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Cet article porte sur l’exemplarité problématique des romans français du XIXe siècle mobilisant une visée prophylactique, soit des romans où l’éthique est explicitement reliée au récit d’une maladie. Exemplarité problématique dans la mesure où le comportement décrit dans la fiction n’est a priori pas le comportement à suivre en dehors de la fiction. Cette tension entre finalité romanesque et finalité éthique recoupe en outre un des enjeux majeurs auquel le roman du xixe siècle doit faire face : prouver sa capacité à produire et à transmettre un savoir en prise avec le réel, en dépit des accusations traditionnelles faisant de lui un art trompeur. This article deals with the problematic exemplarity of 19th century French novels with a prophylactic aim, i.e. novels in which ethics is explicitly linked to the narrative of a disease. This exemplarity is problematic insofar as the behaviour described in the fiction is not a priori the behaviour to be followed outside the fiction. This tension between novel finality and ethical finality also overlaps with one of the major challenges facing the novel in the nineteenth century: proving its capacity to produce and transmit knowledge that is in touch with reality, despite the traditional accusations that it is a deceptive art form.

Cellulose is the utmost plenteous source of biopolymer in our earth, and fungi are the most efficient and ubiquitous organism in degrading the cellulosic biomass by synthesizing cellulases. Tailoring through genetic manipulation has played a substantial role in constructing novel fungal strains towards improved cellulase production of desired traits. However, the traditional methods of genetic manipulation of fungi are time-consuming and tedious. With the availability of the full-genome sequences of several industrially relevant filamentous fungi, CRISPR-CAS (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein) technology has come into the focus for the proficient development of manipulated strains of filamentous fungi. This review summarizes the mode of action of cellulases, transcription level regulation for cellulase expression, various traditional strategies of genetic manipulation with CRISPR-CAS technology to develop modified fungal strains for a preferred level of cellulase production, and the futuristic trend in this arena of research.

Homo sapiens' civilization is a complex adaptive system. Although it is similar to the population of genetic systems, it more closely resembles the network of ecosystems forming the biosphere or a global computer network with its multitude of sub-networks. The author proposed a conceptual model of shaping the culture following the pattern of evolution and succession in biological ecosystems. Using a simulation implementation, he verified its consistency and adequacy both for the process of shaping culture in various environmental conditions and for the "vertical" process of transferring culture between generations

Cet article propose de retracer dans l’œuvre de Foucault la présence d’un engagement critique discret mais continu avec la catégorie aristotélicienne de la phronesis. Au cours des années 1970, Foucault consacre ses recherches à de nombreuses instances de la techné, savoir pratique proche mais distinct de la phronesis. S’il ne mentionne pratiquement pas cette dernière, nous montrerons cependant que ce non-dit est tout sauf un impensé. C’est par un travail de et sur la phronesis que Foucault pensera la complexité des savoirs pratiques et négociera la distinction entre sa propre méthode, dite « généalogique », et les méthodes qu’il prend pour objet. Nous verrons que cette distinction s’articule autour d’un second doublet, celui du cas et de la singularité – une distinction qui prend tout son sens lorsqu’elle est passée au crible de la triade aristotélicienne du savoir : épistémè, techné et phronesis. Nous verrons que la notion foucaldienne de singularité, loin d’être identique au cas particulier, en constitue plutôt le principe de différence interne. En substituant une herméneutique de la singularité à une herméneutique du particulier, Foucault s’autorise à penser une phronesis renouvelée pour les temps présents. This article proposes to trace the presence of a discreet but continuous critical engagement with the Aristotelian category of phronesis in Foucault’s work. During the 1970s, Foucault’s research was devoted to several instances of techne, a form of practical wisdom close to, yet distinct from, phronesis. Although he hardly mentions the latter, we will show that this omission is anything but an oversight. It is through the work of phronesis and on phronesis that Foucault thinks the complexity of practical wisdom and negotiates the distinction between his own “genealogical” method and the methods that he studies. We will see that this distinction is articulated around a second doublet, that of the case and the singularity—a distinction whose meaning becomes clear once it is scrutinised through the lens of the Aristotelian triad of knowledge: episteme, techne, and phronesis. We will see that the Foucauldian notion of singularity, far from being identical to the particular case, constitutes rather its principle of internal difference. By substituting the hermeneutics of singularity for the hermeneutics of the particular, Foucault is able to articulate a renewed phronesis adapted to the present moment.

The gold standard for the treatment of carotid artery stenosis is the carotid endarterectomy (CEA). According to current guidelines, carotid artery stenting (CAS) is an alternative. Randomized control trials (RCTs) show significantly higher rates of peri-interventional strokes after CAS compared to CEA. However, these trials were usually characterized by a great heterogeneity in the CAS procedure. In this retrospective analysis from 2012 to 2020, 202 symptomatic and asymptomatic patients were treated with CAS. Patients were carefully pre-selected according to anatomical and clinical criteria. In all cases, the same steps and material were used. All interventions were performed by five experienced vascular surgeons. Primary endpoints of this study were perioperative death and stroke. Asymptomatic carotid stenosis was present in 77% of the patients and symptomatic in 23%. The mean age was 66 years. The average degree of stenosis was 81%. The CAS technical success rate was 100%. Periprocedural complications occurred in 1.5% of cases, including one major stroke (0.5%) and two minor strokes (1%). The results of this study indicate that through a strict patient selection based on anatomical and clinical criteria, CAS can be performed with very low complication rates. Furthermore, standardization of the materials and the procedure itself is crucial.

ObjectiveCranial autonomic symptoms (CAS), including conjunctival injection, tearing, nasal congestion or rhinorrhea, eyelid edema, miosis or ptosis, and forehead or facial sweating ipsilateral to headache, are often reported by patients with migraine during headache attacks. CAS is a consequence of the activation of the trigeminovascular system, which is the target of monoclonal antibodies acting on the CGRP pathway. Therefore, we hypothesized that patients with CAS might have higher trigeminovascular activation than those without CAS leading to a better response to anti-CGRP treatments.MethodsWe performed a prospective analysis including patients with episodic or chronic migraine treated with anti-CGRP monoclonal antibodies (i.e., erenumab, fremanezumab, and galcanezumab) between 2019 and 2021. The observation period included a 12-week baseline before treatment with anti-CGRP antibodies and a 12-week treatment follow-up. We evaluated the prevalence of CAS in our cohort and compared disease characteristics and treatment response (i.e., 12-week monthly headache days and 0–29, 30–49, 50–74, 75–99, and 100% monthly headache days reduction from baseline) among patients with and without CAS using the χ2 test, Kruskal–Wallis test, and Mann–Whitney U-test.ResultsOut of 136 patients, 88 (65%) had CAS. Both patients with and without CAS reported a significant decrease in monthly headache days from baseline. During the 12-week follow-up, the median difference in monthly headache days from baseline was higher in patients with CAS (-10, IQR−15 to−6) than in those without CAS (6, IQR 12 to 3; P = 0.009). However, the proportions of patients with 0 to 29, 30 to 49, 50 to 74, 75 to 99, and 100% response rates did not differ between the two groups.ConclusionsIn our cohort, the presence of CAS was associated with a greater response to monoclonal antibodies targeting the CGRP pathway. CAS could be a clinical marker of trigeminovascular activation and thus be related to a better response to CGRP treatments.

