Miracle-dz/UniFAR-FTUs huggingface dataset:
Bronchoalveolar cells in advanced pulmonary sarcoidosis.

We performed bronchoalveolar lavage (BAL) in 120 subjects: 94 patients with sarcoidosis, 11 patients with idiopathic pulmonary fibrosis (IPF), and 15 normal volunteers. By counting cells and comparing the results with those from control subjects, we found a high percentage of lymphocytes in BAL fluid from all patients with sarcoidosis and a high percentage of neutrophils (NE) in BAL fluid from patients with IPF. In addition, we observed a significantly higher proportion of NE in the 14 patients with advanced sarcoidosis (i.e., fibrosis and bullous radiological patterns), than was seen in the 80 patients with early stages of involvement (i.e., bilateral hilar lymphadenopathy and/or pulmonary infiltrations) (p less than 0.001). The NE count exceeded the normal value of 3.5% in 9 of the 14 patients with advanced sarcoidosis but only in 1 of the 80 patients with early disease (p less than 0.001). We believe that advanced sarcoidosis is one of the conditions in which a simultaneous increase in both NE and lymphocytes in BAL fluid can be observed. The NE count in bronchoalveolar fluid in patients with sarcoidosis, as in patients with IPF, may indicate evolution of the granulomatous process toward pulmonary fibrosis. These phenomena point out the potential practical value of iterative BAL in patients with sarcoidosis in assessing the prognosis of their disease.
Aggressive differentiated thyroid cancer with multiple metastases and NRAS and TERT promoter mutations: A case report

Sorafenib, a tyrosine kinase inhibitor, is approved for the treatment of advanced differentiated thyroid carcinoma (DTC). Resistance to sorafenib may appear under treatment and may be associated with increased aggressiveness of the neoplasia. The present study reports the case of a 65-year-old male who underwent total thyroidectomy for a follicular thyroid carcinoma, Hürthle cell variant, in February 2005. Until January 2010, the patient received four consecutive 131I doses (total dose, 612 mCi) for increased serum thyroglobulin (Tg) and initial faint lung uptake (which eventually became undetectable). Subsequently, the patient developed several sequential bone (humerus, rib and skull), adrenal and lung metastases, the majority of which were surgically removed. Histological examination in all cases revealed evidence of DTC metastases that were strongly positive for Tg, as revealed by immunohistochemistry. In March 2014, sorafenib therapy was initiated, but it was discontinued 10 months later to allow an undelayable prostatectomy. Immediately upon surgery, the patient developed a large metastatic lesion in the right gluteal muscle, whose biopsy revealed undifferentiated neoplasia of epithelial origin, and the patient succumbed shortly afterwards. An extensive comparative search for biochemical and molecular markers was performed on all available tissues (primary tumor, and differentiated and undifferentiated metastases). The primary tumor and all the available metastases exhibited the same molecular oncogenic markers (namely, the RAS mutation p.Q61R and the telomerase promoter mutation C228T). In addition, the undifferentiated metastasis exhibited a p53 mutation. The present study reports a case of a sudden acceleration of DTC metastatic progression following sorafenib discontinuation, which could have been due to the emergence of sorafenib-resistant undifferentiated p53-positive tumor cell clones.
The Effects of Dietary Myoinositol on Lung Tumor Development in Tobacco Smoke-Exposed Mice

The purpose of these experiments was to investigate whether a diet containing myoinositol could prevent the development of tobacco smoke-induced lung tumors in strain A/J mice. In a positive control experiment, 1% and 3% of myoinositol in AIN-93 diet reduced the development of lung tumors induced by NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] by 69% and 75%. In animals exposed for 5 mo, 6 h/day, 5 days/wk, to a mixture of tobacco sidestream and mainstream smoke, and then fed myoinositol-containing diets once smoke exposure had ceased, no chemopreventive effect was observed. When animals were fed myoinositol during both tobacco smoke exposure and the recovery period, a slight but statistically not significant reduction in tumor multiplicities was found. It was concluded that myoinositol has less chemopreventive activity against the full complex mixture of tobacco smoke than it has against selected constituents such as NNK or benzo[a]pyrene.
Differential Interleukin-10 and Gamma Interferon mRNA Expression in Lungs of Cilium-Associated Respiratory Bacillus-Infected Mice

