Miracle-dz/UniFAR-FTUs huggingface dataset:
Pyrrolo[2,3-c]pyridines as Imaging Agents for Neurofibrilary Tangles.

Title: Pyrrolo[2,3-c]pyridines as imaging agents for neurofibrilary tangles Patent Application Number: WO 2015188368 A2 Publication date: December 17th, 2015 Priority Application: PCT/CN2014/079834 Priority date: June 13th, 2014 Inventors: Abbas, Walji; Hostetler, Eric; Greshock, Thomas; Li, Jing; Moore, Keith P.; Bennacef, Idriss; Mulhearn, James; Selnick, Harold; Wang, Yaode; Yang, Kun; Fu, Jianmin Assignee Company: Merck, Sharpe and Dohme, Inc. Disease Area: CNS Alzheimer’s disease Biological Target: Tau protein and tau aggregates Summary: Alzheimer’s disease (AD), a neurodegenerative disorder characterized by neuronal and synaptic loss, brain atrophy, and slow, progressive dementia first characterized by Dr. Alois Alzheimer in 1901, remains a major unmet medical need. Despite decades of research, a cure remains elusive and treatment options are limited. In 2015, approximately 5.3 million US citizens had Alzheimer’s disease, and the direct cost of AD patient care in the US was ∼$226 billion. In the absence of novel therapies, the US AD patient population is expected to exceed 13.8 million by 2050, and the cost of care will balloon to over $1.1 trillion. Although the pathogenesis of AD has not been determined, there are two major theories that describe its pathogenesis, the amyloid hypothesis and the tau theory. According to the amyloid hypothesis the neurodegeneration and loss of cognitive function associated with AD are caused by the buildup of β-amyloid plaques. These plaques are believed to be the result of improper amyloid precursor protein (APP) processing by β-secretase (BACE) and γ-secretase, which leads to a buildup of the Aβ-42 fragment of APP. Aβ-42 is prone to aggregation and plaque formation, and it has been hypothesized that preventing the formation and/or clearing these materials from the brain will arrest AD progression. The tau theory, however, hypothesizes that AD pathogenesis is caused bymishandling of tubulin-associated unit (tau) proteins. Under normal conditions, this highly solublemicrotubule associated proteinmodulates the stability of axonalmicrotubules. In ADpatients, however, tau becomes hyperphosphorylated, which substantially decreases its solubility. This leads to the formation of tau aggregates and neurofibrillary tangles inside nerve cells. This, in turn, causes neuron death, cognitive impairment, and other symptoms of AD. Diagnostic tools capable of detecting the presence of either β-amyloid plaques or tau aggregates could provide a method of diagnosing AD. The present disclosure describes a series of pyrrolo[2,3-c]pyridines useful as positron emission tomography (PET) imaging agents capable of binding to tau aggregates.
DNA methylation analyses of urothelial carcinoma reveal distinct epigenetic subtypes and an association between gene copy number and methylation status

We assessed DNA methylation and copy number status of 27,000 CpGs in 149 urothelial carcinomas and integrated the findings with gene expression and mutation data. Methylation was associated with gene expression for 1,332 CpGs, of which 26% showed positive correlation with expression, i.e., high methylation and high gene expression levels. These positively correlated CpGs were part of specific transcription factor binding sites, such as sites for MYC and CREBP1, or located in gene bodies. Furthermore, we found genes with copy number gains, low expression and high methylation levels, revealing an association between methylation and copy number levels. This phenomenon was typically observed for developmental genes, such as HOX genes, and tumor suppressor genes. In contrast, we also identified genes with copy number gains, high expression and low methylation levels. This was for instance observed for some keratin genes. Tumor cases could be grouped into four subgroups, termed epitypes, by their DNA methylation profiles. One epitype was influenced by the presence of infiltrating immune cells, two epitypes were mainly composed of non-muscle invasive tumors, and the remaining epitype of muscle invasive tumors. The polycomb complex protein EZH2 that blocks differentiation in embryonic stem cells showed increased expression both at the mRNA and protein levels in the muscle invasive epitype, together with methylation of polycomb target genes and HOX genes. Our data highlights HOX gene silencing and EZH2 expression as mechanisms to promote a more undifferentiated and aggressive state in UC.
Aldose reductase inhibitory, anti-cataract and antioxidant potential of selected medicinal plants from the Marathwada region, India