Although ground troops are equipped with identification, friend or foe (IFF) devices, many fratricide cases still occur during air-to-ground operations. When they are engaged in a firefight, ground troops seek cover and concealment, and consequently, their attached IFF devices are also covered and concealed. The situation is aggravated when firefights happen at night in vegetated areas, presenting additional challenges for air force pilots when conducting close air support (CAS) operations. Hence, ground troops need to be able to deploy a visual reference above the canopy of vegetation while they remain concealed physically. This research project explored how relatively inexpensive commercial off-the-shelf (COTS) technologies can be leveraged to construct a maneuverable aerial identification friend-or-foe (MAIFF) device. A systems engineering approach was employed to produce a prototype MAIFF using a sub-250 gram quadcopter drone mounted with infrared lights. In testing, its illumination lasted up to six hours. Although invisible to the naked eye, its illumination was visible up to one mile away with the use of a night vision device. A scenario-based test is recommended as a step toward MAIFF adoption by military organizations. Testing the MAIFF will determine whether it enhances situation awareness, reduces the occurrence of fratricide, and increases the lethality of CAS. CRUSER (Consortium for Robotics and Unmanned Systems Education and Research) Colonel, Philippine Army Approved for public release. Distribution is unlimited.

Nucleotide-binding domain-leucine-rich repeat-type immune receptors (NLRs) protect plants against pathogenic microbes through intracellular detection of effector proteins. However, this comes at a cost, as NLRs can also induce detrimental autoimmunity in genetic interactions with foreign alleles. This may occur when independently evolved genomes are combined in inter- or intraspecific crosses, or when foreign alleles are introduced by mutagenesis or transgenesis. Most autoimmunity-inducing NLRs are encoded within highly variable NLR gene clusters with no known immune functions, which were termed autoimmune risk loci. Whether risk NLRs differ from sensor NLRs operating in natural pathogen resistance and how risk NLRs are activated in autoimmunity is unknown. Here, we analyzed the DANGEROUS MIX2 risk locus, a major autoimmunity hotspot in Arabidopsis thaliana. By gene editing and heterologous expression, we show that a single gene, DM2h, is necessary and sufficient for autoimmune induction in three independent cases of autoimmunity in accession Landsberg erecta. We focus on autoimmunity provoked by an EDS1-yellow fluorescent protein (YFP)(NLS) fusion protein to characterize DM2h functionally and determine features of EDS1-YFPNLS activating the immune receptor. Our data suggest that risk NLRs function in a manner reminiscent of sensor NLRs, while autoimmunity-inducing properties of EDS1-YFPNLS in this context are unrelated to the protein's functions as an immune regulator. We propose that autoimmunity, at least in some cases, may be caused by spurious, stochastic interactions of foreign alleles with coincidentally matching risk NLRs., GRC grant (Deutsche Forschungsgemeinschaft, DFG)German Research Foundation (DFG) [STU 642-1/1]; Leibniz price from the DFGGerman Research Foundation (DFG); Alfried Krupp von Bohlen und Halbach Stiftung; ERASMUS mobility program; Projekt DEAL, This work was funded by GRC grant STU 642-1/1 (Deutsche Forschungsgemeinschaft, DFG) to JS. UB is grateful for financial support by the Leibniz price from the DFG and the Alfried Krupp von Bohlen und Halbach Stiftung. FF was financed by an ERASMUS mobility program. We are grateful to Bianca Rosinsky for taking care of plant growth facilities and growing plants, and to Ruben Alcazar and Jane Parker for providing plasmids containing SRF3 Kond or RPP1-like R8/DM2h genomic DNA fragments. Jan Kemna is acknowledged for cloning of the DM2h cDNA, and Samuel Grimm for primary screening of DM2h-YFP Arabidopsis transformants. Open Access funding enabled and organized by Projekt DEAL.

Purpose Endovascular robotics is an emerging technology within the developing field of medical robotics. This was a prospective evaluation to assess safety and feasibility of robotic-assisted carotid artery stenting. Materials and Methods Consecutive cases of carotid artery stenting cases performed over period of 24 months, from May 2015 to October 2016, using the Magellan Robotic System (Hansen, Mountain View, CA) were included. All cases utilised the robotic system to navigate the arch, obtain a stable position in the common carotid artery, followed by manual manipulation of Embolic Protection Devices and self-expandable stents through the robotic catheter. Patients demographics, clinical indications, anatomical features, technical and clinical success, complication rate and hospital stay were prospectively recorded. Results Thirteen patients, 10 males (78.5%), with an average age of 68.7 years were treated. Mean follow up time was 30 months. Ten patients (91%) were symptomatic at presentation. Anatomical indications for endovascular stent insertion were previous open surgery to the neck ± radiotherapy (87.5%) and hostile anatomy for open surgery (12.5%). Technical success was 100% and the robotic system demonstrates enhanced stability during arch and lesion crossing. There were no neurological complications post-operatively. Average hospital stay was 3 days (range 2–6 days) and a change in serum creatinine of −7.8 μmol/L. There was no documented case of in stent restenosis, new or worsening neurology during follow-up. Conclusion These results illustrate safety and feasibility of robotic endovascular revascularisation for carotid disease and demonstrates potential to enhance peri-procedural safety through improved control and stability.

In the last decade, collaborative assembly systems (CAS) are becoming increasingly common due to their ability to merge the flexibility of a manual assembly system with the performance of traditional robotics. Technical constraints, e.g., dedicated tools or resources, or performance requirements, e.g., throughput, could encourage the use of a CAS built around a multi-robot and multi-operator layout, i.e., with a number of resources greater than 2. Starting from the development of a prototype multi-robot multi-operator collaborative workcell, a simulation environment was developed to evaluate the makespan and the degree of collaboration in multi-robot multi-operator CAS. From the simulation environment, a mathematical model was conceptualized. The presented model allows estimating, with a certain degree of accuracy, the performances of the system. The results have investigated how several process characteristics, i.e. the number and type of resources, the resources layout, the task allocation method, and the number of feeding devices, influence the degree of collaboration between the resources. Lastly, the authors propose a compact analytic formulation, based on an exponential function, and define the methods and the influence factors to determine its parameters.

Whether it is the Summer Olympics or the Winter Olympics, in order to resolve potential sports disputes, the Court of Arbitration for Sport (CAS) sets up a special ad hoc tribunal in the host city of the Olympic Games. Although CAS ad hoc rules have many similarities with ordinary procedures, they are different in terms of the legal basis, legal remedies, and certain procedural rules. During the Beijing 2022 Winter Olympics (Beijing 2022), the CAS Ad Hoc Division and the CAS Anti-Doping Division heard a total of seven cases. These cases involve issues such as provisional suspension of games, protection of minors, unreasonable delays in test results, cancellation of award ceremonies, and the timing of disputes. the CAS Ad Hoc Division decisions on the above issues can be regarded as the latest developments in the application of international sports arbitration rules.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) is one of the hallmark of biological tools, contemplated as a valid and hopeful alternatives to genome editing. Advancements in CRISPR-based technologies have empowered scientists with an editing kit that allows them to employ their knowledge for deleting, replacing and lately “Gene Surgery”, and provides unique control over genes in broad range of species, and presumably in humans. These fast-growing technologies have high strength and flexibility and are becoming an adaptable tool with implementations that are altering organism’s genome and easily used for chromatin manipulation. In addition to the popularity of CRISPR in genome engineering and modern biology, this major tool authorizes breakthrough discoveries and methodological advancements in science. As scientists are developing new types of experiments, some of the applications are raising questions about what CRISPR can enable. The results of evidence-based research strongly suggest that CRISPR is becoming a practical tool for genome-engineering and to create genetically modified eukaryotes, which is needed to establish guidelines on new regulatory concerns for scientific communities.

