Miracle-dz/UniFAR-FTUs huggingface dataset:
Exome sequencing identifies a DNAJB 6 mutation in a family with dominantly-inherited limb-girdle muscular dystrophy

Limb-girdle muscular dystrophy primarily affects the muscles of the hips and shoulders (the “limb-girdle” muscles), although it is a heterogeneous disorder that can present with varying symptoms. There is currently no cure. We sought to identify the genetic basis of limb-girdle muscular dystrophy type 1 in an American family of Northern European descent using exome sequencing. Exome sequencing was performed on DNA samples from two affected siblings and one unaffected sibling and resulted in the identification of eleven candidate mutations that co-segregated with the disease. Notably, this list included a previously reported mutation in DNAJB6, p.Phe89Ile, which was recently identified as a cause of limb-girdle muscular dystrophy type 1D. Additional family members were Sanger sequenced and the mutation in DNAJB6 was only found in affected individuals. Subsequent haplotype analysis indicated that this DNAJB6 p.Phe89Ile mutation likely arose independently of the previously reported mutation. Since other published mutations are located close by in the G/F domain of DNAJB6, this suggests that the area may represent a mutational hotspot. Exome sequencing provided an unbiased and effective method for identifying the genetic etiology of limb-girdle muscular dystrophy type 1 in a previously genetically uncharacterized family. This work further confirms the causative role of DNAJB6 mutations in limb-girdle muscular dystrophy type 1D. 2014 Elsevier B.V. All rights reserved.
Estimation of isoform expression using hierarchical Bayesian model by RNA-seq

Abnormal expression of isoforms may cause complex human diseases. So it is crucial to estimate isoform expression and identify the abnormal isoforms. RNA-seq technology enables us to monitor the expression on genome-wide scale at single base pair resolution. Many methods are developed to estimate isoform expression based on this technology. But all these methods treat gene expression as a by-product by the way of summing its corresponding isoforms expression and don't exploit the relationship between gene and its isoforms expression. In this paper, we develop a new hierarchical Bayesian method to estimate isoforms expression. In this model, we treat the gene expression as the sum of its corresponding isoforms expression, and we explicitly model the gene expression level and the relationship between gene and corresponding isoforms using Multinomial distribution. By this way, gene expression is treated as a variable and can be included in a unify framework. More importantly, the relationship between gene and its isoforms help us to achieve a higher accuracy on isoform expression level. The simulation and real data studies show that our method is more effective than other state-of-the-art algorithms for isoform expression estimation.
Metamorphic labral axis patterning in the beetle Tribolium castaneum requires multiple upstream, but few downstream, genes in the appendage patterning network

The arthropod labrum is an anterior appendage‐like structure that forms the dorsal side of the preoral cavity. Conflicting interpretations of fossil, nervous system, and developmental data have led to a proliferation of scenarios for labral evolution. The best supported hypothesis is that the labrum is a novel structure that shares development with appendages as a result of co‐option. Here, we use RNA interference in the red flour beetle Tribolium castaneum to compare metamorphic patterning of the labrum to previously published data on ventral appendage patterning. As expected under the co‐option hypothesis, depletion of several genes resulted in similar defects in the labrum and ventral appendages. These include proximal deletions and proximal‐to‐distal transformations resulting from depletion of the leg gap genes homothorax and extradenticle, large‐scale deletions resulting from depletion of the leg gap gene Distal‐less, and smaller distal deletions resulting from knockdown of the EGF ligand Keren. However, depletion of dachshund and many of the genes that function downstream of the leg gap genes in the ventral appendages had either subtle or no effects on labral axis patterning. This pattern of partial similarity suggests that upstream genes act through different downstream targets in the labrum. We also discovered that many appendage axis patterning genes have roles in patterning the epipharyngeal sensillum array, suggesting that they have become integrated into a novel regulatory network. These genes include Notch, Delta, and decapentaplegic, and the transcription factors abrupt, bric à brac, homothorax, extradenticle and the paralogs apterous a and apterous b.
Nuclear matrix proteins in well and poorly differentiated human breast cancer cell lines

