confocal microscopy (CM) to measure corneal epithelial thickness, stromal thickness, and corneal haze. Selected corneas were then processed for immunocytochemistry and Western and Northern blot analyses, to determine stromal cell density, cell cycle entry, and expression of ALDH1A1 and TKT. RESULTS Quantitative measurement of corneal haze showed that the postnatal cornea was hazy after birth and became transparent during the first weeks after eyelid opening. Development of transparency was associated with decreased cytoplasmic light-scattering from postnatal corneal stromal cells, with the appearance of nuclear light-scattering after eyelid opening. Four days after birth, stromal cell density decreased rapidly, and the cells became quiescent, showing decreased staining by Ki67, a cell cycle marker. Whereas expression of TKT showed a gradual increase after birth, ALDH1A1 showed a marked increase after eyelid opening, and the combined expression significantly correlated with the reduction in light-scattering by postnatal stromal cells. CONCLUSIONS The data suggest that development of postnatal corneal transparency is associated with decreased keratocyte density and quiescence and the expression of TKT/ALDH1A1.
Use of Pulsed-Field Gel Electrophoresis and Flagellin Gene Typing in Identifying Clonal Groups ofCampylobacter jejuni and Campylobacter coli in Farm and Clinical Environments

ABSTRACT Although campylobacters have been isolated from a wide range of animal hosts, the association between campylobacters isolated from humans and animals in the farm environment is unclear. We used flagellin gene typing and pulsed-field gel electrophoresis (PFGE) to investigate the genetic diversity among isolates from animals (cattle, sheep, and turkey) in farm environments and sporadic cases of campylobacteriosis in the same geographical area. Forty-eight combinedfla types were seen among the 315 Campylobacterisolates studied. Six were found in isolates from all four hosts and represented 50% of the total number of isolates. Seventy-one differentSmaI PFGE macrorestriction profiles (mrps) were observed, with 86% of isolates assigned to one of 29 different mrps. Fifty-seven isolates from diverse hosts, times, and sources had an identicalSmaI mrp and combined fla type. Conversely, a number of genotypes were unique to a particular host. We provide molecular evidence which suggests a link between campylobacters in the farm environment with those causing disease in the community.
Extensive Chromosomal Repatterning and the Evolution of Sterility Barriers in Hybrid Sunflower Species

New species may arise via hybridization and without a change in ploidy. This process, termed homoploid hybrid speciation, is theoretically difficult because it requires the development of reproductive barriers in sympatry or parapatry. Theory suggests that isolation may arise through rapid karyotypic evolution and/or ecological divergence of hybrid neospecies. Here, we investigate the role of karyotypic change in homoploid hybrid speciation by generating detailed genetic linkage maps for three hybrid sunflower species, Helianthus anomalus, H. deserticola, and H. paradoxus, and comparing these maps to those previously generated for the parental species, H. annuus and H. petiolaris. We also conduct a quantitative trait locus (QTL) analysis of pollen fertility in a BC2 population between the parental species and assess levels of pollen and seed fertility in all cross-combinations of the hybrid and parental species. The three hybrid species are massively divergent from their parental species in karyotype; gene order differences were observed for between 9 and 11 linkage groups (of 17 total), depending on the comparison. About one-third of the karyoypic differences arose through the sorting of chromosomal rearrangements that differentiate the parental species, but the remainder appear to have arisen de novo (six breakages/six fusions in H. anomalus, four breakages/three fusions in H. deserticola, and five breakages/five fusions in H. paradoxus). QTL analyses indicate that the karyotypic differences contribute to reproductive isolation. Nine of 11 pollen viability QTL occur on rearranged chromosomes and all but one map close to a rearrangement breakpoint. Finally, pollen and seed fertility estimates for F1's between the hybrid and parental species fall below 11%, which is sufficient for evolutionary independence of the hybrid neospecies.
A game-theoretic approach to quality control for collecting privacy-preserving data

We consider the design of an incentive mechanism for a principal, who is assumed to be not trustworthy, to collect informative data from privacy-sensitive individuals. The principal offers payments to incentivize participation and informative data reporting. The individuals are strategic and take into account both the payment and the cost for privacy loss during data reporting. Due to privacy concerns, an individual may be willing to report only a “noisy” version of the private data, resulting in quality degradation. To achieve desirable accuracy of data analysis, it is imperative for the principal to have an incentive mechanism under which the quality of the collected data is controllable. In this paper, we exploit a game-theoretic approach to the design of a payment mechanism, such that the quality of the collected data is controllable through a parameter ε by making sure that each individual's strategy in a Nash equilibrium is to participate and symmetrically randomize her data, while guaranteeing ε-differential privacy. With this design, the principal can achieve any given accuracy objective by using the payment mechanism associated with an appropriate ε. In contrast to most of the existing work, which considers trusted principal and thus focuses on designing truthful mechanisms, this work is the first one to consider untrustworthy principal in private data collection and quality control mechanisms in such a scenario. We also show that the total expected payment of the designed mechanism at equilibrium is asymptotically optimal in the high data quality regime.
Soil Amendments to Reduce Bioavailability of Metals in Soils: Experimental Studies and Spectroscopic Verification