It is very common that Engineering students nd difficulties when studying advanced Mathematics subjects. To help in the teaching and learning process of such subjects, the teacher can use an adequate mathematical software. But not always the used given to these specific pieces of software is the right one. The use of a Computer Algebra System (CAS) to achieve this goal is a good idea mainly because programming with a CAS, the solution to a problem can be obtained step by step. This way, the student can check all the intermediate steps to get the solution and can nd the step or steps where the student made a mistake. In this talk, we introduce SPDES, a Stepwise Partial Differential Equation Solver (an extension of SFOPDES). SPDES deals with some second order PDE in addition to the first order PDE considered in SFOPDES. SPDES can be used as a self tutorial for PDE since it solves, step by step, the typical exercises within the topic. The type of PDE that SPDES can solve are: Pfaff Differential Equations, Quasi-linear PDE, Lagrange-Charpit Method for first order PDE, Heat equation, Wave equation and Laplace's equation. SPDES has been developed using the programming capabilities of the CAS Derive, providing not only the final result but also, optionally, the display of all the steps needed to solve typical exercises on PDE. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.

En este trabajo se analiza del uso del pódcast como herramienta de aprendizaje de una lengua extranjera, no solo como material complementario en un curso de idiomas, sino como curso independiente de lengua. Para ello se analizan veinte pódcast para aprender lenguas extranjeras, tanto para aprender español como otros idiomas. Se incide sobre todo en la presentación que hacen estos pódcast de la gramática, las unidades de significado, la pronunciación y la pragmática y se analiza la adaptación de dichos pódcast al nivel establecido por sus creadores. Finalmente, se describe el proceso de creación de un pódcast de ELE original desde la selección de temas, la secuenciación de las actividades y la creación de los guiones

Coronavirus is one of the causative agents for multiple human respiratory illnesses. A novel coronavirus, similar to the one that caused severe acute respiratory syndrome (SARS) in 2003, was identified as the cause of the current pandemic of coronavirus disease (COVID-19), which was first reported in late December 2019 in Wuhan, China. Since then, this novel coronavirus has spread across the globe, with most identified COVID-19 cases and fatalities occurring in the United States. In this Perspective, we discuss coronavirus pathogenicity, conventional antiviral therapies, prophylactic strategies, and novel treatment strategies for COVID-19. We highlight the application of CRISPR technology as an emerging pan-antiviral therapy. We also discuss the challenges of in vivo delivery of CRISPR components and propose novel approaches to achieve selective delivery exclusively into SARS-CoV-2-infected cells with high efficiency by hijacking the surface proteins of SARS-CoV-2.

'Critical Asthma Syndrome' (CAS) is an umbrella term proposed to include several forms of asthma, responsible for acute and life-threatening exacerbations. CAS requires urgent and adequate supportive and pharmacological treatments to prevent serious outcomes.The purpose of this review is to discuss current knowledge on the pharmacotherapeutic strategies for treatment of CAS.Airflow limitation, airway wall edema, and mucus plugs are the pathophysiological targets of pharmacological therapies. Strategies to achieve these goals are based on the use of various classes of drugs. Inhaled beta2-agonists are the mainstay of the initial therapy of CAS. Inhaled anticholinergic agents may be considered in the treatment of CAS in addition to beta 2 agonists. Systemic corticosteroids should be administered as soon as possible in order to counteract airway inflammation and restore normal airway sensitivity. The effectiveness of pharmacological therapies in CAS is linked not only to the timely use of drugsbut also to the dosage and route of administration. Early recognition and aggressive treatment are essential for the management of CAS; however, prevention is the best cure. Although significant progress has been made, further efforts are needed to implement an optimal exacerbation prevention strategy.

Ovaj radi bavi se raznim aspektima ugovora kojima stranke ugovaraju nadležnost Arbitražnog suda za sport za odlučivanje u njihovoj pravnoj stvari, kao i pojavnim oblicima arbitražnih ugovora – kako je propisano, kakav je stav u svojim odlukama zauzeo CAS i kako se o valjanosti takvih ugovora izjasnio Švicarski federalni sud u nekoliko svojih najrelevantnijih odluka. Namjera ovog rada jest ukazati na probleme s kojima se stranke pro futuro mogu susresti, uvođenjem subjektivnih interpretativnih kategorija (od strane tribunala) kao elemenata u strogo formalni zakonski akt, te ponuditi određene alternative nekim postupovnim principima ustanovljenima kroz praksu Švicarskog federalnog suda., This paper deals with the various aspects of contracts by which the parties agree on jurisdiction of the Court of Arbitration for Sport to decide their legal matter, as well as with the various manifestations of arbitration agreements - as prescribed by law; in regards to the CAS legal reasoning and the Swiss federal courts decision on the validity of such contracts in few of its most relevant cases. The purpose of this paper is to highlight the problems that parties may face pro futuro by introducing subjective interpretative categories (by tribunals) as elements in a strictly formal legal act, and to offer certain alternatives to some procedural principles established through the case law of the Swiss Federal Court.

Summary Genome editing and cis‐gene breeding have rapidly accelerated crop improvement efforts, but their impacts are limited by the number of species capable of being genetically transformed. Many dicot species, including some vital potato relatives being used to accelerate breeding and genetics efforts, remain recalcitrant to standard Agrobacterium tumefaciens‐based transformation. Hairy root transformation using Agrobacterium rhizogenes (A. rhizogenes) provides an accelerated approach to generating transgenic material but has been limited to analysis of hairy root clones. In this study, strains of A. rhizogenes were tested in the wild diploid potato relative Solanum chacoense, which is recalcitrant to infection by Agrobacterium tumefaciens. One strain of A. rhizogenes MSU440 emerged as being capable of delivering a T‐DNA carrying the GUS marker and generating transgenic hairy root clones capable of GUS expression and regeneration to whole plants. CRISPR/Cas9 reagents targeting the potato PHYTOENE DESATURASE (StPDS) gene were expressed in hairy root clones and regenerated. We found that 64%–98% of transgenic hairy root clones expressing CRISPR/Cas9 reagents carried targeted mutations, while only 14%–30% of mutations were chimeric. The mutations were maintained in regenerated lines as stable mutations at rates averaging at 38% and were capable of germ‐line transmission to progeny. This novel approach broadens the numbers of genotypes amenable to Agrobacterium‐mediated transformation while reducing chimerism in primary events and accelerating the generation of edited materials.