The water, ethanol and chloroform extracts of selected plants such as Adhatoda vasica (L.) (Acanthaceae), Caesalpinia bonduc (L.), Cassia fistula (L.) (Caesalpiniaceae) and Biophytum sensitivum (L.) (Oxalidaceae) were evaluated for rat lens aldose reductase inhibitory (RLAR) potential, anti-cataract and antioxidant activities. All the samples inhibited the aldose reductase considerably and exhibited anti-cataract activity, while C. fistula (IC50, 0.154 mg mL−1) showed significant RLAR inhibitory activity as compared to the other tested samples, and was further found to be more effective in maintaining sugar-induced lens opacity in the rat lens model. The antioxidant potential of plant extracts was determined using DPPH (2,2-diphenyl-1-picryl hydrazine), hydroxyl (OH), nitric oxide (NO) and hydrogen peroxide (H2O2) scavenging activities, along with determination of reducing power, ferrous ion chelating ability and inhibition of polyphenol oxidase (PPO). The extracts of the tested plant showed significant free radical scavenging activities and inhibited the activity of enzyme PPO, a model oxidising enzyme. The plant samples were found to possess considerable amounts of vitamin C, total polyphenols and flavonoids.
Intake of dietary salt and drinking water: Implications for the development of age-related macular degeneration

Purpose Systemic hypertension is a risk factor of age-related retinal diseases such as diabetic retinopathy and age-related macular degeneration. High intake of dietary salt and low intake of water increase extracellular osmolality resulting in hypertension, in particular in salt-sensitive individuals. This review summarizes the present knowledge regarding the impact of salt and water intake on the regulation of blood pressure, retinal function, and the development of age-related retinal diseases. Methods A literature search of the Medline database and a summary of recent studies that used human RPE cells. Results The salt sensitivity of the blood pressure and plasma osmolality increase with age, and body water deficits are common in older individuals. High plasma osmolality has adverse effects in the retina. In RPE cells, high osmolality induces expression and secretion of angiogenic factors, such as vascular endothelial growth factor (VEGF), placental growth factor, and basic fibroblast growth factor, and expression of aquaporin-5, a water channel implicated in transepithelial water transport. The transcriptional activities of hypoxia-inducible factor-1 (HIF-1) and nuclear factor of activated T cell 5 (NFAT5) are critical for the production of VEGF in response to salt-induced osmotic stress. Salt-induced osmotic stress also induces priming of the NLRP3 inflammasome and activates inflammatory enzymes in RPE cells. Conclusions Raised plasma osmolality may aggravate age-related retinal diseases by stimulation of local inflammation and angiogenic factor production in the RPE. Alterations in salt and water consumption, and of minerals that stimulate renal salt excretion, may offer nutritional approaches to prevent age-related retinal disorders, in particular in salt-sensitive individuals and individuals who show signs of body dehydration.
Divulgación de información sobre sostenibilidad de los aeropuertos como medio de legitimación social

El creciente desarrollo del sector aeroportuario ha puesto en alerta a la sociedad respecto a las repercusiones sociales, economicas y medioambientales que se pueden generar. En concreto, los aeropuertos reciben duras criticas debidas al consumo de territorio, de agua y de energias, al impacto sobre la biodiversidad de zona que ocupan y a la contaminacion acustica y atmosferica, entre otras. Dada esta situacion, el objetivo del trabajo es analizar el contenido informativo de las Memorias sobre responsabilidad social que presentan las empresas de este sector, asi como los posibles factores que le pueden influir. Los resultados de trabajo muestran que en las memorias sobre sostenibilidad de los aeropuertos se divulga fundamentalmente aspectos relativos a medioambiente mas que aspectos economicos y sociales. Respecto a los factores determinantes de la divulgacion de informacion sobre sostenibilidad, el tamano y la reputacion son las variables que estan mas relacionadas con la publicacion de este tipo de informacion.
Optimizing speaker-specific filter banks for speaker verification