The nuclear matrix, besides providing the structural support of the nucleus, is involved in various cellular functions of the nucleus. Nuclear matrix proteins (NMPs), which are both tissue‐ and cell type–specific, are altered with transformation and state of differentiation. Furthermore, NMPs have been identified as informative markers of disease states. Here, the NMP profiles from human breast cancer cell lines and breast tumours were analyzed using two‐dimension gel electrophoresis. We identified NMPs that are associated with well and poorly differentiated human breast cancer cells in vitro and in vivo. Five NMPs (NMBC 1–5) were found to be exclusive for well‐differentiated human breast cancer cells, while one NMP (NMBC‐6) was found to be present only in poorly differentiated human breast cancer cells. The identification of these proteins suggests the potential use of nuclear matrix proteins as prognostic indicators. J. Cell. Biochem. 66:9–15, 1997. © 1997 Wiley‐Liss, Inc.
The Deterrent Effect of Public Surveillance Cameras on Crime

We investigate if there is any effect on crime following the installation of public surveillance cameras. To do so, we benefit from a quasi-experiment that took place in Medellin, Colombia with the installation of 587 cameras between 2013 and 2015. We highlight three main findings. First, there is a statistically significant decline in total crime after the installation of the cameras. On average, total crime reports are 23.5% lower within the coverage zone following the installation of a camera relative to the average baseline level of crime reports. Second, we also find a statistically significant decline in arrests. The magnitude of this effect is 31.5% relative to the average baseline level of arrests. Along with the facts that the monitoring capacity of the system of public surveillance cameras is low and decreased during the installation period, and the two year installation period is unlikely to allow for the public surveillance cameras to be used by the criminal justice system for aggravated sentences, these results suggest that the effect of the surveillance cameras on reported crime are driven by a deterrent effect on potential offenders. Third, we do not find any crime spillover effects after the installation of the cameras nor we see any diffusion of benefits to surrounding places.
The Negative Effects of Mergers and Acquisitions on the Value of Rivals

Average stock price reactions of industry rivals in horizontal U.S. mergers and acquisitions around deal announcements are robustly negative. This finding is in contrast to the results in the existing literature, which focuses on smaller samples of deals involving mostly publicly listed firms. Rivals’ returns are more negative in growing and concentrated industries. Moreover, the negative rivals’ stock price reactions are related to future decreases in operating performance, increased probability of bankruptcy and challenges by antitrust authorities, and increased probability of rivals’ future acquisitions. Overall, these results suggest that M&As have strong competitive effects for the rivals of target companies.
Pharmacophore modelling: applications in drug discovery

This review highlights the concept of using pharmacophore models in modern drug research and reviews some important examples as well as success stories. This includes papers from both method-development and application areas. As indicated by the number of publications available, the pharmacophore approach has proven to be extremely useful not only in virtual screening and library design for efficient hit discovery, but also in the optimisation of lead compounds to clinical candidates. Recent studies focus on the use of parallel screening using pharmacophore models for bioactivity profiling and early stage risk assessment of potential side effects and toxicity, due to the interaction of drug candidates with antitargets.
Identification of New Influenza B Virus Variants by Multiplex Reverse Transcription-PCR and the Heteroduplex Mobility Assay

ABSTRACT A quick genetic approach for the screening of influenza virus variants was developed in this laboratory (S. Zou, J. Clin. Microbiol. 35:2623–2627, 1997). It uses multiplex reverse transcription and multiplex PCR to amplify and differentiate the variable region of the hemagglutinin genes of different types and subtypes of influenza viruses. Variants within the same type or subtype are then identified by the heteroduplex mobility shift assay of the amplicons. The method was used to screen influenza virus isolates received from provincial laboratories during the 1996–1997 season and was able to identify new influenza B virus variants. Sequencing of the amplicons derived from the hemagglutinin gene of the identified variants and comparison with the vaccine strain B/Harbin/7/94 showed substitution rates of 2.26 to 2.55% at the nucleotide level and 4.26 to 4.68% at the amino acid level. The result further demonstrated that the approach provides a quick, sensitive, and reliable screening for influenza virus variants. It also suggested the necessity of close monitoring of influenza B virus isolates in the 1997–1998 season and critical evaluation of the reference strain for the type B influenza virus.
Timing and coordination in tone and intonation — An articulatory-functional perspective