ObjectivesThis retrospective study compared two mandibular reconstruction procedures—conventional reconstruction plates (CR) and patient-specific implants (PSI)—and evaluated their accuracy of reconstruction and clinical outcome.MethodsOverall, 94 patients had undergone mandibular reconstruction with CR (n = 48) and PSI (n = 46). Six detectable and replicable anatomical reference points, identified via computer tomography, were used for defining the mandibular dimensions. The accuracy of reconstruction was assessed using pre- and postoperative differences.ResultsIn the CR group, the largest difference was at the lateral point of the condyle mandibulae (D2) -1.56 mm (SD = 3.8). In the PSI group, the largest difference between preoperative and postoperative measurement was shown at the processus coronoid (D5) with +1.86 mm (SD = 6.0). Significant differences within the groups in pre- and postoperative measurements were identified at the gonion (D6) [t(56) = -2.217; p = .031 ConclusionFor reconstructing mandibular defects, CR and PSI are eligible. In each case, the advantages and disadvantages of these approaches must be assessed. The functional and esthetic outcome of mandibular reconstruction significantly improves with the experience of the surgeon in conducting microvascular grafts and familiarity with computer-assisted surgery. Interoperator variability can be reduced, and training of younger surgeons involved in planning can be reaching better outcomes in the future.

Global navigation satellite systems (GNSSs) provide accurate positioning and timing services in a large gamut of sectors, including financial institutions, Industry 4.0, and Internet of things (IoT). Any industrial system involving multiple devices interacting and/or coordinating their functionalities needs accurate, dependable, and trustworthy time synchronization, which can be obtained by using authenticated GNSS signals. However, GNSS vulnerabilities to time-spoofing attacks may cause security issues for their applications. Galileo is currently developing new services aimed at providing increased security and robustness against attacks, such as the open service navigation message authentication (OS-NMA) and commercial authentication service (CAS). In this paper, we propose a robust and secure timing protocol that is independent of external time sources, and solely relies on assisted commercial authentication service (ACAS) and OS-NMA features. We analyze the performance of the proposed timing protocol and discuss its security level in relation to malicious attacks. Lastly, experimental tests were conducted to validate the proposed protocol.

Purpose of the article: The paper focuses on the potentials and benefits controlling provides for companies in the transition period towards industry 4.0. Operative production controlling provides data that shall be used in the future to apply the concept of smart factories. This article proposes a controlling archtitecture based on computer-aided standardization. Methodology/methods: The paper develops an architecture on operational production controlling based on an international literature review. Literature on controlling 4.0 are found mostly in publications in German language. While this literature has its focus on controlling as a whole or on strategic controlling, the paper has a look on operational controlling and its further usage and development towards smart factories. Scientific aim: The aim of this article is to develop a model of an operational production controlling architecture that is able to suite the requirements of smart factories by using computer-aided standarization. Findings: Research is working on concepts for industry 4.0 and its way towards real implementation. Competitive advantage in industry 4.0 is created through digitization and robotization. An architecture that fully complies to industry 4.0 is still waiting in real companies due to technical limitation in data storing, retrieval and processing as well as storage capacities. Conclusions: The paper discussed the devlopment of a controlling architecture suitable for industry 4.0. Already today controlling is making use of data. Smart factories shall make use of production data. Production controlling together with the CAS, that is able to provide standardized data on all manufacturing, maintenance, and auxiliary processes, systems are able to make a step forward towards smart factories. The concept of production controlling combined with the strengths of a CAS may be seen as the basis from which to target smart factories and industry 4.0.

The coronavirus disease 2019 (COVID-19) outbreak has caused not only significant physical health problems but also mental health disorders. Anxiety and fear appear to be the main psychological symptoms associated with COVID-19. The aim of this study was to investigate whether anxiety and fear related to COVID-19 are influenced by sociodemographics and whether specific conditions, such as positivity for COVID-19 or death among relatives and friends, can further enhance these symptoms. In this cross-sectional study, 697 Italians responded to an online survey assessing sociodemographic information, the presence/absence of positive cases, or deaths due to COVID-19 among relatives or acquaintances. The Coronavirus Anxiety Scale (CAS) and Fear of COVID-19 Scale (FCS-19S) were administered in order to assess the levels of anxiety and fear associated with COVID-19. The data were collected in November 2020. Anxiety and fear scores were positively correlated. Both male and female subjects with higher CAS scores also displayed higher FCS-19S scores. The CAS and FCS-19S scores tended to increase with age, with older subjects exhibiting higher scores than younger subjects. Additionally, respondents with lower educational levels demonstrated higher scores on both the CAS and FCS-19S. Similarly, respondents living with older people and/or experiencing the death of one or more relatives due to COVID-19 exhibited corresponding outcomes. This study demonstrates how the levels of anxiety and fear, measured by CAS and FCS-19S associated with COVID-19, are influenced by gender, age, cohabitation status, educational levels, and the presence of positive cases or deaths due to COVID-19.

Work in yeast models has benefitted tremendously from the insertion of epitope or fluorescence tags at the native gene locus to study protein function and behavior under physiological conditions. In contrast, work in mammalian cells largely relies on overexpression of tagged proteins because high-quality antibodies are only available for a fraction of the mammalian proteome. CRISPR/Cas9-mediated genome editing has recently emerged as a powerful genome-modifying tool that can also be exploited to insert various tags and fluorophores at gene loci to study the physiological behavior of proteins in most organisms, including mammals. Here we describe a versatile toolset for rapid tagging of endogenous proteins. The strategy utilizes CRISPR/Cas9 and microhomology-mediated end joining repair for efficient tagging. We provide tools to insert 3×HA, His(6)FLAG, His(6)-Biotin-TEV-RGSHis(6), mCherry, GFP, and the auxin-inducible degron tag for compound-induced protein depletion. This approach and the developed tools should greatly facilitate functional analysis of proteins in their native environment.

Optimism regarding potential epidemiological and conservation applications of modern gene drives is tempered by concern about the possibility of unintended spread of engineered organisms beyond the target population. In response, several novel gene drive approaches have been proposed that can, under certain conditions, locally alter characteristics of a population. One challenge for these gene drives is the difficulty of achieving high levels of localized population suppression without very large releases in the face of gene flow. We present a new gene drive system, tethered homing (TH), with improved capacity for both localization and population suppression. The TH drive is based on driving a payload gene using a homing construct that is anchored to a spatially restricted gene drive. We use a proof‐of‐concept mathematical model to show the dynamics of a TH drive that uses engineered underdominance as an anchor. This system is composed of a split homing drive and a two‐locus engineered underdominance drive linked to one part of the split drive (the Cas endonuclease). We use simple population genetic simulations to show that the tethered homing technique can offer improved localized spread of costly transgenic payload genes. Additionally, the TH system offers the ability to gradually adjust the genetic load in a population after the initial alteration, with minimal additional release effort. We discuss potential solutions for improving localization and the feasibility of creating TH drive systems. Further research with models that include additional biological details will be needed to better understand how TH drives would behave in natural populations, but the preliminary results shown here suggest that tethered homing drives can be a useful addition to the repertoire of localized gene drives.