ABSTRACT The cilium-associated respiratory (CAR) bacillus is a gram-negative, extracellular bacterium that causes persistent respiratory tract infections in rodents. We have previously demonstrated that BALB/c mice are more susceptible to CAR bacillus-induced disease than resistant C57BL/6 mice, with elevations in pulmonary gamma interferon (IFN-γ) and interleukin (IL)-4. IL-10 is a type 2 cytokine that can increase host susceptibility to bacterial diseases through its anti-inflammatory effects, including suppression of macrophage function. The purpose of this study was to further describe the cytokine profiles associated with histologic lesions in CAR bacillus-infected mice and to assess the effects of cytokine depletion on the pathogenesis of disease. Six-week-old female BALB/c and C57BL/6 mice and mice with targeted mutations in IFN-γ and IL-4 were inoculated intratracheally with 105 CAR bacillus organisms, and samples were collected at 6 to 7 weeks postinoculation. Lung samples were collected for histopathologic examination and analysis of cytokine mRNA. IFN-γ, IL-10, and IL-4 mRNA levels in the lungs of infected mice were semiquantitatively measured using a reverse transcriptase-mediated PCR assay and compared to those in uninfected control animals of each strain. BALB/c mice infected with CAR bacillus had a median lung lesion score of 6 and IL-10 and IL-4 mRNA levels were significantly elevated. The majority of C57BL/6 mice were resistant to disease characterized by lung lesions scores of 2 or less and a dominant IFN-γ mRNA cytokine profile. A few C57BL/6 mice with lesions scores of 5 or greater had elevations in all three cytokines and were susceptible to disease. C57BL/6 IFN-γ knockout mice had increased disease with elevations in IL-10 and IL-4 mRNA, while BALB/c IL-4 knockout mice infected with CAR bacillus had a mild decrease in lesion severity and an attenuated IL-10 mRNA expression compared to wild-type BALB/c mice. These data indicate that IL-10 and IL-4 predominate in CAR bacillus-induced histologic lesions in mice, while IFN-γ may play a role in resistance to disease.
Predicate-Oriented Database Search Algorithms

Abstract : The principal application of this thesis will be in the area of automatic programming. The purpose of that branch of computer science has been to discover how automatic algorithms can be developed which do much of the programming that has traditionally been assigned to human beings. Such automatic algorithms have been advocated by many computer scientists because these procedures would dramatically reduce the cost of writing computer programs. The combined work of the cited authors have shown that; (i) the cost of developing computer software may greatly exceed hardware costs in the 1980's (Boehm has estimated that computer programmer labor costs will constitute 90 percent of all the Air Force's 1985 computer-related expenditures), (ii) and that the health of the computer industry requires lower software development costs (even if this is done in the context of a trade-off that modestly increases the hardware costs). The importance of automatic database search algorithms was further confirmed in a recent panel discussion. The members of that panel concluded that such automatic search algorithms would be extremely useful if these algorithms could be made to be moderately efficient. This thesis will lay the foundations of the theory that should be used in the development of automatic predicate searching algorithms.
When structure leads to sex: Untangling signals in population genetic data sets

A robust signal of population structure often provides the first glimpse into the evolutionary history of a species and its populations. In this issue of Molecular Ecology, new work from Louis Bernatchez's group (Benestan et al., ) starts with an investigation of apparent structure in two marine species and concludes with an identification of sex‐linked genes, and in the process provides a model for robust analysis. Structure is the genetic signal left by natural selection as well as by neutral processes like migration and gene flow. Neutral areas of the genome can reveal the geographical relationships and related gene flow between populations over time and space, while selection can resist the natural genomic turnover created by recombination and generate adaptive structure between populations that can be detected. However, artefacts in a data set can easily hide the true signal of structure; mutation, whether it is a true appearance of a recent, minor allele, or more commonly, an error in SNP calling or molecular library construction, can easily conceal patterns of population structure (e.g., geographical structure in mackerel, Rodriguez‐Ezpeleta et al. ( )). A demographic structure that results from the most “forceful” evolutionary processes can overwhelm another signal generated by other, unrelated phenotypes. For example, the structure among diverged freshwater and marine threespine stickleback populations results from such strong selection and linkage disequilibrium across the genome that it impairs the ability to disentangle the genetic basis of particular evolved morphological traits (e.g., opercle development, Alligood ( )). Finally, there might be conflicting inferences for what underlies structure patterns. Structure may be created by differential patterns of meiotic recombination, and genetic maps are a reliable means for identifying genomic regions that resist recombination. But, without additional information (Anderson et al., ), it can be difficult to distinguish the recombination‐suppressing effect of a segregating genomic inversion (Small et al., ) from that of sex‐linked selection.
FMR2 function: insight from a mouse knockout model