Timing is of critical importance for speech in general and for tone and intonation in particular. Yet our understanding of timing is still limited. In this paper I explore timing related issues from an articulatory-functional perspective, which views speech as communicative functions encoded through an articulation process. Based on this view, timing in speech can be seen as of two kinds, obligatory timing — timing as obligated by articulation, and informational timing — timing that encodes communicative meanings. I will show that the articulatory constraints of minimal movement duration and syllable-bound temporal alignment severely limit the freedom of using timing for information coding, leaving duration as the only controllable aspect of timing. I will further show that duration, as other aspects of speech, is used to encode multiple layers of communicative meanings in parallel, allowing concurrent encoding of lexical contrast, focus, and inter-constituent affinity. Such information coding seems to account for previously reported duration patterns such as polysyllabic shortening and constituent-edge lengthening. Furthermore, to the extent the reported weak isochrony tendency can be explained by information coding and articulatory mechanisms that have little to do with isochrony, speech rhythm seems to be an epiphenomenon rather than a basic mechanism.
Navigation-assisted bronchoscopy for ground-glass opacity lesions.

We thank Dr. Chaves and colleagues for their interest and comments on our article (1). We have attempted to diagnose ground-glass opacity (GGO)-predominant-type lesions by bronchoscopic biopsy using endobronchial ultrasonography with a guide sheath (EBUS-GS) (1,2). The diagnostic rate of GGO-predominant-type lesions is lower than that of solid-type lesions. One of the reasons for this is that the lesions may not be visible under X-ray fluoroscopy.
[C ii] 158-μm emission from the host galaxies of damped Lyman-alpha systems

Gas emission lines from damped Lyman-α systems probe galaxy evolution in the early universe. Identifying the hosts of quasar absorbers If the line of sight from Earth to a distant quasar passes through foreground material, some of the quasar's light is absorbed. If a galaxy-sized quantity of gas intervenes, it forms a damped Lyman α system (DLA), visible as absorption lines in the quasar spectrum. Using the Atacama Large Millimeter/Submillimeter Array, Neeleman et al. observed two quasars with known DLAs. They detected emission from gas and dust in two foreground galaxies associated with the DLAs and were able to measure their star-formation rates. Combining these different tracers of DLAs will help us understand how galaxies evolved in the early universe. Science, this issue p. 1285 Gas surrounding high-redshift galaxies has been studied through observations of absorption line systems toward background quasars for decades. However, it has proven difficult to identify and characterize the galaxies associated with these absorbers due to the intrinsic faintness of the galaxies compared with the quasars at optical wavelengths. Using the Atacama Large Millimeter/Submillimeter Array, we report on detections of [C ii] 158-μm line and dust-continuum emission from two galaxies associated with two such absorbers at a redshift of z ~ 4. Our results indicate that the hosts of these high-metallicity absorbers have physical properties similar to massive star-forming galaxies and are embedded in enriched neutral hydrogen gas reservoirs that extend well beyond the star-forming interstellar medium of these galaxies.
Non-stealth and stealth solid lipid nanoparticles (SLN) carrying doxorubicin: pharmacokinetics and tissue distribution after i.v. administration to rats.

