Discovering Software Reliability Patterns Based On Multiple Software Projects

Discovering patterns that indicate software reliability provides valuable information to software project managers. Software Quality Classification (SQC) modeling is a methodology that can be used to discover reliability patterns of large software projects. However, the patterns found by SQC modeling may not be accurate and robust owing to insufficient information used in the training process. This study compares two genetic programming-based SQC models using different volumes of data. These data were extracted from seven different NASA software projects. The results demonstrate that combining data from different projects can produce more accurate and reliable patterns

Non-random escape pathways from a broadly neutralizing human monoclonal antibody map to a highly conserved region on the hepatitis C virus E2 glycoprotein encompassing amino acids 412-423

A challenge for hepatitis C virus (HCV) vaccine development is to define epitopes that are able to elicit protective antibodies against this highly diverse virus. The E2 glycoprotein region located at residues 412-423 is conserved and antibodies to 412-423 have broadly neutralizing activities. However, an adaptive mutation, N417S, is associated with a glycan shift in a variant that cannot be neutralized by a murine but by human monoclonal antibodies (HMAbs) against 412-423. To determine whether HCV escapes from these antibodies, we analyzed variants that emerged when cell culture infectious HCV virions (HCVcc) were passaged under increasing concentrations of a specific HMAb, HC33.1. Multiple nonrandom escape pathways were identified. Two pathways occurred in the context of an N-glycan shift mutation at N417T. At low antibody concentrations, substitutions of two residues outside of the epitope, N434D and K610R, led to variants having improved in vitro viral fitness and reduced sensitivity to HC33.1 binding and neutralization. At moderate concentrations, a S419N mutation occurred within 412-423 in escape variants that have greatly reduced sensitivity to HC33.1 but compromised viral fitness. Importantly, the variants generated from these pathways differed in their stability. N434D and K610R-associated variants were stable and became dominant as the virions were passaged. The S419N mutation reverted back to N419S when immune pressure was reduced by removing HC33.1. At high antibody concentrations, a mutation at L413I was observed in variants that were resistant to HC33.1 neutralization. Collectively, the combination of multiple escape pathways enabled the virus to persist under a wide range of antibody concentrations. Moreover, these findings pose a different challenge to vaccine development beyond the identification of highly conserved epitopes. It will be necessary for a vaccine to induce high potency antibodies that prevent the formation of escape variants, which can co-exist with lower potency or levels of neutralizing activities

School sanitation programme in Lao PDR

Lao People’s Democratic Republic (Lao PDR) is one of the poorest countries in South-East Asia. However, it is stepping into a progressive phase of expansion, moving from a land-locked country to a land-linked country, and looking to escape from the least-developed country status by 2020 through a National Growth and Poverty Eradication Strategy (NGPES). Since, 1997, the Lao Government (through Ministry of Health) is advancing a Rural Water Supply and Sanitation (RWSS) Sector Strategy involving the pioneering of new institutional solutions. The School Sanitation receives adequate attention by the RWSS Sector Strategy and therefore, the National Centre for Environmental Health and Water Supply (commonly known as Nam Saat) under the Ministry of Health (MoH) in collaboration with the Ministry of Education (MoE) advancing the School Sanitation Programme in Lao PDR through its local counter-parts, with support from NGOs and External Support Agencies. However, some recent studies reveal that there are further scopes existing for the School Sanitation Programme to improve. This paper explains the background of the School Sanitation Programme in Lao PDR and provides a way out on how to further improve the activities in Lao PDR to make the programme more effective and efficient

Potential impacts of selenium on California red-legged frog (Rana DraytonII)

Amphibian stress response to selenium through the hypothalamus-pituitaryinterrenal axis, reflected in corticosterone levels, and its effects on development and growth, is unknown. In our current study, Rana pipiens embryos were exposed to selenium treatments (0 µg/L, 1 µg/L, 5 µg/L, and 13 µg/L) and reared in a laboratory until metamorphosis completed at Gosner stage 46. We also examined Lithobates catesbeiana from a selenium-contaminated pond and a reference site. We then analyzed the selenium accumulation, corticosterone levels, development, and growth in both amphibian species. Lithobates catesbeiana from the contaminated site accumulated higher levels of selenium but had lower corticosterone levels compared to L. catesbeiana from the reference site, which had a significantly higher corticosterone response. Selenium accumulation in R. pipiens tadpoles was 1,000 times the selenium exposure, corticosterone response was at control levels, and there was no affect on both development and growth. Our study demonstrates that selenium exposure does not elicit a stress response

Neutralizing Antibody Response to Hepatitis C Virus

A critical first step in a “rational vaccine design” approach for hepatitis C virus (HCV) is to identify the most relevant mechanisms of immune protection. Emerging evidence provides support for a protective role of virus neutralizing antibodies, and the ability of the B cell response to modify the course of acute HCV infection. This has been made possible by the development of in vitro cell culture models, based on HCV retroviral pseudotype particles expressing E1E2 and infectious cell culture-derived HCV virions, and small animal models that are robust tools in studies of antibody-mediated virus neutralization. This review is focused on the immunogenic determinants on the E2 glycoprotein mediating virus neutralization and the pathways in which the virus is able to escape from immune containment. Encouraging findings from recent studies provide support for the existence of broadly neutralization antibodies that are not associated with virus escape. The identification of conserved epitopes mediating virus neutralization that are not associated with virus escape will facilitate the design of a vaccine immunogen capable of eliciting broadly neutralizing antibodies against this highly diverse virus