Inspired by the entering of computer algebra systems (CAS) in the Danish upper secondary school mathematics program, this article addresses, from a theoretical stance, what may happen when traditional procedures are outsourced to CAS. Looking at the commands “solve” and “desolve,” it is asked what happens when such CAS procedures are objectified in the students’ minds, and what the nature might be of the resulting “objects.” The theoretical analyses draw on a selection of classical mathematics education frameworks on conceptualization and are related to the research literature on technology in mathematics education. The article suggests the following characteristics as elements of negative effects: loss of distinctive features of concept formation, a consequential reclassification of mathematical objects, instability of CAS solutions as objects, and prevailing a posteriori reasoning on students’ behalf when relying solely on CAS in their mathematical work.

Leta 2017 je minilo 50 let od prve objave romana Garcíe Márqueza Sto let samote, enega najpomembnejših romanov v špansko govorečem svetu in sodobni književnosti nasploh. Članek se osredotoča na vprašanje minevanja časa in z njim povezanega zgodovinskega, kolektivnega in osebnega spomina. Že v prvem stavku romana (»Mnogo let zatem, ko je čakal, da ga ustrele, se je polkovnik Aureliano Buendía spomnil tistega daljnega popoldneva, ko ga je oče peljal pogledat led«) se pojavi glagol spomniti se, ki sproži ves tok dogajanja v romanu. Spominjanje in pozabljanje je eden ključnih elementov v romanu, kjer se prepletajo dogodki iz realnega in namišljenega, magičnega sveta. Po eni strani García Márquez svoj roman umešča v zgodovinska dogajanja in s tem prispeva k obujanju spomina na dogodke, ki so bili pogosto zamolčani in o katerih zgodovinske knjige ne pišejo, po drugi strani pa gre tudi za kolektivni in osebni spomin protagonistov. Spominjanja, pozabljanja in obujanja spominov se avtor loti s posebnimi slogovnimi prijemi, s skladenjskimi in semantičnimi pristopi, kot so npr. raba določenih glagolskih oblik, ponavljanja in drugo.

The paper deals with the determination of intangible assets of Czech public sector. On 15 January 2013, the International Public Sector Accounting Standards Board issued new standard IPSAS 31 - Intangible assets. This standard represents a very sophisticated construction of accounting axioms moving public sector much closer to the private sector. The aim of this paper is to identify and make subsequent comparison of methodological elements in the context of intangible assets according to CAS and IPSAS 31. Moreover the paper tries to show the share of intangible fixed assets to the total assets throughout every type of organization of public sector like regions, municipalities, government departments etc. to assess subsequently the extent of possible impacts on financial situation in case of transition of financial reporting to IPSAS.

The aim of this paper is to outline a segment of lex sportiva that is grounded in the idiosyncrasies of the internal rules of the hearing procedure in sports sailing whereby the fundamental principles and concepts of sports law as well as the bodies involved in the process of forming sports law are being analysed. For this purpose, the general notion of sailing, its theoretical systematization and the basic features of its sports variant will be presented, in the context of which the organization, rules and regulations will be considered i.e. basic documents including the fundamental legal principles of sports law represented in the relevant sport, all of which for the purpose of re-establishing the sports law, its concept and nature i.e. its potentially interdisciplinary character. To this extent, the re-establishment of sports law and its specific features will be highlighted particularly through appropriate examples of court and arbitration practices as well as the specific rules of sports sailing, part of which are also the rules on the hearing procedure which will be roughly presented and thereby their compliance with the fundamental principles of sports law will be accordingly analysed.

A lot of nanomaterials are using T1-T2 dual mode magnetic resonance (MR) contrast agents (CAs), but multilayer nanowire (NW) with iron (Fe) and manganese (Mn) as T1-T2 dual modal CAs has not been reported yet. Herein, we synthesized a Fe/Mn multilayer NW with an adjustable Fe layer, as T1-T2 dual-mode CAs. The relaxation performance of Fe/Mn multilayer NW was studied at 1.5 T. Results show that, when the length of the Fe layer is about 10 nm and the Mn is about 5 nm, the r1 value (21.8 mM−1s−1) and r2 value (74.8 mM−1s−1) of the Fe/Mn multilayer NW are higher than that of Mn NW (3.7 mM−1s−1) and Fe NW (59.3 mM−1s−1), respectively. We predict that our Fe/Mn multilayer NW could be used as T1-T2 dual mode MRI CAs in the near future.

All across the country, officials and planners of the first-responder community plan for events of various types, yet their plans do not adequately account for crowd behavior when the event is interrupted by an act of violence that turns into a mass-casualty incident, or a “focus event.” This research contests early crowd psychology studies and presents the contemporary social identity theory, elaborated social identity model, and emergence model as better lenses for crowd behavior in responding to a focus event. Case studies of the 2013 Boston Marathon bombing and the 2017 Las Vegas mass shooting are used to analyze crowds that experienced focus events through the perspective of complex adaptive systems. A new framework that incorporates the elements of stress, panic, chaos, and priming is then presented to assist officials and planners with planning for crowds experiencing a focus event, with the aim of leveraging crowd emergence. The new framework presented in this research leads to a set of actionable recommendations for policymakers and planners. Ultimately, this thesis challenges officials and planners of the first-responder community to evaluate crowds as complex adaptive systems and explore the ability to leverage crowds for a more effective response. Civilian, Las Vegas Fire & Rescue Approved for public release. distribution is unlimited

En este trabajo se presentan resultados de un proyecto desarrollado dentro del Programa de Redes-I3CE de investigación en docencia universitaria del Instituto de Ciencias de la Educación de la Universidad de Alicante (UA). El diseño inicial del proyecto contemplaba una experiencia educativa consistente en realizar una implementación piloto del sistema STACK en asignaturas de Matemáticas de primer curso en distintas titulaciones de Ingeniería impartidas en la Escuela Politécnica Superior (EPS) de la UA, elaborando los materiales de autoaprendizaje y autoevaluación adecuados para los contenidos de las distintas asignaturas y evaluando la respuesta del alumnado participante en la experiencia. Se ha realizado una instalación de Moodle con STACK en un servidor propio del Departamento de Matemática Aplicada de la UA. Las limitaciones temporales y de capacidad del servidor han limitado la experiencia al alumnado pendiente de realizar el examen extraordinario en la asignatura de matemáticas de primer semestre en el Grado en Ingeniería Biomédica. Se han elaborado cuestionarios en STACK como herramienta de estudio y preparación de las pruebas de evaluación, recogiendo y analizando la actividad y opinión del alumnado participante. Como resultado del proyecto, se ha iniciado desde la EPS la instalación de un nuevo servidor, que permitirá la incorporación para el próximo curso de este tipo de actividades en el desarrollo de asignaturas de distintas titulaciones de Ingeniería.