In this work, we investigate speaker-specific filter banks for text-independent speaker verification. The proposed method performs an heuristic search for the best filter-bank configuration using the Artificial Bee Colony (ABC) algorithm and a proper fitness function for the standard i-vectors/PLDA-based speaker verification system. Furthermore, filter-bank decorrelated amplitudes are used instead of the cepstral coefficients produced by Discrete Cosine Transform (DCT). In the experiments, the proposed method is compared to standard Mel and linear scales in both cases where the decorrelation is performed using DCT and high-pass filtering. The comparison is performed on the MIT Mobile Device Speaker Verification Corpus in a gender-dependent trial scheme. The proposed method outperformed the baseline systems in almost all the test sets for both genders. Performance gains of 4.6% and 26.0% are achieved for male and female speakers, respectively.
Le concept de risque au magasin des curiosités

Le concept de risque est utilise comme une evidence en gestion et c'est sur cette evidence que se sont construites, sans aucun recul conceptuel, les methodes de gestion des risques. Ce texte invite a explorer differentes facettes du concept de risque afin de mettre en perspective le corpus qualifie de gestion des risques.
Host range expansion of an introduced insect pest through multiple colonizations of specialized clones

Asexuality confers demographic advantages to invasive taxa, but generally limits adaptive potential for colonizing of new habitats. Therefore, pre‐existing adaptations and habitat tolerance are essential in the success of asexual invaders. We investigated these key factors of invasiveness by assessing reproductive modes and host‐plant adaptations in the pea aphid, Acyrthosiphon pisum, a pest recently introduced into Chile. The pea aphid encompasses lineages differing in their reproductive mode, ranging from obligatory cyclical parthenogenesis to fully asexual reproduction. This species also shows variation in host use, with distinct biotypes specialized on different species of legumes as well as more polyphagous populations. In central Chile, microsatellite genotyping of pea aphids sampled on five crops and wild legumes revealed three main clonal genotypes, which showed striking associations with particular host plants rather than sampling locations. Phenotypic analyses confirmed their strong host specialization and demonstrated parthenogenesis as their sole reproductive mode. The genetic relatedness of these clonal genotypes with corresponding host‐specialized populations from the Old World indicated that each clone descended from a particular Eurasian biotype, which involved at least three successful introduction events followed by spread on different crops. This study illustrates that multiple introductions of highly specialized clones, rather than local evolution in resource use and/or selection of generalist genotypes, can explain the demographic success of a strictly asexual invader.
Quantitative genetic insights into the coevolutionary dynamics of male and female genitalia

The spectacular variability that typically characterizes male genital traits has largely been attributed to the role of sexual selection. Among the evolutionary mechanisms proposed to account for this diversity, two processes in particular have generated considerable interest. On the one hand, females may exploit postcopulatory mechanisms of selection to favour males with preferred genital traits (cryptic female choice; CFC), while on the other hand females may evolve structures or behaviours that mitigate the direct costs imposed by male genitalia (sexual conflict; SC). A critical but rarely explored assumption underlying both processes is that male and female reproductive traits coevolve, either via the classic Fisherian model of preference-trait coevolution (CFC) or through sexually antagonistic selection (SC). Here, we provide evidence for this prediction in the guppy (Poecilia reticulata), a polyandrous livebearing fish in which males transfer sperm internally to females via consensual and forced matings. Our results from a paternal half-sibling breeding design reveal substantial levels of additive genetic variation underlying male genital size and morphology—two traits known to predict mating success during non-consensual matings. Our subsequent finding that physically interacting female genital traits exhibit corresponding levels of genetic (co)variation reveals the potential intersexual coevolutionary dynamics of male and female genitalia, thereby fulfilling a fundamental assumption underlying CFC and SC theory.
Trends in hospital admissions for childhood asthma in Oslo, Norway, 1980–95

