Miracle-dz/UniFAR-FTUs huggingface dataset:
Inferable Centers, Centering Transitions, and the Notion of Coherence

A centering analysis of the corpus of Japanese e-mail that is examined in this article relies heavily on the inclusion of inferable centers. However, utilizing this type of center results in a high level of indeterminacy in labeling transitions and thus in characterizing the coherence of the corpus. The difficulty lies in the requirement of identity of discourse entities in the definitions of transition states. Lexical cohesion is proposed as a well-defined notion to replace the intuitions captured by the use of inferable centers. Two new transitions, based on lexical relatedness instead of identity, supplement the standard definitions and more adequately characterize coherence in this corpus. Implications and extensions of the proposal are discussed.
Surface antigens of melanocytes and melanomas. Markers of melanocyte differentiation and melanoma subsets

The surface antigens of melanocytes from newborn and adult skin have been analyzed with monoclonal antibodies detecting cell surface antigens of malignant melanoma. Antigenic markers that distinguish early, intermediate, and mature stages in melanocyte differentiation have been defined. The characteristics of the normal melanocyte precursor have been inferred from the features of melanomas that express early markers of melanocyte differentiation. A rudimentary surface antigen map of cells undergoing melanocyte differentiation and a new classification of melanomas based on the expression of melanocyte differentiation antigens are proposed.
Pancreatic cancer and FOLFIRINOX: a new era and new questions

FOLFIRINOX (FFX) was introduced to clinical practice in 2010 following publication of the PRODIGE 4/ACCORD 11 study, which compared this novel regimen to gemcitabine in metastatic pancreatic cancer. Median overall survival, progression‐free survival, and objective responses were all superior with FFX and there was improved time to definitive deterioration in quality of life. Despite initial concerns over toxicity, there has been rapid uptake of this regimen, both revolutionizing management and opening the door to innovative research. As experience with FFX has accrued, many questions have arisen including the management of toxicities, the impact of frequent modifications, the optimal number of cycles, integration with other regimens and modalities, interpretation of radiologic and serologic response, utility of molecular signatures, and potential benefit in unique clinical settings such as pre‐ and postsurgery. This review will closely examine these issues, not only to summarize current knowledge but also to fuel scientific debate.
Carpenters, Cabinetmakers, and Risk of Testicular Germ Cell Cancer

Objective: A recent cohort study showed an increased risk of testicular cancer among members of the United Brotherhood of Carpenters and Joiners of America. We explored our data of a German population-based case–control study on the etiology of testicular cancer with regard to this association. Methods: The case–control study included 269 testicular cancer cases and 797 controls. We applied conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CIs). Results: People who worked as cabinetmakers or carpenters had an OR of 0.84 (95% CI = 0.45–1.56). Risks were increased among cabinetmakers who worked at least 15 years ago (OR = 5.81, 95% CI = 1.20–28.09). Ever being employed as a carpenter was associated with a reduced OR of 0.59 (95% CI = 0.24–1.46). Conclusions: Cabinetmakers may be at an increased risk of testicular cancer.
Control of Virulence Gene Expression by the Master Regulator, CfaD, in the Prototypical Enterotoxigenic Escherichia coli Strain, H10407

Enterotoxigenic Escherichia coli (ETEC) is the most common bacterial cause of diarrhea in children in developing countries, as well as in travelers to these countries. To cause disease, ETEC needs to produce a series of virulence proteins including enterotoxins, colonization factors and secretion pathways, which enable this pathogen to colonize the human small intestine and deliver enterotoxins to epithelial cells. Previously, a number of studies have demonstrated that CfaD, an AraC-like transcriptional regulator, plays a key role in virulence gene expression by ETEC. In this study, we carried out a transcriptomic analysis of ETEC strain, H10407, grown under different conditions, and determined the complete set of genes that are regulated by CfaD. In this way, we identified a number of new target genes, including rnr-1, rnr-2, etpBAC, agn43, flu, traM and ETEC_3214, whose expression is strongly activated by CfaD. Using promoter-lacZ reporters, primer extension and electrophoretic mobility shift assays, we characterized the CfaD-mediated activation of several selected target promoters. We also showed that the gut-associated environmental signal, sodium bicarbonate, stimulates CfaD-mediated upregulation of its virulence target operons. Finally, we screened a commercial small molecule library and identified a compound (CH-1) that specifically inhibited the regulatory function of CfaD, and by 2-D analoging, we identified a second inhibitor (CH-2) with greater potency.
The interaction of feature and space based orienting within the attention set