In this paper we propose an asymmetrical approach to Case-licensing where, on the one hand, the functional architecture in the verbal system can license at most one DP, and, on the other, only certain DPs require formal licensing. Our proposal straightforwardly explains long-lasting syntactic problems in the syntax of Spanish and other languages concerning Differential Object Marking (DOM), Raising to Subject asymmetries in se constructions, and Person Case Constraint effects. Then, we analyze the consequences and challenges of our proposal for the explanation of the clitic behavior in laísta dialects in contexts where both internal arguments seem to be independently formally licensed, one of them via DOM, and the other by means of a dative clitic. We show that this dative clitic does not establish an agreement relation, but it is an incorporated determiner, as in the case of third person accusative clitics (Ormazabal and Romero 2013a)., En aquest article proposem una anàlisi asimètrica de la legitimació de cas en què, d’una banda, l’arquitectura funcional del sistema verbal només legitima, com a màxim, un SD, i, de l’altra, només un cert tipus de SD requereix una legitimació formal. La nostra proposta explica, sense complicacions addicionals, els problemes clàssics que afecten la sintaxi de les construccions amb Marcatge Diferenciat de l’Objecte (MDO) i amb elevació d’objecte, així com els efectes de la restricció de persona i cas, tant en espanyol com en altres llengües. També analitzem les conseqüències i els reptes que la nostra proposta planteja per explicar el comportament dels clítics en dialectes laïstes en contextos en què els dos arguments interns semblen legitimar-se de maneres formalment independents: un mitjançant el MDO i l’altre gràcies a un clític de datiu. En aquest sentit, demostrem que aquest clític datiu no estableix cap relació de concordança, sinó que és un determinant que s’incorpora, com passa amb els clítics acusatius de tercera persona (Ormazabal i Romero 2013a).

Type IV CRISPR systems encode CRISPR associated (Cas)-like proteins that combine with small RNAs to form multi-subunit ribonucleoprotein complexes. However, the lack of Cas nucleases, integrases, and other genetic features commonly observed in most CRISPR systems has made it difficult to predict type IV mechanisms of action and biological function. Here we summarize recent bioinformatic and experimental advancements that collectively provide the first glimpses into the function of specific type IV subtypes. We also provide a bioinformatic and structural analysis of type IV-specific proteins within the context of multi-subunit (class 1) CRISPR systems, informing future studies aimed at elucidating the function of these cryptic systems.

Background: Rituximab (RTX), a chimeric human-murine anti-CD20 monoclonal antibody, has been used for treatment of active moderate-severe Graves' orbitopathy (GO) since 2004 as second-line therapy in patients unresponsive to intravenous steroids. We conducted an open-label prospective study (EUDRACT 2012-001980-53) in which patients were treated with a single infusion of only 100 mg RTX to analyze the efficacy and safety of this low dose. Methods: Seventeen patients, of whom nine had disease that was unresponsive to intravenous methylprednisolone and eight with newly diagnosed GO, were enrolled. Disease activity was assessed with the clinical activity score (CAS) and severity with a composite ophthalmic score. Long-term surgical treatment and quality of life were also assessed, as well as treatment-related adverse events. Results: Mean baseline CAS was 4.56 ± 0.96 and decreased to 1.25 ± 1.14 at 24 weeks (p = 0.001). Disease inactivation occurred within 24 weeks in >90% of patients and was unrelated to disease duration. Severity improved in about 60% of patients, with no relapses. All patients showed peripheral depletion of CD20+ and CD19+ cells at the end of RTX infusion (60 minutes). Two patients required surgical orbital decompression because of optic neuropathy (ON). Among adverse events observed, there was one patient who developed a cytokine release syndrome. Conclusions: A dose of 100 mg RTX is effective in patients with active moderate-severe GO. Low doses are better tolerated, expose patients to immune suppression for a shorter period of time, and are extremely cost effective, compared with higher doses. This dose, consistently with all other immunosuppressants, does not prevent the progression of GO to dysthyroid ON.

Graphical abstract, Background It is a long-standing goal of scientists and breeders to precisely control a gene for studying its function as well as improving crop yield, quality, and tolerance to various environmental stresses. The discovery and modification of CRISPR/Cas system, a nature-occurred gene editing tool, opens an era for studying gene function and precision crop breeding. Aim of Review In this review, we first introduce the brief history of CRISPR/Cas discovery followed the mechanism and application of CRISPR/Cas system on gene function study and crop improvement. Currently, CRISPR/Cas genome editing has been becoming a mature cutting-edge biotechnological tool for crop improvement that already used in many different traits in crops, including pathogen resistance, abiotic tolerance, plant development and morphology and even secondary metabolism and fiber development. Finally, we point out the major issues associating with CRISPR/Cas system and the future research directions. Key Scientific Concepts of Review: CRISPR/Cas9 system is a robust and powerful biotechnological tool for targeting an individual DNA and RNA sequence in the genome. It can be used to target a sequence for gene knockin, knockout and replacement as well as monitoring and regulating gene expression at the genome and epigenome levels by binding a specific sequence. Agrobacterium-mediated method is still the major and efficient method for delivering CRISPR/Cas regents into targeted plant cells. However, other delivery methods, such as virus-mediated method, have been developed and enhanced the application potentials of CRISPR/Cas9-based crop improvement. PAM requirement offers the CRISPR/Cas9-targted genetic loci and also limits the application of CRISPR/Cas9. Discovering new Cas proteins and modifying current Cas enzymes play an important role in CRISPR/Cas9-based genome editing. Developing a better CRISPR/Cas9 system, including the delivery system and the methods eliminating off-target effects, and finding key/master genes for controlling crop growth and development is two major directions for CRISPR/Cas9-based crop improvement.

Male sterility is widely used in the production of hybrid seeds in rice, but the use of genic male sterility is limited because of the high labour cost for maintaining male‐sterile lines. Previous studies using T‐DNA insertional mutagenesis demonstrated that disrupting the expression of oxophytodienoic acid reductase 3 (OPR3), which is involved in the jasmonate biosynthesis pathway, results in a kind of male sterility that can be restored to fertility by exogenous jasmonate in Arabidopsis. Here, we created male‐sterile mutations by editing the second and fourth exons of OsOPR7 in rice through clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated system 9. The induced mutagenesis at these exons resulted in 31.8% and 23.9% male‐sterile plants in the T0 generation, respectively. We screened male‐sterile lines that can be restored to fertility by exogenous methyl jasmonate in the T0, T1 and T2 rice populations and characterized the anther and agronomic traits of the transgenic plants. Results showed the successful generation of male‐sterile lines through the silencing of OsOPR7, the orthologous gene of Arabidopsis OPR3, in a field crop, paving the way for the establishment of a two‐line system for rice hybrid production. The system consists of a male‐sterile line that can be maintained by spraying methyl jasmonate and a restoring line that confers pollen.

A decade ago, only six manuscripts would be found on a PubMed search for "CRISPR," compared to 2,011 manuscripts in 2016. The purpose of this review is to discuss this emergent technology that has revolutionized molecular biological research in just a few years. Endogenous CRISPR mechanisms are harbored by bacteria and archaea as an adaptive defense system that targets foreign DNA from viruses and plasmids. CRISPR has been adapted as a genome editing tool in a plethora of organisms ranging from yeast to humans. This tool has been employed to create loss of function mutations, gain of function mutations, and tagged alleles in a wide range of settings. CRISPR is now extensively employed for genetic screens. CRISPR has also been adapted to study transcriptional regulation. This versatile and relatively facile technique has, and will be, tremendously impactful in research areas such as biomedical sciences, agriculture, and the basic sciences.

