Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutagenesis Analysis of the rGTP-Specific Binding Site of Hepatitis C Virus RNA-Dependent RNA Polymerase

ABSTRACT Hepatitis C virus (HCV) nonstructural protein 5B (NS5B) is the virus-encoded RNA-dependent RNA polymerase (RdRp) essential for HCV RNA replication. An earlier crystallographic study identified a rGTP-specific binding site lying at the surface between the thumb domain and the fingertip about 30 Å away from the active site of the HCV RdRp (S. Bressanelli, L. Tomei, F. A. Rey, and R. De Francesco, J. Virol 76:3482-3492, 2002). To determine its physiological importance, we performed a systematic mutagenesis analysis of the rGTP-specific binding pocket by amino acid substitutions. Effects of mutations of the rGTP-specific binding site on enzymatic activity were determined by an in vitro RdRp assay, while effects of mutations on HCV RNA replication were examined by cell colony formation, as well as by transient replication of subgenomic HCV RNAs. Results derived from these studies demonstrate that amino acid substitutions of the rGTP-specific binding pocket did not significantly affect the in vitro RdRp activity of purified recombinant NS5B proteins, as measured by their abilities to synthesize RNA on an RNA template containing the 3′ untranslated region of HCV negative-strand RNA. However, most mutations of the rGTP-specific binding site either impaired or completely ablated the ability of subgenomic HCV RNAs to induce cell colony formation. Likewise, these mutations caused either reduction in or lethality to transient replication of the human immunodeficiency virus Tat-expressing HCV replicon RNAs in the cell. Collectively, these findings demonstrate that the rGTP-specific binding site of the HCV NS5B is not required for in vitro RdRp activity but is important for HCV RNA replication in vivo.
Does Seller Status Matter in Inter-Corporate Asset Sales?

This paper examines the returns of asset acquirers when sellers have different statuses. We find that private sellers create lower returns for acquirers and receive higher premiums than public sellers. Both private equity and private operating sellers generate lower returns for acquirers than public sellers, but their relative gain differences are not significantly different. In addition, the gain difference cannot be explained by acquirer characteristics, sample selection effects, or means of payments, but it increases with sellers’ director ownership. We examine alternative theories to explain our results. While we do not find supportive evidence for the synergy creation and information symmetry hypothesis, we find ample evidence for the manager discretion hypothesis.
Gastrointestinal Complications in Patients with Chronic Kidney Disease—A 5-Year Retrospective Study from a Tertiary Referral Center

Background: Gastrointestinal complications are frequent in patients with renal disease and are responsible for substantial morbidity and mortality among these patients in developing countries. Many times, these patients are subjected to endoscopic evaluation and mucosal biopsies are taken for definitive diagnosis. This study explores the various upper and lower nonneoplastic gastrointestinal complications in patients with chronic kidney disease (CKD) and the role of endoscopic mucosal biopsies in the management of these patients. Methods: Sixty-three patients with CKD, who were referred to endoscopic evaluation and biopsy due to significant gastrointestinal symptoms between January 2007 and December 2011 form the study group. Patients were divided into two groups: group 1 and group 2. Group 1 consisted of patients with CKD stages 1–5 and group 2 consisted of renal allograft recipients. All biopsies were reviewed by an experienced pathologist. Clinical data were collected from patient’s medical records. Results: There were 38 patients in group 1 and 25 patients in group 2. Twenty-nine out of 38 patients in group 1 presented with upper gastrointestinal (GI) symptoms and underwent esophagogastroduodenoscopy (OGD) evaluation, which showed erosive gastritis as the most common biopsy finding followed by ulcerative esophagitis and duodenitis. These patients were also found to be susceptible to develop ischemic colitis due to hypotensive episodes during dialysis, which are likely to occur during the initial stages of dialysis. The most frequent symptom in group 2 was chronic diarrhea (13 out of 25 patients) for which a colonoscopic examination was done which revealed various infection and drug-related colitis, mycophenolate mofetil (MMF) being a major culprit. Conclusion: CKD patients with high urea level are prone to develop upper GI symptoms and mostly show erosive gastritis, ulcerative esophagitis, and duodenitis on biopsy. On the contrary, renal allograft recipients mostly develop opportunistic infections and drug-related toxicity in the colon. MMF-related GI toxicity is an underrecognized entity and further prospective studies are required for its better understanding.
Laser-Assisted Subepithelial Keratectomy (LASEK) without Alcohol versus Photorefractive Keratectomy (PRK)