The processing of sensory information relies on interacting mechanisms of sustained attention and attentional capture, both of which operate in space and on object features. While evidence indicates that exogenous attentional capture, a mechanism previously understood to be automatic, can be eliminated while concurrently performing a demanding task, we reframe this phenomenon within the theoretical framework of the “attention set” (Most et al., 2005). Consequently, the specific prediction that cuing effects should reappear when feature dimensions of the cue overlap with those in the attention set (i.e., elements of the demanding task) was empirically tested and confirmed using a dual-task paradigm involving both sustained attention and attentional capture, adapted from Santangelo et al. (2007). Participants were required to either detect a centrally presented target presented in a stream of distractors (the primary task), or respond to a spatially cued target (the secondary task). Importantly, the spatial cue could either share features with the target in the centrally presented primary task, or not share any features. Overall, the findings supported the attention set hypothesis showing that a spatial cuing effect was only observed when the peripheral cue shared a feature with objects that were already in the attention set (i.e., the primary task). However, this finding was accompanied by differential attentional orienting dependent on the different types of objects within the attention set, with feature-based orienting occurring for target-related objects, and additional spatial-based orienting for distractor-related objects.
Reduced β-catenin expression affects patterning of bone primordia, but not bone maturation

ABSTRACT Wnt/β-catenin signaling is involved in patterning of bone primordia, but also plays an important role in the differentiation of chondrocytes and osteoblasts. During these processes the level of β-catenin must be tightly regulated. Excess β-catenin leads to conditions with increased bone mass, whereas loss of β-catenin is associated with osteoporosis or, in extreme cases, the absence of limbs. In this study, we examined skeletogenesis in mice, which retain only 25% of β-catenin. These embryos showed severe morphological abnormalities of which the lack of hindlimbs and misshaped front paws were the most striking. Surprisingly however, calcification of bone primordia occurred normally. Moreover, the Wnt-dependent regulatory network of transcription factors driving the differentiation of cartilage and bone, as well as the expression of extracellular matrix components, were preserved. These findings show that 25% β-catenin is insufficient for the correct patterning of bone primordia, but sufficient for their mineralization. Our approach helps to identify bone morphogenetic processes that can proceed normally even at low β-catenin levels, in contrast to those that require high β-catenin dosages. This information could be exploited to improve the treatment of bone diseases by fine-tuning the individual β-catenin dosage requirements. Summary: The correct allocation and patterning of skeletal elements during development requires a higher dosage of β-catenin than the maturation and mineralization of these primordia.
Retina Benzo ( e ) pyrene Inhibits Endothelium-Dependent NO-Mediated Dilation of Retinal Arterioles via Superoxide Production and Endoplasmic Reticulum Stress

Citation: Kamiya T, Nagaoka T, Omae T, Ono S, Otani S, Yoshida A. Benzo(e)pyrene inhibits endothelium-dependent NO-mediated dilation of retinal arterioles via superoxide production and endoplasmic reticulum stress. Invest Ophthalmol Vis Sci. 2017;58:5978–5984. DOI:10.1167/ iovs.17-21925 PURPOSE. To investigate whether benzo(e)pyrene (B(e)P), a toxicant in cigarette smoke, affects the endothelium-dependent nitric oxide (NO)-induced vasodilation of the retinal arterioles, and whether oxidative stress, distinct protein kinase signaling pathways, and endoplasmic reticulum (ER) stress are associated with the B(e)P-induced effect on the retinal arterioles.
Global gene expression analysis of transgenic, mannitol-producing, and salt-tolerant Arabidopsis thaliana indicates widespread changes in abiotic and biotic stress-related genes