The Hepatitis C Virus E1 Glycoprotein Undergoes Productive Folding but Accelerated Degradation When Expressed as an Individual Subunit in CHO Cells

Hepatitis C Virus E1E2 heterodimers are components of the viral spike. Although there is a general agreement on the necessity of the co-expression of both E1 and E2 on a single coding unit for their productive folding and assembly, in a previous study using an in vitro system we obtained strong indications that E1 can achieve folding in absence of E2. Here, we have studied the folding pathway of unescorted E1 from stably expressing CHO cells, compared to the folding observed in presence of the E2 protein. A DTT-resistant conformation is achieved by E1 in both situations, consistent with the presence of an E2-independent oxidative pathway. However, while the E1E2 heterodimer is stable inside cells, E1 expressed alone is degraded within a few hours. On the other hand, the oxidation and stability of individually expressed E2 subunits is dependent on E1 co-expression. These data are consistent with E1 and E2 assisting each other for correct folding via different mechanisms: E2 assists E1 by stabilizing a semi-native conformation meanwhile E1 drives E2 towards a productive folding pathway

Tracing writing progression in English for academic purposes: A data-driven possibility in the post-COVID era in Hong Kong

It is rare to use “big data” in writing progression studies in the field of second language acquisition around the globe. The difficulty of recruiting participants for longitudinal studies often results in sample sizes that are too small for quantitative analysis. Due to the global pandemic, students began to face more academic and emotional challenges, and it became more important to track the progression of their writing across courses. This study utilizes big data in a study of over 4,500 students who took a basic English for Academic Purposes (EAP) course followed by an advanced one at a university in Hong Kong. The findings suggest that analytics studies can provide a range of insights into course design and strategic planning, including how students’ language use and citation skills improve. They can also allow researchers to study the progression of students based on the level of achievement and the time elapsed between the two EAP courses. Further, studies using mega-sized datasets will be more generalizable than previous studies with smaller sample sizes. These results indicate that data-driven analytics can be a helpful approach to writing progression studies, especially in the post-COVID era

Hepatitis C Virus E2 Protein Ectodomain Is Essential for Assembly of Infectious Virions

The Hepatitis C virus E1 and E2 envelope proteins are the major players in all events required for virus entry into target cells. In addition, the recently developed HCV cell culture system has indicated that E1E2 heterodimer formation is a prerequisite for viral particle production. In this paper, we explored a new genetic approach to construct intergenotypic 2a/1b chimeras, maintaining the structural region of the infectious strain JFH1 and substituting the soluble portion of E1 and/or E2 proteins. This strategy provides useful information on the role of the surface-exposed domain of the envelope proteins in virus morphogenesis and allows comparative analysis of different HCV genotypes. We found that substituting the E2 protein ectodomain region abolishes the production of chimeric infectious particles. Our data indicate that the soluble part of the E2 protein is involved in a genotype-specific interplay with remaining viral proteins that affect the HCV assembly process

A novel neutralizing human monoclonal antibody broadly abrogates hepatitis C virus infection in vitro and in vivo

Infections with hepatitis C virus (HCV) represent a worldwide health burden and a prophylactic vaccine is still not available. Liver transplantation (LT) is often the only option for patients with HCV-induced end-stage liver disease. However, immediately after transplantation, the liver graft becomes infected by circulating virus, resulting in accelerated progression of liver disease. Although the effi cacy of HCV treatment using direct-acting antivirals has improved significantly, immune compromised LT-patients and patients with advanced liver disease remain difficult to treat. As an alternative approach, interfering with viral entry could prevent infection of the donor liver. We generated a human monoclonal antibody (mAb), designated 2A5, which targets the HCV envelope. The neutralizing activity of mAb 2A5 was assessed using multiple prototype and patient-derived HCV pseudoparticles (HCVpp), cell culture produced HCV (HCVcc), and a human-liver chimeric mouse model. Neutralization levels observed for mAb 2A5 were generally high and mostly superior to those obtained with AP33, a well-characterized HCV-neutralizing monoclonal antibody. Using humanized mice, complete protection was observed after genotype 1a and 4a HCV challenge, while only partial protection was achieved using gt1b and 6a isolates. Epitope mapping revealed that mAb 2A5 binding is conformation-dependent and identified the E2-region spanning amino acids 434 to 446 (epitope II) as the predominant contact domain. Conclusion : mAb 2A5 shows potent anti-HCV neutralizing activity both in vitro and in vivo and could hence represent a valuable candidate to prevent HCV recurrence in LT-patients. In addition, the detailed identification of the neutralizing epitope can be applied for the design of prophylactic HCV vaccines