Purpose To evaluate epithelial healing and visual outcome after laser-assisted subepithelial keratectomy (LASEK) without alcohol de-epithelialization and to compare this technique to photorefractive keratectomy (PRK) in myopia. Methods In a series of 1953 patients undergoing bilateral myopic PRK, an epithelial flap could be obtained by manual de-epithelialization in the left eye of 56 patients without alcohol exposure. The right eye was treated by PRK and the left by LASEK (i.e., repositioning the viable flap after surface ablation). The two eyes were compared in terms of pain, uncorrected visual acuity (UCVA) in decimals, correction achieved, and haze. The epithelial healing pattern was assessed in the LASEK eyes. Results The flap remained viable, showing a peripheral junction, in 25 eyes (45%). Pain was higher in the PRK eye in 11/56 patients (20%), higher in the LASEK eye in 23/56 patients (41%), and the same in both eyes in 22/56 patients (39%). UCVA at one week was slightly better in the LASEK eyes (median 0.7 versus 0.6, p=0.002 with Wilcoxon test), but was the same in PRK and LASEK eyes after 1 month (median 0.9 in both). Median haze at 6 months was 0.5 in the PRK eyes and 0 in the LASEK eyes (Wilcoxon p=0.007). Median postoperative defocus equivalent at 9 months was 0.5 diopters in both the PRK and the LASEK eyes. Conclusion Although our study might have selected patients with loose epithelium, LASEK performed by manual de-epithelialization in the absence of alcohol exposure is not less painful than PRK, even in case of flap survival. Visual recovery speed, as well as haze, is slightly better than in PRK, although the difference is clinically negligible.
SmartSantander: Experimentation and service provision in the smart city

This paper describes the deployment and high-level architecture of the Internet of Things experimentation facility being deployed at Santander city. SmartSantander is a unique in the world city-scale experimental research facility in support of typical applications and services for a smart city. The testbed that has been deployed has a dual purpose. On the one hand it will allow real-world experimentation on Internet-of-Things related technologies (protocols, middlewares, applications, etc.). On the other hand it is currently supporting the provision of smart city services aimed at enhancing the quality of life in the city of Santander. Tangible results are expected to greatly influence definition and specification of Future Internet architecture design from viewpoints of Internet of Things and Internet of Services. This paper presents the physical deployment carried out in the city of Santander and the high-level architecture supporting the experimentation and service provision duality. Moreover, a brief description of the mechanisms supporting the experimentation life cycle will be done. Finally, the services that are being provided to the city will also be sketched.
Lipofuscin in the retina: quantitative assay for an unprecedented autofluorescent compound (pyridinium bis-retinoid, A2-E) of ocular age pigment.

The pyridinium bis-retinoid, A2-E, has been discovered as one of the major autofluorescent components of retinal pigment epithelial lipofuscin. Due to its chemical characteristics, A2-E may contribute to cellular and molecular changes leading to age-related macular degeneration. Because A2-E is the first lipofuscin component that has been identified, purified, and its structure analysed, it represents an important marker molecule for studying lipofuscin formation under various conditions. In order to investigate the role of A2-E in ageing processes of the retinal pigment epithelium, we developed an HPLC assay for this compound using single wavelength UV-absorbance detection with continuous light emission. Standard A2-E was synthetized and purified by sequential TLC. In our assay, A2-E can be detected in amounts lower than 10 pmol. The assay has been applied to quantitative determination of A2-E amounts in albino rat eyes of different age groups. Our results demonstrate that there is a marked increase of A2-E levels in older animals. The method described is the first to allow quantification of this unusual retinoid from small amounts of biological samples.
Rooting for cassava: insights into photosynthesis and associated physiology as a route to improve yield potential.

Contents 50 I. 50 II. 52 III. 54 IV. 55 V. 57 VI. 57 VII. 59 60 References 61 SUMMARY: As a consequence of an increase in world population, food demand is expected to grow by up to 110% in the next 30-35 yr. The population of sub-Saharan Africa is projected to increase by > 120%. In this region, cassava (Manihot esculenta) is the second most important source of calories and contributes c. 30% of the daily calorie requirements per person. Despite its importance, the average yield of cassava in Africa has not increased significantly since 1961. An evaluation of modern cultivars of cassava showed that the interception efficiency (ɛi ) of photosynthetically active radiation (PAR) and the efficiency of conversion of that intercepted PAR (ɛc ) are major opportunities for genetic improvement of the yield potential. This review examines what is known of the physiological processes underlying productivity in cassava and seeks to provide some strategies and directions toward yield improvement through genetic alterations to physiology to increase ɛi and ɛc . Possible physiological limitations, as well as environmental constraints, are discussed.
The Gendered Complexities of Promoting Female Entrepreneurship in the Gulf