Mannitol is a putative osmoprotectant contributing to salt tolerance in several species. Arabidopsis plants transformed with the mannose-6-phosphate reductase (M6PR) gene from celery were dramatically more salt tolerant (at 100 mM NaCl) as exhibited by reduced salt injury, less inhibition of vegetative growth, and increased seed production relative to the wild type (WT). When treated with 200 mM NaCl, transformants produced no seeds, but did bolt, and exhibited less chlorosis/necrosis and greater survival and dry weights than the WT. Without salt there were no M6PR effects on growth or phenotype, but expression levels of 2272 genes were altered. Many fewer differences (1039) were observed between M6PR and WT plants in the presence of salt, suggesting that M6PR pre-conditioned the plants to stress. Previous work suggested that mannitol is an osmoprotectant, but mannitol levels are invariably quite low, perhaps inadequate for osmoprotectant effects. In this study, transcriptome analysis reveals that the M6PR transgene activated the downstream abscisic acid (ABA) pathway by up-regulation of ABA receptor genes (PYL4, PYL5, and PYL6) and down-regulation of protein phosphatase 2C genes (ABI1 and ABI2). In the M6PR transgenic lines there were also increases in transcripts related to redox and cell wall-strengthening pathways. These data indicate that mannitol-enhanced stress tolerance is due at least in part to increased expression of a variety of stress-inducible genes.
Connexin 26 studies in patients with sensorineural hearing loss.

OBJECTIVE To determine the spectrum of connexin 26 (Cx26) mutations and their phenotypes in children with sensorineural hearing loss (SNHL) or mixed hearing loss (MHL). DESIGN Children with SNHL or MHL were prospectively tested for mutations in the entire coding region of the Cx26 gene. PATIENTS Children with SNHL or MHL with no obvious etiology for the hearing loss. RESULTS Between December 1, 1998, and July 1, 2000, 107 patients with SNHL or MHL from 99 families underwent Cx26 testing. Most patients were aged 1 week to 16 years (61 boys and 46 girls). Thirty (30%) of 99 probands had Cx26 mutations: biallelic mutations were detected in 18 (9 homozygous and 9 compound heterozygous) and single mutations were detected in 12. Twelve previously reported mutations (35delG, 167delT, E47X, L90P, M34T, G12V, V37I, R143W, V84L, V153I, V27I, and 310del14) and 3 novel mutations (E129K, T8M, and N206S) were found. Hearing loss in patients with biallelic Cx26 mutations ranged from unilateral high frequency to bilateral profound. Four children, 2 with biallelic mutations, had temporal bone abnormalities. CONCLUSIONS Connexin 26 mutations are common in children with SNHL, and it is likely that the homozygous and compound heterozygous mutations cause the SNHL. However, pathogenicity is less certain when only a single Cx26 mutation is present. Patients with biallelic Cx26 mutations had a slightly higher incidence of milder hearing loss than in previous studies. Children with SNHL or MHL should be tested for Cx26 mutations early in their evaluation.
Elevated expression of protein arginine methyltransferase 5 predicts the poor prognosis of breast cancer

Protein arginine methyltransferase 5 is one of the type II protein arginine methyltransferase family members that can symmetrically dimethylate arginine residues on target proteins in both the cytoplasm and the nucleus. Protein arginine methyltransferase 5 was reported to be an oncoprotein that participates in tumor progression through both epigenetic silencing and organelle biogenesis. So far, it has been implicated in various cancers, but its expression pattern in breast cancer has not been elucidated thoroughly. We analyzed the protein arginine methyltransferase 5 expression patterns in several breast cancer samples and tissue arrays to better characterize its contribution to breast cancer. Primary breast tumors showed increased protein arginine methyltransferase 5 expression compared with adjacent normal tissues in both the fresh tissue samples and tissue arrays. Also, there was a tendency that metastatic lymph nodes demonstrated enhanced protein arginine methyltransferase 5 expression compared to primary sites. Moreover, we found a significant correlation between protein arginine methyltransferase 5 and Ki-67, with higher Ki-67 and protein arginine methyltransferase 5 expressions in primary breast tumors compared with normal breast tissues. Moreover, the Cancer Genome Atlas cohort analysis revealed that high protein arginine methyltransferase 5 messenger RNA expression was associated with an unfavorable prognosis in human epidermal growth factor receptor 2 (HER-2) positive and triple negative breast cancer patients. Finally, the roles and mechanisms of protein arginine methyltransferase 5 in the proliferation, cell cycle progression, and apoptosis of MDA-MB-231 cells were assessed using protein arginine methyltransferase 5 and shPRMT5 transfection. In conclusion, we proposed that protein arginine methyltransferase 5 is an independent prognostic biomarker for breast cancer, and targeting protein arginine methyltransferase 5 might be a promising strategy for breast cancer treatment.
Relaxation Methods Applied to Engineering Problems. VIIIA. Problems Relating to Large Transverse Displacements of Thin Elastic Plates