Non-stealth and stealth solid lipid nanoparticles (SLN) carrying doxorubicin were prepared as drug delivery systems. The pharmacokinetics and tissue distribution of doxorubicin in these SLN were studied after i.v. administration to conscious rats and were compared to the commercial solution of doxorubicin. The same dose of each formulation (6 mg kg(-1)of body weight) of doxorubicin was injected in the rat jugular vein. Blood samples were collected after 1, 15, 30, 45, 60 min and 2, 3, 6, 12, and 24 h after the injection. Rats were sacrificed after intervals of 30 min, 4 h, and 24 h and samples of liver, spleen, heart, lung, kidney, and brain were collected. In all samples, the concentration of doxorubicin and of the metabolite, doxorubicinol, were determined. Doxorubicin and doxorubicinol were still present in the blood 24 h after injection of stealth and non-stealth SLN, while they were not detectable after the injection of the commercial solution. The results confirmed the prolonged circulation time of the SLN compared to the doxorubicin solution. In all rat tissues, except the brain, the amount of doxorubicin was always lower after the injection of the two types of SLN than after the injection of the commercial solution. In particular, SLN significantly decreased the heart concentration of doxorubicin.
Modeling the Innovative Behavior of Firms within the Manufacturing Sector in a Border Regional Perspective

This paper examines innovative behavior of firms by use of probit models. Based on a questionnaire undertaken in Western Denmark (Fuen and Jutland) and Northern Germany (Schleswig-Holstein and Mecklenburg-Vorpommern) a model is set up to identify the factors influencing the probability of a successful innovative action. After a presentation of the design of the questionnaire, and a discussion of the quality of the sample several probit models are estimated. In order to examine the influence of the bias imposed by firms not undertaking any innovative behavior at all the sample is reestimated by use of the Heckman procedure set up in a bivariate set up. It is found that factors such as efficient use of technology and business culture contribute positively to a successful innovation, whereas supply chains contribute negatively. Among the background variables joint ventures contribute positively, whereas public support not has any significant influence. Many of these results are confirmed in a border regional perspective. Finally, taking into account the bias strengthens the results. Key-words: Innovation, regional development, clusters, probit models, sample selection bias. ──────────────────────────────────────────────────── The present paper is a revised version of a paper entitled “Systems of Innovation and Linkages in an Interregional Perspective: A Comparative Analysis of Northern Germany and Western Denmark” published as Chapter 17 (page 475498) in: Karlsson C. , Johansson B, and Stough R.R. (editors) (2005) “Industrial Clusters and Inter-Firm Networks”. Edgar Elgar Publishers ISBN 1-88542-010-1. The paper was originally prepared for ‘The Uddevalla Symposium 2004’ “Regions in Competition and Co-operation” in Fredriksstad, Norway, June 17–19, 2004. The authors like to thank for valuable comments from the discussants at the seminar especially Pillip McCann, University of Reading, UK. ∗ Department of Environmental and Business Studies, Niels Bohrs vej 9, DK-6700 Esbjerg, Denmark. Phone +45 6550 4183. ∗∗ Grundtvigs Alle 150, DK-6400 Sonderborg, Denmark. Phone +45 655
Structured Overlay Networks for a New Generation of Internet Services

The dramatic success and scaling of the Internet was made possible by the core principle of keeping it simple in the middle and smart at the edge (or the end-to-end principle). However, new applications bring new demands, and for many emerging applications, the Internet paradigm presents limitations. For applications in this new generation of Internet services, structured overlay networks offer a powerful framework for deploying specialized protocols that can provide new capabilities beyond what the Internet natively supports by leveraging global state and in-network processing. The structured overlay concept includes three principles: A resilient network architecture, a flexible overlay node software architecture that exploits global state and unlimited programmability, and flow-based processing. We demonstrate the effectiveness of structured overlay networks in supporting today's demanding applications and propose forward-looking ideas for leveraging the framework to develop protocols that push the boundaries of what is possible in terms of performance and resilience.
Educational content in nurse education in Japan: A Delphi study