ABSTRACT This paper explores women’s entrepreneurial activities in the Oman and Qatar in light of the state attention given to promoting entrepreneurship in the region over the past decade. In the Gulf Arab countries, like in many rapidly developing economies, neoliberal growth discourse abounds. Along with this, the promotion of entrepreneurship and embrace of individual enterprise is paramount. Despite the dominance of the state in political and economic spaces, Gulf governments have embraced the rhetoric of the market and entrepreneurship. Drawing from semi-structured interviews, focus groups, and participant observation conducted between 2011 and 2015, this paper examines this phenomenon. In a region stereotyped with weak gender development outcomes, female entrepreneurship is largely cast as a positive development aimed at liberating and empowering women through individual enterprise. In contrast, this paper finds that the same forces that are meant to empower women often reproduce or reinforce certain gender norms while introducing new forms of dependency. Gulf female entrepreneurs confront competing tensions within three intersecting political economy logics: the structural logic of the economy, the logic of development narratives, and the logic of socio-economic organisation.
Expression of c‐fos in the rat brainstem after exposure to hypoxia and to normoxic and hyperoxic hypercapnia

In this study, Fos immunohistochemistry was used to map brainstem neuronal pathways activated during hypercapnia and hypoxia. Conscious rats were exposed to six different gas mixtures: (a) air ; (b) 8% CO2 in air; (c) 10% CO2 in air; (d) 15% CO2 in air; (e) 15% CO2 + 60% O2, balance N2; (f) 9% O2, balance N2. Double‐staining was performed to show the presence of tyrosine hydroxylase. Hypercapnia, in a dose‐dependent way, caused Fos expression in the following areas: caudal nucleus tractus solitarius (NTS), with few labeled A2 noradrenergic neurons; noradrenergic A1 cells and noncatecholaminergic neurons in the caudal ventrolateral medulla; raphe magnus and gigantocellular nucleus pars α (GiA); many noncatecholaminergic (and relatively few C1) neurons in the lateral paragigantocellular nucleus (PGCl), and in the retrotrapezoid nucleus (RTN); locus coeruleus (LC), external lateral parabrachial and Kölliker‐Fuse nuclei, and A5 noradrenergic neurons at pontine level; and in caudal mesencephalon, the ventrolateral column of the periaqueductal gray (vlPAG). In most of these nuclei, hypoxia also induced Fos expression, albeit generally less than after hypercapnia. However, hypoxia did not cause labeling in RTN, juxtafacial PGCl, GiA, LC, or vlPAG. After normoxic hypercapnia, more labeled cells were present in NTS and PGCl than after hyperoxic hypercapnia. Part of the observed labeling could be caused by stress‐ or cardiovascular‐related sequelae of hypoxia and hypercapnia. Possible implications for the neural control of breathing are also discussed, particularly with regard to the finding that several nuclei, not belonging to the classical brainstem respiratory centres, contained labeled cells. J. Comp. Neurol. 388:169–190, 1997. © 1997 Wiley‐Liss, Inc.
Expanding the scope of anatomical sciences: The case of “Human evolution: The fossil evidence” course at the Sackler School of Medicine, Tel‐Aviv University

The Anatomy Department at Tel‐Aviv University Medical School offers its students an elective course of 26 didactic hours on human evolution. The course is open to students from all faculties, who must fulfill all academic requirements, without a prerequisite of a background in anatomy. Approximately 120 students attend annually, a third of them are nonmedical students who major in philosophy, archeology, and sociology. This article discusses the course's contributions to students' understanding of a scientific concept that a scientific theory can be contradicted by new evidence, because facts govern science. Also, research methods of applying scientific principles establish the understanding of the human body, which evidently contributes to health and medicine. In the classes, the students are divided into mini‐groups of 2–3 students, while the lecturer moves among students to examine fossils. In addition, analogies, open‐discussions, and explanations accompany the tangible experiences. The lecturer of the course is an experienced anthropologist–anatomist researcher. He is a role‐model and a mentor, sharing with the students his belief that a scientist should be persistent in his research to overcome difficult circumstances. Students, regardless of their backgrounds, express high appreciation of the course in their feedback questionnaires. The message conveyed by this course is that not only knowledge counts but also its integration with scientific principles. This course teaches us that science can bring students from different areas to study together and share ideas. In conclusion, this is a unique course in the eyes of the faculty and students alike. Anat Sci Educ. © 2012 American Association of Anatomists.
Incorporating user acceptance into usability evaluation scheme for the user interface of mobile services

As the usability of mobile services has become a critical factor of success in market, needs for established usability evaluation methodologies and realistic practices that ensure capturing usability in evaluation are increasing. From a point of user-centered design perspective, customer perceived value (CPV) has recently gained much attention from usability experts and user interface (UI) practitioners due to its important role in predicting purchase behavior and achieving sustainable competitive advantage. User perceived values on the newly introduced mobile services are diverse and rapidly changing However, there are few appropriate evaluation methods for assessing the usability of mobile services considering the CPVs. The purpose of this study is to propose an evaluation scheme incorporating users' subjective values on the usability of mobile services. Based on the CPVs on mobile services from FGI, appropriate usability principles related to UI design components, CPVs from the literature were synthesized for the development of evaluation indexes in the proposed evaluation scheme. Comparing with traditional evaluation methods, it is expected that the proposed approach might enable UI practitioners to capture what users really want as well as to secure the usability of mobile services quickly and easily in the field.
Therapeutic effect of bFGF on retina ischemia-reperfusion injury.