The FMR2 gene is dysregulated by the fragile X E triplet repeat expansion in patients with FRAXE mental retardation syndrome. A CCG triplet, located in the 5′ untranslated region of the FRAXE gene undergoes expansion and methylation in these patients, eliminating detectable gene transcription. FRAXE syndrome is distinct from fragile X syndrome, a more common genetic form of mental retardation caused by expansion and methylation of a similar repeat in the FMR1 gene located 600 kb proximal to FRAXE. FRAXE syndrome is rare, and patients’ phenotypes are highly variable, leading to difficulties with predicting specific FMR2 functions based on the human disease. Recently, Lilliputian(Lilli), a Drosophila FMR2 orthologue, was identified; this gene has been linked with several signal transduction pathways, including the transforming growth factor-β (TGF-β) pathway, the Raf/MEK/MAP kinase (MAPK) pathway, and the P13K/PKB pathway. Mutation of Lilli shows defects in germinal band extension, cytoskeletal structure, cell growth, and organ development. The Lilli gene suggests possible functions for FMR2 (and related genes) in humans and mice, but cannot predict specific functions. Modeling Fmr2 mutation in the mouse will be useful to understand specific functions of this gene in vertebrates. This review presents what has been learned thus far from the Fmr2 knockout mouse model and suggests future studies on this model in order to compare it with the human FRAXE mental retardation disorder, Lilli mutants in Drosophila and other mouse models of genes in this family.
A critical role for adiponectin‐mediated development of endometrial luminal epithelial cells during the peri‐implantation period of pregnancy

Adiponectin is one of the adipokines in the collagen superfamily. It is secreted primarily by white adipocytes and influences reproductive processes including ovarian and uterine functions. Adiponectin regulates energy homeostasis, insulin sensitivity, and is anti‐inflammatory in various tissues. Its receptors (ADIPOR1 and ADIPOR2) are widely expressed in mammalian tissues, including porcine conceptuses and endometrial during the estrous cycle and peri‐implantation period of pregnancy. However, regulatory effects of adiponectin on endometrial epithelial cells are unknown. Therefore, we investigated the effects of parity on expression of ADIPOR1 and ADIPOR2 and the effects of adiponectin in the porcine endometrium during early pregnancy. Results of this study revealed robust expression of ADIPOR1 and ADIPOR2 in uterine luminal (LE) and glandular (GE) epithelia during early pregnancy and expression decreased as with increasing parity. For porcine luminal epithelial (pLE) cells, adiponectin enhanced proliferation, and increased phosphorylation of AKT, P70S6K, S6, ERK1/2, JNK, P38, and P90RSK in a time‐dependent manner. Moreover, the abundance of adiponectin‐activated signaling molecules were suppressed by pharmacological inhibitors including wortmannin, U0126, SP600125, and SB203580, respectively, in pLE cells. Furthermore, inhibition of each targeted signal transduction molecule influenced proliferation of adiponectin‐stimulated pLE cells. In addition, adiponectin inhibited tunicamycin‐induced endoplasmic reticulum (ER)‐stress through effects on ER stress regulated proteins in pLE cells. Collectively, these results suggest that adiponectin affects development of porcine uterine epithelia and reproductive performance through modulation of PI3K/AKT and MAPK cell signaling pathways.
Expressive Speech Driven Talking Avatar Synthesis with DBLSTM Using Limited Amount of Emotional Bimodal Data