Abstract : The overall objective of this study was to attempt to remediate metal-contaminated soils by finding an amendment or combination of amendments that could be applied and reduce chemical lability and bioavailability. We located three soils that were contaminated with at least of the metals Pb, Cd, Cr, and As. The soils were characterized for an array of chemical and physical properties including total metals. All soils had a mixture of metals requiring attention, and made the remediation challenge much greater because the chemistry of each metal was quite different from the others. Our approach to finding remediation solution using in situ amendments was to sequentially address the metals with additives known to target at least one metal. We then examined the soils for chemical lability (concentrations of metals removed from the soil by an extractant), bioaccessibility (metals available for removal from the soil by a sequence of extractants demonstrated to be correlated with availability to a given organism), and biotoxicity. Orthophosphate is a known, successful amendment for Pb, and this was our first amendment. Quite predictably, the addition of orthosphosphate decreased Pb but greatly increased As and sometimes Cr concentrations. Therefore, our challenge was to find additional amendments that could suppress the other metals without impacting the effect of phosphate on Pb. In laboratory studies, combinations of chemical amendments, including rare earth elements, Mn and P, were added to soil with low redox potential to reduce the bioaccessible fraction of As, Cr, Cd and Pb. Lanthanum and Ce were able to form low solubility precipitates with As, as determined in aqueous solutions. Spectroscopic studies confirmed that LaAsO4(s) can form under pH conditions as low as 2.2.
Evaluation of chlorine dioxide based product as a hatchery sanitizer

&NA; Formaldehyde is commonly used to overcome contaminants introduced by hatching eggs or water supply in the hatcher cabinets. However, health risks associated with its use make economical alternatives important. This project evaluated a chlorine dioxide based product (CDBP) (0.3% concentrate) as a hatchery sanitizer in decontaminating microbial populations on the shell surface of hatching eggs (>18 d old), as well as its impact on hatchability and chick performance. Hatchers (0.20 m2) designed to hold approximately 50 eggs and equipped with circulation fans, heaters, and thermostats were used for the evaluation. For each of the 2 trials conducted, 450 hatching eggs were obtained and incubated in a common setter. Eggs used in trial 1 were floor eggs whereas in trial 2 nest eggs were used. On d 18 of incubation, eggs were removed from the setter, and viable eggs were randomly allocated to 9 hatchers. Pre‐treatment egg rinse samples (10 eggs per hatcher) were collected for initial microbial analysis. Three hatchers were treated with CDBP and 3 hatchers with a formaldehyde based product (FBP). Three untreated hatchers served as control (C). Prior to hatch, 10 eggs/incubator, not previously rinsed, were used for post treatment microbial counts. The hatched chicks were reared until d 21 in floor pens with a common starter diet. For the CDBP treated eggs, hatchability and chick performance (weight gains, mortality, and FCR on d 7 and d 21) were similar to the other treatments. The application rate of CDBP evaluated in this study was not an effective antimicrobial alternative to formaldehyde for sanitizing hatching eggs in hatcher cabinets prior to hatch.
Sem1, the yeast ortholog of a human BRCA2-binding protein, is a component of the proteasome regulatory particle that enhances proteasome stability

Degradation of polyubiquitinated proteins by the proteasome often requires accessory factors; these include receptor proteins that bind both polyubiquitin chains and the regulatory particle of the proteasome. Overproduction of one such factor, Dsk2, is lethal in Saccharomyces cerevisiae and we show here that this lethality can be suppressed by mutations in SEM1, a gene previously recognized as an ortholog of the human gene encoding DSS1, which binds the BRCA2 DNA repair protein. Yeast sem1 mutants accumulate polyubiquitinated proteins, are defective for proteasome-mediated degradation and cannot grow under various stress conditions. Moreover, sem1 is synthetically lethal with mutations in proteasome subunits. We show that Sem1 is a component of the regulatory particle of the proteasome, specifically the lid subcomplex. Loss of Sem1 impairs the stability of the 26S proteasome and sem1Δ defects are greatly enhanced by simultaneous deletion of RPN10. The Rpn10 proteasome subunit appears to function with Sem1 in maintaining the association of the lid and base subcomplexes of the regulatory particle. Our data suggest a potential mechanism for this protein-protein stabilization and also suggest that an intact proteasomal regulatory particle is required for responses to DNA damage.
The Role of Rhythm in Speech and Language Rehabilitation: The SEP Hypothesis