The purpose of this study was to clarify the minimum necessary educational content in the area of nursing ethics in a basic nursing education program, and the level of students’ mastery of this content, based on a Delphi study in both educational and clinical settings. A Delphi study was conducted in three rounds with faculty members who teach nursing ethics at all 158 four-year nursing universities in Japan as targeted panelists. In this study the opinions on nursing ethics of nursing instructors responsible for hospital education at all 82 special functioning hospitals were reflected in the panelists’ opinions. Consensus was obtained on 41 items from a total of 63 items in 4 proposed frameworks. There were 20 items related to the Concept of nursing ethics, 7 items related to Ethical codes, 13 items related to Ethical issues and methods to resolve them, and 1 item related to Efforts and issues in practical and educational settings. Consensus as to desired level of mastery was reached on a total of 40 items. This agreed-upon level involved understanding of the concept for 22 items, the ability to explain the concept for 16 items, and the ability to act based on the concept for 2 items.
Histamine Metabolism and Female Sex Hormones in Women

Abstract. Oral combined contraceptives did not seem to alter histamine metabolism in females. During treatment with gonadotrophic hormones in four amenorrhoeic patients there was a tendency towards increasing excretion of methylhistamine (MeHi) followed by a sudden decrease corresponding to changes in the urinary estrogen. the excretion of methylimidazoleacetic acid (MeImAA) seemed to parallel that of MeHi. the findings support the hypothesis that an endogenous surge of estrogen may influence histamine turnover in women. Women of postmenopausal age have about the same histamine metabolism as younger menstruating women. Estrogen medication relieved symptoms of hot flushes or sweats but did not seem to affect the histamine turnover.
Title : Assessing the efficiency of catch-up campaigns for introduction of 1 pneumococcal conjugate vaccine ; a modelling study based on data from Kilifi , 2 Kenya 3 Short title : The efficiency of catch-up campaigns for PCV introduction 4

20 21 Background: The World Health Organisation recommends the use of catch-up campaigns as 22 part of the introduction of pneumococcal conjugate vaccines (PCVs) to accelerate herd 23 protection and hence PCV impact. The value of a catch-up campaign is a trade-off between 24 the costs of vaccinating additional age groups and the benefit of additional direct and 25 indirect protection. There is a paucity of observational data, particularly from low-middle 26 income countries to quantify the optimal breadth of such catch-up campaigns. 27 28 Methods: In Kilifi, Kenya PCV10 was introduced in 2011 using the 3-dose EPI infant schedule 29 and a catch-up campaign in children <5 years old. We fitted a transmission dynamic model 30 to detailed local data including nasopharyngeal carriage and invasive pneumococcal disease 31 (IPD) to infer the marginal impact of the PCV catch-up campaign over hypothetical routine 32 cohort vaccination in that setting, and to estimate the likely impact of alternative campaigns 33 and their dose-efficiency. 34 35 Results: We estimated that, within 10 years of introduction, the catch-up campaign among 36 <5y olds prevents an additional 65 (48 to 84) IPD cases, compared to PCV cohort 37 introduction alone. Vaccination without any catch-up campaign prevented 155 (121 to 193) 38 IPD cases and used 1321 (1058 to 1698) PCV doses per IPD case prevented. In the years 39 after implementation, the PCV programme gradually accrues herd protection and hence its 40 dose-efficiency increases: 10 years after the start of cohort vaccination alone the 41 programme used 910 (732 to 1184) doses per IPD case averted. We estimated that a two42 dose catch-up among <1y olds uses an additional 910 (732 to 1184) doses per additional IPD 43 case averted. Furthermore, by extending a single dose catch-up campaign to children 1 to 44 <2y old and subsequently to 2 to <5y olds the campaign uses an additional 412 (296 to 606) 45 and 543 (403 to 763) doses per additional IPD case averted. These results were not sensitive 46 to vaccine coverage, serotype competition, the duration of vaccine protection or the 47 relative protection of infants. 48 49 Conclusions: We find that catch-up campaigns are a highly dose-efficient way to accelerate 50 population protection against pneumococcal disease. 51 52
Cocirculation of Two Lineages of Toscana Virus in Croatia

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Cocirculation of Two Lineages of Toscana Virus in Croatia Nazli Ayhan, Bülent Alten, Vladimir Ivovic, Franjo Martinkovic, Ozge Kasap, Yusuf Ozbel, Xavier de Lamballerie, Rémi Charrel