Background: Prevalence of asthma and quality of asthma care both influence hospital admission rates for childhood asthma. Therefore, we aimed to assess possible changes in hospital admission rate for acute asthma in Oslo, Norway, from 1980 to 1995, as well as evaluate the possible effect of changes in asthma treatment upon hospitalization for acute asthma in this period.
Angiographic Detection of Carotid Plaque Ulceration: Comparison With Surgical Observations in a Multicenter Study

Background and Purpose Carotid plaque ulceration is used as one of the determinants in deciding which patients should be submitted to carotid endarterectomy. Uncertainties about its importance persist. Its detection by angiography is an important consideration. Methods The detection of ulceration by angiography was compared with observations during endarterectomy in the first 500 patients recruited into the North American Symptomatic Carotid Endarterectomy Trial. This represents the first multicenter compilation of data on this subject and the largest series of patients with both arteriographic and direct surgical observation. Results Sensitivity and specificity of detecting ulcerated plaques were 45.9% and 74.1%, respectively. The positive predictive value of identifying an ulcer was 71.8%. These results remained unchanged with differing degrees of carotid stenosis and were confirmed by analyses based on receiver operating characteristic (ROC) methodology. The area under the ROC curve (Az) was estimated to be 0.61 (95% confidence interval, 0.55 to 0.67). Conclusions These observations from a multicenter study confirm that little agreement exists between angiography and surgical observation in detecting carotid plaque ulceration.
Comparative Proteome Analysis of Brucella melitensis Vaccine Strain Rev 1 and a Virulent Strain , 16 M

Comparative Proteome Analysis of Brucella melitensis Vaccine Strain Rev 1 and a Virulent Strain, 16M Michel Eschenbrenner, Mary Ann Wagner, Troy A. Horn, Jo Ann Kraycer, Cesar V. Mujer, Sue Hagius, Philip Elzer, and Vito G. DelVecchio* Institute of Molecular Biology and Medicine, The University of Scranton, Scranton, Pennsylvania 18510, and Department of Veterinary Science, Louisiana State University AgCenter, Baton Rouge, Louisiana 70803
Some Realism About the Free Speech Critique of Copyright

This article examines from a legal realist point of view the free speech critique of copyright - a cluster of arguments designed to encourage courts to use free speech principles to limit the length and scope of copyright laws, and to give defendants (especially transformative ones) a boost in infringement litigation. The article points out that the free speech critique needs to treat copyright and infringement suits as state action, and tends to treat users as dependent upon, and potentially oppressed by, rights-holders. Both moves - collapsing the public-private distinction and denying the autonomy of individuals - are legal realist staples. By contrast, however, free speech doctrine cannot work without a clear notion of private action and of individual autonomy. Applied consistently, the critique's premises would disable the doctrines they are designed to invoke. In addition, the critique does not turn its realism on free speech doctrine, which has become highly formal. Though the critique contains some wonderfully creative and erudite arguments, these problems are too much for it to overcome.
Scalable and Unsupervised Feature Engineering Using Vibration-Imaging and Deep Learning for Rotor System Diagnosis

This paper proposes a scalable and unsupervised feature engineering method that uses vibration imaging and deep learning. For scalability, a vibration imaging approach is devised that incorporates data from systems with various scales, such as small testbeds and real field-deployed systems. Moreover, a deep learning approach is proposed for unsupervised feature engineering. The overall procedure includes three key steps: 1) vibration image generation; 2) unsupervised feature extraction; and 3) fault classifier design. To demonstrate the validity of the proposed approach, three case studies are conducted using an RK4 rotor kit and a power plant journal bearing system. By incorporating smaller-system data as well as real-system data, the proposed approach can substantially increase the applicability of the fault diagnosis method while maintaining good accuracy. Moreover, the time and effort needed to develop a diagnostic approach for other rotor systems can be reduced considerably.
EEG ALPHA COHERENCE AND PSYCHOPATHOLOGICAL DIMENSIONS OF SCHIZOPHRENIA