For thousands of years, human beings have engaged in rhythmic activities such as drumming, dancing, and singing. Rhythm can be a powerful medium to stimulate communication and social interactions, due to the strong sensorimotor coupling. For example, the mere presence of an underlying beat or pulse can result in spontaneous motor responses such as hand clapping, foot stepping, and rhythmic vocalizations. Examining the relationship between rhythm and speech is fundamental not only to our understanding of the origins of human communication but also in the treatment of neurological disorders. In this paper, we explore whether rhythm has therapeutic potential for promoting recovery from speech and language dysfunctions. Although clinical studies are limited to date, existing experimental evidence demonstrates rich rhythmic organization in both music and language, as well as overlapping brain networks that are crucial in the design of rehabilitation approaches. Here, we propose the “SEP” hypothesis, which postulates that (1) “sound envelope processing” and (2) “synchronization and entrainment to pulse” may help stimulate brain networks that underlie human communication. Ultimately, we hope that the SEP hypothesis will provide a useful framework for facilitating rhythm-based research in various patient populations.
Tradeoffs in Elastographic Imaging

This paper presents the tradeoffs in elastographic imaging. Elastography is viewed as a new imaging modality and presented in terms of three fundamental concepts that constitute the basis for the elastographic imaging process. These are the tissue elastic deformation process, the statistical analysis of strain estimation and the image characterization. The first concept involves the use of the contrast transfer efficiency (CTE) that describes the mapping of a distribution of local tissue elastic moduli into a distribution of local longitudinal tissue strains. The second concept defines the elastographic system and the relationship between ultrasonic and signal processing parameters. This process is described in terms of a stochastic framework (the strain filter) that provides upper and practical performance bounds and their dependence on the various system parameters. Finally, the output image, the elastogram, is characterized by its image parameters, such as signal-to-noise ratio, contrast-to-noise ratio, dynamic range and resolution. Finite-element simulations are used to generate examples of elastograms that are confirmed by the theoretical prediction tools.
Broadening the Application of Evolutionarily Based Genetic Pest Management

Abstract Insect- and tick-vectored diseases such as malaria, dengue fever, and Lyme disease cause human suffering, and current approaches for prevention are not adequate. Invasive plants and animals such as Scotch broom, zebra mussels, and gypsy moths continue to cause environmental damage and economic losses in agriculture and forestry. Rodents transmit diseases and cause major pre- and postharvest losses, especially in less affluent countries. Each of these problems might benefit from the developing field of Genetic Pest Management that is conceptually based on principles of evolutionary biology. This article briefly describes the history of this field, new molecular tools in this field, and potential applications of those tools. There will be a need for evolutionary biologists to interact with researchers and practitioners in a variety of other fields to determine the most appropriate targets for genetic pest management, the most appropriate methods for specific targets, and the potential of natural selection to diminish the effectiveness of genetic pest management. In addition to producing environmentally sustainable pest management solutions, research efforts in this area could lead to new insights about the evolution of selfish genetic elements in natural systems and will provide students with the opportunity to develop a more sophisticated understanding of the role of evolutionary biology in solving societal problems.
Lost Relatives of the Gumbel Trick

© 2017 International Machine Learning Society (IMLS). All rights reserved. The Gumbel trick is a method to sample from a discrete probability distribution, or to estimate its normalizing partition function. The method relies on repeatedly applying a random perturbation to the distribution in a particular way, each time solving for the most likely configuration. We derive an entire family of related methods, of which the Gumbel trick is one member, and show that the new methods have superior properties in several settings with minimal additional computational cost. In particular, for the Gumbel trick to yield computational benefits for discrete graphical models, Gumbel perturbations on all configurations are typically replaced with socalled low-rank perturbations. We show how a subfamily of our new methods adapts to this setting, proving new upper and lower bounds on the log partition function and deriving a family of sequential samplers for the Gibbs distribution. Finally, we balance the discussion by showing how the simpler analytical form of the Gumbel trick enables additional theoretical results.
Visible Light Communication System Using an Organic Bulk Heterojunction Photodetector

A visible light communication (VLC) system using an organic bulk heterojunction photodetector (OPD) is presented. The system has been successfully proven indoors with an audio signal. The emitter consists of three commercial high-power white LEDs connected in parallel. The receiver is based on an organic photodetector having as active layer a blend of poly(3-hexylthiophene) (P3HT) and phenyl C61-butyric acid methyl ester (PCBM). The OPD is opto-electrically characterized, showing a responsivity of 0.18 A/W and a modulation response of 790 kHz at −6 V.