Introduction: Optical Coherence Tomography (OCT) is an intravascular imaging providing high-resolution images of morphological features of arterial wall. Nowadays, OCT is an accepted intravascular modality to study coronary arteries, stent implantation, and vessel injury. In the last decade, an increasing interest have been focused on the application of OCT in carotid arteries.Areas covered: Literature evidence in the application of OCT in carotid arteries still remains debated. So far, OCT has been used as a research tool, aiming to evaluate atherosclerotic plaques' features and stents' behavior after implantation. This paper is intended to summarize clinical evidences and practices in the use of OCT in carotid arteries district and during CAS procedures. Literature review was completed via Pubmed search using Keywords.Expert opinion: CAS is a safe and effective procedure when performed by trained physicians with a tailored approach. In this scenario, ambiguous pictures at ultrasound, angiography, and IVUS might be clarified using OCT.By providing unprecedented microstructural information on atherosclerotic plaques, OCT may identify the features of vulnerable carotid plaque and, by identifying possible defects after stent implantation as malapposition and plaque prolapse, it may help the tailoring approach to CAS.

Membrane bioreactor (MBR) technology offers several advantages compared to the conventional wastewater treatment plants (CAS: conventional activated sludge) but also some disadvantages. Both advantages and disadvantages have implications for capital and operational costs. Therefore, the present chapter illustrates data from literature on costs for MBR and CAS. A comparison of such costs is also presented to assess the feasibility of the MBR for wastewater reclamation. The results obtained show that both capital costs (CAPEX) and operation and maintainance costs (OPEX) for MBR may be similar to those reported for CAS with tertiary treatment. A huge variability of CAPEX and OPEX, however, have been observed in the literature. Such variation depends on the design, management, and cost of the membranes. Since the purchase cost of the membranes has lowered in the last years, such reduction could improve the feasibility of MBR plants. Furthermore, the novel technology for membrane production and management (e.g., fouling control) as well as for process control (e.g., real-time monitoring) may help to optimize the operating conditions and, in turn, reduce the OPEX of MBR. Since municipal wastewater reclamation and reuse will play a major role in the future, commitment of MBR plants is expected to increase in the civil market.

In this paper we introduce SODES (Step-wise Ordinary Differential Equations Solver) which is a new solver for Ordinary Dfferential Equations (ODE). SODES can be used not only as a solver but also as a tutorial for the teaching and learning process of ODE, since it provides the solution displaying all the the steps needed to obtain it. In [1] we introduced SFOPDES (Step-wise First Order Partial Differential Equations Solver) developed in Derive, a Computer Algebra System (CAS). Two of the future works related considered in [1] were the development of new step-wise solvers for different math topics and the use of other CAS and programming with Python. This way, it is possible to develop web applications, freely available, providing different step-wise solvers. In this sense, SODES is the first work related with both ideas. Therefore, SODES is a web solver for ODE, developed in Python (using its CAS module SymPy). SODES increases the types of ODE that SFOPDES can deal with. Specifically, it provides, step by step, the solution of the following types of ODE: 1. First-order ODE: separable equations and equations reducible to them, homogeneous equations and equations reducible to them, exact differential equations and equations reducible to them (integrating factor technique), linear equations, the Bernoulli equation, the Riccati equation, First-order differential equations and nth degree in y', Generic programs to solve first order differential equations. 2. Higher-order ODE: higher order linear equations with constant coefficients. As a final remark, actually, SODES can be used in English, French or Spanish, but it can be easily extendable to other languages. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.

Partial Differential Equations (PDE) are an important topic within the Engineering Degrees syllabus. In addition, many students find some dificulties in the learning process of this topic. Therefore, the use of didactical tools to improve the teaching and learning process of PDE is very helpful. In this talk, we introduce the solver SPDES (Stepwise Partial Differential Equation Solver), an extension of SFOPDES introduced in [1] where only first order PDE were considered. This new solver SPDES deals also with some second order PDE. It can be used as a self tutorial for PDE since it solves, step by step, the typical exercises within the topic. Specifically, the type of PDE that SPDES can solve are: 1. Pfaff Differential Equations. 2. Quasi-linear PDE. 3. Lagrange-Charpit Method for first order PDE. 4. Heat equation. 5. Wave equation. 6. Laplace's equation. where the fi rst three types where considered in SFOPDES and the last three types are new in SPDES. SPDES has been developed using the programming capabilities of a Computer Algebra System (CAS), displaying step by step the solution of the problem to be solved. This way, we potentiate the use of the CAS as a Pedagogical CAS (PeCAS). This fact makes SPDES to be an important tool for students which can use it as a tutorial for their learning process. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.

The authors have approached in the past different railway engineering problems (e.g. [1,2]) and have developed software for the Spanish Railway Foundation [3], mainly using computer algebra systems (CAS). Now a CAS is used for designing and implementing a software package that allows to compare different layout diagrams for overtaking stations [4], from the point of view of its flexibility (for instance in degraded working conditions). The most common cases of overtaking stations (stations on double track lines with one or two sidings each side of the main line and one or two crossovers at the two throats of the overtaking station) are considered as illustration. It will be shown how, surprisingly, the usual position of the crossovers is not optimum from this point of view. The key idea is to use graph theory to determine the number of pairs of non conflicting itineraries (one in each direction) that can be simultaneously authorized by the railway interlocking system. The package can be applied to an overtaking station with any layout diagram. This is an important issue: for instance, the Spanish infrastructure administrator (Adif) is now planning a new track layout for Madrid Chamartín station [5] and the Iberian gauge part of Madrid Atocha station. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.

This paper focuses on the city at night. The distinctive aspect of the discussed topic is the time dimension of spaces and areas - places that "live" at night. The night has economic, cultural, social and formal elements; and it is these elements that underpin how we see and come to know the city at night. A range of topics have been explored: places of retailing and consumption, workplaces, places of entertainment, places that embody the night image of the city and places of socially unacceptable, delinquent behaviour. In the empirical part, we examined the city of Maribor, Slovenia. Prispevek obravnava mesto v nočnem času. Posebnost obravnavane tematike je časovna razsežnost prostora ter območja - kraji, ki "živijo" ponoči. Noč ima ekonomsko, kulturno, oblikovno in socialno vsebino in prav te lastnosti določajo spoznavanje mesta v nočnem času. Izpostavljene so naslednje teme: kraji potrošnje, kraji dela, kraji zabave, kraji nočne podobe mesta ter kraji družbeno nesprejemljivega, delikventnega vedenja. Empirični del se nanaša na mesto Maribor.

The human ABO blood group system is of great importance in blood transfusion and organ transplantation. The ABO system is composed of complex carbohydrate structures that are biosynthesized by A- and B-transferases encoded by the ABO gene. However, the mechanisms regulating ABO gene expression in epithelial cells remain obscure. On the basis of DNase I-hypersensitive sites in and around ABO in epithelial cells, we prepared reporter plasmid constructs including these sites. Subsequent luciferase assays and histone modifications indicated a novel positive regulatory element, designated the +22.6-kb site, downstream from ABO, and this was shown to enhance ABO promoter activity in an epithelial cell-specific manner. Expression of ABO and B-antigen was reduced in gastric cancer KATOIII cells by biallelic deletion of the +22.6-kb site using the CRISPR/Cas9 system. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that the site bound to an epithelial cell-specific transcription factor, Elf5. Mutation of the Ets binding motifs to abrogate binding of this factor reduced the regulatory activity of the +22.6-kb site. Furthermore, ELF5 knockdown with shRNA reduced both endogenous transcription from ABO and B-antigen expression in KATOIII cells. Thus, Elf5 appeared to be involved in the enhancer potential of the +22.6-kb site. These results support the contention that ABO expression is dependent upon a downstream positive regulatory element functioning through a tissue-restricted transcription factor, Elf5, in epithelial cells.