BACKGROUND Basic fibroblast growth factor (bFGF) plays important roles in retina degeneration, light injury, mechanical injury, especially in retina ischemia-reperfusion injury (RIRI). This study was to investigate the therapeutical effect of bFGF on RIRI and its mechanisms. METHODS Experimental RIRI was induced by increasing intraocular pressure (IOP) in the eyes of 48 rats. These rats were divided into normal control, ischemia-reperfusion and bFGF-treated groups. Histological and ultrastructural changes of in the retina of different groups were observed, and the number of retinal ganglion cells (RGCs) was quantitatively analyzed under microscopy. Apoptotic cells were detected using the TdT-dUTP terminal nick-end labeling (TUNEL) method. The expression of caspase-3 was determined by streptavidin peroxidase (SP) immunohistochemistry. Atomic absorption spectrum method was used to evaluate the intracellular calcium changes. RESULTS At the early stage of retinal ischemia-reperfusion injury, retina edema in the treated group was significantly eliminated compared with the untreated ischemic animals. RGCs in the bFGF-treated group was more than those in the untreated ischemic group during the post-reperfusion stages. In ischemic group, apoptotic cells could be found at 6th hour after reperfusion and reached the peak at 24 hours. At 72nd hour no apoptotic cells could be found.The changes in caspase-3 expression had a similar manner. The intracellular calcium of rat retina began to increase at 1st hour, reached the peak at 24 hours, and began to decrease at 72 hours. The change of the three markers in the treatment group showed a similar pattern, but they were all relatively less obvious. CONCLUSION Apoptosis may play a vital role in RIRI. bFGF may has therapeutical effects on RIRI by inhibiting the increase of intracellular calcium and caspase-3 expression.
A Framework for Failure Diagnosis

Testing and debugging is one of the most expensive and challenging phases in the software development life-cycle. One important cost factor in the debugging process is the time required to analyze failures and repair underlying faults. Two types of methods that can help testers to reduce this analysis time are Failure Clustering and Fault Localization. Although there is a plethora of these methods in the literature, there are still some gaps that prevent their operationalization in real world contexts. In addition, the abundance of these methods confuses the practitioners in selecting the suitable method for their own specific domain. To fill the gaps and bring state-of-art closer to practice, we develop a framework for failure diagnosis. To devise this framework, we evaluate existing methods to investigate the possibility of ? nding a method(s) that would be effective in different contexts. Then, we introduce a methodology for adapting this method(s) to different contexts with a priori parameter setting. This framework will empower practitioners to do fast and reliable debugging.
The Evolution of Hayek's Thought on Gold and Monetary Standards

Early in his career, Hayek viewed attempts to stabilize exchange rates by facilitating cooperation between central banks, with respect to their demand for gold, to be at odds with the fundamental mechanisms of the gold standard. He opposed proposals by Irving Fisher, Gustav Cassel, and Ralph Hawtrey that promoted stabilization of demand for gold and price levels as a next best option. Hayek viewed the nations that refused to devalue their currency after monetary expansion during wartime as complicit in degrading the international gold standard. In 1935 Hayek's emphasis began to change, his position sounding much like the arguments of Cassel and Hawtrey. Though he eventually gave up hope that the international gold standard would be reestablished, his later work on money provides theoretical underpinnings for systems that would promote the same sort of stability and predictability that the classical gold standard had provided.
The HIV‐1 Reverse Transcription (RT) Process as Target for RT Inhibitors

Since the Human Immunodeficiency Virus Type 1 (HIV‐1) was identified as the etiologic agent of the Acquired Immune Deficiency Syndrome (AIDS), the HIV‐1 reverse transcriptase (RT) has been the subject of intensive study. The reverse transcription entails the transition of the single‐stranded viral RNA into double‐stranded proviral DNA, which is then integrated into the host chromosome. Therefore, the HIV‐1 reverse transcriptase plays a pivotal role in the life cycle of the virus and is consequently an interesting target for anti‐HIV drug therapy. In the first section, we describe the complex process of reverse transcription and the different activities involved in this process. We then highlight the structure‐function relationship of the HIV‐1 reverse transcriptase, which is of great importance for a better understanding of resistance development, a major problem in anti‐AIDS therapies. Finally, we summarize the mechanisms of HIV resistance toward various RT inhibitors and the implications thereof for the current anti‐HIV drug therapies. © 2000 John Wiley & Sons, Inc. Med Res Rev, 20, No. 2, 129–154, 2000