CD163 receptor editing for resistance to porcine reproductive and respiratory syndrome virus (PRRSV)

Doctor of PhilosophyDepartment of Diagnostic Medicine/PathobiologyMegan C. NiederwerderRaymond R. R. RowlandPorcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically destructive viruses affecting swine worldwide. In the U.S. alone, annual estimates indicate losses to national swine herds of $664 million. PRRSV isolates can be divided into two different genotypes, PRRSV-1 or PRRSV-2, which share only about 70% identity at the nucleotide level. Previous work showed that pigs lacking CD163 expression on macrophages are protected from PRRSV-2 infection (Whitworth et al., 2016). This receptor is composed of nine scavenger receptor cysteine-rich (SRCR) domains and two proline-serine-threonine (PST)-rich regions, one between SRCR6 and SRCR7, and one between SRCR9 and the transmembrane region and cytoplasmic tail. The purpose of the first study was to identify domains in CD163 that are necessary for infection with a PRRSV-2 isolate. The model system consisted of transfecting HEK cells with plasmids that expressed various CD163 domain deletions and an enhanced green fluorescent protein (EGFP) tag. After two days, the cells were infected with a P129 isolate expressing red fluorescent protein (RFP). The results showed that transfected cells possessing a deletion of the 101 amino acid SRCR5 or disruption of any of the conserved disulfide bonds within SRCR5 of CD163 were resistant to infection. Deletion of the 16 amino acid PSTII domain also has a negative impact on infection. The importance of both SRCR5 and PSTII domains in PRRSV infection indicates that the viral protein complex on the surface of the virion may form multiple contacts with CD163. A recent study showed that CD163 pigs containing a SRCR5 domain swap with the corresponding homolog SRCR8 from the hCD163L1 protein became resistant to PRRSV-1 but not PRRSV-2 (Well et al., 2017), showing that the viruses recognize different peptide sequences within SRCR5. An analysis of various studies that demonstrated the requirement of SRCR5 for PRRSV infection showed that some SRCR5 deletion constructs retained the ability to sustain a low-level of infection when retaining the SRCR4/5 inter-domain region, AHRK. Thus, the purpose of the second study was to identify the minimum changes in SRCR5 and the SRCR4/5 interdomain region sufficient to make HEK cells resistant to infection with both PRRSV genotypes. The results from this study showed that the insertion of proline-arginine (PR) after amino acids 57 and 99 inhibits infection with a PRRSV-1 isolate, whereas PR insertion after amino acids 8, 47, 54 and 99, inhibits PRRSV-2 infection. Furthermore, the deletion of the SRCR4/5 interdomain sequence, AHRK, also blocks infection. A monoclonal antibody (mAb) 2A10 was previously produced by immunizing pigs with porcine alveolar macrophages and has been used in various CD163-related experiments. There is currently no information regarding the location of the epitope recognized by this antibody, therefore, the goal of the last study was to determine this. By western blot analysis, immunofluorescence antibody assay and flow cytometry, we identified SRCR1 as the region recognized by the mAb 2A10. The data presented in this dissertation provided valuable tools for refinement of in vitro receptor editing approaches for prevention of PRRSV or other swine diseases

Commercial Activity’s Contribution to Sustainable Development by Social Responsability Actions: a Vision of SMEs

This paper reports on a small study concerning the development of the social responsibility concept, in order to reveal how this concept became an important element of the sustainable development. According to this relationship, there are presented the results of a qualitative research among small and middle- sized companies involved in commercial activity in Bucharest, to show the way in which their activities of social responsibility meet the national strategy of sustainable development. The conclusions of this paper support the literature in the field, that underlines the fact that small and middle companies involved in commercial activity are concerned mostly with the way they succeed in achieving the economic objectives, and social responsibility is understood more at a minimal level, that are connected with legal obligations. The way in which the activity of the company meets the demands of a sustainable development represents a diffuse preoccupation, totally subordinated to the objectives of economic performance.sustainable development, small and middle-sized companies with commercial activity, social responsibility, commercial activity

Analyzing ASR Pretraining for Low-Resource Speech-to-Text Translation

Previous work has shown that for low-resource source languages, automatic speech-to-text translation (AST) can be improved by pretraining an end-to-end model on automatic speech recognition (ASR) data from a high-resource language. However, it is not clear what factors --e.g., language relatedness or size of the pretraining data-- yield the biggest improvements, or whether pretraining can be effectively combined with other methods such as data augmentation. Here, we experiment with pretraining on datasets of varying sizes, including languages related and unrelated to the AST source language. We find that the best predictor of final AST performance is the word error rate of the pretrained ASR model, and that differences in ASR/AST performance correlate with how phonetic information is encoded in the later RNN layers of our model. We also show that pretraining and data augmentation yield complementary benefits for AST.Comment: Accepted at ICASSP 202