Small transverse displacements of a flat elastic plate are governed by a single linear equation, but large displacements entail stretching of the middle surface and consequent tensions, which interacting with the curvatures (i.e. by 9membrane effect’) introduce non-linear terms into the conditions of equilibrium and so make those equations no longer independent. The second-order terms were formulated by von Karman in 1910, but the amended (‘large deflexion’) equations have been solved only in a few cases, and then with considerable difficulty. In this paper four examples are treated approximately by a technique based on relaxation methods. The first and second are relatively simple problems which have been solved exactly and so serve as test cases, viz. ( a ) a circular plate, with clamped edge, which sustains a uniform transverse pressure and ( b ) a circular plate, with ‘simply supported’ edge, which buckles with radial symmetry under uniform edge thrust. The third and fourth examples present great difficulties to orthodox analysis: they are ( c ) a square plate, sustaining uniform transverse pressure, of which the edges are clamped, ( d ) a square plate buckled by actions which, clamping its edges, tend initially to induce a state of uniform shear.
Acetate metabolism in brain mechanisms of adaptation to ethanol.

BACKGROUND The aim of this study was to estimate the role of acetate-induced metabolic changes in brain mechanisms of resistance to the narcotic effect of ethanol. MATERIAL/METHODS Wistar rats were treated daily with ethanol (3.5 g/kg i.p. for 7 days). During alcohol treatment, the duration of ethanol-induced sleep was decreased. Levels of acetate, acetyl-CoA, adenosine, and the pool of AMP+ADP, and the activity of acetyl-CoA synthetase and 5'-nucleotidase in the brain were measured. Synaptosomal adenosine and acetylcholine release were measured in the presence of acetate, adenosine and 2-chloroadenosine. RESULTS The concentration of acetate was higher in all investigated brain regions of ethanol rats in comparison to controls. The activity of acetyl-CoA synthetase and 5'-nucleotidase, as well as the levels of adenosine and the pool of AMP+ADP were raised in cerebral cortex of ethanol rats. The synaptosomal level of adenosine was higher in control rats. Acetate caused a 3-fold increase of extrasynaptosomal adenosine level. Synaptosomes from ethanol rats showed higher rates of Ca-dependent releases of acetylcholine. 2-chloradenosine resulted in inhibition of synaptic acetylcholine release only in control rats. CONCLUSIONS Ethanol causes an increase of acetate in brain and adenosine level in cerebral cortex. Acetate causes an increase of the extrasynaptic adenosine level. Prolonged ethanol treatment results in an increase of synaptic Ca-dependent acetylcholine release. Seven-day treatment with ethanol eliminates the inhibitory effect of 2-chloroadenosine-A1 adenosine receptor agonist on synaptic Ca-dependent acetylcholine release.
A theorem prover for Boolean BI

While separation logic is acknowledged as an enabling technology for large-scale program verification, most of the existing verification tools use only a fragment of separation logic that excludes separating implication. As the first step towards a verification tool using full separation logic, we develop a nested sequent calculus for Boolean BI (Bunched Implications), the underlying theory of separation logic, as well as a theorem prover based on it. A salient feature of our nested sequent calculus is that its sequent may have not only smaller child sequents but also multiple parent sequents, thus producing a graph structure of sequents instead of a tree structure. Our theorem prover is based on backward search in a refinement of the nested sequent calculus in which weakening and contraction are built into all the inference rules. We explain the details of designing our theorem prover and provide empirical evidence of its practicality.
DYNAMIC TRAVEL DEMAND FOR EMERGENCY EVACUATION: THE CASE OF BUSHFIRES