The aim of this study was to evaluate the correlation between psychopathological dimensions in recent-onset neuroleptic-naive schizophrenic patients and EEG alpha coherence in the resting state. 37 neuroleptic-naive recent-onset schizophrenic patients were assessed on the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms, and psychopathological dimension scores on reality distortion, psychomotor poverty and disorganization were calculated. EEG alpha coherence was computed across 14 intra-hemispheric and 8 interhemispheric electrode pairs in the resting eyes closed and eyes open conditions. The relationship between the psychopathological dimension scores and coherence values was assessed using Pearson's product moment correlation with Bonferroni correction for levels of significance. Significant associations between higher psychomotor poverty scores and lower inter-hemispheric coherence values were found across the central and parietal regions in the eyes closed condition and across central regions in the eyes open condition. Reality distortion and disorganization dimensions were not significantly correlated with intra- or inter-hemispheric coherences in both eyes closed and eyes open conditions. However there was a trend for an inverse correlation between disorganization dimension and intra-hemispheric coherence across left frontal, left temporo-parietal and right parieto-occipital regions in the eyes open condition. These findings suggest a possible differential pattern in the extent of brain involvement across the three psychopathological dimensions of schizophrenia in neurolepticnaive patients with recent-onset illness.
Cdc14 targets the Holliday junction resolvase Yen1 to the nucleus in early anaphase

The only canonical Holliday junction (HJ) resolvase identified in eukaryotes thus far is Yen1/GEN1. Nevertheless, Yen1/GEN1 appears to have a minor role in HJ resolution, and, instead, other structure-specific endonucleases (SSE) that recognize branched DNA play the leading roles, Mus81-Mms4/EME1 being the most important in budding yeast. Interestingly, cells tightly regulate the activity of each HJ resolvase during the yeast cell cycle. Thus, Mus81-Mms4 is activated in G2/M, while Yen1 gets activated shortly afterwards. Nevertheless, cytological studies have shown that Yen1 is sequestered out of the nucleus when cyclin-dependent kinase activity is high, i.e., all of the cell cycle but G1. We here show that the mitotic master phosphatase Cdc14 targets Yen1 to the nucleus in early anaphase through the FEAR network. We will further show that this FEAR-mediated Cdc14-driven event is sufficient to back-up Mus81-Mms4 in removing branched DNA structures, which are especially found in the long chromosome arms upon replication stress. Finally, we found that MEN-driven Cdc14 re-activation in late anaphase is essential to keep Yen1 in the nucleus until the next G1. Our results highlight the essential role that early-activated Cdc14, i.e., through the FEAR network, has in removing all kind of non-proteinaceous linkages that preclude faithful sister chromatid segregation in anaphase. In addition, our results support the general idea of Yen1 acting as a last resource endonuclease to deal with any remaining HJ that might compromise genetic stability during chromosome segregation.
The Vanishing Body of Frantz Fanon in Paul Gilroy's Against Race and After Empire

I N Against Race: Imagining Political Culture Beyond the Color Line (2000) and After Empire: Melancholia or Convivial Culture (2004), black British sociologist Paul Gilroy makes a highly provocative contribution to racial theorization. 1 The two books stand together as a radical intervention against what Gilroy calls "raciological thinking," and particularly target ideas about racial formation and identity developed and practiced by black peoples. Indeed, Gilroy links black nationalist thought to fascism, and argues that "democratic and cosmopolitan traditions . have been all but expunged from today's black political imaginary. " Not surprisingly, this work has generated critiques by black scholars from across the theoreticalpolitical spectrum. Patricia Hill Collins faults its failure to address the ghastly material conditions to which contemporary black culture responds. To Don Robotham, Gilroy's promotion of a race-less cosmopolitanism reflects an indifference to both the legislative and economic dimensions of globalization. 4 Simon Gikandi criticizes Gilroy's Enlightenment-derived planetary humanism for overlooking the racism that is integral to this philosophical tradition. Gilroy's preference for white Western over black intellectual, political and cultural expression is discerned, and criticized, in other ways too. Dorothy Roberts complains that he foregrounds the contributions of white liberals over those of black solidarity movements; Carol Boyce Davies points out the Gilroy ignores the important political-cultural work of the Caribbean Arts movement in the United Kingdom.