Deep Learning with Logical Constraints

In recent years, there has been an increasing interest in exploiting logically specified background knowledge in order to obtain neural models (i) with a better performance, (ii) able to learn from less data, and/or (iii) guaranteed to be compliant with the background knowledge itself, e.g., for safety-critical applications. In this survey, we retrace such works and categorize them based on (i) the logical language that they use to express the background knowledge and (ii) the goals that they achieve.Comment: Survey paper. IJCAI 202

Abdominal-pelvic pain in female patients with endometriosis - a review of the literature

Abdominal-pelvic pain is the dominant symptom in endometriosis, one of the most common pathologies that affect women, being also a multifactorial disorder. Exploratory laparoscopy allows the correct assessment of the location as well as severity and extent of the lesions, thus representing the current gold standard in diagnosis. The correlation of pain intensity with the evolutionary stage of endometriosis is inconstant. Surgical treatment, preferably performed laparoscopically, includes the excision of the ectopic endometrium, having as a primary objective the control of persistent pain and the removal of all endometriotic foci. This procedure helps to improve the life quality of the patient, to reduce relapses, to control postoperative pain, and to eliminate the disease. Pre- and post-operative adjuvant medical treatment is used due to its effects on the symptomatology, prolonging the asymptomatic period of the disease. Despite the use of the above procedures, there are cases in which the abdominal-pelvic pain persists even after surgery, which makes endometriosis a significant challenge for both the specialist and the patient, as well as for the medical system itself, as the study of the pathogenic mechanisms is yet the subject of numerous studies. Nutritional education in these patients is essential, given the recommendation to restrict the range of foods and to increase other foods that have an important role in reducing the risk or even leading to regression of the endometrial pathology

Elastography: A New Ultrasound Technique in Nodular Thyroid Pathology

Elastography is a new technique for evaluating the stiffness of nodules. It is generally recognised that malignant thyroid lesions are harder than benign lesions. Different elastographic techniques are presented, with characteristics, advantages and limitations. Qualitative and semiquantitative methods are described. Comparison of the main existing techniques, static and dynamic elastographies, is presented in this chapter. Strain elastography seems to have a better diagnostic quality than shear wave elastography in the diagnosis of thyroid cancer disease. A positive elastogram, suggestive for malignancy is more useful in diagnosis than a positive grey-scale ultrasound evaluation. Elastography increases the specificity of grey scale ultrasound (US), it should be always integrated with its information and should be considered as a complement of conventional US

Can non-small cell lung cancer histologic subtypes predict survival? A single institution experience

Introduction. The latest histological classification of lung adenocarcinoma includes lepidic, acinar, papillary, micropapillary, and solid as subtypes. Testing these subtypes for their prognostic and predictive value is an ongoing scientific challenge. The present research article aims to describe the influence this classification has on patient survival. Materials and Methods. Thirty-three patients were included in the trial. The most important enrollment criterion was the clear specification of the adenocarcinoma subtype in the pathology report. Patients were stratified into three groups which included the adenocarcinoma pathological subtypes as follows: lepidic (LEP), acinar and papillary (ACN/PAP), and micropapillary/solid (MIP/SOL). The primary endpoint was progression-free survival. Other endpoints included overall survival. Results. The lepidic subtype of ADC had superior PFS and OS, regardless of stage. Papillary and acinar subtype showed an intermediate prognosis, whereas micropapillary and solid subtypes were the most aggressive. Conclusions. The experience of this single center confirmed data in the literature. Further studies are needed to demonstrate all the possible implications of this pathology classification

Generation Y’s Work Values and Their Impact on the Hospitality Industry

In the current business environment, it is considered natural to see people from different generations working together. As it seems to be widely accepted that each generation has its own attributes that reflect in a unique manner on the way work is perceived, managers are being confronted with new challenges in managing human resources. As a result, the paper underlines the main differences between the three currently active generations on the labor market (Baby Boomers, generation X and generation Y) and their implications on the workplace. The main purpose of the article is to present bachelors’ of business administration perceptions of the factors considered important for an ideal workplace and whether the hospitality and tourism industry is able to offer these factors. Consequently, the paper brings forward an exploratory research, conducted using a questionnaire-based survey on 2015 bachelor graduates at the Faculty of Business and Tourism (Bucharest University of Economic Studies): out of the 320 students who have been enrolled in the senior year (2014-2015 academic year), 237 graduates completed the questionnaire. The results of the survey indicate that generation Y members’ most valued workplace characteristics are having promotion possibilities, working with people who cooperate effectively, having free time for personal life and having the opportunity of receiving high salary increases, as they advance in their career. These findings are compared to the conclusions of previous studies presented in the literature developed on this subject. The results of the study are relevant for the tourism industry as they reflect the needs and expectations of generation Y, therefore enabling managers to develop new human resources practices in order to attract and retain young graduates and determine them to become loyal, engaged employees. Considering the limitations of the research, the theoretical and practical implications of the findings are discussed