One of the essential problems in synthesizing expressive talking avatar is how to model the interactions between emotional facial expressions and lip movements. Traditional methods either simplify such interactions through separately modeling lip movements and facial expressions, or require substantial high quality emotional audio-visual bimodal training data which are usually difficult to collect. This paper proposes several methods to explore different possibilities in capturing the interactions using a large-scale neutral corpus in addition to a small size emotional corpus with limited amount of data. To incorporate contextual influences, deep bidirectional long short-term memory (DBLSTM) recurrent neural network is adopted as the regression model to predict facial features from acoustic features, emotional states as well as contexts. Experimental results indicate that the method by concatenating neutral facial features with emotional acoustic features as the input of DBLSTM model achieves the best performance in both objective and subjective evaluations.
Predicting bird habitat quality from a geospatial analysis of FIA data

The ability to assess the influence of site-scale forest structure on avian habitat suitability at an ecoregional scale remains a major methodological constraint to effective biological planning for forest land birds in North America. We evaluated the feasibility of using forest inventory and analysis (FIA) data to define vegetation structure within forest patches, which were delineated from independent geospatial data sets of ecological subsection, forest type, and landform class. We used Swainson? s warbler (Limnothlypis swainsonii, Audubon) as a model to demonstrate how to integrate FIA data with geospatial data sets to estimate and monitor habitat suitability for a priority bird species in the West Gulf Coastal Plain/Ouachita Mountains Bird Conservation Region.
An ALMA view of the interstellar medium of the z = 4.77 lensed starburst SPT-S J213242-5802.9

We present ALMA detections of the [NII] 205 μm and CO(12−11) emission lines, and the tentative detection of [CI] ^3P_1–^3P_0 for the strongly lensed (μ = 5.7 ± 0.5) dusty, star-forming galaxy SPT-S J213242-5802.9 (hereafter SPT2132-58) at z = 4.77. The [NII] and CO(12−11) lines are detected at 11.5 and 8. 5σ levels, respectively, by our band 6 observations. The [CI] line is detected at 3. 2σ after a reanalysis of existing band 3 data. The [CI] luminosity implies a gas mass of (3.8 ± 1.2) × 10^(10)M_⊙, and, consequently, a very short depletion timescale of 34 ± 13 Myr and a CO luminosity to gas mass conversion factor α_(CO) of 1.0 ± 0.3 M_⊙ (K km s^(-1) pc^2)^(-1). SPT2132-58 is an extreme starburst with an intrinsic star formation rate of 1100 ± 200 M_⊙/yr. We find a [CII]/[NII] ratio of 26 ± 6, which is the highest ratio reported at z > 4. This suggests that SPT2132-58 hosts an evolved interstellar medium (0.5 Z_⊙< Z < 1.5 Z_⊙), which may be dominated by photodissociation regions. The CO(2−1) and CO(5−4) transitions have lower CO to far-infrared ratios than local and high-redshift samples, while CO(12−11) is similar to these samples, suggesting the presence of an additional very excited component or an active galactic nucleus.
TP 53 intron 1 hotspot rearrangements are specific to sporadic osteosarcoma and can cause Li-Fraumeni syndrome

Somatic mutations of TP53 are among the most common in cancer and germline mutations of TP53 (usually missense) can cause Li-Fraumeni syndrome (LFS). Recently, recurrent genomic rearrangements in intron 1 of TP53 have been described in osteosarcoma (OS), a highly malignant neoplasm of bone belonging to the spectrum of LFS tumors. Using whole-genome sequencing of OS, we found features of TP53 intron 1 rearrangements suggesting a unique mechanism correlated with transcription. Screening of 288 OS and 1,090 tumors of other types revealed evidence for TP53 rearrangements in 46 (16%) OS, while none were detected in other tumor types, indicating this rearrangement to be highly specific to OS. We revisited a four-generation LFS family where no TP53 mutation had been identified and found a 445 kb inversion spanning from the TP53 intron 1 towards the centromere. The inversion segregated with tumors in the LFS family. Cancers in this family had loss of heterozygosity, retaining the rearranged allele and resulting in TP53 expression loss. In conclusion, intron 1 rearrangements cause p53-driven malignancies by both germline and somatic mechanisms and provide an important mechanism of TP53 inactivation in LFS, which might in part explain the diagnostic gap of formerly classified “TP53 wild-type” LFS.
Electrochemical approach for constructing a monolayer of thiophenolates from grafted multilayers of diaryl disulfides.