Background: There has been no effective method to predict ischemic intolerance to temporary internal carotid artery (ICA) occlusion during carotid artery reconstruction. Pencil beam presaturation (BeamSAT) pulse suppresses the flow signal of the target vessel in magnetic resonance angiography (MRA). Applying this method, we constructed ICA-selective MRA images. The aim of this study was to identify patients at risk for ischemic intolerance by ICA-selective MRA. Methods: By evaluating flow of anterior communicating artery (Acom) and A1 portion of anterior cerebral artery with ICA-selective MRA and posterior communicating artery (Pcom) with conventional MRA, we investigated associations of these collateral flow patterns with ischemic intolerance and decrease of regional cerebral oxygen saturation. Results: The study included 58 patients who underwent carotid endarterectomy or carotid artery stenting. Six of 7 patients without Acom flow and Pcom flow demonstrated ischemic intolerance, whereas all patients (n = 51) with Acom and/or Pcom flow demonstrated tolerance. The accuracy of this prediction model according to Acom and Pcom flow patterns for ischemic intolerance was 0.98 (P = 0.01, binomial test). Regional cerebral oxygen saturation decrease after ICA occlusion was significantly larger in patients without Acom flow and Pcom flow (12.0% ± 6.0%) than in patients with Acom flow and Pcom flow (3.0% ± 3.1%, P < 0.01) and in patients with Acom flow but no Pcom flow (2.4% ± 5.2%, P < 0.01). Conclusions: These findings support the importance of Acom flow as a collateral route. ICA-selective MRA enables prediction of ischemic intolerance to temporary ICA occlusion during carotid endarterectomy or carotid artery stenting. This method provides valuable information regarding probability of an ischemic complication.

Given the rapid advances in technology over the past decade, this thesis examines the potential for automatic speech recognition (ASR) technology to expedite the process of objective analysis of speech, particularly for lexical stress patterns in childhood apraxia of speech. This dissertation also investigates the potential for mobile technology to bridge the gap between current service delivery models in Australia and best practice treatment intensity for CAS. To address these two broad aims, this thesis describes three main projects. The first is a systematic literature review summarising the development, implementation and accuracy of automatic speech analysis tools when applied to evaluation and modification of children’s speech production skills. Guided by the results of the systematic review, the second project presents data on the accuracy and clinical utility of a custom-designed lexical stress classification tool, designed as part of a multi-component speech analysis system for a mobile therapy application, Tabby Talks, for use with children with CAS. The third project is a randomised control trial exploring the effect of different types of feedback on response to intervention for children with CAS. The intervention was designed to specifically explore the feasibility and effectiveness of using an app equipped with ASR technology to provide feedback on speech production accuracy during home practice sessions, simulating the common service delivery model in Australia. The thesis concludes with a discussion of future directions for technology-based speech assessment and intensive speech production practice, guidelines for future development of therapy tools that include more game-based practice activities and the contexts in which children can be transferred from predominantly clinician-delivered augmented feedback to ASR-delivered right/wrong feedback and continue to make optimal gains in acquisition and retention of speech production targets.

Partial Differential Equations (PDE) are one of the most difficult topics that Engineering and Sciences students have to study in the different Math subjects in their degree. In this talk we introduce SFOPDES (Stepwise First Order Partial Differential Equations Solver) aimed to be used as a tutorial for helping both the teacher and the students in the teaching and learning process of PDE. The type of problems that SFOPDES solves can be grouped in the following three blocks: 1. Pfaff Differential Equations, which consists on finding the general solution for: P(x; y; z) dx + Q(x; y; z) dy + R(x; y; z) dz = 0 (a) General method. (b) Particular cases: i. Separable equations. ii. Exact Pfaff equations. iii. One-separated variable equations. 2. Quasi-linear Partial Differential Equations, which consists on finding the general solution for: P(x; y; x) p + Q(x; y; z) q = R(x; y; z) (a) General method. (b) Particular solution which contents a given curve. 3. Using Lagrange-Charpit Method for finding a complete integral for a given general first order partial differential equation: F(x; y; z; p; q) = 0. (a) General method. (b) Particular cases: i. F(p; q) = 0 ii. g1(x; p) = g2(y; q) iii. z = px + qy + g(p; q) Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.

The residue theorem is one of the most interesting result in Complex Analysis which allows not only computations in C, the Field of Complex Numbers, but also provides many applications in the Field of Real Numbers R. In this talk we present the library ResidueApplications, that was initially developed in DERIVE since Engineering students in the University of Málaga are still using this software in computer lectures. However, we are migrating this library to PYTHON using the symbolic mathematics library SYMPY. This way it will be also possible to use this package in other CAS as SAGEMATH. The main goals of the ResidueApplications library are not only to provide some important applications of the Residue theorem but also to use it as a pedagogical tool for Engineering students. ResidueApplications can be used as a tutorial in the teaching and learning process of this topic since it provides the results step by step allowing the students to check their computations when they solve an exercise. When developing this package, we were not interesting only in the computations of residues and their applications (which can be easily done using standards functions in different CAS) but mainly on its pedagogical use. In addition of the step by step facility, using this library, the students also can develop their own programs to deal with different applications. This way, the student are the protagonist of their selflearning process. For example, If the students develop a program to compute the residues of a function, they will be better prepared to understand this topic. The programs developed in this tutorial can be grouped in the following blocks: 1. Compute of residues. 2. Compute of complex integrals using the residue theorem. 3. Applications of the residue theorem to compute integrals in R: (a) Trigonometric integrals. (b) Improper integrals. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.

Our group introduced random samples generation using a CAS, specifically Derive, in the Derive session of ACA 2009. This talk was extended in a paper published in The Derive Newsletter. In the year 2017 we presented a new version focused on research of the random samples generator in STATA that was communicated in [2]. Now a new version of the generator is being implemented in Python with the symbolic pack Simpy. In this case, our we are mainly focused in education. We are now researching in extensions of the Conway’s Game of Life, specifically using probabilistic cellular automata. Our long-term goal is the simulation of the growth of cancerous tissues. We have supervised a master thesis with the preliminary works in this topic. For the generation of random numbers involved in the probabilistic automata of this work, we have used the results developed in the previous mentioned work. A summary of this work is about to be published in Advances in Computational Mathematics [3]. This work is both, an education and a research experience for the student who carried out the master thesis. Moreover, the experience of teaching the subject Statistics to engineering students using the material developed for random samples generation has turned out to be useful in the teaching and learning process. The marks obtained in this subject by the students are statistically significantly better than the marks obtained by students of the same subject in others group of engineering where this material has not been used. A brief statistical study about the situation is carried out. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.