There are two types of emergencies: those which can be anticipated and those that cannot. Those that can be anticipated are such events as cyclones, floods, bush fires, and tsunamis. When such events are anticipated, one course of action that may be taken is the evacuation of residents from a threatened area. When evacuation takes place, there often remains a need to provide access for emergency vehicles and personnel to the threatened area creating a conflict between the needs to maximise capacity for evacuation, while continuing to provide access to the threatened area. Relatively little is known about when residents will decide to evacuate. A model of evacuation behaviour is needed that would predict the proportions of the population that would leave within certain time periods, thus leading to the development of an evacuation travel demand model. The authors developed a method to predict evacuation decisions by residents from bush fires. This paper describes the methods used to determine when a household would evacuate, and describes the resulting model that predicts how many partial and full evacuations will take place by time period from when the emergency is first perceived. (a)
CD4-Independent Infection of Two CD4−/CCR5−/CXCR4+ Pre-T-Cell Lines by Human and Simian Immunodeficiency Viruses

ABSTRACT The infection of CD4-negative cells by variants of tissue culture-adapted human immunodeficiency virus type 1 (HIV-1) or HIV-2 strains has been shown to be mediated by the CXCR4 coreceptor. Here we show that two in vitro-established CD4−/CCR5−/CXCR4+ human pre-T-cell lines (A3 and A5) can be productively infected by wild-type laboratory-adapted T-cell-tropic HIV-1 and HIV-2 strains in a CD4-independent, CXCR4-dependent fashion. Despite the absence of CCR5 expression, A3 and A5 cells were susceptible to infection by the simian immunodeficiency viruses SIVmac239 and SIVmac316. Thus, at least in A3 and A5 cells, one or more of the chemokine receptors can efficiently support the entry of HIV and SIV isolates in the absence of CD4. These findings suggest that to infect cells of different compartments, HIV and SIV could have evolved in vivo to bypass CD4 and to interact directly with an alternative receptor.
AMP-Activated Protein Kinase: An Ubiquitous Signaling Pathway With Key Roles in the Cardiovascular System

The AMP-activated protein kinase (AMPK) is a key regulator of cellular and whole-body energy homeostasis, which acts to restore energy homoeostasis whenever cellular energy charge is depleted. Over the last 2 decades, it has become apparent that AMPK regulates several other cellular functions and has specific roles in cardiovascular tissues, acting to regulate cardiac metabolism and contractile function, as well as promoting anticontractile, anti-inflammatory, and antiatherogenic actions in blood vessels. In this review, we discuss the role of AMPK in the cardiovascular system, including the molecular basis of mutations in AMPK that alter cardiac physiology and the proposed mechanisms by which AMPK regulates vascular function under physiological and pathophysiological conditions.
Central Nervous System Entry of Peripherally Injected Umbilical Cord Blood Cells Is Not Required for Neuroprotection in Stroke

Background and Purpose— To date, stem cell graft-mediated neuroprotection is equated with graft survival and secretion of neurotrophic factors in the brain. Here, we examined whether neuroprotection by systemically delivered human umbilical cord blood (HUCB) cells was dependent on their entry into the central nervous system in a rodent model of acute stroke. Methods— Adult male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion for 60 minutes. During the 1-hour occlusion, animals were randomly assigned to 1 of the following treatments: intravenous injection of HUCB (a subtherapeutic dose of 200 000 cells in 10 μL) with blood–brain barrier (BBB) permeabilizer (1.1 mol/L mannitol at 4°C) or vehicle, intravenous vehicle alone, or intravenous mannitol alone. Behavioral tests, using elevated body swing test and passive avoidance test, were conducted at day 3 poststroke, and thereafter, animals were euthanized for: (1) immunohistochemical examination of HUCB, which were lentivirally labeled with green fluorescent protein; (2) cerebral infarction analysis using 2,3,5-triphenyl-tetrazolium chloride; and (3) enzyme-linked immunosorbent assay of trophic factors within the striatal region. Results— We did not detect intravenously administered low dose of HUCB cells in the brains of animals at day 3 after stroke even when cells were coinfused with a BBB permeabilizer (mannitol). However, HUCB–mannitol treatment significantly increased brain levels of neurotrophic factors, which correlated positively with reduced cerebral infarcts and improved behavioral functions. Conclusions— Our data show that central nervous system availability of grafted cells is not a prerequisite for acute neuroprotection provided that therapeutic molecules secreted by these cells could cross the BBB.