An electrochemical approach is presented for constructing a monolayer or near monolayer of molecules on conducting surfaces by degradation of a multilayer film formed via reduction of aryldiazonium salts. Usually, grafting of surfaces employing aryldiazonium salts results in the formation of intertwined multilayers in a difficult controllable polymerization reaction. However, if the chemical system selected contains a cleavable group, a subsequent degradation of the polymeric network may allow the formation of a thin reactive molecular layer. As chemical systems, diazonium salts of diaryl disulfides (ArSSAr) were selected to produce surface-confined thiophenolates, but an extension of the approach to include other functionalities is straightforward. The thiophenolates (ArS-) may be reversibly oxidized to disulfides to establish a covalently attached ArSSAr/ArS- redox pair at the surface. Analysis of the surfaces was carried out by means of cyclic voltammetry, X-ray photoelectron spectroscopy, and atomic f.
Placental Growth Throughout the Last Two Thirds of Pregnancy in Sheep: Vascular Development and Angiogenic Factor Expression1

Abstract Morphometric methodologies were developed and applied to investigate the patterns of vascular development in maternal (caruncular; CAR) and fetal (cotyledonary; COT) sheep placentas throughout the last two thirds of gestation. We also examined the expression levels of the major angiogenic factors and their receptors in CAR and COT sheep placentas. Although the vascularity of the CAR tissues increased continuously from Day 50 through Day 140 of pregnancy, those of the COT tissues increased at about twice the instantaneous rate (i.e., the proportionate increase/day) of the CAR. For CAR, vascularity increased 2-fold from Day 50 through Day 140 via relatively small increases in capillary number and 2- to 3-fold increases in capillary diameter. For COT, the increased vascularity resulted from a 12-fold increase in capillary number associated with a concomitant 2-fold decrease in capillary diameter. This large increase in fetal placental capillary number, which was due to increased branching, resulted in 6-fold increases in total capillary cross-sectional area and total capillary surface, per unit of COT tissue. Different patterns of expression of the mRNAs for angiogenic factors and their receptors were observed for CAR and COT. The dilation-like angiogenesis of CAR was correlated with the expression of vascular endothelial growth factor receptor-1 (FLT1), angiopoietin-2 (ANGPT2), and soluble guanylate cyclase (GUCY1B3) mRNAs. The branching-like angiogenesis of COT was correlated with the expression of vascular endothelial growth factor (VEGF), FLT1, angiopoietin-1 (ANGPT1), ANGPT2, and FGF2 mRNAs. Monitoring the expression of angiogenic factors and correlating the levels with quantitative measures of vascularity enable one to model angiogenesis in a spatiotemporal fashion.
A combined learning algorithm for prostate segmentation on 3D CT images

Purpose: Segmentation of the prostate on CT images has many applications in the diagnosis and treatment of prostate cancer. Because of the low soft‐tissue contrast on CT images, prostate segmentation is a challenging task. A learning‐based segmentation method is proposed for the prostate on three‐dimensional (3D) CT images. Methods: We combine population‐based and patient‐based learning methods for segmenting the prostate on CT images. Population data can provide useful information to guide the segmentation processing. Because of inter‐patient variations, patient‐specific information is particularly useful to improve the segmentation accuracy for an individual patient. In this study, we combine a population learning method and a patient‐specific learning method to improve the robustness of prostate segmentation on CT images. We train a population model based on the data from a group of prostate patients. We also train a patient‐specific model based on the data of the individual patient and incorporate the information as marked by the user interaction into the segmentation processing. We calculate the similarity between the two models to obtain applicable population and patient‐specific knowledge to compute the likelihood of a pixel belonging to the prostate tissue. A new adaptive threshold method is developed to convert the likelihood image into a binary image of the prostate, and thus complete the segmentation of the gland on CT images. Results: The proposed learning‐based segmentation algorithm was validated using 3D CT volumes of 92 patients. All of the CT image volumes were manually segmented independently three times by two, clinically experienced radiologists and the manual segmentation results served as the gold standard for evaluation. The experimental results show that the segmentation method achieved a Dice similarity coefficient of 87.18 ± 2.99%, compared to the manual segmentation. Conclusions: By combining the population learning and patient‐specific learning methods, the proposed method is effective for segmenting the prostate on 3D CT images. The prostate CT segmentation method can be used in various applications including volume measurement and treatment planning of the prostate.